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El aprovechamiento maderable ha sido, históricamente, la actividad económica más relevante en el sector forestal mexicano; aunque la investigación gubernamental en el tema inició después de la creación del Instituto Nacional de Investigaciones Forestales. Recientemente, la generación de servicios ambientales ha surgido como un nuevo campo de investigación. El objetivo fue analizar las aportaciones del Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias (INIFAP) en la investigación científica sobre Manejo y Servicios Ambientales de bosques templados durante los últimos 35 años. Se realizó una revisión exhaustiva de publicaciones científicas nacionales e internacionales arbitradas, en las que investigadores del INIFAP tuvieron una participación relevante. Los resultados se analizaron en tres períodos definidos de desarrollo institucional y en concordancia con la estructura de los sistemas de investigación del INIFAP; en los cuales el Manejo Forestal incluye Biometría, Silvicultura y regímenes de Incendios; y en los Servicios Ambientales se integran: Captura de Carbono, Agua y estudios paleoclimáticos. Se observa un incremento de publicaciones en los dos temas durante el periodo más reciente, atribuible a una mayor disponibilidad de financiamiento a la investigación forestal y a la importancia actual de los bosques en la mitigación del cambio climático. La producción científica se concentró en revistas nacionales, sobresaliendo la revista institucional. La Biometría y Silvicultura son áreas de fortaleza del instituto y corroboran su papel pionero en este tipo de estudios en México; los paleoclimáticos presentan un crecimiento acelerado en el tercer período; en captura de carbono y recarga hídrica el crecimiento es moderado.

In this work, the chemical bath deposition (CBD) technique was utilized in the synthesis of transition metals/GO nanocomposites (Co3O4/MnO2/NiO/GO) for applications in supercapacitor electrodes. The nanocomposites after characterization showed that the electrically conductive nature and wide surface area of graphene oxide (GO) accounted for its incorporation into the nanocomposites. The synergy between the nanocomposites accounts for their improved performance and stable phase. The XRD results revealed cubic, orthorhombic, cubic, and mixed phases for the Co3O4/GO (CG), MnO2/GO (MG), NiO/GO (NG), and Co3O4/MnO2/NiO/GO (CMNG), respectively; their morphologies showed platelet nanoparticles with few agglomerates, with an average particle size of 69 ± 12 nm, 37 ± 09 nm, 58 ± 36 nm, and 36 ± 08 nm, respectively. For the produced materials, electrochemical results revealed maximum specific capacitance values of 2482 F/g from cyclic voltammograms and 1280.48 F/g from the galvanometric test. The results showed that the composites outperform single transition metal oxide (TMO) electrodes, with graphene oxide boosting the electrode performance.

An optimal operation of compressors used onboard vessels for various purposes is very important. In this study, the drawbacks of conventional air compressors are addressed. Interruption of the operations by unpredictable electrical power blackout and corrosion are the key drawbacks. The corrosion occurs due to a manual drain, which depletes the life of the air tank, thereby causing damages to the compressors. To address this challenge, the need for modification of conventional air compressors is imperative. Hence, this study entails the design and fabrication of an air compressor system with rechargeable characteristics, well equipped with an automatic drain sensor and pressure switch, to obtain optimal system efficiency and reliability. From the obtained results of the test and performance of the compressor, it is obvious that it is efficient and reliable for onboard ship operations.

In Buenos Aires, Argentina there are many architectonic heritage objects that represent the history of the population of different places with different degree of deterioration and conservation, so their study and survey were necessary to avoid the complete loss of it. During the study of heritage assets in towns, villages, and cities of Buenos Aires that the LEMIT makes more than 20 years ago, numerous architectonic heritage assets were found with different degree of deterioration and conservation. As result of some surveys, important restoration and conservation interventions were done preserving province heritage. Thus, the aim of this paper was the study of the materials deterioration state from the first ranch built by the settlement of the Jewish settlers in 1891, in Algarrobos city, Carlos Casares, Buenos Aires. This ranch was the first houses of Jews when they arrived from Russia. The material analysis here presented allowed to recognize its state of deterioration and conservation through discerning if these materials were from the mentioned age and consequently, providing fundamental information to know part of settlement history formation. On the other hand, its study allowed generating a plan of interventions and conservation in short – and medium- term.

Abstract: The present paper offers a comparative analysis of Robert Browning’s poems “Fra Lippo Lippi” and “Caliban upon Setebos,” wherein the main point of interest is the interplay between religion and art. I will investigate how religion is depicted and how it influences the artistic viewpoints espoused by the eponymous characters, emphasizing the role these two concepts play in shaping the speakers’ self-presentation and sense of identity. In the case of “Caliban upon Setebos,” I will also delve into Browning’s source of inspiration, Shakespeare’s The Tempest, so as to understand how Browning’s own character can be likened to, or contrasted with, the Renaissance playwright’s. Whereas Lippi the monk justifies his own penchant for naturalistic art through religion, Caliban takes to more rudimentary forms of art to assuage the fury of an unjust and wrathful deity. However, what seems to drive their definitions and redefinitions of artistic and religious discourse is an apparent lack of agency, which spurs them into rebelling against the limitations set upon them by external forces.

La medición en campo de la altura total de los árboles implica dificultades prácticas que incrementan los tiempos y costos del inventario. Además, su medición está propensa a errores, en particular en sitios con sotobosques densos. Las relaciones alométricas son una alternativa viable para estimar en forma eficiente la altura en función del diámetro normal. El objetivo de este estudio fue analizar modelos de crecimiento y alométricos para determinar el de mejor ajuste en la relación altura-diámetro para árboles de Pinus montezumae y Pinus teocote de la región forestal Nanacamilpa, Tlaxcala. Para el análisis, se obtuvieron 583 pares de datos de diámetro normal-altura total para P. montezumae y 468 pares para P. teocote. La muestra abarcó un amplio intervalo de categorías diamétricas. Se evaluaron 14 modelos no lineales y uno lineal, mediante análisis de regresión con el procedimiento MODEL de SAS® para los no lineales, y REG para el lineal. La bondad de ajuste se evaluó con base en la R2adj, el sesgo, la raíz del error cuadrático medio, la suma de cuadrado del error, el cuadrado medio del error y el criterio de información de Akaike. El mejor modelo para estimar la altura de Pinus montezumae fue el propuesto por Yang (M2) con una R2adj=0.91, y para P. teocote el cuadrático (M10) con una R2adj=0.87. Ambos modelos describen con precisión la relación alométrica entre el diámetro y la altura en árboles de las especies estudiadas en la región occidental del estado de Tlaxcala.

Abstract Increasing evidence suggests that antibody-drug conjugates (ADCs) can enhance anti-tumor immunity and improve clinical outcome. Here, we elucidate the therapeutic efficacy and immune-mediated mechanisms of a novel HER2-targeting ADC bearing a potent anthracycline derivate as payload (T-PNU) in a human HER2-expressing syngeneic breast cancer model resistant to trastuzumab and ado-trastuzumab emtansine. Mechanistically, the anthracycline component of the novel ADC induced immunogenic cell death leading to exposure and secretion of danger-associated molecular signals. RNA sequencing derived immunogenomic signatures and TCRβ clonotype analysis of tumor-infiltrating lymphocytes revealed a prominent role of the adaptive immune system in the regulation of T-PNU mediated anti-cancer activity. Depletion of CD8 T cells severely reduced T-PNU efficacy, thus confirming the role of cytotoxic T cells as drivers of the T-PNU mediated anti-tumor immune response. Furthermore, T-PNU therapy promoted immunological memory formation in tumor-bearing animals protecting those from tumor rechallenge. Finally, the combination of T-PNU and checkpoint inhibition, such as α-PD1, significantly enhanced tumor eradication following the treatment. In summary, a novel PNU-armed, HER2-targeting ADC elicited long-lasting immune protection in a murine orthotopic breast cancer model resistant to other HER2-directed therapies. Our findings delineate the therapeutic potential of this novel ADC payload and support its clinical development for breast cancer patients and potentially other HER2 expressing malignancies.

We have evaluated cardiac function and fibrosis in infarcted male Wistar rats treated with MitoQ (50 mg/kg/day) or vehicle for 4 weeks. A cohort of patients admitted with a first episode of acute MI were also analyzed with cardiac magnetic resonance and T1 mapping during admission and at a 12-month follow-up. Infarcted animals presented cardiac hypertrophy and a reduction in the left ventricular ejection fraction (LVEF) and E- and A-waves (E/A) ratio when compared to controls. Myocardial infarction (MI) rats also showed cardiac fibrosis and endoplasmic reticulum (ER) stress activation. Binding immunoglobulin protein (BiP) levels, a marker of ER stress, were correlated with collagen I levels. MitoQ reduced oxidative stress and prevented all these changes without affecting the infarct size. The LVEF and E/A ratio in patients with MI were 57.6 ± 7.9% and 0.96 ± 0.34, respectively. No major changes in cardiac function, extracellular volume fraction (ECV), or LV mass were observed at follow-up. Interestingly, the myeloperoxidase (MPO) levels were associated with the ECV in basal conditions. BiP staining and collagen content were also higher in cardiac samples from autopsies of patients who had suffered an MI than in those who had died from other causes. These results show the interactions between mitochondrial oxidative stress and ER stress, which can result in the development of diffuse fibrosis in the context of MI.

Hydrothermally synthesized electrodes of Co3O4@MnO2@NiO/GO were produced for use in supercapacitors. Graphene oxide (GO) was incorporated into the nanocomposites used for electrode synthesis due to its great surface area and electrical conductivity. The synergistic alliance among these composites and GO enhances electrode performance, life span, and stability. The structural properties obtained from the X-ray diffraction (XRD) results suggest that nanocomposites are crystalline in nature. The synergistic alliance among these composites and GO enhances electrode performance, life span, and stability. Performance assessment of these electrodes indicates that their characteristic performance was enhanced by C2+ radiation, with the uttermost performance witnessed for electrodes radiated with 5.0 × 1015 ions/cm2.

Existe en lo profundo de la obra conjunta Deleuze-Guattari la exigencia de considerarla como una teoría política de la literatura, una política literaria. Los párrafos que prosiguen, en cierta medida responden a dicha exigencia, inscriben la micropolítica de Deleuze-Guattari en una concatenación entre las máquinas revolucionarias y artísticas, en este caso, literarias. Considerando esta conjetura, en el presente artículo nos proponemos abordar las relaciones entre el concepto de literatura menor, las dinámicas espaciales (territoriales) y el orden informativo.

New approaches to ovarian stimulation protocols, such as luteal start, random start or double stimulation, allow for flexibility in ovarian stimulation at different phases of the menstrual cycle. It has been proposed that the success of these methods is based on the continuous growth of multiple cohorts (“waves”) of follicles throughout the menstrual cycle which leads to the availability of ovarian follicles for ovarian controlled stimulation at several time points. Though several preliminary studies have been published, their scientific evidence has not been considered as being strong enough to integrate these results into routine clinical practice. This work aims at adding further scientific evidence about the efficiency of variable-start protocols and underpinning the theory of follicular waves by using mathematical modeling and numerical simulations. For this purpose, we have modified and coupled two previously published models, one describing the time course of hormones and one describing competitive follicular growth in a normal menstrual cycle. The coupled model is used to test ovarian stimulation protocols in silico. Simulation results show the occurrence of follicles in a wave-like manner during a normal menstrual cycle and qualitatively predict the outcome of ovarian stimulation initiated at different time points of the menstrual cycle.

El presente trabajo analiza la existencia de regulaciones para las fintech, neobancos y bigtech en el Ecuador; el objetivo es evidenciar la presencia de estas empresas en el país y como se encuentra su regulación. La metodología del estudio es cualitativa y documental bibliográfico. Como resultado, se encontró que en el Ecuador no existe una ley específica para ninguna de las tres figuras antes mencionadas, pero, en la práctica, existen 32 fintech legalmente inscritas en el Sistema de Rentas Internas del Ecuador. Además, se manejaron más de USD 5 millones y treinta mil transacciones durante 2019, considerando solo las reportadas a la Superintendencia de Bancos. Como conclusión se indica que las fintech, neobancos y bigtech dinamizan la economía ecuatoriana y es de vital importancia crear una regulación; para lo cual, se recomienda tener en cuenta tres ejes: 1. conformación y autorización; 2. operación y control; y 3. sanciones y delitos. Se recomienda que estas empresas cuenten con un Oficial de Seguridad de la Información (OSI), pilar fundamental para evitar que se materialicen los riesgos de seguridad de la información.

We show in this article the possibilities of employing an environmentally friendly, uncomplicated, economical and sustainable green synthesis technique effected by natural extracts from waste maize (zea mays lea) materials to synthesize some functional transition single metal oxide nanoparticles (NPs). Copper oxides (Cu2O and CuO), zinc oxide (ZnO), nickel oxide (NiO), chromium oxide (Cr2O3), iron oxide (Fe2O3) and cadmium oxide (CdO) were successfully synthesized using this facile method. Structural characterizations by X-ray diffraction (XRD) for the various oxides show the phases and space groups corresponding to their individual structures. Images from the high resolution transmission electron microscope (HRTEM) revealed various shapes and sizes of the obtained nanoparticles. Results from the attenuated total reflection-Fourier transform infrared (ATR-FTIR) revealed different kinds of functional groups present in the synthesized metal oxide nanoparticles. We showed that the phytochemicals in the natural extracts obtained from the waste materials from Zea mays lea plant is pivotal to the bio-reduction, stabilization and chelation of the metal oxide nanoparticles.

Los restauradores de áreas degradadas requieren de planta de calidad con atributos morfológicos ideales para lograr su establecimiento con éxito en el sitio de la plantación, aun cuando las condiciones del sitio sean adversas. Para conocer la calidad de seis especies de pino que serán empleadas durante la reforestación y restauración de terrenos forestales en el Estado de México, se realizó la evaluación de cinco atributos morfológicos con base en lo citado en la Norma Mexicana NMX-AA-170-SCFI-2016 y un artículo científico en el Vivero Forestal Héroes Bicentenario de Tecámac: diámetro al cuello de la raíz (DC), altura desde la base hasta la yema apical (Alt), índice de esbeltez (IE=Alt/DC), relación biomasa seca aérea y biomasa seca de raíz (BSA/BSR) e índice de calidad de Dickson (ICD). Para DC, los resultados mostraron que todas las especies, excepto Pinus ayacahuite, tuvieron calidad alta. En Alt, P. greggii y P. leiophylla tuvieron la mejor calidad; mientras que en IE, todos los taxones, menos P. greggii, presentaron alta calidad. Para la relación BSA/BSR: P. cembroides, P. ayacahuite y P. hartwegii fueron los mejores, y para ICD, P. hartwegii presentó el mayor valor de calidad. Al considerar todos los indicadores morfológicos juntos, se determinó que P. cembroides y P. greggii registraron la mejor calidad de planta. Esta información es clave para analizar la supervivencia esperada en campo y tomar decisiones oportunas en la gestión forestal.

Introducción: El infarto agudo de miocardio con elevación del ST es una causa importante de mortalidad en Holguín. Objetivo: Estimar factores pronósticos de muerte intrahospitalaria en pacientes con infarto agudo de miocardio con elevación del ST (IAMCEST). Método: Estudio cohorte de personas enfermas en una muestra de 227 pacientes con IAMCEST, a partir del universo de ingresados en la Unidad de Cuidados Intensivos Coronarios del Hospital Vladímir Ilich Lenin, Holguín, Cuba, entre febrero del 2014 y enero del 2015. Se usaron los test diferencia de medias y chi cuadrado en el programa SPSS Statistics. Se determinaron los Odds Ratio (OR) de los factores pronósticos identificados y sus intervalos de confianza de 95% (IC95%), con un nivel de significación de 5% (p

Copper iron sulfide (CFS) (chalcopyrite) thin-film electrodes have been synthesized for energy storage applications using the SILAR method without the use of a binder. The film’s structural as well as the morphological and electrochemical characteristics were studied to check the effect of varying deposition cycles. The x-ray diffraction (XRD) test reveals a crystalline tetragonal CuFeS _2 (chalcopyrite) with a decreasing peak as the deposition cycle progresses. The micrographs of the films reveal a spherical but fleecy-like shape with particle aggregation at higher deposition cycles. The bandgap increased slightly towards higher cycles and is in the range of 1.15 to 1.22 eV. The CFS electrodes were evaluated in a three-electrode arrangement for supercapacitive application in a 2.0 M KOH electrolyte. The CFS electrodes function admirably. The greatest specific capacitance recorded was 537 F g ^−1 at 10 mV s ^−1 with capacitance retention of 93.5%. This is for CFS electrode deposited at 10 cycles; hence it has the greatest performance. This paper describes a simple, inexpensive, and repeatable method for fabricating electrodes for supercapacitors.

 In this study, software that can analyze ship hydrostatics parameters using Java programming language is developed. Ship hydrostatic parameters are properties of the immersed portion of the ship in water. The analyses of ship hydrostatic parameters are done by employing computer software, but the cost of acquiring the license of such expert software is expensive. Owing to this fact, this research was carried out to meet the need of analyzing ship hydrostatics parameters for both academic and industrial applications at marginal expense. Java programming language was adopted for this research because of its outstanding features such as internet security, portability, variety of integrated development environments (IDEs), platform independent and free to download on internet. The mathematical approximation or integration method as a technique for formulating ship hydrostatics parameters was adopted for this research. This is because it has the ability to make use of computer technology and it can be used to obtain the area of a ship and other hydrostatics parameters. The results produced in this research are reasonable and acceptable as evidenced from the comparison analysis with existing results of offsets values of a cargo-passenger vessel obtained from SNAME.Â

Oaxaca es uno de los estados más ricos de México, tanto por su diversidad cultural como biológica, por lo que es importante el estudio e inventario de su biota. Sus habitantes poseen una vasta tradición en la recolección y consumo de hongos silvestres; sin embargo, para incluirlos en los programas de manejo integral de los bosques es necesario conocer sus requerimientos ecológicos y sus características biológicas, así como sus áreas de distribución, lo que implica el mapeo y monitoreo de sus poblaciones silvestres. En este contexto, se planteó sistematizar el conocimiento sobre el hábitat y distribución geográfica de 13 especies de macromicetos comestibles de importancia biológica y socioeconómica asociados a los bosques templados de Oaxaca, mediante el uso de un sistema de información geográfica (SIG), con el fin de generar un mapa de la distribución espacial conocida para dichos taxa, elaborado a partir de información bibliográfica y de herbarios. Las especies recolectadas en una mayor diversidad de ambientes fueron Cantharellus cibarius y Lycoperdon perlatum. A pesar del sesgo generado por la distribución espacial de las recolectas consideradas, ya que estas se concentran en regiones específicas, los SIG son una herramienta útil para determinar la distribución actual de los recursos fúngicos.

Truth, always the embattled realm, is at the core of Ackroydian novels. Its nuances and delineations, its vagaries and fluctuations, make up the crux of Chatterton (1987), a novel which proposes a motley, synoptic construction of truth. Deeply tied with issues of self and self-effacement, it is a destabilizing force, engendering anxiety through its frightening potential, creating a space that negates identity. Under constant threat of rewriting, the self becomes a matter of caprice, seeking footholds in notions of originality and forgery, in obsessions with roots and root causes, to provide a second, more reliable Truth, free from the confines of ambiguity. This is a hermeneutic effort par excellence, in that it enforces a frantic reinterpretation of the past and its artifacts: whether through poet Chatterton or novelist Scrope, ruminations on plagiarism and literary influence suffuse the text, never affording a clear-cut conclusion, offering mere hints in tantalizing directions. My paper will investigate these places of lived tension through the lens of hermeneutic theories, as provided by Paul Ricoeur, Hans-Georg Gadamer, Merold Westphal, David Couzens Hoy, and others, in order to shed light on the precarious interplay of truth and falsehood, and their configurations within the novel.

The surface functionalization of electrospun nanofibers allows for the introduction of additional functionalities while at the same time retaining the membrane properties of high porosity and surface-to-volume ratio. In this work, we sequentially deposited layers of chitosan and alginate to form a polyelectrolyte complex via layer-by-layer assembly on PLGA nanofibers to introduce pH-responsiveness for the controlled release of ibuprofen. The deposition of the polysaccharides on the surface of the fibers was revealed using spectroscopy techniques and ζ-potential measurements. The presence of polycationic chitosan resulted in a positive surface charge (16.2 ± 4.2 mV, pH 3.0) directly regulating the interactions between a model drug (ibuprofen) loaded within the polyelectrolyte complex and the layer-by-layer coating. The release of ibuprofen was slowed down in acidic pH (1.0) compared to neutral pH as a result of the interactions between the drug and the coating. The provided mesh acts as a promising candidate for the design of drug delivery systems required to bypass the acidic environment of the digestive tract.

Intervertebral disc (IVD) degeneration and its medical consequences is still one of the leading causes of morbidity worldwide. To support potential regenerative treatments for degenerated IVDs, we sought to deconvolute the cell composition of the nucleus pulposus (NP) and the annulus fibrosus (AF) of bovine intervertebral discs. Bovine calf tails have been extensively used in intervertebral disc research as a readily available source of NP and AF material from healthy and young IVDs. We used single-cell RNA sequencing (scRNAseq) coupled to bulk RNA sequencing (RNAseq) to unravel the cell populations in these two structures and analyze developmental changes across the rostrocaudal axis. By integrating the scRNAseq data with the bulk RNAseq data to stabilize the clustering results of our study, we identified 27 NP structure/tissue specific genes and 24 AF structure/tissue specific genes. From our scRNAseq results, we could deconvolute the heterogeneous cell populations in both the NP and the AF. In the NP, we detected a notochordal-like cell cluster and a progenitor stem cell cluster. In the AF, we detected a stem cell-like cluster, a cluster with a predominantly fibroblast-like phenotype and a potential endothelial progenitor cluster. Taken together, our results illustrate the cell phenotypic complexity of the AF and NP in the young bovine IVDs.

El proceso de intercepción de lluvia por la masa arbórea, como componente del ciclo hidrológico en áreas forestales, está determinado, entre otras causas, por las condiciones climáticas, orográficas y por las características de la vegetación. Se presentan resultados de un programa de investigación que tiene como objetivo medir las cantidades de lluvia que interceptan tres comunidades forestales, en la cuenca hidrológico-forestal Río Texcoco. Se establecieron tres módulos de investigación con una superficie de 1.0 ha, en bosques de alta montaña ubicados en un intervalo altitudinal de 2 850 a 3 650 msnm. En cada una, se realizaron mediciones dendrométricas: como diámetro normal, altura total y de fuste limpio, de cada árbol a partir de 7.5 cm de diámetro normal. Durante los periodos de lluvia de los años 2009, 2010 y 201, se realizaron mediciones de precipitación, y se determinaron las cantidades de precipitación y su distribución por periodo de lluvias. Para las mediciones de precipitación total, se emplearon dos pluviómetros ubicados fuera los módulos. La intercepción se midió con 75 pluviómetros de lectura directa distribuidos aleatoriamente bajo el dosel. La precipitación-intercepción se registraron por evento de lluvia. Las cantidades interceptadas por las copas de los árboles se expresaron como porcentajes, para cada uno de los grupos estudiados: oyamel (26.1 %), encino (21.7 %) y pino (19.2 %). Se generaron los modelos estadísticos de la relación: precipitación total (mm) - lluvia interceptada (%), para cada grupo.

Stress is a risk factor for impaired general, mental, and reproductive health. The role of physiological and supraphysiological estradiol concentrations in stress perception and stress processing is less well understood. We, therefore, conducted a prospective observational study to investigate the association between estradiol, stress perception, and stress-related cognitive performance within serial measurements either during the natural menstrual cycle or during fertility treatment, where estradiol levels are strongly above the physiological level of a natural cycle, and consequently, represent a good model to study dose-dependent effects of estradiol. Data from 44 women receiving in vitro fertilization (IVF) at the Department of Reproductive Endocrinology in Zurich, Switzerland was compared to data from 88 women with measurements during their natural menstrual cycle. The German version of the Perceived Stress Questionnaire (PSQ) and the Cognitive Bias Test (CBT), in which cognitive performance is tested under time stress were used to evaluate subjective and functional aspects of stress. Estradiol levels were investigated at four different time points during the menstrual cycle and at two different time points during a fertility treatment. Cycle phases were associated with PSQ worry and cognitive bias in normally cycling women, but different phases of fertility treatment were not associated with subjectively perceived stress and stress-related cognitive bias. PSQ lack of joy and PSQ demands related to CBT in women receiving fertility treatment but not in women with a normal menstrual cycle. Only strong changes of the estradiol level during fertility treatment were weakly associated with CBT, but not with subjectively experienced stress. Our research emphasizes the multidimensional character of stress and the necessity to adjust stress research to the complex nature of stress perception and processing. Infertility is associated with an increased psychological burden in patients. However, not all phases of the process to overcome infertility do significantly increase patient stress levels. Also, research on the psychological burden of infertility should consider that stress may vary during the different phases of fertility treatment.Clinical trial registration: ClinicalTrials.gov # NCT02098668.

Receptor tyrosine kinase-like orphan receptor 2 (ROR2) has been identified as a highly relevant tumor-associated antigen in a variety of cancer indications of high unmet medical need, including renal cell carcinoma and osteosarcoma, making it an attractive target for targeted cancer therapy. Here, we describe the de novo discovery of fully human ROR2-specific antibodies and potent antibody drug conjugates (ADCs) derived thereof by combining antibody discovery from immune libraries of human immunoglobulin transgenic animals using the Transpo-mAb mammalian cell-based IgG display platform with functional screening for internalizing antibodies using a secondary ADC assay. The discovery strategy entailed immunization of transgenic mice with the cancer antigen ROR2, harboring transgenic IgH and IgL chain gene loci with limited number of fully human V, D, and J gene segments. This was followed by recovering antibody repertoires from the immunized animals, expressing and screening them as full-length human IgG libraries by transposon-mediated display in progenitor B lymphocytes (“Transpo-mAb Display”) for ROR2 binding. Individual cellular “Transpo-mAb” clones isolated by single cell sorting and capable of expressing membrane-bound as well as secreted human IgG were directly screened during antibody discovery, not only for high affinity binding to human ROR2, but also functionally as ADCs using a cytotoxicity assay with a secondary anti-human IgG-toxin-conjugate. Using this strategy, we identified and validated 12 fully human, monoclonal anti-human ROR2 antibodies with nanomolar affinities that are highly potent as ADCs and could be promising candidates for the therapy of human cancer. The screening for functional and internalizing antibodies during the early phase of antibody discovery demonstrates the utility of the mammalian cell-based Transpo-mAb Display platform to select for functional binders and as a powerful tool to improve the efficiency for the development of therapeutically relevant ADCs.

We introduce a new benchtop microgravity simulator (MGS) that is scalable and easy to use. Its working principle is similar to that of random positioning machines (RPM), commonly used in research laboratories and regarded as one of the gold standards for simulating microgravity. The improvement of the MGS concerns mainly the algorithms controlling the movements of the samples and the design that, for the first time, guarantees equal treatment of all the culture flasks undergoing simulated microgravity. Qualification and validation tests of the new device were conducted with human bone marrow stem cells (bMSC) and mouse skeletal muscle myoblasts (C2C12). bMSC were cultured for 4 days on the MGS and the RPM in parallel. In the presence of osteogenic medium, an overexpression of osteogenic markers was detected in the samples from both devices. Similarly, C2C12 cells were maintained for 4 days on the MGS and the rotating wall vessel (RWV) device, another widely used microgravity simulator. Significant downregulation of myogenesis markers was observed in gravitationally unloaded cells. Therefore, similar results can be obtained regardless of the used simulated microgravity devices, namely MGS, RPM, or RWV. The newly developed MGS device thus offers easy and reliable long-term cell culture possibilities under simulated microgravity conditions. Currently, upgrades are in progress to allow real-time monitoring of the culture media and liquids exchange while running. This is of particular interest for long-term cultivation, needed for tissue engineering applications. Tissue grown under real or simulated microgravity has specific features, such as growth in three-dimensions (3D). Growth in weightlessness conditions fosters mechanical, structural, and chemical interactions between cells and the extracellular matrix in any direction.

Nanocomposite films grown by incorporating varying concentrations of Yttrium, a d-block rare-earth ion, into the binary chalcogenide Arsenic selenide host matrix is here presented. Films were grown via the wet-chemical electro-deposition technique and characterized for structural, optical, surface morphology, and photoluminescence (PL) properties. The X-ray Diffraction (XRD) result of the host matrix (pristine film) showed films of monoclinic structure with an average grain size of 36.2 nm. The composite films, on the other hand, had both cubic YAs and tetragonal YSe structures with average size within 36.5–46.8 nm. The fairly homogeneous nano-sized films are shown by the Scanning Electron Microscopy (SEM) micrographs while the two phases of the composite films present in the XRD patterns were confirmed by the Raman shifts due to the cleavage of the As-Se host matrix and formation of new structural units. The refractive index peaked at 2.63 within 350–600 nm. The bandgap energy lies in the range of 3.84–3.95 eV with a slight decrease with increasing Y addition; while the PL spectra depict emission bands across the Vis-NIR spectral regions. Theoretically, the density functional theory (DFT) simulations provided insight into the changes induced in the structure, bonding, and electronic properties. Besides reducing the bandgap of the As2Se3, the yttrium addition has induced a lone pair p-states of Se contributing nearby to Fermi energy level. The optical constants, and structural and electronic features of the films obtained present suitable features of film for IR applications as well as in optoelectronics.

The impact of the mitochondria-targeted antioxidant MitoQ was evaluated in the cardiac alterations associated with obesity. Male Wistar rats were fed either a high fat diet (HFD, 35% fat) or a standard diet (CT, 3.5% fat) for 7 weeks and treated with MitoQ (200 µM). The effect of MitoQ (5 nM) in rat cardiac myoblasts treated for 24 h with palmitic acid (PA, 200 µM) was evaluated. MitoQ reduced cardiac oxidative stress and prevented the development of cardiac fibrosis, hypertrophy, myocardial 18-FDG uptake reduction, and mitochondrial lipid remodeling in HFD rats. It also ameliorated cardiac mitochondrial protein level changes observed in HFD: reductions in fumarate hydratase, complex I and II, as well as increases in mitofusin 1 (MFN1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha, and cyclophilin F (cycloF). In vitro, MitoQ prevented oxidative stress and ameliorated alterations in mitochondrial proteins observed in palmitic acid (PA)-stimulated cardiac myoblasts: increases in carnitine palmitoyltransferase 1A, cycloF, and cytochrome C. PA induced phosphorylation of extracellular signal-regulated kinases and nuclear factor-κB p65. Therefore, the data show the beneficial effects of MitoQ in the cardiac damage induced by obesity and suggests a crosstalk between lipotoxicity and mitochondrial oxidative stress in this damage

This research focus on the Influence of Dopant Concentration on Polycrystalline Ytterbium-doped ZrSe (Yb-ZrSe) material for possible photovoltaic application using the electrochemical deposition method. The cationic precursor was an aqueous solution of 0.01 mol ZrOCl _2 .8H _2 O while the anionic precursor was 0.15 mol selenium was prepared by dissolving with 5 ml of Hydrochloric acid (HCl), and then 0.05 mol Yb (NO _3 ) _3 .5H _2 O was used as the dopant. The films were characterized using UV-1800 Visible Spectrophotometer, Bruker D8 Advance x-ray diffractometer with Cu K α line ( λ = 1.54056 Å) in 2 θ range from 10°–90°and Scanning Electron Microscopy. X-ray diffraction (XRD) of the deposited films on FTO substrate studies reveals that films are polycrystalline by exhibiting diffraction peaks at (111), (200), (200) and (210) corresponds to the following angle (27.00°), (38.01°), (46.02°), (66.02°). (SEM) revealed that the grain size was uniformly distributed on the surface of the substrate. The optical band gap energy $2.29-1.57\,{\rm{eV}}$ was obtained.

Introduction: Since M-mode measurements can assess deformation of specific regions of the left ventricle, we hypothesized that M-mode measurements like M-mode apical systolic excursion (MMASE) and mitral annular plane systolic excursion (MAPSE) may be correlated with left ventricular longitudinal strain (LVLS). Methods: All subjects of the study underwent a full echocardiographic evaluation and MMASE and MAPSE measurement. Three-dimensional wall motion tracking (3D-WMT) was performed. Results: Thirty-one patients were evaluated. Significant correlations between MAPSE and LVLS (−0.372; p=0.04) and between MMASE and LVLS (−0.398; p=0.027) were found. LVLS was linearly related to MAPSE and MMASE (in mm) as follows: ST=−10.6 −0.4 * MAPSE (r2=0.14) and ST=−13.1 −0.5 * MMASE (r2=0.16). Conclusions: Our results demonstrate that simpler and faster methods than strain based on complex speckle analysis can also have a role in predicting subclinical left ventricular systolic dysfunction. Resumo: Introdução: Uma vez que as medições em Modo-M podem determinar a deformação de regiões específicas do ventrículo esquerdo, neste trabalho é colocada a hipótese de que medidas como a excursão sistólica apical em modo-M (MMASE) e a MAPSE podem ser correlacionadas com o Strain Longitudinal do Ventrículo Esquerdo (SLVE). Métodos: Todos os indivíduos do estudo foram submetidos a uma avaliação ecocardiográfica completa, à medição da MMASE e da MAPSE. Foi ainda realizado o 3D-wall motion tracking (3D-WMT). Resultados: Foram avaliados 31 pacientes, tendo sido obtida uma correlação estatisticamente significativa entre a MAPSE e o SLVE (−0.372; p=0.04) e entre a MMASE e o SLVE (−0,398; p=0,027). Estas medidas apresentaram uma correlação linear: ST=−10,6 -0,4 * MAPSE (r2=0.14) and ST=−13,1 −0,5 * MMASE (r2=0,16). Conclusão: Os nossos resultados demonstram que métodos mais simples e rápidos que o strain podem também ser úteis na determinação da disfunção subclínica sistólica do ventrículo esquerdo. Keywords: M-mode echocardiography, Longitudinal strain, 3D wall motion tracking, Palavras-chave: Ecocardiograma Modo-M, Strain longitudinal, 3D wall motion tracking

Background: Interpretation of observational studies on associations between prefrontal cognitive functioning and hormone levels across the female menstrual cycle is complicated due to small sample sizes and poor replicability.Methods: This observational multisite study comprised data of n = 88 menstruating women from Hannover, Germany, and Zurich, Switzerland, assessed during a first cycle and n = 68 re-assessed during a second cycle to rule out practice effects and false-positive chance findings. We assessed visuospatial working memory, attention, cognitive bias and hormone levels at four consecutive time-points across both cycles. In addition to inter-individual differences we examined intra-individual change over time (i.e., within-subject effects).Results: Estrogen, progesterone and testosterone did not relate to inter-individual differences in cognitive functioning. There was a significant negative association between intra-individual change in progesterone and change in working memory from pre-ovulatory to mid-luteal phase during the first cycle, but that association did not replicate in the second cycle. Intra-individual change in testosterone related negatively to change in cognitive bias from menstrual to pre-ovulatory as well as from pre-ovulatory to mid-luteal phase in the first cycle, but these associations did not replicate in the second cycle.Conclusions: There is no consistent association between women's hormone levels, in particular estrogen and progesterone, and attention, working memory and cognitive bias. That is, anecdotal findings observed during the first cycle did not replicate in the second cycle, suggesting that these are false-positives attributable to random variation and systematic biases such as practice effects. Due to methodological limitations, positive findings in the published literature must be interpreted with reservation.

Due to the limited self-repair capacity of articular cartilage, the surgical restoration of defective cartilage remains a major clinical challenge. The cell-based approach, which is known as autologous chondrocyte transplantation (ACT), has limited success, presumably because the chondrocytes acquire a fibroblast-like phenotype in monolayer culture. This unwanted dedifferentiation process is typically addressed by using three-dimensional scaffolds, pellet culture, and/or the application of exogenous factors. Alternative mechanical unloading approaches are suggested to be beneficial in preserving the chondrocyte phenotype. In this study, we examined if the random positioning machine (RPM) could be used to expand chondrocytes in vitro such that they maintain their phenotype. Bovine chondrocytes were exposed to (a) eight days in static monolayer culture; (b) two days in static monolayer culture, followed by six days of RPM exposure; and, (c) eight days of RPM exposure. Furthermore, the experiment was also conducted with the application of 20 mM gadolinium, which is a nonspecific ion-channel blocker. The results revealed that the chondrocyte phenotype is preserved when chondrocytes go into suspension and aggregate to cell clusters. Exposure to RPM rotation alone does not preserve the chondrocyte phenotype. Interestingly, the gene expression (mRNA) of the mechanosensitive ion channel TRPV4 decreased with progressing dedifferentiation. In contrast, the gene expression (mRNA) of the mechanosensitive ion channel TRPC1 was reduced around fivefold to 10-fold in all of the conditions. The application of gadolinium had only a minor influence on the results. This and previous studies suggest that the chondrocyte phenotype is preserved if cells maintain a round morphology and that the ion channel TRPV4 could play a key role in the dedifferentiation process.

Here, we describe a method enabling the phenotypic profiling of genome-scale deletion collections of fungal mutants to detect phenotypes for various stress conditions. These stress conditions include among many others antifungal drug susceptibility, temperature-induced and osmotic as well as heavy metal or oxidative stress. The protocol was extensively used to phenotype a collection of gene deletion mutants in the human fungal pathogen Candida glabrata (C. glabrata) (Schwarzmüller et al., 2014).

Here, we report a method for the transformation of Candida glabrata using a heat shock method. The protocol can be used for transformations in single well or in 96-well scale. It has been employed as an alternative method to the electroporation protocol to construct a genome-scale gene deletion collection in the human fungal pathogen Candida glabrata ATCC2001 and related strains. Furthermore, the protocol can be used to generate gene deletions in clinical isolates of Candida glabrata (C. glabrata).

Here, we report a method for the transformation by electroporation of the human fungal pathogen Candida glabrata (C. glabrata). The protocol can be used for transformations in single well or in 96-well microtiter plates. It has been extensively used to generate a genome-scale gene deletion library using the C. glabrata background recipient strain ATCC2001 (Schwarzmüller et al., 2014).

The objective of the study was to evaluate the implications of different classifications of rheumatic heart disease on estimated prevalence, and to systematically assess the importance of incidental findings from echocardiographic screening among schoolchildren in Peru.We performed a cluster randomized observational survey using portable echocardiography among schoolchildren aged 5 to 16 years from randomly selected public and private schools in Arequipa, Peru. Rheumatic heart disease was defined according to the modified World Health Organization (WHO) criteria and the World Heart Federation (WHF) criteria.Among 1395 eligible students from 40 classes and 20 schools, 1023 (73%) participated in the present survey. The median age of the children was 11 years (interquartile range [IQR] 8-13 years) and 50% were girls. Prevalence of possible, probable and definite rheumatic heart disease according to the modified WHO criteria amounted to 19.7/1000 children and ranged from 10.2/1000 among children 5 to 8 years of age to 39.8/1000 among children 13 to 16 years of age; the prevalence of borderline/definite rheumatic heart disease according to the WHF criteria was 3.9/1000 children. 21 children (2.1%) were found to have congenital heart disease, 8 of which were referred for percutaneous or surgical intervention.Prevalence of RHD in Peru was considerably lower compared to endemic regions in sub-Saharan Africa, southeast Asia, and Oceania; and paralleled by a comparable number of undetected congenital heart disease. Strategies to address collateral findings from echocardiographic screening are necessary in the setup of active surveillance programs for RHD.ClinicalTrials.gov identifier: NCT02353663.

Virulent Agrobacterium tumefaciens strains integrate their T-DNA into the plant genome where the encoded agrobacterial oncogenes are expressed and cause crown gall disease. Essential for crown gall development are IaaH (indole-3-acetamide hydrolase), IaaM (tryptophan monooxygenase) and Ipt (isopentenyl transferase), which encode enzymes for the biosynthesis of auxin (IaaH, IaaM) and cytokinin (Ipt). Although these oncogenes are well studied as the tumor-inducing principle, nothing is known about the regulation of oncogene expression in plant cells. Our studies show that the intergenic regions (IGRs) between the coding sequences (CDS) of the three oncogenes function as promoters in plant cells. These promoters possess a eukaryotic sequence organization and cis-regulatory elements for the binding of plant transcription factors. WRKY18, WRKY40, WRKY60 and ARF5 were identified as activators of the Ipt promoter whereas IaaH and IaaM is constitutively expressed and no transcription factor further activates their promoters. Consistent with these results, the wrky triple mutant plants in particular, develops smaller crown galls than wild-type and exhibits a reduced Ipt transcription, despite the presence of an intact ARF5 gene. WRKY40 and WRKY60 gene expression is induced by A. tumefaciens within a few hours whereas the ARF5 gene is transcribed later during crown gall development. The WRKY proteins interact with ARF5 in the plant nucleus, but only WRKY40 together with ARF5 synergistically boosts the activation of the Ipt promoter in an auxin-dependent manner. From our data, we propose that A. tumefaciens initially induces WRKY40 gene expression as a pathogen defense response of the host cell. The WRKY protein is recruited to induce Ipt expression, which initiates cytokinin-dependent host cell division. With increasing auxin levels triggered by ubiquitous expression of IaaH and IaaM, ARF5 is activated and interacts with WRKY40 to potentiate Ipt expression and balance cytokinin and auxin levels for further cell proliferation.

Tec family kinases are intracellular non-receptor tyrosine kinases implicated in numerous functions, including T cell and B cell regulation. However, a role in microbial pathogenesis has not been described. Here, we identified Tec kinase as a novel key mediator of the inflammatory immune response in macrophages invaded by the human fungal pathogen C. albicans. Tec is required for both activation and assembly of the noncanonical caspase-8, but not of the caspase-1 inflammasome, during infections with fungal but not bacterial pathogens, triggering the antifungal response through IL-1β. Furthermore, we identify dectin-1 as the pathogen recognition receptor being required for Syk-dependent Tec activation. Hence, Tec is a novel innate-specific inflammatory kinase, whose genetic ablation or inhibition by small molecule drugs strongly protects mice from fungal sepsis. These data demonstrate a therapeutic potential for Tec kinase inhibition to combat invasive microbial infections by attenuating the host inflammatory response.

Michael Kinori1, Iris Moroz1,2, Ygal Rotenstreich1,2, Hagith Yonath2,3, Ido Didi Fabian1, Vicktoria Vishnevskia-Dai1,21Department of Ophthalmology, Chaim Sheba Medical Center, Tel Hashomer, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Danek Gertner Genetic Institute and Internal Medicine A, Chaim Sheba Medical Center, Tel Hashomer, IsraelAbstract: Retinal astrocytic hamartomas are benign intraocular tumors classically associated with phacomatoses. Their appearance in isolation is rare. An association between astrocytic hamartomas and retinitis pigmentosa (RP) has been described previously, but controversy still exists regarding the precise nature of these lesions in RP patients. The authors present a case report of a 24-year-old male with RP and multiple bilateral lesions clinically consistent with retinal astrocytic hamartomas. Optical coherence tomography revealed multiple bilateral hyper-reflective intraretinal masses, loss of retinal architecture, intralesional calcifications, and prominent optical posterior shadowing. Comprehensive systemic evaluation was negative for phacomatoses. However, given that a biopsy was not performed, the diagnosis of optic nerve head drusen could not be excluded.Keywords: giant drusen, optic nerve head drusen, optical coherence tomography, intraocular tumor