Photorefractive nonlinear propagation of single beams in undoped LiNbO3: Self-defocusing and beam break-up

Beam propagation in photorefractive LiNbO3 planar waveguides has been studied at different beam intensities and propagation lengths. Self-defocusing and beam break-up have been observed and explained using BPM simulations under a 2-centre band transport model

Arteriovenous uterine malformation: case report

The case of a 49-year-old patient is reported, with a particular history of obstetric risk, who presented with severe transvaginal hemorrhage, was performed doppler arteriography and ultrasound, finding data suggestive of arteriovenous uterine malformation, surgery was decided due to heavy menstrual bleeding with anemia, the pathology report shows characteristics of an arteriovenous uterine malformation

Noninvasive detection of microsatellite instability in patients with endometrial cancer

Endometrial cancer; Liquid biopsy; Uterine aspirateCàncer d'endometri; Biòpsia líquida; Aspirat uteríCáncer de endometrio; Biopsia líquida; Aspirado uterinoThe analysis of mismatch repair proteins in solid tissue is the standard of care (SoC) for the microsatellite instability (MSI) characterization in endometrial cancer (EC). Uterine aspirates (UAs) or circulating-DNA (cfDNA) samples capture the intratumor heterogeneity and provide a more comprehensive and dynamic molecular diagnosis. Thus, MSI analysis by droplet-digital PCR (ddPCR) in UAs and cfDNA can provide a reliable tool to characterize and follow-up the disease. The UAs, paraffin-embedded tumor tissue (FFPE) and longitudinal plasma samples from a cohort of 90 EC patients were analyzed using ddPCR panel and compared to the SoC. A high concordance (96.67%) was obtained between the analysis of MSI markers in UAs and the SoC. Three discordant cases were validated as unstable by ddPCR on FFPE samples. Besides, a good overall concordance (70.27%) was obtained when comparing the performance of the ddPCR assay on UAs and cfDNA in high-risk tumors. Importantly, our results also evidenced the value of MSI analysis to monitor the disease evolution. MSI evaluation in minimally invasive samples shows great accuracy and sensitivity and provides a valuable tool for the molecular characterization and follow-up of endometrial tumors, opening new opportunities for personalized management of EC.Centro de Investigación Biomédica en Red de Cáncer, Grant/Award Numbers: CB16/12/00295, CB16/12/00328; Fundación Científica Asociación Española Contra el Cáncer, Grant/Award Numbers: FC_AECC PROYE19036MOR, 2018-AECC, INVES20051COLA; Fundación Instituto de Investigación Sanitaria de Santiago de Compostela; Instituto de Salud Carlos III and FEDER, Grant/Award Numbers: CM19/00087, CP20/00119, PI20/00969, PI20/01566, PI21/00990; Spanish Ministry of Economy and Innovation, Grant/Award Number: PID2019-104644RB-I0

Low-latitude equinoctial spread-F occurrence at different longitude sectors under low solar activity

We present the results of a comparative study of spread-F signatures over five low-latitude sites: Chiangmai (CGM; 18.8° N, 98.9° E, mag. Lat. 8.8° N), Thailand; Tanjungsari (TNJ; 6.9° S, 107.6° E, mag. Lat. 16.9° S), Indonesia; Palmas (PAL; 10.2° S, 311.8° E, mag. Lat. 0.9° S) and São José Dos Campos (SJC; 23.2° S, 314.1° E, mag. Lat. 14.0° S), Brazil; and Tucumán (TUC; 26.9° S, 294.6° E, mag. Lat. 16.8° S), Argentina. The investigation was based on simultaneous ionograms recorded by an FMCW (frequency-modulated continuous-wave) at CGM, an IPS-71 (digital ionosonde from KEL aerospace) at TNJ, a CADI (Canadian Advanced Digital Ionosonde) at PAL and SJC, and an AIS-INGV (Advanced Ionospheric Sounder – Istituto Nazionale di Geofisica e Vulcanologia) at TUC, during the equinoctial periods March–April (R12 = 2.0 and R12 = 2.2) and September–October (R12 = 6.1 and R12 = 7.0) 2009, for very low solar activity. Spread-F signatures were categorized into two types: the range spread-F (RSF) and the frequency spread-F (FSF). The study confirms that the dynamics and the physical processes responsible for these phenomena are actually complicated. In fact, the features that arise from the investigation are different, depending on both the longitude sector and on the hemisphere. For instance, TUC, under the southern crest of the ionospheric equatorial ionization anomaly (EIA), shows a predominance of RSF signatures, while both SJC, under the southern crest of EIA but in a different longitude sector, and CGM, under the northern crest of EIA, show a predominance of FSF signatures. Moreover, the spread-F occurrence over the longitude sector that includes CGM and TNJ is significantly lower than the spread-F occurrence over the longitude sector of PAL, SJC, and TUC.Fil: Pezzopane, M.. Istituto Nazionale Di Geofisica E Vulcanologia; Italia;Fil: Zuccheretti, E.. Istituto Nazionale Di Geofisica E Vulcanologia; Italia;Fil: Abadi, P.. Indonesian National Institute of Aeronautics and Space. Space Science Center. Division of Ionosphere and Telecommunication; Indonesia;Fil: de Abreu, A. J.. Universidade do Vale do Paraíba; Brazil;Fil: de Jesus, R.. Universidade do Vale do Paraíba; Brazil;Fil: Fagundes, P. R.. Universidade do Vale do Paraíba; Brazil;Fil: Supnithi, P.. King Mongkut’s Institute of Technology Ladkrabang . Faculty of Engineering; Tailandia;Fil: Rungraengwajiake, S.. King Mongkut’s Institute of Technology Ladkrabang . Faculty of Engineering; Tailandia;Fil: Nagatsuma, T.. National Institute of Information and Communications Technology. Space Weather and Environment Informatics Laboratory; Japón;Fil: Tsugawa, T.. National Institute of Information and Communications Technology. Space Weather and Environment Informatics Laboratory; Japón;Fil: Cabrera, Miguel Angel. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Física. Laboratorio de Ionosfera; Argentina; Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Electricidad, Electrónica y Computación. Laboratorio de Telecomunicaciones; Argentina; Universidad Tecnológica Nacional. Facultad Regional Tucumán. Centro de Investigación de Atmósfera Superior y Radiopropagación; Argentina;Fil: Ezquer, Rodolfo Gerardo. Universidad Tecnológica Nacional. Facultad Regional Tucumán. Centro de Investigación de Atmósfera Superior y Radiopropagación; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina; Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Física. Laboratorio de Ionosfera; Argentina

"Bioadsorption of silver ions by calcareous chitin, chitin and chitosan"

"Context: Calcareous chitin, chitin, chitosan, and their modifications are used as bioadsorbents of metals and dyes that cause environmental pollution, endocrine disruption, and human diseases. Aims: To evaluate the selective bioadsorption of silver ions (Ag+ ) by calcareous chitin, chitin, and chitosan. Methods: Experimental and prospective study. The presence of functional groups of the bioadsorbents was identified by Fourier-transformed infrared spectroscopy (FT-IR), 1H-NMR spectroscopy and scanning electron microscopy (SEM). The Langmuir, Freundlich, and Elovich models were applied to describe the adsorption capacity of bioadsorbents according to granule size (20-40, 40-60, 60-80 meshes) and temperature (10, 20, and 30°C). Results: The FT-IR spectrum of calcareous chitin indicates the presence of carbonate (CO3 = 1420 cm-1 ), amide III (1313 cm-1 ), –OH groups (3441.90 cm-1 ), and pyranose structure (952.83 cm-1 ); chitin has –OH groups (3441.90 cm-1 ), NH (3268 cm-1 ), amide I (1654 cm-1 ) and II (1559 cm-1 ); chitosan has –OH groups (3419.90 cm-1 ), –NH (3200 cm-1 ), amide I (1712.18 cm-1 ), –NH2 (1654.46 cm-1 ), amide III (1317.11 cm-1 ) and pyranose structure (1070.12 cm-1 and 1031 cm-1 ). The Langmuir model indicates greater bioadsorption of Ag+ ions at smaller particle sizes (60-80 = 0.25-0.18 mm) and at a temperature of 20-30°C. Conclusions: The bioadsorption of silver ions (Ag+ ) by chitosan is greater with respect to calcareous chitin and chitin; the Langmuir model fits for the Ag+ isotherm and suggests that the process is controlled by physisorption.

Coral Reef Resilience Index for Novel Ecosystems: A Spatial Planning Tool for Managers and Decision Makers - A Case Study from Puerto Rico

Timely information is critical for coral reef managers and decision-makers to implement sustainable management measures. A Coral Reef Resilience Index (CRRI) was developed with a GIS-coupled decision-making tool applicable for Caribbean coral reef ecosystems. The CRRI is based on a five-point scale parameterized from the quantitative characterization of benthic assemblages. Separate subindices such as the Coral Index, the Threatened Species Index, and the Algal Index also provide specific information regarding targeted benthic components. This case study was based on assessments conducted in 2014 on 11 reef sites located across 3 geographic zones and 3 depth zones along the southwestern shelf of the island of Puerto Rico, Caribbean Sea. There was a significant spatial and bathymetric gradient (p < 0.05) in the distribution of CRRI values indicating higher degradation of inshore reefs. Mean global CRRI ranged from 2.78 to 3.17 across the shelf, ranking them as “fair.” The Coral Index ranged from 2.60 to 3.76, ranking reefs from “poor” to “good,” showing a general cross-shelf trend of improving conditions with increasing distance from pollution sources. Turbidity and ammonia were significantly correlated to CRRI scores. Multiple recommendations are provided based on coral reef conditions according to observed CRRI rankings

Pranlukast Antagonizes CD49f and Reduces Sternness in Triple-Negative Breast Cancer Cells

Introduction: Cancer stem cells (CSCs) drive the initiation, maintenance, and therapy response of breast tumors. CD49f is expressed in breast CSCs and functions in the maintenance of stemness. Thus, blockade of CD49f is a potential therapeutic approach for targeting breast CSCs. In the present study, we aimed to repurpose drugs as CD49f antagonists. Materials and Methods: We performed consensus molecular docking using a subdomain of CD49f that is critical for heterodimerization and a collection of pharmochemicals clini-cally tested. Molecular dynamics simulations were employed to further characterize drug-target binding. Using MDA-MB-231 cells, we evaluated the effects of potential CD49f antagonists on 1) cell adhesion to laminin; 2) mammosphere formation; and 3) cell viability. We analyzed the effects of the drug with better CSC-selectivity on the activation of CD49f-downstream signaling by Western blot (WB) and co-immunoprecipitation. Expressions of the stem cell markers CD44 and SOX2 were analyzed by flow cytometry and WB, respectively. Transactivation of SOX2 promoter was evaluated by luciferase reporter assays. Changes in the number of CSCs were assessed by limiting-dilution xenotransplantation. Results: Pranlukast, a drug used to treat asthma, bound to CD49f in silico and inhibited the adhesion of CD49f+ MDA-MB-231 cells to laminin, indicating that it antagonizes CD49f-containing integrins. Molecular dynamics analysis showed that pranlukast binding induces con-formational changes in CD49f that affect its interaction with β1-integrin subunit and constrained the conformational dynamics of the heterodimer. Pranlukast decreased the clonogenicity of breast cancer cells on mammosphere formation assay but had no impact on the viability of bulk tumor cells. Brief exposure of MDA-MB-231 cells to pranlukast altered CD49f-dependent signaling, reducing focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K) activation. Further, pranlukast-treated cells showed decreased CD44 and SOX2 expression, SOX2 promoter transacti-vation, and in vivo tumorigenicity, supporting that this drug reduces the frequency of CSC. Conclusion: Our results support the function of pranlukast as a CD49f antagonist that reduces the CSC population in triple-negative breast cancer cells. The pharmacokinetics and toxicology of this drug have already been established, rendering a potential adjuvant therapy for breast cancer patients

IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System

PURPOSE: To improve persistence of adoptively transferred T-cell receptor (TCR)-engineered T cells and durable clinical responses, we designed a clinical trial to transplant genetically-modified hematopoietic stem cells (HSCs) together with adoptive cell transfer of T cells both engineered to express an NY-ESO-1 TCR. Here, we report the preclinical studies performed to enable an investigational new drug (IND) application. EXPERIMENTAL DESIGN: HSCs transduced with a lentiviral vector expressing NY-ESO-1 TCR and the PET reporter/suicide gene HSV1-sr39TK and T cells transduced with a retroviral vector expressing NY-ESO-1 TCR were coadministered to myelodepleted HLA-A2/Kb mice within a formal Good Laboratory Practice (GLP)-compliant study to demonstrate safety, persistence, and HSC differentiation into all blood lineages. Non-GLP experiments included assessment of transgene immunogenicity and in vitro viral insertion safety studies. Furthermore, Good Manufacturing Practice (GMP)-compliant cell production qualification runs were performed to establish the manufacturing protocols for clinical use. RESULTS: TCR genetically modified and ex vivo-cultured HSCs differentiated into all blood subsets in vivo after HSC transplantation, and coadministration of TCR-transduced T cells did not result in increased toxicity. The expression of NY-ESO-1 TCR and sr39TK transgenes did not have a detrimental effect on gene-modified HSC's differentiation to all blood cell lineages. There was no evidence of genotoxicity induced by the lentiviral vector. GMP batches of clinical-grade transgenic cells produced during qualification runs had adequate stability and functionality. CONCLUSIONS: Coadministration of HSCs and T cells expressing an NY-ESO-1 TCR is safe in preclinical models. The results presented in this article led to the FDA approval of IND 17471