Overlay Accuracy Limitations of Soft Stamp UV Nanoimprint Lithography and Circumvention Strategies for Device Applications

In this work multilevel pattering capabilities of Substrate Conformal Imprint Lithography (SCIL) have been explored. A mix & match approach combining the high throughput of nanoimprint lithography with the excellent overlay accuracy of electron beam lithography (EBL) has been exploited to fabricate nanoscale devices. An EBL system has also been utilized as a benchmarking tool to measure both stamp distortions and alignment precision of this mix & match approach. By aligning the EBL system to 20 mm x 20 mm and 8 mm x 8 mm cells to compensate pattern distortions of order of $3 \mu m$ over 6 inch wafer area, overlay accuracy better than $1.2 \mu m$ has been demonstrated. This result can partially be attributed to the flexible SCIL stamp which compensates deformations caused by the presence of particles which would otherwise significantly reduce the alignment precision

Memoria 1987

La memoria que presentamos trata de significar, con criterios lo más objetivos posible, los hechos más destacados de la actividad científica y técnica del CSIC a lo largo del año 1987 El hecho más destacado del año es sin duda la aprobación del Programa Sectorial del CSIC por la Junta de Gobierno, en su reunión del día 8 de Mayo. Este Programa enlaza con las anteriores programaciones trianuales que han enmarcado la actividad del Organismo durante 1982-1984 y 1985-1987, y su objetivo es contribuir, mediante la investigación científica y el desarrollo tecnológico, a la consecución de los objetivos de interés general que establece el artículo 2 de la Ley de la Ciencia. También merece señalarse la creación de la Oficina de Relaciones con la Comunidad Económica Europea, adscrita al Gabinete de Estudios de la Presidencia, que obedece a la necesidad de canalizar la participación del CSIC en el Programa Marco 1 y D de la Comunidad Europea. En el mes de Diciembre se fallaron los Premios de Periodismo Científico, en su segunda edición; galardones que fueron creados el año anterior para reconocer la labor de los profesionales de la información, —personas y empresas periodísticas—, que han realizado una tarea relevante en el campo de la divulgación científica y técnica en los medios de comunicación españoles. Por último, cabe reseñar que toda la documentación recogida en esta publicación se ha dividido en dos partes bien diferenciadas. En la primera, que tiene un carácter más conceptual, se exponen datos globales relativos a la información general del organismo, en tanto que la segunda parte —con datos más individualizados—, se dedica exclusivamente a la información o actividad científica acontecida en los distintos Centros o Institutos.N

Angiotensin II AT1 Receptor Blockade Changes Expression of Renal Sodium Transporters in Rats with Chronic Renal Failure

We aimed to examine the effects of angiotensin II AT1 receptor blocker on the expression of major renal sodium transporters and aquaporin-2 (AQP2) in rats with chronic renal failure (CRF). During 2 wks after 5/6 nephrectomy or sham operation, both CRF rats (n=10) and sham-operated control rats (n=7) received a fixed amount of low sodium diet and had free access to water. CRF rats (n=10) were divided into two groups which were either candesartan-treated (CRF-C, n=4) or vehicletreated (CRF-V, n=6). Both CRF-C and CRF-V demonstrated azotemia, decreased GFR, polyuria, and decreased urine osmolality compared with sham-operated rats. When compared with CRF-V, CRF-C was associated with significantly higher BUN levels and lower remnant kidney weight. Semiquantitative immunoblotting demonstrated decreased AQP2 expression in both CRF-C (54% of control levels) and CRF-V (57%), whereas BSC-1 expression was increased in both CRF groups. Particularly, CRF-C was associated with higher BSC-1 expression (611%) compared with CRF-V (289%). In contrast, the expression of NHE3 (25%) and TSC (27%) was decreased in CRF-C, whereas no changes were observed in CRF-V. In conclusion, 1) candesartan treatment in an early phase of CRF is associated with decreased renal hypertrophy and increased BUN level; 2) decreased AQP2 level in CRF is likely to play a role in the decreased urine concentration, and the downregulation is not altered in response to candesartan treatment; 3) candesartan treatment decreases NHE3 and TSC expression; and 4) an increase of BSC-1 is prominent in candesartan-treated CRF rats, which could be associated with the increased delivery of sodium and water to the thick ascending limb

Chaperone-like protein DAY plays critical roles in photomorphogenesis.

Photomorphogenesis, light-mediated development, is an essential feature of all terrestrial plants. While chloroplast development and brassinosteroid (BR) signaling are known players in photomorphogenesis, proteins that regulate both pathways have yet to be identified. Here we report that DE-ETIOLATION IN THE DARK AND YELLOWING IN THE LIGHT (DAY), a membrane protein containing DnaJ-like domain, plays a dual-role in photomorphogenesis by stabilizing the BR receptor, BRI1, as well as a key enzyme in chlorophyll biosynthesis, POR. DAY localizes to both the endomembrane and chloroplasts via its first transmembrane domain and chloroplast transit peptide, respectively, and interacts with BRI1 and POR in their respective subcellular compartments. Using genetic analysis, we show that DAY acts independently on BR signaling and chlorophyll biogenesis. Collectively, this work uncovers DAY as a factor that simultaneously regulates BR signaling and chloroplast development, revealing a key regulator of photomorphogenesis that acts across cell compartments

The Safety and efficacy of a new self-expandable intratracheal nitinol stent for the tracheal collapse in dogs

To evaluate the potential utility of a self-expandable intratracheal nitinol stent with flared ends for the treatment of tracheal collapse in dogs, endotracheal stenting therapy was performed under fluoroscopic guidance in four dogs with severe tracheal collapse. During the 4 to 7 month follow-up, after stent implantation, clinical signs, including dyspnea and respiratory distress, dramatically improved in all dogs. The radiographs showed that the implanted stents improved the tracheal collapse, and there were no side effects such as collapse, shortening or migration of the stents. In conclusion, the self-expandable intratracheal nitinol stents provided adequate stability to the trachea and were effective for attenuating the clinical signs associated with severe tracheal collapse

Long-term efficacy, safety and immunogenicity in patients with rheumatoid arthritis continuing on an etanercept biosimilar (LBEC0101) or switching from reference etanercept to LBEC0101: an open-label extension of a phase III multicentre, randomised, double-blind, parallel-group study

Background To evaluate the long-term efficacy, safety and immunogenicity of continuing LBEC0101; the etanercept (ETN) biosimilar; or switching from the ETN reference product (RP) to LBEC0101 in patients with rheumatoid arthritis (RA). Methods This multicentre, single-arm, open-label extension study enrolled patients who had completed a 52-week randomised, double-blind, parallel phase III trial of LBEC0101 vs ETN-RP. Patients treated with ETN-RP during the randomised controlled trial switched to LBEC0101; those treated with LBEC0101 continued to receive LBEC0101 in this study. LBEC0101 (50 mg) was administered subcutaneously once per week for 48 weeks with a stable dose of methotrexate. Efficacy, safety and immunogenicity of LBEC0101 were assessed up to week 100. Results A total of 148 patients entered this extension study (70 in the maintenance group and 78 in the switch group). The 28-joint disease activity scores (DAS28)-erythrocyte sedimentation rate (ESR) were maintained in both groups from week 52 to week 100 (from 3.068 to 3.103 in the maintenance group vs. from 3.161 to 3.079 in the switch group). ACR response rates at week 100 for the maintenance vs. switch groups were 79.7% vs. 83.3% for ACR20, 65.2% vs. 66.7% for ACR50 and 44.9% vs. 42.3% for ACR70. The incidence of adverse events and the proportion of patients with newly developed antidrug antibodies were similar in the maintenance and switch groups (70.0% and 70.5%, 1.4% and 1.3%, respectively). Conclusions Administration of LBEC0101 showed sustained efficacy and acceptable safety in patients with RA after continued therapy or after switching from ETN-RP to LBEC0101. Trial registration ClinicalTrials.gov, NCT02715908. Registered 22 March 2016.This extension study was funded by LG Chem, Ltd. (formerly, LG Life Sciences, Ltd), Mochida Pharmaceutical Co., Ltd. and Korea Health Industry Development Institute

Numerical learning of deep features from drug-exposed cell images to calculate IC50 without staining

To facilitate rapid determination of cellular viability caused by the inhibitory effect of drugs, numerical deep learning algorithms was used for unlabeled cell culture images captured by a light microscope as input. In this study, A549, HEK293, and NCI-H1975 cells were cultured, each of which have different molecular shapes and levels of drug responsiveness to doxorubicin (DOX). The microscopic images of these cells following exposure to various concentrations of DOX were trained with the measured value of cell viability using a colorimetric cell proliferation assay. Convolutional neural network (CNN) models for the study cells were constructed using augmented image data; the predicted cell viability using CNN models was compared to the cell viability measured by colorimetric assay. The linear relationship coefficient (r2) between measured and predicted cell viability was determined as 0.94–0.95 for the three cell types. In addition, the measured and predicted IC50 values were not statistically different. When drug responsiveness was estimated using allogenic models that were trained with a different cell type, the correlation coefficient decreased to 0.004085–0.8643. Our models could be applied to label-free cells to conduct rapid and large-scale tests while minimizing cost and labor, such as high-throughput screening for drug responsiveness. © 2022, The Author(s).TRU