gebhart/patrepeval huggingface dataset:
The effect of the PI3K/AKT pathway inhibition on leiomyosarcoma cells (2004)

9002 Background: Leiomyosarcomas (LMS) are one of the most common histological types of soft tissue sarcomas and are usually resistant to standard chemotherapy. Novel agents that can cause apoptosis must be explored. The PI3K/AKT pathway is an important survival pathway and is upregulated in many tumor cells. Recent publications have shown that the AKT pathway is an important survival pathway for a uterine LMS cell line, SKLMS-1. In this study we examined the effects of LY294002, a specific PI 3-kinase inhibitor on the survival of the SKLMS-1 cell line. Methods: Various doses of LY294002 were added to growing SKLMS-1 cells for 24, 48 and 72 hours. Cells were harvested at these time points and counted. Cell cycle distribution was analyzed by propidium iodide staining. Apoptosis was analyzed by both TUNEL assay and cleavage of PARP by western blotting. Cell lysates were analyzed for cyclin D3, cyclin A, and p27 by western blot. Results: At all doses (10, 20 and 50 μM) LY294002 caused G0/G1 growth arrest at 24hours in a dose-dependent manner. Cells that were treated for 48 and 72 hours were killed as demonstrated by decreased cell counts, TUNEL assay and PARP cleavage. Apoptosis occurred in both a time and dose dependent manner. At a dose of 10 μM, a 5-fold and 14-fold decrease in cell number was found at 48 and 72 hours respectively, compared to cells treated with the control DMSO. At a dose of 50 μM, cell count revealed more than a 12-fold decrease in cell numbers for both 48 and 72 hours. Analysis of the cell cycle distribution correlated with the cell counts. Results showed that LY294002 arrested the cells early in G0/G1 allowing them to transverse through one cell cycle, and then become trapped in G0 and ultimately die through apoptosis. Expression of cyclin A and cyclin D3 was reduced in the treated cells. Interestingly, p27 levels did not increase with treatment. Conclusions: The PI3K inhibitor, LY294002 caused apoptosis in a both dose and time dependent manner. At 24 hours cells were arrested in G0/G1. At higher doses and at 48 and 72 hours, cells were killed by apoptosis. These preclinical data may provide an opportunity for the development of novel therapies that target the P13K/AKT pathway No significant financial relationships to disclose.
Influence of interferon-alpha on the expression of cellular oncogenes in primary chronic lymphocytic leukemia cells. (1988)

The influence of interferon-alpha 2 (IFN-alpha 2) on the mRNA levels of cellular proto-oncogenes was studied in malignant cells from patients with chronic lymphocytic leukemia (CLL). These cells can be induced to blast transform, differentiate and, in some cases, proliferate upon exposure to IFN. Treatment with IFN-alpha enhanced the levels of c-myc mRNA in malignant cells from the patients, whereas the levels of c-myb mRNA decreased, as measured by slot blot hybridizations. In cells from some patients, an enhanced expression of c-fos and k-ras was observed following exposure to IFN-alpha. No major effect on the expression of c-raf or of enolase was observed in any of the patients following exposure to IFN-alpha, whereas the levels of beta 2-microglobulin mRNA increased. In contrast to the observed effects on oncogene expression in CLL cells, IFN had no major effect on the expression of any of the tested oncogenes in lymphocytes from healthy donors or in B-cells from three neoplastic cell lines (380, FL18, RS). We conclude that IFN-alpha can enhance or repress the expression of several oncogenes in nondividing primary malignant cells from patients with leukemia. We also show that the response of malignant cells from patients to IFN-alpha is different than that seen with neoplastic cell lines which represent a similar stage of B-cell differentiation.
The PRE4 gene codes for a subunit of the yeast proteasome necessary for peptidylglutamyl-peptide-hydrolyzing activity. Mutations link the proteasome to stress- and ubiquitin-dependent proteolysis. (1993)

Proteinase yscE, the yeast proteasome, is a member of the nonlysosomal, high molecular mass (approximately 700 kDa) multifunctional proteinase complexes that are highly conserved from yeast to man. We have isolated mutants defective in one of the three proteolytic activities of the enzyme complex, i.e. in cleavage of peptide bonds after acidic amino acids. Using one of these mutants (pre4-1), we cloned the PRE4 gene and uncovered an open reading frame with 266 amino acids coding for a predicted protein of 29.4 kDa. The protein proved to be a subunit of proteinase yscE. The Pre4 amino acid sequence shows strong homology to the beta-subunit of the Xenopus laevis proteasome. Chromosomal deletion of the PRE4 gene is lethal. The pre4-1 mutant allele was cloned and sequenced. The mutant protein is shortened by 15 amino acids at the carboxyl terminus. Mutations (pre1-1, pre2-2) in the chymotrypsin-like activity of proteinase yscE uncovered the enzyme to be involved in ubiquitin-linked and stress-dependent proteolytic pathways. In contrast to these mutants, pre4-1 mutants did not exhibit any apparent stress-dependent phenotypes. However, pre1-1 pre4-1 double mutants showed enhanced canavanine sensitivity and increased accumulation of ubiquitin protein conjugates, as compared with pre1-1 single mutants.
Heterologous Prime-Boost Combinations Highlight the Crucial Role of Adjuvant in Priming the Immune System (2018)

The induction and modulation of the immune response to vaccination can be rationally designed by combining different vaccine formulations for priming and boosting. Here, we investigated the impact of heterologous prime-boost approaches on the vaccine-specific cellular and humoral responses specific for a mycobacterial vaccine antigen. C57BL/6 mice were primed with the chimeric vaccine antigen H56 administered alone or with the CAF01 adjuvant, and boosted with H56 alone, or combined with CAF01 or with the squalene-based oil-in-water emulsion adjuvant (o/w squalene). A strong secondary H56-specific CD4<sup>+</sup> T cell response was recalled by all the booster vaccine formulations when mice had been primed with H56 and CAF01, but not with H56 alone. The polyfunctional nature of T helper cells was analyzed and visualized with the multidimensional flow cytometry FlowSOM software, implemented as a package of the R environment. A similar cytokine profile was detected in groups primed with H56 + CAF01 and boosted with or without adjuvant, except for some clusters of cells expressing high level of IL-17 together with TNF-α, IL-2, and IFN-γ, that were significantly upregulated only in groups boosted with the adjuvants. On the contrary, the comparison between groups primed with or without the adjuvant showed a completely different clusterization of cells, strengthening the impact of the formulation used for primary immunization on the profiling of responding cells. The presence of the CAF01 adjuvant in the priming formulation deeply affected also the secondary humoral response, especially in groups boosted with H56 alone or o/w squalene. In conclusion, the presence of CAF01 adjuvant in the primary immunization is crucial for promoting primary T and B cell responses that can be efficiently reactivated by booster immunization also performed with antigen alone.
Chip-scale 3D topography synthesis (1998)

We propose a novel approach to perform the chip scale mask to topography mapping by building a library of repetitive mask patterns. We call them vicinity patterns. They describe a collection of mask features in close proximity. This pattern library is used to synthesize 3-D topography of an arbitrary part of the chip topography. We define some process-related parameters, which we call critical interaction lengths, as a basis for mask decomposition into the vicinity patterns.
The platelet-derived growth factor alpha-receptor is encoded by a growth-arrest-specific (gas) gene. (1996)

Using the Escherichia coli lacZ gene to identify chromosomal loci that are transcriptionally active during growth arrest of NIH 3T3 fibroblasts, we found that an mRNA expressed preferentially in serum-deprived cells specifies the previously characterized alpha-receptor (alphaR) for platelet-derived growth factor (PDGF), which mediates mitogenic responsiveness to all PDGF isoforms. Both PDGFalphaR mRNA, which was shown to include a 111-nt segment encoded by a DNA region thought to contain only intron sequences, and PDGFalphaR protein accumulated in serum-starved cells and decreased as cells resumed cycling. Elevated PDGFalphaR gene expression during serum starvation was not observed in cells that had been transformed with oncogenes erbB2, src, or raf, which prevent starvation-induced growth arrest. Our results support the view that products of certain genes expressed during growth arrest function to promote, rather than restrict, cell cycling. We suggest that accumulation of the PDGFalphaR gene product may facilitate the exiting of cells from growth arrest upon mitogenic stimulation by PDGF, leading to the state of "competence" required for cell cycling.
Multi-Resolution Block Matching Algorithm and Its VLSI Architecture for Fast Motion Estimation in an MPEG-2 Video Encoder (2004)

This paper proposes a high-performance multi-resolution motion estimation algorithm (HMRME) for MPEG-2 video encoding, which satisfies high estimation performance and efficient very large scale integration (VLSI) implementation. HMRME is based on a characteristic that field motion vectors (MVs) are very similar to their corresponding frame MV. Firstly, HMRME performs frame-based motion estimation (ME) as follows: at the coarsest level, two MV candidates are found on the basis of minimum matching error. The two MV candidates from the coarsest level search and the other one based on spatial MV correlation are used as center points for three local searches at the middle level. At the finest level, a frame MV is obtained from a local search around a single candidate from the middle level search. Field MVs are estimated with the single MV candidate from the middle level search of frame ME as initial estimates at the finest level, without any coarser level searches. This paper also describes a VLSI architecture based on HMRME. This architecture is designed to provide a good tradeoff between on-chip memory size and I/O bandwidth with high throughput. We implemented this architecture with about 140 K gates and 2.5 K bytes static random access memory for a large search range of [-192.0, +191.5] by using a synthesizable Verilog HDL.
Organic Light‐Emitting Diodes with Field‐Effect‐Assisted Electron Transport Based on α‐bi;,ω‐bi;‐Diperfluorohexyl‐quaterthiophene (2008)

Abstract Materials commonly used in the carrier transport layers of organic light‐emitting diodes, where transport occurs through the bulk, are in general very different from materials used in organic field‐effect transistors, where transport takes place in a very thin accumulation channel. In this paper, the use of a high‐performance electron‐conducting field‐effect transistor material, diperfluorohexyl‐substituted quaterthiophene (DFH‐4T), as the electron‐transporting material in an organic light‐emitting diode structure is investigated. The organic light‐emitting diode has an electron accumulation layer in DFH‐4T at the organic hetero‐interface with the host of the light‐emitting layer, tris(8‐hydroxyquinoline) aluminum (Alq 3 ). This electron accumulation layer is used to transport electrons and inject them into the active emissive host‐guest layer. By optimizing the growth conditions of DFH‐4T for electron transport at the organic hetero‐interface, high electron current densities of 750 A cm −2 are achieved in this innovative light‐emitting structure.
CRISPR/Cas9 directed to the Ube3a antisense transcript improves Angelman syndrome phenotype in mice (2021)

Gene editing holds the potential to correct mutations and cure devastating genetic disorders. The technology has not yet proven efficacious for therapeutic use in CNS diseases with ubiquitous neuronal defects. Angelman syndrome (AS), a severe neurodevelopmental disorder, is caused by a lack of maternal expression of the UBE3A gene. Because of genomic imprinting, only neurons are affected. One therapeutic approach focuses on the intact paternal UBE3A copy in patients with AS that is silenced by an antisense transcript (UBE3A-ATS). We show here that gene editing of Ube3a-ATS in the mouse brain resulted in the formation of base pair insertions/deletions (indels) in neurons and the subsequent unsilencing of the paternal Ube3a allele in neurons, which partially corrected the behavioral phenotype of a murine AS model. This study provides compelling evidence to further investigate editing of the homologous region of the human UBE3A-ATS because this may provide a lasting therapeutic effect for patients with AS.
Microstrip antenna-coupled infrared detector (1999)

A novel type of antenna-coupled infrared detector consisting of a niobium microbolometer integrated with two microstrip patch antennas is reported. This is the first microstrip antenna structure proven to detect thermal infrared radiation. A polarisation ratio of &gt; 20:1 and a time constant of &lt; 150 ns have been measured for this type of detector.
Modeling the Triboelectric Behaviors of Elastomeric Nonwoven Fabrics (2021)

Theoretical modeling of triboelectric nanogenerators (TENGs) is fundamental to their performance optimization, since it can provide useful guidance on the material selection, structure design, and parameter control of relevant systems. Built on the theoretical model of film-based TENGs, here, an analytical model is introduced for conductor-to-dielectric contact-mode nonwoven-based TENGs, which copes with the unique hierarchical structure of nonwovens and details the correlation between the triboelectric output (maximum transferred charge density) and nonwoven structural parameters (thickness, solidity, and average fiber diameter). A series of styrene-ethylene-butylene-styrene nonwoven samples are fabricated through a melt-blowing process to map nonwoven structural features within certain ranges, while an ion-injection protocol is adopted to quantify the triboelectric output with superior consistency and reproducibility. With a database containing structural features and triboelectric output of 43 nonwoven samples, a good model fitting is achieved via nonlinear regression analysis in Python, which also shows good predictive power and suggests the existing of tribo-output maxima at a specific thickness, solidity, or average fiber diameter when other structural parameters are fixed. The model is also successfully applied to a group of polypropylene meltblown nonwovens, which verifies its universality on meltblown-nonwoven-based TENGs.
Multimodal treatment strategies combining neoadjuvant hormonal therapy and/or chemotherapy with radical prostatectomy in high-risk localised prostate cancer (2004)

By combining the readily available clinical parameters of tumour stage, Gleason score of the diagnostic biopsy specimen and serum prostate-specific antigen level, men with newly diagnosed prostate cancer can be assessed as to their risk of treatment failure after radiotherapy or radical prostatectomy. For men considered to be at high-risk of treatment failure after local therapy alone, multimodal treatment strategies may result in improved cancer-control outcomes. This strategy has proven effective in the setting of clinical stage T3 - T4 tumours in which the combination of radiotherapy followed by hormonal therapy has improved patient survival. The benefit of neoadjuvant or adjuvant hormonal and/or chemotherapy followed by radical prostatectomy in this setting is unclear but is the subject of ongoing or planned Phase III clinical trials. These studies will help examine the role of multimodal treatment strategies in these high-risk patients.
Fabrication of field-effect transistor utilizing oriented thin film of octahexyl-substituted phthalocyanine and its electrical anisotropy based on columnar structure (2018)

Field-effect transistors with molecularly oriented thin films of metal-free non-peripherally octahexyl-substituted phthalocyanine (C6PcH2), which characteristically form a columnar structure, have been fabricated, and the electrical anisotropy of C6PcH2 has been investigated. The molecularly oriented thin films of C6PcH2 were prepared by the bar-coating technique, and the uniform orientation in a large area and the surface roughness at a molecular level were observed by polarized spectroscopy and atomic force microscopy, respectively. The field effect mobilities parallel and perpendicular to the column axis of C6PcH2 were estimated to be (1.54 ± 0.24) × 10−2 and (2.10 ± 0.23) × 10−3 cm2 V−1 s−1, respectively. The electrical anisotropy based on the columnar structure has been discussed by taking the simulated results obtained by density functional theory calculation into consideration.
Periodic Mesoporous Organosilicas: Self‐Assembly from Bridged Cyclic Silsesquioxane Precursors (2005)

No holes barred: Trimethylene-bridged 1 can be prepared from [{SiCH2(OEt)2}3]. Compound 1 can be directed to self-assemble by a tri-block copolymer template to form a periodic mesoporous organosilica with highly ordered and uniform-diameter mesopores in which practically all the building blocks remain intact within the as-synthesized and template-extracted material.
Propelling Health Care into the Twenties (2020)

The scope and potential of personalised health care are underappreciated and underrealised, often because of resistance to change. The consequence is that many inadequacies of health care in Europe persist unnecessarily, and many opportunities for improvement are neglected. This article identifies the principal challenges, outlines possible approaches to resolving them, and highlights the benefits that could result from greater adoption of personalised health care. It locates the discussion in the context of European policy, focusing particularly on the most recent and authoritative reviews of health care in the EU Member States, and on the newly acquired spirit of readiness and pragmatism among European officials to embrace change and innovative technologies in a new decade. It highlights the attention now being given by policymakers to incentives, innovation, and investment as levers to improve European citizens' prospects in a rapidly evolving world, and how these distinct and disruptive themes contribute to a renaissance in thinking about delivering optimal health care in Europe. It explores the chances offered to patients by specific initiatives in health domains such as cancer and antimicrobial resistance, and by innovative science, novel therapies, earlier diagnosis tools, and deeper understanding of health promotion and prevention. And it reflects on how health care providers could benefit from a shift towards better primary care and towards deploying health data more effectively, including the use of artificial intelligence, coupled with a move to a smoother organisational/regulatory structure and realigned professional responsibilities. The conclusion is that preparing Europe's health care systems for the inevitable strains of the coming years is both possible and necessary. A more courageous approach to embracing personalised health care could guarantee the sustainability of Europe's health care systems before rising demands and exponential costs overwhelm them - an exercise in future-proofing, in ensuring that they are equipped to withstand whatever lies ahead. A focus on the potential and implementation of personalised care would permit more efficient use of resources and deliver better quality health-preserving care.
Osteogenic Differentiation of Pre-Osteoblasts on Biomimetic Tyrosine-Derived Polycarbonate Scaffolds (2011)

The osteogenic potential of biomimetic tyrosine-derived polycarbonate (TyrPC) scaffolds containing either an ethyl ester or a methyl ester group combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) was assessed using the preosteoblast cell line MC3T3-E1. Each composition of TyrPC was fabricated into 3D porous scaffolds with a bimodal pore distribution of micropores <20 μm and macropores between 200 and 400 μm. Scanning electron microscopy (SEM) characterization suggested MC3T3-E1 cell attachment on the TyrPC scaffold surface. Moreover, the 3D TyrPC-containing ethyl ester side chains supported osteogenic lineage progression, alkaline phosphatase (ALP), and osteocalcin (OCN) expression as well as an increase in calcium content compared with the scaffolds containing the methyl ester group. The release profiles of rhBMP-2 from the 3D TyrPC scaffolds by 15 days suggested a biphasic rhBMP-2 release. There was no significant difference in bioactivity between rhBMP-2 releasate from the scaffolds and exogenous rhBMP-2. Lastly, the TyrPC containing rhBMP-2 promoted more ALP activity and mineralization of MC3T3-E1 cells compared with TyrPC without rhBMP-2. Consequently, the data strongly suggest that TyrPC scaffolds will provide a highly useful platform for bone tissue engineering.
Silicate-Glass/Sapphire Interfaces Probed with Micromechanical Testing Instruments: Sem and Tem Combined Characterization (1996)

The presence of intergranular phases is a common feature in today's polycrystalline ceramics prepared through traditional sintering routes. Although it has been shown that the chemistry and the microstructure of these phases may be altered, for example, by manipulating the heat treatments to tailor the final material's properties, very little is known about the mechanical properties of the interfaces on the microscopic scale. The mechanical behavior of the interfaces between calcium-alumino-silicate (CAS) glasses and single-crystal α-AI 2 O 3 substrates has been studied with two different types of micromechanical testers. The emphasis of this work is to correlate irregularities observed in the load-displacement curves produced using these testing instruments with the morphology of the deformation regions observed for the microindentations and microscratches. The effect of the substrate orientation on the interfacial properties has also been studied. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) have been used to characterize the deformation structures associated with the microscratches and microindentations.
Structures of chiral smectic-Cmesophases revealed by polarization-analyzed resonant x-ray scattering (1999)

We report polarization-analyzed, resonant x-ray diffraction at the sulfur K edge performed upon free-standing liquid-crystal films. Our studies of the thiobenzoate liquid-crystal enantiomer 10OTBBB1M7 yield the polarization states of resonant satellite peaks arising from characteristic superlattices in the chiral smectic-C (SmC(*)) variant phases, including the antiferroelectric SmC(*)(A), ferrielectric SmC(*)(FI1) and SmC(*)(FI2), as well as SmC(*)(alpha). The observed polarizations agree with the clock model of chiral smectic-C variants, and rule out other proposals made to date for these structures. Data from the 10OTBBB1M7 racemate also support the clock model. Our resonant diffraction results from a thiophene liquid-crystal compound reveal the same superlattice periodicities seen in corresponding antiferroelectric and ferrielectric phases of 10OTBBB1M7.