gebhart/patrepeval huggingface dataset:
Crystal structure, stability and in vitro RNAi activity of oligoribonucleotides containing the ribo-difluorotoluyl nucleotide: insights into substrate requirements by the human RISC Ago2 enzyme (2007)

Short interfering RNA (siRNA) duplexes are currently being evaluated as antisense agents for gene silencing. Chemical modification of siRNAs is widely expected to be required for therapeutic applications in order to improve delivery, biostability and pharmacokinetic properties. Beyond potential improvements in the efficacy of oligoribonucleotides, chemical modification may also provide insight into the mechanism of mRNA downregulation mediated by the RNA-protein effector complexes (RNA-induced silencing complex or RISC). We have studied the in vitro activity in HeLa cells of siRNA duplexes against firefly luciferase with substitutions in the guide strand of U for the apolar ribo-2,4-difluorotoluyl nucleotide (rF) [Xia, J. et al. (2006) ACS Chem. Biol., 1, 176-183] as well as of C for rF. Whereas an internal rF:A pair adjacent to the Ago2 ('slicer' enzyme) cleavage site did not affect silencing relative to the native siRNA duplex, the rF:G pair and other mismatches such as A:G or A:A were not tolerated. The crystal structure at atomic resolution determined for an RNA dodecamer duplex with rF opposite G manifests only minor deviations between the geometries of rF:G and the native U:G wobble pair. This is in contrast to the previously found, significant deviations between the geometries of rF:A and U:A pairs. Comparison between the structures of the RNA duplex containing rF:G and a new structure of an RNA with A:G mismatches with the structures of standard Watson-Crick pairs in canonical duplex RNA leads to the conclusion that local widening of the duplex formed by the siRNA guide strand and the targeted region of mRNA is the most likely reason for the intolerance of human Ago2 (hAgo2), the RISC endonuclease, toward internal mismatch pairs involving native or chemically modified RNA. Contrary to the influence of shape, the thermodynamic stabilities of siRNA duplexes with single rF:A, A:A, G:A or C:A (instead of U:A) or rF:G pairs (instead of C:G) show no obvious correlation with their activities. However, incorporation of three rF:A pairs into an siRNA duplex leads to loss of activity. Our structural and stability data also shed light on the role of organic fluorine as a hydrogen bond acceptor. Accordingly, UV melting (T(M)) data, osmotic stress measurements, X-ray crystallography at atomic resolution and the results of semi-empirical calculations are all consistent with the existence of weak hydrogen bonds between fluorine and the H-N1(G) amino group in rF:G pairs of the investigated RNA dodecamers.
Issues in Value‐Added Products from Biomass (2001)

This chapter contains section titled: Thermochemical Conversion to Value-Added Products Biomass Feedstock Sources and Pretreatment Processing Biomass Utilization Issues Conclusions References
Dual Immunostimulatory Pathway Agonism through a Synthetic Nanocarrier Triggers Robust Anti‐Tumor Immunity in Murine Glioblastoma (2022)

Myeloid cells are abundant, create a highly immunosuppressive environment in glioblastoma (GBM), and thus contribute to poor immunotherapy responses. Based on the hypothesis that small molecules can be used to stimulate myeloid cells to elicit anti-tumor effector functions, a synthetic nanoparticle approach is developed to deliver dual NF-kB pathway-inducing agents into these cells via systemic administration. Synthetic, cyclodextrin-adjuvant nanoconstructs (CANDI) with high affinity for tumor-associated myeloid cells are dually loaded with a TLR7 and 8 (Toll-like receptor, 7 and 8) agonist (R848) and a cIAP (cellular inhibitor of apoptosis protein) inhibitor (LCL-161) to dually activate these myeloid cells. Here CANDI is shown to: i) readily enter the GBM tumor microenvironment (TME) and accumulate at high concentrations, ii) is taken up by tumor-associated myeloid cells, iii) potently synergize payloads compared to monotherapy, iv) activate myeloid cells, v) fosters a "hot" TME with high levels of T effector cells, and vi) controls the growth of murine GBM as mono- and combination therapies with anti-PD1. Multi-pathway targeted myeloid stimulation via the CANDI platform can efficiently drive anti-tumor immunity in GBM.
Novel Type of Analgesic — Synthesis and Analgesic Activity (1980)

Two 4a-(3-hydroxyphenyl)decahydr0~1nnnlines (7 and 9) have been synthesised from 2-(3-benzyloxyphenyl)-2-hydr0~y~arb0nyl methylcyclohexanone (I), and both showed stronger analgesic activity than mor~hlne.Previously we have reported the synthesis of many azamorphinan derivatives, some
Overview of the role of nanotechnological innovations in the detection and treatment of solid tumors (2014)

Nanotechnology, although still in its infantile stages, has the potential to revolutionize the diagnosis, treatment, and monitoring of disease progression and success of therapy for numerous diseases and conditions, not least of which is cancer. As it is a leading cause of mortality worldwide, early cancer detection, as well as safe and efficacious therapeutic intervention, will be indispensable in improving the prognosis related to cancers and overall survival rate, as well as health-related quality of life of patients diagnosed with cancer. The development of a relatively new field of nanomedicine, which combines various domains and technologies including nanotechnology, medicine, biology, pharmacology, mathematics, physics, and chemistry, has yielded different approaches to addressing these challenges. Of particular relevance in cancer, nanosystems have shown appreciable success in the realm of diagnosis and treatment. Characteristics attributable to these systems on account of the nanoscale size range allow for individualization of therapy, passive targeting, the attachment of targeting moieties for more specific targeting, minimally invasive procedures, and real-time imaging and monitoring of in vivo processes. Furthermore, incorporation into nanosystems may have the potential to reintroduce into clinical practice drugs that are no longer used because of various shortfalls, as well as aid in the registration of new, potent drugs with suboptimal pharmacokinetic profiles. Research into the development of nanosystems for cancer diagnosis and therapy is thus a rapidly emerging and viable field of study.
Abstract 1393: Correlating the expression of protein kinase C isozymes with the transformed phenotype in colorectal cancer (2014)

Abstract Protein Kinase C (PKC) is a family of serine/threonine kinases that are involved in almost every signal transduction pathway. Their regulation is mediated by several factors and by binding to a group of scaffolding proteins called RACKs (Adams et al. 2011). The development of PKC modulators with anti-cancer therapeutic value is a major target in cancer. However, this task is made difficult because PKC has an important role to play in normal processes and the PKC family consists of at least 12 different isozymes. In colon cancer, there is differential expression of the PKC isozymes, giving the cancer cells a migratory advantage and thus promote cancer progression. Our hypothesis is that PKC expression, activity and localisation are altered as colon epithelial cells switch from normal to the transformed state. We are confident that being able to recognise these changes has the potential to be used as a biomarker and prognostic marker in the early detection of colon cancer. Using novel 3D culture techniques, we examined the gene expression pattern of the 12 different PKC isozymes. We found that the isozymes were differentially expressed and that their expression pattern changed depending on whether the cells were grown under 2-dimensional or 3-dimensional culture systems. Using patient samples, we also document differential expression of several isozymes when compared to matched normal tissue. Using a series of PKC activators, together with a series of synergistic cellular and molecular approaches, we follow the migration of specific PKC isoforms to the membrane fraction in cells. This migration is dependent on the expression of RACK1 as when we use siRNA against RACK1, we disrupt PKC translocation in colon cancer cells. Taken together, our findings confirm that there is differential expression of PKC isozymes in cancer cells. We also confirm that specific PKC isozymes colocalise with RACK1 at the membrane supporting our hypothesis that RACK1 plays a central role in translocating PKC in the colon epithelium. Differential PKC expression and PKC translocation may be an important mechanism regulating the transformed phenotype of colon cancer cells. Citation Format: Catríona M. Dowling, Jennifer Hanly, Tara Dalton, Patrick A. Kiely. Correlating the expression of protein kinase C isozymes with the transformed phenotype in colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1393. doi:10.1158/1538-7445.AM2014-1393
Modern NMR Pulse Experiments: A Graphical Description of the Evolution of Spin Systems (1990)

Abstract Many modern methods designed to enhance the power of NMR spectroscopy have been widely adopted by the scientific community. Some of the best known among these techniques are one‐dimensional methods for polarization enhancement and spectral editing (“INEPT” and “DEPT”) and various two‐dimensional experiments such as correlation spectroscopy (“COSY”) and nuclear Overhauser spectroscopy (“NOESY”). Most of these methods cannot be described in terms of classical magnetization vectors, and although they can be understood with the help of the density operator formalism, this approach remains difficult for many users, in part because of its cumbersome notation, which prevents one from recognizing the important features at a glance. In this paper, a set of graphical conventions is described which allows one to represent the effect of sequences of radio‐frequency pulses on spin systems in a variety of experiments. The graphs provide a concise description of the network of spins that are coupled through scalar and dipolar interactions, of the state of a spin system expressed in terms of products of operators, and, most importantly, of the transformations from one state to another due to the effect of radio‐frequency pulses, chemical shifts, and scalar couplings. The graphical approach also allows one to represent the effect of phase‐cycling and multiple‐quantum filtration, cross‐relaxation (Overhauser effects) and cross‐correlated relaxation.
Investigation of the annealing time effects on Cu deposited CdTe thin films for photovoltaic application (2015)

Firstly, Cadmium Telluride (CdTe) thin films have been deposited on cleaned soda lime glass substrates at 300°C by using the RF magnetron sputtering technique. After that, Cu thin film was deposited for 5 minutes at 200°C on top of CdCl2 treated CdTe thin films by sputtering. Subsequently, CdTe and Cu stacks were annealed at 400°C for 15 minutes, 20 minutes and 25 minutes in a vacuum furnace. The influence of different annealing times on the structural, topographical and electrical properties of Cu sputtered CdTe thin films were then examined by XRD, AFM and Hall Effect measurement, respectively. XRD patterns reveal that, one CdTe peak corresponding to the (111)cub reflection planes at 2θ=23.8º and another low intensity Cu2Te peak representing (200)hex hexagonal reflection planes at around 2θ=24.8º were found for all the annealing times. Surface roughness and topography were viewed from the AFM images. Noteworthy changes were observed in the films surface roughness due to the different annealing times. The surface roughness values imply rising trend for lower annealing times. Bulk carrier density was in the order of 1018cm−3. The highest carrier concentration of 7.1×1018cm−3 was achieved for the films annealed for 15 min.
Emulsion Polymerization of 2, 6-Xylenol Catalyzed by Copper-Partially-Quaternized Poly(vinylpyridine) Complex (1972)

部分四級化ポリ(ビニルピリジン)(QPVP)を水溶性の高分子配位子とする銅錯体を触媒として用い,2,6-キシレノール(XOH)の酸化重合を水,ベンゼン(Bz)混合溶媒中で行ない,QPVP配位子の効果を重合機構とあわせて考察した。Cu-QPVP錯体は水溶性であり,pH5以上ではQPVPがキレート配位した錯体を形成しているため銅-ピリジン(Py)低分子錯体にくらべ広いpH範囲(pH5～10)で安定である。反応生成物は水相のpHにより変化し,pH7以下ではピフェノキノン(BQ),pH7以上でポリフェニレンオキシド(PPO)が主生成物となり,PPO収率は錯体の安定度および単量体の酸化電位などが関与しpH9付近で最大となる。重合は水,あるいはB2単-相のみでは進行せず,各反応成分の溶解性などから反応が水-Bz界面付近で進行して炉ることが明らかになった。Cu-QPVP系はCu-Py系より重合速度が大きく,QPVP配位子が界面活性に作用していることなどが考えられる。
ReaxFF Reactive Force-Field Study of Molybdenum Disulfide (MoS2) (2017)

Two-dimensional layers of molybdenum disulfide, MoS<sub>2</sub>, have been recognized as promising materials for nanoelectronics due to their exceptional electronic and optical properties. Here we develop a new ReaxFF reactive potential that can accurately describe the thermodynamic and structural properties of MoS<sub>2</sub> sheets, guided by extensive density functional theory simulations. This potential is then applied to the formation energies of five different types of vacancies, various vacancy migration barriers, and the transition barrier between the semiconducting 2H and metallic 1T phases. The energetics of ripplocations, a recently observed defect in van der Waals layers, is examined, and the interplay between these defects and sulfur vacancies is studied. As strain engineering of MoS<sub>2</sub> sheets is an effective way to manipulate the sheets' electronic and optical properties, the new ReaxFF description can provide valuable insights into morphological changes that occur under various loading conditions and defect distributions, thus allowing one to tailor the electronic properties of these 2D crystals.
Interpretable Epilepsy Detection in Routine, Interictal EEG Data using Deep Learning (2020)

current state-of-the-art.Averaging window predictions per recording improved the t-VGG's respective AUPR performances further to 95.52% and 77.27%.The Gradient-weighted Class Activation Mapping method for interpretability confirmed that the model was able to learn sensible features with connections to well-known epilepsy markers.
Data from Induction of programmed cell death in ErbB2/HER2-expressing cancer cells by targeted delivery of apoptosis-inducing factor (2023)

&lt;div&gt;Abstract&lt;p&gt;Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein with NADH oxidase activity that has a vital function in healthy cells but is also an important mediator of caspase-independent programmed cell death in stressed and damaged cells. Here, we generated a truncated AIF derivative (AIF&lt;sub&gt;Δ100&lt;/sub&gt;) that lacks the mitochondrial import signal of the protein. Bacterially expressed AIF&lt;sub&gt;Δ100&lt;/sub&gt; was functionally active and induced cell death on microinjection into Vero cells accompanied by clear signs of apoptosis. For specific targeting to tumor cells, AIF&lt;sub&gt;Δ100&lt;/sub&gt; was genetically fused to the scFv(FRP5) antibody fragment that recognizes the ErbB2 (HER2) receptor tyrosine kinase frequently overexpressed in many human cancers. Recombinant scFv(FRP5)-AIF&lt;sub&gt;Δ100&lt;/sub&gt; (5-AIF&lt;sub&gt;Δ100&lt;/sub&gt;) protein and a similar scFv(FRP5)-ETA&lt;sub&gt;252-366&lt;/sub&gt;-AIF&lt;sub&gt;Δ100&lt;/sub&gt; (5-E-AIF&lt;sub&gt;Δ100&lt;/sub&gt;) molecule harboring in addition the nontoxic translocation domain of &lt;i&gt;Pseudomonas&lt;/i&gt; exotoxin A as an endosome escape function displayed binding to ErbB2-expressing cells followed by protein internalization and accumulation in intracellular vesicles. In the presence of the endosomolytic reagent chloroquine 5-E-AIF&lt;sub&gt;Δ100&lt;/sub&gt; but not the similar 5-AIF&lt;sub&gt;Δ100&lt;/sub&gt; protein displayed potent cell killing activity, which was strictly dependent on the expression of ErbB2 on the target cell surface. Our results show that recombinant AIF specifically targeted to human cancer cells and delivered into the cytosol has potent cell killing activity, suggesting this molecule as an effector function suitable for the development of humanized immunotoxin-like molecules. [Mol Cancer Ther 2009;8(6):1526–35]&lt;/p&gt;&lt;/div&gt;
MIMO Broadcasting for Simultaneous Wireless Information and Power Transfer: Weighted MMSE Approaches (2014)

We consider simultaneous wireless information and power transfer (SWIPT) in MIMO Broadcast networks where one energy harvesting (EH) user and one information decoding (ID) user share the same time and frequency resource. In contrast to previous SWIPT systems based on the information rate, this paper addresses the problem in terms of the weighted minimum mean squared error (WMMSE) criterion. First, we formulate the WMMSE-SWIPT problem which minimizes the weighted sum-MSE of the message signal arrived at the ID user, while satisfying the requirement on the energy that can be harvested from the signal at the EH user. Then, we propose the optimal precoder structure of the problem and identify the best possible MSE-energy tradeoff region through the alternative update of the linear precoder at the transmitter with the linear receiver at the ID user. From the derived solution, several interesting observations are made compared to the conventional SWIPT designs.
Influence of mask material on the electrical properties of selective area epitaxy GaN microstructures (2018)

The authors have investigated the effect of dielectric (SiO2/SiNx) and metal (W) masks on impurity incorporation and electrical properties of selective area epitaxy (SAE) GaN microstructures. It is shown that SAE growths result in highly conductive n-type material. Carrier concentrations greater than metal-nonmetal transition level and low resistivity in the range of 0.18–0.29 mΩ cm were observed from Hall measurements for these structures. Two terminal current-voltage measurements showed a 40× increase in current for SAE GaN microstructure devices compared to that of conventional planar GaN devices. Secondary ion mass spectroscopy (SIMS) measurements of unintentional Si and O dopants in these structures showed dependency on the mask type. Similar dopant and carrier concentrations were obtained from SIMS and Hall data, indicating low compensation from acceptors in the SAE growths.
Biocatalytically Templated Synthesis of Titanium Dioxide (2003)

Silicatein, an enzymatic biocatalyst purified from the glassy skeletal elements of a marine sponge, and previously shown capable of catalyzing and structurally directing the hydrolysis and polycondensation of silicon alkoxides to yield silica and silsesquioxanes at low temperature and pressure and neutral pH, is shown to be capable of catalyzing and templating the hydrolysis and subsequent polycondensation of a water-stable alkoxide-like conjugate of titanium to form titanium dioxide. The structure and behavior of the TiO2 formed through this biocatalytic route, including thermally induced crystal grain growth and phase transformation from anatase to rutile, differ from those of TiO2 formed from the same precursor via alkali catalysis or thermal pyrolysis. This enzymatic route affords a path to templated synthesis that avoids the high temperatures and extremes of pH typically required for synthesis of metallo-oxanes from the corresponding alkoxide-like precursors, and thus provides access to a new and potentially useful parameter space of structures and properties. The proteins may also be nanoscopically structure-directing, as evidenced by the formation of nanocrystallites of anatase, a polymorph usually formed at much higher temperatures. The summation of weak interactions between the protein and mineral may induce this stabilization and thus may afford a new level of nanostructural control, with associated enhancement of selected performance properties.
Structure–Activity Relationships for Withanolides as Inducers of the Cellular Heat-Shock Response (2014)

To understand the relationship between the structure and the remarkably diverse bioactivities reported for withanolides, we obtained withaferin A (WA; 1) and 36 analogues (2-37) and compared their cytotoxicity to cytoprotective heat-shock-inducing activity (HSA). By analyzing structure-activity relationships for the series, we found that the ring A enone is essential for both bioactivities. Acetylation of 27-OH of 4-epi-WA (28) to 33 enhanced both activities, whereas introduction of β-OH to WA at C-12 (29) and C-15 (30) decreased both activities. Introduction of β-OAc to 4,27-diacetyl-WA (16) at C-15 (37) decreased HSA without affecting cytotoxicity, but at C-12 (36), it had minimal effect. Importantly, acetylation of 27-OH, yielding 15 from 1, 16 from 14, and 35 from 34, enhanced HSA without increasing cytotoxicity. Our findings demonstrate that the withanolide scaffold can be modified to enhance HSA selectively, thereby assisting development of natural product-inspired drugs to combat protein aggregation-associated diseases by stimulating cellular defense mechanisms.
Cross neutralization of coral snake venoms by commercial Australian snake antivenoms (2016)

Our findings confirm the limited effectiveness of the Brazilian coral snake antivenom and indicate that antivenoms made from Australian snakes venoms are an effective alternative for coral snake bites in South America and also in the United States were coral snake antivenom production has been discontinued.
Selective Extraction from Food Plants and Residues by Pulsed Electric Field (2015)

The applications of pulsed electric field (PEF) for green extraction are reviewed. Recent scientific and practical efforts show full correspondence of PEF with the main concepts of green extraction. The use of pulsed electric fields allows obtention of safe and high-quality extracts, use of eco-solvents, enhancement in productivity, reduction in energy consumption, and noticeable acceleration in processing. PEF-assisted processing allows preservation of the quality of extracts (e.g., purity, color, texture, aroma, flavor, nutrients, proteins and polysaccharides, and other bioactive substances) and also inactivation of the pathogenic and spoilage microorganisms. The modern applications of PEF for enhancement of the solid–liquid extraction in the processing of fruits, vegetables, herbs, leaves, mushrooms, food oils, juice, wine, beverages, and biosuspensions are discussed.
Milk – A new source for bioactive phospholipids for use in food formulations (2008)

Abstract The fat globules of milk are surrounded by a membrane, which contains a triple layer of phospholipids. Concentrated cream is thus a very good raw material for further processing in order to make a powder, enriched in phospholipids. A powder can in this way easily be produced with 20% phospholipids using only common dairy processes such as centrifugation and membrane filtration. Milk phospholipids differ in compositions from existing commercial sources such as soybean lecithins and egg lecithins particularly with respect to the content of two bioactive phospholipids namely sphingomyelin (about 24%) and phosphatidylserine (12%). Sphingomyelin is an active agent controlling the intestinal uptake of cholesterol and triacylglycerols in human nutrition. Intake of phosphatidyl serine has clinically documented effects in maintaining cognitive performance like memory and stress control. A milk phospholpids enriched product thus offers a 100% natural alternative to the well‐established, semi‐synthetic head‐group exchanged phosphatidyl serine from soy lecithin now existing on the market for functional foods formulations.
Supplementary Figure 1 from TLR3 as a Biomarker for the Therapeutic Efficacy of Double-stranded RNA in Breast Cancer (2023)

Supplementary Figure 1 from TLR3 as a Biomarker for the Therapeutic Efficacy of Double-stranded RNA in Breast Cancer