gebhart/patrepeval huggingface dataset:
279 COMPARISONS OF BONE MARROW AND PUTATIVE SKIN-DERIVED MESENCHYMAL STEM CELLS AS DONOR FOR NUCLEAR TRANSFER IN MINIATURE PIG (2008)

Since the birth of the first cloned sheep was reported, fibroblasts are commonly used as donor cells for nuclear transfer. However, in some species there is a higher incidence of abnormal fetuses, still births, and neonatal deaths as a consequence of reprogramming disorders including DNA methylation and histone acetylation. Cloned embryos with mesenchymal stem cells (MSC) have shown higher developmental ability compared to fibroblast, suggesting that undifferentiated genome can required ease reprogramming. Because MSC are relatively difficult to collect from bone marrow, skin is an alternative source of the donor cells. However, molecular and functional analyses remain uncertain between MSC derived from bone marrow and skin stem cells isolated from ear. The present study compared the expression of early transcription factors (Oct-4, Nanog and Sox-2), and differentiation capability to osteocytes, adipocytes and chondrocytes of MSC isolated from bone marrow and skin-derived putative stem cells from miniature pig. Bone marrow was isolated by Ficoll density gradient method, and skin separated from epidermis and dermis was diced into 2-mm diameter explants, and attached to tissue culture dishes. Cells were then cultured in DMEM/F12 supplemented with 10% FBS, 10 ng mL–1 bFGF, 10 ng mL–1 EGF at 38.5°C, in a humidified atmosphere of 5% CO2 in air. Expression of Oct-4, Nanog, Sox2 was analysed by RT-PCR. Osteogenic and adipogenic differentiation were induced following the protocols described previously (Jin et al. 2007 Int. J. Dev. Biol. 51, 85–90; Mohana Kumar et al. 2007 Mol. Cells 24, 343–350) and compared by histological staining and RT-PCR. Osteocytes were defined by the formation of the mineral nodules of deposition of calcium by Von Kossa staining and differentiations into adipocytes and chondrocytes were identified by oil red O staining of lipid vacuoles and alcian blue of proteoglycan, respectively. Skin-derived MSC were revealed to similar mRNA expression of Oct-4, Nanog, Sox2 compared to bone marrow derived MSC. However, bone marrow derived MSC were higher mRNA expression about of osteocytic genes (osteoclacin and osteonectin), chondrocytic gene (collagen type) and adipocytic genes (aP2) than those of skin-derived MSC. In addition, bone marrow derived MSC were revealed greater deposition of calcium, proteoglycan, and lipid vacuoles than those of skin derived MSC by histological staining. The results of present study suggest that cells isolated from skin have lower potential than MSC isolated from bone marrow. However, skin-derived stem cells have properties of multi-lineage differentiation and can be obtained easily. These stem cells, therefore, can serve as easily accessible and expandable source possessing donor cells for cloning, potential animal model, and clinical applications. This work was supported by Grant No. 20070301034040 from Bio-organ, Republic of Korea.
Abstract 4296: The EphA2/EGFR pathway dysregulation associates with poor prognosis and cetuximab treatment response in colorectal cancer (2020)

Abstract Tumor heterogeneity and the presence of stem-like cells have been identified as key features for resistance to anticancer treatments including targeted therapy. The Eph receptors comprise a large family of receptor tyrosine kinases that marks stem-like cells in different tissues. In colorectal cancer (CRC), EphA2 receptor overexpression has been linked to stem-like properties of cells and malignancy. In particular, EphA2 is involved in multiple cross-talks with other cellular networks including EGFR, FAK and VEGF pathways, with which it collaborates to stimulate cell migration, invasion and metastasis. We investigated the molecular crosstalk and miRNAs modulation of the EphA2 and EGFR pathways in CRC. We also explored the role of EphA2/EGFR pathway mediators as prognostic factors or predictors of cetuximab benefit in CRC patients. We used a strategy to uncover in murine homogeneous tumor EphA2high cells a novel potential molecular signature involving EphA2 and EGFR pathways. Gene expression analysis was performed in EphA2high cells isolated from colorectal adenocarcinoma obtained from the AOM/DSS-induced CRC murine model. Six independent cohorts of patients were analyzed to determine the potential prognostic role of a EphA2/EGFR signature and its effect on cetuximab treatment response. We identified a gene expression pattern, including a coherent miRNAs dysregulation, reflecting the activation of EphA2 and EGFR pathways. Such pattern showed prognostic significance in stage I-III CRC patients, in both univariate and multivariate analysis. In patients with stage IV and WT KRAS, EphA2/Efna1/EGFR gene expression status was significantly associated with poor response to cetuximab. Furthermore, EphA2 and EGFR overexpression showed a combined effect relative to cetuximab resistance, independently from KRAS mutation status. Collectively, our data indicate that EphA2/Efna1/EGFR genes, linked to a possible control by miRNAs, could be proposed as novel prognostic biomarkers in CRC. Moreover, EphA2 could be linked to a mechanism of resistance to cetuximab alternative to KRAS mutations. Since cetuximab resistance, associated to an intrinsic genetic heterogeneity, remains the most critical issue in treating CRC, this study sheds light on new potential biomarkers and therapeutically actionable kinase targets in the EphA2/EGFR-linked pathway. Citation Format: Mariangela De Robertis, Luisa Loiacono, Caterina Fusilli, Maria Luana Poeta, Tommaso Mazza, Massimo Sanchez, Luigi Marchionni, Emanuela Signori, Giuseppe Lamorte, Angelo Luigi Vescovi, Jesus Garcia-Foncillas, Vito Michele Fazio. The EphA2/EGFR pathway dysregulation associates with poor prognosis and cetuximab treatment response in colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4296.
Discovery and Preclinical Characterization of 1-Methyl-3-(4-methylpyridin-3-yl)-6-(pyridin-2-ylmethoxy)-1 H -pyrazolo-[3,4- b ]pyrazine (PF470): A Highly Potent, Selective, and Efficacious Metabotropic Glutamate Receptor 5 (mGluR5) Negative Allosteric Modulator (2014)

A novel series of pyrazolopyrazines is herein disclosed as mGluR5 negative allosteric modulators (NAMs). Starting from a high-throughput screen (HTS) hit (1), a systematic structure-activity relationship (SAR) study was conducted with a specific focus on balancing pharmacological potency with physicochemical and pharmacokinetic (PK) properties. This effort led to the discovery of 1-methyl-3-(4-methylpyridin-3-yl)-6-(pyridin-2-ylmethoxy)-1H-pyrazolo[3,4-b]pyrazine (PF470, 14) as a highly potent, selective, and orally bioavailable mGluR5 NAM. Compound 14 demonstrated robust efficacy in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-rendered Parkinsonian nonhuman primate model of l-DOPA-induced dyskinesia (PD-LID). However, the progression of 14 to the clinic was terminated because of a potentially mechanism-mediated finding consistent with a delayed-type immune-mediated type IV hypersensitivity in a 90-day NHP regulatory toxicology study.
Securing the download of radio configuration files for software defined radio devices (2004)

Radio configuration (R-CFG) files for software defined radio (SDR) devices can be downloaded over the air, allowing these devices to support multi-mode functionality using a single transceiver. SDR device manufacturers are likely to provide the R-CFGs, which may contain proprietary information. In such cases, it is necessary to secure the server/SDR device connection during the R-CFG download. Therefore, a protocol to securely connect manufacturer's server and SDR devices, called LSSL, is proposed. The LSSL is a lightweight protocol based on the SSL protocol, but it takes up less bandwidth, thus, it is more suitable for SDR handheld devices operating under low-capabilities, low-bandwidth and error-prone wireless links. However, securing the R-CFG download connection does not guarantee that a valid R-CFG, that is, an R-CFG that has been approved by the regulatory agency, has been downloaded. In order to install only valid R-CFGs, a secure download protocol is presented. The secure protocol includes, besides the LSSL, steps of mutual authentication, public/private key mechanisms for data encryption and decryption, and fingerprint calculations to check data integrity. Finally, the secure protocol is analyzed and shown to be deadlock and livelock-free, and to properly terminate. Experiments using Java 2 Micro Edition (J2ME) are performed to compare the LSSL and the SSL, and to demonstrate the feasibility of the secure protocol.
Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. (1998)

This study indicates that although postoperative external-beam radiotherapy is highly effective in preventing LRs, selected patients with extremity soft tissue sarcoma who have a low risk of LR may not require adjuvant XRT after limb-sparing surgery (LSS).
Class III Antiarrhythmic Drugs Block HERG, a Human Cardiac Delayed Rectifier K+Channel (1996)

We recently reported that mutations in HERG, a potassium channel gene, cause long QT syndrome. Heterologous expression of HERG in Xenopus oocytes revealed that this channel had biophysical properties nearly identical to a cardiac delayed rectifier K+ current I(Kr), but had dissimilar pharmacological properties. Class III antiarrhythmic drugs such as E-4031 and MK-499 are potent and specific blockers of I (Kr) in cardiac myocytes. Our initial studies indicated that these compounds did not block HERG at a concentration of 1 micromol/L. In the present study, we used standard two-microelectrode voltage-clamp techniques to further characterize the effects of these drugs on HERG channels expressed in oocytes. Consistent with initial findings, 1 micromol/L MK-499 and E-4031 had not effect on HERG when oocytes were voltage clamped at a negative potential and not pulsed during equilibration with the drug. However, MK-499 did block HERG current if oocytes were repetitively pulsed, or clamped at a voltage positive to the threshold potential for channel activation. This finding is in contrast to previous studies that showed significant block of I(Kr) in isolated myocytes by similar drugs, even in the absence of pulsing. This apparent discrepancy may be due to differences in channel characteristics (HERG versus guinea pig and mouse I (Kr)), tissue (oocytes versus myocytes), or specific drugs. Under steady state conditions, block of HERG by MK-499 was half maximal at 123 +/- 12 nmol/L at a test potential of -20 mV. MK-499 (150 nmol/L) did not affect the voltage dependence of activation and rectification nor the kinetics of activation and deactivation of HERG. These data indicate that MK-499 preferentially blocks open HERG channels and further support the conclusion that HERG subunits form I(Kr) channels in cardiac myocytes.
No Code AI: Automatic Generation of Function Block Diagrams from Documentation and Associated Heuristic for Context-Aware ML Algorithm Training (2022)

Industrial process engineering and PLC program development have traditionally favored Function Block Diagram (FBD) programming over classical imperative style programming like the object oriented and functional programming paradigms. The increasing momentum in the adoption and trial of ideas now classified as “No Code” or “Low Code” alongside the mainstream success of statistical learning theory or the so-called machine learning is redefining the way in which we structure programs for the digital machine to execute. A principal focus of “No Code” is deriving executable programs directly from a set of requirement documents or any other documentation that defines consumer or customer expectation. We present a method for generating Function Block Diagram (FBD) programs as either the intermediate or final artifact that can be executed by a target system from a set of requirement documents using a constrained selection algorithm that draws from the top line of an associated recommender system. The results presented demonstrate that this type of No-code generative model is a viable option for industrial process design.
Recent Advances in Intravesical Drug/Gene Delivery (2020)

Targeting of the drugs administered systemically relies on the higher affinity of ligands for specific receptors to obtain selectivity in drug response. However, achieving the same goal inside the bladder is much easier with an intelligent pharmaceutical approach that restricts drug effects by exploiting the pelvic anatomical architecture of the human body. This regional therapy involves placement of drugs directly into the bladder through a urethral catheter. It is obvious that drug administration by this route holds advantage in chemotherapy of superficial bladder cancer and it has now become the most widely used treatment modality for this ailment. In recent years, the intravesical route has also been exploited either as an adjunct to an oral regimen or as a second-line treatment for neurogenic bladder 1, 2. Instillation of DNA via this route using different vectors has been able to restrict the transgene expression in organs other than bladder. The present review article will discuss the shortcomings of the current options available for intravesical drug delivery (IDD) and lay a perspective for future developments in this field.
Watermark-Induced High-Density Via Failures in Submicron CMOS Fabrication (May 2006) (2007)

High via resistance was detected in the high-density via structure in our 0.15-mum back-end-of-line (BEOL) yield monitoring test vehicle. A localized insulating layer was found on top of the plug in test vehicle causing high via resistance. The failure was attributed to watermark-induced contaminants on top of the W plug. It was shown that the failure could be avoided by eliminating watermark formation on the wafer in the post-chemical-mechanical polishing scrub process.
Rapid device prototyping using the CORNERSTONE platform (Conference Presentation) (2019)

The field of silicon photonics has expanded rapidly over the past several decades. This has led to a degree of standardisation in the commercial device fabrication foundries that are available for universities and fabless companies alike. Whilst this is advantageous in terms of yield, repeatability etc., it is not conducive for researchers to develop new and novel devices for future systems. CORNERSTONE offers researchers a flexible device prototyping capability that can support photonics research around the world. The CORNERSTONE project (Capability for OptoelectRoNics, mEtamateRialS, nanoTechnOlogy, aNd sEnsing) is a UK Engineering and Physical Sciences Research Council (EPSRC) funded project between 3 UK universities: University of Southampton, University of Glasgow and University of Surrey. The project is based on deep-ultraviolet (DUV) photolithography equipment, installed at the University of Southampton, centred around a 248 nm Scanner, the first of its kind in a UK university. Utilising these facilities, CORNERSTONE will offer a multi-project wafer (MPW) service on several silicon-on-insulator (SOI) platforms (220 nm, 340 nm & 500 nm) for both passive and active silicon photonic devices. This talk will give an overview of the CORNERSTONE project, present some of its early data, and summarise future MPW offerings.
A Direct Drive Wave Energy Converter: Simulations and Experiments (2005)

A novel wave energy converter concept is developed at Uppsala University, Department of Engineering Science. The concept is based on a synchronous permanent magnet linear generator, placed on the seabed. The piston of the generator is directly connected to a surface-floating buoy with a rope. The tension in the rope is maintained with springs that pull the piston downward. The three-phase current induced in the stator coil has a varying amplitude and frequency and a conversion is therefore necessary. Research has been carried out in three main areas: generator design, dynamic behavior and grid connection. The generator is modeled by full physics numeric simulations, based on a 2-dimensional finite element formulation of the time dependent electromagnetic field. A first set up is built to experimentally verify the simulated results. The impact of different parameters are estimated with mathematical models and verified by experiments. This paper includes both simulated and experimental results.
Functional Heterogeneity of CD11c-positive Adipose Tissue Macrophages in Diet-induced Obese Mice (2010)

Obesity represents a state of chronic, low grade inflammation and is associated with infiltration of increased numbers of adipose tissue macrophages (ATMs). Diet-induced obesity leads to an increase in non-inflammatory M1-like ATMs displaying the CD11c surface marker. We assessed the function of CD11c-positive ATMs when insulin resistant high fat diet (HFD) mice become insulin-sensitive after switching from HFD to normal chow (NC). HFD mice rapidly become insulin-sensitive in all major insulin-target tissues, including muscle, liver, and adipose tissue, after the diet switch. In adipose tissue the CD11c-positive macrophages remain constant in number despite the presence of insulin sensitivity, but these macrophages now assume a new phenotype in which they no longer exhibit increased inflammatory pathway markers. Adipose tissue markers of apoptosis and necrosis were elevated on HFD and remain high after the HFD --> NC diet switch. Furthermore, ATM accumulation preceded detectable adipocyte necrosis at the early phase of HFD. Together, these results indicate that 1) CD11c-positive M1-like ATMs can exhibit phenotypic plasticity and that the polarization of these cells between inflammatory and non-inflammatory states is well correlated to the presence of absence of insulin resistance, and 2) adipocyte necrosis and apoptosis can be dissociated from ATM accumulation.
Prácticas de fundamento de ciencias de la materia: destilación. Preparación de disoluciones. (2021)

En esta práctica se repasarán distintas formas de expresar la concentración de una disolución. Así mismo, se procederá a la preparación de volúmenes predeterminados de dos disoluciones con dos concentraciones en molaridad dadas, a partir de dos productos de partida en distintos estados: un sólido (NaCl) y una disolución acuosa de un gas (NH3). En esta práctica se detalla el procedimiento práctico a llevar a cabo para preparar una disolución de un determinado soluto a una concentración estipulada. Para ello, primero es necesario calcular la cantidad de soluto que habría que usar, teniendo en cuenta el volumen deseado de la disolución y la concentración fijada. Una vez tomada la cantidad requerida de soluto (ya sea sólido o líquido), este se añade al matraz aforado adecuado (según el volumen de disolución que se quiere preparar) y se añade disolvente hasta la señal de enrase del matraz. Una vez hecho esto, sólo habría que agitar la muestra para disolver o distribuir el soluto uniformemente.
Procollagen complementary DNA, a probe for messenger RNA purification and the number of type I collagen genes (1978)

Type I procollagen mRNAs were separated from contaminating low-abundance messenger and nuclear RNAs by chromatography over Sepharose 4B in 0.65 M NaCl at room temperature. All of 27S rRNA and four-fifths of procollagen mRNAs bind to Sepharose under these conditions, while 18S rRNA and about three-fourths of other poly(A)-containing RNAs do not bind. AMV reverse transcriptase was used to prepare complementary DNA to procollagen mRNA at each purification step. Hybridization studies, in RNA excess, were carried out to establish the enrichment at each step both with respect to total RNA and to poly(A)-containing RNA. While "purified" procollagen mRNA preparations still consist of about 50% 27S rRNA, over 80% of cDNA prepared from it back hybridizes to its template at a log of cr0t1/2 of -1.9. This type I procollagen cDNA hybridizes in DNA excess to DNA isolated from chicken erythrocytes and from embryonic chick calvaria at a log c0t1/2 of 3.1, demonstrating that procollagen cDNA is complementary to unique gene sequences in both tissues and that procollagen genes are not reiterated.
Rodlike Bimetallic Ruthenium and Osmium Complexes Bridged by Phenylene Spacers. Synthesis, Electrochemistry, and Photophysics (2005)

In the search for light-addressable nanosized compounds we have synthesized 10 dinuclear homometallic trisbipyridyl complexes of linear structure with the general formula [M(bpy)3-BL-M(bpy)3]4+ [M = Ru(II) or Os(II); BL = polyphenylenes (2, 3, 4, or 5 units) or indenofluorene; bpy = 2,2'-bipyridine]. By using a "chemistry on the complex" approach, different sizes of rodlike systems have been obtained with a length of 19.8 and 32.5 A for the shortest and longest complex, respectively. For one of the ruthenium precursors, [Rubpy-ph2-Si(CH3)3][PF6]2, single crystals were obtained by recrystallization from methanol. Their photophysical and electrochemical properties are reported. All the compounds are luminescent both at room and low temperature with long excited-state lifetimes due to an extended delocalization. Nanosecond transient absorption showed that the lowest excited state involves the chelating unit attached to the bridging ligand. Electrochemical data indicated that the first reduction is at a slightly more positive potential than for the reference complexes [M(bpy)3]2+ (M = Ru, Os). This result confirms that the best acceptor is the bipyridine moiety connected to the conjugated spacers. The role of the tilt angle between the phenylene units, in the two series of complexes, for the ground and excited states is discussed.
An investigation of the radiochemical stability of ionic liquids (2002)

Ionic liquids have been considered for their potential applications within the nuclear fuel cycle. If ionic liquids are to be successful in their application as solvents for highly radioactive materials in any future process, there will be a requirement for them to be robust to high radiation doses. A preliminary assessment of the radiation stability of 1,3-dialkylimidazolium cation based ionic liquids containing nitrate and chloride anions has been performed. The results of radiolysis studies are reported, in which the samples were exposed to alpha radiation from a tandem Van der Graaff generator, beta radiation from a linear accelerator and gamma radiation from cobalt 60 sources. These results suggest that their stability is similar to that of benzene and that they are much more stable than mixtures of tributylphosphate and odourless kerosene under similar irradiation conditions. The radiolysis of 1,3-dialkylimidazolium cation based ionic liquids reflects their combination of the properties of a salt, an alkane and an aromatic. They appear to be relatively radiation resistant and there is certainly no major decomposition of the organic component.