gebhart/patrepeval huggingface dataset:
Shear Stress Induced by an Interstitial Level of Slow Flow Increases the Osteogenic Differentiation of Mesenchymal Stem Cells through TAZ Activation (2014)

Shear stress activates cellular signaling involved in cellular proliferation, differentiation, and migration. However, the mechanisms of mesenchymal stem cell (MSC) differentiation under interstitial flow are not fully understood. Here, we show the increased osteogenic differentiation of MSCs under exposure to constant, extremely low shear stress created by osmotic pressure-induced flow in a microfluidic chip. The interstitial level of shear stress in the proposed microfluidic system stimulated nuclear localization of TAZ (transcriptional coactivator with PDZ-binding motif), a transcriptional modulator of MSCs, activated TAZ target genes such as CTGF and Cyr61, and induced osteogenic differentiation. TAZ-depleted cells showed defects in shear stress-induced osteogenic differentiation. In shear stress induced cellular signaling, Rho signaling pathway was important forthe nuclear localization of TAZ. Taken together, these results suggest that TAZ is an important mediator of interstitial flow-driven shear stress signaling in osteoblast differentiation of MSCs.
Double common-path interferometer for flexible optical probe of optical coherence tomography (2012)

A flexible curled optical cord is useful for a common-path optical coherence tomography (OCT) system because a bending-insensitive arbitrary length can be chosen for the endoscopic imaging probe. However, there has been a critical problem that the partial reflector needs to be placed in between the sample and the objective lens. It limits the structure design of optical probe and leads to a low transverse resolution OCT imaging. Instead of a conventional single common-path interferometer, we propose a novel double common-path interferometer configuration in order to generate an interference signal that is independent of the optical distance between the partial reflector and sample. Due to the limitless tuning of the objective distance, an objective lens with a high numerical aperture (NA) up to 0.85 can be successfully used for phase-sensitive optical coherence tomography to achieve a 3-dimensional profile image of a transverse resolution of 0.7 μm. The intensity and phase terms of the interference signal can be obtained simultaneously from a Fourier-domain mode locked swept laser source for fast data acquisition with a phase stability of 979 pm.
Therapeutic targets: MTOR and related pathways (2006)

AbstractThe mammalian target of rapamycin (mTOR), a protein kinase of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, has a central role in controlling malignant cellular growth. As a result, mTOR is viewed as an important target for anticancer drug development. Inhibitors of mTOR currently under evaluation in cancer clinical trials are rapamycin (also known as sirolimus, Wyeth) and derivatives temsirolimus (CCI-779, Wyeth), everolimus, (RAD001, Novartis Pharma AG ), and AP23573 (Ariad Pharmaceuticals). Preclinical studies suggest that sensitivity to mTOR inhibitors may correlate with activation of the PI3K pathway and/or with aberrant expression of cell cycle regulatory or anti-apoptotic proteins. Clinical trial results show that mTOR inhibitors are well tolerated and may induce prolonged stable disease and tumor regressions in cancer patients. Future research should evaluate optimal, schedule, patient selection, and combination strategies for this novel class of agents.
Targeting thyroid hormone receptor-β agonists to the liver reduces cholesterol and triglycerides and improves the therapeutic index (2007)

Despite efforts spanning four decades, the therapeutic potential of thyroid hormone receptor (TR) agonists as lipid-lowering and anti-obesity agents remains largely unexplored in humans because of dose-limiting cardiac effects and effects on the thyroid hormone axis (THA), muscle metabolism, and bone turnover. TR agonists selective for the TRbeta isoform exhibit modest cardiac sparing in rodents and primates but are unable to lower lipids without inducing TRbeta-mediated suppression of the THA. Herein, we describe a cytochrome P450-activated prodrug of a phosphonate-containing TR agonist that exhibits increased TR activation in the liver relative to extrahepatic tissues and an improved therapeutic index. Pharmacokinetic studies in rats demonstrated that the prodrug (2R,4S)-4-(3-chlorophenyl)-2-[(3,5-dimethyl-4-(4'-hydroxy-3'-isopropylbenzyl)phenoxy)methyl]-2-oxido-[1,3,2]-dioxaphosphonane (MB07811) undergoes first-pass hepatic extraction and that cleavage of the prodrug generates the negatively charged TR agonist (3,5-dimethyl-4-(4'-hydroxy-3'-isopropylbenzyl)phenoxy)methylphosphonic acid (MB07344), which distributes poorly into most tissues and is rapidly eliminated in the bile. Enhanced liver targeting was further demonstrated by comparing the effects of MB07811 with 3,5,3'-triiodo-l-thyronine (T(3)) and a non-liver-targeted TR agonist, 3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenylacetic acid (KB-141) on the expression of TR agonist-responsive genes in the liver and six extrahepatic tissues. The pharmacologic effects of liver targeting were evident in the normal rat, where MB07811 exhibited increased cardiac sparing, and in the diet-induced obese mouse, where, unlike KB-141, MB07811 reduced cholesterol and both serum and hepatic triglycerides at doses devoid of effects on body weight, glycemia, and the THA. These results indicate that targeting TR agonists to the liver has the potential to lower both cholesterol and triglyceride levels with an acceptable safety profile.
Mutations of BRAF and KRAS Precede the Development of Ovarian Serous Borderline Tumors (2004)

Molecular genetic changes that are associated with the initiating stage of tumor development are important in tumorigenesis. Ovarian serous borderline tumors (SBTs), putative precursors of low-grade serous carcinomas, are among the few human neoplasms with a high frequency of activating mutations in BRAF and KRAS genes. However, it remains unclear as to how these mutations contribute to tumor progression. To address this issue, we compared the mutational status of BRAF and KRAS in both SBTs and the adjacent epithelium from cystadenomas, the presumed precursor of SBTs. We found that three of eight SBTs contained mutant BRAF, and four SBTs contained mutant KRAS. All specimens with mutant BRAF harbored wild-type KRAS and vice versa. Thus, seven (88%) of eight SBTs contained either BRAF or KRAS mutations. The same mutations detected in SBTs were also identified in the cystadenoma epithelium adjacent to the SBTs in six (86%) of seven informative cases. As compared to SBTs, the cystadenoma epithelium, like ovarian surface epithelium, lacks cytological atypia. Our findings provide cogent evidence that mutations of BRAF and KRAS occur in the epithelium of cystadenomas adjacent to SBTs and strongly suggest that they are very early events in tumorigenesis, preceding the development of SBT.
Low delay random linear coding over a stream (2014)

We introduce a random linear code construction for erasure packet channel. We then analyze its in-order delivery delay behavior. We show that for rates below the capacity, the mean in-order-delivery delay of our scheme is better than the mean delay introduced by the scheme which implements the random linear block coding. We also compute the decoding failure probability and encoding and decoding complexity of our scheme.
Chronic Low‐Dose Oxidative Stress Induces Caspase‐3‐Dependent PKCδ Proteolytic Activation and Apoptosis in a Cell Culture Model of Dopaminergic Neurodegeneration (2008)

Oxidative stress has been implicated as a key event in the degenerative process of dopaminergic neurons; however, the cellular mechanisms underlying chronic oxidative stress-induced neurodegeneration remain to be established. In this study, N27 cells, a dopaminergic neuronal cell line derived from rat mesencephalon, exposed to low doses of H(2)O(2) (0-30 muM for 12-24 hr) exhibited dose- and time-dependent increases in cytotoxicity and ROS generation. In addition, the H(2)O(2)-induced neurotoxicity was accompanied by increased caspase-3 activity and PKCdelta cleavage. Notably, treatment with antioxidants Trolox and MnTBAP or PKCdelta cleavage inhibitor z-DIPD-fmk significantly protected against oxidative stress-induced apoptotic cell death. These results demonstrate that the N27 cell line is a useful model for the study of the chronic low-dose oxidative stress-induced apoptotic cell death cascade and that caspase-3-dependent PKCdelta proteolytic activation may be important in the apoptotic process in dopaminergic neurons undergoing chronic oxidative insult.
Encapsulation of palladium in polyurea microcapsules (2002)

An interfacial polymerisation approach is adopted to encapsulate palladium(II) acetate and palladium nanoparticles in polyurea microcapsules for use in catalysis.
Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial (2000)

Fluticasone propionate 500 microgram twice daily did not affect the rate of decline in FEV(1) but did produce a small increase in FEV(1). Patients on fluticasone propionate had fewer exacerbations and a slower decline in health status. These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease.
Report of Objective Clinical Responses of Cancer Patients to Pharmaceutical-grade Synthetic Cannabidiol (2018)

Pharmaceutical-grade synthetic cannabidiol is a candidate for treating breast cancer and glioma patients.
The Whitney Reduction Network: A Method for Computing Autoassociative Graphs (2001)

This article introduces a new architecture and associated algorithms ideal for implementing the dimensionality reduction of an m-dimensional manifold initially residing in an n-dimensional Euclidean space where n >> m. Motivated by Whitney's embedding theorem, the network is capable of training the identity mapping employing the idea of the graph of a function. In theory, a reduction to a dimension d that retains the differential structure of the original data may be achieved for some d < or = 2m + 1. To implement this network, we propose the idea of a good-projection, which enhances the generalization capabilities of the network, and an adaptive secant basis algorithm to achieve it. The effect of noise on this procedure is also considered. The approach is illustrated with several examples.
217. Widespread Distribution of Beta-Glucuronidase in the Mouse Brain Is Achieved after a Single Inoculation with a Neuroattenuated HSV Vector: Distribution Differs with Inoculation Site (2004)

Neovascularization leads to blindness in numerous ocular diseases, including diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, and sickle cell disease. More effective and stable treatments for ocular neovascularization are needed, as are animal models to test new interventions. In order to develop primate models of diabetic retinopathy and choroidal neovascularization (CNV), rhesus macaques were injected subretinally (n = 2) or intravitreally (n = 2) with an AAV2 vector carrying the cDNA encoding human vascular endothelial growth factor (VEGF) in the left eye or a control vector (AAV2.CMV.eGFP) in the right eye. Vector doses of the control and the treatment vector were 6.34 × 109 (n = 1) or 3 × 1011 (n = 1) infectious particles for each injection group. Overexpression of VEGF in the intraocular fluid was measured by ELISA at designated timepoints throughout the study. VEGF expression in the ocular fluids was significantly higher after intravitreal injection than after subretinal injection of the corresponding dose. VEGF expression in the control eye and serum were negligibly low. Neovascularization was evaluated by ophthalmoscopy, angiography, optical coherence tomography, and ultimately, histopathology. A prominent feature after intravitreal injection of AAV2.CMV.VEGF was the development of iris neovascularization, which was not seen in the subretinally injected and control eyes. Over-expression of VEGF through AAV2 resulted in rapid development of features of diabetic retinopathy or CNV depending on the targeted cell type/injection route and diffusion of VEGF. After intravitreal injection, low dose of AAV.VEGF did not have any effects on the neural retina or choroid, whereas high dose of AAV.VEGF induced inner retinal neovascularization. After subretinal injection, low dose of AAV.VEGF caused choroidal neovascularization and cystoid macular edema, whereas high dose of AAV.VEGF in addition led to inner retinal neovascularization.
Endothelial cell-derived lipase mediates uptake and binding of high-density lipoprotein (HDL) particles and the selective uptake of HDL-associated cholesterol esters independent of its enzymic activity (2002)

Endothelial cell-derived lipase (EDL) is a new member of the lipase gene family with high sequence homology with lipoprotein lipase (LPL). EDL is a phospholipase with very little triacylglycerol lipase activity. To investigate the effects of EDL on binding and uptake of high-density lipoprotein (HDL), as well as on the selective uptake of HDL-derived cholesterol esters (CEs), HepG2 cells were infected with adenovirus coding for EDL. For comparison, cells were also infected with LPL and with lacZ as a control. Both HDL binding and particle uptake were increased 1.5-fold and selective HDL-CE uptake was increased 1.8-fold in EDL-infected HepG2 cells compared with controls. The effect of LPL was less pronounced, resulting in 1.1-fold increase in particle uptake and 1.3-fold increase in selective uptake. Inhibition of the enzymic activity with tetrahydrolipstatin (THL) significantly enhanced the effect of EDL, as reflected by a 5.2-fold increase in binding, a 2.6-fold increase in particle uptake and a 1.1-fold increase in CE selective uptake compared with incubations without THL. To elucidate the mechanism responsible for the effects of THL, we analysed the abundance of heparin-releasable EDL protein from infected HepG2 cells upon incubations with THL, HDL and free (non-esterified) fatty acids (FFAs). In the presence of THL, vastly more EDL protein remained bound to the cell surface. Additionally, HDL and FFAs reduced the amount of cell-surface-bound EDL, suggesting that fatty acids that are liberated from phospholipids in HDL release EDL from the cell surface. This was substantiated further by the finding that, in contrast with EDL, the amount of cell-surface-bound enzymically inactive mutant EDL (MUT-EDL) was not reduced in the presence of HDL and foetal calf serum. The increased amount of cell-surface-bound MUT-EDL in the presence of THL suggested that the enzymic inactivity of MUT-EDL, as well as an augmenting effect of THL that is independent of its ability to inactivate the enzyme, are responsible for the increased amount of cell-surface-bound EDL in the presence of THL. Furthermore, in cells expressing MUT-EDL, binding and holoparticle uptake were markedly higher compared with cells expressing the active EDL, and could be increased further in the presence of THL. Despite 1.7-fold higher binding and 1.8-fold higher holoparticle uptake, the selective CE uptake by MUT-EDL-expressing cells was comparable with EDL-expressing cells and was even decreased 1.3-fold with THL. Experiments in CLA-1 (CD-36 and LIMPII analogous 1, the human homologue of scavenger receptor class B type I)-deficient HEK-293 cells demonstrated that EDL alone has the ability to stimulate HDL-CE selective uptake independently of CLA-1. Thus our results demonstrate that EDL mediates both HDL binding and uptake, and the selective uptake of HDL-CE, independently of lipolysis and CLA-1.
Thrombin stimulates c-sis gene expression in microvascular endothelial cells. (1986)

We have determined whether expression of the c-sis gene product, platelet-derived growth factor (PDGF), is regulated in cultured renal microvascular endothelial cells by factors to which vascular endothelial cells may be exposed at sites of perivascular cellular proliferation. Thrombin exposure increased endothelial cell levels of c-sis message by 3-5-fold over a time course that peaked at 4 h after exposure. Similarly, thrombin-exposed microvascular endothelial cells released increased amounts of PDGF activity into their media. The thrombin effect was not mediated through the proteolytic activity of thrombin, as proteolytically inactive thrombin stimulated the c-sis expression as well as native thrombin. This stimulation was mimicked by exposure of cells to biologically active phorbol esters, suggesting that thrombin action may be mediated through activation of kinase C (Ca2+/phospholipid-dependent enzyme). Thus, thrombin regulates the expression and release of PDGF activity from endothelial cells in culture and may act in vivo to stimulate mitogen release from endothelial cells, thereby inducing proliferation of perivascular cells.
Structural insights into the degradation of Mcl-1 induced by BH3 domains (2007)

Apoptosis is held in check by prosurvival proteins of the Bcl-2 family. The distantly related BH3-only proteins bind to and antagonize them, thereby promoting apoptosis. Whereas binding of the BH3-only protein Noxa to prosurvival Mcl-1 induces Mcl-1 degradation by the proteasome, binding of another BH3-only ligand, Bim, elevates Mcl-1 protein levels. We compared the three-dimensional structures of the complexes formed between BH3 peptides of both Bim and Noxa, and we show that a discrete C-terminal sequence of the Noxa BH3 is necessary to instigate Mcl-1 degradation.
Single Wall Carbon Nanotube−Nafion Composite Actuators (2002)

Single wall carbon nanotube (SWNT)−Nafion composite actuators have been demonstrated for 0.1−18% w/w doping of purified SWNTs within the polymer matrix. The high purity SWNTs, >95% w/w, were homogeneously dispersed into the polymer through a series of homogenization and high sheer mixing techniques. The efficient distribution of the high aspect ratio, conductive SWNT materials allowed for the actuation of the Nafion membrane to be reached at SWNT doping levels as low as 0.5% w/w. Utilizing a two-electrode bimorph cantilever actuator immersed into an aqueous lithium chloride solution, tip deflections up to 4.5 mm were observed.
Tumor Necrosis Factor Promotes Runx2 Degradation through Up-regulation of Smurf1 and Smurf2 in Osteoblasts (2005)

Tumor necrosis factor (TNF) plays an important role in the pathogenesis of inflammatory bone loss through stimulation of osteoclastic bone resorption and inhibition of osteoblastic bone formation. Compared with the well established role of TNF in osteoclastogenesis, mechanisms by which TNF inhibits osteoblast function have not been fully determined. Runx2 is an osteoblast-specific transcription factor whose steady-state protein levels are regulated by proteasomal degradation, mediated by the E3 ubiquitin ligases, Smurf1 and Smurf2. We hypothesized that TNF inhibits osteoblast function through Smurf-mediated Runx2 degradation. We treated C2C12 and 2T3 osteoblast precursor cell lines and primary osteoblasts with TNF and found that TNF, but not interleukin-1, significantly increased Smurf1 and Smurf2 expression. TNF increased the degradation of endogenous or transfected Runx2 protein, which was blocked by treating cells with a proteasomal inhibitor or by infecting cells with small interfering (si)RNA against Smurf1 or Smurf2. TNF inhibited the expression of bone morphogenetic protein and transforming growth factor-beta signaling reporter constructs, and the inhibition of each was blocked by Smurf1 siRNA and Smurf2 siRNA, respectively. Overexpression of Smurf1 and/or Smurf2 siRNAs prevented the inhibitory effect of TNF on Runx2 reporter. Consistent with these in vitro findings, bones from TNF transgenic mice or TNF-injected wild type mice had increased Smurf1 and decreased Runx2 protein levels. We propose that one of the mechanisms by which TNF inhibits bone formation in inflammatory bone disorders is by promoting Runx2 proteasomal degradation through up-regulation of Smurf1 and Smurf2 expression.
The tapered slot antenna-a new integrated element for millimeter-wave applications (1989)

Tapered slot antennas (TSAs) with a number of potential applications as single elements and focal plane arrays are discussed. TSAs are fabricated with photolithographic techniques and integrated in either hybrid or MMIC circuits with receiver or transmitter components. They offer considerably narrower beams than other integrated antenna elements and have high aperture efficiency and packing density as array elements. Both the circuit and radiation properties of TSAs are reviewed. Topics covered include: antenna beamwidth, directivity, and gain of single-element TSAs; their beam shape and the effect of different taper shapes; and the input impedance and the effects of using thick dielectrics. These characteristics are also given for TSA arrays as are the circuit properties of the array elements. Different array structures and their applications are also described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Structure of human type II 5 alpha-reductase gene. (1992)

The best known activity of steroid 5 alpha-reductase is the transformation of testosterone into dihydrotestosterone, the most potent androgen. Two types of human steroid 5 alpha-reductase cDNAs and the type I gene have previously been isolated and characterized. This report describes the isolation and characterization of the human type II 5 alpha-reductase gene, the gene most likely responsible for male pseudohermaphroditism due to 5 alpha-reductase deficiency as well as the one presumed to be involved in a major androgen-related diseases such as prostate cancer and benign prostatic hyperplasia. The type II 5 alpha-reductase gene contains five exons of 352, 164, 102, 151 and 1695 bp, respectively, which share 43.8% to 64.1% homology with exons of the corresponding type I gene. These exons are separated by four introns of greater than 29, and approximately 2.3, 2.0 and 3.0 kb. Analysis of primer extension products by polyacrylamide gel electrophoresis as well as by subcloning and sequencing reveals a start site located 71 nucleotides upstream the ATG initiating codon.
Does Autophagy Mediate Cardiac Myocyte Death During Stress? (2016)

Although autophagy generally promotes survival of cardiac myocytes, it also promotes death of cardiac myocytes in some conditions. Here we describe how activation of autophagy leads to death of cardiac myocytes, introduce a novel concept of autosis, a unique form of cell death by autophagy, and discuss the functional significance of autophagic cell death in cardiac myocytes.
Interactions between terminal mobility and personal mobility (2002)

Wireless access networks support terminal mobility by providing wireless terminals with access to their subscribed services across multiple networks. Universal Personal Telecommunication (UPT) supports personal mobility by providing users with access to their subscribed services across multiple networks at any terminal. To support terminal mobility, it is necessary to associate service subscription with the terminal itself, not the point at which it accesses the network as was done traditionally. This terminal-related service information can then be shared across networks so that the same services can be provided at any location. Personal mobility requires a similar approach but with a focus on users. However, when a UPT user makes use of a wireless terminal there results an interaction between terminal mobility and personal mobility which is not necessarily straightforward and needs to be investigated.