gebhart/patrepeval huggingface dataset:
Kilohertz Electrical Stimulation Nerve Conduction Block: Effects of Electrode Surface Area (2017)

Kilohertz electrical stimulation (KES) induces repeatable and reversible conduction block of nerve activity and is a potential therapeutic option for various diseases and disorders resulting from pathological or undesired neurological activity. However, successful translation of KES nerve block to clinical applications is stymied by many unknowns, such as the relevance of the onset response, acceptable levels of waveform contamination, and optimal electrode characteristics. We investigated the role of electrode geometric surface area on the KES nerve block threshold using 20- and 40-kHz current-controlled sinusoidal KES. Electrodes were electrochemically characterized and used to characterize typical KES waveforms and electrode charge characteristics. KES nerve block amplitudes, onset duration, and recovery of normal conduction after delivery of the KES were evaluated along with power requirements for effective KES nerve block. Results from this investigation demonstrate that increasing electrode geometric surface area provides for a more power-efficient KES nerve block. Reductions in block threshold by increased electrode surface area were found to be KES-frequency-dependent, with block thresholds and average power consumption reduced by greater than two times with 20-kHz KES waveforms and greater than three times for 40-kHz KES waveforms.
Aldose Reductase Inhibitor Fidarestat Prevents Retinal Oxidative Stress and Vascular Endothelial Growth Factor Overexpression in Streptozotocin-Diabetic Rats (2003)

The study addressed the role for aldose reductase (AR) in 1) retinal oxidative stress and vascular endothelial growth factor (VEGF) overexpression in early diabetes, and 2) high glucose-induced oxidative stress in retinal endothelial cells. In vivo experiments were performed on control rats and diabetic rats treated with or without low or high dose of the AR inhibitor (ARI) fidarestat (2 or 16 mg. kg(-1). day(-1)). In vitro studies were performed on bovine retinal endothelial cells (BREC) cultured in either 5 or 30 mmol/l glucose with or without 1 micro mol/l fidarestat. Intracellular reactive oxygen species were assessed using the 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (H(2)DCFDA) probe and flow cytometry. Both low and high doses of fidarestat (i.e., the doses that partially and completely inhibited sorbitol pathway hyperactivity) arrested diabetes-induced retinal lipid peroxidation. This was achieved due to upregulation of the key antioxidative defense enzyme activities rather than changes in reduced glutathione, oxidized glutathione, ascorbate and dehydroascorbate concentrations, and the glutathione and ascorbate redox states. Diabetes-associated 2.1-fold VEGF protein overexpression (enzyme-linked immunosorbent assay; ELISA) was dose-dependently prevented by fidarestat, whereas total VEGF mRNA and VEGF-164 mRNA (RT-PCR) abundance were not affected by either diabetes or the ARI. In BREC, fidarestat corrected hyperglycemia-induced increase in H(2)DCFDA fluorescence but not oxidative stress caused by three different pro-oxidants in normoglycemic conditions. In conclusion, increased AR activity contributes to retinal oxidative stress and VEGF protein overexpression in early diabetes. The findings justify the rationale for evaluation of fidarestat on diabetic retinopathy.
Manganese-Enhanced MRI Studies of Alterations of Intraretinal Ion Demand in Models of Ocular Injury (2007)

MEMRI measurements of uptake of systemically administered and nontoxic doses of manganese appear to be a powerful approach for measuring alteration in intraretinal ion demand in models of ocular injury.
Learning-based linguistic indexing of pictures with 2--d MHMMs (2002)

Automatic linguistic indexing of pictures is an important but highly challenging problem for researchers in computer vision and content-based image retrieval. In this paper, we introduce a statistical modeling approach to this problem. Categorized images are used to train a dictionary of hundreds of concepts automatically based on statistical modeling. Images of any given concept category are regarded as instances of a stochastic process that characterizes the category. To measure the extent of association between an image and the textual description of a category of images, the likelihood of the occurrence of the image based on the stochastic process derived from the category is computed. A high likelihood indicates a strong association. In our experimental implementation, the ALIP (Automatic Linguistic Indexing of Pictures) system, we focus on a particular group of stochastic processes for describing images, that is, the two-dimensional multiresolution hidden Markov models (2-D MHMMs). We implemented and tested the system on a photographic image database of 600 different semantic cat- egories, each with about 40 training images. Tested using 3,000 images outside the training database, the system has demonstrated good accuracy and high potential in linguistic indexing of these test images.
Dissociation of Rabies Virus Matrix Protein Functions in Regulation of Viral RNA Synthesis and Virus Assembly (2003)

Recently, we have shown that the rabies virus (RV) matrix (M) protein regulates the balance of virus RNA synthesis by shifting synthesis activity from transcription to replication (S. Finke, R. Mueller-Waldeck, and K. K. Conzelmann, J. Gen. Virol. 84:1613-1621, 2003). Here we describe the identification of an M residue critical for regulation of RV RNA synthesis. By analyzing the phenotype of heterotypic RV M proteins with respect to RNA synthesis of RV SAD L16, we identified the M proteins of the RV ERA and PV strains as deficient. Comparison of M sequences suggested that a single residue, arginine 58, was critical. A recombinant virus having this amino acid exchanged with a glycine, SAD M(R58G), has lost the abilities to downregulate RV transcription and to stimulate replication. This resulted in an increase in the transcription rate of more than 15-fold, as previously observed for M deletion mutants. Most importantly, the efficiencies of virus assembly and budding were equal for wild-type M and M(R58G), as determined in assays studying the transient complementation of an M- and G-deficient RV construct, NPgrL. In addition, virus particle density, protein composition, and specific infectivity of SAD L16 and SAD M(R58G) viruses were identical. Thus, we have identified mutations that affect the function of M only in regulation of RNA synthesis, but not in assembly and budding, providing evidence that these functions are genetically separable.
Inducible Gene Expression in Tumors Colonized by Modified Oncolytic Vaccinia Virus Strains (2014)

Oncolytic virotherapy of cancer can greatly benefit from the expression of heterologous genes. It is reasonable that some of those heterologous gene products could have detrimental effects either on the cancer patient or on the oncolytic virus itself if they are expressed at the wrong time or if the expression levels are too high. Therefore, exogenous control of gene expression levels by administration of a nontoxic inducer will have positive effects on the safety as well as the therapeutic outcome of oncolytic virotherapy. In addition, it paves the way for the introduction of new therapeutic genes into the genome of oncolytic viruses that could not have been tested otherwise.
The regulated expression of erythropoietin by two human hepatoma cell lines. (1987)

The development of a cell culture system that produces erythropoietin (Epo) in a regulated manner has been the focus of much effort. We have screened multiple renal and hepatic cell lines (including MDCK, LLC-PK1, BHK, WRL 68, CLCL, A704, CRFK, A498, ACHN, TCMK-1, LLC-MK2, CaKi-2, HepG2, and Hep3B) for either constitutive or regulated expression of Epo. Only the human hepatoma cell lines, Hep3B and HepG2, made significant amounts of Epo as measured both by radioimmunoassay and in vitro bioassay (as much as 330 milliunits per 10(6) cells in 24 hr). The constitutive production of Epo increased dramatically as a function of cell density in both cell lines. At cell densities less than 3.3 X 10(5) cells per cm2, there was little constitutive release of Epo in the medium (less than 30 milliunits per 10(6) cells in 24 hr). With Hep3B cells grown at low cell densities, a mean 18-fold increase in Epo expression was seen in response to hypoxia and a 6-fold increase was observed in response to incubation in medium containing 50 microM cobalt(II) chloride. At similar low cell densities, Epo production in HepG2 cells could be enhanced an average of about 3-fold by stimulation with either hypoxia or cobalt(II) chloride. Upon such stimulation, both cell lines demonstrated markedly elevated levels of Epo mRNA. Hence, both Hep3B and HepG2 cell lines provide an excellent in vitro system in which to study the physiological regulation of Epo expression.
Safety profile of topical diclofenac: a meta-analysis of blinded, randomized, controlled trials in musculoskeletal conditions (2011)

Topical diclofenac appears to be generally well tolerated for cutaneous use in acute and chronic musculoskeletal conditions.
Hypermethylation of multiple tumor-related genes associated with DMNT3b up-regulation served as a biomarker for early diagnosis of esophageal squamous cell carcinoma (2011)

This study was designed to determine the significance of DNA methyltransferases (DNMTs) in DNA hypermethylation in esophageal squamous cell carcinoma (ESCC) and to identify DNA methylation markers in serum for the early diagnosis of ESCC. A promoter methylation profile of 12 tumor-related genes was assessed using methylation-specific PCR in ESCC and paired non-tumor tissue samples from 47 patients. Expression levels of DNMTs were examined by real-time reverse transcription-PCR and immunohistochemistry. Using MethyLight, the methylation status of 5 genes was analyzed in serum samples from 45 patients and 15 healthy individuals. A total of 46 (97.9%) of 47 ESCC samples showed methylation in at least one of the examined genes, and methylation was most frequent for RAR-β (46.8%), DAPK (46.8%), p16 (44.7%), and CDH1 (42.6%). Methylation of RASSF1A was significantly correlated with the poorly differentiated tumors and the early pathologic tumor classification (P=0.035 and P=0.046, respectively). Tumoral DNMT3b mRNA up-regulation was significantly correlated with hypermethylation of multiple tumor-related genes (P=0.021). In addition, hypermethylation of cell-free serum DNA was common in ESCC patients, and diagnostic accuracy was increased when methylation of multiple genes (RAR-β, DAPK, CDH1, p16 and RASSF1A) were analyzed in combination (ROC AUC 0.911, 82.2% sensitivity and 100% specificity). The present study suggests that hypermethylation of multiple tumor-related genes may be involved in the pathogenesis of ESCC and mediated by the increase of DNMT3b expression. A cluster of multiple methylated genes in serum DNA has the potential as a novel biomarker for ESCC diagnosis.
Días sin TV: la salud del hombre (2004)

Hoy hace una tarde tranquila. Por la ventana lateral del apartamento se cuela un zumbido espasmódico y ligero, lo producen los escasos automóviles que cruzan la avenida de cuando en cuando. El edificio que habito parece un Titán dormido, trasmite una molicie áspera y duradera, pero eso no quiebra la armonía del ambiente, por el contrario, le otorga sentido al clima, que es casi tibio. Son las cinco pasado el meridiano y los árboles juguetean con una brisa ligera y torpe, que de cuando en cuando choca con los cristales de las ventanas y se dispersa en fuga. Yo me acerco al balcón y observo las construcciones vecinas. Son moles grises, aunque su color sea blanco, verde o azul, parecen grises y dormitan igual que la antigua estructura desde donde fisgoneo. Vivo en una zona residencial de clase media, construida al interés de personas dispuestas a la caminata diurna y la larga y serena conversación vespertina. A doscientos metros de donde estoy hay una plaza, muchos árboles, una estación del Metro, varios locales comerciales y una gran avenida principal. Vivo en Altamira, baluarte de la reacción sociopolítica al gobierno del ex teniente coronel del ejército Hugo Chávez Frías.
Industry First Field Trial of Reservoir Nanoagents (2011)

Abstract The promise of nanotechnology becomes limitless with the possibility of having functionalized molecular agents to "illuminate" the reservoir and intervene to alter adverse oil recovery conditions. The future reality of the reservoir nanoagents concept is herein lab and field demonstrated with the industry first building block nanoagents' template. The template is intentionally geared towards the harsh but prolific Arab-D carbonate formation of the giant Ghawar field of Saudi Arabia. The challenge is magnified by a condition of 100 °C or greater temperature and 120,000 ppm or more connate water salinity. The industry's first proven reservoir nanoagents template is introduced and demonstrated via a push-pull field trial in an observation well. The testing objectives, processes, and results are outlined and further detailed in the paper.
Can disturbed brain microcirculation cause Alzheimer’s disease? (1993)

Recent ultrastructural studies demonstrate characteristic and extensive angio-architectural distortions of cerebral capillaries in Alzheimer's brains. Alzheimer's disease subjects additionally show reduced cerebral blood flow (CBF), glucose metabolism and oxygen utilization which appear inversely proportional to the disease severity. These findings led us to develop a hypothetical model which appears consistent with the pathogenesis and progression of AD. During ageing, brain capillaries (site of the blood-brain barrier) may undergo progressive degeneration caused by amyloid deposits, thickened basement membrane, cerebral atrophy, reduced vessel elasticity, or genetic predisposition. When these structural abnormalities of the brain microvasculature begin to interfere with basic laws of fluid dynamics, haemorheological compromise will result in cerebral capillary resistance, high blood viscosity, abnormal flow patterns, and changes in shear stress and shear rate in vessel walls. The net effect is chronic 'disturbed' blood flow to the brain that impairs the delivery of essential nutrients, particularly oxygen and glucose, to cerebral neurons. As ischaemic-sensitive neurons lower their oxidative phosphorylation and ATP production to subfunctional levels, they release a diffusible glial mitogen that directly stimulates reactive astrocytosis. These reactive glia differ significantly from normal glia because they proliferate mostly in response to brain injury and can spread to unaffected tissue. It has been suggested that amyloid precursor protein (APP) may be expressed from reactive glia following neuronal injury thus providing the nidus of plaque formation. As brain tissue space is invaded by reactive glia and microglia, neuronal cytoskeletal damage can result in neurofibrillary tangles.(ABSTRACT TRUNCATED AT 250 WORDS)
Eye-length measurement by interferometry with partially coherent light (1988)

With a multimode semiconductor laser we have been able to measure the optical length of the eye within a precision of 0.03 mm. A first series of in vivo measurements acoustically determined eye length.
Bovine papillomavirus transcriptional regulation: localization of the E2-responsive elements of the long control region (1987)

The long control region (LCR) of the bovine papillomavirus type 1 genome can function as a conditional transcriptional enhancer which can be specifically trans-activated by the viral E2 gene product. To precisely map the target(s) of this trans-activation, BAL 31 exonuclease was used to generate two overlapping series of deleted DNA segments through the LCR. These fragments were assayed for their ability to activate transcription from the enhancer-deleted simian virus 40 early promoter of pA10CAT in the presence or absence of the viral E2 gene product. Two different E2-responsive elements were localized within the LCR. The major target for E2 trans-activation (E2-responsive element 1) was mapped to a 196-base-pair fragment between nucleotides 7611 and 7806, just upstream from promoters P7940 and P89. Further deletions which destroyed or impaired enhancer function revealed that the ACCN6GGT sequence motifs at each end of E2-responsive element 1 are critical components of this element. Primer extension analysis of RNA extracted from acute transfections with plasmids containing the bovine papillomavirus type 1 LCR driving the CAT gene revealed that each of the P7940 and P89 promoters is responsive to E2 trans-activation.
The JNK Pathway Regulates the In Vivo Deletion of Immature CD4+CD8+ Thymocytes (1998)

The extracellular signal-regulated kinase (ERK), the c-Jun NH2-terminal kinase (JNK), and p38 MAP kinase pathways are triggered upon ligation of the antigen-specific T cell receptor (TCR). During the development of T cells in the thymus, the ERK pathway is required for differentiation of CD4(-)CD8(-) into CD4(+)CD8(+) double positive (DP) thymocytes, positive selection of DP cells, and their maturation into CD4(+) cells. However, the ERK pathway is not required for negative selection. Here, we show that JNK is activated in DP thymocytes in vivo in response to signals that initiate negative selection. The activation of JNK in these cells appears to be mediated by the MAP kinase kinase MKK7 since high levels of MKK7 and low levels of Sek-1/MKK4 gene expression were detected in thymocytes. Using dominant negative JNK transgenic mice, we show that inhibition of the JNK pathway reduces the in vivo deletion of DP thymocytes. In addition, the increased resistance of DP thymocytes to cell death in these mice produces an accelerated reconstitution of normal thymic populations upon in vivo DP elimination. Together, these data indicate that the JNK pathway contributes to the deletion of DP thymocytes by apoptosis in response to TCR-derived and other thymic environment- mediated signals.
Morphological, Electrophysiological, and Synaptic Properties of Corticocallosal Pyramidal Cells in the Neonatal Rat Neocortex (2006)

Neocortical pyramidal cells (PCs) project to various cortical and subcortical targets. In layer V, the population of thick tufted PCs (TTCs) projects to subcortical targets such as the tectum, brainstem, and spinal cord. Another population of layer V PCs projects via the corpus callosum to the contralateral neocortical hemisphere mediating information transfer between the hemispheres. This subpopulation (corticocallosally projecting cells [CCPs]) has been previously described in terms of their morphological properties, but less is known about their electrophysiological properties, and their synaptic connectivity is unknown. We studied the morphological, electrophysiological, and synaptic properties of CCPs by retrograde labeling with fluorescent microbeads in P13-P16 Wistar rats. CCPs were characterized by shorter, untufted apical dendrites, which reached only up to layers II/III, confirming previous reports. Synaptic connections between CCPs were different from those observed between TTCs, both in probability of occurrence and dynamic properties. We found that the CCP network is about 4 times less interconnected than the TTC network and the probability of release is 24% smaller, resulting in a more linear synaptic transmission. The study shows that layer V pyramidal neurons projecting to different targets form subnetworks with specialized connectivity profiles, in addition to the specialized morphological and electrophysiological intrinsic properties.
Is There a Role for Hematopoietic Growth Factors During Sepsis? (2018)

Sepsis is a complex syndrome characterized by simultaneous activation of pro- and anti-inflammatory processes. After an inflammatory phase, patients present signs of immunosuppression and possibly persistent inflammation. Hematopoietic growth factors (HGFs) are glycoproteins that cause immune cells to mature and/or proliferate. HGFs also have a profound effect on cell functions and behavior. HGFs play crucial role in sepsis pathophysiology and were tested in several clinical trials without success to date. This review summarizes the role played by HGFs during sepsis and their potential therapeutic role in the Management of sepsis-related immune disturbances.
Alternate Paths from Epidermal Growth Factor Receptor to Akt in Malignant Versus Nontransformed Lung Epithelial Cells (2005)

In many human lung adenocarcinoma cell lines, a pathway involving epidermal growth factor receptor (EGFR), ErbB2 and ErbB3 receptors, phosphatidyl inositol 3-kinase (PI3K), Akt, glycogen synthase kinase 3-beta (GSK3-beta), and cyclin D1 controls cell growth, survival, and invasiveness. We have investigated this pathway in paired transformed/nontransformed cell lines from murine peripheral lung epithelium, E9/E10 and A5/C10. The E9 and A5 carcinoma lines expressed ErbB3 and transforming growth factor-alpha (TGF-alpha) and responded to TGF-alpha stimulation with protein complex formation including the p85 regulatory subunit of PI3K, activation of Akt, phosphorylation of GSK3-beta, and increased cyclin D1 protein and the cell cycle. ErbB3 and TGF-alpha were not detected in the nontransformed E10 and C10 cell lines. Nevertheless, exposure of E10 or C10 cells to TGF-alpha activated PI3K and Akt and increased cyclin D1 and cell growth. The effector pathway from the EGFR to PI3K in these nontransformed cells included the adaptor Grb2, the docking protein Gab1, and the phosphatase Shp2. Gab1 was highly expressed in E10 and C10 cells but not in the malignant E9 and A5 sister lines. Complexes of EGFR/Grb2/Gab1/Shp2 after TGF-alpha stimulation were prominent only in E10 and C10 cells. Thus, alternate pathways downstream of EGFR regulate mitosis in these paired malignant versus nontransformed lung cell lines.
Interaction of [fluorescein-Trp25]Glucagon with the Human Glucagon Receptor Expressed in Drosophila Schneider 2 Cells (1995)

The human glucagon receptor was expressed at high density in Drosophila Schneider 2 (S2) cells. Following selection with G418 and induction with CuSO4, the cells expressed the receptor at a level of 250 pmol/mg of membrane protein. The glucagon receptor was functionally coupled to increases in cyclic AMP in S2 cells. Protein immunoblotting with anti-peptide antibodies revealed the expressed receptor to have an apparent molecular mass of 48 kDa, consistent with low levels of glycosylation in this insect cell system. Binding of [fluorescein-Trp25]glucagon to S2 cells expressing the glucagon receptor was monitored as an increase in fluorescence anisotropy along with an increase in fluorescence intensity. Anisotropy data suggest that the mobility of the fluorescein is restricted when the ligand is bound to the receptor. Kinetic analysis indicates that the binding of glucagon to its receptor proceeds via a bimolecular interaction, with a forward rate constant that is several orders of magnitude slower than diffusion-controlled. These data would be consistent with a conformational change upon the binding of agonist to the receptor. The combination of [fluorescein-Trp25]glucagon with the S2 cell expression system should be useful for analyzing glucagon receptor structure and function.
Cloning the mRNA encoding 1-aminocyclopropane-1-carboxylate synthase, the key enzyme for ethylene biosynthesis in plants. (1989)

Ethylene is the plant hormone that controls several features of plant growth and development. The rate-limiting step in its synthesis is the formation of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) from S-adenosylmethionine (AdoMet), catalyzed by ACC synthase. We have isolated a complementary DNA sequence encoding ACC synthase from zucchini (Cucurbita) fruits. The biological activity of the clone was confirmed by the ability of the cloned sequence to direct ACC synthase activity in Escherichia coli and yeast. In vivo studies using the ACC cDNA as probe showed that the ACC synthase gene is induced by a diverse group of inducers, including wounding, Li+ ions, and the plant hormone auxin.