gebhart/patrepeval huggingface dataset:
Decoding the role of the nuclear receptor SHP in regulating hepatic stellate cells and liver fibrogenesis (2017)

The small heterodimer partner (SHP) is an orphan nuclear receptor that lacks the DNA binding domain while conserves a putative ligand-binding site, thought that endogenous ligands for this receptor are unknown. Previous studies have determined that SHP activation protects against development of liver fibrosis a process driven by trans-differentiation and activation of hepatic stellate cells (HSCs), a miofibroblast like cell type, involved in extracellular matrix (ECM) deposition. To dissect signals involved in this activity we generated SHP-overexpressing human and rat HSCs. Forced expression of SHP in HSC-T6 altered the expression of 574 genes. By pathway and functional enrichment analyses we detected a cluster of 46 differentially expressed genes involved in HSCs trans-differentiation. Using a isoxazole scaffold we designed and synthesized a series of SHP agonists. The most potent member of this group, ISO-COOH (EC<sub>50</sub>: 9 μM), attenuated HSCs trans-differentiation and ECM deposition in vitro, while in mice rendered cirrhotic by carbon tetrachloride (CCl<sub>4</sub>) or α-naphthyl-isothiocyanate (ANIT), protected against development of liver fibrosis as measured by morphometric analysis and expression of α-SMA and α1-collagen mRNAs. In aggregate, present results identify SHP as a counter-regulatory signal for HSCs transactivation and describe a novel class of SHP agonists endowed with anti-fibrotic activity.
Regulation of basic fibroblast growth factor (bFGF) gene and protein expression following its release from sublethally injured endothelial cells (1995)

Basic fibroblast growth factor (bFGF; FGF-2) lacks a signal sequence and thus is not secreted by classical pathways. It has been speculated that one mode of bFGF release may be injury, either sublethal or lethal; and, transient disruption of the plasma membrane has been shown to release bFGF [Muthukrihnan et al. (1991): J Cell Physiol 148:1-16]. This observation has led to the concept of bFGF as a "wound hormone," involved in tissue integrity and repair. Findings of elevated bFGF following injury in vivo support this concept. Using an in vitro model, we have examined the regulation of bFGF gene expression following its release by sublethal injury. Analysis of bFGF protein by ELISA revealed that scraping subconfluent bovine aortic EC (BAE) released up to 80% of their bFGF. Following scraping, there was a 4- to 10-fold increase in the steady state level of bFGF mRNA, which reached a maximum at 2-3 h. There was a parallel increase in protein so that by 6 h after the scrape-induced release, bFGF levels were restored to those measured prior to scraping. Since bFGF has been reported to induce its own expression, we hypothesized that the released bFGF might be responsible for the increase in bFGF mRNA. However, inclusion of neutralizing antibodies against bFGF had a negligible effect on the scrape-induced increase in bFGF mRNA levels. Because of the important role of transforming growth factor type-beta 1 (TGF-beta 1), the plasminogen/plasminogen activator system, and thrombin in wound healing, we investigated their potential contributions to the increase in bFGF expression. Addition of anti-TGF-beta 1 antibodies, plasminogen activator inhibitor-1 (PAI-1), or the thrombin inhibitory combination of heparin and anti-thrombin III (AT III) to the cells at the time of scraping blocked about 50% of the increase in bFGF mRNA; the effects of these agents were not additive. The suppression of bFGF mRNA was associated with a proportional reduction in bFGF protein. Inclusion of the antagonists for 2 h at the time of scraping led to reduced cell proliferation, suggesting that cell-associated bFGF may be required for recovery and growth. Finally, studies to characterize the molecular mechanisms underlying the increased bFGF mRNA following sublethal injury revealed an increase in the transcriptional activation of bFGF gene. These results indicate that in spite of the fact that bFGF is not a secreted protein, levels of bFGF in the cell are tightly regulated. Furthermore, these findings suggest a role for bFGF in recovery from cell injury.
N ε-(Carboxymethyl)Lysine Adducts of Proteins Are Ligands for Receptor for Advanced Glycation End Products That Activate Cell Signaling Pathways and Modulate Gene Expression (1999)

Recent studies suggested that interruption of the interaction of advanced glycation end products (AGEs), with the signal-transducing receptor receptor for AGE (RAGE), by administration of the soluble, extracellular ligand-binding domain of RAGE, reversed vascular hyperpermeability and suppressed accelerated atherosclerosis in diabetic rodents. Since the precise molecular target of soluble RAGE in those settings was not elucidated, we tested the hypothesis that predominant specific AGEs within the tissues in disorders such as diabetes and renal failure, N(epsilon)-(carboxymethyl)lysine (CML) adducts, are ligands of RAGE. We demonstrate here that physiologically relevant CML modifications of proteins engage cellular RAGE, thereby activating key cell signaling pathways such as NF-kappaB and modulating gene expression. Thus, CML-RAGE interaction triggers processes intimately linked to accelerated vascular and inflammatory complications that typify disorders in which inflammation is an established component.
Tumor necrosis factor-beta in the serum of adult T-cell leukemia with hypercalcemia (1991)

Serum tumor necrosis factor-beta (TNF-beta) from patients with adult T- cell leukemia (ATL) was studied by a sandwich enzyme-linked immunosorbent assay (ELISA) developed in our laboratory using biotinylated monoclonal anti-TNF-beta and recombinant TNF-beta. Seven of eight patients with hypercalcemia showed elevation of serum TNF- beta. On the other hand, TNF-beta could not be detected by the ELISA in 28 patients without hypercalcemia. The lower detection limit in this assay was 100 pg/mL, corresponding to 500 pg/mL by the conventional method. In two patients serum TNF-beta level decreased after treatment in association with the level of serum calcium. Furthermore, immuno- staining using anti-TNF-beta and avidin-biotin complex showed the presence of cytoplasmic TNF-beta in not only human T-cell leukemia virus type I infected cell lines, but also freshly isolated cells from ATL patients with hypercalcemia. The actual biologic activity of TNF- beta in serum was confirmed by a conventional bioassay in a patient with hypercalcemia, and its cytotoxic activity was inhibited by the addition of anti-TNF-beta antibody in the assay. These results suggested that serum TNF-beta might be one of the factors contributing to the hypercalcemia, at least in patients with ATL.
Activation of the silent progesterone receptor gene by ectopic expression of estrogen receptors in a rat fibroblast cell line (1993)

We describe the construction and characterization of a novel estrogen (E2)-responsive cell line, Rat1+ER, which ectopically expresses estrogen receptor (ER). Human ER cDNA was introduced by retrovirus-mediated gene transfer into the Rat1 cell line, which does not express functional ER endogenously. Rat1+ER cells express functional ER based on radioreceptor assays, immunoblotting, and transient transfection experiments using E2-responsive reporter plasmids. The effects of this ectopic ER expression were studied on three endogenous E2-responsive genes, prolactin (PRL), progesterone receptor (PR), and epidermal growth factor receptor (EGFR). PRL, usually expressed in the lactotrophs of the pituitary, is not expressed at all in Rat1+ER cells, with or without E2 addition, and appears to require other factors for expression. In contrast, although PR is not expressed in Rat1 cells, it is induced in Rat1+ER cells upon the addition of E2. This induction appears to occur at the transcriptional level and is insensitive to cycloheximide treatment. This is one of the few examples where the expression of one gene activates an otherwise silent gene. Another contrasting observation is that, although EGFR is basally expressed in Rat1+ER cells, the addition of E2 has no effect. Our studies paint a complicated picture of E2 regulation of endogenous genes: the activation of the PR gene may only require the presence of E2 and ER, whereas EGFR and PRL genes require factors in addition to ER for basal as well as E2-regulated expression.
Experimental demonstration of 2.5 Gbit/s transmissionwith 1 mpolymer optical backplane (2001)

An optical backplane for high-speed data transmission was experimentally examined. The transmission of 2.5 Gbit/s per channel over a 1 m multimode polymer waveguide is demonstrated.
Rapid Molecular Screening for Multidrug-Resistant Tuberculosis in a High-Volume Public Health Laboratory in South Africa (2008)

This molecular assay is a highly accurate screening tool for MDR TB, which achieves a substantial reduction in diagnostic delay. With overall performance characteristics that are superior to conventional culture and drug susceptibility testing and the possibility for high throughput with substantial cost savings, molecular testing has the potential to revolutionize MDR TB diagnosis.
Extended endoscopic endonasal approach to the pterygopalatine fossa: anatomical study and clinical considerations (2005)

In this anatomical study the endoscopic endonasal approach to the pterygopalatine fossa has been found to be a safe approach for the removal of lesions in this region. The approach could be proposed as an alternative to the standard microsurgical transmaxillary-transantral route.
An Economic Evaluation of Asthma in the United States (1992)

Potential reductions in the costs related to asthma in the United States may be identified through a closer examination of the effectiveness of care associated with each category of cost. Future health policy efforts to improve the effectiveness of primary care interventions for asthma in the ambulatory setting may reduce the costs of this common illness.
Site-Specific Recombinase Strategy to Create Induced Pluripotent Stem Cells Efficiently with Plasmid DNA (2011)

Induced pluripotent stem cells (iPSCs) have revolutionized the stem cell field. iPSCs are most often produced by using retroviruses. However, the resulting cells may be ill-suited for clinical applications. Many alternative strategies to make iPSCs have been developed, but the nonintegrating strategies tend to be inefficient, while the integrating strategies involve random integration. Here, we report a facile strategy to create murine iPSCs that uses plasmid DNA and single transfection with sequence-specific recombinases. PhiC31 integrase was used to insert the reprogramming cassette into the genome, producing iPSCs. Cre recombinase was then used for excision of the reprogramming genes. The iPSCs were demonstrated to be pluripotent by in vitro and in vivo criteria, both before and after excision of the reprogramming cassette. This strategy is comparable with retroviral approaches in efficiency, but is nonhazardous for the user, simple to perform, and results in nonrandom integration of a reprogramming cassette that can be readily deleted. We demonstrated the efficiency of this reprogramming and excision strategy in two accessible cell types, fibroblasts and adipose stem cells. This simple strategy produces pluripotent stem cells that have the potential to be used in a clinical setting.
Comparison of Direct and Indirect Effects of Non‐Thermal Atmospheric‐Pressure Plasma on Bacteria (2007)

Abstract Direct and indirect influence on microorganisms of non‐thermal atmospheric‐pressure DBD in air is compared in terms of bacterial inactivation rates. It is demonstrated that direct influence of the plasma, where charged particles contact bacteria directly, produces inactivation much faster than the indirect treatment, where plasma afterglow is delivered to the bacteria with a gas flow through the plasma region. This leads to an important conclusion that the effect of charged particles on plasma plays the essential role in interaction with living organisms, although synergy with longer living active molecules and atoms as well as UV radiation generated in plasma and at the surface of tissues may also play a role in inactivation. magnified image
Cultured Skin Substitutes: A Review (1996)

Skin substitutes composed of cultured cells and biopolymers provide alternative materials for study of skin biology and pathology, treatment of skin wounds, safety testing of consumer products, and therapeutic delivery of gene products. Most frequently, substitutes for epidermis consist of cultured keratinocytes and dermal substitutes consist of resorbable biopolymers populated with cultured fibroblasts. Preclinical models characterize cellular morphogenesis, antigen expression, and barrier properties in vitro, and recovery of tissue function after grafting. Clinical considerations include time required to prepare cultured autografts, time required for graft vascularization, management of microbial contamination in wounds, mechanical fragility of cultured grafts, and high cost. Safety in graft preparation generally requires the use of materials and procedures that comply with standards for quality assurance. Efficacy of engineered skin substitutes has been evaluated predominantly by subjective criteria, but evaluation may become more objective and quantitative by application of noninvasive biophysical instrumentation. Future directions with engineered skin substitutes are expected to include gene therapy by addition or deletion of selected gene products and establishment of international standards for fabrication and assessment of engineered skin.
Safe 3D navigation (2008)

Typical commercial 3D CAD tools provide modal tools such as pan, zoom, orbit, look, etc. to facilitate freeform navigation in a 3D scene. Mastering these navigation tools requires a significant amount of learning and even experienced computer users can find learning confusing and error-prone. To address this we have developed a concept called "Safe 3D Navigation" where we augment these modal tools with properties to reduce the occurance of confusing situations and improve the learning experience. In this paper we describe the major properties needed for safe navigation, the features we implemented to realize these properties, and usability tests on the effectiveness of these features. We conclude that indeed these properties do improve the learning experience for users that are new to 3D. Furthermore, many of the features we implemented for safe navigation are also very popular with experienced 3D users. As a result, these features have been integrated into six commercial 3D CAD applications and we recommend other application developers include these features to improve 3D navigation.
Activation of immediate-early, early, and late promoters by temperature-sensitive and wild-type forms of herpes simplex virus type 1 protein ICP4. (1985)

To better define the activities on herpes simplex virus type 1 gene expression of temperature-sensitive and wild-type forms of the transcriptional regulatory protein ICP4, regulatory sequences from immediate-early, early, and late herpes simplex virus genes were fused to the gene for chloramphenicol acetyltransferase (CAT). These constructs were used in trans induction and cotransfection experiments with wild-type and temperature-sensitive mutant alleles of ICP4. The ICP4 genes used in this study were cloned from the KOS strain (wild type) and two phenotypically distinct temperature-sensitive ICP4 mutants, tsB32 and tsL14 (DeLuca et al., J. Virol. 52:767-776, 1984), both alone and in conjunction with three other immediate-early genes. The latter series of plasmids was used to assess the influence of additional immediate-early gene products on gene expression in the presence of a given ICP4 allele. The results of this study demonstrate that the phenotypes of these ICP4 mutants observed in cell culture at the nonpermissive temperature were determined in part by activities associated with the mutant ICP4 polypeptides and that these activities differed from those of wild-type ICP4. Low levels of wild-type ICP4 had a marginal but reproducible stimulatory effect on immediate-early CAT gene expression, especially the pIE4/5CAT chimera. This effect was diminished with increasing quantities of ICP4, suggesting an inhibitory role for the wild-type form of the protein. The ICP4 mutants had a strong stimulatory effect on immediate-early CAT expression, consistent with their phenotypes at 39 degrees C. The mutant forms of the ICP4 polypeptide differed in their ability to induce CAT activity from an early chimeric gene. Thus, the tsL14 form of ICP4 was effective in early gene induction (i.e., ptkCAT was induced), whereas the ICP4 derived from tsB32 was slightly inhibitory. Cotransfection of tsB32 ICP4 simultaneously with other immediate-early genes resulted in a marginal increase in ptkCAT induction. This induction was enhanced when the gene for ICP4 was inactivated by restriction enzyme cleavage, substantiating the inhibitory effect of the tsB32 form of ICP4. The two mutant ICP4 genes (tsB32 and tsL14) were unable to trans-activate either of the late CAT constructs (p5CAT and pL42CAT) tested. Cotransfecting tsL14 ICP4 with the other immediate-early genes resulted in activation of p5CAT but not pL42CAT. Taken together, these studies demonstrate that (i) low levels of wild-type ICP4 have stimulatory effect on immediate-early promoters and that higher concentrations of wild-type ICP4 have an inhibitory effect on these promoters, (ii) isolated mutant form of ICP4 exhibit activities that reflect the phenotypes of the mutants from which they were isolated, and (iii) immediate-early gene products other than ICP4 are involved in determining the distinct phenotypes of the two mutants at 39 degrees Celsius.
Optimum systems control (1977)

The book contains a comprehensive, up-to-date introduction to the basic concepts and principles employed in the optimization estimation and control of dynamic systems. Fifteen chapters are contained in the text. (1) Introduction, (2) Calculus of extrema and single stage decision processes, (3) Variational calculus and continuous optimal control, (4) The maximum principle and Hamilton Jacobi theory, (5) Optimum systems control examples, (6) Discrete variational calculus and the discrete maximum principle, (7) Optimum control of distributed parameter systems, (8) Optimum state estimation in linear stationary systems, (9) Optimum filtering for nonstationary continuous systems, (10) Least- squares curve fitting and state estimation in discrete linear systems, (11) Controllability and observability--the separation theorem, (12) Sensitivity in optimum systems control, (13) Direct computational methods in optimum systems control, (14) Quasilinearization, (15) Invariant imbedding. (Author)
Emerging Nanotechnologies for Site Remediation and Wastewater Treatment (2005)

The impacts of nanotechnology are increasingly evident in all areas of science and technology, including the field of environmental studies and treatment. Experts anticipate the development and implementation of environmentally beneficial nanotechnologies in the categories of sensing and detecting, pollution prevention, and treatment and remediation. Of the three, the category of treatment and remediation has seemingly experienced the most growth in recent years. In terms of site remediation, the development and deployment of nanotechnology for contaminant destruction has already taken place. Nanoscale iron particles and the subsequent derivatives (bimetallic iron particles and emulsified iron) represent a viable commercially available nanotechnology for remediation. Currently, over 15 academic and commercial field scale tests involving nano-iron particles are underway or have reached completion. Many more sites have scheduled field studies and consequently the number of vendors supplying this product continues to grow. In addition, a multitude of nanotechnology applications for site remediation and wastewater treatment are currently in the research and development stages. From dendritic polymers to functionalized ceramics, the technologies poised to impact the treatment field are considerably diverse.
Activation of Orphan Receptors by the Hormone Relaxin (2002)

Relaxin is a hormone important for the growth and remodeling of reproductive and other tissues during pregnancy. Although binding sites for relaxin are widely distributed, the nature of its receptor has been elusive. Here, we demonstrate that two orphan heterotrimeric guanine nucleotide binding protein (G protein)-coupled receptors, LGR7 and LGR8, are capable of mediating the action of relaxin through an adenosine 3',5'-monophosphate (cAMP)-dependent pathway distinct from that of the structurally related insulin and insulin-like growth factor family ligand. Treatment of antepartum mice with the soluble ligand-binding region of LGR7 caused parturition delay. The wide and divergent distribution of the two relaxin receptors implicates their roles in reproductive, brain, renal, cardiovascular, and other functions.
Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice. (1991)

We describe preliminary studies of the pharmacokinetics, biodistribution, and excretion of an oligodeoxy-nucleotide phosphorothioate ([S]oligonucleotide) in mice. After either intravenous or intraperitoneal administration of a single dose (30 mg/kg of body weight), [S]oligonucleotide (35S-labeled at each internucleotide linkage) was found in most of the tissues for up to 48 hr. About 30% of the dose was excreted in urine within 24 hr, irrespective of the mode of administration; the excreted [S]oligonucleotide was found to be extensively degraded. In plasma, stomach, heart, and intestine, the [S]oligonucleotide was degraded by only 15%, whereas in the kidney and liver degradation was about 50% in 48 hr. The surprising observation was made that chain length extension of administered [S]oligonucleotide occurred in kidney, liver, and intestine. These results provide an initial definition of parameters for the pharmaceutical development of antisense oligonucleotides.
Proximity X-ray Lithography Using Self-Assembled Alkylsiloxane Films:  Resolution and Pattern Transfer (2000)

Self-assembled films of octadecyltrichlorosilane (OTS) on Si/SiO2 were patterned with proximity X-rays (λ = 1.0 nm) in air, resulting in the incorporation of oxygen-containing functional groups, that is, hydroxyl and aldehyde, into the film. Unexposed and exposed OTS exhibited sufficient chemical contrast for patterning processes based on differences in wetting behavior and chemical reactivity. Latent images of features as small as ∼70 nm, defined by the X-ray mask, were successfully fabricated in the OTS with high fidelity over areas of ∼1 cm2. Patterned OTS was imaged directly with lateral force microscopy and indirectly through atomic force microscopy of three-dimensional structures formed on the surface of thin films of diblock copolymers after deposition and annealing on the patterned OTS. Pattern transfer of features with dimensions as small as ∼150 nm into the underlying silicon substrate was achieved by reactive ion etching using thin films of nickel selectively deposited onto the exposed areas of the OTS as etch masks.