gebhart/patrepeval huggingface dataset:
Single Cell Kinetics of Intracellular, Nonviral, Nucleic Acid Delivery Vehicle Acidification and Trafficking (2005)

Mechanistic understanding of the intracellular trafficking of nonviral nucleic acid delivery vehicles remains elusive. A live, single cell-based assay is described here that is used to investigate and quantitate the spatiotemporal, intracellular pH microenvironment of polymeric-based nucleic acid delivery vehicles. Polycations such as polyethylenimine (PEI), poly-l-lysine (PLL), beta-cyclodextrin-containing polymers lacking or possessing imidazole termini (CDP or CDP-imid), and cyclodextrin-grafted PEI (CD-PEI) are used to deliver an oligonucleotide containing a single fluorophore with two emission lines that can be employed to measure the pH. Delivery vehicles were also sterically stabilized by addition of poly(ethylene glycol) (PEG) and investigated. The intracellular trafficking data obtained via this new methodology show that vectors such as PEI and CDP-imid can buffer the endocytic vesicles while PLL and CDP do not. Additionally, the PEGylated vectors reveal the same buffering capacity as their unstabilized variants. Here, the live cell, spatiotemporal mapping of these behaviors is demonstrated and, when combined with cell uptake and luciferase expression data, shows that there is not a correlation between buffering capacity and gene expression.
Nitrofurantoin quadruple therapy for Helicobacter pylori infection: effect of metronidazole resistance (2001)

Because nitrofurantoin quadruple therapy performed inadequately in the presence of metronidazole resistance, we conclude that nitrofurantoin is unlikely to find clinical utility for the eradication of H. pylori.
From Split-Pool Libraries to Spatially Addressable Microarrays and Its Application to Functional Proteomic Profiling (2001)

Small molecules encoded with peptidonucleic acid (PNA) were used to probe protein function in a microarray format. The PNA tag served to encode the synthetic history of the small molecule and to positionally encode the identity of the small molecule by its location upon hybridization to an oligonucleotide microarray.
IL‐6 Expression in Neurons of Transgenic Mice Causes Reactive Astrocytosis and Increase in Ramified Microglial Cells but no Neuronal Damage (1995)

Growing evidence suggests that aberrant production of inflammatory cytokines within the central nervous system (CNS) contributes to the development of pathological conditions. To test the cause-effect relationship between the overproduction of interleukin-6 (IL-6) in the CNS and the onset of neuropathological changes, we have generated transgenic mice in which human IL-6 expression has been targeted to the neurons by using the rat neuron-specific enolase promoter. These mice develop reactive astrocytosis and an increase in ramified microglial cells but do not show histological or behavioural signs of neuron damage at the light microscope level. We thus conclude that a constant release of human IL-6 by neuronal subpopulations in mice is sufficient to activate cells potentially capable of modulating the local immune response, but at the same time is compatible with normal neuron functions.
Effects of atrial natriuretic peptide on type II alveolar epithelial cells of the rat lung. Autoradiographic and morphometric studies. (1989)

Effects of atrial natriuretic peptides (ANP) on Type II cells of the rat lung were examined, using autoradiographic and morphometric techniques. The injection of an excess of ANP, together with [125I]ANP, significantly inhibited the uptake of radioactive ANP in the lung tissue. Following autoradiography, silver grains of [125I]ANP labelled Type II cells, endothelial cells and smooth muscle cells of vessels, bronchi and bronchioles. As for morphometric changes in subcellular structures of Type II cells after the injection of ANP, the volume and surface densities of the rough endoplasmic reticulum increased at 15 minutes, while those of the Golgi complex increased from 5 minutes, peaking at 30 minutes. At 15 minutes the volume and surface densities of mitochondria significantly increased. The volume and surface densities of multivesicular bodies with an electron-dense matrix also increased from 15 minutes after the injection. Lamellar bodies showed decreased volume and surface densities at 15 minutes whereas the densities showed an increase at 30 minutes and were higher at 60 minutes than those in the control. These results suggest that Type II cells provide a binding site for ANP which facilitates the production of lamellar bodies in addition to their secretion.
High PD-L1 Expression Correlates with Metastasis and Poor Prognosis in Oral Squamous Cell Carcinoma (2015)

PD-L1 has been widely demonstrated to contribute to failed antitumor immunity. Blockade of PD-L1 with monoclonal antibody could modulate the tumor immune environment to augment immunotherapy. PD-L1 expression is also detected in several types of cancer and is associated with poor prognosis. However, the prognostic role of PD-L1 in oral squamous cell carcinoma (OSCC) is still controversial. Our aim was to determine the role of PD-L1 in the prognosis of OSCC patients to identify its potential therapeutic relevance. PD-L1 immunoreactivity was analyzed by immunohistochemistry in 305 cancer specimens from primary OSCC patients. The medium follow-up time after surgery was 3.8 years (range from 0.1 to 11.1 years). The prognostic value of PD-L1 on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. Higher PD-L1 expression is more likely in tumor tissues of female than male OSCC patients (P = 0.0062). Patients with distant metastasis also had high PD-L1 expression (P = 0.0103). Multivariate analysis identified high PD-L1 expression as an independent risk factor in males and smokers (males: hazard ratio = 1.556, P = 0.0077; smokers: hazard ratio = 2.058, P = 0.0004). We suggest that PD-L1 expression, determined by IHC staining, could be an independent prognostic marker for OSCC patients who are male or who have a smoking habit.
Attenuation of Experimental Autoimmune Demyelination in Complement-Deficient Mice (2000)

Abstract The exact mechanisms leading to CNS inflammation and myelin destruction in multiple sclerosis and in its animal model, experimental allergic encephalomyelitis (EAE) remain equivocal. In both multiple sclerosis and EAE, complement activation is thought to play a pivotal role by recruiting inflammatory cells, increasing myelin phagocytosis by macrophages, and exerting direct cytotoxic effects through the deposition of the membrane attack complex on oligodendrocytes. Despite this assumption, attempts to evaluate complement’s contribution to autoimmune demyelination in vivo have been limited by the lack of nontoxic and/or nonimmunogenic complement inhibitors. In this report, we used mice deficient in either C3 or factor B to clarify the role of the complement system in an Ab-independent model of EAE. Both types of complement-deficient mice presented with a markedly reduced disease severity. Although induction of EAE led to inflammatory changes in the meninges and perivascular spaces of both wild-type and complement-deficient animals, in both C3−/− and factor B−/− mice there was little infiltration of the parenchyma by macrophages and T cells. In addition, compared with their wild-type littermates, the CNS of both C3−/− and factor B−/− mice induced for EAE are protected from demyelination. These results suggest that complement might be a target for the therapeutic treatment of inflammatory demyelinating diseases of the CNS.
Flight management of multiple aerial vehicles using genetic algorithms (2006)

Flight management system (FMS) plays an important role in automatic and fuel-efficient flight from take-off to landing and reducing the pilot's workload. Path planning and tracking are two major functions of FMS. Most flight control algorithms assume that reference trajectory is available, which is not the case in real world. In this paper we introduce a new FMS that not only generates the optimal trajectory but also produces smooth control action for path tracking. Genetic algorithms (GAs) is used to generate the optimal flight path when the target positions are given. Unknown obstacles also are considered. A memory based control strategy is developed to steer the vehicle along the generated trajectory, which can be dynamically adjusted according to the varying flight conditions. Simulation is conducted for verification
Sustained improvement in rheumatoid arthritis following a protocol designed to deplete B lymphocytes (2001)

Objectives. An open study of B‐lymphocyte depletion was undertaken in rheumatoid arthritis (RA) patients to test the hypothesis that B lymphocytes may be essential to disease perpetuation.
Down-Regulation of Stromal Cell-Derived Factor-1α-Induced T Cell Chemotaxis by a Peptide Based on the Complementarity-Determining Region 1 of an Anti-DNA Autoantibody via Up-Regulation of TGF-β Secretion (2005)

Systemic lupus erythematosus (SLE) can be induced in mice by immunizing them with a monoclonal human anti-DNA Ab that expresses a major Id, designated 16/6Id. In addition, a peptide based on the sequence of the CDR 1 (hCDR1) of the 16/6Id ameliorated the clinical manifestations of SLE in experimental models. In this study we examined the effects of treating mice with human complementary-determining region 1 (hCDR1) on the subsequent chemotaxis of T cells derived from 16/6Id-primed mice. First we demonstrated elevated levels of stromal cell-derived factor-1alpha (SDF-1alpha) in the sera of SLE-afflicted mice and in the sera and lymphoid tissues of 16/6Id-immunized BALB/c mice shortly after the immunization. We then found that administration of hCDR1 to 16/6Id-immunized mice specifically down-regulated SDF1alpha-induced T cell chemotaxis through fibronectin and collagen type I. This was accompanied by diminished SDF1-alpha-induced T cell adhesion and ERK phosphorylation. Treatment with hCDR1 up-regulated TGF-beta secretion, which, in turn, inhibited the murine T cell adhesion to and chemotaxis through fibronectin as well as their ERK phosphorylation. Thus, the secretion of TGF-beta after treatment of 16/6Id-immunized mice with hCDR1 plays an important role in the down-regulation of SDF-1alpha-mediated T cell activation and the interactions with extracellular matrix moieties observed in the present study.
Sublingual buprenorphine used postoperatively: clinical observations and preliminary pharmacokinetic analysis. (1981)

1 Buprenorphine is a long-acting opiate analgesic. This study was designed to investigate the pharmacokinetics of this drug when given by the sublingual route to ten postoperative patients. Plasma levels of buprenorphine were measured by a specific radioimmunoassay. 2 Plasma levels of the drug following sublingual administration of 0.4 mg showed an apparent delay in absorption and then rose slowly to reach low but significant levels by 3 h. There was considerable variation in the time at which peak levels were achieved. The average systemic availability of the drug by this route was estimated to be 30% by 3 h. 3 Analgesic efficacy and duration of sublingual buprenorphine were assessed using demand analgesia. The analgesia was of about 9 h duration, similar to that achieved by parenteral administration of 0.3 mg of the drug to an equivalent group of patients. The sublingual dose caused a significant fall in the postoperatively elevated group of patients. The sublingual dose caused a significant fall in the postoperatively elevated plasma glucose, and prevented any further rise in plasma cortisol. 4 Reasons for the efficacy of the sublingual route are discussed and it is suggested that this route may be particularly appropriate for highly lipophilic drugs like buprenorphine.
Synthesis and pharmacological evaluation of 2,3-dihydro-1H-thieno[2,3-e][1,4]diazepines (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and pharmacological evaluation of 2,3-dihydro-1H-thieno[2,3-e][1,4]diazepinesFrancis J. Tinney, Joseph P. Sanchez, and Joan A. NogasCite this: J. Med. Chem. 1974, 17, 6, 624–630Publication Date (Print):June 1, 1974Publication History Published online1 May 2002Published inissue 1 June 1974https://pubs.acs.org/doi/10.1021/jm00252a011https://doi.org/10.1021/jm00252a011research-articleACS PublicationsRequest reuse permissionsArticle Views353Altmetric-Citations48LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Yeast TATA-binding protein TFIID binds to TATA elements with both consensus and nonconsensus DNA sequences. (1989)

The DNA binding properties of the yeast TATA element-binding protein TFIID were investigated. The affinity (apparent equilibrium dissociation constant) of TFIID for the adenovirus major late promoter consensus TATA element is 2 x 10(-9) M, a value similar to the affinity of gene-specific regulatory proteins for their binding sites. TFIID binding is highly specific and recognizes nonspecific sites with approximately 10(5)-fold lower affinity. Despite this specificity, TFIID also binds with high affinity to several TATA elements that do not match the consensus TATA sequences (TATAAA and TATATA): the yeast LEU2 TATA (TATTATTTA), the simian virus 40 TATA (CTTATTTAT), and the yeast CYC1 -10 TATA (TTATACATT) all bound TFIID. Furthermore, TFIID was active in promoting transcription in vitro from the nonconsensus TATA elements. Thus, contrary to previous suggestions, the existence of nonconsensus TATA elements does not itself indicate the existence of multiple TATA-binding factors.
Nucleotide oligomerization domain-containing proteins instruct T cell helper type 2 immunity through stromal activation (2011)

Although a number of studies have examined the development of T-helper cell type 2 (Th2) immunity in different settings, the mechanisms underlying the initiation of this arm of adaptive immunity are not well understood. We exploited the fact that immunization with antigen plus either nucleotide-binding oligomerization domain-containing proteins 1 (Nod1) or 2 (Nod2) agonists drives Th2 induction to understand how these pattern-recognition receptors mediate the development of systemic Th2 immune responses. Here, we show in bone-marrow chimeric mice that Nod1 and Nod2 expression within the stromal compartment is necessary for priming of effector CD4(+) Th2 responses and specific IgG1 antibodies. In contrast, sensing of these ligands by dendritic cells was not sufficient to induce Th2 immunity, although these cells contribute to the response. Moreover, we determined that CD11c(+) cells were the critical antigen-presenting cells, whereas basophils and B cells did not affect the capacity of Nod ligands to induce CD4(+) Th2 effector function. Finally, we found that full Th2 induction upon Nod1 and Nod2 activation was dependent on both thymic stromal lymphopoietin production by the stromal cells and the up-regulation of the costimulatory molecule, OX40 ligand, on dendritic cells. This study provides in vivo evidence of how systemic Th2 immunity is induced in the context of Nod stimulation. Such understanding will influence the rational design of therapeutics that could reprogram the immune system during an active Th1-mediated disease, such as Crohn's disease.
A novel single-feed circular polarized slotted loop antenna (2003)

A novel single feed circular polarized (CP) slotted loop at L-band for low cost application is reported. This antenna uses a microstrip transmission line to feed a square loop slot on the opposite side of the substrate, two slotted stubs are placed across the diagonal line of the square loop. A wide bandwidth of 11% for less than 3 dB axial ratio (AR) and 10 dB return loss have been achieved.
Regulation of mTOR and Cell Growth in Response to Energy Stress by REDD1 (2005)

The tuberous sclerosis tumor suppressors TSC1 and TSC2 regulate the mTOR pathway to control translation and cell growth in response to nutrient and growth factor stimuli. We have recently identified the stress response REDD1 gene as a mediator of tuberous sclerosis complex (TSC)-dependent mTOR regulation by hypoxia. Here, we demonstrate that REDD1 inhibits mTOR function to control cell growth in response to energy stress. Endogenous REDD1 is induced following energy stress, and REDD1-/- cells are highly defective in dephosphorylation of the key mTOR substrates S6K and 4E-BP1 following either ATP depletion or direct activation of the AMP-activated protein kinase (AMPK). REDD1 likely acts on the TSC1/2 complex, as regulation of mTOR substrate phosphorylation by REDD1 requires TSC2 and is blocked by overexpression of the TSC1/2 downstream target Rheb but is not blocked by inhibition of AMPK. Tetracycline-inducible expression of REDD1 triggers rapid dephosphorylation of S6K and 4E-BP1 and significantly decreases cellular size. Conversely, inhibition of endogenous REDD1 by short interfering RNA increases cell size in a rapamycin-sensitive manner, and REDD1-/- cells are defective in cell growth regulation following ATP depletion. These results define REDD1 as a critical transducer of the cellular response to energy depletion through the TSC-mTOR pathway.
Mesenchymal Stem Cell Transplantation Reverses Multiorgan Dysfunction in Systemic Lupus Erythematosus Mice and Humans (2009)

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that, despite the advances in immunosuppressive medical therapies, remains potentially fatal in some patients, especially in treatment-refractory patients. Here, we reported that impairment of bone marrow mesenchymal stem cells (BMMSCs) and their associated osteoblastic niche deficiency contribute in part to the pathogenesis of SLE-like disease in MRL/lpr mice. Interestingly, allogenic BMMSC transplantation (MSCT) is capable of reconstructing the bone marrow osteoblastic niche and more effectively reverses multiorgan dysfunction when compared with medical immunosuppression with cyclophosphamide (CTX). At the cellular level, MSCT, not CTX treatment, was capable to induce osteoblastic niche reconstruction, possibly contributing to the recovery of regulatory T-cells and reestablishment of the immune homeostasis. On the basis of the promising clinical outcomes in SLE mice, we treated four CTX/glucocorticoid treatment-refractory SLE patients using allogenic MSCT and showed a stable 12-18 months disease remission in all treated patients. The patients benefited an amelioration of disease activity, improvement in serologic markers and renal function. These early evidences suggest that allogenic MSCT may be a feasible and safe salvage therapy in refractory SLE patients.
Clinical Experience with Inorganic, Non-radioactive Iodine/Iodide (2005)

I have been interested in iodine supplementation for years. I have a holistic family practice in West Bloomfield, Michigan. Michigan resides in the Goiter Belt of the United States where the soil is deficient in iodine. Although I long suspected iodine deficiency in many of my patients, the use of potassium iodide (SSKI) in my patients gave suboptimal results. Some patients did improve, but many did not notice any appreciable improvement. This article was written to assist health care practitioners in the implementation of orthoiodosupplementation in their practice. Orthoiodosupplementation is the daily amount of iodine and iodide needed for whole body sufficiency. 1 Whole body sufficiency for iodine is assessed by an iodine/iodide loading test. 2,3 This article will be divided into two parts: the first part will describe a doctor’s (your author) introduction and education on the clinical uses of iodine and iodide, while the second part will give the reader “clinical pearls” about how to integrate and use iodine in a practice.
Novel Receptor-Targeted Fluorescent Contrast Agents for In Vivo Tumor Imaging (2000)

Optical detection of tumors with a receptor-targeted fluorescent contrast agent has been demonstrated. This result represents a new direction in cancer diagnosis and patient management.
Role of Glutamine in Protection of Intestinal Epithelial Tight Junctions (2012)

Glutamine, a conditionally essential amino acid, is consumed predominantly in the gastrointestinal tract as a source of energy, particularly under the conditions of trauma, sepsis and surgery. In this article, we discuss the unique role of glutamine in the preservation of epithelial barrier function in the gastrointestinal tract. Glutamine supplementation protects the gastrointestinal mucosal homeostasis during total parenteral nutrition, diarrhea, radiation injury, starvation, sepsis and trauma. A significant body of evidence indicates that glutamine preserves the gut barrier function and prevents permeability to toxins and pathogens from the gut lumen into mucosal tissue and circulation. Recent studies demonstrated that the mucosal barrier protective effect of glutamine relates to its effect on preservation of epithelial tight junction integrity. The current understanding of glutamine-mediated protection of intestinal epithelial tight junction integrity and the potential mechanisms involved in this protective effect of glutamine are discussed.
Disparate Inotropic and Lusitropic Responses to Pimobendan in Conscious Dogs with Tachycardia-Induced Heart Failure (1994)

Summary Left ventricular (LV) inotropic and lusitropic responses to a calcium sensitizer, pimobendan, were compared between normal and failing hearts. Heart failure was induced by rapid ventricular pacing in 6 dogs instrumented with a micromanometer and a conductance catheter. The effects of pimobendan were evaluated in the conscious state before and after development of heart failure. Pimobendan dose-dependently increased the slope of the end-systolic pressure-volume (P-V) relation (Ees) in both normal and failing hearts, whereas its magnitude was markedly attenuated in failing hearts. Heart rate (HR) was increased by pimobendan in normal heart but did not change in failing heart. LV relaxation, assessed by peak - dP/dt and the time constant of isovolumic pressure decay (Td), was substantially improved to the same extent in failing and normal hearts. Consequently, Ees and Td exhibited a hyperbolic relation over a wide range of contractility states. In normal heart, pimobendan caused a leftward shift of the diastolic P-V relation while maintaining a similar curve. In failing heart, however, this relation shifted directly downward with a concomitant increase in end-diastolic volume, indicating a reduction in the constraints on LV distention and a resultant increase in preload reserve. Thus, pimobendan accelerated LV isovolumic relaxation and improved distensibility in conscious dogs with tachycardia-induced heart failure despite the marked attenuation of inotropic responses.
Tracheal Reconstruction Using Tissue-Engineered Cartilage (2004)

Cartilage can be tissue engineered in rabbits using PGA mesh embedded with alginate-encapsulated autologous chondrocytes. It is also possible to reconstruct tracheal defects with this method of cartilage engineering, although the mortality rate in this study is high.