gebhart/patrepeval huggingface dataset:
Pulmonary Passage is a Major Obstacle for Intravenous Stem Cell Delivery: The Pulmonary First-Pass Effect (2008)

Intravenous (IV) stem cell delivery for regenerative tissue therapy has been increasingly used in both experimental and clinical trials. However, recent data suggest that the majority of administered stem cells are initially trapped in the lungs. We sought to investigate variables that may affect this pulmonary first-pass effect. In anesthetized Sprague-Dawley rats, silicone tubing catheters were placed in the left internal jugular vein and common carotid artery. We investigated four different cell types: mesenchymal stromal cells (MSC), multipotent adult progenitor cells (MAPCs), bone marrow-derived mononuclear cells (BMMC), and neural stem cells (NSC). Cells were co-labeled with Qtracker 655 (for flow cytometry) and Qtracker 800 (for infrared imaging) and infused intravenously with continual arterial sample collection. Samples were analyzed via flow cytometry to detect labeled cells reaching the arterial circulation. Following sampling and exsanguination, heart, lungs, spleen, kidney, and liver were harvested and placed on an infrared imaging system to identify the presence of labeled cells. The majority of MSCs were trapped inside the lungs following intravenous infusion. NSC and MAPC pulmonary passage was 2-fold and BMMC passage was 30-fold increased as compared to MSCs. Inhibition of MSC CD49d significantly increased MSC pulmonary passage. Infusion via two boluses increased pulmonary MSC passage as compared to single bolus administration. Infrared imaging revealed stem cells evenly distributed over all lung fields. Larger stem and progenitor cells are initially trapped inside the lungs following intravenous administration with a therapeutically questionable number of cells reaching the arterial system acutely.
Suppression of experimental autoimmune encephalomyelitis using estrogen receptor-selective ligands (2005)

Estrogens have been shown to modulate disease activity in experimental autoimmune encephalomyelitis (EAE), the mouse model for multiple sclerosis. Consistent with these findings, the severity of disease is reduced in pregnant women with multiple sclerosis when levels of estrogens are high. Estrogens bind to two known estrogen receptors (ER), ERalpha and ERbeta. The relative contribution of these receptors to estrogen-mediated suppression of EAE was explored using ER-selective ligands. The ER antagonist ICI 182 780 reversed the suppressive effects of 17beta-estradiol (E2), demonstrating that the protective effects of E2 on disease are dependent upon ER signaling. Treatment of SJL mice with the ERalpha-selective agonist proteolipid protein (PPT) prior to the induction of disease resulted in suppression of clinical symptoms of disease, whereas treatment with an ERbeta-selective agonist (WAY-202041) had no effect. Treatment of mice with PLP peptide 139-151 (PPT) was also associated with decreased immune responses associated with disease. Consistent with its lack of effect on disease, the ERbeta agonist had minimal effects on immune responses. The use of selective estrogen receptor modulators (SERMs) in this model was also explored, and we show that raloxifene and WAY-138923 were also effective in suppressing disease. These results demonstrate the beneficial effects of estrogen receptor ligands, in particular ERalpha-selective ligands, and may have implications in the development of therapeutic strategies for multiple sclerosis.
Overexpression of glucose transporter 1 and increased FDG uptake in pancreatic carcinoma. (1997)

The concomitant enhancement of glucose utilization and selective overexpression of Glut-1 mRNA in pancreatic cancer but not in MFP suggested constitutive activation of Glut-1 gene or decreased degradation of Glut-1 mRNA in human pancreatic cancer. These findings may imply a potential for the early detection of pancreatic cancer with FDG and PET and identify new targets for anticancer therapy.
[Collagen as a basic element of the periodontium: immunohistochemical aspects in the human and animals. 2. Cementum and periodontal ligament]. (1991)

Immunohistochemical knowledge of the distribution of the collagen types in the cementum and periodontal ligament were reported in this paper. Because of the different localization of each of these collagenous components in the two periodontal tissues its function in the matrix was explored. It was also possible to clarify the role of collagen in healthy periodontium as well as in regeneration and wound healing mechanisms.
Science, medicine, and the future: Microdialysis (2002)

Monitoring tissue chemistry in patients by microdialysis is likely to become routine in clinical practice


Many diagnostic and therapeutic decisions in medical practice are based on measuring blood concentrations of endogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Assessing tissue chemistry should theoretically provide more accurate data, and this can now be achieved relatively cheaply and minimally invasively with microdialysis. This review describes the technique of microdialysis and its application in clinical research, drug monitoring, and drug development. It also discusses how, in the future, measurement of tissue rather than blood chemistry may become the standard for some clinical investigations. 


Summary points


Microdialysis enables the in vivo measurement of tissue chemistry in humans and is feasible in virtually every human organ


It is currently being used to monitor brain ischaemia and metabolic control


The technique is set to become a standard tool in drug monitoring and development


In the future “bedside” microdialysis will allow monitoring of tissue metabolism in a wide range of diseases
Markov-modulated flow model for the output queues of a packet switch (1992)

The output queues of an M*N packet switch are studied using a Markov-modulated flow model. The switching element is a central server which sequentially routes packets from the inputs to the outputs. The focus is on systems in which the server speed is such that the bulk of the queuing takes place in the output queues. The conventional point process approach neglects the impact of switching and transmission time. An attempt is made to account for these finite system speeds by using a Markov-modulated continuous flow to approximate the arrival process to an output queue. This model captures the dependency between arrivals at different outputs and reflects the fact that packet arrivals and departures are not instantaneous. The output queue content distribution is obtained, for both infinite and finite buffer systems, from the spectral expansion of the solution of a system of differential equations. Numerical examples and comparisons with the results of an M/M/1 approximation are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Highly Reversible Lithium Storage in Nanostructured Silicon (2003)

Anode materials of nanostructured silicon have been prepared by physical vapor deposition and characterized using electrochemical methods. The electrodes were prepared in thin-film form as nanocrystalline particles (12 nm mean diameter) and as continuous amorphous thin films (100 nm thick). The nanocrystalline silicon exhibited specific capacities of around 1100 mAh/g with a 50% capacity retention after 50 cycles. The amorphous thin-film electrodes exhibited initial capacities of 3500 mAh/g with a stable capacity of 2000 mAh/g over 50 cycles. We suggest that the nanoscale dimensions of the silicon circumvents conventional mechanisms of mechanical deterioration, permitting good cycle life.
Effects of Chronic Left Vagal Stimulation on Visceral Vagal Function in Man (1992)

We examined the effects of chronic left vagal electrostimulation on afferent and efferent gastrointestinal vagal function in eight patients. Afferent function was assessed using cortical evoked responses to electrical stimulation of the esophagus and to direct vagal stimulation using the implanted left vagal electrode. Efferent gastrointestinal vagal function was measured by examining the basal, maximal, and sham fed stimulated gastric acid output prior to and with chronic left vagal electrostimulation. Esophageal electrostimulation produced a cortical evoked response consisting of three negative and three positive peaks within 400 msec after stimulation. Prior to vagal electrostimulation the mean conduction velocity of the afferent signal was measured at 8.72 +/- 3.39 m/sec, compatible with A-delta fibers involvement. Basal, maximal, and sham fed acid output were 1.11, 21.87, and 9.37 mmol/hour, respectively. The evoked response to esophageal electrical stimulation was not changed with chronic left vagal electrostimulation. Direct vagal stimulation also produced evoked potentials that were comparable to those obtained with esophageal stimulation. The mean conduction velocity was 6.26 +/- 2.72 m/sec (NS) so that there was no evidence of loss of myelinated fibers with chronic stimulation. No differences were detected in basal (1.29 mmol/h), maximal (21.64 mmol/h), or sham fed stimulated (8.03 mmol/h) acid output, showing that vagal electrostimulation has no effect on either total or vagally mediated acid output, an efferent vagal function. In conclusion, chronic left vagal electrostimulation has no significant adverse effect on gastrointestinal vagal function.
Production of VEGF and expression of the VEGF receptors Flt-1 and KDR in primary cultures of epithelial and stromal cells derived from breast tumours (1999)

Production of vascular endothelial growth factor (VEGF) and expression of its receptors Flt-1 and KDR was determined in primary cultures of separated epithelial and stromal-enriched cultures derived from ten primary human breast carcinomas. By enzyme-linked immunosorbent assay, epithelial cells produced a mean VEGF of 33 +/- 7 pg ml(-1) microg(-1) RNA (range 11-70). Stromal cells produced similar levels, with a mean of 48 +/- 11 pg ml(-1) microg(-1) RNA (range 7-92). This was significantly greater than the amount produced by similar cultures derived from normal breast tissue (epithelial mean 19 +/- 5 pg ml(-1) microg(-1) RNA, range 9-34, P < 0.05 vs tumour epithelial culture; stromal mean 26 +/- 8 pg ml(-1) microg(-1) RNA, range 3-56). Flt-1 and KDR receptors were analysed by semi-quantitative reverse transcription polymerase chain reaction. Flt-1 was expressed by four of six epithelial and five of six stromal cultures. When expressed by both cell types, Flt-1 appeared to be significantly more abundant on stromal cells compared with epithelial cultures. Only a single tumour, a lobular carcinoma, failed to express Flt-1 on either cell type. With KDR, the reverse was true with constitutive expression of this receptor by epithelial cultures and zero or reduced (3/6) expression by stromal cultures. Differences in the expression pattern of VEGF receptors may reflect a differential response to VEGF by specific cell types. Thus, production of VEGF and expression of VEGF receptors Flt-1 and KDR by breast cancer epithelial and stromal cells suggests that VEGF may fulfil not only an angiogenic role, but also play a fundamental role as an autocrine/paracrine regulator in breast cancer, thereby facilitating tumour proliferation and subsequent invasion.
Confirmation of diosmetin 3-O-glucuronide as major metabolite of diosmin in humans, using micro-liquid-chromatography–mass spectrometry and ion mobility mass spectrometry (2013)

Diosmin is a flavonoid often administered in the treatment of chronic venous insufficiency, hemorrhoids, and related affections. Diosmin is rapidly hydrolized in the intestine to its aglicone, diosmetin, which is further metabolized to conjugates. In this study, the development and validations of three new methods for the determination of diosmetin, free and after enzymatic deconjugation, and of its potential glucuronide metabolites, diosmetin-3-O-glucuronide, diosmetin-7-O-glucuronide, and diosmetin-3,7-O-glucuronide from human plasma and urine are presented. First, the quantification of diosmetin, free and after deconjugation, was carried out by high-performance liquid chromatography coupled with tandem mass spectrometry, on an Ascentis RP-Amide column (150 × 2.1 mm, 5 μm), in reversed-phase conditions, after enzymatic digestion. Then glucuronide metabolites from plasma were separated by micro-liquid chromatography coupled with tandem mass spectrometry on a HALO C18 (50 × 0.3 mm, 2.7 μm, 90 Å) column, after solid-phase extraction. Finally, glucuronides from urine were measured using a Discovery HSF5 (100 × 2.1 mm, 5 μm) column, after simple dilution with mobile phase. The methods were validated by assessing linearity, accuracy, precision, low limit of quantification, selectivity, extraction recovery, stability, and matrix effects; results in agreement with regulatory (Food and Drug Administration and European Medicines Agency) guidelines acceptance criteria were obtained in all cases. The methods were applied to a pharmacokinetic study with diosmin (450 mg orally administered tablets). The mean C max of diosmetin in plasma was 6,049.3 ± 5,548.6 pg/mL. A very good correlation between measured diosmetin and glucuronide metabolites concentrations was obtained. Diosmetin-3-O-glucuronide was identified as a major circulating metabolite of diosmetin in plasma and in urine, and this finding was confirmed by supplementary experiments with differential ion-mobility mass spectrometry.
Spatial hole burning in a quantum dot laser (1999)

Detailed theoretical analysis of the longitudinal spatial hole burning in quantum dot (QD) lasers is given. The multimode generation threshold is calculated as a function of the parameters of structure (surface density of QDs, QD size dispersion, and cavity length) and temperature. Unlike conventional semiconductor lasers, thermally excited escapes of carriers away from QDs, rather than diffusion, are shown to control smoothing-out spatially nonuniform population inversion and hence the multimode generation threshold in QD lasers. A decrease in the QD size dispersion is shown to increase considerably the relative multimode generation threshold. The maximum tolerable QD size dispersion and the minimum tolerable cavity length, at which the lasing is possible to attain, are shown to exist. Concurrent with the decrease of threshold current, the reduction of multimode generation threshold is shown to occur with decreased temperature. For the structures optimized to minimize the threshold current density for the main longitudinal mode, the dependences of the multimode generation threshold on the QD size dispersion, cavity length, and temperature are obtained. The ways to optimizing the QD laser structure, aimed at maximizing the multimode generation threshold, are outlined.
Escaping High Viral Load Exhaustion (2002)

Deletion, anergy, and a spectrum of functional impairments can affect virus-specific CD8 cells in chronic viral infections. Here we characterize a low frequency population of CD8 cells present in chronic hepatitis B virus (HBV) infection which survive in the face of a high quantity of viral antigen. Although they do not appear to exert immunological pressure in vivo, these CD8 cells are not classically "tolerant" since they proliferate, lyse, and produce antiviral cytokines in vitro. They are characterized by altered HLA/peptide tetramer reactivity, which is not explained by TCR down-regulation or reduced functional avidity and which can be reversed with repetitive stimulation. CD8 cells with altered tetramer binding appear to have a specificity restricted to envelope antigen and not to other HBV antigens, suggesting that mechanisms of CD8 cell dysfunction are differentially regulated according to the antigenic form and presentation of individual viral antigens.
Genetically Engineered Phages: a Review of Advances over the Last Decade (2016)

Soon after their discovery in the early 20th century, bacteriophages were recognized to have great potential as antimicrobial agents, a potential that has yet to be fully realized. The nascent field of phage therapy was adversely affected by inadequately controlled trials and the discovery of antibiotics. Although the study of phages as anti-infective agents slowed, phages played an important role in the development of molecular biology. In recent years, the increase in multidrug-resistant bacteria has renewed interest in the use of phages as antimicrobial agents. With the wide array of possibilities offered by genetic engineering, these bacterial viruses are being modified to precisely control and detect bacteria and to serve as new sources of antibacterials. In applications that go beyond their antimicrobial activity, phages are also being developed as vehicles for drug delivery and vaccines, as well as for the assembly of new materials. This review highlights advances in techniques used to engineer phages for all of these purposes and discusses existing challenges and opportunities for future work.
Microarray analysis reveals novel gene expression changes associated with erectile dysfunction in diabetic rats (2005)

To investigate the full range of molecular changes associated with erectile dysfunction (ED) in Type 1 diabetes, we examined alterations in penile gene expression in streptozotocin-induced diabetic rats and littermate controls. With the use of Affymetrix GeneChip arrays and statistical filtering, 529 genes/transcripts were considered to be differentially expressed in the diabetic rat cavernosum compared with control. Gene Ontology (GO) classification indicated that there was a decrease in numerous extracellular matrix genes (e.g., collagen and elastin related) and an increase in oxidative stress-associated genes in the diabetic rat cavernosum. In addition, PubMatrix literature mining identified differentially expressed genes previously shown to mediate vascular dysfunction [e.g., ceruloplasmin (Cp), lipoprotein lipase, and Cd36] as well as genes involved in the modulation of the smooth muscle phenotype (e.g., Kruppel-like factor 5 and chemokine C-X3-C motif ligand 1). Real-time PCR was used to confirm changes in expression for 23 relevant genes. Further validation of Cp expression in the diabetic rat cavernosum demonstrated increased mRNA levels of the secreted and anchored splice variants of Cp. CP protein levels showed a 1.9-fold increase in tissues from diabetic rats versus controls. Immunohistochemistry demonstrated localization of CP protein in cavernosal sinusoids of control and diabetic animals, including endothelial and smooth muscle layers. Overall, this study broadens the scope of candidate genes and pathways that may be relevant to the pathophysiology of diabetes-induced ED as well as highlights the potential complexity of this disorder.
Impurity photovoltaic effect: Fundamental energy conversion efficiency limits (2002)

In the past, minimal improvements have been predicted for efficiency enhancement of solar cells using the impurity photovoltaic (IPV) effect, where optical excitation through midgap defect levels allows the use of long wavelength photons to increase the conversion efficiency of sunlight to electricity. In the present work, the principle of detailed balance is used to calculate the limiting efficiency of solar cells with the inclusion of the impurity photovoltaic effect, in the idealized case when all transitions are assumed to be radiative. Based on these calculations, the limiting efficiency of the IPV device with a large number of different defect species is determined to be 77.2%. The terrestrial performance of the IPV device is also investigated by comparing its spectral sensitivity with that of tandem solar cell designs.
Identifying aggregates in hypertext structures (1991)

Article Free Access Share on Identifying aggregates in hypertext structures Authors: Rodrigo A. Botafogo Human-Computer Interaction Laboratory & Department of Computer Science, University of Maryland, College Park, MD Human-Computer Interaction Laboratory & Department of Computer Science, University of Maryland, College Park, MDView Profile , Ben Shneiderman Human-Computer Interaction Laboratory & Department of Computer Science, University of Maryland, College Park, MD Human-Computer Interaction Laboratory & Department of Computer Science, University of Maryland, College Park, MDView Profile Authors Info & Claims HYPERTEXT '91: Proceedings of the third annual ACM conference on HypertextSeptember 1991 Pages 63–74https://doi.org/10.1145/122974.122981Published:01 September 1991Publication History 78citation573DownloadsMetricsTotal Citations78Total Downloads573Last 12 Months17Last 6 weeks6 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Spectral broadening of ultrashort pulses in a nonlinear medium (1984)

Spectral superbroadening of ultrashort-pulse propagation in a nonlinear medium is calculated by solving the nonlinear-wave equation more exactly. The effects of four-wave mixing and pulse deformation on phase modulation are included. The results yield an asymmetric Stokes-anti-Stokes broadening in fair agreement with the experimental observation.
Transcriptional initiation and postinitiation effects of murine leukemia virus long terminal repeat R-region sequences (1991)

Sequences within the R components of the long terminal repeats (LTRs) of several retroviruses are known to be involved at various steps in expression of the viral genomes. A series of experiments was performed to test whether sequences within the R regions of the murine leukemia viruses Akv and SL3-3 affect viral expression. By using plasmid clones of the viral LTRs linked to a reporter gene, deletion of the R region was found to decrease expression to variable extents in a series of mammalian cell lines, with the largest effects being detected in murine fibroblasts. R-region sequences from the human immunodeficiency virus type 1 LTR or a random sequence were unable to substitute for the murine leukemia virus sequences. Transcripts from the R-region-deleted templates were initiated at the proper site in the LTR, but their levels were decreased at least 10-fold. Nuclear run-on assays showed that the decrease caused by the R-region deletions was due, in part, to an effect on RNA polymerase loading, suggesting an effect on transcriptional initiation. The remainder of the activity was presumably due to a posttranscriptional effect. Analysis of the R-region sequences of murine leukemia viruses and related retroviruses led to the prediction of a conserved secondary structure in the transcribed RNA that might have a role in activity. We conclude that R-region sequences are of importance for the expression of a variety of retroviruses.