gebhart/patrepeval huggingface dataset:
A novel peptide, PLAEIDGIELTY, for the targeting of α9β1‐integrins (1998)

Targeting gene therapy vectors to abundant receptors on airway epithelia may allow a significant enhancement of gene delivery and thereby be of particular importance for the gene therapy of cystic fibrosis. Alpha9beta1-integrins are highly expressed throughout the human airway epithelia in vivo, irrespective of any particular clinical status. Aiming to improve the targeting of our non-viral integrin-mediated gene transfer systems to airway epithelia, we searched for a short tenascin C-derived peptide which would bind to these integrins. By utilizing recombinant bacteriophages that display overlapping regions of the third fibronectin type III repeat of tenascin C (TNfn3), we were able to localize its alpha9beta1-integrin binding site to the B-C loop of TNfn3. A synthetic Pro-Leu-Ala-Glu-Ile-Asp-Gly-Ile-Glu-Leu-Thr-Tyr peptide (PLAEIDGIELTY) was shown to displace alpha9beta1-integrin-expressing cells completely from binding to TNfn3. This peptide, therefore, may prove useful both for the examination of the functional importance of alpha9beta1-integrins in vivo and the development of gene therapy vectors or drugs targeting these integrins.
Serum endometrial IgG antibodies and soluble CD23 concentrations in patients with endometriosis (1996)

These data suggest the existence of B cell activation in patients with endometriosis with a significant correlation between endometrial antibodies and soluble CD23. Mild endometriosis appears to be immunologically more active than the severe form. The value of soluble CD23 in the management of endometriosis needs further evaluation.
The Determination of Enzyme Dissociation Constants (1934)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Determination of Enzyme Dissociation ConstantsHans Lineweaver and Dean BurkCite this: J. Am. Chem. Soc. 1934, 56, 3, 658–666Publication Date (Print):March 1, 1934Publication History Published online1 May 2002Published inissue 1 March 1934https://doi.org/10.1021/ja01318a036RIGHTS & PERMISSIONSArticle Views17226Altmetric-Citations9769LEARN 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 InReddit PDF (854 KB) Get e-Alertsclose Get e-Alerts
Short-Interfering RNA-Mediated Lck Knockdown Results in Augmented Downstream T Cell Responses (2005)

The Src family kinase Lck is essential for T cell Ag receptor-mediated signaling. In this study, we report the effects of acute elimination of Lck in Jurkat TAg and primary T cells using RNA interference mediated by short-interfering RNAs. In cells with Lck knockdown (kd), proximal TCR signaling was strongly suppressed as indicated by reduced zeta-chain phosphorylation and intracellular calcium mobilization. However, we observed sustained and elevated phosphorylation of ERK1/2 in Lck kd cells 30 min to 2 h after stimulation. Downstream effects on immune function as determined by activation of a NFAT-AP-1 reporter, and TCR/CD28-stimulated IL-2 secretion were strongly augmented in Jurkat and primary T cells, respectively. As expected, overexpression of SHP-1 in Jurkat cells inhibited TCR-induced NFAT-AP-1 activation, but this effect could be overcome by simultaneous kd of Lck. Furthermore, acute elimination of Lck also suppressed TCR-mediated activation of SHP-1, suggesting the possible role of SHP-1 in a negative feedback loop originating from Lck. This report underscores Lck as an important mediator of proximal TCR signaling, but also indicates a suppressive role on downstream immune function.
IL-27 Production and STAT3-Dependent Upregulation of B7-H1 Mediate Immune Regulatory Functions of Liver Plasmacytoid Dendritic Cells (2012)

Plasmacytoid dendritic cells (pDCs) are highly specialized APCs that, in addition to their well-recognized role in anti-viral immunity, also regulate immune responses. Liver-resident pDCs are considerably less immunostimulatory than those from secondary lymphoid tissues and are equipped to promote immune tolerance/regulation through various mechanisms. IL-27 is an IL-12 family cytokine that regulates the function of both APCs and T cells, although little is known about its role in pDC immunobiology. In this study, we show that mouse liver pDCs express higher levels of IL-27p28 and EBV-induced protein 3 (Ebi3) compared with those of splenic pDCs. Both populations of pDCs express the IL-27Rα/WSX-1; however, only liver pDCs significantly upregulate expression of the coregulatory molecule B7 homolog-1 (B7-H1) in response to IL-27. Inhibition of STAT3 activation completely abrogates IL-27-induced upregulation of B7-H1 expression on liver pDCs. Liver pDCs treated with IL-27 increase the percentage of CD4(+)Foxp3(+) T cells in MLR, which is dependent upon expression of B7-H1. pDCs from Ebi3-deficient mice lacking functional IL-27 show increased capacity to stimulate allogeneic T cell proliferation and IFN-γ production in MLR. Liver but not spleen pDCs suppress delayed-type hypersensitivity responses to OVA, an effect that is lost with Ebi3(-/-) and B7-H1(-/-) liver pDCs compared with wild-type liver pDCs. These data suggest that IL-27 signaling in pDCs promotes their immunoregulatory function and that IL-27 produced by pDCs contributes to their capacity to regulate immune responses in vitro and in vivo.
One-Dimensional Coordination Polymers Based upon Bridging Terephthalate Ions (1998)

The reaction between transition metal halides MX2 (where M = Co(II) and Ni(II)) in an aqueous solution containing disodium terephthalate along with pyridine-based ligands gives rise to one-dimensional coordination polymers. Both [M(terephthalate)(4-picoline)2(H2O)2]·2(4-picoline) (1) and [M(terephthalate)(pyridine)2(H2O)2]·2(pyridine)·2(H2O) (2) have been isolated. These frameworks exhibit hydrogen bond donors running along the backbone of each polymer, which gives rise to inclusion chemistry between the framework and pyridine guest molecules.
[Decrease in systemic fungal infections in hematological neoplasms with empirical use of amphotericin B therapy]. (1989)

An incidence of up to 30% of systemic fungal infections at autopsy, and difficulties in diagnosing systemic mycosis antemortem, have led to the empiric use of amphotericin B in patients with hematological malignancies. Routine empiric anti-fungal treatment was initiated at our institution in 1982. Amphotericin B and initially for 3 days flucytosine was given to granulocytopenic patients with unremitting (after 48-72 h) or recurrent fever during antibiotic treatment, or with newly detected pulmonary infiltrates, sinusitis, and skin and retinal lesions suggestive of fungal infection. With this approach the rate of systemic fungal infections decreased from 10% to 4% (p less than 0.02). The reduction was most prominent in patients with acute myelogenous leukemia, where fungal infections decreased from 16% to 4% (p less than 0.025).
Neutralization of Autocrine Transforming Growth Factor‐β in Human Cord Blood CD34+CD38−Lin−Cells Promotes Stem‐Cell‐Factor‐Mediated Erythropoietin‐Independent Early Erythroid Progenitor Development and Reduces Terminal Differentiation (2003)

Transforming growth factor (TGF)-beta1 exerts autocrine and paracrine effects on hematopoiesis. Here, we have attempted to evaluate the effect of endogenous TGF-beta1 on early erythroid development from primitive human hematopoietic stem cells (HSCs) and to assess the effects of TGF-beta1 on different phases of erythropoiesis. Cord blood CD34(+)CD38(-) lineage-marker-negative (Lin(-)) cells were cultured in serum-free conditions using various combinations of stem cell factor (SCF), erythropoietin (Epo), and TGF-beta-neutralizing antibody. Generation of erythroid progenitors was assessed using colony assay and flow cytometry. Terminal erythroid differentiation was examined when SCF/Epo-stimulated cells were recultured in the presence of Epo with and without TGF-beta1. Anti-TGF-beta augmented the proliferation of CD34(+)CD38(-)Lin(-) cells (day 21) in SCF-stimulated (6.4-fold +/- 1.5-fold) and SCF/Epo-stimulated (2.9-fold +/- 1.2-fold) cultures. Cells stimulated by SCF/Epo underwent similar levels of erythroid differentiation with and without anti-TGF-beta. While SCF alone stimulated the production of tryptase-positive mast cells, cells stimulated by SCF/anti-TGF-beta were predominantly erythroid (CD36(+)CD14(-) and glycophorin A positive). A distinct expansion of erythroid progenitors (CD34(+)CD36(+)CD14(-)) with the potential to form erythroid colonies was seen, revealing early Epo-independent erythroid development. In contrast, the kinetics of erythroid progenitor generation from primitive HSCs indicate that TGF-beta1 is not inhibitory in late erythropoiesis, but it accelerated the conversion of large BFU-E into colony-forming units-erythroid. Finally, TGF-beta1 accelerated Epo-induced terminal erythroid differentiation and resulted in a greater level of enucleation (22% +/- 6% versus 7% +/- 3%) in serum-free conditions. Serum addition stimulated enucleation (54% +/- 18%), which was lower (26% +/- 14%) with anti-TGF-beta, suggesting that optimal erythroid enucleation is Epo dependent, requiring serum factors including TGF-beta1.
Pharmacological activation of cloned intermediate- and small-conductance Ca2+-activated K+channels (2000)

We previously characterized 1-ethyl-2-benzimidazolinone (1-EBIO), as well as the clinically useful benzoxazoles, chlorzoxazone (CZ), and zoxazolamine (ZOX), as pharmacological activators of the intermediate-conductance Ca(2+)-activated K(+) channel, hIK1. The mechanism of activation of hIK1, as well as the highly homologous small-conductance, Ca(2+)-dependent K(+) channel, rSK2, was determined following heterologous expression in Xenopus oocytes using two-electrode voltage clamp (TEVC) and excised, inside-out patch-clamp techniques. 1-EBIO, CZ, and ZOX activated both hIK1 and rSK2 in TEVC and excised inside-out patch-clamp experiments. In excised, inside-out patches, 1-EBIO and CZ induced a concentration-dependent activation of hIK1, with half-maximal (K(1/2)) values of 84 microM and 98 microM, respectively. Similarly, CZ activated rSK2 with a K(1/2) of 87 microM. In the absence of CZ, the Ca(2+)-dependent activation of hIK1 was best fit with a K(1/2) of 700 nM and a Hill coefficient (n) of 2.0. rSK2 was activated by Ca(2+) with a K(1/2) of 700 nM and an n of 2.5. Addition of CZ had no effect on either the K(1/2) or n for Ca(2+)-dependent activation of either hIK1 or rSK2. Rather, CZ increased channel activity at all Ca(2+) concentrations (V(max)). Event-duration analysis revealed hIK1 was minimally described by two open and three closed times. Activation by 1-EBIO had no effect on tau(o1), tau(o2), or tau(c1), whereas tau(c2) and tau(c3) were reduced from 9.0 and 92.6 ms to 5.0 and 44.1 ms, respectively. In conclusion, we define 1-EBIO, CZ, and ZOX as the first known activators of hIK1 and rSK2. Openers of IK and SK channels may be therapeutically beneficial in cystic fibrosis and vascular diseases.
Mitochondrial permeability transition is a central coordinating event of apoptosis. (1996)

In a number of experimental systems, the early stage of the apoptotic process, i.e., the stage that precedes nuclear disintegration, is characterized by the breakdown of the inner mitochondrial transmembrane potential (delta psi m). This delta psi m disruption is mediated by the opening of permeability transition (PT) pores and appears to be critical for the apoptotic cascade, since it is directly regulated by Bcl-2 and since mitochondria induced to undergo PT in vitro become capable of inducing nuclear chromatinolysis in a cell-free system of apoptosis. Here, we addressed the question of which apoptotic events are secondary to mitochondrial PT. We tested the effect of a specific inhibitor of PT, bongkrekic acid (BA), a ligand of the mitochondrial adenine nucleotide translocator, on a prototypic model of apoptosis glucocorticoid-induced thymocyte death. In addition to abolishing the apoptotic delta psi m disruption, BA prevents a number of phenomena linked to apoptosis: depletion of nonoxidized glutathione, generation of reactive oxygen species, translocation of NF kappa B, exposure of phosphatidylserine residues on the outer plasma membrane, cytoplasmic vacuolization, chromatin condensation, and oligonucleosomal DNA fragmentation. BA is also an efficient inhibitor of p53-dependent thymocyte apoptosis induced by DNA damage. These data suggest that a number of apoptotic phenomena are secondary to PT. In addition, we present data indicating that apoptotic delta psi m disruption is secondary to transcriptional events. These data connect the PT control point to the p53- and ICE/ Ced 3-regulated control points of apoptosis and place PT upstream of nuclear and plasma membrane features of PCD.
Graphical Tests for Power Comparison of Competing Designs (2012)

Lineups have been established as tools for visual testing similar to standard statistical inference tests, allowing us to evaluate the validity of graphical findings in an objective manner. In simulation studies lineups have been shown as being efficient: the power of visual tests is comparable to classical tests while being much less stringent in terms of distributional assumptions made. This makes lineups versatile, yet powerful, tools in situations where conditions for regular statistical tests are not or cannot be met. In this paper we introduce lineups as a tool for evaluating the power of competing graphical designs. We highlight some of the theoretical properties and then show results from two studies evaluating competing designs: both studies are designed to go to the limits of our perceptual abilities to highlight differences between designs. We use both accuracy and speed of evaluation as measures of a successful design. The first study compares the choice of coordinate system: polar versus cartesian coordinates. The results show strong support in favor of cartesian coordinates in finding fast and accurate answers to spotting patterns. The second study is aimed at finding shift differences between distributions. Both studies are motivated by data problems that we have recently encountered, and explore using simulated data to evaluate the plot designs under controlled conditions. Amazon Mechanical Turk (MTurk) is used to conduct the studies. The lineups provide an effective mechanism for objectively evaluating plot designs.
Succinate Secreted by Trypanosoma brucei Is Produced by a Novel and Unique Glycosomal Enzyme, NADH-dependent Fumarate Reductase (2002)

In all trypanosomatids, including Trypanosoma brucei, glycolysis takes place in peroxisome-like organelles called glycosomes. These are closed compartments wherein the energy and redox (NAD(+)/NADH) balances need to be maintained. We have characterized a T. brucei gene called FRDg encoding a protein 35% identical to Saccharomyces cerevisiae fumarate reductases. Microsequencing of FRDg purified from glycosome preparations, immunofluorescence, and Western blot analyses clearly identified this enzyme as a glycosomal protein that is only expressed in the procyclic form of T. brucei but is present in all the other trypanosomatids studied, i.e. Trypanosoma congolense, Crithidia fasciculata and Leishmania amazonensis. The specific inactivation of FRDg gene expression by RNA interference showed that FRDg is responsible for the NADH-dependent fumarate reductase activity detected in glycosomal fractions and that at least 60% of the succinate secreted by the T. brucei procyclic form (in the presence of d-glucose as the sole carbon source) is produced in the glycosome by FRDg. We conclude that FRDg plays a key role in the energy metabolism by participating in the maintenance of the glycosomal NAD(+)/NADH balance. We have also detected a significant pyruvate kinase activity in the cytosol of the T. brucei procyclic cells that was not observed previously. Consequently, we propose a revised model of glucose metabolism in procyclic trypanosomes that may also be valid for all other trypanosomatids except the T. brucei bloodstream form. Interestingly, H. Gest has hypothesized previously (Gest, H. (1980) FEMS Microbiol. Lett. 7, 73-77) that a soluble NADH-dependent fumarate reductase has been present in primitive organisms and evolved into the present day fumarate reductases, which are quinol-dependent. FRDg may have the characteristics of such an ancestral enzyme and is the only NADH-dependent fumarate reductase characterized to date.
Invasive brain drug delivery (2001)

Invasive brain drug delivery strategies have been the most widely used for circum-venting the blood–brain barrier (BBB) drug delivery problem. The invasive strategies require either a craniotomy by a neurosurgeon or access to the carotid artery by an interventional radiologist. The neurosurgery-based strategies include intracerebroventricular (ICV) infusion of drugs, or intracerebral implants of either genetically engineered cells or biodegradable polymers. Thus, the neurosurgicalbased strategies fundamentally emanate from the material sciences and employ controlled-release formulations, which is a classical drug delivery strategy (Figure 2.1). In contrast, the theme of this book is that brain drug targeting emanates from transport biology science, and is focused on the endogenous BBB transport systems (Figure 2.1). In the absence of brain drug-targeting strategies that allow drugs to be transported through the BBB, thenit is necessary to employ invasive strategies. These approaches either deliver drug behind the BBB, as with either ICV infusion or intracerebral implants, or physically disrupt the BBB following the intracarotid arterial infusion of noxious agents.
High Density Scaffolding of Functional Polymer Brushes: Surface Initiated Atom Transfer Radical Polymerization of Active Esters (2009)

In this Article, we describe a method for the polymerization of active esters based on N-hydroxysuccinimide 4-vinyl benzoate (NHS4VB) using surface initiated atom transfer radical polymerization (SI-ATRP). Poly(NHS4VB) brushes have high grafting density and a uniform and smooth morphology, and film thickness increases linearly with reaction time. Block copolymer brushes with 2-hydroxyethyl acrylate, tert-butyl acrylate, and styrene were synthesized from surface bound poly(NHS4VB) macroinitiators. The active ester brushes show rapid and quantitative conversion under aminolysis conditions with primary amines, which was studied using grazing incidence attenuated total reflection Fourier transform infrared (GATR-FTIR) and UV-vis spectroscopy. UV-vis was also used to quantify the amount of reactive groups in polymer brush layers of differing thickness. Functionalization of the active ester pendant groups with chromophores containing primary amines showed a linear correlation between the amount of chromophore incorporated into the brush layer and brush thickness. Grafting densities as high as 25.7 nmol/cm(2) were observed for a 50 nm brush. Block copolymer brushes with buried active ester functional moieties also undergo quantitative conversion with primary amines as confirmed by GATR-FTIR. We discuss the potential of activated ester brushes as universal scaffolds for sensor and microarray surfaces, where the twofold control of functionalizable active ester polymer and block copolymers provides well-ordered, tunable microenvironments.
Exercise-Induced Changes in Oxygen Saturation in the Calf Muscles of Elderly Subjects With Peripheral Vascular Disease (1994)

This study noninvasively measured hemoglobin oxygen saturation in young (n = 6, 28 +/- 6 yrs), old healthy (n = 20, 68 +/- 7 yrs), and old subjects with mild peripheral vascular disease (PVD) (n = 8, 72 +/- 4 yrs). Hemoglobin oxygen saturation was measured as the difference in absorption at 760 and 850 nm light using near-infrared spectroscopy (NIRS). The lateral soleus muscle was studied after mild plantar flexion exercise. The time constant of recovery of oxygen saturation (HBO2Tc) was 21.5 +/- 8.6 s in young, 26.9 +/- 13.5 s in old healthy subjects. PVD subjects had HbO2Tc values of 104.4 +/- 41.1 s in their "bad" leg and 57.6 +/- 42.2 s in their "good" leg. The correlation between HbO2Tc and ankle-arm pressures was significant (r2 = .63, p < .001). Six younger normal, five older normal, and seven PVD subjects also performed a progressive walking test. Normal subjects completed the test without difficulty, and older normal subjects showed progressive deoxygenation. PVD subjects complained of calf pain (4 out of 5 were able to finish) and showed near-maximal deoxygenation throughout the test. In summary, NIRS measurements show promise as a method of evaluating the kinetics of oxygen saturation, particularly in patients with mild peripheral vascular disease.
Novel treatment strategies in congenital adrenal hyperplasia (2016)

The promising recent progress made in CAH treatment brings new perspectives for individualized care in this complex disease.
Rank Modulation for Flash Memories (2009)

We explore a novel data representation scheme for multilevel flash memory cells, in which a set of <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</i> cells stores information in the permutation induced by the different charge levels of the individual cells. The only allowed charge-placement mechanism is a ldquopush-to-the-toprdquo operation, which takes a single cell of the set and makes it the top-charged cell. The resulting scheme eliminates the need for discrete cell levels, as well as overshoot errors, when programming cells. We present unrestricted Gray codes spanning all possible n-cell states and using only "push-to-the-top" operations, and also construct balanced Gray codes. One important application of the Gray codes is the realization of logic multilevel cells, which is useful in conventional storage solutions. We also investigate rewriting schemes for random data modification. We present both an optimal scheme for the worst case rewrite performance and an approximation scheme for the average-case rewrite performance.