gebhart/patrepeval huggingface dataset:
Biochemical Characterization of a Haemophilus influenzae Periplasmic Iron Transport Operon (1995)

Bacterial iron transport is critical for growth of pathogens in the host environment, where iron is limited as a form of nonspecific immunity. For Gram-negative bacteria such as Haemophilus influenzae, iron first must be transported across the outer membrane and into the periplasmic space, then from the periplasm to the cytosol. H. influenzae express a periplasmic iron-binding protein encoded by the hitA gene. This gene is organized as the first of a three-gene operon purported to encode a classic high affinity iron acquisition system that includes hitA, a cytoplasmic permease (hitB), and a nucleotide binding protein (hitC). In this study we describe the cloning, overexpression, and purification of the H. influenzae hitA gene product. The function of this protein is unambiguously assigned by demonstrating its ability to compete for iron bound to the chemical iron chelator 2,2'-dipyridyl, both in vitro and within the periplasmic space of a siderophore-deficient strain of Escherichia coli. Finally, the importance of a functional hitABC operon for iron acquisition is demonstrated by complementation of this siderophore-deficient E. coli to growth on dipyridyl-containing medium. These studies represent a detailed genetic, biochemical, and physiologic description of an active transport system that has evolved to efficiently transport iron and consequently is widely distributed among Gram-negative pathogenic bacteria.
Inhibition of Decarboxylase and Levels of Dopa and 3-O-Methyldopa: A Comparative Study of Benserazide versus Carbidopa in Rodents and of Madopar Standard versus Madopar HBS in Volunteers (1987)

The combinations of benserazide and levodopa (1:4, Madopar) and of carbidopa and levodopa (1:10 and 1:4, Sinemet) are currently the most effective treatment of Parkinson's disease. In the present comparative study some effects of the peripheral aromatic L-amino acid decarboxylase (AADC) inhibitors benserazide and carbidopa administered alone or in combination with levodopa by the oral route were investigated in two animal species (rat and mouse) and in healthy volunteers. Benserazide is about 10 times more potent than carbidopa as inhibitor of peripheral AADC both in animals and man. Even at relatively high doses (up to 60 mumol/kg p.o.) benserazide is shown in animals to inhibit the decarboxylation of levodopa only in the extracerebral tissues, thus permitting the formation of dopamine in the striatum and in the hypothalamus. As benserazide is the most potent peripheral AADC inhibitor presently available, is well tolerated and relatively nontoxic even when used chronically, it appears to be the peripheral AADC inhibitor of choice for the development of controlled-release formulations in which Dopa is combined with a peripheral AADC inhibitor. When administered to healthy subjects the pharmacokinetics of the new drug delivery system named Madopar HBS (hydrodynamically balanced system) was characterized by lower and delayed plasma peak concentrations but a longer-lasting concentration of Dopa than after Madopar standard. Therefore, this new controlled-release system may reduce the clinical fluctuations occurring in patients with 'wearing-off' and 'on-off' phenomena.
Tumor Detection by Imaging Proteolytic Activity (2010)

The cell surface protease membrane-type serine protease-1 (MT-SP1), also known as matriptase, is often upregulated in epithelial cancers. We hypothesized that dysregulation of MT-SP1 with regard to its cognate inhibitor hepatocyte growth factor activator inhibitor-1 (HAI-1), a situation that increases proteolytic activity, might be exploited for imaging purposes to differentiate malignant from normal tissue. In this study, we show that MT-SP1 is active on cancer cells and that its activity may be targeted in vivo for tumor detection. A proteolytic activity assay with several MT-SP1-positive human cancer cell lines showed that MT-SP1 antibodies that inhibit recombinant enzyme activity in vitro also bind and inhibit the full-length enzyme expressed on cells. In contrast, in the same assay, MT-SP1-negative cancer cell lines were inactive. Fluorescence microscopy confirmed the cell surface localization of labeled antibodies bound to MT-SP1-positive cells. To evaluate in vivo targeting capability, 0.7 to 2 nmoles of fluorescently labeled antibodies were administered to mice bearing tumors that were positive or negative for MT-SP1. Antibodies localized to MT-SP1-positive tumors (n = 3), permitting visualization of MT-SP1 activity, whereas MT-SP1-negative tumors (n = 2) were not visualized. Our findings define MT-SP1 activity as a useful biomarker to visualize epithelial cancers using a noninvasive antibody-based method.
On the dynamics of the oxidation-induced stacking-fault ring in as-grown Czochralski silicon crystals (1997)

The behavior of the oxidation-induced stacking-fault ring (OSF ring) in Czochralski (CZ)-grown silicon crystals is predicted based on the dynamics of point defects during growth. Preexponential constants for the equilibrium point defect concentrations and diffusivities are determined by fitting the predictions of the model to a single set of experimental data for OSF-ring dynamics. Other experimental data is well fit by this model. Moreover, point defect properties used are consistent with other estimates. Asymptotic analysis of the point defect model leads to a closed-form expression for the dependence of the OSF-ring location on processing conditions and thermophysical properties of point defects at the melting temperature. These results indicate that differentiation between defect types in CZ-grown material can be done entirely on the basis of point defect dynamics.
The Hydrolysis of Some Alkyl Lactates. II. “Neutral” and Acid Hydrolyses1 (1953)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Hydrolysis of Some Alkyl Lactates. II. "Neutral" and Acid Hydrolyses1A. Alberto Colon, Kenneth H. Vogel, and J. C. WarnerCite this: J. Am. Chem. Soc. 1953, 75, 23, 6074–6075Publication Date (Print):December 1, 1953Publication History Published online1 May 2002Published inissue 1 December 1953https://pubs.acs.org/doi/10.1021/ja01119a538https://doi.org/10.1021/ja01119a538research-articleACS PublicationsRequest reuse permissionsArticle Views89Altmetric-Citations3LEARN 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
Isolation of the CXC chemokines ENA‐78, GROα and GROγ from tumor cells and leukocytes reveals NH2‐terminal heterogeneity (1999)

Chemokines are a family of chemotactic peptides affecting leukocyte migration during the inflammatory response. Post-translational modification of chemokines has been shown to affect their biological potency. Here, the isolation and identification of natural isoforms of the neutrophil chemoattractants GRO alpha and GRO gamma and the epithelial-cell-derived neutrophil attractant-78 (ENA-78), is reported. Cultured tumor cells produced predominantly intact chemokine forms, whereas peripheral blood monocytes secreted mainly NH2-terminally truncated forms. The order of neutrophil chemotactic potency of these CXC chemokines was GRO alpha > GRO gamma > ENA-78 both for intact and truncated forms. However, truncated GRO alpha (4,5,6-73), GRO gamma (5-73) and ENA-78(8,9-78) were 30-fold, fivefold and threefold more active than the corresponding intact chemokine. As a consequence, truncated GRO alpha (4,5,6-73) was 300-fold more potent than intact ENA-78 indicating that both the type of chemokine and its mode of processing determine the chemotactic potency. Similar observations were made when intact and truncated GRO alpha, GRO gamma and ENA-78 were compared for their capacity to induce an increase in the intracellular calcium concentration in neutrophilic granulocytes, and to desensitize the calcium response towards the CXC chemokine granulocyte chemotactic protein-2 (GCP-2). It must be concluded that physiological proteolytic cleavage of CXC chemokines in general enhances the inflammatory response, whereas for CC chemokines NH2-terminal processing mostly results in reduced chemotactic potency.
In vivo efficacy of the CD40 agonist antibody CP-870,893 against a broad range of tumor types: Impact of tumor CD40 expression, dendritic cells, and chemotherapy (2006)

2514 Background: CP-870,893 is a fully human IgG 2 CD40 agonist antibody currently in early clinical trials. In vitro studies demonstrate its ability to bind human CD40 and enhance dendritic cell costimulatory molecule expression and cytokine production. Methods: In order to assess its potential for cancer therapy, we evaluated the anti-tumor efficacy of CP-870,893 against several CD40 pos and CD40 neg human tumors in SCID beige mice. We specifically addressed the role of tumor CD40 expression, the impact of re-population with human dendritic and T cells on efficacy, and it’s potential to act in synergy with chemotherapeutic agents. Results: We demonstrate that a single i.p. injection of CP-870,893 (T 1/2 ∼ 7 days) prevented the growth of several subcutaneous CD40 pos tumors including two B cell lymphomas, the breast carcinoma BT-474, and the prostate tumor PC-3 (ED 50 = 0.02 mg/kg; C eff ∼100 ng/mL). Efficacy was demonstrated when CP-870,893 was administered at the time of tumor challenge, but was also observed when treatment was delayed until tumors were well established. Although efficacious against CD40 pos tumors, CP-870,893 had no effect on the growth of CD40 neg/low tumors unless mice were repopulated at the tumor site with both naïve human dendritic cells and T cells. In these repopulated animals, i.p. administration of CP-870,893 inhibited the growth of a CD40 low colon carcinoma and a CD40 neg erythroleukemic tumor (ED 50 = 0.005 mg/kg). The presence of human T cells and dendritic cells at the tumor site also improved the activity of CP-870,893 against CD40 pos tumors, reducing the ED 50 and C eff &gt;10-fold as compared to its effects in the absence of these cells, suggesting a synergy between direct CD40 mediated tumor killing and immune activation. Further, when administered as part of a combination treatment with a sub-optimal dose of cisplatin, improved activity was observed which resulted in tumor regression. Conclusions: These studies demonstrate the potent, broad-spectrum anti-tumor activity of CP-870,893 through both direct and immune mediated effects, its increased efficacy when co-administered with chemotherapeutic agents, and suggest its potential utility as a therapy for human cancer. [Table: see text]
Treating sickle cell disease by targeting HbS polymerization (2017)

Although the root cause of sickle cell disease is the polymerization of hemoglobin S (HbS) to form fibers that make red cells less flexible, most drugs currently being assessed in clinical trials are targeting the downstream sequelae of this primary event. Less attention has been devoted to investigation of the multiple ways in which fiber formation can be inhibited. In this article, we describe the molecular rationale for 5 distinct approaches to inhibiting polymerization and also discuss progress with the few antipolymerization drugs currently in clinical trials.
Ontogenetic Expression of Spot 35 Protein (Calbindin-D28K) in Human Olfactory Receptor Neurons and its Decrease in Alzheimer's Disease Patients (1996)

Expression of a calcium-binding protein, spot 35 protein (S-35, calbindin-D28k), was investigated immunohistochemically in the human olfactory mucosa of patients who ranged in age from 16 weeks of fetal development to 98 years old, including some with Alzheimer's disease (AD). S-35 immunoreactivity was observed clearly in olfactory receptor neurons (ORNs) and olfactory nerve bundles that were identified previously with antibodies to olfactory marker protein (OMP) and neuron-specific enolase (NSE). Throughout all ages, the mean number of ORNs immunoreactive for OMP did not change significantly, whereas the mean number of NSE- and S-35-immunoreactive ORNs declined markedly in the postnatal infant, young, and old patients when compared with that of the prenatal fetuses. S-35-immunoreactive ORNs decreased significantly in AD patients when compared with AD control patients. These results indicate that ORNs in humans express S-35 and that there is an age-related trend in the expression of S-35. Furthermore, the marked decrease of S-35 expression in ORNs of AD patients suggests that cell excitability associated with calcium ions and cell protective function against overload of intracellular calcium ions decline in these patients.
Bootstrapped ring oscillator with propagation delay time below 1.0 nsec/stage by standard 0.5&#x00B5;m bottom-gate amorphous Ga<inf>2</inf>O<inf>3</inf>-In<inf>2</inf>O<inf>3</inf>-ZnO TFT technology (2008)

This paper describes the design and fabrication of the high performance ring oscillator with the standard 0.5 mum bottom-gate amorphous Ga <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> -In <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> -ZnO TFT technology. A series of process and geometry parameters of devices are sophistically optimized to decrease the circuit signal's propagation delay and, in particular, a novel 3 TFTs bootstrapped inverter structure using the load-transistor's overlap capacitance as the bootstrapped capacitor is applied. Finally, the propagation delay time of 0.94 ns/stage for a supply voltage of 9 V is achieved in the 5-stage ring oscillator, which is over 75 times faster than previous report.
PolycyclicN‐hetero compounds.XXXVII. A convenient synthesis and evaluation of anti‐platelet aggregation activity of 1,2,4,5‐tetrahydro[1]‐ benzothiepino[4,5‐e]imidazo[1,2‐c]pyrimidine and its related compounds (1991)

Abstract A simple and highly efficient methodology for the synthesis of 1,2,4,5‐tetrahydro[1]benzothiepino[4,5‐ e ]‐imidazo[1,2‐ c ]pyrimidine ( XI ) having a novel ring system via 4‐substituted 5,6‐dihydro[1]benzothiepino‐[5,4‐ d ]pyrimidines VII‐X is described. The anti‐platelet aggregation activity for it and its related compounds against collagen‐induced aggregation of rabbit blood platelets in vitro was found.
Serotonin and Parkinson's disease: On movement, mood, and madness (2009)

An appreciation of the multiple roles that serotonin (5-HT) may play in Parkinson's disease (PD) has increased in recent years. Early pathological studies in PD demonstrated nonselective reductions of 5-HT in brain tissue but little correlation to comorbidities such as dyskinesia and mood disturbance. This, combined with treatment failures using serotonergic drugs in comparison to levodopa, meant the field was largely neglected until recently. The multitude of subtypes of 5-HT receptors in the brain and an increased understanding of the potential function 5-HT may play in modulating other neurotransmitter systems, including dopamine, GABA, and glutamate, have meant an expansion in efforts to develop potential serotonergic drugs for both motor and nonmotor symptoms in PD. However, several unanswered questions remain, and future studies need to focus on correlating changes in 5-HT neurotransmission in both pathological and in vivo imaging studies with a full clinical phenotype.
Multi-skew detection of Indian script documents (2002)

There are many documents where text lines are not parallel to each other i.e. these lines have different inclinations with the horizontal lines (multi-skew documents). For the OCR of such a document we have to estimate the skew angle of individual text lines because a single rotation cannot de-skew all text lines of the document. In this paper, we describe a robust technique for multi-skew angle detection from Indian documents containing the most popular Indian scripts Devnagari and Bangla. Most characters in these scripts have horizontal lines at the top, called head-lines. The character head-lines usually connect one another in a word and the word appears as a single component. In the proposed method, the connected components are at first labeled and selected. The upper envelopes of selected components are found by column-wise scanning from the top of the component. Portions of the upper envelope satisfying the properties of a digital straight line are detected. They are then clustered into groups belonging to single text lines. Estimates from these individual clusters give the skew angle of each text line. The proposed multi-skew detection technique has an accuracy about 98.3%.
Tag Strategy for Separation and Recovery (2002)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTag Strategy for Separation and RecoveryJun-ichi Yoshida and Kenichiro ItamiView Author Information Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Yoshida, Kyoto 606-8501, Japan Cite this: Chem. Rev. 2002, 102, 10, 3693–3716Publication Date (Web):August 30, 2002Publication History Received18 March 2002Published online30 August 2002Published inissue 1 October 2002https://doi.org/10.1021/cr0103524Copyright © 2002 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views2400Altmetric-Citations162LEARN 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 Read OnlinePDF (779 KB) Get e-AlertsSUBJECTS:Catalysts,Chemical reactions,Molecules,Reagents,Solvents Get e-Alerts
Methyl Carbonium Ion Migration during the Reaction of 4-Chloro-5-methoxyl-3(2H)-pyridazinone with Trifluoroethylation Agents (2009)

To synthesize 4-chloro-5-methoxy-2-(b-trifluoroethyl)-3(2H)-pyridazinone (4), the reactions of 4-chloro-5-methoxy-3(2H)-pyridazinone (5) with RCH(2)CF(3)(R = I, TsO, MsO, TfO) in different solvents were studied. It was found that methyl group migration took place during this reaction. An oxonium salt 9 was suggested as the active intermediate for the formation of the byproduct 4-chloro-5-methoxy-2-methyl-3(2H)-pyridazinone (7) and 4-chloro-2-methyl-5-(b-trifluoroethoxy)-3(2)-pyridazinone(8).
Identification of laminin alpha1 and beta1 chain peptides active for endothelial cell adhesion, tube formation, and aortic sprouting. (1999)

Laminin-1 is a basement membrane glycoprotein that promotes several biological activities including cell attachment, tumor metastasis, and angiogenesis. Angiogenesis plays an important role in tissue formation, reproduction, wound healing, and several pathological conditions. In this study, we screened 405 synthetic peptides from the alpha1 and beta1 chains to identify potential sites on laminin-1 active with endothelial cells. Peptides were initially screened by testing both endothelial cell adhesion to peptide-coated wells and tube formation on Matrigel in the presence of soluble peptide. Twenty active peptides were identified in these screens. A secondary screen using the rat aortic ring sprouting assay identified 13 of the 20 peptides that stimulated endothelial sprouting. Several of these active peptides were also found to stimulate human umbilical vein endothelial cell migration in Boyden chamber assays. Differences in the amount of peptide needed for the response and in the resultant morphologies/responses were observed between the peptides in all of the assays. Our results suggest that several active domains on laminin-1 may play important roles in stimulating different steps in angiogenesis.
A Comparison of Standard-Dose and High-Dose Epinephrine in Cardiac Arrest outside the Hospital (1992)

In this study, we were unable to demonstrate any difference in the overall rate of return of spontaneous circulation, survival to hospital admission, survival to hospital discharge, or neurologic outcome between patients treated with a standard dose of epinephrine and those treated with a high dose.
The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes (2007)

Cationic liposomes are being used increasingly as efficient adjuvants for subunit vaccines but their precise mechanism of action is still unknown. Here, we investigated the adjuvant mechanism of cationic liposomes based on the synthetic amphiphile dimethyldioctadecylammonium (DDA). The liposomes did not have an effect on the maturation of murine bone-marrow-derived dendritic cells (BM-DCs) related to the surface expression of major histocompatibility complex (MHC) class II, CD40, CD80 and CD86. We found that ovalbumin (OVA) readily associated with the liposomes (> 90%) when mixed in equal concentrations. This efficient adsorption onto the liposomes led to an enhanced uptake of OVA by BM-DCs as assessed by flow cytometry and confocal fluorescence laser-scanning microscopy. This was an active process, which was arrested at 4 degrees and by an inhibitor of actin-dependent endocytosis, cytochalasin D. In vivo studies confirmed the observed effect because adsorption of OVA onto DDA liposomes enhanced the uptake of the antigen by peritoneal exudate cells after intraperitoneal injection. The liposomes targeted antigen preferentially to antigen-presenting cells because we only observed a minimal uptake by T cells in mixed splenocyte cultures. The adsorption of antigen onto the liposomes increased the efficiency of antigen presentation more than 100 times in a responder assay with MHC class II-restricted OVA-specific T-cell receptor transgenic DO11.10 T cells. Our data therefore suggest that the primary adjuvant mechanism of cationic DDA liposomes is to target the cell membrane of antigen-presenting cells, which subsequently leads to enhanced uptake and presentation of antigen.