gebhart/patrepeval huggingface dataset:
The heparin binding 25 kDa fragment of thrombospondin‐1 promotes angiogenesis and modulates gelatinase and TIMP‐2 production in endothelial cells (2000)

The hypothesis that thrombospondin‐1 (TSP‐1) can exert opposite effects on angiogenesis depending on the functional status of its domains/fragments was investigated. In the rabbit cornea, TSP‐1 inhibited angiogenesis induced by fibroblast growth factor‐2 (FGF‐2). However, when tested per se, TSP‐1 was able to elicit an angiogenic response comparable to that induced by FGF‐2. Induction of angiogenesis was dose‐dependent (20 ng ‐ 2 μg/pellet), was prevented by anti‐TSP antibodies or by heat‐inactivation of TSP‐1, and was not due to inflammatory mediators, to FGF‐2 or to TGF‐β. Equimolar concentrations of the 25 kDa heparin binding fragment of TSP‐1 were even more efficient than the whole molecule, and promoted the angiogenic activity of FGF‐2. On the contrary, the 140 kDa fragment of TSP‐1 did not induce angiogenesis and turned off the angiogenic response to FGF‐2. The 25 kDa fragment and TSP‐1, but not the 140 kDa fragment, increased endothelial cell invasiveness and stimulated the production and activation of matrix metalloproteinase‐2 (MMP‐2). Moreover, the 25 kDa fragment reduced the synthesis of the MMP‐2 inhibitor TIMP‐2, while the 140 kDa fragment caused a twofold increase in TIMP‐2 production and inhibited MMPs stimulation by TSP‐1 and FGF‐2. We conclude that TSP‐1 is a source of smaller mediators of angiogenesis, which affect in an opposite way endothelial cell functions and proteolytic activity, thus resulting in an opposite final effect on angiogenesis.
Electrical connection of enzyme redox centers to electrodes (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrical connection of enzyme redox centers to electrodesAdam HellerCite this: J. Phys. Chem. 1992, 96, 9, 3579–3587Publication Date (Print):April 1, 1992Publication History Published online1 May 2002Published inissue 1 April 1992https://pubs.acs.org/doi/10.1021/j100188a007https://doi.org/10.1021/j100188a007research-articleACS PublicationsRequest reuse permissionsArticle Views2050Altmetric-Citations526LEARN 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 options Get e-Alerts
TRANSCRANIAL MAGNETIC STIMULATION (TMS) FOR MAJOR DEPRESSION: A MULTISITE, NATURALISTIC, OBSERVATIONAL STUDY OF ACUTE TREATMENT OUTCOMES IN CLINICAL PRACTICE (2012)

Outcomes demonstrated response and adherence rates similar to research populations. These data indicate that TMS is an effective treatment for those unable to benefit from initial antidepressant medication.
A Mutation in Caenorhabditis elegans NDUF-7 Activates the Mitochondrial Stress Response and Prolongs Lifespan via ROS and CED-4 (2015)

The mevalonate pathway is responsible for the synthesis of cholesterol, coenzyme Q, and prenyl groups essential for small GTPase modification and function, and for the production of dolichols important for protein glycosylation. Statins, i.e., cholesterol-lowering drugs that inhibit the rate-limiting enzyme in the mevalonate pathway, HMG-CoA reductase, are lethal to Caenorhabditis elegans even though this animal lacks the branch of the mevalonate pathway that leads to cholesterol synthesis. To better understand the effects of statins that are not related to cholesterol, we have adopted the strategy of isolating statin-resistant C. elegans mutants. Previously, we showed that such mutants often have gain-of-function mutations in ATFS-1, a protein that activates the mitochondrial unfolded protein response. Here, we describe the isolation of a statin-resistant mutant allele of the NDUF-7 protein, which is a component of complex I in the mitochondrial electron transport chain. The novel nduf-7(et19) mutant also exhibits constitutive and ATFS-1-dependent activation of the mitochondrial unfolded protein response (UPR(mt)) and prolonged life span, both of which are mediated through production of ROS. Additionally, lifespan extension, but not activation, of the mitochondrial unfolded protein response was dependent on the pro-apoptotic gene ced-4. We conclude that the nduf-7(et19) mutant allele causes an increase in reactive oxygen species that activate ATFS-1, hence UPR(mt)-mediated statin resistance, and extends life span via CED-4.
Selection of tests and services to generate revenue for reference laboratories. (1989)

The 1980s have brought heightened awareness of the operating costs of immunohematology reference laboratories. Revenues can be increased by raising existing charges, expanding services, and acquiring new customers. Selection of tests and services to further increase revenue is best made following a thorough assessment of community needs and the capabilities and resources of the reference Laboratory.
Analysis of the Bacillus subtilis S10 ribosomal protein gene cluster identifies two promoters that may be responsible for transcription of the entire 15-kilobase S10-spc-alpha cluster (1997)

We have sequenced a previously uncharacterized region of the Bacillus subtilis S10 ribosomal protein gene cluster. The new segment includes genes for S10, L3, L4, L23, L2, S19, L22, S3, and part of L16. These B. subtilis genes map in the same order as the genes in the Escherichia coli S10 ribosomal protein operon. Two potential promoter sequences were identified, one approximately 200 bases and the other approximately 140 bases upstream of the S10 gene. The activities of the two promoters were demonstrated by primer extension analysis, in vitro transcription experiments, and in vivo promoter fusion plasmid studies. In agreement with previous reports, our Northern analysis of exponentially growing cells failed to identify terminators or other active promoters within the S10-spc-alpha region. Our observations suggest that the two S10 promoters reported here are responsible for transcribing a 15-kb-long transcript for all of the genes in the B. subtilis S10, spc, and alpha clusters.
Clinical and Pathological Aspects of Parkinsonism in Alzheimer's Disease (1989)

To examine the natural history and pathogenesis of parkinsonism in Alzheimer's disease, 44 subjects with clearly established senile dementia of the Alzheimer type were studied during a 66-month period. Sixteen subjects (36%) developed idiopathic parkinsonism, and 12 subjects (27%) developed drug-induced parkinsonism; the chief clinical features of both types were bradykinesia and rigidity, but not resting tremor. The presence of parkinsonism was associated with global (rather than selective) cognitive impairment, as determined by psychometric testing, and with more rapid progression to advanced stages of dementia. The pathological correlates of clinical parkinsonism were heterogeneous in 10 subjects with Alzheimer's disease who were examined post mortem. Coexistent Parkinson's disease was observed in five cases and nonspecific nigral degenerative lesions were present in another three; however, two cases had neither histological changes nor reduced neuronal densities in the substantia nigra. These two cases suggested that extranigral lesions, possibly involving mesocortical dopaminergic pathways, may contribute to the development of parkinsonism in subjects with Alzheimer's disease.
CDKI‐71, a novel CDK9 inhibitor, is preferentially cytotoxic to cancer cells compared to flavopiridol (2011)

Cancer cells appear to depend heavily on antiapoptotic proteins for survival and so targeted inhibition of these proteins has therapeutic potential. One innovative strategy is to inhibit the cyclin-dependent kinases (CDKs) responsible for the regulation of RNA polymerase II (RNAPII). In our study, we investigated the detailed cellular mechanism of a novel small-molecule CDK inhibitor (CDKI-71) in cancer cell lines, primary leukemia cells, normal B - & T- cells, and embryonic lung fibroblasts and compared the cellular and molecular responses to the clinical CDK inhibitor, flavopiridol. Like flavopiridol, CDKI-71 displayed potent cytotoxicity and caspase-dependent apoptosis induction that were closely associated with the inhibition of RNAPII phosphorylation at serine-2. This was caused by effective targeting of cyclinT-CDK9 and resulted in the downstream inhibition of Mcl-1. No correlation between apoptosis and inhibition of cell-cycle CDKs 1 and 2 was observed. CDKI-71 showed a 10-fold increase in potency in tumor cell lines when compared to MRC-5 human fibroblast cells. Significantly, CDKI-71 also demonstrated potent anti-chronic lymphocytic leukemia activity with minimal toxicity in normal B- and T-cells. In contrast, flavopiridol showed little selectivity between cancer and normal cells. Here, we provide the first cell-based evidence that flavopiridol induces DNA double-strand breaks: a fact which may explain why flavopiridol has such a narrow therapeutic window in preclinical and clinical settings. Taken together, our data provide a rationale for the development of selective CDK inhibitors as therapeutic agents and CDKI-71 represents a promising lead in this context.
RESUSCITATION FROM HEMORRHAGIC SHOCK WITH MalPEG-ALBUMIN: COMPARISON WITH MalPEG-HEMOGLOBIN (2004)

Our aim was to determine the efficacy of polyethylene glycol-conjugated human albumin (MalPEG-Alb) in restoring circulatory volume after 1 h of hemorrhagic shock. Experiments were performed in the awake condition in the hamster skin fold preparation. Microhemodynamic parameters and tissue Po2 were assessed with intravital microscopy and the use of the phosphorescence quenching technique. One hour after shock induction by withdrawal of 50% of the blood volume, animals were resuscitated with MalPEG-Alb (n = 6). Systemic and microhemodynamic parameters following resuscitation were identical to those obtained with the same protocol using MalPEG-Hb (1). However, parameters related to microvascular oxygen distribution were significantly lower in the MalPEG-Alb group compared with the previous data from the MalPEG-Hb group in that tissue oxygen partial pressure was 5 +/- 2 mmHg (vs. 8 +/- 3 mmHg, P < 0.05), oxygen delivery was reduced to 60 +/- 27% (P < 0.05), and oxygen consumption was reduced to 69 +/- 28% (P < 0.05). Both molecules were matched in composition (4.2 g/dL) and surface chemistry. MalPEG-Alb colloid osmotic pressure was 37 mmHg (vs. 49 mmHg for MalPEG-Hb), and viscosity was 2.7 cP (vs. 2.5 cP for MalPEG-Hb). The present results show that both solutions are efficacious plasma expanders and that the hemoglobin-based solution provides improved oxygen distribution and tissue Po2 in the hamster chamber model.
Gap junction-mediated interactions between cells (2001)

Abstract Gap junction channels are expressed in almost all types of cell. Their roles are diverse and are crucial for normal embryonic development and the functioning of adult organs. Point mutations, in a growing number of members of the gap junction family, appear to underlie several human diseases including profound non-syndromic deafness, heart disease, peripheral nerve myopathy, skin disorders, and cataract promotion. This has led to a rapid increase in the number of researchers investigating gap junctional communication in these disease conditions. In order to study gap junctional interactions between cells, there are three basic approaches which, when integrated, provide a rounded picture of communication in any particular system.
Predictive value of a simple asthma morbidity index in a general practice population. (1999)

The revised morbidity index is a simple and valid tool for the opportunistic surveillance of asthma in primary care.
Functions of peroxisome proliferator‐activated receptors (PPAR) in skin homeostasis (2004)

The peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that belong to the nuclear hormone receptor family. Three isotypes (PPAR alpha, PPAR beta or delta, and PPAR gamma) with distinct tissue distributions and cellular functions have been found in vertebrates. All three PPAR isotypes are expressed in rodent and human skin. They were initially investigated for a possible function in the establishment of the permeability barrier in skin because of their known function in lipid metabolism in other cell types. In vitro studies using specific PPAR agonists and in vivo gene disruption approaches in mice indeed suggest an important contribution of PPAR alpha in the formation of the epidermal barrier and in sebocyte differentiation. The PPAR gamma isotype plays a role in stimulating sebocyte development and lipogenesis, but does not appear to contribute to epidermal tissue differentiation. The third isotype, PPAR beta, regulates the late stages of sebaceous cell differentiation, and is the most effective isotype in stimulating lipid production in these cells, both in rodents and in humans. In addition, PPAR beta activation has pro-differentiating effects in keratinocytes under normal and inflammatory conditions. Finally, preliminary studies also point to a potential role of PPAR in hair follicle growth and in melanocyte differentiation. By their diverse biological effects on cell proliferation and differentiation in the skin, PPAR agonists or antagonists may offer interesting opportunities for the treatment of various skin disorders characterized by inflammation, cell hyperproliferation, and aberrant differentiation.
Air-coupled acoustic imaging with zero-group-velocity Lamb modes (2003)

A Lamb wave resonance has been found that allows unusually efficient transmission of airborne sound waves through plates. This occurs at the zero-group-velocity point at the frequency minimum of the first-order symmetric (S1) Lamb mode. At this frequency, plane waves with a range of incident angles can couple between the air and the Lamb mode in the solid plate, dominating the spectrum of transmitted focused sound beams by 10 dB or more. We use this frequency for C-scan imaging, and demonstrate the detection of both a 3.2-mm-diameter buried flaw and a subwavelength thickness changes of .005λ (1%).
Identification of a source of biologically active CD40 ligand (1992)

We have identified the murine thymoma line EL4 as a source of biologically active CD40 ligand. Using a biotin-labeled soluble CD40.Fc fusion protein, consisting of the extracellular domain of human CD40 and the Fc region of human IgG1, EL4 cells were subjected to repeated flow cytometric cell sorting to select for cells with enhanced biotinylated CD40.Fc binding. After nine rounds of sorting, the number of CD40.Fc binding sites/cell had risen from 450 on the unsorted parental EL4 cells to 15,000 on EL40.9 cells (EL4 cells sorted with biotinylated CD40.Fc for nine rounds). Scatchard analysis of radiolabeled CD40.Fc binding revealed that the surface-expressed CD40 ligand on parental EL4 and EL40.9 cells bound its receptor with a single class of high-affinity sites (Kd = 0.5 nM). Supernatant (SN) from the sorted EL40.9 cells was found to contain human and murine B cell stimulatory activity which could be removed by preclearing with immobilized CD40.Fc, confirming the presence of soluble CD40 ligand in the preparations. EL40.9 supernatant enhanced soluble CD23 (sCD23) release and induced IgE secretion from interleukin 4-stimulated human B cells. In addition, EL40.9 SN contained proliferative activity for anti-IgM-activated murine B cells which could be removed by treatment with immobilized CD40.Fc. However, the same SN had no demonstrable activity on the proliferation of human B cells. The results presented here describe, for the first time, a source of membrane-bound and soluble CD40 ligand. The soluble form of this murine ligand has activity on murine and human B cells and induces some of the functional responses predicted for the ligand based on the action of stimulatory antibodies directed against the human CD40 surface molecule.
Photogenerated reagents for biological receptor-site labeling (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticlePhotogenerated reagents for biological receptor-site labelingJeremy R. KnowlesCite this: Acc. Chem. Res. 1972, 5, 4, 155–160Publication Date (Print):April 1, 1972Publication History Published online1 May 2002Published inissue 1 April 1972https://pubs.acs.org/doi/10.1021/ar50052a006https://doi.org/10.1021/ar50052a006research-articleACS PublicationsRequest reuse permissionsArticle Views650Altmetric-Citations299LEARN 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
A tangible interface for IP network simulation (2003)

We present the IP Network Design Workbench which supports collaborative network design and simulation by a group of experts and customers. This system is based on a tangible user interface platform called "Sensetable," which can wirelessly detect the location and orientation of physical pucks. Using this system, users can directly manipulate network topologies, control parameters of nodes and links using physical pucks on the sensing table, and simultaneously see the simulation results projected onto the table in real-time.
RAM-induced Allostery Facilitates Assembly of a Notch Pathway Active Transcription Complex (2008)

The Notch pathway is a conserved cell-to-cell signaling mechanism, in which extracellular signals are transduced into transcriptional outputs through the nuclear effector CSL. CSL is converted from a repressor to an activator through the formation of the CSL-NotchIC-Mastermind ternary complex. The RAM (RBP-J associated molecule) domain of NotchIC avidly interacts with CSL; however, its role in assembly of the CSL-NotchIC-Mastermind ternary complex is not understood. Here we provide a comprehensive thermodynamic, structural, and biochemical analysis of the RAM-CSL interaction for components from both mouse and worm. Our binding data show that RAM and CSL form a high affinity complex in the presence or absence of DNA. Our structural studies reveal a striking distal conformational change in CSL upon RAM binding, which creates a docking site for Mastermind to bind to the complex. Finally, we show that the addition of a RAM peptide in trans facilitates formation of the CSL-NotchIC-Mastermind ternary complex in vitro.
Electric signalling controls wound healing, cell proliferation and division, and nerve regeneration. (2004)

In this project we designed four different level of electrotaxis experiment from &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;, from single cell monolayer cells then further to stratified multiple layers of cells, to prove that cell directional migration, wound healing and nerve regeneration are all controlled by endogenous electric field. Using single cell model and monolayer scratch wound model &lt;i&gt;in vitro&lt;/i&gt;, we demonstrated the electrotactic response of directional cell migration and wound healing were all controlled by physiological EF. Using a three dimensional stratified cornea epithelium wound model &lt;i&gt; ex vivo&lt;/i&gt;, we further proved that electric signals could modulate the directional cell migration in a wound. We then used an &lt;i&gt;in vivo&lt;/i&gt; rat corneal model, which generates its own endogenous EF, to show that the direction of nerve growth, the rate of epithelial wound healing and the orientation of the cell division in wound healing were all controlled by the wound-induced engenous EF. Wounding the cornea generates endogenous EFs in the plane of the epithelial sheet because the transcorneal potential difference (TCPD); +40mb internally positive) collapses at the wound edge, but is maintained at normal levels 0.5 mm back from the wound. We manipulated the endogenous EF this creates using clinically proved drugs with differing actions. The wound-induced EF controlled the orientation of cell division; most epithelial cells divided with a cleavage plane parallel to the wound edge and perpendicular to the EF vector. Increasing or decreasing the EF pharmacological, respectively increased or decreased the extent of oriented cell division. IN addition, cells closest to the wound edge where the EF was highest, were oriented most strongly by the EF. Remarkably, an endogenous EF also enhanced the frequency of cell division. This also was regulated by enhancing or suppressing the EF pharmacologically. Since the endogenous EF also regulated the wound healing rate, it may act as one control of the interplay between cell migration and cell division during healing.
Efficient matching and indexing of graph models in content-based retrieval (2001)

In retrieval from image databases, evaluation of similarity, based both on the appearance of spatial entities and on their mutual relationships, depends on content representation based on attributed relational graphs. This kind of modeling entails complex matching and indexing, which presently prevents its usage within comprehensive applications. In this paper, we provide a graph-theoretical formulation for the problem of retrieval based on the joint similarity of individual entities and of their mutual relationships and we expound its implications on indexing and matching. In particular, we propose the usage of metric indexing to organize large archives of graph models, and we propose an original look-ahead method which represents an efficient solution for the (sub)graph error correcting isomorphism problem needed to compute object distances. Analytic comparison and experimental results show that the proposed lookahead improves the state-of-the-art in state-space search methods and that the combined use of the proposed matching and indexing scheme permits for the management of the complexity of a typical application of retrieval by spatial arrangement.