gebhart/patrepeval huggingface dataset:
Effect Of Purified Poloxamer 188 and Various Dextrans On Erythrocyte Sedimentation Rate In Healthy Subjects and Patients With Sickle Cell Disease (2013)

Introduction Purified poloxamer188 (P188) (Mast Therapeutics) is a non-ionic, linear block copolymer composed of a central chain of hydrophobic polyoxypropylene and two flanking chains of hydrophylic polyoxyethylene (MW 8.5 kDa). This agent has hemorheologic properties which result in improved microvascular blood flow. P188 has been investigated in a number of indications and is currently under study in an international phase 3 clinical trial in sickle cell patients with vaso-occlusive crisis. Dextrans represent branched polysaccharides of 10-70 kDa that have been used as antithrombotic agents and plasma expanders. Sickle cell disease (SCD) represents a complex hemorheologic condition due to RBC aggregation and cell-fibrin/fibrinogen interactions. The erythrocyte sedimentation rate (ESR) is reflective of RBC and plasma interactions. This study was designed to compare the effect of P188 and dextrans on ESR’s in blood obtained from healthy subjects and patients with sickle cell disease who were seen at Loyola University Medical Center clinics. Material and Methods Whole EDTA blood collected from normal individuals (n=8) and sickle cell patients confirmed by electrophoresis (n=11) were supplemented with P188 or dextran 10K, 18K , 40K and 70K at various concentrations (or saline control). ESR was measured using standard laboratory technique. Results The ESR’s for sickle cell patients (26.4 ± 7.1 mm/hr) were significantly higher in comparison to the ESR’s for healthy subjects (14.6 ± 2.1 mm/hr). Supplementation of P188 decreased ESR’s in both populations. Normal blood ESR’s decreased to 9.1 ± 1.3 mm/hr (38%), whereas the sickle cell patient values decreased to 14.1 ± 4.6 mm/hr (47%). At comparable concentrations, none of the dextrans changed ESR’s in healthy subjects or patients with sickle cell disease. Discussion These results demonstrate that ESR in SCD patients are elevated compared to healthy subjects. P188 supplementation decreased (up to 50%) ESR’s in both the healthy subjects and sickle cell patients. This may be due to the inhibition of rouleaux formation resulting from P188 effects on RBC membranes or cell-protein interactions. None of the dextrans produced a similar decrease, suggesting that the observed lowering of ESR by P188 is unlikely to be due to a non-specific effect related to polymer molecular weight. Clinical Implications P188 is a potential therapeutic agent which may facilitate blood flow and reduce cell-fibrin/fibrinogen interactions in a variety of hemorrheologic disorders. The observed decrease in ESR both in normal and sickle cell blood samples by P188 may primarily be due to increased membrane hydration, fibrinogen dispersion and anti-adhesive effects of this agent. Disclosures: Emanuele: Mast Therapeutics: Employment. Fareed:Mast Therapeutics: Research Funding.
Synthesis of novel coumarin derivatives and its biological evaluations (2012)

Coumarins possess a number of biological activities like anticoagulant, antimicrobial, anti-inflammatory, analgesic, antioxidant, anticancer, antiviral, antimalarial etc. Coumarin belongs to a group as benzopyrones, which consists of a benzene ring joined to a pyrone nucleus. In the present study, the thirteen new coumarin derivatives are synthesized and characterized by IR and 1H NMR spectra. These newly formed Coumarin derivatives were screened for anti-inflammatory activity by carrageenan induced rat paw edema model and antibacterial activity against Stophylococcus aureus as well as Escherichia coli by cup plate method. The synthesized coumarin derivatives were administered orally in the dose of 10 mg/kg. Ibuprofen and amoxicillin were taken as standard for antiinflammatory and antibacterial activity respectively. The result of present investigation showed that the compounds 7, 8 & 12 showed significantly (P < 0.001) inhibition against Carrageenan induced rat paw edema, but all new compounds(1-13) significantly (P<0.001) zone of inhibition against bacterial activity as compared to control group.
Automatic partitioning of data and computations on scalable shared memory multiprocessors (2002)

This paper describes an algorithm for deriving data and computation partitions on scalable shared memory multiprocessors. The algorithm establishes affinity relationships between where computations are performed and where data is located based on array accesses in the program. The algorithm then uses these affinity relationships to determine both static and dynamic partitions for arrays and parallel loops. Experimental results from a prototype implementation of the algorithm demonstrate that it is computationally efficient and that it improves the parallel performance of standard benchmarks. The results also show the necessity of taking shared memory effects (memory contention, cache locality, false-sharing and synchronization) into account-partitions derived to minimize only interprocessor communications do not necessarily result in the best performance.
Upregulation of DR5 by proteasome inhibitors potently sensitizes glioma cells to TRAIL‐induced apoptosis (2008)

This study was undertaken to explore the potential of new therapeutic approaches designed to reactivate cell death pathways in apoptosis-refractory gliomas and to characterize the underlying molecular mechanisms of this reactivation. Here we investigated the sensitivity of a panel of glioma cell lines (U87, U251, U343, U373, MZ-54, and MZ-18) to apoptosis induced by the death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAIL in combination with gamma irradiation, and TRAIL in combination with proteasome inhibitors (MG132 and epoxomicin). Analysis of these six glioma cell lines revealed drastic differences in their sensitivity to these treatments, with two of the six cell lines revealing no significant induction of cell death in response to TRAIL alone. Interestingly, the proteasome inhibitors MG132 and epoxomicin were capable of potentiating TRAIL-induced apoptosis in TRAIL-sensitive U87 and U251 cells and of reactivating apoptosis in TRAIL-resistant U343 and U373 cells. In contrast, gamma irradiation had no synergistic effects with TRAIL in the two TRAIL-resistant cell lines. RNA interference against death receptor 5 (DR5) revealed that reactivation of TRAIL-induced apoptosis by proteasome inhibitors depended on enhanced transcription and surface expression of DR5. Transient knockdown of the transcription factor GADD153/C/EBP homologous protein and application of the synthetic c-Jun N-terminal kinase inhibitor SP600125 indicated that enhanced DR5 expression occurred independently of GADD153/C/EBP homologous protein, but required activation of the c-Jun N-terminal kinase/c-Jun signaling pathway. Novel therapeutic approaches using TRAIL or agonistic TRAIL receptor antibodies in combination with proteasome inhibitors may represent a promising approach to reactivate apoptosis in therapy-resistant high-grade gliomas.
The Eyellipse and Considerations in the Driver’s Forward Field of View - Part 1 (1968)

&lt;div class="htmlview paragraph"&gt;The effect of pillar size on vision obscuration in the forward field of view is discussed.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The SAE J941a Eyellipse has become an accepted design tool and is one of the first of its kind to be used in automotive driver work space design. A review of this recommended practice will include a brief reminder of its value and also of its limitations. An expansion of the tools limitations covering a driver head turned consideration is included. A review of a study in process for developing an Eyellipse for use in truck packaging is also included.&lt;/div&gt;
Cure of Overt Diabetes in NOD Mice by Transient Treatment With Anti-Lymphocyte Serum and Exendin-4 (2004)

Treatment of overtly diabetic NOD mice with anti-lymphocyte serum (ALS), a polyclonal anti-T-cell antibody, abrogates autoimmunity and achieves partial clinical remission. Here we investigated whether the addition of exendin-4, a hormone that stimulates insulin secretion and beta-cell replication and differentiation, improves induction of remission by ALS. Transient treatment of overtly diabetic NOD mice with ALS and exendin-4 achieved complete remission in 23 of 26 mice (88%) within 75 days, accompanied by progressive normalization of glucose tolerance, improved islet histology, increased insulin content in the pancreas, and insulin release in response to a glucose challenge. Syngeneic islets transplanted into mice cured by treatment with ALS plus exendin-4 remained intact, and cotransfer of lymphocytes from cured mice delayed diabetes induction by adoptive transfer, suggesting the long-lasting presence of autoimmune regulatory cells. Although ALS alone also achieved reversal of diabetes, the frequency of remission was low (40%). No treatment or exendin-4 alone failed to produce remission. These results show that exendin-4 synergistically augments the remission-inducing effect of ALS. The addition of beta-cell growth factors, such as exendin-4, to immunotherapy protocols with anti-T-cell antibodies presents a potential novel approach to the cure of patients with new-onset type 1 diabetes.
Unfractionated and low molecular weight heparin affect fibrin structure and angiogenesis in vitro. (2000)

Cancer patients treated for venous thromboembolism with low molecular weight heparin (LMWH) have a better survival rate than patients treated with unfractionated heparin (UFH). Because fibrin-associated angiogenesis is an important determinant in the progression and metastasis of many solid tumors, the effects of heparins on in vitro angiogenesis were investigated. Both UFH and LMWH inhibited bFGF-induced proliferation of human microvascular endothelial cells (hMVECs) to the same the extent (36-60%). VEGF165-induced proliferation was inhibited to a to a lesser extent (19-33%). Turbidity measurements and electron microscopy showed that the presence of LMWH during polymerization of the fibrin matrix led to a more transparent rigid network with thin fibrin bundles, whereas the presence of UFH resulted in a more opaque more porous network with thick fibrin fibers. We used a human in vitro angiogenesis model, which consisted of hMVECs seeded on top of a fibrin matrix, and stimulated the cells with basic fibroblast growth factor plus tumor necrosis factor a to induce capillary-like tubular structures. The formation of capillary-like tubular structures was retarded with matrices polymerized in the presence of LMWH (46% inhibition compared with a control matrix for both 1.5 and 10 units/ml LMWH), whereas matrices polymerized in the presence of UFH facilitated tubular structure formation (72 and 36% stimulation compared with a control matrix for 1.5 and 10 units/ml UFH, respectively). Similar results were obtained for cells stimulated with vascular endothelial growth factor plus tumor necrosis factor alpha. These data demonstrate the inhibitory effect of heparins on proliferation of hMVECs and provide a novel mechanism by which LMWH may affect tumor progression, namely reduced ingrowth of microvascular structures in a fibrinous stroma matrix by rendering it less permissive for invasion.
Absence of SPARC results in increased cardiac rupture and dysfunction after acute myocardial infarction (2008)

The matricellular protein SPARC (secreted protein, acidic and rich in cysteine, also known as osteonectin) mediates cell-matrix interactions during wound healing and regulates the production and/or assembly of the extracellular matrix (ECM). This study investigated whether SPARC functions in infarct healing and ECM maturation after myocardial infarction (MI). In comparison with wild-type (WT) mice, animals with a targeted inactivation of SPARC exhibited a fourfold increase in mortality that resulted from an increased incidence of cardiac rupture and failure after MI. SPARC-null infarcts had a disorganized granulation tissue and immature collagenous ECM. In contrast, adenoviral overexpression of SPARC in WT mice improved the collagen maturation and prevented cardiac dilatation and dysfunction after MI. In cardiac fibroblasts in vitro, reduction of SPARC by short hairpin RNA attenuated transforming growth factor beta (TGF)-mediated increase of Smad2 phosphorylation, whereas addition of recombinant SPARC increased Smad2 phosphorylation concordant with increased Smad2 phosphorylation in SPARC-treated mice. Importantly, infusion of TGF-beta rescued cardiac rupture in SPARC-null mice but did not significantly alter infarct healing in WT mice. These findings indicate that local production of SPARC is essential for maintenance of the integrity of cardiac ECM after MI. The protective effects of SPARC emphasize the potential therapeutic applications of this protein to prevent cardiac dilatation and dysfunction after MI.
Cellular Interactions in the Stem Cell Niche (2004)

Stem cells are capable of both self-renewal and differentiation into many different cell types. These hallmark characteristics are regulated by other cells within the stem cell niche. In their Perspective,
 Wurmser
 et al.
 discuss the finding that endothelial cells in the neural stem cell niche secrete factors that influence neural stem cells to proliferate and become neurons (
 Shen
 et al.).
Study of fundamental laser material interaction parameters in solid and powder melting (2016)

This study attempts to develop a set of parameters controlling the bead profile&#13;\nof deposits in powder melting, based on the spatial energy distribution of laser.&#13;\nFour parameters, identified as the laser material interaction parameters were&#13;\nused to study the bead profile formation in powder melting. The focus is put on&#13;\ncontrol of the dimensional accuracy of powder deposits independently of the&#13;\noptical set-up and laser system.&#13;\nIn the initial stage to understand the effect of welding parameters on the&#13;\ndevelopment of the fusion zone, a solid metal with homogenous and known&#13;\nthermal properties was used. The results indicate that for large beam diameters,&#13;\ntypically used in cladding, power density and interaction time control the depth&#13;\nof penetration and beam diameter and interaction time controls the weld width.&#13;\nHowever, for small beam diameters, typically used in powder bed additive&#13;\nmanufacturing, it was found that it is more difficult to achieve steady state&#13;\nconduction welds due to high conduction losses to the bulk material and rapid&#13;\ntransition to keyhole regime. Therefore, with small beam diameters it is&#13;\nchallenging to achieve pure conduction welds, which should guarantee good&#13;\nquality of deposits and low spatter.&#13;\nIn the second part, the melting behaviour of solid material and powder for the&#13;\nsame material type was compared. The build height in powder melting depends&#13;\non layer thickness of the deposited powder and energy density, which needs to&#13;\nbe provided to fuse the powder to the workpiece, which is equivalent to&#13;\npenetration in laser welding of solids. Similar to solid melting, the build width in&#13;\npowder melting is controlled by beam diameter and the interaction time. It was&#13;\nalso found that with small beam diameters and large particle sizes it is more&#13;\ndifficult to generate keyhole in the base plate, as compared to solid material.&#13;\nTherefore, despite the presence of spatter in the process, a full keyhole is often&#13;\nnot generated.&#13;\nA set of parameters to describe the conduction welding process based on&#13;\nspatial distribution of laser energy has been developed. This enables achievement of a particular weld profile with various optical set-ups and&#13;\npotentially transfers of results between machines. However, more complex&#13;\nmelting characteristics of powder requires some additional factors to be&#13;\nincluded to develop a similar model for powders.
Immunity, neuroglia and neuroinflammation in autism (2005)

Autism is a complex neurodevelopmental disorder of early onset that is highly variable in its clinical presentation. Although the causes of autism in most patients remain unknown, several lines of research support the view that both genetic and environmental factors influence the development of abnormal cortical circuitry that underlies autistic cognitive processes and behaviors. The role of the immune system in the development of autism is controversial. Several studies showing peripheral immune abnormalities support immune hypotheses, however until recently there have been no immune findings in the CNS. We recently demonstrated the presence of neuroglial and innate neuroimmune system activation in brain tissue and cerebrospinal fluid of patients with autism, findings that support the view that neuroimmune abnormalities occur in the brain of autistic patients and may contribute to the diversity of the autistic phenotypes. The role of neuroglial activation and neuroinflammation are still uncertain but could be critical in maintaining, if not also in initiating, some of the CNS abnormalities present in autism. A better understanding of the role of neuroinflammation in the pathogenesis of autism may have important clinical and therapeutic implications.
Cohort migration of carcinoma cells: differentiated colorectal carcinoma cells move as coherent cell clusters or sheets. (1999)

Active migration of tumor cells is usually assessed as single cell locomotion in vitro using Boyden chamber-type assays. In vivo, however, carcinoma cells, malignant cells of epithelial origin, frequently invade the surrounding tissue as coherent clusters or nests of cells. We have called this type of movement "cohort migration". In our work, the invasion front of colon carcinomas consisted of compact tumor glands, partially resolved glands or markedly resolved glands with scattered tumor cell clusters or single cells lying ahead. In the former two types, which constituted about a half of all cases, cohort migration seems to be the predominant mechanism, whereas both cohort migration and single cell locomotion may be involved in the last one. In this light, it is very advantageous to investigate the mechanisms involved in the cohort migration. In this review, we present a two-dimensional motility assay as a cohort migration model, in which human colorectal carcinoma cells move outwards from the cell islands mainly as localized coherent sheets of cells when stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA) or hepatocyte growth factor/scatter factor (HGF/SF). Within the migrating cell sheets, wide intercellular gaps occur at the lower portion of the cells to allow the cells to extend leading lamellae forward while close cell-cell contacts remain at the upper portion of the cells. This localized modulation of cell-cell adhesion at the lower portion of the cells is associated with increased tyrosine phosphorylation of the E-cadherin-catenin complex in TPA-induced cohort migration and with reduced alpha-catenin complexed with E-cadherin in HGF/SF-induced cohort migration. Furthermore, fibronectin deposited by migrating cells is essential for their movement, and on the gelatin-coated substrate even degradation and remodeling of the substrate by matrix metalloproteinases are also needed. Thus, in cohort migration it is likely that cells are released from cell-cell adhesion only at the lower portion of the cells via modulation of E-cadherin-catenin-based mechanism, and this change allows the cells to extend leading lamellae onto the extracellular matrix substrate remodeled by deposition of fibronectin and organized digestion.
Thermal reactions of cyclopropenone ketals. Application of the cycloaddition reactions of delocalized singlet vinylcarbenes: three-carbon 1,1-/1,3-dipoles. An alternative synthesis of deacetamidocolchiceine: formal total synthesis of colchicine (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThermal reactions of cyclopropenone ketals. Application of the cycloaddition reactions of delocalized singlet vinylcarbenes: three-carbon 1,1-/1,3-dipoles. An alternative synthesis of deacetamidocolchiceine: formal total synthesis of colchicineDale L. Boger and Christine E. BrothertonCite this: J. Am. Chem. Soc. 1986, 108, 21, 6713–6719Publication Date (Print):October 1, 1986Publication History Published online1 May 2002Published inissue 1 October 1986https://pubs.acs.org/doi/10.1021/ja00281a042https://doi.org/10.1021/ja00281a042research-articleACS PublicationsRequest reuse permissionsArticle Views706Altmetric-Citations61LEARN 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
Biogenic Synthesis, Purification, and Chemical Characterization of Anti-inflammatory Resolvins Derived from Docosapentaenoic Acid (DPAn-6) (2009)

Enzymatically oxygenated derivatives of the omega-3 fatty acids cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) and cis-5,8,11,14,17-eicosapentaenoic acid, known as resolvins, have potent inflammation resolution activity (Serhan, C. N., Clish, C. B., Brannon, J., Colgan, S. P., Chiang, N., and Gronert, K. (2000) J. Exp. Med. 192, 1197-1204; Hong, S., Gronert, K., Devchand, P. R., Moussignac, R., and Serhan, C. N. (2003) J. Biol. Chem. 278, 14677-14687). Our objective was to determine whether similar derivatives are enzymatically synthesized from other C-22 fatty acids and whether these molecules possess inflammation resolution properties. The reaction of DHA, DPAn-3, and DPAn-6 with 5-, 12-, and 15-lipoxygenases produced oxylipins, which were identified and characterized by liquid chromatography coupled with tandem mass-spectrometry. DPAn-6 and DPAn-3 proved to be good substrates for 15-lipoxygenase. 15-Lipoxygenase proved to be the most efficient enzyme of the three tested for conversion of long chain polyunsaturated fatty acids to corresponding oxylipins. Since DPAn-6 is a major component of Martek DHA-S oil, we focused our attention on reaction products obtained from the DPAn-6 and 15-lipoxygenase reaction. (17S)-hydroxy-DPAn-6 and (10,17S)-dihydroxy-DPAn-6 were the main products of this reaction. These compounds were purified by preparatory high performance liquid chromatography techniques and further characterized by NMR, UV spectrophotometry, and tandem mass spectrometry. We tested both compounds in two animal models of acute inflammation and demonstrated that both compounds are potent anti-inflammatory agents that are active on local intravenous as well as oral administration. These oxygenated DPAn-6 compounds can thus be categorized as a new class of DPAn-6-derived resolvins.