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Sample records for molecular weight inhibitors

  1. Recent Developments in Low Molecular Weight Complement Inhibitors

    PubMed Central

    Qu, Hongchang; Ricklin, Daniel; Lambris, John D.

    2009-01-01

    As a key part of the innate immune system, complement plays an important role not only in defending invading pathogens but also in many other biological processes. Inappropriate or excessive activation of complement has been linked to many autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. A wide array of low molecular weight complement inhibitors has been developed to target various components of the complement cascade. Their efficacy has been demonstrated in numerous in vitro and in vivo experiments. Though none of these inhibitors has reached the market so far, some of them have entered clinical trials and displayed promising results. This review provides a brief overview of the currently developed low molecular weight complement inhibitors, including short peptides and synthetic small molecules, with an emphasis on those targeting components C1 and C3, and the anaphylatoxin receptors. PMID:19800693

  2. A low molecular weight proteinase inhibitor produced by T lymphocytes.

    PubMed Central

    Ganea, D; Teodorescu, M; Dray, S

    1986-01-01

    A low molecular weight (MW) proteinase inhibitor, between 6500 and 21,500 MW, appeared in the supernatant of rabbit spleen cells cultured at high density for 24 hr. The inhibitor inhibited the enzymatic activity of trypsin for both a high MW natural substrate, fibrinogen, and for a low MW artificial substrate, Chromozym TRY. The low MW proteinase inhibitor is protein in nature and is different, in terms of specificity for enzymes, MW and sensitivity to different physical or chemical treatments, from aprotinin, a low MW proteinase inhibitor (6500 MW) of bovine origin, and from the soybean trypsin inhibitor, a relatively high MW proteinase inhibitor (21,500 MW). The inhibitor was found in the supernatant of purified T cells but not B cells, and its production was increased in the presence of an optimal concentration of Con A. The possibility that this proteinase inhibitor has a role in the regulation of trypsin-like proteinases involved to the immune response remains to be investigated. Images Figure 4 PMID:2417942

  3. Examination of the change in returning molecular weight obtained during inhibitor squeeze treatments using polyacrylate based inhibitors

    SciTech Connect

    Graham, G.M.; Sorbie, K.S.

    1995-11-01

    Scale inhibitors based on small polyelectrolytes are often employed in oilfield scale prevention treatments. These materials are injected into the near-well formation of producers in a scale inhibitor squeeze treatment. When the well is brought back on production, the objective is for the return concentration level of the inhibitor in the produced brine to be at or above a certain threshold level, C{sub t}. This threshold level is the minimum inhibitor concentration required to prevent the formation of mineral carbonate or sulfate scales in that well. The squeeze lifetime depends strongly on the nature of the interaction between the inhibitor and the formation either through an adsorption or precipitation mechanism. Both adsorption and precipitation processes depend on the molecular weight of the scale inhibitor, as well as on a range of other factors. However, polymeric inhibitor species always display some degree of polydispersity (spread of molecular weight). In this paper, the authors examine the effects of molecular weight on adsorption/desorption phenomena for polyacrylate based inhibitor species. This work shows that, in the inhibitor effluent after a squeeze treatment, the molecular weight of the returning inhibitor may be different from that which was injected. For commercially available polymeric inhibitor species, they demonstrate using core floods that preferential retention of higher molecular weight components occurs and preferential desorption of lower molecular weight components is observed. This leads to a gradation in molecular weight in the return profile, which can lead to increased molecular weight components returning as the inhibitor concentration approaches the threshold level. The significance of this observation to field application of polymeric inhibitor species is discussed.

  4. Low molecular weight squash trypsin inhibitors from Sechium edule seeds.

    PubMed

    Laure, Hélen J; Faça, Vítor M; Izumi, Clarice; Padovan, Júlio C; Greene, Lewis J

    2006-02-01

    Nine chromatographic components containing trypsin inhibitor activity were isolated from Sechium edule seeds by acetone fractionation, gel filtration, affinity chromatography and RP-HPLC in an overall yield of 46% of activity and 0.05% of protein. The components obtained with highest yield of total activity and highest specific activity were sequenced by Edman degradation and their molecular masses determined by mass spectrometry. The inhibitors contained 31, 32 and 27 residues per molecule and their sequences were: SETI-IIa, EDRKCPKILMRCKRDSDCLAKCTCQESGYCG; SETI-IIb, EEDRKCPKILMRCKRDSDCLAKCTCQESGYCG and SETI-V, CPRILMKCKLDTDCFPTCTCRPSGFCG. SETI-IIa and SETI-IIb, which differed by an amino-terminal E in the IIb form, were not separable under the conditions employed. The sequences are consistent with consensus sequences obtained from 37 other inhibitors: CPriI1meCk_DSDCla_C_C_G_CG, where capital letters are invariant amino acid residues and lower case letters are the most preserved in this position. SETI-II and SETI-V form complexes with trypsin with a 1:1 stoichiometry and have dissociation constants of 5.4x10(-11)M and 1.1x10(-9)M, respectively. PMID:16406091

  5. Low-molecular-weight inhibitors of NF-κB signalling pathways

    NASA Astrophysics Data System (ADS)

    Dolinnaya, N. G.; Kubareva, Elena A.; Kazanova, E. V.; Zigangirova, N. A.; Naroditsky, B. S.; Gintsburg, A. L.; Oretskaya, Tat'yana S.

    2008-11-01

    The nuclear factor κB (NF-κB) is a transcription factor involved in inducible expression of cellular genes playing a key role in cardiovascular pathologies, carcinogenesis, inflammatory and viral diseases. The review describes the stimuli and processes inducing NF-κB activation and the components of a signalling cascade that could constitute targets for NF-κB inhibition. The molecular action and properties of various low-molecular weight inhibitors aiming to prevent NF-κB activity are summarised.

  6. Three low molecular weight cysteine proteinase inhibitors of human seminal fluid: purification and enzyme kinetic properties.

    PubMed

    Yadav, Vikash Kumar; Chhikara, Nirmal; Gill, Kamaldeep; Dey, Sharmistha; Singh, Sarman; Yadav, Savita

    2013-08-01

    The cystatins form a superfamily of structurally related proteins with highly conserved structural folds. They are all potent, reversible, competitive inhibitors of cysteine proteinases (CPs). Proteins from this group present differences in proteinase inhibition despite their high level of structural similarities. In this study, three cysteine proteinase inhibitors (CPIs) of low molecular weight were isolated from human seminal fluid (HSF) by affinity chromatography on carboxymethyl (CM)-papain-Sepharose column, purified using various chromatographic procedures and checked for purity on sodium-dodecyl PAGE (SDS-PAGE). Matrix-assisted laser desorption-ionization-time-of flight-mass spectrometry (MALDI-TOF-MS) identified these proteins as cystatin 9, cystatin SN, and SAP-1 (an N-terminal truncated form of cystatin S). All three CPIs suppressed the activity of papain potentially and showed remarkable heat stability. Interestingly SAP-1 also inhibits the activity of trypsin, chymotrypsin, pepsin, and PSA (prostate specific antigen) and acts as a cross-class protease inhibitor in in vitro studies. Using Surface Plasmon Resonance, we have also observed that SAP-1 shows a significant binding with all these proteases. These studies suggest that SAP-1 is a cross-class inhibitor that may regulate activity of various classes of proteases within the reproductive systems. To our knowledge, this is the first report about purification of CPIs from HSF; the identification of such proteins could provide better insights into the physiological processes and offer intimation for further research. PMID:23619703

  7. Observation of high and low molecular weight inhibitors of angiotensin-converting enzyme in rat lung.

    PubMed

    Brecher, A S; Thevananther, S; Wilson, S

    1996-01-01

    Fractionation of the rat lung yielded a 54,000 g supernate, and DOC-solubilized 775 g, 3100 g and 54,000 g sediments, each of these preparations displaying an increasing angiotensin-converting enzyme activity with increasing dilution, suggesting the presence of freely reversible angiotensin-converting enzyme inhibitors. The solubilized 775 g sediment was applied to an immobilized captopril column, eluted successively with 20 mM Pi(K+), pH 7.8 buffer, buffer/0.5 M NaCl, and buffer/0.01M cysteine to obtain four major protein bands, two of which appeared with the cysteine eluant. The first two protein peaks were each pooled and subjected to ultrafiltration with 10,000 molecular weight cutoff filters. The pooled peaks, retentates and ultrafiltrates each inhibited the angiotensin-converting enzyme activity, suggesting the presence of large and small molecular weight reversible angiotensin-converting enzyme inhibitors in association with the solubilized (membranous) particulate angiotensin-converting enzyme fraction. These results expand upon earlier observations on the existence of angiotensin-converting enzyme inhibitors in mammalian serum by observing an increasing angiotensin-converting enzyme activity with increasing dilution. This activity was eluted in multiple peaks, including elution with the cysteine eluate, suggesting that the angiotensin-converting enzyme, as well as other proteins, may react covalently with the sulfhydryl functional group of the immobilized captopril in a transsulfhydration reaction cleaving the disulfide bonds in proteins. Subsequent elution with cysteine affects an additional transsulfhydration reaction, releasing the proteins from the column. It is further postulated that air oxidation of the proteins permits reformation of disulfide bonds, yielding some active angiotensin-converting enzyme. Having in mind the possibility of lipophilic angiotensin-converting enzyme inhibitors crossing the blood-brain barrier as a means of treatment of

  8. Ex vivo inhibition of Clostridium botulinum neurotoxin types B, C, E, and F by small molecular weight inhibitors.

    PubMed

    Montgomery, Vicki A; Ahmed, S Ashraf; Olson, Mark A; Mizanur, Rahman M; Stafford, Robert G; Roxas-Duncan, Virginia I; Smith, Leonard A

    2015-05-01

    Two small molecular weight inhibitors, compounds CB7969312 and CB7967495, that displayed inhibition of botulinum neurotoxin serotype A in a previous study, were evaluated for inhibition of botulinum neurotoxin serotypes B, C, E, and F. The small molecular weight inhibitors were assessed by molecular modeling, UPLC-based peptide cleavage assay; and an ex vivo assay, the mouse phrenic nerve - hemidiaphragm assay (MPNHDA). While both compounds were inhibitors of botulinum neurotoxin (BoNT) serotypes B, C, and F in the MPNHDA, compound CB7969312 was effective at lower molar concentrations than compound CB7967495. However, compound CB7967495 was significantly more effective at preventing BoNTE intoxication than compound CB7969312. In the UPLC-based peptide cleavage assay, CB7969312 was also more effective against LcC. Both compounds inhibited BoNTE, but not BoNTF, LcE, or LcF in the UPLC-based peptide cleavage assay. Molecular modeling studies predicted that both compounds would be effective inhibitors of BoNTs B, C, E, and F. But CB7967495 was predicted to be a more effective inhibitor of the four serotypes (B, C, E, and F) than CB7969312. This is the first report of a small molecular weight compound that inhibits serotypes B, C, E, and F in the ex vivo assay. PMID:25707753

  9. Low Molecular Weight Antagonists of Plasminogen Activator Inhibitor-1: Therapeutic Potential in Cardiovascular Disease.

    PubMed

    Simone, Tessa M; Higgins, Paul J

    2012-08-01

    Plasminogen activator inhibitor-1 (PAI-1; SERPINE1) is the major physiologic regulator of the plasmin-based pericellular proteolytic cascade, a modulator of vascular smooth muscle cell (VSMC) migration and a causative factor in cardiovascular disease and restenosis, particularly in the context of increased vessel transforming growth factor- β1 (TGF-β1) levels. PAI-1 limits conversion of plasminogen to plasmin (and, thereby, fibrin degradation) by inhibiting its protease targets urokinase and tissue-type plasminogen activators (uPA, tPA). PAI-1 also has signaling functions and binds to the low density lipoprotein receptor-related protein 1 (LRP1) to regulate LRP1-dependent cell motility that, in turn, contributes to neointima formation. PAI-1/uPA/uPA receptor/LRPI/integrin complexes are endocytosed with subsequent uPAR/LRP1/integrin redistribution to the leading edge, initiating an "adhesion-detachment-readhesion" cycle to promote cell migration. PAI-1 also interacts with LRP1 in a uPA/uPAR-independent manner triggering Jak/Stat1 pathway activation to stimulate cell motility. PAI-1 itself is a substrate for extracellular proteases and exists in a "cleaved" form which, while unable to interact with uPA and tPA, retains LRP1-binding and migratory activity. These findings suggest that there are multiple mechanisms through which inhibition of PAI-1 may promote cardiovascular health. Several studies have focused on the design, synthesis and preclinical assessment of PAI-1 antagonists including monoclonal antibodies, peptides and low molecular weight (LMW) antagonists. This review discusses the translational impact of LMW PAI-1 antagonists on cardiovascular disease addressing PAI-1-initiated signaling, PAI-1 structure, the design and characteristics of PAI-1-targeting drugs, results of in vitro and in vivo studies, and their clinical implications. PMID:23936868

  10. Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors

    PubMed Central

    Frett, Brendan; McConnell, Nick; Smith, Catherine C.; Wang, Yuanxiang; Shah, Neil P.; Li, Hong-yu

    2015-01-01

    The FLT3 kinase represents an attractive target to effectively treat AML. Unfortunately, no FLT3 targeted therapeutic is currently approved. In line with our continued interests in treating kinase related disease for anti-FLT3 mutant activity, we utilized pioneering synthetic methodology in combination with computer aided drug discovery and identified low molecular weight, highly ligand efficient, FLT3 kinase inhibitors. Compounds were analyzed for biochemical inhibition, their ability to selectively inhibit cell proliferation, for FLT3 mutant activity, and preliminary aqueous solubility. Validated hits were discovered that can serve as starting platforms for lead candidates. PMID:25765758

  11. Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors.

    PubMed

    Frett, Brendan; McConnell, Nick; Smith, Catherine C; Wang, Yuanxiang; Shah, Neil P; Li, Hong-yu

    2015-04-13

    The FLT3 kinase represents an attractive target to effectively treat AML. Unfortunately, no FLT3 targeted therapeutic is currently approved. In line with our continued interests in treating kinase related disease for anti-FLT3 mutant activity, we utilized pioneering synthetic methodology in combination with computer aided drug discovery and identified low molecular weight, highly ligand efficient, FLT3 kinase inhibitors. Compounds were analyzed for biochemical inhibition, their ability to selectively inhibit cell proliferation, for FLT3 mutant activity, and preliminary aqueous solubility. Validated hits were discovered that can serve as starting platforms for lead candidates. PMID:25765758

  12. Discovery of Sanggenon G as a natural cell-permeable small-molecular weight inhibitor of X-linked inhibitor of apoptosis protein (XIAP)

    PubMed Central

    Seiter, Maximilian A.; Salcher, Stefan; Rupp, Martina; Hagenbuchner, Judith; Kiechl-Kohlendorfer, Ursula; Mortier, Jérémie; Wolber, Gerhard; Rollinger, Judith M.; Obexer, Petra; Ausserlechner, Michael J.

    2014-01-01

    Defects in the regulation of apoptosis are one main cause of cancer development and may result from overexpression of anti-apoptotic proteins such as the X-linked inhibitor of apoptosis protein (XIAP). XIAP is frequently overexpressed in human leukemia and prostate and breast tumors. Inhibition of apoptosis by XIAP is mainly coordinated through direct binding to the initiator caspase-9 via its baculovirus-IAP-repeat-3 (BIR3) domain. XIAP inhibits caspases directly making it to an attractive target for anti-cancer therapy. In the search for novel, non-peptidic XIAP inhibitors in this study we focused on the chemical constituents of sāng bái pí (mulberry root bark). Most promising candidates of this plant were tested biochemically in vitro by a fluorescence polarization (FP) assay and in vivo via protein fragment complementation analysis (PCA). We identified the Diels Alder adduct Sanggenon G (SG1) as a novel, small-molecular weight inhibitor of XIAP. As shown by FP and PCA analyses, SG1 binds specifically to the BIR3 domain of XIAP with a binding affinity of 34.26 μM. Treatment of the transgenic leukemia cell line Molt3/XIAP with SG1 enhances caspase-8, -3 and -9 cleavage, displaces caspase-9 from XIAP as determined by immunoprecipitation experiments and sensitizes these cells to etoposide-induced apoptosis. SG1 not only sensitizes the XIAP-overexpressing leukemia cell line Molt3/XIAP to etoposide treatment but also different neuroblastoma cell lines endogenously expressing high XIAP levels. Taken together, Sanggenon G (SG1) is a novel, natural, non-peptidic, small-molecular inhibitor of XIAP that can serve as a starting point to develop a new class of improved XIAP inhibitors. PMID:25161875

  13. Recalcitrant High-Molecular-Weight Material, an Inhibitor of Microbial Metabolism in River Biofilms

    PubMed Central

    Freeman, Christopher; Lock, Maurice A.

    1992-01-01

    Recalcitrant high (>1,000)-molecular-weight materials (>1K materials) have been proposed to inhibit the metabolic activity of river biofilms. Evidence is presented to support the hypothesis that the mode of action is through occlusion of the surface of the biofilm by recalcitrant >1K materials. The evidence includes the following. (i) The phenomenon was particularly prominent in brown-water rivers, which are rich in recalcitrant >1K material. (ii)Temporal changes in inhibition intensity were observed, which coincided with seasonal changes in the relative recalcitrance of river water >1K materials. (iii) Stores of intracellular carbon (poly-β-hydroxyalkanoates) were progressively compromised by increasing the supply of recalcitrant >1K materials. (iv) Nontoxic synthetic analogs of recalcitrant >1K materials were also demonstrated to be capable of producing an identical inhibitory effect. Finally, it was suggested that the application of recalcitrant >1K materials may represent a novel approach to the control of deleterious microbial communities. PMID:16348723

  14. Identification of the first low-molecular-weight inhibitors of matriptase-2.

    PubMed

    Sisay, Mihiret Tekeste; Steinmetzer, Torsten; Stirnberg, Marit; Maurer, Eva; Hammami, Maya; Bajorath, Jürgen; Gütschow, Michael

    2010-08-12

    As recently discovered, matriptase-2, a type II transmembrane serine protease, plays a crucial role in body iron homeostasis by down-regulating hepcidin expression, which results in increased iron levels. Thus, matriptase-2 represents a novel target for the development of enzyme inhibitors potentially useful for the treatment of systemic iron overload (hemochromatosis). A comparative three-dimensional model of the catalytic domain of matriptase-2 was generated and utilized for structure-based virtual screening in combination with similarity searching and knowledge-based compound design. Two N-protected dipeptide amides containing a 4-amidinobenzylamide as P1 residue (compounds 1 and 3) were identified as the first small molecule inhibitors of matriptase-2 with K(i) values of 170 and 460 nM, respectively. An inhibitor of the closely related protease matriptase (compound 2, K(i) = 220 nM), with more than 50-fold selectivity over matriptase-2, was also identified. PMID:20684597

  15. Distribution of low molecular weight platelet aggregation inhibitors from snake venoms.

    PubMed

    Oyama, Etsuko; Takahashi, Hidenobu

    2007-03-01

    An assay of platelet aggregation inhibitors measured by the turbidimeter using Aggregometer PAM 8C (Mebanix) was performed after each crude snake venom (57 species) was subjected to ultrafiltration using MILLIPORE UFP 1 LGC. The snake venoms of Viperidae (three species), Elapidae (11 species), and Hydrophiidae (two species) inhibited ADP-induced rabbit platelet aggregation. In particular, six venoms of Bitis gabonica, Pseudocerastes persicus, Dendroaspis angusticeps, D. polylepis, Ophiophagus hannah, and N. nigricollis crawshawii strongly inhibited platelet aggregation. Furthermore, adenosine was identified from Bitis gabonica venom using HPLC and FAB/MS analysis. PMID:17141819

  16. FGFR Inhibitor Ameliorates Hypophosphatemia and Impaired Engrailed-1/Wnt Signaling in FGF2 High Molecular Weight Isoform Transgenic Mice.

    PubMed

    Du, Erxia; Xiao, Liping; Hurley, Marja M

    2016-09-01

    High molecular weight FGF2 transgenic (HMWTg) mouse phenocopies the Hyp mouse, homolog of human X-linked hypophosphatemic rickets with hypophosphatemis, and abnormal FGF23, FGFR, Klotho signaling in kidney. Since abnormal Wnt signaling was reported in Hyp mice we assessed whether Wnt signaling was impaired in HMWTg kidneys and the effect of blocking FGF receptor (FGFR) signaling. Bone mineral density and bone mineral content in female HMWTg mice were significantly reduced. HMWTg mice were gavaged with FGFR inhibitor NVP-BGJ398, or vehicle and were euthanized 24 h post treatment. Serum phosphate was significantly reduced and urine phosphate was significantly increased in HMWTg and was rescued by NVP-BGJ398. Analysis of kidneys revealed a significant reduction in Npt2a mRNA in HMWTg that was significantly increased by NVP-BGJ398. Increased FGFR1, KLOTHO, P-ERK1/2, and decreased NPT2a protein in HMWTg were rescued by NVP-BGJ398. Wnt inhibitor Engrailed-1 mRNA and protein was increased in HMWTg and was decreased by BGJ398. Akt mRNA and protein was decreased in HMWTg and was increased by NVP-BGJ398. The active form of glycogen synthase 3 beta (pGSK3-β) and phosphor-β-catenin were increased in HMWTg and were both decreased by NVP-BGJ398 while decreased active-β-catenin in HMWTg was increased by NVP-BGJ398. We conclude that FGFR blockade rescued hypophosphatemia by regulating FGF and WNT signaling in HMWTg kidneys. J. Cell. Biochem. 117: 1991-2000, 2016. © 2016 Wiley Periodicals, Inc. PMID:26762209

  17. Low-molecular-weight heparin modulates vein wall fibrotic response in a plasminogen activator inhibitor 1-dependent manner

    PubMed Central

    Obi, Andrea T.; Diaz, Jose A.; Ballard-Lipka, Nicole L.; Roelofs, Karen J.; Farris, Diana M.; Lawrence, Daniel A.; Henke, Peter K.; Wakefield, Thomas W.

    2014-01-01

    Background Treatment with low-molecular-weight heparin (LMWH) favorably alters the vein wall response to deep venous thrombosis (DVT), although the mechanisms remain unclear. Previous studies have suggested that LMWH alters the levels of circulating plasminogen activator inhibitor 1 (PAI-1), a known mediator of fibrosis, and may improve endogenous fibrinolysis. We hypothesized that LMWH favorably alters the vein wall response by binding of PAI-1 and acceleration of fibrinolysis. Methods Wild-type and PAI-1 −/− mice underwent treatment with LMWH after induction of occlusive DVT. Vein wall and plasma were harvested and analyzed by enzyme-linked immunosorbent assay, zymography, real-time polymerase chain reaction, and immunohistochemistry. Results Wild-type mice treated with LMWH exhibited diminished vein wall fibrosis (0.6 ± 0.6 vs 1.4 ± 0.2; P < .01; n = 5) and elevation of circulating PAI-1 (1776 ± 342 vs 567 ± 104 ρg/mL; P < .01; n = 5) compared with untreated controls after occlusive DVT. PAI-1−/− mice treated with LMWH were not similarly protected from fibrosis, despite improved thrombus resolution. Treatment with LMWH was associated with decreased intrathrombus interleukin-lβ (68.6 ± 31.0 vs 223.4 ± 28.9 ρg/mg total protein; P < .01; n = 5) but did not alter inflammatory cell recruitment to the vein wall. PAI-1 −/− mice exhibited significantly elevated intrathrombus (257.2 ± 51.5 vs 4.3 ± 3.8 ρg/mg total protein; n = 5) and vein wall interleukin-13 (187.2 ± 57.6 vs 9.9 ± 1.1 ρg/mg total protein; P < .05; n = 5) as well as vein wall F4/80 positively staining monocytes (53 ± 11 vs 16 ± 2 cells/5 high-power fields; P < .05; n = 4). Conclusions LMWH did not accelerate venous thrombosis resolution but did protect against vein wall fibrosis in a PAI-1-dependent manner in an occlusive DVT model. Lack of PAI-1 correlated with accelerated venous thrombosis resolution but no protection from fibrosis. PAI-1 inhibition as a treatment strategy

  18. Preliminary safety evaluation of a taurocholate-conjugated low-molecular-weight heparin derivative (LHT7): a potent angiogenesis inhibitor.

    PubMed

    Alam, Farzana; Chung, Seung Woo; Hwang, Seung Rim; Kim, Ji-Young; Park, Jooho; Moon, Hyun Tae; Byun, Youngro

    2015-01-01

    In our previous studies, taurocholic acid (TA)-conjugated low-molecular-weight heparin derivative (LHT7) has been proven to be a potent anti-angiogenic agent by demonstrated successful blockage capability of vascular endothelial growth factors (VEGF). Preliminary safety evaluations were conducted based on its mechanism of action and chemical behavior. For this purpose, acute toxicity study, and hematological and serological evaluations were carried out. Additionally, in order to evaluate mechanism-related side effects, both blood pressure and the occurrence of proteinuria were measured using a treatment regime of multiple high doses of LHT7 in a biodistribution study. LD50 values for LHT7 in female and male mice were 56.9 and 64.7 mg kg(-1) doses, respectively. There were no vital fluctuations in the serological and hematological parameters, except for the elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at 100 and 200 mg kg(-1) doses of LHT7, representing vital changes in the liver function. Moreover, the results of mechanism-related studies showed that blood pressure at 50 mg kg(-1) did not change but showed elevated levels of protein in urine. In the biodistribution study, a slight accumulation of LHT7 in the kidney and the liver were observed at the 50 mg kg(-1) repeated dose owing to the presence of bile acid. No fatal damage was observed in this study; most observations were related to the chemical composition or the mechanism of action of the material. PMID:24532548

  19. The spectrum of low molecular weight alpha-amylase/protease inhibitor genes expressed in the US bread wheat Butte 86

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The complement of genes encoding alpha-amylase/protease inhibitors expressed in Triticum aestivum cv. Butte 86 was characterized by transcript and proteomic analysis. Coding sequences for 18 distinct proteins were identified among a collection of expressed sequence tags (ESTs) from Butte 86 developi...

  20. Molecular Weight and Molecular Weight Distributions in Synthetic Polymers.

    ERIC Educational Resources Information Center

    Ward, Thomas Carl

    1981-01-01

    Focuses on molecular weight and molecular weight distributions (MWD) and models for predicting MWD in a pedagogical way. In addition, instrumental methods used to characterize MWD are reviewed with emphasis on physical chemistry of each, including end-group determination, osmometry, light scattering, solution viscosity, fractionation, and…

  1. Structures of Human Cyctochrome P450 2E1: Insights Into the Binding of Inhibitors And Both Small Molecular Weight And Fatty Acid Substrates

    SciTech Connect

    Porubsky, P.R.; Meneely, K.M.; Scott, E.E.

    2009-05-21

    Human microsomal cytochrome P-450 2E1 (CYP2E1) monooxygenates >70 low molecular weight xenobiotic compounds, as well as much larger endogenous fatty acid signaling molecules such as arachidonic acid. In the process, CYP2E1 can generate toxic or carcinogenic compounds, as occurs with acetaminophen overdose, nitrosamines in cigarette smoke, and reactive oxygen species from uncoupled catalysis. Thus, the diverse roles that CYP2E1 has in normal physiology, toxicity, and drug metabolism are related to its ability to metabolize diverse classes of ligands, but the structural basis for this was previously unknown. Structures of human CYP2E1 have been solved to 2.2 {angstrom} for an indazole complex and 2.6 {angstrom} for a 4-methylpyrazole complex. Both inhibitors bind to the heme iron and hydrogen bond to Thr{sup 303} within the active site. Complementing its small molecular weight substrates, the hydrophobic CYP2E1 active site is the smallest yet observed for a human cytochrome P-450. The CYP2E1 active site also has two adjacent voids: one enclosed above the I helix and the other forming a channel to the protein surface. Minor repositioning of the Phe{sup 478} aromatic ring that separates the active site and access channel would allow the carboxylate of fatty acid substrates to interact with conserved {sup 216}QXXNN{sup 220} residues in the access channel while positioning the hydrocarbon terminus in the active site, consistent with experimentally observed {omega}-1 hydroxylation of saturated fatty acids. Thus, these structures provide insights into the ability of CYP2E1 to effectively bind and metabolize both small molecule substrates and fatty acids.

  2. The antithrombotic effect of synthetic low molecular weight human factor Xa inhibitor, DX-9065a, on He-Ne laser-induced thrombosis in rat mesenteric microvessels.

    PubMed

    Yamashita, T; Tsuji, T; Matsuoka, A; Giddings, J C; Yamamoto, J

    1997-01-01

    The effect of a synthetic low molecular weight factor Xa (FXa) inhibitor, DX9065a, on thrombosis in vivo were examined in a rat animal model using a Helium-Neon (He-Ne) laser method. DX-9065a administered either intravenously or orally promoted anti factor Xa activity in a dose dependent manner. Anti Xa activity was maximal immediately after intravenous injection and persisted for approximately 30 minutes. Inhibitory activity was maximal 15-30 minutes after oral administration and persisted for approximately 90 minutes. Similarly DX-9065a inhibited platelet-rich thrombosis formation in mesenteric arterioles and venules. In these instances inhibition was relatively transient after intravenous injection (10-20 minutes), but persisted for more than 3 hours after oral administration. The minimum effective doses of DX-9065a given intravenously and orally were 3.89 mg/kg and 25.9 mg/kg, respectively. The results confirmed that DX-9065a selectively modulates thrombotic mechanisms, and suggest that development of this synthetic FXa antagonist could constitute an effective intravenous and oral antithrombotic agent. PMID:8983124

  3. Apparatus for molecular weight separation

    DOEpatents

    Smith, Richard D.; Liu, Chuanliang

    2001-01-01

    The present invention relates generally to an apparatus and method for separating high molecular weight molecules from low molecular weight molecules. More specifically, the invention relates to the use of microdialysis for removal of the salt (low molecular weight molecules) from a nucleotide sample (high molecular weight molecules) for ESI-MS analysis. The dialysis or separation performance of the present invention is improved by (1) increasing dialysis temperature thereby increasing desalting efficiency and improving spectrum quality; (2) adding piperidine and imidazole to the dialysis buffer solution and reducing charge states and further increasing detection sensitivity for DNA; (3) using low concentrations (0-2.5 mM NH4OAc) of dialysis buffer and shifting the DNA negative ions to higher charge states, producing a nearly 10-fold increase in detection sensitivity and a slightly decreased desalting efficiency, (4) conducting a two-stage separation or (5) any combination of (1), (2), (3) and (4).

  4. HMG CoA reductase inhibitor-induced myotoxicity: pravastatin and lovastatin inhibit the geranylgeranylation of low-molecular-weight proteins in neonatal rat muscle cell culture.

    PubMed

    Flint, O P; Masters, B A; Gregg, R E; Durham, S K

    1997-07-01

    In previous studies, inhibition of cholesterol synthesis by HMG CoA reductase inhibitors (HMGRI) was associated with myotoxicity in cultures of neonatal rat skeletal myotubes, and rhabdomyolysis in rats, rabbits, and humans in vivo. In vitro myotoxicity was directly related to HMGRI-induced depletion of mevalonate, farnesol, and geranylgeraniol, since supplementation with these intermediate metabolites abrogated the toxicity. Both farnesol and geranylgeraniol are required for the posttranslational modification, or isoprenylation, of essential regulatory proteins in mammalian cells. The objective of the present study was to measure changes in protein isoprenylation in cultured neonatal rat skeletal muscle cells exposed for 24 hr to increasing concentrations of pravastatin or lovastatin. Proteins were labeled with [3H]mevalonate, [3H]farnesyl pyrophosphate (FPP), or [3H]geranylgeranyl pyrophosphate (GGPP), and then separated by SDS-PAGE and quantitated by scintillation counting and densitometry of autoradiographs. Mevalonate and FPP labeling of the majority of proteins increased in a concentration-dependent manner, even at concentrations greater than 2 microM lovastatin and 25 microM pravastatin that completely inhibited cholesterol synthesis. In contrast, mevalonate and FPP labeling of three protein bands with molecular weights of 26.6, 27.7, and 28.9 kDa was markedly inhibited at concentrations higher than 1 microM lovastatin and 400 microM pravastatin, which inhibited protein synthesis and disrupted myotube morphology after longer exposures in a previous study. In contrast, these proteins were equally well labeled by GGPP at all HMGRI concentrations tested, suggesting that isoprenylation of the 26.9-, 27.8-, and 28.9-kDa proteins requires geranylgeraniol. The results of this study indicate that HMGRI-induced myotoxicity is most likely related to reduced posttranslational modification of specific regulatory proteins by geranylgeraniol. PMID:9221829

  5. The Molecular Weight Distribution of Polymer Samples

    ERIC Educational Resources Information Center

    Horta, Arturo; Pastoriza, M. Alejandra

    2007-01-01

    Various methods for the determination of the molecular weight distribution (MWD) of different polymer samples are presented. The study shows that the molecular weight averages and distribution of a polymerization completely depend on the characteristics of the reaction itself.

  6. Effect of molecular weight on polymer processability

    SciTech Connect

    Karg, R.F.

    1983-01-01

    Differences in rheological behavior due to the polymer molecular weight and molecular weight distribution have been shown with the MPT. SBR polymers having high molecular weight fractions develop higher stress relaxation time values due to the higher degree of polymer entanglements. Tests conducted at increasing temperatures show the diminishing influence of the polymer entanglements upon stress relaxation time. EPDM polymers show stress relaxation time and head pressure behavior which correlates with mill processability. As anticipated, compounded stock of EPDM have broad molecular weight distribution has higher stress relaxation time values than EPDM compounds with narrow molecular weight distribution.

  7. Ultrahigh molecular weight aromatic siloxane polymers

    NASA Technical Reports Server (NTRS)

    Ludwick, L. M.

    1982-01-01

    The condensation of a diol with a silane in toluene yields a silphenylene-siloxane polymer. The reaction of stiochiometric amounts of the diol and silane produced products with molecular weights in the range 2.0 - 6.0 x 10 to the 5th power. The molecular weight of the product was greatly increased by a multistep technique. The methodology for synthesis of high molecular weight polymers using a two step procedure was refined. Polymers with weight average molecular weights in excess of 1.0 x 10 to the 6th power produced by this method. Two more reactive silanes, bis(pyrrolidinyl)dimethylsilane and bis(gamma butyrolactam)dimethylsilane, are compared with the dimethyleminodimethylsilane in ability to advance the molecular weight of the prepolymer. The polymers produced are characterized by intrinsic viscosity in tetrahydrofuran. Weight and number average molecular weights and polydispersity are determined by gel permeation chromatography.

  8. Cloning and characterization of bovine low molecular weight GTPases (Rac1 and Rac2) and rho GDP-dissociation inhibitor 2 (D4-GDI).

    PubMed

    Davis, A R; Clements, M K; Bunger, P L; Siemsen, D W; Quinn, M T

    2000-05-23

    GTPases of the Rho family play important roles in human leukocyte signal transduction pathways; however, little is known about the function of these proteins in bovine cells. In the present studies, we isolated molecular clones of bovine Rac1, Rac2, and the Rac/Rho GTPase regulatory protein D4-GDP dissociation inhibitor (D4-GDI) from a bovine bone marrow cDNA library. These clones contained complete open reading frames, encoding 192, 192, and 200 amino acids, respectively. Comparison of the bovine amino acid sequences with those of other species demonstrated a high degree of identity of these proteins across all species, suggesting that these proteins likely play conserved functional roles in bovine leukocyte signal transduction pathways. Comparative Western blotting of these proteins in human and bovine neutrophil cytosol demonstrated that Rac2 was the predominant Rac species and that D4-GDI was the predominant GDI species in bovine neutrophil cytosol. Despite the high degree of homology between human and bovine Rac2, some of the anti-peptide antibody probes prepared against human Rac2 failed to recognize the bovine homologue. We also showed by subcellular fractionation techniques that Rac2 is localized primarily to the cytosolic compartment of resting bovine neutrophils, but is translocated to the plasma membrane after stimulation with PMA. These findings suggest that Rac2 does play a role in bovine neutrophil activation. In addition, these data will be helpful in developing more specific probes for investigating the role of these proteins in bovine leukocyte signal transduction pathways and for studying various inflammatory diseases in cattle. PMID:10802295

  9. Effect of molecular weight on polyphenylquinoxaline properties

    NASA Technical Reports Server (NTRS)

    Jensen, Brian J.

    1991-01-01

    A series of polyphenyl quinoxalines with different molecular weight and end-groups were prepared by varying monomer stoichiometry. Thus, 4,4'-oxydibenzil and 3,3'-diaminobenzidine were reacted in a 50/50 mixture of m-cresol and xylenes. Reaction concentration, temperature, and stir rate were studied and found to have an effect on polymer properties. Number and weight average molecular weights were determined and correlated well with viscosity data. Glass transition temperatures were determined and found to vary with molecular weight and end-groups. Mechanical properties of films from polymers with different molecular weights were essentially identical at room temperature but showed significant differences at 232 C. Diamine terminated polymers were found to be much less thermooxidatively stable than benzil terminated polymers when aged at 316 C even though dynamic thermogravimetric analysis revealed only slight differences. Lower molecular weight polymers exhibited better processability than higher molecular weight polymers.

  10. Soluble high molecular weight polyimide resins

    NASA Technical Reports Server (NTRS)

    Jones, R. J.; Lubowitz, H. R.

    1970-01-01

    High molecular weight polyimide resins have greater than 20 percent /by weight/ solubility in polar organic solvents. They permit fabrication into films, fibers, coatings, reinforced composite, and adhesive product forms. Characterization properties for one typical polyimide resin are given.

  11. Production of high molecular weight polylactic acid

    SciTech Connect

    Bonsignore, Patrick V.

    1995-01-01

    A degradable high molecular weight poly(lactic acid). A poly(lactic acid) has a terminal end group of one of carboxyl or hydroxyl groups with low molecular weight poly(lactic acid) units coupled with linking agents of di-isocyanates, bis-epoxides, bis-oxazolines and bis-ortho esters. The resulting high molecular weight poly(lactic acid) can be used for applications taking advantage of the improved physical properties.

  12. Production of high molecular weight polylactic acid

    SciTech Connect

    Bonsignore, P.V.

    1995-11-28

    A degradable high molecular weight poly(lactic acid) is described. The poly(lactic acid) has a terminal end group of one of carboxyl or hydroxyl groups with low molecular weight poly(lactic acid) units coupled with linking agents of di-isocyanates, bis-epoxides, bis-oxazolines and bis-ortho esters. The resulting high molecular weight poly(lactic acid) can be used for applications taking advantage of the improved physical properties.

  13. Molecular weight determinations of biosolubilized coals

    SciTech Connect

    Linehan, J.C.; Clauss, S.; Bean, R.; Campbell, J.

    1991-05-01

    We have compared several different methods for determining the molecular weight of biosolubilized coals: Aqueous gel permeation Chromatography (GPC), organic GPC, preparative GPC, dynamic laser light scattering (LLS), static LLS, static LLS, mass spectrometry, vapor phase osmometry (VPO) and ultrafiltration. We have found that careful consideration must be given to the molecular weight result obtained from each method. The average molecular weight and the molecular weight distribution were found to be dependent upon many factors, including the technique used; molecular weight standards, pH, and the percentage of sample analyzed. Weight average molecular weights, M{sub w}, obtained for biosolubilized leonardite range from 800,000 daltons for neutral pH aqueous GPC based on polyethylene glycol molecular weight standards to 570 daltons for pH 11.5 buffered aqueous GPC based on a fulvic acid standard. It is clear that the state of association of the biocoal analyte, as well as the interactions of sample with the separation matrix, can have large influence of the observed result, and these must be understood before reliable GPC measurements can be made. Furthermore, a uniform set of molecular weight standards for biodegraded coals is needed. 10 refs., 1 tab.

  14. Microdialysis unit for molecular weight separation

    DOEpatents

    Smith, Richard D.; Liu, Chuanliang

    1999-01-01

    The present invention relates generally to an apparatus and method for separating high molecular weight molecules from low molecular weight molecules. More specifically, the invention relates to the use of microdialysis for removal of the salt (low molecular weight molecules) from a nucleotide sample (high molecular weight molecules) for ESI-MS analysis. The dialysis or separation performance of the present invention is improved by (1) increasing dialysis temperature thereby increasing desalting efficiency and improving spectrum quality; (2) adding piperidine and imidazole to the dialysis buffer solution and reducing charge states and further increasing detection sensitivity for DNA; (3) using low concentrations (0-2.5 mM NH4OAc) of dialysis buffer and shifting the DNA negative ions to higher charge states, producing a nearly 10-fold increase in detection sensitivity and a slightly decreased desalting efficiency, or (4) any combination of (1), (2), and (3).

  15. Microdialysis unit for molecular weight separation

    SciTech Connect

    Smith, R.D.; Liu, C.

    1999-09-21

    The present invention relates generally to an apparatus and method for separating high molecular weight molecules from low molecular weight molecules. More specifically, the invention relates to the use of microdialysis for removal of the salt (low molecular weight molecules) from a nucleotide sample (high molecular weight molecules) for ESI-MS analysis. The dialysis or separation performance of the present invention is improved by (1) increasing dialysis temperature thereby increasing desalting efficiency and improving spectrum quality; (2) adding piperidine and imidazole to the dialysis buffer solution and reducing charge states and further increasing detection sensitivity for DNA; (3) using low concentrations of dialysis buffer and shifting the DNA negative ions to higher charge states, producing a nearly 10-fold increase in detection sensitivity and a slightly decreased desalting efficiency, or (4) any combination of (1), (2), and (3).

  16. MEK1/2 Inhibitors: Molecular Activity and Resistance Mechanisms.

    PubMed

    Wu, Pui-Kei; Park, Jong-In

    2015-12-01

    Aberrant activation of the three-layered protein kinase cascade, Raf/MEK/ERK, is often detected in human cancer, which is mainly attributed to the oncogenic alterations of RAF, or its upstream activators RAS or cell surface receptor tyrosine kinases. Deregulated activity of the Raf/MEK/ERK pathway drives uncontrolled tumor cell proliferation and survival, thus providing a rational therapeutic target for the treatment of many cancers. While Raf, MEK1/2, and ERK1/2 are equally important targets for the design of therapeutic small molecular weight inhibitors, the effort to develop MEK1/2-specific inhibitors has been greatly successful. Particularly, MEK1/2 have been relatively advantageous for the design of highly selective adenosine triphosphate (ATP)-noncompetitive inhibitors. Indeed, a plethora of highly selective and potent MEK1/2 inhibitors are now available and many of those inhibitors have been evaluated for their therapeutic potential. Herein, we review different MEK1/2 inhibitors that have been studied for their inhibitory mechanisms and therapeutic potential in cancer. Some of the key structural features of MEK1/2 that are important for the efficacy of these inhibitors are also discussed. In addition, we discuss current challenges and future prospective in using these advanced MEK1/2 inhibitors for cancer therapy. PMID:26615130

  17. Biodegradation of high molecular weight polylactic acid

    NASA Astrophysics Data System (ADS)

    Stloukal, Petr; Koutny, Marek; Sedlarik, Vladimir; Kucharczyk, Pavel

    2012-07-01

    Polylactid acid seems to be an appropriate replacement of conventional non-biodegradable synthetic polymer primarily due to comparable mechanical, thermal and processing properties in its high molecular weight form. Biodegradation of high molecular PLA was studied in compost for various forms differing in their specific surface area. The material proved its good biodegradability under composting conditions and all investigated forms showed to be acceptable for industrial composting. Despite expectations, no significant differences in resulting mineralizations were observed for fiber, film and powder sample forms with different specific surface areas. The clearly faster biodegradation was detected only for the thin coating on porous material with high specific surface area.

  18. Ultrahigh Molecular Weight Aromatic Siloxane Polymers

    NASA Technical Reports Server (NTRS)

    Ludwick, L. M.

    1983-01-01

    Silphenylene-siloxane polymers can be prepared by a condensation reaction of a diol 1,4-bis(hydroxydimethylsilyl)benzene and a silane bis(dimethylamino)dimethylsilane. Using a stepwise condensation technique, a polymer (R=CH3) with a molecular weight in excess of 1.0 x 1 million has been produced. The polymer exhibits increased thermal stability, compared to a methyl siloxane polymer without the aromatic phenyl ring in the backbone. The use of bis(dimethylamino)methylvinylsilane should allow for ready crosslinking at the vinyl sites (R=-CH=CH2) introduced into the backbone. However, under the conditions of the reaction system a high molecular weight polymer was not obtained or the polymer underwent a crosslinking process during the synthesis.

  19. Biocompatible composites of ultrahigh molecular weight polyethylene

    NASA Astrophysics Data System (ADS)

    Panin, S. V.; Kornienko, L. A.; Suan, T. Nguen; Ivanova, L. P.; Korchagin, M. A.; Chaikina, M. V.; Shilko, S. V.; Pleskachevskiy, Yu. M.

    2015-10-01

    Mechanical and tribotechnical characteristics of biocompatible, antifriction and extrudable composites based on ultrahigh molecular weight polyethylene (UHMWPE) as well as hybrid matrix "UHMWPE + PTFE" with biocompatible hydroxyapatite filler under the dry friction and boundary lubrication were investigated. A comparative analysis of effectiveness of adding the hydroxyapatite to improve the wear resistance of composites based on these two matrices was performed. It is shown that the wear intensity of nanocomposites based on the hybrid matrix is lower than that for the composites based on pure UHMWPE. Possibilities of using the composites of the polymer "UHMWPE-PTFE" mixture as a material for artificial joints implants are discussed.

  20. Polymer Molecular Weight Analysis by [Superscript 1]H NMR Spectroscopy

    ERIC Educational Resources Information Center

    Izunobi, Josephat U.; Higginbotham, Clement L.

    2011-01-01

    The measurement and analysis of molecular weight and molecular weight distribution remain matters of fundamental importance for the characterization and physical properties of polymers. Gel permeation chromatography (GPC) is the most routinely used method for the molecular weight determination of polymers whereas matrix-assisted laser…

  1. Determinations of molecular weight and molecular weight distribution of high polymers by the rheological properties

    NASA Technical Reports Server (NTRS)

    Huang, J. Y.; Hou, T. H.; Tiwari, S. N.

    1989-01-01

    Several methods are reviewed by which the molecular weight (MW) and the molecular weight distribution (MWD) of polymeric material were determined from the rheological properties. A poly(arylene ether) polymer with six different molecular weights was used in this investigation. Experimentally measured MW and MWD were conducted by GPC/LALLS (gel permeation chromatography/low angle laser light scattering), and the rheological properties of the melts were measured by a Rheometric System Four rheometer. It was found that qualitative information of the MW and MWD of these polymers could be derived from the viscoelastic properties, with the methods proposed by Zeichner and Patel, and by Dormier et al., by shifting the master curves of the dynamic storage modulus, G', and the loss modulus, G'', along the frequency axis. Efforts were also made to calculate quantitative profiles of MW and MWD for these polymers from their rheological properties. The technique recently proposed by Wu was evaluated. It was found that satisfactory results could only be obtained for polymers with single modal distribution in the molecular weight.

  2. Molecular modeling of auxin transport inhibitors

    SciTech Connect

    Gardner, G.; Black-Schaefer, C.; Bures, M.G. )

    1990-05-01

    Molecular modeling techniques have been used to study the chemical and steric properties of auxin transport inhibitors. These bind to a specific site on the plant plasma membrane characterized by its affinity for N-1-naphthylphthalamic acid (NPA). A three-dimensional model was derived from critical features of ligands for the NPA receptor, and a suggested binding conformation is proposed. This model, along with three-dimensional structural searching techniques, was then used to search the Abbott corporate database of chemical structures. Of the 467 compounds that satisfied the search criteria, 77 representative molecules were evaluated for their ability to compete for ({sup 3}H)NPA binding to corn microsomal membranes. Nineteen showed activity that ranged from 16 to 85% of the maximum NPA binding. Four of the most active of these, from chemical classes not included in the original compound set, also inhibited polar auxin transport through corn coleoptile sections.

  3. Unexpected Molecular Weight Effect in Polymer Nanocomposites

    NASA Astrophysics Data System (ADS)

    Cheng, Shiwang; Holt, Adam P.; Wang, Huiqun; Fan, Fei; Bocharova, Vera; Martin, Halie; Etampawala, Thusitha; White, B. Tyler; Saito, Tomonori; Kang, Nam-Goo; Dadmun, Mark D.; Mays, Jimmy W.; Sokolov, Alexei P.

    2016-01-01

    The properties of the interfacial layer between the polymer matrix and nanoparticles largely determine the macroscopic properties of polymer nanocomposites (PNCs). Although the static thickness of the interfacial layer was found to increase with the molecular weight (MW), the influence of MW on segmental relaxation and the glass transition in this layer remains to be explored. In this Letter, we show an unexpected MW dependence of the interfacial properties in PNC with attractive polymer-nanoparticle interactions: the thickness of the interfacial layer with hindered segmental relaxation decreases as MW increases, in sharp contrast to theoretical predictions. Further analyses reveal a reduction in mass density of the interfacial layer with increasing MW, which can elucidate these unexpected dynamic effects. Our observations call for a significant revision of the current understandings of PNCs and suggest interesting ways to tailor their properties.

  4. Unexpected molecular weight effect in polymer nanocomposites

    DOE PAGESBeta

    Cheng, Shiwang; Holt, Adam P.; Wang, Huiqun; Fan, Fei; Bocharova, Vera; Martin, Halie J.; Etampawala, Thusitha N.; White, Benjamin Tyler; Saito, Tomonori; Kang, Nam -Goo; et al

    2016-01-22

    Here, the properties of the interfacial layer between the polymer matrix and nanoparticles largely determine the macroscopic properties of polymer nanocomposites (PNCs). Although the static thickness of the interfacial layer was found to increase with the molecular weight (MW), the influence of MW on segmental relaxation and the glass transition in this layer remains to be explored. In this Letter, we show an unexpected MW dependence of the interfacial properties in PNC with attractive polymer-nanoparticle interactions: the thickness of the interfacial layer with hindered segmental relaxation decreases as MW increases, in sharp constrast to theoretical predictions. Further analyses reveal amore » reduction in mass density of the interfacial layer with increasing MW, which can explain these unexpected dynamic effects. Our observations call for a significant revision of the current understandings of PNCs and suggest interesting ways to tailor their properties.« less

  5. Unexpected Molecular Weight Effect in Polymer Nanocomposites.

    PubMed

    Cheng, Shiwang; Holt, Adam P; Wang, Huiqun; Fan, Fei; Bocharova, Vera; Martin, Halie; Etampawala, Thusitha; White, B Tyler; Saito, Tomonori; Kang, Nam-Goo; Dadmun, Mark D; Mays, Jimmy W; Sokolov, Alexei P

    2016-01-22

    The properties of the interfacial layer between the polymer matrix and nanoparticles largely determine the macroscopic properties of polymer nanocomposites (PNCs). Although the static thickness of the interfacial layer was found to increase with the molecular weight (MW), the influence of MW on segmental relaxation and the glass transition in this layer remains to be explored. In this Letter, we show an unexpected MW dependence of the interfacial properties in PNC with attractive polymer-nanoparticle interactions: the thickness of the interfacial layer with hindered segmental relaxation decreases as MW increases, in sharp contrast to theoretical predictions. Further analyses reveal a reduction in mass density of the interfacial layer with increasing MW, which can elucidate these unexpected dynamic effects. Our observations call for a significant revision of the current understandings of PNCs and suggest interesting ways to tailor their properties. PMID:26849618

  6. Interaction of proteases with legume seed inhibitors. Molecular features.

    PubMed

    de Seidl, D S

    1996-12-01

    After having found that raw black beans (Phaseolus vulgaris) were toxic, while the cooked ones constitute the basic diet of the underdeveloped peoples of the world, in the sixties, our research directed by Dr. Jaffé, concentrated mainly around the detection and identification of the heat labile toxic factors in legume seeds. A micromethod for the detection of protease inhibitors (PI) in individual seeds was developed, for the purpose of establishing that the multiple trypsin inhibitors (TI) found in the Cubagua variety were expressions of single seeds and not a mixture of a non homogenous bean lot. Six isoinhibitors were isolated and purified, all of which were "double-headed" and interacted with trypsin (T) and chymotrypsin (CHT) independently and simultaneously, as shown by electrophoresis of their binary and ternary complexes with each and both enzymes. However, their affinity for the enzymes, including elastases, was rather variable, as well as their amino acid composition which consisted of 51 units for inhibitor V, the smallest, and 83 amino acids for inhibitor I, the largest. A low molecular weight protein fraction that inhibited subtilisin (S), but recognized neither T, CHT nor pancreatic elastase was detected in 63 varieties of Phaseolus vulgaris as well as in broad beans (Vicia faba), chick peas (Cicer arietinum), jack beans (Canavalia ensiformis), kidney beans (Vigna aureus), etc., It was absent though, in soybeans (Glycine max), lentils (Lens culinaris), green peas (Pisum sativum), cowpea (Vigna sinensis) and lupine seeds (Lupinus sp). Subtilisin inhibitors (SI) were isolated from black beans, broad beans, chick peas and jack beans. Their Mr is between 8-9KD and they show a rather high stability in the presence of denaturing agents. They are specific toward microbial proteases, in addition to subtilisins, Carlsberg and BPN', they inhibit the alkaline protease from Tritirachium album (Protease K), from Aspergillus oryzae and one isolated from

  7. Rubber molecular weight regulation, in vitro, in plant species that produce high and low molecular weights in vivo.

    PubMed

    Cornish, K; Castillón, J; Scott, D J

    2000-01-01

    In three rubber-producing species, in vitro, the rates of initiation and polymerization and the biopolymer molecular weight produced were affected by the concentration of farnesyl diphosphate (FPP) initiator and isopentenyl diphosphate (IPP) elongation substrate (monomer). Ficus elastica, a low molecular weight-producer in vivo, synthesized rubber polymers approximately twice the molecular weight of those made by Hevea brasiliensis or Parthenium argentatum (which produce high molecular weights in vivo), possibly due to its lower IPP Km. In all species, increasing FPP concentrations increased rubber biosynthetic rate and new molecules initiated but decreased molecular weight by competition with the allylic diphosphate (APP) end of elongating rubber molecules for the APP binding site. Increasing IPP concentrations increased rubber biosynthetic rate and rubber molecular weight, but only when FPP concentrations were below the FPP Km's or where negative cooperativity operated. In conclusion, rubber transferase is not the prime regulator of rubber molecular weight in vivo. PMID:11710193

  8. The Molecular Weight Distribution of Polymer Samples

    NASA Astrophysics Data System (ADS)

    Horta, Arturo; Pastoriza, M. Alejandra

    2007-07-01

    Introductory polymer courses and textbooks discuss the statistical distribution of chain lengths or molecular weight that exists in polymers and connect the averages and breadth of such distribution with the mechanism of the polymerization, for example, with the degree of advancement or stoichiometry in step-growth polymerization or with the existence of transferences or with the type of termination in chain addition polymerization. To determine averages and breadth of the distribution, the polymer has to be separated from the reaction medium and converted into a "sample". In this process, the shorter chains, which are most soluble, may be lost with the result that the sample is not identical to the original polymer. A student exercise is proposed and developed, in which we calculate the difference between "sample" and original polymer. We use standard material given in the introductory courses or textbooks such that the calculation can be performed easily by the students. The results are discussed to ascertain whether the different distribution of the sample may alter the interpretation of the mechanism by which the original polymer was obtained.

  9. Recovery of petroleum with chemically treated high molecular weight polymers

    SciTech Connect

    Gibb, C.L.; Rhudy, J.S.

    1980-11-18

    Plugging of reservoirs with high molecular weight polymers, e.g. Partially hydrolyzed polyacrylamide, is overcome by chemically treating a polymer having an excessively high average molecular weight prior to injection into a reservoir with an oxidizing chemical, e.g. sodium hypochlorite, and thereafter incorporating a reducing chemical, e.g., sodium sulfite, to stop degradation of the polymer when a desired lower average molecular weight and flooding characteristics are attained.

  10. Molecular Weight Effects on the Viscoelastic Response of a Polyimide

    NASA Technical Reports Server (NTRS)

    Nicholson, Lee M.; Whitley, Karen S.; Gates, Thomas S.

    2000-01-01

    The effect of molecular weight on the viscoelastic performance of an advanced polymer (LaRC -SI) was investigated through the use of creep compliance tests. Testing consisted of short-term isothermal creep and recovery with the creep segments performed under constant load. The tests were conducted at three temperatures below the glass transition temperature of each material with different molecular weight. Through the use of time-aging-time superposition procedures, the material constants, material master curves and aging-related parameters were evaluated at each temperature for a given molecular weight. The time-temperature superposition technique helped to describe the effect of temperature on the timescale of the viscoelastic response of each molecular weight. It was shown that the low molecular weight materials have increased creep compliance and creep compliance rate, and are more sensitive to temperature than the high molecular weight materials. Furthermore, a critical molecular weight transition was observed to occur at a weight-average molecular weight of approximately 25000 g/mol below which, the temperature sensitivity of the time-temperature superposition shift factor increases rapidly.

  11. Molecular mechanism of respiratory syncytial virus fusion inhibitors

    PubMed Central

    Battles, Michael B; Langedijk, Johannes P; Furmanova-Hollenstein, Polina; Chaiwatpongsakorn, Supranee; Costello, Heather M; Kwanten, Leen; Vranckx, Luc; Vink, Paul; Jaensch, Steffen; Jonckers, Tim H M; Koul, Anil; Arnoult, Eric; Peeples, Mark E; Roymans, Dirk; McLellan, Jason S

    2016-01-01

    Respiratory syncytial virus (RSV) is a leading cause of pneumonia and bronchiolitis in young children and the elderly. Therapeutic small molecules have been developed that bind the RSV F glycoprotein and inhibit membrane fusion, yet their binding sites and molecular mechanisms of action remain largely unknown. Here we show that these inhibitors bind to a three-fold-symmetric pocket within the central cavity of the metastable prefusion conformation of RSV F. Inhibitor binding stabilizes this conformation by tethering two regions that must undergo a structural rearrangement to facilitate membrane fusion. Inhibitor-escape mutations occur in residues that directly contact the inhibitors or are involved in the conformational rearrangements required to accommodate inhibitor binding. Resistant viruses do not propagate as well as wild-type RSV in vitro, indicating a fitness cost for inhibitor escape. Collectively, these findings provide new insight into class I viral fusion proteins and should facilitate development of optimal RSV fusion inhibitors. PMID:26641933

  12. Molecular mechanism of respiratory syncytial virus fusion inhibitors.

    PubMed

    Battles, Michael B; Langedijk, Johannes P; Furmanova-Hollenstein, Polina; Chaiwatpongsakorn, Supranee; Costello, Heather M; Kwanten, Leen; Vranckx, Luc; Vink, Paul; Jaensch, Steffen; Jonckers, Tim H M; Koul, Anil; Arnoult, Eric; Peeples, Mark E; Roymans, Dirk; McLellan, Jason S

    2016-02-01

    Respiratory syncytial virus (RSV) is a leading cause of pneumonia and bronchiolitis in young children and the elderly. Therapeutic small molecules have been developed that bind the RSV F glycoprotein and inhibit membrane fusion, yet their binding sites and molecular mechanisms of action remain largely unknown. Here we show that these inhibitors bind to a three-fold-symmetric pocket within the central cavity of the metastable prefusion conformation of RSV F. Inhibitor binding stabilizes this conformation by tethering two regions that must undergo a structural rearrangement to facilitate membrane fusion. Inhibitor-escape mutations occur in residues that directly contact the inhibitors or are involved in the conformational rearrangements required to accommodate inhibitor binding. Resistant viruses do not propagate as well as wild-type RSV in vitro, indicating a fitness cost for inhibitor escape. Collectively, these findings provide new insight into class I viral fusion proteins and should facilitate development of optimal RSV fusion inhibitors. PMID:26641933

  13. Molecular weight of aquatic fulvic acids by vapor pressure osmometry

    USGS Publications Warehouse

    Aiken, G.R.; Malcolm, R.L.

    1987-01-01

    The molecular weights of aquatic fulvic acids extracted from five rivers were determined by vapor pressure osmometry with water and tetrahydrofuran as solvents. The values obtained ranged from 500 to 950 dallons, indicating that the molecular weights of aquatic fulvic acids are not as great as has been suggested in some other molecular weight studies. The samples were shown to be relatively monodisperse from radii of gyration measurements determined by small angle x-ray scattering. THF affords greater precision and accuracy than H2O in VPO measurements, and was found to be a suitable solvent for the determination of molecular weight of aquatic fulvic acid because it obviates the dissociation problem. An inverse correlation was observed with these samples between the concentration of Ca++ and Mg++ in the river water and the radii of gyration and molecular weights of the corresponding fulvic acid samples. ?? 1987.

  14. Evaluation of ultrafiltration for determining molecular weight of fulvic acid

    USGS Publications Warehouse

    Aiken, G.R.

    1984-01-01

    Two commonly used ultrafiltration membranes are evaluated for the determination of molecular weights of humic substances. Polyacrylic acids of Mr 2000 and 5000 and two well-characterized fulvic acids are used as standards. Molecular size characteristics of standards, as determined by small-angle X-ray scattering, are presented. Great care in evaluating molecular weight data obtained by ultrafiltration is needed because of broad nominal cutoffs and membrane-solute interactions.

  15. Size-exclusion chromatography of ultrahigh molecular weight methylcellulose ethers and hydroxypropyl methylcellulose ethers for reliable molecular weight distribution characterization.

    PubMed

    Li, Yongfu; Shen, Hongwei; Lyons, John W; Sammler, Robert L; Brackhagen, Meinolf; Meunier, David M

    2016-03-15

    Size-exclusion chromatography (SEC) coupled with multi-angle laser light scattering (MALLS) and differential refractive index (DRI) detectors was employed for determination of the molecular weight distributions (MWD) of methylcellulose ethers (MC) and hydroxypropyl methylcellulose ethers (HPMC) having weight-average molecular weights (Mw) ranging from 20 to more than 1,000kg/mol. In comparison to previous work involving right-angle light scattering (RALS) and a viscometer for MWD characterization of MC and HPMC, MALLS yields more reliable molecular weight for materials having weight-average molecular weights (Mw) exceeding about 300kg/mol. A non-ideal SEC separation was observed for cellulose ethers with Mw>800kg/mol, and was manifested by upward divergence of logM vs. elution volume (EV) at larger elution volume at typical SEC flow rate such as 1.0mL/min. As such, the number-average molecular weight (Mn) determined for the sample was erroneously large and polydispersity (Mw/Mn) was erroneously small. This non-ideality resulting in the late elution of high molecular weight chains could be due to the elongation of polymer chains when experimental conditions yield Deborah numbers (De) exceeding 0.5. Non-idealities were eliminated when sufficiently low flow rates were used. Thus, using carefully selected experimental conditions, SEC coupled with MALLS and DRI can provide reliable MWD characterization of MC and HPMC covering the entire ranges of compositions and molecular weights of commercial interest. PMID:26794765

  16. Low molecular weight species in humic and fulvic fractions

    USGS Publications Warehouse

    Wilson, M.A.; Collin, P.J.; Malcolm, R.L.; Perdue, E.M.; Cresswell, P.

    1988-01-01

    Fourier transform solution 1H nuclear magnetic resonance (NMR) spectrometry with homogated water peak irradiation is a useful method for detecting low molecular weight substances in humic extracts. Succinate, acetate, methanol, formate, lactate and some aryl methoxyl compounds have been detected in extracts from a wide range of sources. In view of the controversy over whether low molecular weight substances are contaminants in humic extracts introduced by the concentration procedure, we report that some of these materials are not contaminants since 1H-NMR can be used to follow their formation from higher molecular weight species. ?? 1988.

  17. Free volume model for molecular weights of polymers

    NASA Technical Reports Server (NTRS)

    Singh, J. J.; Eftekhari, A.

    1992-01-01

    A free volume model has been developed for determining molecular weights of linear polymers. It is based on the size of free volume cells in two geometries of poly(arylene ether ketone)s. Free volume cell sizes in test samples were measured using positron lifetime spectroscopy. The molecular weights computed from free volume cell sizes are in good agreement with the values measured by gel permeation chromatography, with a low angle laser light scattering photometer as the detector. The model has been further tested on two atactic polystyrene samples, where it predicted the ratio of their molecular weights with reasonable accuracy.

  18. Free volume variation with molecular weight of polymers

    NASA Technical Reports Server (NTRS)

    Singh, Jag J.; Eftekhari, Abe; Hinkley, Jeffrey A.; St.clair, Terry L.; Jensen, Brian J.

    1992-01-01

    Free volume measurements were made in several molecular weight fractions of two different geometries of poly(arylene ether ketone)s. Free volumes were measured using positron lifetime spectroscopy. It has been observed that the free volume cell size V(sub f) varies with the molecular weight M of the test samples according to an equation of the form V(sub f) = AM(B), where A and B are constants. The molecular weights computed from the free volume cell sizes are in good agreement with the values measured by gel permeation chromatography.

  19. Extraction of high molecular weight DNA from microbial mats.

    PubMed

    Bey, Benjamin S; Fichot, Erin B; Dayama, Gargi; Decho, Alan W; Norman, R Sean

    2010-09-01

    Due to the presence of inhibitors such as extracellular polymeric substances (EPSs) and salts, most microbial mat studies have relied on harsh methods of direct DNA extraction that result in DNA fragments too small for large-insert vector cloning. High molecular weight (HMW) DNA is crucial in functional metagenomic studies, because large fragments present greater access to genes of interest. Here we report improved methodologies for extracting HMW DNA from EPS-rich hypersaline microbial mats. The protocol uses a combination of microbial cell separation with mechanical and chemical methods for DNA extraction and purification followed by precipitation with polyethylene glycol (PEG). The protocol yields >2 µg HMW DNA (>48 kb) per gram of mat sample, with A260:280 ratios >1.7. In addition, 16S rRNA gene analysis using denaturing gradient gel electrophoresis and pyrosequencing showed that this protocol extracts representative DNA from microbial mat communities and results in higher overall calculated diversity indices compared with three other standard methods of DNA extraction. Our results show the importance of validating the DNA extraction methods used in metagenomic studies to ensure optimal recovery of microbial richness. PMID:20854264

  20. Do Low Molecular Weight Agents Cause More Severe Asthma than High Molecular Weight Agents?

    PubMed Central

    Meca, Olga; Cruz, María-Jesús; Sánchez-Ortiz, Mónica; González-Barcala, Francisco-Javier; Ojanguren, Iñigo; Munoz, Xavier

    2016-01-01

    Introduction The aim of this study was to analyse whether patients with occupational asthma (OA) caused by low molecular weight (LMW) agents differed from patients with OA caused by high molecular weight (HMW) with regard to risk factors, asthma presentation and severity, and response to various diagnostic tests. Methods Seventy-eight patients with OA diagnosed by positive specific inhalation challenge (SIC) were included. Anthropometric characteristics, atopic status, occupation, latency periods, asthma severity according to the Global Initiative for Asthma (GINA) control classification, lung function tests and SIC results were analysed. Results OA was induced by an HMW agent in 23 patients (29%) and by an LMW agent in 55 (71%). A logistic regression analysis confirmed that patients with OA caused by LMW agents had a significantly higher risk of severity according to the GINA classification after adjusting for potential confounders (OR = 3.579, 95% CI 1.136–11.280; p = 0.029). During the SIC, most patients with OA caused by HMW agents presented an early reaction (82%), while in patients with OA caused by LMW agents the response was mainly late (73%) (p = 0.0001). Similarly, patients with OA caused by LMW agents experienced a greater degree of bronchial hyperresponsiveness, measured as the difference in the methacholine dose-response ratio (DRR) before and after SIC (1.77, range 0–16), compared with patients with OA caused by HMW agents (0.87, range 0–72), (p = 0.024). Conclusions OA caused by LMW agents may be more severe than that caused by HMW agents. The severity of the condition may be determined by the different mechanisms of action of these agents. PMID:27280473

  1. Molecular-Weight-Controlled, End-Capped Polybenzimidazoles

    NASA Technical Reports Server (NTRS)

    Connell, John W.; Hergenrother, Paul M.; Smith, Joseph G., Jr.

    1993-01-01

    Novel molecular-weight-controlled end-capped poly(arylene ether benzimidazole)s (PAEBI's) prepared by nucleophilic displacement reaction of di(hydroxyl)benzimidazole monomers with activated aromatic dihalides. Polymers prepared at various molecular weights by upsetting stoichiometry of monomers and end-capped with monohydroxybenzimidazole. Exhibit favorable physical and mechanical properties, improved solubility in polar aprotic solvents and better compression moldability. Potential applications as adhesives, coatings, films, fibers, membranes, moldings, and composite matrix resins.

  2. Human Lactate Dehydrogenase A Inhibitors: A Molecular Dynamics Investigation

    PubMed Central

    Shi, Yun; Pinto, B. Mario

    2014-01-01

    Lactate dehydrogenase A (LDHA) is an important enzyme in fermentative glycolysis, generating most energy for cancer cells that rely on anaerobic respiration even under normal oxygen concentrations. This renders LDHA a promising molecular target for the treatment of various cancers. Several efforts have been made recently to develop LDHA inhibitors with nanomolar inhibition and cellular activity, some of which have been studied in complex with the enzyme by X-ray crystallography. In this work, we present a molecular dynamics (MD) study of the binding interactions of selected ligands with human LDHA. Conventional MD simulations demonstrate different binding dynamics of inhibitors with similar binding affinities, whereas steered MD simulations yield discrimination of selected LDHA inhibitors with qualitative correlation between the in silico unbinding difficulty and the experimental binding strength. Further, our results have been used to clarify ambiguities in the binding modes of two well-known LDHA inhibitors. PMID:24466056

  3. Phase Behavior of Binary Blends of High Molecular Weight Diblock Copolymers with a Low Molecular Weight Triblock

    SciTech Connect

    Mickiewicz, Rafal A.; Ntoukas, Eleftherios; Avgeropoulos, Apostolos; Thomas, Edwin L.

    2009-08-26

    Binary blends of four different high molecular weight poly(styrene-b-isoprene) (SI) diblock copolymers with a lower molecular weight poly(styrene-b-isoprene-b-styrene) (SIS) triblock copolymer were prepared, and their morphology was characterized by transmission electron microscopy and ultra-small-angle X-ray scattering. All the neat block copolymers have nearly symmetric composition and exhibit the lamellar morphology. The SI diblock copolymers had number-average molecular weights, Mn, in the range 4.4 x 10{sup 5}--1.3 x 10{sup 6} g/mol and volume fractions of poly(styrene), {Phi}{sub PS}, in the range 0.43--0.49, and the SIS triblock had a molecular weight of Mn 6.2 x 10{sup 4} g/mol with {Phi}{sub PS} = 0.41. The high molecular weight diblock copolymers are very strongly segregating, with interaction parameter values, {chi}N, in the range 470--1410. A morphological phase diagram in the parameter space of molecular weight ratio (R = M{sub n}{sup diblock}/1/2M{sub n}{sup triblock}) and blend composition was constructed, with R values in the range between 14 and 43, which are higher than previously reported. The phase diagram revealed a large miscibility gap for the blends, with macrophase separation into two distinct types of microphase-separated domains for weight fractions of SI, w{sub SI} < 0.9, implying virtually no solubility of the much higher molecular weight diblocks in the lower molecular weight triblock. For certain blend compositions, above R 30, morphological transitions from the lamellar to cylindrical and bicontinuous structures were also observed.

  4. Evaluation of a Viscosity-Molecular Weight Relationship.

    ERIC Educational Resources Information Center

    Mathias, Lon J.

    1983-01-01

    Background information, procedures, and results are provided for a series of graduate/undergraduate polymer experiments. These include synthesis of poly(methylmethacrylate), viscosity experiment (indicating large effect even small amounts of a polymer may have on solution properties), and measurement of weight-average molecular weight by light…

  5. Microbial detection with low molecular weight RNA

    NASA Technical Reports Server (NTRS)

    Kourentzi, K. D.; Fox, G. E.; Willson, R. C.

    2001-01-01

    The need to monitor microorganisms in the environment has increased interest in assays based on hybridization probes that target nucleic acids (e.g., rRNA). We report the development of liquid-phase assays for specific bacterial 5S rRNA sequences or similarly sized artificial RNAs (aRNAs) using molecular beacon technology. These beacons fluoresce only in the presence of specific target sequences, rendering as much as a 27-fold fluorescence enhancement. The assays can be used with both crude cell lysates and purified total RNA preparations. Minimal sample preparation (e.g., heating to promote leakage from cells) is sufficient to detect many Gram-negative bacteria. Using this approach it was possible to detect an aRNA-labeled Escherichia coli strain in the presence of a large background of an otherwise identical E. coli strain. Finally, by using a longer wavelength carboxytetramethylrhodamine beacon it was possible to reduce the fraction of the signal due to cellular autofluorescence to below 0.5%.

  6. SEDFIT-MSTAR: Molecular weight and molecular weight distribution analysis of polymers by sedimentation equilibrium in the ultracentrifuge

    PubMed Central

    Schuck, Peter; Gillis, Richard B.; Besong, Tabot M.D.; Almutairi, Fahad; Adams, Gary G.; Rowe, Arthur J.; Harding, Stephen E.

    2014-01-01

    Sedimentation equilibrium (analytical ultracentrifugation) is one of the most inherently suitable methods for the determination of average molecular weights and molecular weight distributions of polymers, because of its absolute basis (no conformation assumptions) and inherent fractionation ability (without the need for columns or membranes and associated assumptions over inertness). With modern instrumentation it is also possible to run up to 21 samples simultaneously in a single run. Its application has been severely hampered because of difficulties in terms of baseline determination (incorporating estimation of the concentration at the air/solution meniscus) and complexity of the analysis procedures. We describe a new method for baseline determination based on a smart-smoothing principle and built into the highly popular platform SEDFIT for the analysis of the sedimentation behavior of natural and synthetic polymer materials. The SEDFIT-MSTAR procedure – which takes only a few minutes to perform - is tested with four synthetic data sets (including a significantly non-ideal system) a naturally occurring protein (human IgG1) and two naturally occurring carbohydrate polymers (pullulan and λ–carrageenan) in terms of (i) weight average molecular weight for the whole distribution of species in the sample (ii) the variation in “point” average molecular weight with local concentration in the ultracentrifuge cell and (iii) molecular weight distribution. PMID:24244936

  7. Molecular weight, polydispersity, and spectroscopic properties of aquatic humic substances

    USGS Publications Warehouse

    Chin, Y.-P.; Aiken, G.; O'Loughlin, E.

    1994-01-01

    The number- and weight-averaged molecular weights of a number of aquatic fulvic acids, a commercial humic acid, and unfractionated organic matter from four natural water samples were measured by high-pressure size exclusion chromatography (HPSEC). Molecular weights determined in this manner compared favorably with those values reported in the literature. Both recent literature values and our data indicate that these substances are smaller and less polydisperse than previously believed. Moreover, the molecular weights of the organic matter from three of the four natural water samples compared favorably to the fulvic acid samples extracted from similar environments. Bulk spectroscopic properties of the fulvic substances such as molar absorptivity at 280 nm and the E4/E6 ratio were also measured. A strong correlation was observed between molar absorptivity, total aromaticity, and the weight average molecular weights of all the humic substances. This observation suggests that bulk spectroscopic properties can be used to quickly estimate the size of humic substances and their aromatic contents. Both parameters are important with respect to understanding humic substance mobility and their propensity to react with both organic and inorganic pollutants. ?? 1994 American Chemical Society.

  8. Rheological investigation of highly filled polymers: Effect of molecular weight

    NASA Astrophysics Data System (ADS)

    Hnatkova, Eva; Hausnerova, Berenika; Hales, Andrew; Jiranek, Lukas; Vera, Juan Miguel Alcon

    2015-04-01

    The paper deals with rheological properties of highly filled polymers used in powder injection molding. Within the experimental framework seven PIM feedstocks based on superalloy Inconel 718 powder were prepared. Each feedstock contains the fixed amount of powder loading and the same composition of binder system consisting of three components: polyethylene glycol (PEG) differing in molecular weight, poly (methyl methacrylate) (PMMA) and stearic acid (SA). The aim is to investigate the influence of PEG's molecular weight on the flow properties of feedstocks. Non-Newtonian indices, representing the shear rate sensitivity of the feedstocks, are obtained from a polynomial fit, and found to vary within measured shear rates range from 0.2 to 0.8. Temperature effect is considered via activation energies, showing decreasing trend with increasing of molecular weight of PEG (except of feedstock containing 1,500 g.mol-1 PEG).

  9. Inhibition of phagocytosis by high molecular weight hyaluronate.

    PubMed Central

    Forrester, J V; Balazs, E A

    1980-01-01

    The effect of sodium hyaluronate on phagocytosis was studied using a sensitive polystyrene latex sphere assay in mouse peritoneal macrophage monolayers. Viscous solutions of high molecular weight hyaluronate (4.6 X 10(5)--2.8 X 10(6)) caused a dose-dependent inhibition of phagocytosis, but low molecular weight hyaluronate (9.0 X 10(4)) was not inhibitory at equivalent viscosity. The inhibitory effect of high molecular weight hyaluronate did not appear to be mediated by the polyanionic charge of the molecule since sulphated glycosaminoglycans with greater charge density (heparin and chondroitin sulphate) were ineffective. In addition, competitive inhibition studies indicated that a direct effect on possible cell surface membrane receptors was unlikely. Instead, physical factors such as steric hindrance by the continuous polymeric network, were considered of more importance. Alternatively, the hydrophilic polysaccharide may have inhibited phagocytosis by providing an unsuitable surface for adhesive contact between the latex beads and the cell surface. PMID:7429537

  10. Influence of Molecular Weight and Degree of Deacetylation of Low Molecular Weight Chitosan on the Bioactivity of Oral Insulin Preparations

    PubMed Central

    Qinna, Nidal A.; Karwi, Qutuba G.; Al-Jbour, Nawzat; Al-Remawi, Mayyas A.; Alhussainy, Tawfiq M.; Al-So’ud, Khaldoun A.; Al Omari, Mahmoud M. H.; Badwan, Adnan A.

    2015-01-01

    The objective of the present study was to prepare and characterize low molecular weight chitosan (LMWC) with different molecular weight and degrees of deacetylation (DDA) and to optimize their use in oral insulin nano delivery systems. Water in oil nanosized systems containing LMWC-insulin polyelectrolyte complexes were constructed and their ability to reduce blood glucose was assessed in vivo on diabetic rats. Upon acid depolymerization and testing by viscosity method, three molecular weights of LMWC namely, 1.3, 13 and 18 kDa were obtained. As for the DDA, three LMWCs of 55%, 80% and 100% DDA were prepared and characterized by spectroscopic methods for each molecular weight. The obtained LMWCs showed different morphological and in silico patterns. Following complexation of LMWCs with insulin, different aggregation sizes were obtained. Moreover, the in vivo tested formulations showed different activities of blood glucose reduction. The highest glucose reduction was achieved with 1.3 kDa LMWC of 55% DDA. The current study emphasizes the importance of optimizing the molecular weight along with the DDA of the incorporated LMWC in oral insulin delivery preparations in order to ensure the highest performance of such delivery systems. PMID:25826718

  11. Influence of molecular weight and degree of deacetylation of low molecular weight chitosan on the bioactivity of oral insulin preparations.

    PubMed

    Qinna, Nidal A; Karwi, Qutuba G; Al-Jbour, Nawzat; Al-Remawi, Mayyas A; Alhussainy, Tawfiq M; Al-So'ud, Khaldoun A; Al Omari, Mahmoud M H; Badwan, Adnan A

    2015-04-01

    The objective of the present study was to prepare and characterize low molecular weight chitosan (LMWC) with different molecular weight and degrees of deacetylation (DDA) and to optimize their use in oral insulin nano delivery systems. Water in oil nanosized systems containing LMWC-insulin polyelectrolyte complexes were constructed and their ability to reduce blood glucose was assessed in vivo on diabetic rats. Upon acid depolymerization and testing by viscosity method, three molecular weights of LMWC namely, 1.3, 13 and 18 kDa were obtained. As for the DDA, three LMWCs of 55%, 80% and 100% DDA were prepared and characterized by spectroscopic methods for each molecular weight. The obtained LMWCs showed different morphological and in silico patterns. Following complexation of LMWCs with insulin, different aggregation sizes were obtained. Moreover, the in vivo tested formulations showed different activities of blood glucose reduction. The highest glucose reduction was achieved with 1.3 kDa LMWC of 55% DDA. The current study emphasizes the importance of optimizing the molecular weight along with the DDA of the incorporated LMWC in oral insulin delivery preparations in order to ensure the highest performance of such delivery systems. PMID:25826718

  12. RHEOLOGICAL PROPERTIES & MOLECULAR WEIGHT DISTRIBUTIONS OF FOUR PERFLUORINATED THERMOPLASTIC POLYMERS

    SciTech Connect

    Hoffman, D M; Shields, A L

    2009-02-24

    Dynamic viscosity measurements and molecular weight estimates have been made on four commercial, amorphous fluoropolymers with glass transitions (Tg) above 100 C: Teflon AF 1600, Hyflon AD 60, Cytop A and Cytop M. These polymers are of interest as binders for the insensitive high explosive 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) because of their high density and Tg above ambient, but within a suitable processing range of TATB. As part of this effort, the rheological properties and molecular weight distributions of these polymers were evaluated.

  13. Mean molecular weight and hydrogen abundance of Titan's atmosphere

    NASA Technical Reports Server (NTRS)

    Samuelson, R. E.; Hanel, R. A.; Kunde, V. G.; Maguire, W. C.

    1981-01-01

    The 200-600/cm continuum opacity in the troposphere and lower stratosphere of Titan is inferred from thermal emission spectra from the Voyager 1 IR spectrometer (IRIS). The surface temperature and mean molecular weight are between 94 and 97 K and between 28.3 and 29.2 AMU, respectively. The mole fraction of molecular hydrogen is 0.002 + or - 0.001, which is equivalent to an abundance of approximately 0.2 + or - 0.1 km amagat.

  14. Polyacrylamide molecular weight effects on soil infiltration and erosion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seal formation at the surface of smectitic soils during rainstorms reduces soil infiltration rate (IR) and causes runoff and erosion. Surface application of dry anionic polyacrylamide (PAM) with high molecular weight (MW) has been found to be effective in stabilizing soil aggregates, and decreasing ...

  15. DETERMINATION OF MOLECULAR WEIGHT CITRUS PECTIN USING ION CHROMATOGRAPHY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective was to investigate the use of ELS as a mass detector coupled with MALLS for determining the molecular weights of pectins and other polysaccharides under changing buffer concentrations using HPLC. This would permit the direct determination of the charge to size ratio of pectin which is imp...

  16. Ultra-High-Molecular-Weight Silphenylene/Siloxane Polymers

    NASA Technical Reports Server (NTRS)

    Patterson, W. J.; Hundley, N. H.; Ludwick, L. M.

    1986-01-01

    Elastomers having molecular weights above 1 million made by twostage polymerization. Two-stage process proves far more successful than synthesis from reactive monomers. Process involves synthesis of silanolterminated prepolymer and subsequent extension of prepolymer chain with additional aminosilane monomer. Multistage method allows chain-extending monomer added in precise amounts between stages.

  17. Preparation of soybean oil polymers with high molecular weight

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cationic polymerization of soybean oils was initiated by boron trifluoride diethyl etherate BF3.O(C2H5)2 in supercritical carbon dioxide (scCO2) medium. The resulting polymers had molecular weight ranging from 21,842 to 118,300 g/mol. Nuclear magnetic resonance spectroscopy (NMR) and gel perme...

  18. A Pan-GTPase Inhibitor as a Molecular Probe

    PubMed Central

    Hong, Lin; Guo, Yuna; BasuRay, Soumik; Agola, Jacob O.; Romero, Elsa; Simpson, Denise S.; Schroeder, Chad E.; Simons, Peter; Waller, Anna; Garcia, Matthew; Carter, Mark; Ursu, Oleg; Gouveia, Kristine; Golden, Jennifer E.; Aubé, Jeffrey; Wandinger-Ness, Angela; Sklar, Larry A.

    2015-01-01

    Overactive GTPases have often been linked to human diseases. The available inhibitors are limited and have not progressed far in clinical trials. We report here a first-in-class small molecule pan-GTPase inhibitor discovered from a high throughput screening campaign. The compound CID1067700 inhibits multiple GTPases in biochemical, cellular protein and protein interaction, as well as cellular functional assays. In the biochemical and protein interaction assays, representative GTPases from Rho, Ras, and Rab, the three most generic subfamilies of the GTPases, were probed, while in the functional assays, physiological processes regulated by each of the three subfamilies of the GTPases were examined. The chemical functionalities essential for the activity of the compound were identified through structural derivatization. The compound is validated as a useful molecular probe upon which GTPase-targeting inhibitors with drug potentials might be developed. PMID:26247207

  19. Uncovering Molecular Bases Underlying Bone Morphogenetic Protein Receptor Inhibitor Selectivity

    PubMed Central

    Alsamarah, Abdelaziz; LaCuran, Alecander E.; Oelschlaeger, Peter; Hao, Jijun; Luo, Yun

    2015-01-01

    Abnormal alteration of bone morphogenetic protein (BMP) signaling is implicated in many types of diseases including cancer and heterotopic ossifications. Hence, small molecules targeting BMP type I receptors (BMPRI) to interrupt BMP signaling are believed to be an effective approach to treat these diseases. However, lack of understanding of the molecular determinants responsible for the binding selectivity of current BMP inhibitors has been a big hindrance to the development of BMP inhibitors for clinical use. To address this issue, we carried out in silico experiments to test whether computational methods can reproduce and explain the high selectivity of a small molecule BMP inhibitor DMH1 on BMPRI kinase ALK2 vs. the closely related TGF-β type I receptor kinase ALK5 and vascular endothelial growth factor receptor type 2 (VEGFR2) tyrosine kinase. We found that, while the rigid docking method used here gave nearly identical binding affinity scores among the three kinases; free energy perturbation coupled with Hamiltonian replica-exchange molecular dynamics (FEP/H-REMD) simulations reproduced the absolute binding free energies in excellent agreement with experimental data. Furthermore, the binding poses identified by FEP/H-REMD led to a quantitative analysis of physical/chemical determinants governing DMH1 selectivity. The current work illustrates that small changes in the binding site residue type (e.g. pre-hinge region in ALK2 vs. ALK5) or side chain orientation (e.g. Tyr219 in caALK2 vs. wtALK2), as well as a subtle structural modification on the ligand (e.g. DMH1 vs. LDN193189) will cause distinct binding profiles and selectivity among BMP inhibitors. Therefore, the current computational approach represents a new way of investigating BMP inhibitors. Our results provide critical information for designing exclusively selective BMP inhibitors for the development of effective pharmacotherapy for diseases caused by aberrant BMP signaling. PMID:26133550

  20. Application of Molecular Modeling to Urokinase Inhibitors Development

    PubMed Central

    Sulimov, V. B.; Katkova, E. V.; Oferkin, I. V.; Sulimov, A. V.; Romanov, A. N.; Roschin, A. I.; Beloglazova, I. B.; Plekhanova, O. S.; Tkachuk, V. A.; Sadovnichiy, V. A.

    2014-01-01

    Urokinase-type plasminogen activator (uPA) plays an important role in the regulation of diverse physiologic and pathologic processes. Experimental research has shown that elevated uPA expression is associated with cancer progression, metastasis, and shortened survival in patients, whereas suppression of proteolytic activity of uPA leads to evident decrease of metastasis. Therefore, uPA has been considered as a promising molecular target for development of anticancer drugs. The present study sets out to develop the new selective uPA inhibitors using computer-aided structural based drug design methods. Investigation involves the following stages: computer modeling of the protein active site, development and validation of computer molecular modeling methods: docking (SOL program), postprocessing (DISCORE program), direct generalized docking (FLM program), and the application of the quantum chemical calculations (MOPAC package), search of uPA inhibitors among molecules from databases of ready-made compounds to find new uPA inhibitors, and design of new chemical structures and their optimization and experimental examination. On the basis of known uPA inhibitors and modeling results, 18 new compounds have been designed, calculated using programs mentioned above, synthesized, and tested in vitro. Eight of them display inhibitory activity and two of them display activity about 10 μM. PMID:24967388

  1. Molecular physiology of weight regulation in mice and humans

    PubMed Central

    Leibel, RL

    2009-01-01

    Evolutionary considerations relating to efficiency in reproduction, and survival in hostile environments, suggest that body energy stores are sensed and actively regulated, with stronger physiological and behavioral responses to loss than gain of stored energy. Many physiological studies support this inference, and suggest that a critical axis runs between body fat and the hypothalamus. The molecular cloning of leptin and its receptor—projects based explicitly on the search for elements in this axis—confirmed the existence of this axis and provided important tools with which to understand its molecular physiology. Demonstration of the importance of this soma-brain reciprocal connection in body weight regulation in humans has been pursued using both classical genetic approaches and studies of physiological responses to experimental weight perturbation. This paper reviews the history of the rationale and methodology of the cloning of leptin (Lep) and the leptin receptor (Lepr), and describes some of the clinical investigation characterizing this axis. PMID:19136999

  2. High molecular weight tropomyosins regulate osteoclast cytoskeletal morphology.

    PubMed

    Kotadiya, Preeyal; McMichael, Brooke K; Lee, Beth S

    2008-11-01

    Tropomyosins are coiled-coil dimers that bind to the major groove of F-actin and regulate its accessibility to actin-modifying proteins. Although approximately 40 tropomyosin isoforms have been identified in mammals, they can broadly be classified into two groups based on protein size, that is, high molecular weight and low molecular weight isoforms. Osteoclasts, which undergo rounds of polarization and depolarization as they progress through the resorptive cycle, possess an unusual and highly dynamic actin cytoskeleton. To further define some of the actin regulatory proteins involved in osteoclast activity, we previously performed a survey of tropomyosin isoforms in resting and resorbing osteoclasts. Osteoclasts were found to express two closely related tropomyosins of the high molecular weight type, which are not expressed in monocytic and macrophage precursors. These isoforms, Tm-2 and Tm-3, are not strongly associated with actin-rich adhesion structures, but are instead distributed diffusely throughout the cell. In this study, we found that Tm-2/3 expression occurs late in osteoclastogenesis and continues to increase as cells mature. Knockdown of these isoforms via RNA interference results in flattening and increased spreading of osteoclasts, accompanied by diminished motility and altered resorptive capacity. In contrast, overexpression of Tm-2, but not Tm-3, caused morphological changes that include decreased spreading of the cells and induction of actin patches or stress fiber-like actin filaments, also with effects on motility and resorption. Suppression of Tm-2/3 or overexpression of Tm-2 resulted in altered distribution of gelsolin and microfilament barbed ends. These data suggest that high molecular weight tropomyosins are expressed in fusing osteoclasts to regulate the cytoskeletal scaffolding of these large cells, due at least in part by moderating accessibility of gelsolin to these microfilaments. PMID:18674650

  3. Ultra-High-Molecular-Weight Silphenylene/Siloxane Elastomers

    NASA Technical Reports Server (NTRS)

    Hundley, N. H.; Patterson, W. J.

    1989-01-01

    Elastomers enhance thermal and mechancial properties. Capable of performing in extreme thermal/oxidative environments and having molecular weights above 10 to the sixth power prepared and analyzed in laboratory experiments. Made of methylvinylsilphenylene-siloxane terpolymers, new materials amenable to conventional silicone-processing technology. Similarly formulated commercial methyl-vinyl silicones, vulcanized elastomers exhibit enhance thermal/oxidative stability and equivalent or superior mechanical properties.

  4. High molecular weight polysaccharide that binds and inhibits virus

    DOEpatents

    Konowalchuk, Thomas W

    2014-01-14

    This invention provides a high molecular weight polysaccharide capable of binding to and inhibiting virus and related pharmaceutical formulations and methods on inhibiting viral infectivity and/or pathogenicity, as well as immunogenic compositions. The invention further methods of inhibiting the growth of cancer cells and of ameliorating a symptom of aging. Additionally, the invention provides methods of detecting and/or quantifying and/or isolating viruses.

  5. Molecular targets in osteoarthritis: metalloproteinases and their inhibitors.

    PubMed

    Burrage, P S; Brinckerhoff, C E

    2007-02-01

    The debilitating destruction of joint tissues seen in osteoarthritis (OA) is due, in large part, to the degradative activity of metalloproteinase (MP) enzymes that target extracellular matrix (ECM) components within articular cartilage. Although successful in suppressing the pain and inflammation associated with this disease, conventional OA therapeutics do not inhibit the underlying tissue catabolism, allowing the disease to progress into irreversible ECM loss and chronic disability. Therapeutic inhibition of metalloproteinase activity is not a new concept, however, its transfer into clinical use has been frustrating. Disappointing results from clinical trials with small molecule inhibitors of metalloproteinases have highlighted the critical importance of inhibitor specificity, and the need to identify the individual metalloproteinases responsible for joint destruction. We discuss strategies of inhibition using small molecule inhibitors and tissue inhibitors of metalloproteinases (TIMPs) engineered to increase inhibitory specificity, and present new data using of new reagents such as ribozymes and inhibitory RNAs that repress expression of specific enzymes. Recent data has implicated the disease stage-dependent involvement of matrix metalloproteinase-1, -2, -3, -9, -13, ADAM-17/TACE (tumor-necrosis factor-alpha converting enzyme), and ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin 1 motifs) as major in vivo mediators of the ECM degradation seen in OA, and as such, they represent promising therapeutic targets. We conclude that the concept of molecular polypharmacy, in which the relevant enzymes are selectively targeted with multiple directed therapies, may offer a new therapeutic strategy that prevents joint destruction and minimizes toxicities. PMID:17305507

  6. Buckling in polymer monolayers: Molecular-weight dependence

    SciTech Connect

    Srivastava, S.; Basu, J.K.

    2010-11-12

    We present systematic investigations of buckling in Langmuir monolayers of polyvinyl acetate formed at the air-water interface. On compression the polymer monolayers are converted to a continuous membrane with a thickness of {approx}2-3 nm of well-defined periodicity, {lambda}{sub b}. Above a certain surface concentration the membrane undergoes a morphological transition buckling, leading to the formation of striped patterns. The periodicity seems to depend on molecular weight as per the predictions of the gravity-bending buckling formalism of Milner et al. for fluidlike films on water. However anomalously low values of bending rigidity and Young's modulus are obtained using this formalism. Hence we have considered an alternative model of buckling-based solidlike films on viscoelastic substrates. The values of bending rigidity and Young's modulus obtained by this method, although lower than expected, are closer to the bulk values. Remarkably, no buckling is found to occur above a certain molecular weight. We have tried to explain the observed molecular-weight dependence in terms of the variation in isothermal compressive modulus of the monolayers with surface concentration as well as provided possible explanations for the obtained low values of mechanical properties similar to that observed for ultrathin polymer films.

  7. Application of Molecular Modeling to Development of New Factor Xa Inhibitors

    PubMed Central

    Sulimov, Vladimir B.; Gribkova, Irina V.; Kochugaeva, Maria P.; Katkova, Ekaterina V.; Sulimov, Alexey V.; Kutov, Danil C.; Shikhaliev, Khidmet S.; Medvedeva, Svetlana M.; Krysin, Michael Yu.; Sinauridze, Elena I.; Ataullakhanov, Fazoil I.

    2015-01-01

    In consequence of the key role of factor Xa in the clotting cascade and absence of its activity in the processes that do not affect coagulation, this protein is an attractive target for development of new blood coagulation inhibitors. Factor Xa is more effective and convenient target for creation of anticoagulants than thrombin, inhibition of which may cause some side effects. This study is aimed at finding new inhibitors of factor Xa by molecular computer modeling including docking SOL and postdocking optimization DISCORE programs. After validation of molecular modeling methods on well-known factor Xa inhibitors the virtual screening of NCI Diversity and Voronezh State University databases of ready-made low molecular weight species has been carried out. Seventeen compounds selected on the basis of modeling results have been tested experimentally in vitro. It has been found that 12 of them showed activity against factor Xa (IC50 = 1.8–40 μM). Based on analysis of the results, the new original compound was synthesized and experimentally verified. It shows activity against factor Xa with IC50 value of 0.7 μM. PMID:26484350

  8. Determination of molecular-weight distribution and average molecular weights of block copolymers by gel-permeation chromatography.

    PubMed

    Nesterov, V V; Kurenbin, O I; Krasikov, V D; Belenkii, B G

    1987-01-01

    The problem of preparation of a block copolymer of precise molecular-weight distribution (MWD) and with heterogeneous composition on the basis of gel-permeation chromatography (GPC) data has been investigated. It has been shown that in MWD calculations the distribution f(p) of the composition p in individual GPC fractions should be taken into account. The type of the f(p) functions can be simultaneously established by an independent method, such as use of adsorption-column or thin-layer chromatography sensitive to the composition of the copolymer. It has also been shown that the actual f(p) may be replaced by a corresponding piecewise distribution, of simple form, without decrease in the precision of calculation of the MWD and average molecular weights of most known block copolymers. PMID:18964273

  9. High Sulfation and a High Molecular Weight Are Important for Anti-hepcidin Activity of Heparin.

    PubMed

    Asperti, Michela; Naggi, Annamaria; Esposito, Emiliano; Ruzzenenti, Paola; Di Somma, Margherita; Gryzik, Magdalena; Arosio, Paolo; Poli, Maura

    2015-01-01

    Heparins are efficient inhibitors of hepcidin expression even in vivo, where they induce an increase of systemic iron availability. Heparins seem to act by interfering with BMP6 signaling pathways that control the expression of liver hepcidin, causing the suppression of SMAD1/5/8 phosphorylation. The anti-hepcidin activity persists also when the heparin anticoagulant property is abolished or reduced by chemical reactions of oxidation/reduction (glycol-split, Gs-Heparins) or by high sulfation (SS-Heparins), but the structural characteristics needed to optimize this inhibitory activity have not been studied in detail. To this aim we analyzed three different heparins (Mucosal Heparin, the Glycol split RO-82, the partially desulfated glycol-split RO-68 and the oversulfated SSLMWH) and separated them in fractions of molecular weight in the range 4-16 kD. Since the distribution of the negative charges in heparins contributes to the activity, we produced 2-O- and 6-O-desulfated heparins. These derivatives were analyzed for the capacity to inhibit hepcidin expression in hepatic HepG2 cells and in mice. The two approaches produced consistent results and showed that the anti-hepcidin activity strongly decreases with molecular weight below 7 kD, with high N-acetylation and after 2-O and 6-O desulfation. The high sulfation and high molecular weight properties for efficient anti-hepcidin activity suggest that heparin is involved in multiple binding sites. PMID:26955355

  10. High Sulfation and a High Molecular Weight Are Important for Anti-hepcidin Activity of Heparin

    PubMed Central

    Asperti, Michela; Naggi, Annamaria; Esposito, Emiliano; Ruzzenenti, Paola; Di Somma, Margherita; Gryzik, Magdalena; Arosio, Paolo; Poli, Maura

    2016-01-01

    Heparins are efficient inhibitors of hepcidin expression even in vivo, where they induce an increase of systemic iron availability. Heparins seem to act by interfering with BMP6 signaling pathways that control the expression of liver hepcidin, causing the suppression of SMAD1/5/8 phosphorylation. The anti-hepcidin activity persists also when the heparin anticoagulant property is abolished or reduced by chemical reactions of oxidation/reduction (glycol-split, Gs-Heparins) or by high sulfation (SS-Heparins), but the structural characteristics needed to optimize this inhibitory activity have not been studied in detail. To this aim we analyzed three different heparins (Mucosal Heparin, the Glycol split RO-82, the partially desulfated glycol-split RO-68 and the oversulfated SSLMWH) and separated them in fractions of molecular weight in the range 4–16 kD. Since the distribution of the negative charges in heparins contributes to the activity, we produced 2-O- and 6-O-desulfated heparins. These derivatives were analyzed for the capacity to inhibit hepcidin expression in hepatic HepG2 cells and in mice. The two approaches produced consistent results and showed that the anti-hepcidin activity strongly decreases with molecular weight below 7 kD, with high N-acetylation and after 2-O and 6-O desulfation. The high sulfation and high molecular weight properties for efficient anti-hepcidin activity suggest that heparin is involved in multiple binding sites. PMID:26955355

  11. Stable, concentrated solutions of high molecular weight polyaniline and articles therefrom

    DOEpatents

    Mattes, Benjamin R.; Wang, Hsing-Lin

    1999-11-09

    Stable, concentrated solutions of high molecular weight polyaniline. In order to process high quality fibers and other articles possessing good mechanical properties, it is known that solution concentrations of the chosen polymer should be in the range from 15-30% (w/w). Moreover, it is desirable to use the highest molecular weight consistent with the solubility properties of the polymer. However, such solutions are inherently unstable, forming gels before processing can be achieved. The present invention describes the addition gel inhibitors (GIs) to the polymer solution, thereby permitting high concentrations (between 15% and 30% (w/w)) of high molecular weight ((M.sub.w)>120,000, and (M.sub.n)>30,000) emeraldine base (EB) polyaniline to be dissolved. Secondary amines have been used for this purpose in concentrations which are small compared to those which might otherwise be used in a cosolvent role therefor. The resulting solutions are useful for generating excellent fibers, films, coatings and other objects, since the solutions are stable for significant time periods, and the GIs are present in too small concentrations to cause polymer deterioration. It is demonstrated that the GIs found to be useful do not act as cosolvents, and that gelation times of the solutions are directly proportional to the concentration of GI. In particular, there is a preferred concentration of GI, which if exceeded causes structural and electrical conductivity degradation of resulting articles. Heating of the solutions significantly improves solubility.

  12. Stable, concentrated solutions of high molecular weight polyaniline and articles therefrom

    DOEpatents

    Mattes, Benjamin R.; Wang, Hsing-Lin

    2000-01-01

    Stable, concentrated solutions of high molecular weight polyaniline. In order to process high quality fibers and other articles possessing good mechanical properties, it is known that solution concentrations of the chosen polymer should be in the range from 15-30% (w/w). Moreover, it is desirable to use the highest molecular weight consistent with the solubility properties of the polymer. However, such solutions are inherently unstable, forming gels before processing can be achieved. The present invention describes the addition gel inhibitors (GIs) to the polymer solution, thereby permitting high concentrations (>15% (w/w)) of high molecular weight ((M.sub.w)>120,000, and (M.sub.n)>30,000) emeraldine base (EB) polyaniline to be dissolved. Secondary amines have been used for this purpose in concentrations which are small compared to those which might otherwise be used in a cosolvent role therefor. The resulting solutions are useful for generating excellent fibers, films, coatings and other objects, since the solutions are stable for significant time periods, and the GIs are present in too small concentrations to cause polymer deterioration. It is demonstrated that the GIs found to be useful do not act as cosolvents, and that gelation times of the solutions are directly proportional to the concentration of GI. In particular, there is a preferred concentration of GI, which if exceeded causes structural and electrical conductivity degradation of resulting articles. Heating of the solutions significantly improves solubility.

  13. Molecular modeling study of dihydrofolate reductase inhibitors. Molecular dynamics simulations, quantum mechanical calculations, and experimental corroboration.

    PubMed

    Tosso, Rodrigo D; Andujar, Sebastian A; Gutierrez, Lucas; Angelina, Emilio; Rodríguez, Ricaurte; Nogueras, Manuel; Baldoni, Héctor; Suvire, Fernando D; Cobo, Justo; Enriz, Ricardo D

    2013-08-26

    A molecular modeling study on dihydrofolate reductase (DHFR) inhibitors was carried out. By combining molecular dynamics simulations with semiempirical (PM6), ab initio, and density functional theory (DFT) calculations, a simple and generally applicable procedure to evaluate the binding energies of DHFR inhibitors interacting with the human enzyme is reported here, providing a clear picture of the binding interactions of these ligands from both structural and energetic viewpoints. A reduced model for the binding pocket was used. This approach allows us to perform more accurate quantum mechanical calculations as well as to obtain a detailed electronic analysis using the quantum theory of atoms in molecules (QTAIM) technique. Thus, molecular aspects of the binding interactions between inhibitors and the DHFR are discussed in detail. A significant correlation between binding energies obtained from DFT calculations and experimental IC₅₀ values was obtained, predicting with an acceptable qualitative accuracy the potential inhibitor effect of nonsynthesized compounds. Such correlation was experimentally corroborated synthesizing and testing two new inhibitors reported in this paper. PMID:23834278

  14. Molecular response to aromatase inhibitor treatment in primary breast cancer

    PubMed Central

    Mackay, Alan; Urruticoechea, Ander; Dixon, J Michael; Dexter, Tim; Fenwick, Kerry; Ashworth, Alan; Drury, Suzanne; Larionov, Alexey; Young, Oliver; White, Sharon; Miller, William R; Evans, Dean B; Dowsett, Mitch

    2007-01-01

    Background Aromatase inhibitors such as anastrozole and letrozole are highly effective suppressants of estrogen synthesis in postmenopausal women and are the most effective endocrine treatments for hormone receptor positive breast cancer in such women. Little is known of the molecular effects of these agents on human breast carcinomas in vivo. Methods We randomly assigned primary estrogen receptor positive breast cancer patients to treatment with anastrozole or letrozole for 2 weeks before surgery. Expression profiling using cDNA arrays was conducted on pretreatment and post-treatment biopsies. Sample pairs from 34 patients provided sufficient RNA for analysis. Results Profound changes in gene expression were seen with both aromatase inhibitors, including many classical estrogen-dependent genes such as TFF1, CCND1, PDZK1 and AGR2, but also many other genes that are likely to represent secondary responses; decrease in the expression of proliferation-related genes were particularly prominent. Many upregulated genes are involved in extracellular matrix remodelling, including collagens and members of the small leucine-rich proteoglycan family (LUM, DCN, and ASPN). No significant differences were seen between letrozole and anastrozole in terms of molecular effects. The gene changes were integrated into a Global Index of Dependence on Estrogen (GIDE), which enumerates the genes changing by at least twofold with therapy. The GIDE varied markedly between tumours and related significantly to pretreatment levels of HER2 and changes in immunohistochemically detected Ki67. Conclusion Our findings identify the transcriptional signatures associated with aromatase inhibitor treatment of primary breast tumours. Larger datasets using this approach should enable identification of estrogen-dependent molecular changes, which are the determinants of benefit or resistance to endocrine therapy. PMID:17555561

  15. [Treatment and prophylaxis of deep venous thrombosis with low molecular weight heparins (meta-analysis of clinical trials)].

    PubMed

    Valiukiene, Laimute; Naudziūnas, Albinas; Unikauskas, Alvydas

    2003-01-01

    Deep-vein thrombosis is a relevant problem of today's medicine, because the risk to fall ill with this pathology is 2-5%; it increases in senior age. Direct and indirect acting thrombin inhibitors are used for treatment and prevention of vein thrombosis. Though great efficiency and safety of new anticoagulants (especially factor Xa inhibitors) were proven in clinical studies, unfractionated heparin and low molecular weight heparins are still most widely used in clinical practice. Low molecular weight heparins are obtained by depolymerizing heparin: its molecular weight is being decreased to 3-7 kDa, or 18-20 monosaccharides. Low molecular weight heparins strongly inhibit Xa coagulation factor and faintly - IIa, that's why their anti-Xa/anti-IIa proportion is >1 (unfractionated heparin = 1); enoxaparine and nadroparine show up the highest proportion. The low weight of these heparins determines good pharmacodynamic characteristics: excellent assimilation from subcutaneous layer, long circulation in plasma, infrequent side effects. Due to these characteristics they are convenient, safe and economically worth using (used by subcutaneous injections, prescribed only 1-2 times per day, coagulation control not required, possibility for patient to be treated at home); therefore low molecular weight heparins are more and more often used in treatment of deep-vein thrombosis and also in primary and secondary prevention. They are one of the most efficacious contemporary anticoagulants, which allow to decrease the deep-vein thrombosis treatment and prevention costs. This article presents literature review about low molecular weight heparins, their appliance in treatment and prophylaxis of deep-vein thrombosis. PMID:12738903

  16. Comparison of antimicrobial activities of newly obtained low molecular weight scorpion chitosan and medium molecular weight commercial chitosan.

    PubMed

    Kaya, Murat; Asan-Ozusaglam, Meltem; Erdogan, Sevil

    2016-06-01

    In this study the antimicrobial activity of low molecular weight (3.22 kDa) chitosan, obtained for the first time from a species belonging to the Scorpiones, was screened against nine pathogenic microorganisms (seven bacteria and two yeasts) and compared with that of medium molecular weight commercial chitosan (MMWCC). It was observed that the antimicrobial activity of the low molecular weight scorpion chitosan (LMWSC) was specific to bacterial species in general rather than gram-negative or gram-positive bacterial groups. It was also determined that LMWSC had a stronger inhibitory effect than the MMWCC, particularly on the bacterium Listeria monocytogenes and the yeast Candida albicans, which are important pathogens for public health. In addition, it was recorded that the MMWCC had a greater inhibitory effect on Bacillus subtilis than LMWSC. According to the results obtained by the disc diffusion method, the antibacterial activity of both LMWSC and MMWCC against B. subtilis and Salmonella enteritidis was higher than the widely used antibiotic Gentamicin (CN, 10 μg/disc). PMID:26702952

  17. Influence of Molecular Weight on the Mechanical Performance of a Thermoplastic Glassy Polyimide

    NASA Technical Reports Server (NTRS)

    Nicholson, Lee M.; Whitley, Karen S.; Gates, Thomas S.; Hinkley, Jeffrey A.

    1999-01-01

    Mechanical Testing of an advanced thermoplastic polyimide (LaRC-TM-SI) with known variations in molecular weight was performed over a range of temperatures below the glass transition temperature. The physical characterization, elastic properties and notched tensile strength were all determined as a function of molecular weight and test temperature. It was shown that notched tensile strength is a strong function of both temperature and molecular weight, whereas stiffness is only a strong function of temperature. A critical molecular weight (Mc) was observed to occur at a weight-average molecular weight (Mw) of approx. 22000 g/mol below which, the notched tensile strength decreases rapidly. This critical molecular weight transition is temperature-independent. Furthermore, inelastic analysis showed that low molecular weight materials tended to fail in a brittle manner, whereas high molecular weight materials exhibited ductile failure. The microstructural images supported these findings.

  18. Impact resistance and fractography in ultra high molecular weight polyethylenes.

    PubMed

    Puértolas, J A; Pascual, F J; Martínez-Morlanes, M J

    2014-02-01

    Highly crosslinked ultra high molecular weight polyethylenes (UHMWPE) stabilized by a remelting process or by the addition of an antioxidant are highly wear resistant and chemically stable. However, these polyethylenes currently used in total joint replacements suffer a loss of mechanical properties, especially in terms of fracture toughness. In this study we analyze the impact behavior of different polyethylenes using an instrumented double notch Izod test. The materials studied are three resins: GUR1050, GUR1020 with 0.1wt% of vitamin E, and MG003 with 0.1wt% of vitamin E. These resins were gamma irradiated at 90kGy, and pre and post-irradiation remelting processes were applied to GUR1050 for two different time periods. Microstructural data were determined by means of differential scanning calorimetry and transmission electron microscopy. Fractography carried out on the impact fracture surfaces and images obtained by scanning electron microscopy after etching indicated the existence of a fringe structure formed by consecutive ductile-brittle and brittle-ductile transitions, which is related to the appearance of discontinuities in the load-deflection curves. A correlation has been made of the macroscopic impact strength results and the molecular chain and microstructural characteristics of these aforementioned materials, with a view to designing future resins with improved impact resistance. The use of UHMWPE resins with low molecular weight or the application of a remelting treatment could contribute to obtain a better impact strength behavior. PMID:24275347

  19. Intramolecular Hydrogen Bonds in Low-Molecular-Weight Polyethylene Glycol.

    PubMed

    Kozlowska, Mariana; Goclon, Jakub; Rodziewicz, Pawel

    2016-04-18

    We used static DFT calculations to analyze, in detail, the intramolecular hydrogen bonds formed in low-molecular-weight polyethylene glycol (PEG) with two to five repeat subunits. Both red-shifted O-H⋅⋅⋅O and blue-shifting C-H⋅⋅⋅O hydrogen bonds, which control the structural flexibility of PEG, were detected. To estimate the strength of these hydrogen bonds, the quantum theory of atoms in molecules was used. Car-Parrinello molecular dynamics simulations were used to mimic the structural rearrangements and hydrogen-bond breaking/formation in the PEG molecule at 300 K. The time evolution of the H⋅⋅⋅O bond length and valence angles of the formed hydrogen bonds were fully analyzed. The characteristic hydrogen-bonding patterns of low-molecular-weight PEG were described with an estimation of their lifetime. The theoretical results obtained, in particular the presence of weak C-H⋅⋅⋅O hydrogen bonds, could serve as an explanation of the PEG structural stability in the experimental investigation. PMID:26864943

  20. [The low-molecular weight antioxidants of microorganisms].

    PubMed

    Skorokhod, I O; Kurdysh, I K

    2014-01-01

    Support of optimum redox-homeostasis in the cells of microorganisms plays a substantial role in the processes of DNA synthesis, respiration, providing of immune and protective reactions, activity of enzymes, etc. The changes of the redox-status can be accompanied by the increase of the level of reactive oxygen species (ROS) which predetermine the damage of biologically active molecules. Adjusting of ROS concentrations is a very important process in development of microorganisms. Low-molecular antioxidants are effective inhibitors of free-radical processes. The authors of the review present the description of oxidants and consider the ways of origin and consequences of their influence on the living cells. An accent is done on phenomenological description of low-molecular antioxidants. The basic mechanisms of their action are considered. Special attention is given to the question of synergism between these protectors. The detailed study of mechanisms of functioning of low-molecular antioxidants in the cells of microorganisms will allow using these living objects in different spheres of human activity. PMID:25007444

  1. Identification of a 31,500 molecular weight islet cell protease as cathepsin B.

    PubMed Central

    Docherty, K; Carroll, R; Steiner, D F

    1983-01-01

    A method for the preparation of a radioisotopically labeled active-site directed reagent for proteases (125I-Tyr-Ala-Lys-ArgCH2Cl) is described, and an example of its use as a sensitive method for identifying trypsin-like proteases is provided. This high specific activity reagent was then used in an attempt to identify proteases in rat islets of Langerhans involved in the conversion of proinsulin to insulin. Previous studies have indicated that the endoprotease involved in proinsulin conversion is a cysteine proteinase and that 125I-Tyr-Ala-Lys-ArgCH2Cl affinity labels an islet crude granule fraction protein having a molecular weight of 31,500. Here we demonstrate, using a probe of higher specific activity, that the major affinity-labeled proteins of the islet crude granule fraction, when displayed by sodium dodecyl sulfate gel electrophoresis, have molecular weights of approximately 39,000 (5%), 31,500 (53%), and 5,000-6,000 (37%), with several other minor proteins (less than 5%) also labeled. The two predominant labeled proteins were mainly soluble rather than membrane bound, and they exhibited patterns of competition with various inhibitors that were similar to the pattern shown by the conversion of proinsulin to insulin in vitro. A rabbit antibody to rat liver cathepsin B immunoprecipitated both affinity-labeled 31,500 and 5,000-6,000 molecular weight proteins, and on the basis of this and structural considerations the 31,500 molecular weight cysteine protease is identified as cathepsin B. The 5,000-6,000 molecular weight peptide is an NH2-terminal, active site cysteine-containing, proteolytic fragment of the 31,500 molecular weight protein. Because cathepsin B is not per se a candidate for the proinsulin convertase because of its excessively broad substrate specificity, these studies suggest that a similar enzyme or a modified form of this enzyme is active within the secretory progranules, whereas the more typical cathepsin B may be largely confined to

  2. Diffusion of low molecular weight siloxane from bulk to surface

    SciTech Connect

    Homma, H.; Kuroyagi, T.; Mirley, C.L.; Ronzello, J.; Boggs, S.A.

    1996-12-31

    Silicone-based materials for outdoor insulators have the advantage that low molecular weight (LMW) components migrate through the material and coat the surface, thereby restoring hydrophobicity over a period of hours. By measuring the infrared (IR) absorption of siloxane migrating to the silicone surface through a thin carbon coating, the aspect of the LMW siloxane migration was observed as a real time plot and the time constant of the migration was calculated. According to the time dependence of IR-absorbance, the migration mostly saturated within only 12 hours after the carbon coating was applied. Also, the time constant showed a dependence on the concentration of added filler in the silicone samples.

  3. Conformations of Low-Molecular-Weight Lignin Polymers in Water.

    PubMed

    Petridis, Loukas; Smith, Jeremy C

    2016-02-01

    Low-molecular-weight lignin binds to cellulose during the thermochemical pretreatment of biomass for biofuel production, which prevents the efficient hydrolysis of the cellulose to sugars. The binding properties of lignin are influenced strongly by the conformations it adopts. Here, we use molecular dynamics simulations in aqueous solution to investigate the dependence of the shape of lignin polymers on chain length and temperature. Lignin is found to adopt collapsed conformations in water at 300 and 500 K. However, at 300 K, a discontinuous transition is found in the shape of the polymer as a function of the chain length. Below a critical degree of polymerization, Nc =15, the polymer adopts less spherical conformations than above Nc. The transition disappears at high temperatures (500 K) at which only spherical shapes are adopted. An implication relevant to cellulosic biofuel production is that lignin will self-aggregate even at high pretreatment temperatures. PMID:26763657

  4. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors.

    PubMed

    Loftus, T M; Jaworsky, D E; Frehywot, G L; Townsend, C A; Ronnett, G V; Lane, M D; Kuhajda, F P

    2000-06-30

    With the escalation of obesity-related disease, there is great interest in defining the mechanisms that control appetite and body weight. We have identified a link between anabolic energy metabolism and appetite control. Both systemic and intracerebroventricular treatment of mice with fatty acid synthase (FAS) inhibitors (cerulenin and a synthetic compound C75) led to inhibition of feeding and dramatic weight loss. C75 inhibited expression of the prophagic signal neuropeptide Y in the hypothalamus and acted in a leptin-independent manner that appears to be mediated by malonyl-coenzyme A. Thus, FAS may represent an important link in feeding regulation and may be a potential therapeutic target. PMID:10875926

  5. Synthesis of high molecular weight PEO using non-metal initiators

    DOEpatents

    Yang, Jin; Sivanandan, Kulandaivelu; Pistorino, Jonathan; Eitouni, Hany Basam

    2015-05-19

    A new synthetic method to prepare high molecular weight poly(ethylene oxide) with a very narrow molecular weight distribution (PDI<1.5) is described. The method involves a metal free initiator system, thus avoiding dangerous, flammable organometallic compounds.

  6. 21 CFR 172.820 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ethylene oxide and water with a mean molecular weight of 200 to 9,500. (2) It contains no more than 0.2... the total ethylene and diethylene glycol content of polyethylene glycols having mean molecular weights... and diethylene glycol content of polyethylene glycols having mean molecular weights below...

  7. 21 CFR 172.820 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ethylene oxide and water with a mean molecular weight of 200 to 9,500. (2) It contains no more than 0.2... the total ethylene and diethylene glycol content of polyethylene glycols having mean molecular weights... and diethylene glycol content of polyethylene glycols having mean molecular weights below...

  8. Molecular weight characterization of virgin and explanted polyester arterial prostheses.

    PubMed

    Maarek, J M; Guidoin, R; Aubin, M; Prud'homme, R E

    1984-10-01

    The macromolecular properties of 17 virgin commercial arterial prostheses and a series of explanted prostheses, both manufactured from poly(ethylene terephthalate) (PET) yarns, have been studied by gel permeation chromatography (GPC) and by differential scanning calorimetry (DSC). Only small differences were found between the average molecular weights and the degree of crystallinity of the unused reference grafts. A broadening of the DSC curves was observed for the prostheses containing texturized yarns compared with those made solely from flat, untexturized yarns. This broadening may be due to greater heterogeneity of the crystal sizes caused by the texturizing process and to the use of two or more different yarns with dissimilar thermal histories in the same prosthesis. Average molecular weights of the explant series were significantly lower than those of the corresponding reference grafts but almost time independent. The polydispersity index and the degree of crystallinity of the explants remained constant as a function of time. These results are discussed in regard to others available in the literature. PMID:6242474

  9. LARC-TPI 1500 series controlled molecular weight polyimide

    NASA Technical Reports Server (NTRS)

    Progar, Donald; St. Clair, Terry; Burks, Harold; Gautreaux, Carol; Yamaguchi, Akihiro

    1990-01-01

    LARC-TPI, a linear high temperature thermoplastic polyimide, was developed several years ago at NASA Langley Research Center. This material has been commercialized by Mitsui Toatsu Chemicals, Inc., Tokyo, Japan, as a varnish and powder. More recently, a melt-extruded film of a controlled molecular weight of this same polymer has been supplied to NASA Langley Research Center for evaluation. This new form, called LARC-TPI 1500 series, has been prepared in three molecular weights - high, medium and low flow polymers. The subject of this investigation deals with the rheological properties of the high and medium flow powders and the adhesive properties of the medium flow melt-extruded film. Rheological studies indicate that the high and medium flow forms of the polymer fall in the flow range of injection moldable materials. Adhesive data generated on the medium flow extruded film shows this form to be well suited for structural adhesive bonding. The data are as good or better than that for LARC-TPI data of previous studies.

  10. Determination of molecular weight distributions in native and pretreated wood.

    PubMed

    Leskinen, Timo; Kelley, Stephen S; Argyropoulos, Dimitris S

    2015-03-30

    The analysis of native wood components by size-exclusion chromatography (SEC) is challenging. Isolation, derivatization and solubilization of wood polymers is required prior to the analysis. The present approach allowed the determination of molecular weight distributions of the carbohydrates and of lignin in native and processed woods, without preparative component isolation steps. For the first time a component selective SEC analysis of sawdust preparations was made possible by the combination of two selective derivatization methods, namely; ionic liquid assisted benzoylation of the carbohydrate fraction and acetobromination of the lignin in acetic acid media. These were optimized for wood samples. The developed method was thus used to examine changes in softwood samples after degradative mechanical and/or chemical treatments, such as ball milling, steam explosion, green liquor pulping, and chemical oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The methodology can also be applied to examine changes in molecular weight and lignin-carbohydrate linkages that occur during wood-based biorefinery operations, such as pretreatments, and enzymatic saccharification. PMID:25563943

  11. Ice Nucleation by High Molecular Weight Organic Compounds

    NASA Astrophysics Data System (ADS)

    Cantrell, W.

    2003-12-01

    Deep convection in the tropics is frequently associated with biomass burning. Recent work has suggested that the size of ice crystals in the anvils of tropical cumulonimbus clouds may be affected by biomass burning, though the mechanism for such an effect is uncertain (Sherwood, 2002). We will present results of an investigation of the role that high molecular weight organic compounds, known to be produced in biomass burning (Elias et al., 1999), may play in tropical cirrus anvils through heterogeneous nucleation of ice. In particular, we examine the mechanisms underlying heterogeneous nucleation of ice by films of long chain alcohols by studying the interaction of the alcohols and water/ice using temperature controlled, Attenuated Total Reflection - Fourier Transform Infrared spectroscopy. The mechanisms are interpreted in the context of recent criticisms of some aspects of classical nucleation theory (Seeley and Seidler, 2001; Oxtoby, 1998). References V. Elias, B. Simoneit, A. Pereira, J. Cabral, and J. Cardoso, Detection of high molecular weight organic tracers in vegetation smoke samples by high-temperature gas chromatography-mass spectrometry. Environ. Sci. Tecnol., 33, 2369-2376, 1999. D. Oxtoby, Nucleation of first-order phase transitions. Acc. Chem. Res., 31, 91-97, 1998. L. Seeley and G. Seidler, Preactivation in the nucleation of ice by Langmuir films of aliphatic alcohols. J. Chem. Phys., 114, 10464-10470, 2001. S. Sherwood, Aerosols and ice particle size in tropical cumulonimbus. J. Climate, 15, 1051-1063, 2002.

  12. Viscoelastic Behavior of Low Molecular Weight Sulfonated Polystyrene Ionomers

    NASA Astrophysics Data System (ADS)

    Zhao, Hongying

    Ionomers are those hydrophobic polymers having small amounts of bonded ionic groups. The introduction of the ionic groups into polymer chain produces large changes in the physical, mechanical and rheological properties of the parent polymer. Characterization of the effect of the ionic interactions on the rheology is complicated by the difficulty in separating effects due to molecular entanglements and the ionic interactions. In this study, low molecular weight (Mw=4000) sulfonated polystyrene (SPS) was used to study the dynamic and steady shear rheology of SPS ionomers. The polymer chain length used was far below the entanglement molecular weight of polystyrene and effects of molecular entanglements will be absent. Any polymer chain entanglements or lengthening behavior on the melt rheology should be due to the ionic interactions. Random SPS ionomers with two sulfonation levels were examined, 2.5 and 4.8 mol%, which corresponded, respectively, to one and two sulfonate groups per chain on average. The metal counterions was varied across the alkali metal series of the periodic table. Morphology of the ionomer was characterized by using small angle x-ray scattering (SAXS) analysis, and dynamic and steady shear measurements were performed to investigate rheological behavior of the ionomers. Glass transition temperatures of the ionomers increased with increasing ion concentration but were insensitive to cation used. The scattering peak in SAXS indicates the existence of the nanophase separated ionic clusters. The strong ionic nanophase persist up to very high temperatures and is not sensitive to the external stress. Time-temperature superposition (TTS) of G' worked reasonably well while TTS of G" failed for most ionomers. Ionic interactions increased the terminal relaxation time of the melts as much as seven orders of magnitude greater than the unentangled PS melt. The zero shear viscosity and first normal stress coefficients scaled with cq/a, where c was the

  13. Trypsin inhibitor from tamarindus indica L. seeds reduces weight gain and food consumption and increases plasmatic cholecystokinin levels

    PubMed Central

    do Nascimento Campos Ribeiro, Joycellane Alline; Serquiz, Alexandre Coellho; dos Santos Silva, Priscila Fabíola; Barbosa, Patrícia Batista Barra Medeiros; Sampaio, Tarcísio Bruno Montenegro; de Araújo, Raimundo Fernandes; de Oliveira, Adeliana Silva; Machado, Richele Janaina Araújo; Maciel, Bruna Leal Lima; Uchôa, Adriana Ferreira; dos Santos, Elizeu Antunes; de Araújo Morais, Ana Heloneida

    2015-01-01

    OBJECTIVES: Seeds are excellent sources of proteinase inhibitors, some of which may have satietogenic and slimming actions. We evaluated the effect of a trypsin inhibitor from Tamarindus indica L. seeds on weight gain, food consumption and cholecystokinin levels in Wistar rats. METHODS: A trypsin inhibitor from Tamarindus was isolated using ammonium sulfate (30–60%) following precipitation with acetone and was further isolated with Trypsin-Sepharose affinity chromatography. Analyses were conducted to assess the in vivo digestibility, food intake, body weight evolution and cholecystokinin levels in Wistar rats. Histological analyses of organs and biochemical analyses of sera were performed. RESULTS: The trypsin inhibitor from Tamarindus reduced food consumption, thereby reducing weight gain. The in vivo true digestibility was not significantly different between the control and Tamarindus trypsin inhibitor-treated groups. The trypsin inhibitor from Tamarindus did not cause alterations in biochemical parameters or liver, stomach, intestine or pancreas histology. Rats treated with the trypsin inhibitor showed significantly elevated cholecystokinin levels compared with animals receiving casein or water. CONCLUSION: The results indicate that the isolated trypsin inhibitor from Tamarindus reduces weight gain by reducing food consumption, an effect that may be mediated by increased cholecystokinin. Thus, the potential use of this trypsin inhibitor in obesity prevention and/or treatment should be evaluated. PMID:25789523

  14. Mechanical Properties of LaRC(tm) SI Polymer for a Range of Molecular Weights

    NASA Technical Reports Server (NTRS)

    Whitley, Karen S.; Gates, Thomas S.; Hinkley, Jeffrey A.; Nicholson, Lee M.

    2000-01-01

    Mechanical testing of an advanced polyimide resin (LaRC(tm)-SI) with known variations in molecular weight was performed over a range of temperatures below the glass transition temperature. Elastic and inelastic properties were characterized as a function of molecular weight and test temperature. It was shown that notched tensile strength is a strong function of both temperature and molecular weight, whereas stiffness is only a strong function of temperature. The combined analysis of calculated yield stress and notched tensile strength indicated that low molecular weight materials tended to fail in a brittle manner, whereas high molecular weight materials exhibited ductile failure. The microphotographs of the failure surfaces also supported these findings.

  15. Tubulin inhibitors: pharmacophore modeling, virtual screening and molecular docking

    PubMed Central

    Niu, Miao-miao; Qin, Jing-yi; Tian, Cai-ping; Yan, Xia-fei; Dong, Feng-gong; Cheng, Zheng-qi; Fida, Guissi; Yang, Man; Chen, Haiyan; Gu, Yue-qing

    2014-01-01

    Aim: To construct a quantitative pharmacophore model of tubulin inhibitors and to discovery new leads with potent antitumor activities. Methods: Ligand-based pharmacophore modeling was used to identify the chemical features responsible for inhibiting tubulin polymerization. A set of 26 training compounds was used to generate hypothetical pharmacophores using the HypoGen algorithm. The structures were further validated using the test set, Fischer randomization method, leave-one-out method and a decoy set, and the best model was chosen to screen the Specs database. Hit compounds were subjected to molecular docking study using a Molecular Operating Environment (MOE) software and to biological evaluation in vitro. Results: Hypo1 was demonstrated to be the best pharmacophore model that exhibited the highest correlation coefficient (0.9582), largest cost difference (70.905) and lowest RMSD value (0.6977). Hypo1 consisted of one hydrogen-bond acceptor, a hydrogen-bond donor, a hydrophobic feature, a ring aromatic feature and three excluded volumes. Hypo1 was validated with four different methods and had a goodness-of-hit score of 0.81. When Hypo1 was used in virtual screening of the Specs database, 952 drug-like compounds were revealed. After docking into the colchicine-binding site of tubulin, 5 drug-like compounds with the required interaction with the critical amino acid residues and the binding free energies <-4 kcal/mol were selected as representative leads. Compounds 1 and 3 exhibited inhibitory activity against MCF-7 human breast cancer cells in vitro. Conclusion: Hypo1 is a quantitative pharmacophore model for tubulin inhibitors, which not only provides a better understanding of their interaction with tubulin, but also assists in discovering new potential leads with antitumor activities. PMID:24909516

  16. Molecular Pathways: Molecular Basis for Sensitivity and Resistance to JAK Kinase Inhibitors

    PubMed Central

    Meyer, Sara C.; Levine, Ross L.

    2014-01-01

    Janus kinases (JAK) are the mediators of a variety of cytokine signals via their cognate receptors that result in activation of intracellular signaling pathways. Alterations in JAK1, JAK2, JAK3 and TYK2 signaling contribute to different disease states, and dysregulated JAK-STAT signaling is associated with hematological malignancies, autoimmune disorders and immune-deficient conditions. Genetic alterations of JAK2 occur in the majority of patients with myeloproliferative neoplasms (MPN) and occur in a subset of patients with acute leukemias. JAK-mediated signaling critically relies on STAT transcription factors, and on activation of the MAPK and PI3K/Akt signaling axes. Hyperactive JAK at the apex of these potent oncogenic signaling pathways therefore represents an important target for small molecule kinase inhibitors in different disease states. The JAK1/2 inhibitor ruxolitinib and the JAK3 inhibitor tofacitinib were recently approved for the treatment of myelofibrosis and rheumatoid arthritis, respectively and additional ATP-competitive JAK inhibitors are in clinical development. Although these agents show clinical activity, the ability of these JAK inhibitors to induce clinical/molecular remissions in hematological malignancies appears limited and resistance upon chronic drug exposure is seen. Alternative modes of targeting JAK2 such as allosteric kinase inhibition or HSP-90 inhibition are under evaluation as is the use of histone deacetylase inhibitors. Combination therapy approaches integrating inhibition of STAT, PI3K/Akt and MAPK pathways with JAK kinase inhibitors might be critical to overcome malignancies characterized by dysregulated JAK signaling. PMID:24583800

  17. Molecular weight degradation and rheological properties of schizophyllan under ultrasonic treatment.

    PubMed

    Zhong, Kui; Zhang, Qi; Tong, Litao; Liu, Liya; Zhou, Xianrong; Zhou, Sumei

    2015-03-01

    Molecular weight degradation effects of schizophyllan (SPG) under ultrasonic treatments were investigated in this study. The degradation product was treated by alcohol fractional precipitation technology, and the molecular weight and rheological properties of ultrasonic-treated SPG (USPG) fractions were evaluated. Average molecular weight of SPG decreased significantly after ultrasonic treatments, and degradation product had more narrow distribution of molecular weight. The molecular weight degradation kinetics of SPG is adequately described by a second-order reaction. USPG fractions with different molecular weight were obtained by fractional precipitation for final alcohol concentration fractions 0-40%, 40-60% and 60-80%, respectively. USPG fractions had near-Newtonian flow behaviors, and USPG₈₀% exhibited viscous responses over the entire accessible frequency range. Therefore, ultrasonic treatment is a viable modification technology for SPG and other polymer materials with high molecular weight. PMID:25263766

  18. Hydrophobic composition based on mixed-molecular weight polyethylene

    NASA Astrophysics Data System (ADS)

    Gorlenko, Nikolay; Debelova, Natalya; Sarkisov, Yuriy; Volokitin, Gennadiy; Zavyalova, Elena; Lapova, Tatyana

    2016-01-01

    The paper presents investigations of compositions based on low and high molecular weight polyethylene so as to synthesize a hydrophobic composition for moisture protection of timber. X-ray phase analysis and measurements of the tear-off force of hydrophobic coating needed to apply to the timber surface and the limiting wetting angle are carried out to detect the hydrophobic, adhesive, electrophysical, and physicochemical properties of compositions. Kinetic dependencies are given for moisture absorption of timber specimens. It is shown that the preliminary formation of the texture by the surface patterning or its treatment with low-temperature plasma with the following protective coating results in the improvement of hydrophobic properties of the suggested compositions. These compositions can be used in the capacity of water repellents to protect building materials from moisture including restoration works.

  19. Ultra-high molecular weight silphenylene-siloxane polymers

    NASA Technical Reports Server (NTRS)

    Patterson, W. J.; Hundley, N. H.; Ludwick, L. M.

    1984-01-01

    Silphenylene-siloxane copolymers with molecular weights above one million were prepared using a two stage polymerization technique. The technique was successfully scaled up to produce 50 grams of this high polymer in a single run. The reactive monomer approach was also investigated using the following aminosilanes: bis(dimethylamino)dimethylsilane, N,N-bis(pyrrolidinyl)dimethylsilane and N,N-bis(gamma-butyrolactam)dimethylsilane). Thermal analyses were performed in both air and nitrogen. The experimental polymers decomposed at 540 to 562 C, as opposed to 408 to 426 C for commercial silicones. Differential scanning calorimetry showed a glass transition (Tg) at -50 to -55 C for the silphenylene-siloxane copolymer while the commercial silicones had Tg's at -96 to -112 C.

  20. Apparatus and method of determining molecular weight of large molecules

    DOEpatents

    Fuerstenau, Stephen; Benner, W. Henry; Madden, Norman; Searles, William

    1998-01-01

    A mass spectrometer determines the mass of multiply charged high molecular weight molecules. This spectrometer utilizes an ion detector which is capable of simultaneously measuring the charge z and transit time of a single ion as it passes through the detector. From this transit time, the velocity of the single ion may then be derived, thus providing the mass-to-charge ratio m/z for a single ion which has been accelerated through a known potential. Given z and m/z, the mass m of the single ion can then be calculated. Electrospray ions with masses in excess of 1 MDa and charge numbers greater than 425 e.sup.- are readily detected. The on-axis single ion detection configuration enables a duty cycle of nearly 100% and extends the practical application of electrospray mass spectrometry to the analysis of very large molecules with relatively inexpensive instrumentation.

  1. Apparatus and method of determining molecular weight of large molecules

    DOEpatents

    Fuerstenau, S.; Benner, W.H.; Madden, N.M.; Searles, W.

    1998-06-23

    A mass spectrometer determines the mass of multiply charged high molecular weight molecules. This spectrometer utilizes an ion detector which is capable of simultaneously measuring the charge z and transit time of a single ion as it passes through the detector. From this transit time, the velocity of the single ion may then be derived, thus providing the mass-to-charge ratio m/z for a single ion which has been accelerated through a known potential. Given z and m/z, the mass m of the single ion can then be calculated. Electrospray ions with masses in excess of 1 MDa and charge numbers greater than 425 e{sup {minus}} are readily detected. The on-axis single ion detection configuration enables a duty cycle of nearly 100% and extends the practical application of electrospray mass spectrometry to the analysis of very large molecules with relatively inexpensive instrumentation. 14 figs.

  2. Lipid solubility and molecular weight: whose idea was that.

    PubMed

    Kasting, G B

    2013-01-01

    Gene Cooper was a bright theoretician, a skilled product developer, and a motivational leader who applied his talents to the skin science area early in his career. His work led to the development of finite dose skin absorption models, chemical penetration enhancer technologies and quantitative structure-penetration relationships for chemicals contacting human skin. His ideas regarding the impact of molecular weight and lipid solubility on skin transport catalyzed the later development by Potts and Guy of the first successful skin permeability model. But Gene's most important contribution to the field was as a scientific role model and an inspirational leader who launched the careers of several young scientists, including the author of this article. PMID:23921116

  3. Soluble, High Molecular Weight Polysilsesquioxanes with Carboxylate Functionalities

    SciTech Connect

    RAHIMIAN,KAMYAR; LOY,DOUGLAS A.; WHEELER,DAVID R.

    2000-07-14

    Trialkoxysilyl-containing monomers of the type (RO){sub 3}Si(CH{sub 2}){sub 3}C(O)OtBu (R = Me, Et) were prepared by hydrosilation of the corresponding vinylic tert-butyl esters CH{sub 3}CHCH{sub 2}C(O)OtBu. Acid- or base-catalyzed polymerization of the monomers leads to very high molecular weight polymers with relatively narrow polydispersities. The polymerization results in complete condensation of the alkoxy groups while the tert-butyl ester functionality remains fully intact. Partial or full deprotection of the tert-butyl group can easily be achieved to yield the corresponding carboxylic acid polymers. The ester and carboxylic acid functionalities of these new materials allow for their potential use in a variety of applications such as scavenging of heavy metals.

  4. Diffuse alveolar hemorrhage associated with low molecular weight heparin

    PubMed Central

    Hayashi, Shinichi; Maruoka, Shuichiro; Nakagawa, Yoshiko; Takahashi, Noriaki; Hashimoto, Shu

    2013-01-01

    Diffuse alveolar hemorrhage (DAH) has a varied etiology, including anticoagulation drugs. There is conflicting evidence whether low molecular weight heparin (LMWH) has a low risk of bleeding complications compared to unfractionated heparin. We report here a case of DAH in a 74-year-old woman who was administered enoxaparin, a LMWH, after bilateral total knee arthroplasty. Although congestive heart failure after blood transfusion and fluid infusion could in part be associated with the bleeding, LMWH may be a major cause of DAH since the patient quickly recovered after its cessation. DAH should be of concern when acute respiratory failure with ground-glass shadow develops in both lungs during anticoagulation therapy with LMWH. PMID:25473525

  5. Massive choroidal hemorrhage associated with low molecular weight heparin therapy.

    PubMed

    Neudorfer, M; Leibovitch, I; Goldstein, M; Loewenstein, A

    2002-04-01

    An 84-year-old woman with unstable angina pectoris was treated with subcutaneous enoxaparine (Clexane) for several days before presenting with severe pain and decreased vision in her left eye. The intraocular pressure was 70 mmHg, and fundus examination showed a pigmented choroidal lesion and associated choroidal and retinal detachment. Ultrasonography was consistent with choroidal hemorrhage, and she was diagnosed as having acute glaucoma secondary to massive subchoroidal hemorrhage. Medical control of the intraocular pressure resulted in a significant clinical improvement. Intraocular hemorrhage and angle-closure glaucoma are rare and previously unreported complications in patients treated with low molecular weight heparin. It is important to be aware of this ocular complication as these drugs are so often used. PMID:11943940

  6. Dairy Wastewater Treatment Using Low Molecular Weight Crab Shell Chitosan

    NASA Astrophysics Data System (ADS)

    Geetha Devi, M.; Dumaran, Joefel Jessica; Feroz, S.

    2012-08-01

    The investigation of possible use of low molecular weight crab shell chitosan (MW 20 kDa) in the treatment of dairy waste water was studied. Various experiments have been carried out using batch adsorption technique to study the effects of the process variables, which include contact time, stirring speed, pH and adsorbent dosage. Treated effluent characteristics at optimum condition showed that chitosan can be effectively used as adsorbent in the treatment of dairy wastewater. The optimum conditions for this study were at 150 mg/l of chitosan, pH 5 and 50 min of mixing time with 50 rpm of mixing speed. Chitosan showed the highest performance under these conditions with 79 % COD, 93 % turbidity and 73 % TSS reduction. The result showed that chitosan is an effective coagulant, which can reduce the level of COD, TSS and turbidity in dairy industry wastewater.

  7. [Anaphylactic reactions to low-molecular weight chemicals].

    PubMed

    Nowak, Daria; Panaszek, Bernard

    2015-01-01

    Low-molecular weight chemicals (haptens) include a large group of chemical compounds occurring in work environment, items of everyday use (cleaning products, clothing, footwear, gloves, furniture), jewelry (earrings, bracelets), drugs, especially in cosmetics. They cause type IV hypersensitive reactions. During the induction phase of delayed-type hypersensitivity, haptens form complexes with skin proteins. After internalization through antigen presenting cells, they are bound to MHC class II molecules. Next, they are exposed against specific T-lymphocytes, what triggers activation of Th1 cells mainly. After repeating exposition to that hapten, during effector phase, Th1 induce production of cytokines affecting non-specific inflammatory cells. Usually, it causes contact dermatitis. However, occasionally incidence of immediate generalized reactions after contact with some kinds of haptens is noticed. A question arises, how the hapten does induce symptoms which are typical for anaphylaxis, and what contributes to amplification of this mechanism. It seems that this phenomenon arises from pathomechanism occurring in contact urticaria syndrome in which an anaphylactic reaction may be caused either by contact of sensitized skin with protein antigens, high-molecular weight allergens, or haptens. One of the hypotheses indicates the leading role of basophiles in this process. Their contact with haptens, may cause to release mediators of immediate allergic reaction (histamine, eicosanoids) and to produce cytokines corresponding to Th2 cells profile. Furthermore, Th17 lymphocytes secreting pro-inflammatory interleukin-17 might be engaged into amplifying hypersensitivity into immediate reactions and regulatory T-cells may play role in the process, due to insufficient control of the activity of effector cells. PMID:25661919

  8. Mechanistic information from analysis of molecular weight distributions of starch.

    PubMed

    Castro, Jeffrey V; Dumas, Céline; Chiou, Herbert; Fitzgerald, Melissa A; Gilbert, Robert G

    2005-01-01

    A methodology is developed for interpreting the molecular weight distributions of debranched amylopectin, based on techniques developed for quantitatively and qualitatively finding mechanistic information from the molecular weight distributions of synthetic polymers. If the only events occurring are random chain growth and stoppage (i.e., the rates are independent of degree of polymerization over the range in question), then the number of chains of degree of polymerization N, P(N), is linear in ln P(N) with a negative slope, where the slope gives the ratio of the stoppage and growth rates. This starting point suggests that mechanistic inferences can be made from a plot of lnP against N. Application to capillary electrophoresis data for the P(N) of debranched starch from across the major taxa, from bacteria (Escherichia coli), green algae (Chlamydomonas reinhardtii), mammals (Bos), and flowering plants (Oryza sativa, rice; Zea mays, maize; Triticum aestivum, wheat; Hordeum vulgare, barley; and Solanum tuberosum, potato), gives insights into the biosynthetic pathways, showing the differences and similarities of the alpha-1,4-glucans produced by the various species. Four characteristic regions for storage starch from the higher plants are revealed: (1) an initial increasing region corresponding to the formation of new branches, (2) a linear ln P region with negative slope, indicating random growth and stoppage, (3) a region corresponding to the formation of the crystalline lamellae and subsequent elongation of chains, and (4) a second linear ln P with negative slope region. Each region can be assigned to specific enzymatic processes in starch synthesis, including determining the ranges of degrees of polymerization which are subject to random and nonrandom processes. PMID:16004469

  9. Human neutrophils contain and bind high molecular weight kininogen.

    PubMed Central

    Gustafson, E J; Schmaier, A H; Wachtfogel, Y T; Kaufman, N; Kucich, U; Colman, R W

    1989-01-01

    Because plasma kallikrein activates human neutrophils, and in plasma prekallikrein (PK) circulates complexed with high molecular weight kininogen (HMWK), we determined whether HMWK could mediate kallikrein's association with neutrophils. HMWK antigen (237 +/- 61 ng HMWK/10(8) neutrophils) was present in lysates of washed human neutrophils. Little if any plasma HMWK was tightly bound and nonexchangeable with the neutrophil surface. Human neutrophils were found to possess surface membrane-binding sites for HMWK but no internalization was detected at 37 degrees C. 125I-HMWK binding to neutrophils was dependent upon Zn2+. Binding of 125I-HMWK to neutrophils was specific and 90% reversible. 125I-HMWK binding to neutrophils was saturable with an apparent Kd of 9-18 nM and 40,000-70,000 sites per cell. Upon binding to neutrophils, 125I-HMWK was proteolyzed by human neutrophil elastase (HNE) into lower relative molecular mass derivatives. Furthermore, HMWK found in neutrophils also served as a cofactor for HNE secretion because neutrophils deficient in HMWK have reduced HNE secretion when stimulated in plasma deficient in HMWK or with purified kallikrein. These studies indicate that human neutrophils contain a binding site for HMWK that could serve to localize plasma or neutrophil HMWK on their surface to possibly serve as a receptor for kallikrein and to participate in HNE secretion by this enzyme. Images PMID:2738152

  10. Biosynthesis of high molecular weight polylactosamine-type glycopeptides in rat Zajdela hepatoma ascites cells.

    PubMed

    Saunier, B; Goulut, C; Nato, F; Bourrillon, R

    1989-05-10

    The first steps of the biosynthetic pathway of high molecular weight polylactosamine-type glycopeptides from rat Zajdela hepatoma cells were studied by pulse-chase experiments, biochemical analysis and by inhibition of N-glycosylation. It is clear that this process involves firstly the transfer of a lipid-linked high-mannose oligosaccharide precursor to a protein moiety in a similar way to that of N-linked glycopeptides of a more common size range according to the classical 'cycle of dolichol'. In the presence of enzymes which are inhibitors of the processing of high-mannose oligosaccharide chains, this class of oligosaccharides was considerably increased, whereas polylactosamine chains and lower complex N-linked glycopeptides were concomitantly decreased in the same kinetics and the same ratio. As expected in the presence of N-methyldeoxynojirimycin, which is an alpha-glucosidase inhibitor, high-mannose oligosaccharides remained glycosylated and are mostly of the Glc1-3Man9GlcNAc type. In the presence of swainsonine, which is an alpha-mannosidase (EC 3.2.1.24) inhibitor, these chains were devoid of glucose residues. In addition, some chains displayed hybrid structures. It appears, therefore, that the first steps of the biosynthesis of polylactosamine-type and N-linked oligosaccharides of a more common size range proceed similarly and that differences between their biosynthetic pathways occur during the elongation phase, which leads to their final respective structures. Glycopeptides prepared from the cell surface by mild trypsin treatment as well as from entire cells, previously treated or not by processing inhibitors, display the same gel filtration patterns indicating that modifications in protein glycosylation do not prevent glycoprotein insertion into the cell membrane. PMID:2713399

  11. Anti-heparanase activity of ultra-low-molecular-weight heparin produced by physicochemical depolymerization.

    PubMed

    Achour, Oussama; Poupard, Nicolas; Bridiau, Nicolas; Bordenave Juchereau, Stephanie; Sannier, Fredéric; Piot, Jean-Marie; Fruitier Arnaudin, Ingrid; Maugard, Thierry

    2016-01-01

    Heparanase is an endo-β-D-glucuronidase that plays an important role in cancer progression, in particular during tumor angiogenesis and metastasis. Inhibiting this enzyme is considered as one of the most promising approaches in cancer therapy. Heparin is a complex glycoaminoglycan known as a strong inhibitor of heparanase. It is primarily used in clinical practice for its anticoagulant activities, which may not be compatible with its use as anti-angiogenic agent. In this study, we described the production of ultra-low-molecular-weight heparins (ULMWH) by a physicochemical method that consists in a hydrogen peroxide-catalyzed radical hydrolysis assisted by ultrasonic waves. We assessed the structural characteristics, anticoagulant and anti-heparanase activities of the obtained heparin derivatives and compared them with three commercial low-molecular-weight heparins (LMWH), glycol-split non-anticoagulant heparins and heparins produced by enzymatic methods. ULMWH generated by the physicochemical method were characterized by high anti-heparanase and moderate anticoagulant activities. These heparin derivatives might be potential candidates for cancer therapy when a compromise is needed between anti-heparanase and anticoagulant activities. PMID:26453883

  12. 21 CFR 178.3750 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Polyethylene glycol (mean molecular weight 200-9... molecular weight 200-9,500). Polyethylene glycol identified in this section may be safely used as a... conditions: (a) The additive is an addition polymer of ethylene oxide and water with a mean molecular...

  13. 21 CFR 178.3750 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Polyethylene glycol (mean molecular weight 200-9... molecular weight 200-9,500). Polyethylene glycol identified in this section may be safely used as a... conditions: (a) The additive is an addition polymer of ethylene oxide and water with a mean molecular...

  14. Optimization of parameters for coverage of low molecular weight proteins

    PubMed Central

    Müller, Stephan A.; Kohajda, Tibor; Findeiß, Sven; Stadler, Peter F.; Washietl, Stefan; Kellis, Manolis; von Bergen, Martin

    2010-01-01

    Proteins with molecular weights of <25 kDa are involved in major biological processes such as ribosome formation, stress adaption (e.g., temperature reduction) and cell cycle control. Despite their importance, the coverage of smaller proteins in standard proteome studies is rather sparse. Here we investigated biochemical and mass spectrometric parameters that influence coverage and validity of identification. The underrepresentation of low molecular weight (LMW) proteins may be attributed to the low numbers of proteolytic peptides formed by tryptic digestion as well as their tendency to be lost in protein separation and concentration/desalting procedures. In a systematic investigation of the LMW proteome of Escherichia coli, a total of 455 LMW proteins (27% of the 1672 listed in the SwissProt protein database) were identified, corresponding to a coverage of 62% of the known cytosolic LMW proteins. Of these proteins, 93 had not yet been functionally classified, and five had not previously been confirmed at the protein level. In this study, the influences of protein extraction (either urea or TFA), proteolytic digestion (solely, and the combined usage of trypsin and AspN as endoproteases) and protein separation (gel- or non-gel-based) were investigated. Compared to the standard procedure based solely on the use of urea lysis buffer, in-gel separation and tryptic digestion, the complementary use of TFA for extraction or endoprotease AspN for proteolysis permits the identification of an extra 72 (32%) and 51 proteins (23%), respectively. Regarding mass spectrometry analysis with an LTQ Orbitrap mass spectrometer, collision-induced fragmentation (CID and HCD) and electron transfer dissociation using the linear ion trap (IT) or the Orbitrap as the analyzer were compared. IT-CID was found to yield the best identification rate, whereas IT-ETD provided almost comparable results in terms of LMW proteome coverage. The high overlap between the proteins identified with IT

  15. Low Molecular Weight Norbornadiene Derivatives for Molecular Solar-Thermal Energy Storage.

    PubMed

    Quant, Maria; Lennartson, Anders; Dreos, Ambra; Kuisma, Mikael; Erhart, Paul; Börjesson, Karl; Moth-Poulsen, Kasper

    2016-09-01

    Molecular solar-thermal energy storage systems are based on molecular switches that reversibly convert solar energy into chemical energy. Herein, we report the synthesis, characterization, and computational evaluation of a series of low molecular weight (193-260 g mol(-1) ) norbornadiene-quadricyclane systems. The molecules feature cyano acceptor and ethynyl-substituted aromatic donor groups, leading to a good match with solar irradiation, quantitative photo-thermal conversion between the norbornadiene and quadricyclane, as well as high energy storage densities (396-629 kJ kg(-1) ). The spectroscopic properties and energy storage capability have been further evaluated through density functional theory calculations, which indicate that the ethynyl moiety plays a critical role in obtaining the high oscillator strengths seen for these molecules. PMID:27492997

  16. Application of 1H DOSY for Facile Measurement of Polymer Molecular Weights

    PubMed Central

    Li, Weibin; Chung, Hoyong; Daeffler, Christopher; Johnson, Jeremiah A.; Grubbs, Robert H.

    2012-01-01

    To address the practical issues of polymer molecular weight determination, the first accurate polymer weight-average molecular weight determination method in diverse living/controlled polymerization via DOSY (diffusion-ordered NMR spectroscopy) is reported. Based on the linear correlation between the logarithm of diffusion coefficient (log D) and the molecular weights (log Mw), external calibration curves were created to give predictions of molecular weights of narrowly-dispersed polymers. This method was successfully applied to atom transfer radical polymerization (ATRP), reversible addition–fragmentation chain transfer (RAFT), and ring-opening metathesis polymerization (ROMP), with weight-average molecular weights given by this method closely correlated to those obtained from GPC measurement. PMID:23335819

  17. Molecular assembly for high-performance bivalent nucleic acid inhibitor.

    PubMed

    Kim, Youngmi; Cao, Zehui; Tan, Weihong

    2008-04-15

    It is theorized that multivalent interaction can result in better affinity and selectivity than monovalent interaction in the design of high-performance ligands. Accordingly, biomolecular engineers are increasingly taking advantage of multivalent interactions to fabricate novel molecular assemblies, resulting in new functions for ligands or enhanced performance of existing ligands. Substantial efforts have been expended in using small molecules or epitopes of antibodies for designing multifunctional or better-performing ligands. However, few attempts to use nucleic acid aptamers as functional domains have been reported. In this study, we explore the design of bivalent nucleic acid ligands by using thrombin and its aptamers as the model by which to evaluate its functions. By assembling two thrombin-binding aptamers with optimized design parameters, this assembly has resulted in the successful development of a nucleic acid-based high-performance bivalent protein inhibitor. Our experimentation proved (i) that the simultaneous binding of two aptamers after linkage achieved 16.6-fold better inhibition efficiency than binding of the monovalent ligand and (ii) that such an improvement originated from changes in the kinetics of the binding interactions, with a k(off) rate approximately 1/50 as fast. In addition, the newly generated aptamer assembly is an excellent anticoagulant reagent when tested with different samples. Because this optimized ligand design offers a simple and noninvasive means of accomplishing higher performance from known functional aptamers, it holds promise as a potent antithrombin agent in the treatment of various diseases related to abnormal thrombin activities. PMID:18398007

  18. Molecular Modeling and Design of Arylthioindole Derivatives as Tubulin Inhibitors

    NASA Astrophysics Data System (ADS)

    Liao, Si-yan; Miao, Ti-fang; Chen, Jin-can; Lu, Hai-liang; Zheng, Kang-cheng

    2009-10-01

    Three-dimensional quantitative structure activity relationship (3D-QSAR) and docking studies of a series of arylthioindole derivatives as tubulin inhibitors against human breast cancer cell line MCF-7 have been carried out. An optimal 3D-QSAR model from the comparative molecular field analysis (CoMFA) for training set with significant statistical quality (R2 = 0.898) and predictive ability (q2 = 0.654) was established. The same model was further applied to predict pIC50 values of the compounds in test set, and the resulting predictive correlation coefficient R2(pred) reaches 0.816, further showing that this CoMFA model has high predictive ability. Moreover, the appropriate binding orientations and conformations of these compounds interacting with tubulin are located by docking study, and it is very interesting to find the consistency between the CoMFA field distribution and the 3D topology structure of active site of tubulin. Based on CoMFA along with docking results, some important factors improving the activities of these compounds were discussed in detail and were summarized as follows: the substituents R3-R5 (on the phenyl ring) with higher electronegativity, the substituent R6 with higher electropositivity and bigger bulk, the substituent R7 with smaller bulk, and so on. In addition, five new compounds with higher activities have been designed. Such results can offer useful theoretical references for experimental works.

  19. Investigating molecular dynamics-guided lead optimization of EGFR inhibitors.

    PubMed

    Lavecchia, Martin J; Puig de la Bellacasa, Raimon; Borrell, José I; Cavasotto, Claudio N

    2016-02-15

    The epidermal growth factor receptor (EGFR) is part of an extended family of proteins that together control aspects of cell growth and development, and thus a validated target for drug discovery. We explore in this work the suitability of a molecular dynamics-based end-point binding free energy protocol to estimate the relative affinities of a virtual combinatorial library designed around the EGFR model inhibitor 6{1} as a tool to guide chemical synthesis toward the most promising compounds. To investigate the validity of this approach, selected analogs including some with better and worse predicted affinities relative to 6{1} were synthesized, and their biological activity determined. To understand the binding determinants of the different analogs, hydrogen bonding and van der Waals contributions, and water molecule bridging in the EGFR-analog complexes were analyzed. The experimental validation was in good qualitative agreement with our theoretical calculations, while also a 6-dibromophenyl-substituted compound with enhanced inhibitory effect on EGFR compared to the reference ligand was obtained. PMID:26810832

  20. Adsorption of low molecular weight halocarbons by montmorillonite

    SciTech Connect

    Estes, T.J.; Shah, R.V.; Vilker, V.L. )

    1988-04-01

    Montmorillonite clay from Clay Spur, WY, was found to adsorb several low molecular weight, hydrophobic halocarbons from aqueous solution at sub-parts-per-million levels. The halocarbons studied were trichloroethylene, tetrachloroethylene, hexachloroethane, and dibromochloropropane. When the montmorillonite was treated with sodium citrate-bicarbonate-dithionite (CBD), it adsorbed higher levels of halocarbons than the untreated clay. In addition, the CBD-treated clay exhibited a maximum in halocarbon adsorption around pH 4, while untreated clay showed little variation in adsorption over the pH range 2-10. Adsorption of trichloroethylene was inhibited by low concentrations of sodium chloride (0.01 M or greater) in solution. Aging the CBD-treated clay in water decreased its capacity to adsorb trichloroethylene. Desorption studies showed that the sorption of tetrachloroethylene to CBD-treated clay is an irreversible process when compared to sorption by fumed silica. The ability of montmorillonite to adsorb halocarbons and the instability of the clay in water are postulated to involve changes in the oxide surface coating on the clay.

  1. Association between cationic liposomes and low molecular weight hyaluronic acid.

    PubMed

    Gasperini, Antonio A M; Puentes-Martinez, Ximena E; Balbino, Tiago Albertini; Rigoletto, Thais de Paula; Corrêa, Gabriela de Sá Cavalcanti; Cassago, Alexandre; Portugal, Rodrigo Villares; de La Torre, Lucimara Gaziola; Cavalcanti, Leide P

    2015-03-24

    This work presents a study of the association between low molecular weight hyaluronic acid (16 kDa HA) and cationic liposomes composed of egg phosphatidylcholine (EPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). The cationic liposome/HA complexes were evaluated to determine their mesoscopic structure, average size, zeta potential, and morphology as a function of the amount of HA in the system. Small angle X-ray scattering results revealed that neighboring cationic liposomes either stick together after a partial coating of low concentration HA or disperse completely in excess of HA, but they never assemble as multilamellar vesicles. Cryo-transmission electron microscopy images confirm the existence of unilamellar vesicles and large aggregates of unilamellar vesicles for HA fractions up to 80% (w/w). High concentrations of HA (> 20% w/w) proved to be efficient for coating extruded liposomes, leading to particle complexes with sizes in the nanoscale range and a negative zeta potential. PMID:25730494

  2. Antiaging activity of low molecular weight peptide from Paphia undulate

    NASA Astrophysics Data System (ADS)

    Chen, Xin; Cai, Bingna; Chen, Hua; Pan, Jianyu; Chen, Deke; Sun, Huili

    2013-05-01

    Low molecular weight peptide (LMWP) was prepared from clam Paphia undulate and its antiaging effect on D-galactose-induced acute aging in rats, aged Kunming mice, ultraviolet-exposed rats, and thermally injured rats was investigated. P. undulate flesh was homogenized and digested using papain under optimal conditions, then subjected to Sephadex G-25 chromatography to isolate the LMWP. Administration of LMWP significantly reversed D-galactose-induced oxidative stress by increasing the activities of glutathione peroxidase (GPx) and catalase (CAT), and by decreasing the level of malondialdehyde (MDA). This process was accompanied by increased collagen synthesis. The LMWP prevented photoaging and promoted dermis recovery and remission of elastic fiber hyperplasia. Furthermore, treatment with the LMWP helped to regenerate elastic fibers and the collagen network, increased superoxide dismutase (SOD) in the serum and significantly decreased MDA. Thermal scald-induced inflammation and edema were also relieved by the LWMP, while wound healing in skin was promoted. These results suggest that the LMWP from P. undulate could serve as a new antiaging substance in cosmetics.

  3. Arterial indications for the low molecular weight heparins

    PubMed Central

    Ageno, Walter; Huisman, Menno V

    2001-01-01

    Antithrombotic treatment is of proven importance in patients with acute coronary syndromes. There is now accumulating evidence from several clinical trials in patients with unstable angina pectoris that the low molecular weight heparins (LMWHs) are at least as effective as unfractionated heparin. The LMWHs are easier to use, with the potential to facilitate long-term outpatient treatment. The results of the trials have actually failed to show any clear advantage, however, of the LMWHs over the standard antiplatelet treatment, despite the evidence of a sustained hypercoagulability. Potentially, the use of higher doses of LMWHs could improve the outcomes, but this is as yet unproven and could be associated with unacceptably increased risk of bleeding. During the acute phase of a stroke, aspirin is the first choice of antithrombotic drug because it reduces the risk of recurrent stroke. LMWH cannot be recommended as an antithrombotic agent for the acute treatment of stroke. Prophylactic use of low dose LMWH for the prevention of venous thromboembolism should be considered in every patient with a stroke. PMID:11806802

  4. Preparation and hemostatic property of low molecular weight silk fibroin.

    PubMed

    Lei, Caihong; Zhu, Hailin; Li, Jingjing; Feng, Xinxing; Chen, Jianyong

    2016-04-01

    Effective hemorrhage control becomes increasingly significant in today's military and civilian trauma, while the topical hemostats currently available in market still have various disadvantages. In this study, three low molecular weight silk fibroins (LMSF) were prepared through hydrolysis of silk fibroin in a ternary solvent system of CaCl2/H2O/EtOH solution at different hydrolysis temperatures. Fourier transform infrared spectroscopy analysis showed that the content of β sheet structure in the LMSF decreased with the increase in hydrolysis temperature. The results of thromboelastographic and activated partial thromboplastin time methods showed that the LMSF hydrolyzed at 50 °C can significantly strengthen the coagulation in blood and activate the intrinsic pathway of coagulation cascade. In the murine hepatic injury model, the LMSF hydrolyzed at 50 °C can promote the blood clotting and decrease the blood loss and bleeding time. Based on these results, it can be suggested that the developed LMSF has the excellent hemostatic effect and may be a promising material in clinical hemostatic application. PMID:26732018

  5. Preparation of high-molecular-weight DNA from Drosophila embryos.

    PubMed

    Karpen, Gary H

    2009-07-01

    Standard methods for extracting DNA from cells or organisms (e.g., phenol extraction and ethanol precipitation) produce fragments with an average size of 50-200 kb under optimal conditions. The shearing forces that are applied to DNA in solution during mechanical vortexing or mixing and pipetting produce frequent double-stranded breaks. To prepare high-molecular-weight (HMW) DNA, it is necessary to guard against such damaging forces by performing all extractions and manipulations on DNA that is embedded within a protective matrix. Preparation of HMW DNA from Drosophila embryos is described in detail here because, in our hands, it is the simplest and most reliable protocol and can be used for large- or small-scale preparations. The overall strategy is to purify nuclei, gently embed them in molten agarose, and then extract proteins and perform other enzymatic reactions by transferring the solidified agarose block into the appropriate solutions. Salts, soaps, and enzymes act on the DNA by diffusing through the agarose matrix, while the matrix protects the DNA from shearing forces. PMID:20147219

  6. Photochemical Preparation of a Novel Low Molecular Weight Heparin

    PubMed Central

    Higashi, Kyohei; Hosoyama, Saori; Ohno, Asami; Masuko, Sayaka; Yang, Bo; Sterner, Eric; Wang, Zhenyu; Linhardt, Robert J.; Toida, Toshihiko

    2011-01-01

    Commercial low molecular weight heparins (LMWHs) are prepared by several methods including peroxidative cleavage, nitrous acid cleavage, chemical ß-elimination, and enzymatic β-elimination. The disadvantages of these methods are that strong reaction conditions or harsh chemicals are used and these can result in decomposition or modification of saccharide units within the polysaccharide backbone. These side-reactions reduce product quality and yield. Here we show the partial photolysis of unfractionated heparin can be performed in distillated water using titanium dioxide (TiO2). TiO2 is a catalyst that can be easily removed by centrifugation or filtration after the photochemical reaction takes place, resulting in highly pure products. The anticoagulant activity of photodegraded LMWH (pLMWH) is comparable to the most common commercially available LMWHs (i.e., Enoxaparin and Dalteparin). 1H NMR spectra obtained show that pLMWH maintains the same core structure as unfractionated heparin. This photochemical reaction was investigated using liquid chromatography/mass spectrometry (LC/MS) and unlike other processes commonly used to prepare LMWHs, photochemically preparation affords polysaccharide chains of reduced length having both odd and even of saccharide residues. PMID:22205826

  7. Mean Molecular Weight Gradients in Proto-Jupiter

    NASA Astrophysics Data System (ADS)

    Helled, R.; Bodenheimer, P.; Rosenberg, E. D.; Podolak, M.; Lozovsky, M.

    2015-12-01

    The distribution of heavy elements in Jupiter cannot be directly measured, and must be inferred from structure models. Typically, structure models assume that Jupiter is fully convective with the heavy elements being uniformly distributed. However, in the case of layered-convection there is a gradient in the distribution of heavy elements which affects the temperature profile of the planet, and as a result also its derived composition. We simulate the formation of Jupiter and investigate whether mean molecular weight gradients that can lead to layered-convection are created. We show that planetesimal accretion naturally leads to compositional gradients in the region above the core. It is shown that after about 10^5 years the core of Jupiter is hot and is surrounded by layers that consist mostly heavy-elements but also some hydrogen and helium. As a result, Jupiter's core mass is expected to be 2-5 M_Earth with no sharp transition between the core and the envelope. These findings are important for the interpretation of Juno data and for linking giant planet internal structure with origins.

  8. The Effect of Low Molecular Weight Heparins on Fracture Healing

    PubMed Central

    Kapetanakis, Stylianos; Nastoulis, Evangelos; Demesticha, Theano; Demetriou, Thespis

    2015-01-01

    Venous Thromboembolism is a serious complication in the trauma patient. The most commonly studied and used anticoagulant treatment in prophylaxis of thrombosis is heparin. The prolonged use of unfractionated heparin has been connected with increased incidence of osteoporotic fractures. Low molecular-weight-heparins (LMWHs) have been the golden rule in antithrombotic therapy during the previous two decades as a way to overcome the major drawbacks of unfractioned heparin. However there are few studies reporting the effects of LMWHs on bone repair after fractures. This review presents the studies about the effects of LMWHs on bone biology (bone cells and bone metabolism) and underlying the mechanisms by which LMWHs may impair fracture healing process. The authors’ research based on literature concluded that there are no facts and statistics for the role of LMWHs on fracture healing process in humans and the main body of evidence of their role comes from in vitro and animal studies. Further large clinical studies designed to compare different types of LMWHs, in different dosages and in different patient or animal models are needed for exploring the effects of LMWHs on fracture healing process. PMID:26161162

  9. Ultra High Molecular Weight Polyethylene: Mechanics, Morphology, and Clinical Behavior

    PubMed Central

    Sobieraj, MC; Rimnac, CM

    2013-01-01

    Ultra high molecular weight polyethylene (UHMWPE) is a semicrystalline polymer that has been used for over four decades as a bearing surface in total joint replacements. The mechanical properties and wear properties of UHMWPE are of interest with respect to the in vivo performance of UHMWPE joint replacement components. The mechanical properties of the polymer are dependent on both its crystalline and amorphous phases. Altering either phase (i.e., changing overall crystallinity, crystalline morphology, or crosslinking the amorphous phase) can affect the mechanical behavior of the material. There is also evidence that the morphology of UHMWPE, and, hence, its mechanical properties evolve with loading. UHMWPE has also been shown to be susceptible to oxidative degradation following gamma radiation sterilization with subsequent loss of mechanical properties. Contemporary UHMWPE sterilization methods have been developed to reduce or eliminate oxidative degradation. Also, crosslinking of UHMWPE has been pursued to improve the wear resistance of UHMWPE joint components. The 1st generation of highly crosslinked UHMWPEs have resulted in clinically reduced wear; however, the mechanical properties of these materials, such as ductility and fracture toughness, are reduced when compared to the virgin material. Therefore, a 2nd generation of highly crosslinked UHMWPEs are being introduced to preserve the wear resistance of the 1st generation while also seeking to provide oxidative stability and improved mechanical properties. PMID:19627849

  10. The Effect of Low Molecular Weight Heparins on Fracture Healing.

    PubMed

    Kapetanakis, Stylianos; Nastoulis, Evangelos; Demesticha, Theano; Demetriou, Thespis

    2015-01-01

    Venous Thromboembolism is a serious complication in the trauma patient. The most commonly studied and used anticoagulant treatment in prophylaxis of thrombosis is heparin. The prolonged use of unfractionated heparin has been connected with increased incidence of osteoporotic fractures. Low molecular-weight-heparins (LMWHs) have been the golden rule in antithrombotic therapy during the previous two decades as a way to overcome the major drawbacks of unfractioned heparin. However there are few studies reporting the effects of LMWHs on bone repair after fractures. This review presents the studies about the effects of LMWHs on bone biology (bone cells and bone metabolism) and underlying the mechanisms by which LMWHs may impair fracture healing process. The authors' research based on literature concluded that there are no facts and statistics for the role of LMWHs on fracture healing process in humans and the main body of evidence of their role comes from in vitro and animal studies. Further large clinical studies designed to compare different types of LMWHs, in different dosages and in different patient or animal models are needed for exploring the effects of LMWHs on fracture healing process. PMID:26161162

  11. High molecular weight kininogen binds to unstimulated platelets.

    PubMed Central

    Gustafson, E J; Schutsky, D; Knight, L C; Schmaier, A H

    1986-01-01

    Studies were performed to determine if the unstimulated platelet membrane has a site for high molecular weight kininogen (HMWK) binding. 125I-HMWK bound to unstimulated platelets. Zn++ was required for 125I-HMWK binding to unstimulated platelets and binding was maximal at 50 microM Zn++. Neither Mg++ nor Ca++ substituted for Zn++ in supporting 125I-HMWK binding to unstimulated platelets, and neither ion potentiated binding in the presence of 50 microM zinc. 125I-HMWK competed with equal affinity with HMWK for binding, and excess HMWK inhibited 125I-HMWK-platelet binding. Only HMWK, not prekallikrein, Factor XII, Factor XI, Factor V, fibrinogen, or fibronectin inhibited 125I-HMWK-platelet binding. 125I-HMWK binding to unstimulated platelets was 89% reversible within 10 min with a 50-fold molar excess of HMWK. Unstimulated platelets contained a single set of saturable, high affinity binding sites for 125I-HMWK with an apparent dissociation constant of 0.99 nM +/- 0.35 and 3,313 molecules/platelet +/- 843. These studies indicate that the unstimulated external platelet membrane has a binding site for HMWK that could serve as a surface to modulate contact phase activation. Images PMID:3722381

  12. Anti-cancer glycosidase inhibitors from natural products: a computational and molecular modelling perspective.

    PubMed

    Singh, Ashona; Mhlongo, Ndumiso; Soliman, Mahmoud E S

    2015-01-01

    The implementation of computational tools in pharmaceutics has proven an effectual strategy in creating harmony between the physical and chemical aspects of proteins and potential inhibitors. This is achieved by bringing to life the three dimensional retrospect of biological systems, which takes into consideration computational approaches such as quantum mechanics and molecular dynamics to facilitate drug design and discovery. In this work, we aim to provide a summary of the computational aspects of naturally derived anti-cancer inhibitors targeting the enzyme family of glycosidases. Our study offers insight into the evolution of drug discovery, molecular modelling and molecular binding modes of natural product inhibitors associated with glycosidase enzymes. PMID:25706917

  13. Molecular basis underlying resistance to Mps1/TTK inhibitors

    PubMed Central

    Koch, A; Maia, A; Janssen, A; Medema, R H

    2016-01-01

    Mps1/TTK is a dual-specificity kinase, with an essential role in mitotic checkpoint signaling, which has emerged as a potential target in cancer therapy. Several Mps1/TTK small-molecule inhibitors have been described that exhibit promising activity in cell culture and xenograft models. Here, we investigated whether cancer cells can develop resistance to these drugs. To this end, we treated various cancer cell lines with sublethal concentrations of a potent Mps1/TTK inhibitor in order to isolate inhibitor-resistant monoclonal cell lines. We identified four point mutations in the catalytic domain of Mps1/TTK that gave rise to inhibitor resistance but retained wild-type catalytic activity. Interestingly, cross-resistance of the identified mutations to other Mps1/TTK inhibitors is limited. Our studies predict that Mps1/TTK inhibitor-resistant tumor cells can arise through the acquisition of mutations in the adenosine triphosphate-binding pocket of the kinase that prevent stable binding of the inhibitors. In addition, our results suggest that combinations of inhibitors could be used to prevent acquisition of drug resistance. Interestingly, cross-resistance seems nonspecific for inhibitor scaffolds, a notion that can be exploited in future drug design to evict possible resistance mutations during clinical treatment. PMID:26364596

  14. Extraction of high molecular weight DNA from microbial mats.

    PubMed

    Bey, Benjamin S; Fichot, Erin B; Norman, R Sean

    2011-01-01

    Successful and accurate analysis and interpretation of metagenomic data is dependent upon the efficient extraction of high-quality, high molecular weight (HMW) community DNA. However, environmental mat samples often pose difficulties to obtaining large concentrations of high-quality, HMW DNA. Hypersaline microbial mats contain high amounts of extracellular polymeric substances (EPS)1 and salts that may inhibit downstream applications of extracted DNA. Direct and harsh methods are often used in DNA extraction from refractory samples. These methods are typically used because the EPS in mats, an adhesive matrix, binds DNA during direct lysis. As a result of harsher extraction methods, DNA becomes fragmented into small sizes. The DNA thus becomes inappropriate for large-insert vector cloning. In order to circumvent these limitations, we report an improved methodology to extract HMW DNA of good quality and quantity from hypersaline microbial mats. We employed an indirect method involving the separation of microbial cells from the background mat matrix through blending and differential centrifugation. A combination of mechanical and chemical procedures was used to extract and purify DNA from the extracted microbial cells. Our protocol yields approximately 2 μg of HMW DNA (35-50 kb) per gram of mat sample, with an A(260/280) ratio of 1.6. Furthermore, amplification of 16S rRNA genes suggests that the protocol is able to minimize or eliminate any inhibitory effects of contaminants. Our results provide an appropriate methodology for the extraction of HMW DNA from microbial mats for functional metagenomic studies and may be applicable to other environmental samples from which DNA extraction is challenging. PMID:21775955

  15. Characterization and analysis of the molecular weight of lignin for biorefining studies

    SciTech Connect

    Tolbert, Allison; Akinosho, Hannah; Khunsupat, Taya Ratayakorn; Naskar, Amit K; Ragauskas, Arthur

    2014-01-01

    The molecular weight of lignin is a fundamental property that infl uences the recalcitrance of biomass and the valorization of lignin. The determination of the molecular weight of lignin in native biomass is dependent on the bioresources used and the isolation and purifi cation procedures employed. The three most commonly employed isolation methods are milled wood lignin (MWL), cellulolytic enzyme lignin (CEL), and enzymatic mild acidolysis lignin (EMAL). Common characterization techniques for determining the molecular weight of lignin will be addressed, with an emphasis on gel permeation chromatography (GPC). This review also examines the mechanisms behind several biological, physical, and chemical pre-treatments and their impact on the molecular weight of lignin. The number average molecular weight (Mn), weight average molecular weight (Mw) and polydispersity index (D) all vary in magnitude depending on the biomass source, pre-treatment conditions, and isolation method. Additionally, there is a growing body of literature that supports changes in the molecular weight of lignin in response to genetic modifi cations in the lignin biosynthetic pathways. This review summarizes different procedures for obtaining the molecular weight of lignin that have been used in recent years and highlight future opportunities for applications of lignin.

  16. Molecular mechanisms of scar-sourced axon growth inhibitors

    PubMed Central

    Ohtake, Yosuke; Li, Shuxin

    2014-01-01

    Astrogliosis is a defense response of the CNS to minimize primary damage and to repair injured tissues, but it ultimately generates harmful effects by upregulating inhibitory molecules to suppress neuronal elongation and forming potent barriers to axon regeneration. Chondroitin sulfate proteoglycans (CSPGs) are highly expressed by reactive scars and are potent contributors to the non-permissive environment in mature CNS. Surmounting strong inhibition by CSPG-rich scar is an important therapeutic goal for achieving functional recovery after CNS injuries. Currently, enzymatic digestion of CSPGs with locally applied chondroitinase ABC is the main in vivo approach to overcome scar inhibition, but several disadvantages may prevent using this bacterial enzyme as a therapeutic option for patients. A better understanding of molecular mechanisms underlying CSPG function may facilitate development of new effective therapies to overcome scar-mediated inhibition. Previous studies support that CSPGs act by non-specifically hindering the binding of matrix molecules to their cell surface receptors through steric interactions, but two members of the leukocyte common antigen related (LAR) phosphatase subfamily, protein tyrosine phosphatase σ and LAR, are functional receptors that bind CSPGs with high affinity and mediate CSPG inhibition. CSPGs may also act by binding two receptors for myelin-associated growth inhibitors, Nogo receptors 1 and 3. Thus, CSPGs inhibit axon growth through multiple mechanisms, making them especially potent and difficult therapeutic targets. Identification of CSPG receptors is not only important for understanding the scar-mediated growth suppression, but also for developing novel and selective therapies to promote axon sprouting and/or regeneration after CNS injuries. PMID:25192646

  17. High molecular weight insulating polymers can improve the performance of molecular solar cells

    NASA Astrophysics Data System (ADS)

    Huang, Ye; Wen, Wen; Kramer, Edward; Bazan, Guillermo

    2014-03-01

    Solution-processed molecular semiconductors for the fabrication of solar cells have emerged as a competitive alternative to their conjugated polymer counterparts, primarily because such materials systems exhibit no batch-to-batch variability, can be purified to a greater extent and offer precisely defined chemical structures. Highest power conversion efficiencies (PCEs) have been achieved through a combination of molecular design and the application of processing methods that optimize the bulk heterojunction (BHJ) morphology. However, one finds that the methods used for controlling structural order, for example the use of high boiling point solvent additives, have been inspired by examination of the conjugated polymer literature. It stands to reason that a different class of morphology modifiers should be sought that address challenges unique to molecular films, including difficulties in obtaining thicker films and avoiding the dewetting of active photovoltaic layers. Here we show that the addition of small quantities of high molecular weight polystyrene (PS) is a very simple to use and economically viable additive that improves PCE. Remarkably, the PS spontaneously accumulates away from the electrodes as separate domains that do not interfere with charge extraction and collection or with the arrangement of the donor and acceptor domains in the BHJ blend.

  18. Using molecular recognition of beta-cyclodextrin to determine molecular weights of low-molecular-weight explosives by MALDI-TOF mass spectrometry.

    PubMed

    Zhang, Min; Shi, Zhen; Bai, Yinjuan; Gao, Yong; Hu, Rongzu; Zhao, Fenqi

    2006-02-01

    This study presents a novel method for determining the molecular weights of low molecular weight (MW) energetic compounds through their complexes of beta-cyclodextrin (beta-CD) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in a mass range of 500 to 1700 Da, avoiding matrix interference. The MWs of one composite explosive composed of 2,6-DNT, TNT, and RDX, one propellant with unknown components, and 14 single-compound explosives (RDX, HMX, 3,4-DNT, 2,6-DNT, 2,5-DNT, 2,4,6-TNT, TNAZ, DNI, BTTN, NG, TO, NTO, NP, and 662) were measured. The molecular recognition and inclusion behavior of beta-CD to energetic materials (EMs) were investigated. The results show that (1) the established method is sensitive, simple, accurate, and suitable for determining the MWs of low-MW single-compound explosives and energetic components in composite explosives and propellants; and (2) beta-CD has good inclusion and modular recognition abilities to the above EMs. PMID:16406809

  19. Formation of high molecular weight products from benzene during boundary lubrication

    NASA Technical Reports Server (NTRS)

    Morales, W.

    1985-01-01

    High molecular weight products were detected on the wear track of an iron disk at the end of a sliding friction and wear test using benzene as a lubricant. Size exclusion chromagography in conjunction with UV analysis gave evidence that the high molecular weight products are polyphenyl ether type substances. Organic electrochemistry was used to elucidate the possible surface reaction mechanisms.

  20. Synthesis and self-assembly of 1-deoxyglucose derivatives as low molecular weight organogelators

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low molecular weight gelators are an important class of molecules. The supramolecular gels formed by carbohydrate derived low molecular weight gelators, are interesting soft materials that show great potential for many applications. Previously, we synthesized a series of methyl 4,6-O-benzylidene-a-D...

  1. 21 CFR 178.3750 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Polyethylene glycol (mean molecular weight 200-9..., PRODUCTION AIDS, AND SANITIZERS Certain Adjuvants and Production Aids § 178.3750 Polyethylene glycol (mean molecular weight 200-9,500). Polyethylene glycol identified in this section may be safely used as...

  2. 21 CFR 178.3750 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Polyethylene glycol (mean molecular weight 200-9..., PRODUCTION AIDS, AND SANITIZERS Certain Adjuvants and Production Aids § 178.3750 Polyethylene glycol (mean molecular weight 200-9,500). Polyethylene glycol identified in this section may be safely used as...

  3. 21 CFR 178.3750 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Polyethylene glycol (mean molecular weight 200-9... Adjuvants and Production Aids § 178.3750 Polyethylene glycol (mean molecular weight 200-9,500). Polyethylene... chapter. (c) The provisions of paragraph (b) of this section are not applicable to polyethylene...

  4. Molecular Weight Determination by an Improved Temperature-Monitored Vapor-Density Method.

    ERIC Educational Resources Information Center

    Grider, Douglas J.; And Others

    1988-01-01

    Recommends determining molecular weights of liquids by use of a thermocouple. Utilizing a mathematical gas equation, the molecular weight can be determined from the measurement of the vapor temperature upon complete evaporation. Lists benefits as reduced time and cost, and improved safety factors. (ML)

  5. A Simple, Inexpensive Molecular Weight Measurement for Water-Soluble Polymers Using Microemulsions.

    ERIC Educational Resources Information Center

    Mathias, Lon J.; Moore, D. Roger

    1985-01-01

    Describes an experiment involving use of a microemulsion and its characteristic thermal phase change to determine molecular weights of polyoxyethylene samples. The experiment provides students with background information on polymers and organized media and with experience in evaluating polymer molecular weight by using a unique property of a…

  6. Effect of resin molecular weight on the resolution of DUV negative photoresists

    NASA Astrophysics Data System (ADS)

    Thackeray, James W.; Orsula, George W.; Denison, Mark

    1994-05-01

    A wide range of molecular weights (3500 to 240000) of poly(p- vinyl)phenol was studied. Polymer dissolution rate vs. molecular weight followed a simple kinetic equation, with the kinetic order m equals2.0. The photospeed of the resist was not strongly affected by the starting resin molecular weight; however, resolution decreased rapidly with increasing Mw. Also, the higher the starting molecular weight, the greater the tendency for the resist to form microbridges between features. The microbridges could be as long as 1.0micrometers for the highest molecular weight resin, Mw equals240000. The lowest molecular weight resins, Mw molecular weight, showed no evidence of microbridging in the higher normality developer. The reason for this difference is that the novolak does not crosslink as effectively as PVP does. Based on extraction experiments, it has been shown that the molecular weight at a sizing dose is 164000 for PVP and 6500 for the novolak. Thus, the novolak must react with the melamine primarily through an intrachain reaction, whereas the PVP- melamine reaction is an interchain reaction. Finally, a mechanism for microbridge formation is discussed.

  7. Low molecular weight proteinuria in Chinese herbs nephropathy.

    PubMed

    Kabanda, A; Jadoul, M; Lauwerys, R; Bernard, A; van Ypersele de Strihou, C

    1995-11-01

    Urinary excretion of five low molecular weight proteins (LMWP) [beta 2-microglobulin (beta 2m), cystatin C (cyst C), Clara cell protein (CC16), retinol-binding protein (RBP) and alpha 1-microglobulin (alpha 1m)], albumin and N-acetyl-beta-D-glucosaminidase (NAG) were quantified in 16 patients who followed a weight reduction program which included Chinese herbs, which have been incriminated in the genesis of Chinese herbs nephropathy (CHN). An additional group of four patients transplanted for CHN were investigated. Urinary data were obtained for comparison purpose in five groups of proteinuric patients: two groups with normal serum creatinine (SCr) and glomerular albuminura [12 patients with diabetes mellitus and microalbuminuria (DN), 10 patients with primary nephrotic syndrome (NS)]; two groups with normal SCr and toxic nephropathy [6 patients with analgesic (AN), 9 patients with cadmium nephropathy (CdN)]; and one group of seven patients with glomerular diseases and increased SCr (GN). Patients were classified according to serum level S beta 2m to take into account the possibility of overflow proteinuria at S beta 2m > or = 5 mg/liter. Three patients (CHN0) with a S beta 2m < 5 mg/liter, had a normal urinary protein pattern including NAG and a normal S beta 2m. Eight patients (CHN1) with a S beta 2m < 5 mg/liter had various abnormalities of their urinary protein pattern. In four of them (CHN1a) only beta 2m, RBP and CC16 were increased while total proteinuria and SCr were normal. In the other four (CHN1b and c) albumin, cyst C, alpha 1m and NAG were also elevated, while total proteinuria and SCr were moderately raised. Five patients (CHN2) with a S beta 2m > or = 5 mg/liter had a markedly increased excretion of all LMWP, albumin and NAG (CHN1 vs. CHN2, P < 0.05) as well as a further increase in total proteinuria and SCr. The urinary LMWP/albumin concentration ratio was strikingly higher in CHN patients than in patients with glomerular albuminuria (CHN1 vs. DN

  8. Molecular chaperone properties of the high molecular weight aggregate from aged lens

    NASA Technical Reports Server (NTRS)

    Takemoto, L.; Boyle, D.; Spooner, B. S. (Principal Investigator)

    1994-01-01

    The high molecular weight aggregate (HMWA) fraction was isolated from the water soluble proteins of aged bovine lenses. Its composition and ability to inhibit heat-induced denaturation and aggregation were compared with the lower molecular weight, oligomeric fraction of alpha isolated from the same lens. Although the major components of both fractions were the alpha-A and alpha-B chains, the HMWA fraction possessed a decreased ability to protect other proteins against heat-induced denaturation and aggregation. Immunoelectron microscopy of both fractions demonstrated that alpha particles from the HMWA fraction contained increased amounts of beta and gamma crystallins, bound to a central region of the supramolecular complex. Together, these results demonstrate that alpha crystallins found in the HMWA fraction possess a decreased ability to protect against heat-induced denaturation and aggregation, and suggest that at least part of this decrease could be due to the increased presence of beta and gamma crystallins complexed to the putative chaperone receptor site of the alpha particles.

  9. Small-molecule caspase inhibitors

    NASA Astrophysics Data System (ADS)

    Zhenodarova, S. M.

    2010-02-01

    The review considers low-molecular weight inhibitors of caspases, cysteine proteases being key contributors to apoptosis (programmed cell death). The inhibitors with aspartic acid residues or various heterocyclic systems (both synthetic and natural) are covered. Their possible mechanisms of action are discussed. Data on inhibitor structure-activity relationship studies are systematically surveyed. The interactions of the non-peptide fragments of an inhibitor with the enzymes are examined. Examples of the use of some inhibitors for apoptosis suppression are provided.

  10. Bioremediation of Mixtures of High Molecular Weight Polycyclic Aromatic Hydrocarbons

    NASA Astrophysics Data System (ADS)

    Xu, H.; Wu, J.; Shi, X.; Sun, Y.

    2014-12-01

    Although bioremediation has been considered as one of the most promising means to remove polycyclic aromatic hydrocarbons (PAHs) from polluted environments, the efficacy of PAHs bioremediation still remains challenged, especially for high molecular weight PAHs (HMW PAHs) and their mixtures. This study was focused on (a) isolation and characterization of pure strain and mixed microbial communities able to degrade HMW PAHs and (b) further evaluation of the ability of the isolated microbes to degrade HMW PAHs mixtures in the absence and presence of indigenous flora. Fluoranthene, benzo[b]fluoranthene and pyrene were selected as the representative HMW PAHs in this study. A pure bacterial strain, identified as Herbaspirillum chlorophenolicum FA1, was isolated from activated sludge. A mixed bacterial community designated as consortium-4 was isolated from petroleum contaminated soils, containing Pseudomonas sp. FbP1、Enterobacter sp. FbP2、Hydrogenophaga sp. FbP3 and Luteolibacter pohnpeiensis. FbP4. To our knowledge, this is the first study to demonstrate that bacterial strains of Herbaspirillum chlorophenolicum FA1 and Luteolibacter pohnpeiensis. FbP4 can also degrade fluoranthene, benzo[b]fluoranthene and pyrene. Experiment results showed that both strain FA1 and consortium-4 could degrade fluoranthene, benzo[b]fluoranthene and pyrene within a wide range of temperature, pH and initial PAHs concentration. Degradation of HMW PAHs mixtures (binary and ternary) demonstrated the interactive effects that can alter the rate and extent of biodegradation within a mixture. The presence of indigenous flora was found to either increase or decrease the degradation of HMW PAHs, suggesting possible synergistic or competition effects. Biodegradation kinetics of HMW PAHs for sole substrates, binary and ternary systems was evaluated, with the purpose to better characterize and compare the biodegradation process of individual HMW PAH and mixtures of HMW PAHs. Results of this study

  11. Low molecular weight carboxylic acids in oxidizing porphyry copper tailings.

    PubMed

    Dold, Bernhard; Blowes, David W; Dickhout, Ralph; Spangenberg, Jorge E; Pfeifer, Hans-Rudolf

    2005-04-15

    The distribution of low molecular weight carboxylic acids (LMWCA) was investigated in pore water profiles from two porphyry copper tailings impoundments in Chile (Piuquenes at La Andina and Cauquenes at El Teniente mine). The objectives of this study were (1) to determine the distribution of LMWCA, which are interpreted to be the metabolic byproducts of the autotroph microbial community in this low organic carbon system, and (2) to infer the potential role of these acids in cycling of Fe and other elements in the tailings impoundments. The speciation and mobility of iron, and potential for the release of H+ via hydrolysis of the ferric iron, are key factors in the formation of acid mine drainage in sulfidic mine wastes. In the low-pH oxidation zone of the Piuquenes tailings, Fe(III) is the dominant iron species and shows high mobility. LMWCA, which occur mainly between the oxidation front down to 300 cm below the tailings surface at both locations (e.g., max concentrations of 0.12 mmol/L formate, 0.17 mmol/L acetate, and 0.01 mmol/L pyruvate at Piuquenes and 0.14 mmol/L formate, 0.14 mmol/L acetate, and 0.006 mmol/L pyruvate at Cauquenes), are observed at the same location as high Fe concentrations (up to 71.2 mmol/L Fe(II) and 16.1 mmol/L Fe(III), respectively). In this zone, secondary Fe(III) hydroxides are depleted. Our data suggest that LMWCA may influence the mobility of iron in two ways. First, complexation of Fe(III), through formation of bidentate Fe(III)-LMWCA complexes (e.g., pyruvate, oxalate), may enhance the dissolution of Fe(III) (oxy)hydroxides or may prevent precipitation of Fe(III) (oxy)hydroxides. Soluble Fe(III) chelate complexes which may be mobilized downward and convert to Fe(II) by Fe(III) reducing bacteria. Second, monodentate LMWCA (e.g., acetate and formate) can be used by iron-reducing bacteria as electron donors (e.g., Acidophilum spp.), with ferric iron as the electron acceptor. These processes may, in part, explain the low abundances

  12. Effects of molecular weight of dextran on the adherence of Streptococcus sanguis to damaged heart valves.

    PubMed Central

    Ramirez-Ronda, C H

    1980-01-01

    Dextran-producing streptococci such as Streptococcus sanguis are the organisms most frequently associated with infective endocarditis in humans. A series of experiments was designed to study how the molecular weight of dextrans affects the adherence of an endocarditis strain of S. sanguis to canine heart valves covered with platelets and fibrin. The data indicated that this adherence was dependent on dextrans of high molecular weight, such as dextran T-2000 or glucans isolated from S. sanguis or S. mutans. The adherence properties of the strain studied were not modified by prior exposure of the bacterial cells of valve leaflets to high-molecular-weight dextrans. Preexposure of bacterial cells or valve leaflets to low-molecular-weight dextrans decreased their adherence. Low-molecular-weight dextrans interfered with adherence of dextran-positive strains to damaged heart valves. PMID:6156909

  13. Isolation of low-molecular-weight heparin/heparan sulfate from marine sources.

    PubMed

    Saravanan, Ramachandran

    2014-01-01

    The glycosaminoglycan (heparin and heparan sulfate) are polyanionic sulfated polysaccharides mostly recognized for its anticoagulant activity. In many countries, low-molecular-weight heparins have replaced the unfractionated heparin, owing to its high bioavailability, half-life, and less adverse effect. The low-molecular-weight heparins differ in mode of preparation (chemical or enzymatic synthesis and chromatography fractionations) and as a consequence in molecular weight distribution, chemical structure, and pharmacological activities. Bovine and porcine body parts are at present used for manufacturing of commercial heparins, and the appearance of mad cow disease and Creutzfeldt-Jakob disease in humans has limited the use of bovine heparin. Consequently, marine organisms come across the new resource for the production of low-molecular-weight heparin and heparan sulfate. The importance of this chapter suggests that the low-molecular-weight heparin and heparan sulfate from marine species could be alternative sources for commercial heparin. PMID:25081076

  14. The influence of polyacid molecular weight on some properties of glass-ionomer cements.

    PubMed

    Wilson, A D; Hill, R G; Warrens, C P; Lewis, B G

    1989-02-01

    The influence of the molecular weight of the poly(acrylic acid) component on some properties of glass-ionomer cement has been investigated. The results can be explained by treatment of glass-ionomer cements as thermoplastic composites. Many of the concepts of polymer science can be applied successfully in a qualitative way to these cements, including the ideas of entanglements and reptation. Molecular weight of the polyacid had a pronounced influence on setting rate, acid erosion rate, toughness, fracture toughness, and wear resistance. The chain length of the polyacid was found to be an important parameter in formulation of a cement, and the higher the molecular weight, the better the properties. However, in practice the molecular weight is limited by viscosity, and some balance has to be achieved among concentration, molecular weight, and viscosity. PMID:2918140

  15. Spectroscopic investigations, molecular interactions, and molecular docking studies on the potential inhibitor "thiophene-2-carboxylicacid"

    NASA Astrophysics Data System (ADS)

    Karthick, T.; Balachandran, V.; Perumal, S.

    2015-04-01

    Thiophene derivatives have been focused in the past decades due to their remarkable biological and pharmacological activities. In connection with that the conformational stability, spectroscopic characterization, molecular (inter- and intra-) interactions, and molecular docking studies on thiophene-2-carboxylicacid have been performed in this work by experimental FT-IR and theoretical quantum chemical computations. Experimentally recorded FT-IR spectrum in the region 4000-400 cm-1 has been compared with the scaled theoretical spectrum and the spectral peaks have been assigned on the basis of potential energy distribution results obtained from MOLVIB program package. The conformational stability of monomer and dimer conformers has been examined. The presence of inter- and intramolecular interactions in the monomer and dimer conformers have been explained by natural bond orbital analysis. The UV-Vis spectra of the sample in different solvents have been simulated and solvent effects were predicted by polarisable continuum model with TD-DFT/B3LYP/6-31+G(d,p) method. To test the biological activity of the sample, molecular docking (ligand-protein) simulations have been performed using SWISSDOCK web server. The full fitness (FF) score and binding affinity values revealed that thiophene-2-carboxylicacid can act as potential inhibitor against inflammation.

  16. Endurance of high molecular weight carboxymethyl cellulose in corrosive environments

    NASA Astrophysics Data System (ADS)

    Murodov, M. M.; Rahmanberdiev, G. R.; Khalikov, M. M.; Egamberdiev, E. A.; Negmatova, K. C.; Saidov, M. M.; Mahmudova, N.

    2012-07-01

    Lignin obtained from the waste cooking liquor, formed after soda pulping process, is used as an inhibitor of NaCMC thermo oxidative degradation in presence of in extreme conditions during drilling oil wells. In this paper the schematic process of obtaining NaCMC by the principle of "monoapparat" on the basis of cellulose produced by non-wood cellulose materials is presented.

  17. Optical properties of polycarbonate/styrene-co-acrylonitrile blends: effects of molecular weight of the matrix.

    PubMed

    Yi, Ping; Xiong, Ying; Guo, Shaoyun

    2015-12-01

    In this paper, the effects of the molecular weight of a polycarbonate (PC) matrix on the phase morphology and optical properties of a PC/styrene-co-acrylonitrile (SAN) blend were investigated. A scanning electron microscope is used to analyze the phase morphology of the blends, and Mie scattering theory is used to analyze the changing laws of the optical properties of PC/SAN blends with the increasing of PC molecular weight. Results show that the average particle diameter is not strongly changed with different PC molecular weight because the values of the viscosity ratios are very close to each other. But it is obvious that the number of large particles gradually reduced while small particles (especially d<2  μm) significantly increased with the increasing of PC molecular weight. And the increase in small particles will result in an increase in backward scattering so the transmittance of PC/SAN blends decreases with the increase of PC molecular weight. However, the balance of the scattering coefficients and the number concentration of particles eventually lead to the haze of the blends being very close, despite having different PC molecular weights. Meanwhile, the photographs of scattering patterns indicate that the PC/SAN blends whose component weight ratios are fixed at 70:30 have excellent antiglare properties, despite the changes in molecular weight of the PC matrix. PMID:26836652

  18. Influence of molecular-weight polydispersity on the glass transition of polymers.

    PubMed

    Li, Shu-Jia; Xie, Shi-Jie; Li, Yan-Chun; Qian, Hu-Jun; Lu, Zhong-Yuan

    2016-01-01

    It is well known that the polymer glass transition temperature T_{g} is dependent on molecular weight, but the role of molecular-weight polydispersity on T_{g} is unclear. Using molecular-dynamics simulations, we clarify that for polymers with the same number-average molecular weight, the molecular-weight distribution profile (either in Schulz-Zimm form or in bimodal form) has very little influence on the glass transition temperature T_{g}, the average segment dynamics (monomer motion, bond orientation relaxation, and torsion transition), and the relaxation-time spectrum, which are related to the local nature of the glass transition. By analyzing monomer motions in different chains, we find that the motion distribution of monomers is altered by molecular-weight polydispersity. Molecular-weight polydispersity dramatically enhances the dynamic heterogeneity of monomer diffusive motions after breaking out of the "cage," but it has a weak influence on the dynamic heterogeneity of the short time scales and the transient spatial correlation between temporarily localized monomers. The stringlike cooperative motion is also not influenced by molecular-weight polydispersity, supporting the idea that stringlike collective motion is not strongly correlated with chain connectivity. PMID:26871128

  19. Influence of molecular-weight polydispersity on the glass transition of polymers

    NASA Astrophysics Data System (ADS)

    Li, Shu-Jia; Xie, Shi-Jie; Li, Yan-Chun; Qian, Hu-Jun; Lu, Zhong-Yuan

    2016-01-01

    It is well known that the polymer glass transition temperature Tg is dependent on molecular weight, but the role of molecular-weight polydispersity on Tg is unclear. Using molecular-dynamics simulations, we clarify that for polymers with the same number-average molecular weight, the molecular-weight distribution profile (either in Schulz-Zimm form or in bimodal form) has very little influence on the glass transition temperature Tg, the average segment dynamics (monomer motion, bond orientation relaxation, and torsion transition), and the relaxation-time spectrum, which are related to the local nature of the glass transition. By analyzing monomer motions in different chains, we find that the motion distribution of monomers is altered by molecular-weight polydispersity. Molecular-weight polydispersity dramatically enhances the dynamic heterogeneity of monomer diffusive motions after breaking out of the "cage," but it has a weak influence on the dynamic heterogeneity of the short time scales and the transient spatial correlation between temporarily localized monomers. The stringlike cooperative motion is also not influenced by molecular-weight polydispersity, supporting the idea that stringlike collective motion is not strongly correlated with chain connectivity.

  20. Identification of inhibitor binding site in human sirtuin 2 using molecular docking and dynamics simulations.

    PubMed

    Sakkiah, Sugunadevi; Arooj, Mahreen; Kumar, Manian Rajesh; Eom, Soo Hyun; Lee, Keun Woo

    2013-01-01

    The ability to identify the site of a protein that can bind with high affinity to small, drug-like compounds has been an important goal in drug design. Sirtuin 2 (SIRT2), histone deacetylase protein family, plays a central role in the regulation of various pathways. Hence, identification of drug for SIRT2 has attracted great interest in the drug discovery community. To elucidate the molecular basis of the small molecules interactions to inhibit the SIRT2 function we employed the molecular docking, molecular dynamics simulations, and the molecular mechanism Poisson-Boltzmann/surface area (MM-PBSA) calculations. Five well know inhibitors such as suramin, mol-6, sirtinol, 67, and nf675 were selected to establish the nature of the binding mode of the inhibitors in the SIRT2 active site. The molecular docking and dynamics simulations results revealed that the hydrogen bonds between Arg97 and Gln167 are crucial to inhibit the function of SIRT2. In addition, the MM-PBSA calculations revealed that binding of inhibitors to SIRT2 is mainly driven by van der Waals/non-polar interactions. Although the five inhibitors are very different in structure, shape, and electrostatic potential, they are able to fit in the same binding pocket. These findings from this study provide insights to elucidate the binding pattern of SIRT2 inhibitors and help in the rational structure-based design of novel SIRT2 inhibitors with improved potency and better resistance profile. PMID:23382805

  1. High Molecular Weight Petrogenic and Pyrogenic Hydrocarbons in Aquatic Environments

    NASA Astrophysics Data System (ADS)

    Abrajano, T. A., Jr.; Yan, B.; O'Malley, V.

    2003-12-01

    Geochemistry is ultimately the study of sources, movement, and fate of chemicals in the geosphere at various spatial and temporal scales. Environmental organic geochemistry focuses such studies on organic compounds of toxicological and ecological concern (e.g., Schwarzenbach et al., 1993, 1998; Eganhouse, 1997). This field emphasizes not only those compounds with potential toxicological properties, but also the geological systems accessible to the biological receptors of those hazards. Hence, the examples presented in this chapter focus on hydrocarbons with known health and ecological concern in accessible shallow, primarily aquatic, environments.Modern society depends on oil for energy and a variety of other daily needs, with present mineral oil consumption throughout the 1990s exceeding 3×109 t yr-1 (NRC, 2002). In the USA, e.g., ˜40% of energy consumed and 97% of transportation fuels are derived from oil. In the process of extraction, refinement, transport, use, and waste production, a small but environmentally significant fraction of raw oil materials, processed products, and waste are released inadvertently or purposefully into the environment. Because their presence and concentration in the shallow environments are often the result of human activities, these organic materials are generally referred to as "environmental contaminants." Although such reference connotes some form of toxicological or ecological hazard, specific health or ecological effects of many organic "environmental contaminants" remain to be demonstrated. Some are, in fact, likely innocuous at the levels that they are found in many systems, and simply adds to the milieu of biogenic organic compounds that naturally cycle through the shallow environment. Indeed, virtually all compounds in crude oil and processed petroleum products have been introduced naturally to the shallow environments as oil and gas seepage for millions of years ( NRC, 2002). Even high molecular weight (HMW) polyaromatic

  2. Two-chain high molecular weight kininogen induces endothelial cell apoptosis and inhibits angiogenesis: partial activity within domain 5.

    PubMed

    Zhang, J C; Claffey, K; Sakthivel, R; Darzynkiewicz, Z; Shaw, D E; Leal, J; Wang, Y C; Lu, F M; McCrae, K R

    2000-12-01

    We previously reported that the binding of two-chain high molecular weight kininogen (HKa) to endothelial cells may occur through interactions with endothelial urokinase receptors. Since the binding of urokinase to urokinase receptors activates signaling responses and may stimulate mitogenesis, we assessed the effect of HKa binding on endothelial cell proliferation. Unexpectedly, HKa inhibited proliferation in response to several growth factors, with 50% inhibition caused by approximately 10 nM HKa. This activity was Zn(2+) dependent and not shared by either single-chain high molecular weight kininogen (HK) or low molecular weight kininogen. HKa selectively inhibited the proliferation of human umbilical vein and dermal microvascular endothelial cells, but did not affect that of umbilical vein or human aortic smooth muscle cells, trophoblasts, fibroblasts, or carcinoma cells. Inhibition of endothelial proliferation by HKa was associated with endothelial cell apoptosis and unaffected by antibodies that block the binding of HK or HKa to any of their known endothelial receptors. Recombinant HK domain 5 displayed activity similar to that of HKa. In vivo, HKa inhibited neovascularization of subcutaneously implanted Matrigel plugs, as well as rat corneal angiogenesis. These results demonstrate that HKa is a novel inhibitor of angiogenesis, whose activity is dependent on the unique conformation of the two-chain molecule. PMID:11099478

  3. Effect of molecular weight distribution on e-beam exposure properties of polystyrene

    NASA Astrophysics Data System (ADS)

    Dey, Ripon Kumar; Cui, Bo

    2013-06-01

    Polystyrene is a negative electron beam resist whose exposure properties can be tuned simply by using different molecular weights (Mw). Most previous studies have used monodisperse polystyrene with a polydispersity index (PDI) of less than 1.1 in order to avoid any uncertainties. Here we show that despite the fact that polystyrene’s sensitivity is inversely proportional to its Mw, no noticeable effect of very broad molecular weight distribution on sensitivity, contrast and achievable resolution is observed. It is thus unnecessary to use the costly monodisperse polystyrene for electron beam lithography. Since the polydispersity is unknown for general purpose polystyrene, we simulated a high PDI polystyrene by mixing in a 1:1 weight ratio two polystyrene samples with Mw of 170 and 900 kg mol-1 for the high Mw range, and 2.5 and 13 kg mol-1 for the low Mw range. The exposure property of the mixture resembles that of a monodisperse polystyrene with similar number averaged molecular weight \\overline{{Mn}}, which indicates that it is \\overline{{Mn}} rather than \\overline{{Mw}} (weight averaged molecular weight) that dominates the exposure properties of polystyrene resist. This also implies that polystyrene of a certain molecular weight can be simulated by a mixture of two polystyrenes having different molecular weights.

  4. Perchlorate-induced combustion of organic matter with variable molecular weights: Implications for Mars missions

    NASA Astrophysics Data System (ADS)

    Sephton, Mark A.; Lewis, James M. T.; Watson, Jonathan S.; Montgomery, Wren; Garnier, Carole

    2014-11-01

    Instruments on the Viking landers and Curiosity rover analyzed samples of Mars and detected carbon dioxide and organic compounds of uncertain origin. Mineral-assisted reactions are leading to uncertainty, particularly those involving perchlorate minerals which thermally decompose to produce chlorine and oxygen which can then react with organic matter to generate organochlorine compounds and carbon dioxide. Although generally considered a problem for interpretation, the release profiles of generated gases can indicate the type of organic matter present. We have performed a set of experiments with perchlorate and organic matter of variable molecular weights. Results indicate that organic susceptibility to thermal degradation and mineral-assisted reactions is related to molecular weight. Low molecular weight organic matter reacts at lower temperatures than its high molecular weight counterparts. The natural occurrence and association of organic matter with differing molecular weights helps to discriminate between contamination (usually low molecular weight organic matter only) and indigenous carbon (commonly low and high molecular weight organic matter together). Our results can be used to provide insights into data returning from Mars.

  5. How does the preparation of rye porridge affect molecular weight distribution of extractable dietary fibers?

    PubMed

    Rakha, Allah; Aman, Per; Andersson, Roger

    2011-01-01

    Extractable dietary fiber (DF) plays an important role in nutrition. This study on porridge making with whole grain rye investigated the effect of rest time of flour slurries at room temperature before cooking and amount of flour and salt in the recipe on the content of DF components and molecular weight distribution of extractable fructan, mixed linkage (1→3)(1→4)-β-d-glucan (β-glucan) and arabinoxylan (AX) in the porridge. The content of total DF was increased (from about 20% to 23% of dry matter) during porridge making due to formation of insoluble resistant starch. A small but significant increase in the extractability of β-glucan (P = 0.016) and AX (P = 0.002) due to rest time was also noted. The molecular weight of extractable fructan and AX remained stable during porridge making. However, incubation of the rye flour slurries at increased temperature resulted in a significant decrease in extractable AX molecular weight. The molecular weight of extractable β-glucan decreased greatly during a rest time before cooking, most likely by the action of endogenous enzymes. The amount of salt and flour used in the recipe had small but significant effects on the molecular weight of β-glucan. These results show that whole grain rye porridge made without a rest time before cooking contains extractable DF components maintaining high molecular weights. High molecular weight is most likely of nutritional importance. PMID:21686191

  6. How Does the Preparation of Rye Porridge Affect Molecular Weight Distribution of Extractable Dietary Fibers?

    PubMed Central

    Rakha, Allah; Åman, Per; Andersson, Roger

    2011-01-01

    Extractable dietary fiber (DF) plays an important role in nutrition. This study on porridge making with whole grain rye investigated the effect of rest time of flour slurries at room temperature before cooking and amount of flour and salt in the recipe on the content of DF components and molecular weight distribution of extractable fructan, mixed linkage (1→3)(1→4)-β-d-glucan (β-glucan) and arabinoxylan (AX) in the porridge. The content of total DF was increased (from about 20% to 23% of dry matter) during porridge making due to formation of insoluble resistant starch. A small but significant increase in the extractability of β-glucan (P = 0.016) and AX (P = 0.002) due to rest time was also noted. The molecular weight of extractable fructan and AX remained stable during porridge making. However, incubation of the rye flour slurries at increased temperature resulted in a significant decrease in extractable AX molecular weight. The molecular weight of extractable β-glucan decreased greatly during a rest time before cooking, most likely by the action of endogenous enzymes. The amount of salt and flour used in the recipe had small but significant effects on the molecular weight of β-glucan. These results show that whole grain rye porridge made without a rest time before cooking contains extractable DF components maintaining high molecular weights. High molecular weight is most likely of nutritional importance. PMID:21686191

  7. Enhancement by heparin of thrombin-induced antithrombin III proteolysis: its relation to the molecular weight and anticoagulant activity of heparin

    SciTech Connect

    Marciniak, E.; Gora-Maslak, G.

    1982-11-01

    Previous findings indicated that binding of heparin to antithrombin III (AT III) facilitates thrombin-induced proteolysis of the inhibitor. Researchers now studied this property of heparin in regard to its molecular weight and anticoagulant activity. Commercial heparin was resolved on Sephadex G-200 into six fractions of decreasing molecular weight. From each fraction high affinity (HA) heparin was isolated by chromatography on AT III-Sepharose and examined in reaction of alpha-thrombin with a molar excess of /sup 125/I AT III. Proteolysis of the inhibitor was assessed by SDS polyacrylamide gel electrophoresis. In the presence of the HA heparin from 18% to 38% of AT III participating in reaction appeared in the form of inactive 50,000-dalton fragment, as opposed to 7% of AT III fragmented in the absence of heparin. Although the ability to potentiate proteolysis was at its peak in the medium-molecular-size heparin fraction, the amount of degraded inhibitor relative to anticoagulant activity increased with decreasing molecular weight of the polysaccharide. These findings are consistent with the possibility that the ability of bound heparin to facilitate the cleavage of AT III by thrombin is generally less contingent upon secondary characteristics of the polysaccharide than the anticoagulant activity.

  8. Physics and gel electrophoresis: using terminal velocity to characterize molecular weight

    NASA Astrophysics Data System (ADS)

    Viney, Christopher; Fenton, Richard A.

    1998-11-01

    Protein molecular weights are commonly characterized by gel electrophoresis. Biology textbooks typically quote an empirical, approximate relationship between migration rate and molecular weight, relying on an inappropriately simplistic model of spherical particles travelling at their terminal velocity through a viscous medium. We show how the model can be modified to derive a physically realistic equation that relates migration rate and molecular weight, and that mirrors experimentally observed behaviour. We suggest that gel electrophoresis provides an interesting interdisciplinary context in which to exercise several basic principles that are encountered through introductory physics courses. Finally, we provide additional examples of practical situations where the concept of terminal velocity can be elaborated and applied.

  9. Effect of sterilization irradiation on friction and wear of ultrahigh-molecular-weight polyethylene

    NASA Technical Reports Server (NTRS)

    Jones, W. R., Jr.; Hady, W. F.; Crugnola, A.

    1979-01-01

    The effect of sterilization gamma irradiation on the friction and wear properties of ultrahigh molecular weight polyethylene (UHMWPE) sliding against 316L stainless steel in dry air at 23 C was determined. A pin-on-disk apparatus was used. Experimental conditions included a 1-kilogram load, a 0.061- to 0.27-meter-per-second sliding velocity, and a 32000- to 578000-meter sliding distance. Although sterilization doses of 2.5 and 5.0 megarads greatly altered the average molecular weight and the molecular weight distribution, the friction and wear properties of the polymer were not significantly changed.

  10. Molecular Weight Determinations of Proteins by Californium Plasma Desorption Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Sundqvist, B.; Roepstorff, Peter; Fohlman, J.; Hedin, A.; Hakansson, P.; Kamensky, I.; Lindberg, M.; Salehpour, M.; Sawe, G.

    1984-11-01

    The plasma desorption mass spectrometry method is used to determine the molecular weights of larger molecules than before, to determine the molecular weights of proteins and peptides in mixtures, and to monitor protein modification reactions. Proteins up to molecular weight 25,000 can now be studied with a mass spectrometric technique. Protein-peptide mixtures that could not be resolved with conventional techniques were successfully analyzed by this technique. The precision of the method is good enough to permit one to follow the different steps in the conversion of porcine insulin to human insulin.

  11. High molecular weight first generation PMR polyimides for 343 C applications

    NASA Technical Reports Server (NTRS)

    Malarik, Diane C.; Vannucci, Raymond D.

    1991-01-01

    The effect of molecular weight on 343 C thermo-oxidative stability (TOS), mechanical properties, and processability, of the first generation PMR polyimides was studied. Graphite fiber reinforced PMR-15, PMR-30, PMR-50, and PMR-75 composites (corresponding to formulated molecular weights of 1500, 3000, 5000, and 7500, respectively) were fabricated using a simulated autoclave process. The data reveals that while alternate autoclave cure schedules are required for the high molecular weight resins, low void laminates can be fabricated which have significantly improved TOS over PMR-15, with only a small sacrifice in mechanical properties.

  12. High molecular weight first generation PMR polyimides for 343 C applications

    NASA Technical Reports Server (NTRS)

    Malarik, D. C.; Vannucci, R. D.

    1992-01-01

    The effect of molecular weight on 343 C thermo-oxidative stability (TOS), mechanical properties, and processability, of the first generation PMR polyimides was studied. Graphite fiber reinforced PMR-15, PMR-30, PMR-50, and PMR-75 composites (corresponding to formulated molecular weights of 1500, 3000, 5000, and 7500, respectively) were fabricated using a simulated autoclave process. The data reveal that while alternate autoclave cure schedules are required for the high molecular weight resins, low void laminates can be fabricated which have significantly improved TDS over PMR-15, with only a small sacrifice in mechanical properties.

  13. A low molecular weight component of serum inhibits biofilm formation in Staphylococcus aureus

    PubMed Central

    Abraham, Nabil; Jefferson, Kimberly K.

    2010-01-01

    Staphylococcus aureus has a variety of genes that can influence the process of biofilm formation. The ability to establish a biofilm is an important virulence factor for this pathogen, and yet, the regulation of this process in vivo is not well understood. S. aureus can form biofilms on intravenous catheters and this process plays a key role in the pathogenesis of catheter infections. In order to investigate whether or not serum is conducive to the process of biofilm formation, we grew S. aureus in serum and analyzed biofilm thickness and expression of biofilm-related genes. Whereas serum supported planktonic bacterial growth, it was a potent inhibitor of biofilm formation. The inhibitory serum component had a molecular weight less than 3,000 kDa. The component was protease-resistant and heat stable. The serum component induced a significant increase in the transcription of the intercellular adhesin gene icaA and the fibronectin binding protein gene fnbA. Transcription of other biofilm-related genes were affected in a strain-dependent manner. These results reveal that serum inhibits biofilm formation despite the fact that biofilms form on intravenous catheters. This may suggest that in vivo, biofilm formation is “selected for” by the force of blood flow and/or immune pressure rather than “induced” by serum. PMID:20673798

  14. Low molecular weight protein tyrosine phosphatase: Multifaceted functions of an evolutionarily conserved enzyme.

    PubMed

    Caselli, Anna; Paoli, Paolo; Santi, Alice; Mugnaioni, Camilla; Toti, Alessandra; Camici, Guido; Cirri, Paolo

    2016-10-01

    Originally identified as a low molecular weight acid phosphatase, LMW-PTP is actually a protein tyrosine phosphatase that acts on many phosphotyrosine-containing cellular proteins that are primarily involved in signal transduction. Differences in sequence, structure, and substrate recognition as well as in subcellular localization in different organisms enable LMW-PTP to exert many different functions. In fact, during evolution, the LMW-PTP structure adapted to perform different catalytic actions depending on the organism type. In bacteria, this enzyme is involved in the biosynthesis of group 1 and 4 capsules, but it is also a virulence factor in pathogenic strains. In yeast, LMW-PTPs dephosphorylate immunophilin Fpr3, a peptidyl-prolyl-cis-trans isomerase member of the protein chaperone family. In humans, LMW-PTP is encoded by the ACP1 gene, which is composed of three different alleles, each encoding two active enzymes produced by alternative RNA splicing. In animals, LMW-PTP dephosphorylates a number of growth factor receptors and modulates their signalling processes. The involvement of LMW-PTP in cancer progression and in insulin receptor regulation as well as its actions as a virulence factor in a number of pathogenic bacterial strains may promote the search for potent, selective and bioavailable LMW-PTP inhibitors. PMID:27421795

  15. Synthesis of low molecular weight thiols in response to Cd exposure in Thlaspi caerulescens.

    PubMed

    Hernández-Allica, J; Garbisu, C; Becerril, J M; Barrutia, O; García-Plazaola, J I; Zhao, F J; Mcgrath, S P

    2006-07-01

    In this study, we investigated the accumulation of phytochelatins (PCs) and other low molecular weight (LMW) thiols in response to Cd exposure in two contrasting ecotypes differing in Cd accumulation. Using a root elongation test, we found that the highly accumulating ecotype Ganges was more tolerant to Cd than the low Cd-accumulation ecotype Prayon. L-buthionine-(S,R)-sulphoximine (BSO), a potent inhibitor of the gamma-glutamylcysteine synthetase gamma-ECS) (an enzyme involved in the PC biosynthetic pathway), increased the Cd sensitivity of Prayon, but had no effect on Ganges. Although PC accumulation increased in response to Cd exposure, no significant differences were observed between the two ecotypes. Cd exposure induced a dose-dependent accumulation of both Cys and a still unidentified LMW thiol in roots of both ecotypes. Root accumulation of Cys and this thiol was higher in Ganges than in Prayon; the ecotypic differences were more pronounced when the plants were treated with BSO. These findings suggest that PCs do not contribute to the Cd hypertolerance displayed by the Ganges ecotype of Thlaspi caerulescens, whereas Cys and other LMW thiols might be involved. PMID:17080963

  16. Effect of PEO molecular weight on the miscibility and dynamics in epoxy/PEO blends.

    PubMed

    Lu, Shoudong; Zhang, Rongchun; Wang, Xiaoliang; Sun, Pingchuan; Lv, Weifeng; Liu, Qingjie; Jia, Ninghong

    2015-11-01

    In this work, the effect of poly(ethylene oxide) (PEO) molecular weight in blends of epoxy (ER) and PEO on the miscibility, inter-chain weak interactions and local dynamics were systematically investigated by multi-frequency temperature modulation DSC and solid-state NMR techniques. We found that the molecular weight (M(w)) of PEO was a crucial factor in controlling the miscibility, chain dynamics and hydrogen bonding interactions between PEO and ER. A critical PEO molecular weight (M(crit)) around 4.5k was found. PEO was well miscible with ER when the molecular weight was below M(crit), where the chain motion of PEO was restricted due to strong inter-chain hydrogen bonding interactions. However, for the blends with high molecular weight PEO (M(w) > M(crit)), the miscibility between PEO and ER was poor, and most of PEO chains were considerably mobile. Finally, polarization inversion spin exchange at magic angle (PISEMA) solid-state NMR experiment further revealed the different mobility of the PEO in ER/PEO blends with different molecular weight of PEO at molecular level. Based on the DSC and NMR results, a tentative model was proposed to illustrate the miscibility in ER/PEO blends. PMID:26577817

  17. De novo design of caseinolytic protein proteases inhibitors based on pharmacophore and 2D molecular fingerprints.

    PubMed

    Wu, Guanzhong; Zhang, Zhen; Chen, Hong; Lin, Kejiang

    2015-06-01

    Caseinolytic protein proteases (ClpP) are large oligomeric protein complexes that contribute to cell homeostasis as well as virulence regulation in bacteria. Inhibitors of ClpP can significantly attenuate the capability to produce virulence factors of the bacteria. In this work, we developed a workflow to expand the chemical space of potential ClpP inhibitors based on a set of β-lactones. In our workflow, an artificial pharmacophore model was generated based on HipHop and HYPOGEN method. A de novo compound library based on molecular fingerprints was constructed and virtually screened by the pharmacophore model. The results were further investigated by molecular docking study. The workflow successfully achieved potential ClpP inhibitors. It could be applied to design more novel potential ClpP inhibitors and provide theoretical basis for the further optimization of the hit compounds. PMID:25937012

  18. Study on the active mechanism of β-secretase inhibitors by molecular simulations.

    PubMed

    Tian, Yue Li; Lv, Min; Li, Jiao Jiao; Xu, Tao; Zhai, Hong Lin; Zhang, Xiao Yun

    2015-08-30

    The proteolytic enzyme β-secretase (BACE-1) is one of potential drug targets for treating Alzheimers's disease. First, the reliable and accurate models of three-dimensional quantitative structure-activity relationship for the BACE-1 inhibitors were established, and the several important structural factors that mainly influence the inhibitory activity were obtained. Second, the results of molecular docking presented the binding mode between BACE-1 and its inhibitors, and molecular dynamic simulations provided the details of the receptor-ligand interactions. Furthermore, several new derivatives were designed and validated based on these theoretical analyses. Our studies revealed the binding mechanism between BACE-1 and its inhibitors, and provide some insights into the further structural modification and the design of new inhibitors with higher activity. PMID:25965961

  19. Molecular design of potent tyrosinase inhibitors having the bibenzyl skeleton.

    PubMed

    Oozeki, Hiromi; Tajima, Reiko; Nihei, Ken-ichi

    2008-10-01

    In order to develop water soluble tyrosinase inhibitors, bibenzyl xyloside 1 isolated from Chlorophytum arundinaceum (liliaceae), and its derivatives 2 and 3 were synthesized by using Wittig reaction and trichloroimidate glycosylation procedure as key steps. Xylosides 1-3 showed potent tyrosinase inhibitory activity with IC(50)s of 1.6, 0.43, and 0.73 microM, respectively, although each NMR data of synthetic bibenzyls was not identical to that of naturally occurring xyloside 1. PMID:18782667

  20. Oxidation reaction of high molecular weight carboxylic acids in supercritical water.

    PubMed

    Jin, Fangming; Moriya, Takehiko; Enomoto, Heiji

    2003-07-15

    Stearic acid, being a model compound of high molecular weight carboxylic acids, was oxidized in a batch reactor by changing the oxygen supply with an insufficient oxygen supply at a constant reaction time at 420 degrees C. On the basis of the intermediate products identified by GC/MS, NMR, and HPLC analyses and the free-radical reaction mechanism, the oxidation pathways of high molecular weight carboxylic acids in supercritical water are discussed. The reaction of carboxylic acids in supercritical water proceeds with the consecutive oxidation of higher molecular weight carboxylic acids to lower molecular weight carboxylic acids through several major pathways. The attack of the hydroxyl radical occurs not only at the carbons in alpha-, beta-, gamma-positions to a --COOH group but also at the carbons ((omega-1)-carbon and/or omega-carbon) far in the alkyl chain from a --COOH group, which may lead to the formation of dicarboxylic acids. PMID:12901673

  1. EPDM polymers with intermolecular asymmetrical molecular weight, crystallinity and diene distribution

    SciTech Connect

    Datta, S.; Cheremishinoff, N.P.; Kresge, E.N.

    1993-12-31

    Rapid extrusion of EPDM elastomers require low viscosity and thus low molecular weights for the polymer. Efficient vulcanization of these elastomers requires network perfection and thus high molecular weights for the polymer. The benefits of these apparently mutually exclusive goals is important in uses of EPDM elastomers which require extrusion of profiles which are later cured. This paper shows that by introducing simultaneously asymmetry in the distribution of molecular weights, crystallinity and vulcanizable sites these apparently contradictory goals can be resolved. While these polymers cannot be made from a single Ziegler polymerization catalyst, the authors show the synthesis of these model EPDM polymers by blending polymers with very different molecular weights, ethylene and ENB contents. These blends can be rapidly extruded without melt fracture and can be cured to vulcanizates which have excellent tensile properties.

  2. Bacillus subtilis 168 levansucrase (SacB) activity affects average levan molecular weight.

    PubMed

    Porras-Domínguez, Jaime R; Ávila-Fernández, Ángela; Miranda-Molina, Afonso; Rodríguez-Alegría, María Elena; Munguía, Agustín López

    2015-11-01

    Levan is a fructan polymer that offers a variety of applications in the chemical, health, cosmetic and food industries. Most of the levan applications depend on levan molecular weight, which in turn depends on the source of the synthesizing enzyme and/or on reaction conditions. Here we demonstrate that in the particular case of levansucrase from Bacillus subtilis 168, enzyme concentration is also a factor defining the molecular weight levan distribution. While a bimodal distribution has been reported at the usual enzyme concentrations (1 U/ml equivalent to 0.1 μM levansucrase) we found that a low molecular weight normal distribution is solely obtained al high enzyme concentrations (>5 U/ml equivalent to 0.5 μM levansucrase) while a high normal molecular weight distribution is synthesized at low enzyme doses (0.1 U/ml equivalent to 0.01 μM of levansucrase). PMID:26256357

  3. PolyPEGA with predetermined molecular weights from enzyme-mediated radical polymerization in water.

    PubMed

    Ng, Yeap-Hung; di Lena, Fabio; Chai, Christina L L

    2011-06-14

    The preparation of acrylic polymers with predetermined molecular weights using metalloenzymes as catalysts, ascorbic acid as reducing agent and alkyl halides as initiators is reported. The mechanism of polymerization resembles an ARGET ATRP process. PMID:21552589

  4. Effect of protein molecular weight on the mass transfer in protein mixing

    NASA Astrophysics Data System (ADS)

    Asad, Ahmed; Chai, Chuan; Wu, JiangTao

    2012-03-01

    The mixing of protein solutions with that of precipitating agents is very important in protein crystallization experiments. In this work, the interferometry images were recorded during the mixing of two proteins with different molecular weights: lysozyme of ˜14.6 kDa, trypsin of ˜23.3 kDa and pepsin of ˜34.8 kDa were placed in a Mach-Zehnder interferometer. The protein molecular weight dependence on the competition of the transport process and kinetics at the interface was studied. The concentration profiles of protein solutions were calculated to analyze the mass transfer during the mixing process. It was observed that the mass transfer process is more efficient during the mixing of proteins with higher molecular weights. In addition, the more rapid concentration changes above the interface suggest that convection may dominate the diffusion. The phenomenon of convection is higher in the protein solutions with higher molecular weight.

  5. The effect of maltose on dextran yield and molecular weight distribution.

    PubMed

    Rodrigues, Sueli; Lona, Liliane M F; Franco, Telma T

    2005-11-01

    Dextran synthesis has been studied since the Second World War, when it was used as blood plasma expander. This polysaccharide composed of glucose units is linked by an alpha-1,6-glucosidic bond. Dextransucrase is a bacterial extra cellular enzyme, which promotes the dextran synthesis from sucrose. When, besides sucrose, another substrate (acceptor) is also present in the reactor, oligosaccharides are produced and part of the glucosyl moieties from glucose is consumed to form these acceptor products, decreasing the dextran yield. Although dextran enzymatic synthesis has been extensively studied, there are few published studies regarding its molecular weight distribution. In this work, the effect of maltose on yield and dextran molecular weight synthesized using dextransucrase from Leuconostoc mesenteroides B512F, was investigated. According to the obtained results, maltose is not able to control and reduce dextran molecular weight distribution and synthesis carried out with or without maltose presented the same molecular weight distribution profile. PMID:16163491

  6. Antioxidant activity of low molecular weight alginate produced by thermal treatment.

    PubMed

    Kelishomi, Zahra Habibi; Goliaei, Bahram; Mahdavi, Hossein; Nikoofar, Alireza; Rahimi, Mahmood; Moosavi-Movahedi, Ali Akbar; Mamashli, Fatemeh; Bigdeli, Bahareh

    2016-04-01

    By definition, antioxidants are molecules that inhibit the oxidation of other molecules. Therefore, such compounds have very important clinical roles. In this study alginate polymer was depolymerized by heat treatment. The resulting low molecular weight alginates were investigated by UV-visible spectroscopy, Viscometry, Dynamic light scattering and FT-IR spectroscopy techniques. Antioxidant properties of these heat products were studied by ABTS and superoxide radical scavenging assays. Results showed that heating caused breaks in the polymer chain and so generation of low molecular weight alginates. Antioxidant measurements confirmed antioxidant activity of alginate increased upon a decrease in molecular weight. Therefore, low molecular weight alginate produced by heating could be considered as a stronger antioxidant than alginate polymer. These products could be useful for industrial and biomedical applications. PMID:26593570

  7. MOLECULAR PATHWAYS: JAK/STAT PATHWAY: MUTATIONS, INHIBITORS, AND RESISTANCE

    PubMed Central

    Quintás-Cardama, Alfonso; Verstovsek, Srdan

    2016-01-01

    Aberrant activation of the JAK/STAT pathway has been reported in a variety of disease states, including inflammatory conditions, hematologic malignancies, and solid tumors. For instance, a large proportion of patients with myeloproliferative neoplasms (MPNs) carry the acquired gain-of-function JAK2 V617F somatic mutation. This knowledge has dramatically improved our understanding of the pathogenesis of MPNs and it has facilitated the development of therapeutics capable of suppressing the constitutive activation of the JAK/STAT pathway, now recognized as a common underlying biological abnormality in MPNs. Ruxolitinib is an oral JAK1 and JAK2 inhibitor that has recently been approved for the treatment of myelofibrosis and has been tested against other hematologic malignancies. A series of agents with different specificities against different members of the JAK family of proteins is currently undergoing evaluation in clinical trials for patients with MPNs, lymphoma, and solid tumors such as breast or pancreatic cancer. Despite their significant clinical activity exhibited in myelofibrosis, some patients fail to respond or progress during JAK kinase inhibitor therapy. Recent reports have shed light into the mechanisms of resistance to JAK kinase inhibitor therapy. Several approaches hold promise to overcome such resistance. PMID:23406773

  8. Corner rounding in EUV photoresist: tuning through molecular weight, PAG size, and development time

    SciTech Connect

    Anderson, Christopher; Daggett, Joe; Naulleau, Patrick

    2009-12-31

    In this paper, the corner rounding bias of a commercially available extreme ultraviolet photoresist is monitored as molecular weight, photoacid generator (PAG) size, and development time are varied. These experiments show that PAG size influences corner biasing while molecular weight and development time do not. Large PAGs are shown to exhibit less corner biasing, and in some cases, lower corner rounding, than small PAGs. In addition, heavier resist polymers are shown to exhibit less corner rounding than lighter ones.

  9. Permeability of the small intestine to substances of different molecular weight

    PubMed Central

    Loehry, C. A.; Axon, A. T. R.; Hilton, P. J.; Hider, R. C.; Creamer, B.

    1970-01-01

    The permeability of the rabbit small intestine has been studied by measuring the plasma clearances of water-soluble molecules over the molecular weight range 60-33,000. An inverse relationship has been demonstrated between permeability and molecular weight. The significance of these findings in relation to current concepts of the `pore hypotheses' is discussed, and the possible physiological and pathological implications are considered. PMID:5430371

  10. High and low molecular weight hyaluronic acid differentially influence macrophage activation

    PubMed Central

    Rayahin, Jamie E.; Buhrman, Jason S.; Zhang, Yu; Koh, Timothy J.; Gemeinhart, Richard A.

    2015-01-01

    Macrophages exhibit phenotypic diversity permitting wide-ranging roles in maintaining physiologic homeostasis. Hyaluronic acid, a major glycosaminoglycan of the extracellular matrix, has been shown to have differential signaling based on its molecular weight. With this in mind, the main objective of this study was to elucidate the role of hyaluronic acid molecular weight on macrophage activation and reprogramming. Changes in macrophage activation were assessed by activation state selective marker measurement, specifically quantitative real time polymerase chain reaction, and cytokine enzyme-linked immunoassays, after macrophage treatment with differing molecular weights of hyaluronic acid under four conditions: the resting state, concurrent with classical activation, and following inflammation involving either classically or alternatively activated macrophages. Regardless of initial polarization state, low molecular weight hyaluronic acid induced a classically activated-like state, confirmed by up-regulation of pro-inflammatory genes, including nos2, tnf, il12b, and cd80, and enhanced secretion of nitric oxide and TNF-α. High molecular weight hyaluronic acid promoted an alternatively activated-like state, confirmed by up regulation of pro-resolving gene transcription, including arg1, il10, and mrc1, and enhanced arginase activity. Overall, our observations suggest that macrophages undergo phenotypic changes dependent on molecular weight of hyaluronan that correspond to either (1) pro-inflammatory response for low molecular weight HA or (2) pro-resolving response for high molecular weight HA. These observations bring significant further understanding of the influence of extracellular matrix polymers, hyaluronic acid in particular, on regulating the inflammatory response of macrophages. This knowledge can be used to guide the design of HA-containing biomaterials to better utilize the natural response to HAs. PMID:26280020

  11. Control of molecular weight of polystyrene using the reverse iodine transfer polymerization (RITP)-emulsion technique.

    PubMed

    Oh, Hyeong Geun; Shin, Hongcheol; Jung, Hyejun; Lee, Byung Hyung; Choe, Soonja

    2011-01-15

    The RITP-emulsion polymerization of styrene in the presence of molecular iodine has been successfully performed using potassium persulfate (KPS) as an initiator and 1-hexadecanesulfonate as an emulsifier under argon atmosphere at 80°C for 7 hrs in the absence of light. The effects of the iodine concentration, molar ratio between KPS and iodine, and solid contents on the molecular weight of polystyrene (PS) were studied. As the iodine concentration increased from 0.05 to 0.504 mmol under the fixed [KPS]/[I(2)] ratio at 4.5, the weight-average molecular weight of PS substantially decreased from 126,120 to 35,690 g/mol, the conversion increased from 85.0% to 95.2%, and the weight-average particle diameter decreased from 159 to 103 nm. In addition, as the ratio of [KPS]/[I(2)] increased from 0.5 to 6.0 at the fixed [I(2)] of 0.504 mmol, the weight-average molecular weight of PS decreased from 72,170 to 30,640 g/mol with high conversion between 81.7% and 96.5%. Moreover, when the styrene solid content increased from 10 to 40 wt.% at the fixed [KPS]/[I(2)] ratio of 4.5, the weight-average molecular weight of PS varied between 33,500 and 37,200 g/mol, the conversion varied between 94.9% and 89.7% and the weight-average diameter varied from 122 to 205 nm. Thus, the control of molecular weight of PS less than 100,000g/mol with high conversion (95%) and particle stability of up to 40 wt.% solid content were easily achieved through the usage of iodine with suitable ratio of [KPS]/[I(2)] in the RITP-emulsion polymerization technique, which is of great industrial importance. PMID:20950818

  12. A low molecular weight antioxidant decreases weight and lowers tumor incidence.

    PubMed

    Mitchell, James B; Xavier, Sandhya; DeLuca, Anne M; Sowers, Anastasia L; Cook, John A; Krishna, Murali C; Hahn, Stephen M; Russo, Angelo

    2003-01-01

    Stable free radical nitroxides are potent antioxidants possessing superoxide dismutase- and catalase-mimetic activity that protect cells and animals against a variety of oxidative insults. Tempol, as a representative nitroxide, was evaluated for its influence on weight maintenance and spontaneous tumor incidence in C3H mice. Tempol administered in either the drinking water or food did not show any untoward effects and prevented animals from becoming obese. Tempol-treated animals' leptin levels were reduced. Long-term treatment with Tempol significantly decreased tumorigenesis when compared to controls (10 vs. 40%, respectively). Selected tissues from Tempol-treated animals exhibited elevated levels of mitochrondrial uncoupling protein-2 (UCP-2) and HSP70. The present data suggest that nitroxides upregulate UCP-2, obviate weight gain, and decrease age-related spontaneous tumor incidence. As a class, nitroxides may provide overall health benefits by contributing to decreased obesity and tumor incidence. PMID:12498984

  13. Hybrid Quantum Mechanical/Molecular Mechanical Molecular Dynamics Simulations of HIV-1 Integrase/Inhibitor Complexes

    PubMed Central

    Nunthaboot, Nadtanet; Pianwanit, Somsak; Parasuk, Vudhichai; Ebalunode, Jerry O.; Briggs, James M.; Kokpol, Sirirat

    2007-01-01

    Human immunodeficiency virus (HIV)-1 integrase (IN) is an attractive target for development of acquired immunodeficiency syndrome chemotherapy. In this study, conventional and coupled quantum mechanical and molecular mechanical (QM/MM) molecular dynamics (MD) simulations of HIV-1 IN complexed with 5CITEP (IN-5CITEP) were carried out. In addition to differences in the bound position of 5CITEP, significant differences at the two levels of theory were observed in the metal coordination geometry and the areas involving residues 116–119 and 140–166. In the conventional MD simulation, the coordination of Mg2+ was found to be a near-perfect octahedral geometry whereas a distorted octahedral complex was observed in QM/MM. All of the above reasons lead to a different pattern of protein-ligand salt link formation that was not observed in the classical MD simulation. Furthermore to provide a theoretical understanding of inhibition mechanisms of 5CITEP and its derivative (DKA), hybrid QM/MM MD simulations of the two complexes (IN-5CITEP and IN-DKA) have been performed. The results reveal that areas involving residues 60–68, 116–119, and 140–149 were substantially different among the two systems. The two systems show similar pattern of metal coordination geometry, i.e., a distorted octahedron. In IN-DKA, both OD1 and OD2 of Asp-64 coordinate the Mg2+ in a monodentate fashion whereas only OD1 is chelated to the metal as observed in IN-5CITEP. The high potency of DKA as compared to 5CITEP is supported by a strong salt link formed between its carboxylate moiety and the ammonium group of Lys-159. Detailed comparisons between HIV-1 IN complexed with DKA and with 5CITEP provide information about ligand structure effects on protein-ligand interactions in particular with the Lys-159. This is useful for the design of new selective HIV-1 IN inhibitors. PMID:17693479

  14. An Investigation of Molecular Docking and Molecular Dynamic Simulation on Imidazopyridines as B-Raf Kinase Inhibitors.

    PubMed

    Xie, Huiding; Li, Yupeng; Yu, Fang; Xie, Xiaoguang; Qiu, Kaixiong; Fu, Jijun

    2015-01-01

    In the recent cancer treatment, B-Raf kinase is one of key targets. Nowadays, a group of imidazopyridines as B-Raf kinase inhibitors have been reported. In order to investigate the interaction between this group of inhibitors and B-Raf kinase, molecular docking, molecular dynamic (MD) simulation and binding free energy (ΔGbind) calculation were performed in this work. Molecular docking was carried out to identify the key residues in the binding site, and MD simulations were performed to determine the detail binding mode. The results obtained from MD simulation reveal that the binding site is stable during the MD simulations, and some hydrogen bonds (H-bonds) in MD simulations are different from H-bonds in the docking mode. Based on the obtained MD trajectories, ΔGbind was computed by using Molecular Mechanics Generalized Born Surface Area (MM-GBSA), and the obtained energies are consistent with the activities. An energetic analysis reveals that both electrostatic and van der Waals contributions are important to ΔGbind, and the unfavorable polar solvation contribution results in the instability of the inhibitor with the lowest activity. These results are expected to understand the binding between B-Raf and imidazopyridines and provide some useful information to design potential B-Raf inhibitors. PMID:26580609

  15. An Investigation of Molecular Docking and Molecular Dynamic Simulation on Imidazopyridines as B-Raf Kinase Inhibitors

    PubMed Central

    Xie, Huiding; Li, Yupeng; Yu, Fang; Xie, Xiaoguang; Qiu, Kaixiong; Fu, Jijun

    2015-01-01

    In the recent cancer treatment, B-Raf kinase is one of key targets. Nowadays, a group of imidazopyridines as B-Raf kinase inhibitors have been reported. In order to investigate the interaction between this group of inhibitors and B-Raf kinase, molecular docking, molecular dynamic (MD) simulation and binding free energy (ΔGbind) calculation were performed in this work. Molecular docking was carried out to identify the key residues in the binding site, and MD simulations were performed to determine the detail binding mode. The results obtained from MD simulation reveal that the binding site is stable during the MD simulations, and some hydrogen bonds (H-bonds) in MD simulations are different from H-bonds in the docking mode. Based on the obtained MD trajectories, ΔGbind was computed by using Molecular Mechanics Generalized Born Surface Area (MM-GBSA), and the obtained energies are consistent with the activities. An energetic analysis reveals that both electrostatic and van der Waals contributions are important to ΔGbind, and the unfavorable polar solvation contribution results in the instability of the inhibitor with the lowest activity. These results are expected to understand the binding between B-Raf and imidazopyridines and provide some useful information to design potential B-Raf inhibitors. PMID:26580609

  16. Effect of molecular weight, calcium stearate, and sterilization methods on the wear of ultra high molecular weight polyethylene acetabular cups in a hip joint simulator.

    PubMed

    McKellop, H A; Shen, F W; Campbell, P; Ota, T

    1999-05-01

    Orthopaedic surgeons must currently choose from several types of ultra high molecular weight polyethylene acetabular cups that differ in their material properties and in the methods used for their sterilization. Information on the wear resistance of these different cups may help in the selection process. This study included two separate tests for wear run on a hip simulator to investigate the effect of molecular weight, calcium stearate, and sterilization methods on the wear resistance of ultra high molecular weight polyethylene acetabular cups. Test 1 revealed nearly identical wear rates for acetabular cups with molecular weights in two distinct ranges, as well as for cups with molecular weights in the same range but with or without calcium stearate added. In Test 2, cups that were sterilized in air with gamma irradiation exhibited lower rates of wear than those sterilized with ethylene oxide, presumably due to the crosslinking induced by the irradiation. In addition, cups that were irradiated while packed in a partial vacuum to minimize oxygen absorbed in the surface layer initially showed lower rates of wear than those irradiated in air, with the wear rates becoming similar as wear penetrated the more oxidized surface layer and the more crosslinked subsurface region. Because these tests were run a few months after the irradiation, the potential effects of long-term oxidation of any residual free radicals in the irradiated materials could not be taken into account. After artificial aging to accelerate oxidative degradation of the materials, the wear rates could be markedly different. Analyses performed after wear indicated that the irradiated (i.e., crosslinked) cups exhibited a smaller proportion of, as well as shorter, fibrils in the wear debris and an increased crystallinity and melting temperature and that gamma irradiation in the low-oxygen environment reduced the level of oxidation and increased the level of crosslinking in the surface region of the cups

  17. Potent Human Telomerase Inhibitors: Molecular Dynamic Simulations, Multiple Pharmacophore-Based Virtual Screening, and Biochemical Assays.

    PubMed

    Shirgahi Talari, Faezeh; Bagherzadeh, Kowsar; Golestanian, Sahand; Jarstfer, Michael; Amanlou, Massoud

    2015-12-28

    Telomere maintenance is a universal cancer hallmark, and small molecules that disrupt telomere maintenance generally have anticancer properties. Since the vast majority of cancer cells utilize telomerase activity for telomere maintenance, the enzyme has been considered as an anticancer drug target. Recently, rational design of telomerase inhibitors was made possible by the determination of high resolution structures of the catalytic telomerase subunit from a beetle and subsequent molecular modeling of the human telomerase complex. A hybrid strategy including docking, pharmacophore-based virtual screening, and molecular dynamics simulations (MDS) were used to identify new human telomerase inhibitors. Docking methodology was applied to investigate the ssDNA telomeric sequence and two well-known human telomerase inhibitors' (BIBR1532 and MST-312) modes of interactions with hTERT TEN domain. Subsequently molecular dynamic simulations were performed to monitor and compare hTERT TEN domain, TEN-ssDNA, TEN-BIBR1532, TEN-MST-312, and TEN-ssDNA-BIBR1532 behavior in a dynamic environment. Pharmacophore models were generated considering the inhibitors manner in the TEN domain anchor site. These exploratory studies identified several new potent inhibitors whose IC50 values were generated experimentally in a low micromolar range with the aid of biochemical assays, including both the direct telomerase and the telomeric repeat amplification protocol (TRAP) assays. The results suggest that the current models of human telomerase are useful templates for rational inhibitor design. PMID:26529120

  18. Western blotting of high and low molecular weight proteins using heat.

    PubMed

    Kurien, Biji T; Scofield, R Hal

    2015-01-01

    A method for the electrophoretic transfer of high and low molecular weight proteins to nitrocellulose membranes following sodium dodecyl sulfate (SDS) polyacrylamide gel is described here. The transfer was performed with heated (70-75 °C) normal transfer buffer from which methanol had been omitted. Complete transfer of high and low molecular weight antigens (molecular weight protein standards, a purified protein, and proteins from a human tissue extract) could be carried out in 10 min for a 7 % (0.75 mm) SDS polyacrylamide gel. For 10 and 12.5 % gels (0.75 mm) the corresponding time was 15 min. A complete transfer could be carried out in 20 min for 7, 10, and 12.5 % gels (1.5 mm gels). The permeability of the gel is increased by heat, such that the proteins trapped in the polyacrylamide gel matrix can be easily transferred to the membrane. The heat mediated transfer method was compared with a conventional transfer protocol, under similar conditions. The conventional method transferred minimal low molecular weight proteins while retaining most of the high molecular weight proteins in the gel. In summary, this procedure is particularly useful for the transfer of high molecular weight proteins, very rapid, and avoids the use of methanol. PMID:26044007

  19. Molecular weight dependent vertical composition profiles of PCDTBT:PC71BM blends for organic photovoltaics

    NASA Astrophysics Data System (ADS)

    Kingsley, James W.; Marchisio, Pier Paolo; Yi, Hunan; Iraqi, Ahmed; Kinane, Christy J.; Langridge, Sean; Thompson, Richard L.; Cadby, Ashley J.; Pearson, Andrew J.; Lidzey, David G.; Jones, Richard A. L.; Parnell, Andrew J.

    2014-06-01

    We have used Soxhlet solvent purification to fractionate a broad molecular weight distribution of the polycarbazole polymer PCDTBT into three lower polydispersity molecular weight fractions. Organic photovoltaic devices were made using a blend of the fullerene acceptor PC71BM with the molecular weight fractions. An average power conversion efficiency of 5.89% (peak efficiency of 6.15%) was measured for PCDTBT blend devices with a number average molecular weight of Mn = 25.5 kDa. There was significant variation between the molecular weight fractions with low (Mn = 15.0 kDa) and high (Mn = 34.9 kDa) fractions producing devices with average efficiencies of 5.02% and 3.70% respectively. Neutron reflectivity measurements on these polymer:PC71BM blend layers showed that larger molecular weights leads to an increase in the polymer enrichment layer thickness at the anode interface, this improves efficiency up to a limiting point where the polymer solubility causes a reduction of the PCDTBT concentration in the active layer.

  20. Molecular weight dependent vertical composition profiles of PCDTBT:PC71BM blends for organic photovoltaics

    PubMed Central

    Kingsley, James W.; Marchisio, Pier Paolo; Yi, Hunan; Iraqi, Ahmed; Kinane, Christy J.; Langridge, Sean; Thompson, Richard L.; Cadby, Ashley J.; Pearson, Andrew J.; Lidzey, David G.; Jones, Richard A. L.; Parnell, Andrew J.

    2014-01-01

    We have used Soxhlet solvent purification to fractionate a broad molecular weight distribution of the polycarbazole polymer PCDTBT into three lower polydispersity molecular weight fractions. Organic photovoltaic devices were made using a blend of the fullerene acceptor PC71BM with the molecular weight fractions. An average power conversion efficiency of 5.89% (peak efficiency of 6.15%) was measured for PCDTBT blend devices with a number average molecular weight of Mn = 25.5 kDa. There was significant variation between the molecular weight fractions with low (Mn = 15.0 kDa) and high (Mn = 34.9 kDa) fractions producing devices with average efficiencies of 5.02% and 3.70% respectively. Neutron reflectivity measurements on these polymer:PC71BM blend layers showed that larger molecular weights leads to an increase in the polymer enrichment layer thickness at the anode interface, this improves efficiency up to a limiting point where the polymer solubility causes a reduction of the PCDTBT concentration in the active layer. PMID:24924096

  1. Molecular weight dependent vertical composition profiles of PCDTBT:PC₇₁BM blends for organic photovoltaics.

    PubMed

    Kingsley, James W; Marchisio, Pier Paolo; Yi, Hunan; Iraqi, Ahmed; Kinane, Christy J; Langridge, Sean; Thompson, Richard L; Cadby, Ashley J; Pearson, Andrew J; Lidzey, David G; Jones, Richard A L; Parnell, Andrew J

    2014-01-01

    We have used Soxhlet solvent purification to fractionate a broad molecular weight distribution of the polycarbazole polymer PCDTBT into three lower polydispersity molecular weight fractions. Organic photovoltaic devices were made using a blend of the fullerene acceptor PC₇₁BM with the molecular weight fractions. An average power conversion efficiency of 5.89% (peak efficiency of 6.15%) was measured for PCDTBT blend devices with a number average molecular weight of Mn = 25.5 kDa. There was significant variation between the molecular weight fractions with low (Mn = 15.0 kDa) and high (Mn = 34.9 kDa) fractions producing devices with average efficiencies of 5.02% and 3.70% respectively. Neutron reflectivity measurements on these polymer:PC₇₁BM blend layers showed that larger molecular weights leads to an increase in the polymer enrichment layer thickness at the anode interface, this improves efficiency up to a limiting point where the polymer solubility causes a reduction of the PCDTBT concentration in the active layer. PMID:24924096

  2. Effect of matrix molecular weight on the coarsening mechanism of polymer-grafted gold nanocrystals.

    PubMed

    Jia, Xiaolong; Listak, Jessica; Witherspoon, Velencia; Kalu, E Eric; Yang, Xiaoping; Bockstaller, Michael R

    2010-07-20

    A systematic evaluation of the effect of polymer matrix molecular weight on the coarsening kinetics of uniformly dispersed polystyrene-grafted gold nanoparticles is presented. Particle coarsening is found to proceed via three stages (i.e., atomic-diffusion-based Ostwald ripening (OR), particle-migration-based collision-coalescence, and the subsequent reshaping of particle assemblies). The relative significance of each stage and hence the evolution of particle size and shape have been found to depend sensitively upon time, temperature, and the molecular weight of the host polymer. At temperatures close to the matrix glass-transition temperature, Ostwald ripening has been observed to be dominant on all experimental timescales. With increasing annealing temperature, collision coalescence becomes the dominant mode of coarsening, leading to rapid particle growth. The onset of the latter process is found to be increasingly delayed with increasing molecular weight of the polymer host. Particle coalescence is observed to proceed via two fundamental modes (i.e., diffusion-limited aggregation and growth resulting in the formation of fractal particle clusters and the subsequent recrystallization into more spherical monolithic aggregate structures). Interestingly, particle coarsening in high-molecular-weight matrix polymers is found to proceed significantly faster than predicted on the basis of the bulk polymer viscosity; this acceleration is interpreted to be a consequence of the network characteristics of high-molecular-weight polymers by analogy to the phenomenon of nanoviscosity that has been reported in the context of nanoparticle diffusion within high-molecular-weight polymers. PMID:20575544

  3. Chromatin to clinic: The molecular rationale for PARP1 inhibitor function

    PubMed Central

    Knudsen, Karen E.; de Bono, Johann S.; Rubin, Mark A.; Feng, Felix Y.

    2015-01-01

    Poly(ADP-ribose) polymerase 1 (PARP1) inhibitors were recently shown to have clinical impact in a number of disease settings, particularly as related to cancer therapy, treatment for cardiovascular dysfunction, and suppression of inflammation. The molecular basis for PARP1 inhibitor function is complex, and appears to depend on the dual roles of PARP1 in DNA damage repair and transcriptional regulation. Here, the mechanisms by which PARP-1 inhibitors elicit clinical response are discussed, and strategies for translating the preclinical elucidation of PARP-1 function into advances in disease management are reviewed. PMID:26091341

  4. 21 CFR 177.1440 - 4,4′-Isopropylidenediphenol-epichlorohydrin resins minimum molecular weight 10,000.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... resins minimum molecular weight 10,000. 177.1440 Section 177.1440 Food and Drugs FOOD AND DRUG...′-Isopropylidenediphenol-epichlorohydrin resins minimum molecular weight 10,000. 4,4′-Isopropylidenediphenol-epichlo-rohydrin resins having a minimum molecular weight of 10,000 may be safely used as articles or components...

  5. 21 CFR 177.1440 - 4,4′-Isopropylidenediphenol-epichlorohydrin resins minimum molecular weight 10,000.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... resins minimum molecular weight 10,000. 177.1440 Section 177.1440 Food and Drugs FOOD AND DRUG... Contact Surfaces § 177.1440 4,4′-Isopropylidenediphenol-epichlorohydrin resins minimum molecular weight 10,000. 4,4′-Isopropylidenediphenol-epichlo-rohydrin resins having a minimum molecular weight of...

  6. Prediction of Selective Serotonin Reuptake Inhibitor Response Using Diffusion-Weighted MRI

    PubMed Central

    DeLorenzo, Christine; Delaparte, Lauren; Thapa-Chhetry, Binod; Miller, Jeffrey M.; Mann, J. John; Parsey, Ramin V.

    2013-01-01

    Pre-treatment differences in serotonergic binding between those who remit to antidepressant treatment and those who do not have been found using Positron Emission Tomography (PET). To investigate these differences, an exploratory study was performed using a second imaging modality, diffusion-weighted MRI (DW-MRI). Eighteen antidepressant-free subjects with Major Depressive Disorder received a 25-direction DW-MRI scan prior to 8 weeks of selective serotonin reuptake inhibitor treatment. Probabilistic tractography was performed between the midbrain/raphe and two target regions implicated in depression pathophysiology (amygdala and hippocampus). Average fractional anisotropy (FA) within the derived tracts was compared between SSRI remitters and non-remitters, and correlation between pre-treatment FA values and SSRI treatment outcome was assessed. Results indicate that average FA in DW-MRI-derived tracts to the right amygdala was significantly lower in non-remitters (0.55 ± 0.04) than remitters (0.61 ± 0.04, p < 0.01). In addition, there was a significant correlation between average FA in tracts to the right amygdala and SSRI treatment response. These relationships were found at a trend level when using the left amygdala as a tractography target. No significant differences were observed when using the hippocampus as target. These regional differences, consistent with previous PET findings, suggest that the integrity and/or number of white matter fibers terminating in the right amygdala may be compromised in SSRI non-remitters. Further, this study points to the benefits of multimodal imaging and suggests that DW-MRI may provide a pre-treatment signature of SSRI depression remission at 8 weeks. PMID:23508528

  7. Molecular dynamics of protein kinase-inhibitor complexes: a valid structural information.

    PubMed

    Caballero, Julio; Alzate-Morales, Jans H

    2012-01-01

    Protein kinases (PKs) are key components of protein phosphorylation based signaling networks in eukaryotic cells. They have been identified as being implicated in many diseases. High-resolution X-ray crystallographic data exist for many PKs and, in many cases, these structures are co-complexed with inhibitors. Although this valuable information confirms the precise structure of PKs and their complexes, it ignores the dynamic movements of the structures which are relevant to explain the affinities and selectivity of the ligands, to characterize the thermodynamics of the solvated complexes, and to derive predictive models. Atomistic molecular dynamics (MD) simulations present a convenient way to study PK-inhibitor complexes and have been increasingly used in recent years in structure-based drug design. MD is a very useful computational method and a great counterpart for experimentalists, which helps them to derive important additional molecular information. That enables them to follow and understand structure and dynamics of protein-ligand systems with extreme molecular detail on scales where motion of individual atoms can be tracked. MD can be used to sample dynamic molecular processes, and can be complemented with more advanced computational methods (e.g., free energy calculations, structure-activity relationship analysis). This review focuses on the most commonly applications to study PK-inhibitor complexes using MD simulations. Our aim is that researchers working in the design of PK inhibitors be aware of the benefits of this powerful tool in the design of potent and selective PK inhibitors. PMID:22571663

  8. A theoretical study of the molecular mechanism of the GAPDH Trypanosoma cruzi enzyme involving iodoacetate inhibitor

    NASA Astrophysics Data System (ADS)

    Carneiro, Agnaldo Silva; Lameira, Jerônimo; Alves, Cláudio Nahum

    2011-10-01

    The glyceraldehyde-3-phosphate dehydrogenase enzyme (GAPDH) is an important biological target for the development of new chemotherapeutic agents against Chagas disease. In this Letter, the inhibition mechanism of GAPDH involving iodoacetate (IAA) inhibitor was studied using the hybrid quantum mechanical/molecular mechanical (QM/MM) approach and molecular dynamic simulations. Analysis of the potential energy surface and potential of mean force show that the covalent attachment of IAA inhibitor to the active site of the enzyme occurs as a concerted process. In addition, the energy terms decomposition shows that NAD+ plays an important role in stabilization of the reagents and transition state.

  9. Histone deacetylase inhibitors increase glucocerebrosidase activity in Gaucher disease by modulation of molecular chaperones

    PubMed Central

    Yang, Chunzhang; Rahimpour, Shervin; Lu, Jie; Pacak, Karel; Ikejiri, Barbara; Brady, Roscoe O.; Zhuang, Zhengping

    2013-01-01

    Gaucher disease is caused by mutations of the GBA gene that encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA mutations often result in protein misfolding and premature degradation, but usually exert less effect on catalytic activity. In this study, we identified the molecular mechanism by which histone deacetylase inhibitors increase the quantity and activity of GCase. Specifically, these inhibitors limit the deacetylation of heat shock protein 90, resulting in less recognition of the mutant peptide and GCase degradation. These findings provide insight into a possible therapeutic strategy for Gaucher disease and other genetic disorders by modifying molecular chaperone and protein degradation pathways. PMID:23277556

  10. Use of Kinematic Viscosity Data for the Evaluation of the Molecular Weight of Petroleum Oils

    ERIC Educational Resources Information Center

    Maroto, J. A.; Quesada-Perez, M.; Ortiz-Hernandez, A. J.

    2010-01-01

    A new laboratory procedure for the evaluation of the mean molecular weight (mean relative molecular mass) of petroleum oils with high accuracy is described. The density and dynamic viscosity of three commercial petroleum oils are measured at different temperatures. These experimental data are used to calculate the kinematic viscosity as a function…

  11. Inhibitors to Polyhydroxyalkanoate (PHA) Synthases: Synthesis, Molecular Docking, and Implications

    PubMed Central

    Cao, Ruikai; Maurmann, Leila; Li, Ping

    2015-01-01

    Polyhydroxyalkanoate (PHA) synthases (PhaCs) catalyze the formation of biodegradable PHAs that are considered as an ideal alternative to nonbiodegradable synthetic plastics. However, study of PhaC has been challenging because the rate of PHA chain elongation is much faster than that of initiation. This difficulty along with lack of a structure has become the main hurdle to understand and engineer PhaCs for economical PHA production. Here we reported the synthesis of two carbadethia CoA analogs, sT-CH2-CoA 26a and sTet-CH2-CoA 26b as well as sT-aldehyde 29 as new PhaC inhibitors. Study of these analogs with PhaECAv revealed that 26a/b and 29 are competitive and mixed inhibitors, respectively. It was observed that CoA moiety and PHA chain extension can increase binding affinity, which is consistent with the docking study. Estimation from Kic of 26a/b predicts that a CoA analog attached with an octameric-HB chain may facilitate the formation of a kinetically well-behaved synthase. PMID:25394180

  12. ROS1 Kinase Inhibitors for Molecular-Targeted Therapies.

    PubMed

    Al-Sanea, M M; Abdelazem, A Z; Park, B S; Yoo, K H; Sim, T; Kwon, Y J; Lee, S H

    2016-01-01

    ROS1 is a pivotal transmembrane receptor protein tyrosine kinase which regulates several cellular processes like apoptosis, survival, differentiation, proliferation, cell migration, and transformation. There is increasing evidence supporting that ROS1 plays an important role in different malignancies including glioblastoma, colorectal cancer, gastric adenocarcinoma, inflammatory myofibroblastic tumor, ovarian cancer, angiosarcoma, and non small cell lung cancer; thus, ROS1 has become a potential drug discovery target. ROS1 shares about 49% sequence homology with ALK primary structure; therefore, wide range of ALK kinase inhibitors have shown in vitro inhibitory activity against ROS1 kinase. After Crizotinib approval by FDA for the management of ALK-rearranged lung cancer, ROS1-positive tumors have been focused. Although significant advancements have been achieved in understanding ROS1 function and its signaling pathways plus recent discovery of small molecules modulating ROS1 protein, a vital need of medicinal chemistry efforts is still required to produce selective and potent ROS1 inhibitors as an important therapeutic strategy for different human malignancies. This review focuses on the current knowledge about different scaffolds targeting ROS1 rearrangements, methods to synthesis, and some biological data about the most potent compounds that have delivered various scaffold structures. PMID:26438251

  13. Inhibitors of polyhydroxyalkanoate (PHA) synthases: synthesis, molecular docking, and implications.

    PubMed

    Zhang, Wei; Chen, Chao; Cao, Ruikai; Maurmann, Leila; Li, Ping

    2015-01-01

    Polyhydroxyalkanoate (PHA) synthases (PhaCs) catalyze the formation of biodegradable PHAs that are considered to be ideal alternatives to non-biodegradable synthetic plastics. However, study of PhaCs has been challenging because the rate of PHA chain elongation is much faster than that of initiation. This difficulty, along with lack of a crystal structure, has become the main hurdle to understanding and engineering PhaCs for economical PHA production. Here we report the synthesis of two carbadethia CoA analogues--sT-CH2-CoA (26 a) and sTet-CH2-CoA (26 b)--as well as sT-aldehyde (saturated trimer aldehyde, 29), as new PhaC inhibitors. Study of these analogues with PhaECAv revealed that 26 a/b and 29 are competitive and mixed inhibitors, respectively. Both the CoA moiety and extension of PHA chain will increase binding affinity; this is consistent with our docking study. Estimation of the Kic values of 26 a and 26 b predicts that a CoA analogue incorporating an octameric hydroxybutanoate (HB) chain might facilitate the formation of a kinetically well-behaved synthase. PMID:25394180

  14. Interaction Analysis of T7 RNA Polymerase with Heparin and Its Low Molecular Weight Derivatives - An In Silico Approach.

    PubMed

    Borkotoky, Subhomoi; Meena, Chetan Kumar; Murali, Ayaluru

    2016-01-01

    The single subunit T7 RNA polymerase (T7RNAP) is a model enzyme for studying the transcription process and for various biochemical and biophysical studies. Heparin is a commonly used inhibitor against T7RNAP and other RNA polymerases. However, exact interaction between heparin and T7RNAP is still not completely understood. In this work, we analyzed the binding pattern of heparin by docking heparin and few of its low molecular weight derivatives to T7RNAP, which helps in better understanding of T7RNAP inhibition mechanism. The efficiency of the compounds was calculated by docking the selected compounds and post-docking molecular mechanics/generalized Born surface area analysis. Evaluation of the simulation trajectories and binding free energies of the complexes after simulation showed enoxaparin to be the best among low molecular weight heparins. Binding free energy analysis revealed that van der Waals interactions and polar solvation energy provided the substantial driving force for the binding process. Furthermore, per-residue free energy decomposition analysis revealed that the residues Asp 471, Asp 506, Asp 537, Tyr 571, Met 635, Asp 653, Pro 780, and Asp 812 are important for heparin interaction. Apart from these residues, most favorable contribution in all the three complexes came from Asp 506, Tyr 571, Met 635, Glu 652, and Asp 653, which can be essential for binding of heparin-like structures with T7RNAP. The results obtained from this study will be valuable for the future rational design of novel and potent inhibitors against T7RNAP and related proteins. PMID:27594785

  15. Interaction Analysis of T7 RNA Polymerase with Heparin and Its Low Molecular Weight Derivatives – An In Silico Approach

    PubMed Central

    Borkotoky, Subhomoi; Meena, Chetan Kumar; Murali, Ayaluru

    2016-01-01

    The single subunit T7 RNA polymerase (T7RNAP) is a model enzyme for studying the transcription process and for various biochemical and biophysical studies. Heparin is a commonly used inhibitor against T7RNAP and other RNA polymerases. However, exact interaction between heparin and T7RNAP is still not completely understood. In this work, we analyzed the binding pattern of heparin by docking heparin and few of its low molecular weight derivatives to T7RNAP, which helps in better understanding of T7RNAP inhibition mechanism. The efficiency of the compounds was calculated by docking the selected compounds and post-docking molecular mechanics/generalized Born surface area analysis. Evaluation of the simulation trajectories and binding free energies of the complexes after simulation showed enoxaparin to be the best among low molecular weight heparins. Binding free energy analysis revealed that van der Waals interactions and polar solvation energy provided the substantial driving force for the binding process. Furthermore, per-residue free energy decomposition analysis revealed that the residues Asp 471, Asp 506, Asp 537, Tyr 571, Met 635, Asp 653, Pro 780, and Asp 812 are important for heparin interaction. Apart from these residues, most favorable contribution in all the three complexes came from Asp 506, Tyr 571, Met 635, Glu 652, and Asp 653, which can be essential for binding of heparin-like structures with T7RNAP. The results obtained from this study will be valuable for the future rational design of novel and potent inhibitors against T7RNAP and related proteins. PMID:27594785

  16. From oligomers to molecular giants of soybean oil in supercritical carbon dioxide medium: 1. Preparation of polymers with lower molecular weight from soybean oil.

    PubMed

    Liu, Zengshe; Sharma, Brajendra K; Erhan, Sevim Z

    2007-01-01

    Polymers with a low molecular weight derived from soybean oil have been prepared in a supercritical carbon dioxide medium by cationic polymerization. Boron trifluoride diethyl etherate was used as an initiator. Influences of polymerization temperature, amount of initiator, and carbon dioxide pressure on the molecular weight were investigated. It is shown that the higher polymerization temperature favors polymers with relatively higher molecular weights. Larger amounts of initiator also provide polymers with higher molecular weights. Higher pressure favors polymers with relatively higher molecular weights. The applications of these soy-based materials will be in the lubrication and hydraulic fluid areas. PMID:17206812

  17. Determination of molecular weights of humic substances by analytical (UV scanning) ultracentrifugation

    NASA Astrophysics Data System (ADS)

    Reid, Patrick M.; Wilkinson, Alan E.; Tipping, Edward; Jones, Malcolm N.

    1990-01-01

    Samples of peat humic acid (PHA) and surface water humic (WBHA) and fulvic (WBFA) acids have been extracted from Whitray Beck in North Yorkshire, U.K. The molecular weights of the extracts have been investigated by sedimentation equilibrium using an analytical ultracentrifuge equipped with a UV scanning system. The system allows measurements to be made at low concentrations of humic substances, comparable to those existing in natural humic-rich water. A method is described for correcting UV scanning data for changes in the optical properties of the materials with changing molecular weight. Measurements have also been made on reference samples of Suwannee river humic (SRHA) and fulvic (SRFA) acids from the International Humic Substances Society (IHSS). The weight-average molecular weights of the extracted samples range from approximately 2000 to 17000 and follow a series PHA > WBHA > WBFA. Apparent specific volumes of these materials were in a range from 0.45 to 0.58 cm 3 g -1 as measured by digital densimetry. All the samples studied were analysed by gel filtration, but the molecular weights determined by this method based on a globular protein calibration are not in good accord with the absolute determinations by the sedimentation-equilibrium technique. The molecular weight of the SRHA determined by sedimentation equilibrium is in good agreement with that reported by BECKETT (1987) et al., based on flow field-flow fractionation.

  18. Effect of high-speed jet on flow behavior, retrogradation, and molecular weight of rice starch.

    PubMed

    Fu, Zhen; Luo, Shun-Jing; BeMiller, James N; Liu, Wei; Liu, Cheng-Mei

    2015-11-20

    Effects of high-speed jet (HSJ) treatment on flow behavior, retrogradation, and degradation of the molecular structure of indica rice starch were investigated. Decreasing with the number of HSJ treatment passes were the turbidity of pastes (degree of retrogradation), the enthalpy of melting of retrograded rice starch, weight-average molecular weights and weight-average root-mean square radii of gyration of the starch polysaccharides, and the amylopectin peak areas of SEC profiles. The areas of lower-molecular-weight polymers increased. The chain-length distribution was not significantly changed. Pastes of all starch samples exhibited pseudoplastic, shear-thinning behavior. HSJ treatment increased the flow behavior index and decreased the consistency coefficient and viscosity. The data suggested that degradation of amylopectin was mainly involved and that breakdown preferentially occurred in chains between clusters. PMID:26344255

  19. Slip of polydisperse polymers: Molecular weight distribution above and below the plane of slip

    NASA Astrophysics Data System (ADS)

    Sabzevari, Seyed Mostafa; Strandman, Satu; Wood-Adams, Paula Marie

    2015-04-01

    When strong slip occurs during the drag flow of highly entangled polybutadienes (PBD) in a sliding plate rheometer equipped with stainless steel parallel plates, a thin film of polymer debris remains on the substrate after the slip. This debris is assumed to be formed by the disentanglement process that occurs in strong slip at a distance of about one molecular size from the plate. In order to evaluate the composition of the debris we collected it with tetrahydrofuran and subjected it to gel permeation chromatography. It was found that the molecular weight distribution (MWD) of the debris is significantly different from that of the bulk. Moreover, in mixtures prepared from long and short PBDs with distinctly different molecular weight distributions, the MWD of the debris was found to be richer in low molecular weight components and leaner in the high molecular weight components compared to the bulk. This information is important since it reveals the compositional difference between the bulk and interfacial layer above and below the plane of slip. The difference in MWD is likely a consequence of the strong slip in which some of long chains are pulled away from the surface-adsorbed chains by the flow leaving a debris lean in the high molecular weight component.

  20. Novel Cancer Chemotherapy Hits by Molecular Topology: Dual Akt and Beta-Catenin Inhibitors

    PubMed Central

    Morell, Cecilia; Rodríguez-Henche, Nieves; Recio-Iglesias, Maria Carmen; Garcia-Domenech, Ramon

    2015-01-01

    Background and Purpose Colorectal and prostate cancers are two of the most common types and cause of a high rate of deaths worldwide. Therefore, any strategy to stop or at least slacken the development and progression of malignant cells is an important therapeutic choice. The aim of the present work is the identification of novel cancer chemotherapy agents. Nowadays, many different drug discovery approaches are available, but this paper focuses on Molecular Topology, which has already demonstrated its extraordinary efficacy in this field, particularly in the identification of new hit and lead compounds against cancer. This methodology uses the graph theoretical formalism to numerically characterize molecular structures through the so called topological indices. Once obtained a specific framework, it allows the construction of complex mathematical models that can be used to predict physical, chemical or biological properties of compounds. In addition, Molecular Topology is highly efficient in selecting and designing new hit and lead drugs. According to the aforementioned, Molecular Topology has been applied here for the construction of specific Akt/mTOR and β-catenin inhibition mathematical models in order to identify and select novel antitumor agents. Experimental Approach Based on the results obtained by the selected mathematical models, six novel potential inhibitors of the Akt/mTOR and β-catenin pathways were identified. These compounds were then tested in vitro to confirm their biological activity. Conclusion and Implications Five of the selected compounds, CAS n° 256378-54-8 (Inhibitor n°1), 663203-38-1 (Inhibitor n°2), 247079-73-8 (Inhibitor n°3), 689769-86-6 (Inhibitor n°4) and 431925-096 (Inhibitor n°6) gave positive responses and resulted to be active for Akt/mTOR and/or β-catenin inhibition. This study confirms once again the Molecular Topology’s reliability and efficacy to find out novel drugs in the field of cancer. PMID:25910265

  1. Proteasome inhibitors - molecular basis and current perspectives in multiple myeloma.

    PubMed

    Kubiczkova, Lenka; Pour, Ludek; Sedlarikova, Lenka; Hajek, Roman; Sevcikova, Sabina

    2014-06-01

    Inhibition of proteasome, a proteolytic complex responsible for the degradation of ubiquitinated proteins, has emerged as a powerful strategy for treatment of multiple myeloma (MM), a plasma cell malignancy. First-in-class agent, bortezomib, has demonstrated great positive therapeutic efficacy in MM, both in pre-clinical and in clinical studies. However, despite its high efficiency, a large proportion of patients do not achieve sufficient clinical response. Therefore, the development of a second-generation of proteasome inhibitors (PIs) with improved pharmacological properties was needed. Recently, several of these new agents have been introduced into clinics including carfilzomib, marizomib and ixazomib. Further, new orally administered second-generation PI oprozomib is being investigated. This review provides an overview of main mechanisms of action of PIs in MM, focusing on the ongoing development and progress of novel anti-proteasome therapeutics. PMID:24712303

  2. Hyaluronic Acid Molecular Weight Determines Lung Clearance and Biodistribution after Instillation.

    PubMed

    Kuehl, Christopher; Zhang, Ti; Kaminskas, Lisa M; Porter, Christopher J H; Davies, Neal M; Forrest, Laird; Berkland, Cory

    2016-06-01

    Hyaluronic acid (HA) has emerged as a versatile polymer for drug delivery. Multiple commercial products utilize HA, it can be obtained in a variety of molecular weights, and it offers chemical handles for cross-linkers, drugs, or imaging agents. Previous studies have investigated multiple administration routes, but the absorption, biodistribution, and pharmacokinetics of HA after delivery to the lung is relatively unknown. Here, pharmacokinetic parameters were investigated by delivering different molecular weights of HA (between 7 and 741 kDa) to the lungs of mice. HA was labeled with either a near-infrared dye or with iodine-125 conjugated to HA using a tyrosine linker. In initial studies, dye-labeled HA was instilled into the lungs and fluorescent images of organs were collected at 1, 8, and 24 h post administration. Data suggested longer lung persistence of higher molecular weight HA, but signal diminished for all molecular weights at 8 h. To better quantitate pharmacokinetic parameters, different molecular weights of iodine-125 labeled HA were instilled and organ radioactivity was determined after 1, 2, 4, 6, and 8 h. The data showed that, after instillation, the lungs contained the highest levels of HA, as expected, followed by the gastrointestinal tract. Smaller molecular weights of HA showed more rapid systemic distribution, while 67 and 215 kDa HA showed longer persistence in the lungs. Lung exposure appeared to be optimum in this size range due to the rapid absorption of <67 kDa HA and the poor lung penetration and mucociliary clearance of viscous solutions of HA > 215 kDa. The versatility of HA molecular weight and conjugation chemistries may, therefore, provide new opportunities to extend pulmonary drug exposure and potentially facilitate access to lymph nodes draining the pulmonary bed. PMID:27157508

  3. Adsorption of dissolved organics in lake water by aluminum oxide. Effect of molecular weight

    USGS Publications Warehouse

    Davis, J.A.; Gloor, R.

    1981-01-01

    Dissolved organic compounds in a Swiss lake were fractionated into three molecular size classes by gel exclusion chromatography, and adsorption of each fraction on colloidal alumina was studied as a function of pH. Organic compounds with molecular weight (Mr) greater than 1000 formed strong complexes with the alumina surface, but low molecular weight compounds were weakly adsorbed. Electrophoretic mobility measurements indicated that alumina particles suspended in the original lake water were highly negatively charged because of adsorbed organic matter. Most of the adsorbed organic compounds were in the Mr range 1000 < Mr < 3000. Adsorption of these compounds during the treatment of drinking water by alum coagulation may be responsible for the preferential removal of trihalomethane precursors. Adsorption may also influence the molecular-weight distribution of dissolved organic material in lakes. surface, the present work will focus on the influence of molecular size and pH on the adsorption behavior of dissolved organic material of a Swiss lake. From a geochemical point of view, it is important to know the molecular-weight distribution of adsorbed organic matter so that we may better assess its reactivity with trace elements. The study also serves as a first step in quantifying the role of adsorption in the geochemical cycle of organic carbon in lacustrine environments. For water-treatment practice, we need to determine whether molecular weight fractionation occurs during adsorption by aluminum oxide. Such a fractionation could be significant in the light of recent reports that chloroform and other organochlorine compounds are preferentially produced by particular molecular-weight fractions (25-27). ?? 1981 American Chemical Society.

  4. Low molecular weight components of pollen alter bronchial epithelial barrier functions

    PubMed Central

    Blume, Cornelia; Swindle, Emily J; Gilles, Stefanie; Traidl-Hoffmann, Claudia; Davies, Donna E

    2015-01-01

    The bronchial epithelium plays a key role in providing a protective barrier against many environmental substances of anthropogenic or natural origin which enter the lungs during breathing. Appropriate responses to these agents are critical for regulation of tissue homeostasis, while inappropriate responses may contribute to disease pathogenesis. Here, we compared epithelial barrier responses to different pollen species, characterized the active pollen components and the signaling pathways leading to epithelial activation. Polarized bronchial cells were exposed to extracts of timothy grass (Phleum pratense), ragweed (Ambrosia artemisifolia), mugwort (Artemisia vulgaris), birch (Betula alba) and pine (Pinus sylvestris) pollens. All pollen species caused a decrease in ionic permeability as monitored trans-epithelial electrical resistance (TER) and induced polarized release of mediators analyzed by ELISA, with grass pollen showing the highest activity. Ultrafiltration showed that the responses were due to components <3kDa. However, lipid mediators, including phytoprostane E1, had no effect on TER, and caused only modest induction of mediator release. Reverse-phase chromatography separated 2 active fractions: the most hydrophilic maximally affected cytokine release whereas the other only affected TER. Inhibitor studies revealed that JNK played a more dominant role in regulation of barrier permeability in response to grass pollen exposure, whereas ERK and p38 controlled cytokine release. Adenosine and the flavonoid isorhamnetin present in grass pollen contributed to the overall effect on airway epithelial barrier responses. In conclusion, bronchial epithelial barrier functions are differentially affected by several low molecular weight components released by pollen. Furthermore, ionic permeability and innate cytokine production are differentially regulated. PMID:26451347

  5. Mucin Agarose Gel Electrophoresis: Western Blotting for High-molecular-weight Glycoproteins.

    PubMed

    Ramsey, Kathryn A; Rushton, Zachary L; Ehre, Camille

    2016-01-01

    Mucins, the heavily-glycosylated proteins lining mucosal surfaces, have evolved as a key component of innate defense by protecting the epithelium against invading pathogens. The main role of these macromolecules is to facilitate particle trapping and clearance while promoting lubrication of the mucosa. During protein synthesis, mucins undergo intense O-glycosylation and multimerization, which dramatically increase the mass and size of these molecules. These post-translational modifications are critical for the viscoelastic properties of mucus. As a result of the complex biochemical and biophysical nature of these molecules, working with mucins provides many challenges that cannot be overcome by conventional protein analysis methods. For instance, their high-molecular-weight prevents electrophoretic migration via regular polyacrylamide gels and their sticky nature causes adhesion to experimental tubing. However, investigating the role of mucins in health (e.g., maintaining mucosal integrity) and disease (e.g., hyperconcentration, mucostasis, cancer) has recently gained interest and mucins are being investigated as a therapeutic target. A better understanding of the production and function of mucin macromolecules may lead to novel pharmaceutical approaches, e.g., inhibitors of mucin granule exocytosis and/or mucolytic agents. Therefore, consistent and reliable protocols to investigate mucin biology are critical for scientific advancement. Here, we describe conventional methods to separate mucin macromolecules by electrophoresis using an agarose gel, transfer protein into nitrocellulose membrane, and detect signal with mucin-specific antibodies as well as infrared fluorescent gel reader. These techniques are widely applicable to determine mucin quantitation, multimerization and to test the effects of pharmacological compounds on mucins. PMID:27341489

  6. Molecular mechanisms that could contribute to prolonged effectiveness of PDE5 inhibitors to improve erectile function.

    PubMed

    Francis, S H; Morris, G Z; Corbin, J D

    2008-01-01

    Cyclic guanosine monophosphate (cGMP) in penile vascular smooth muscle cells (VSMC) plays a key role in promoting penile erection. Phosphodiesterase-5 (PDE5) in VSMC breaks down cGMP to counter this effect. Sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis), treatments for erectile dysfunction, inhibit PDE5 action. Many men with erectile dysfunction have improved erectile function after plasma inhibitor concentration falls below therapeutic levels. Maximum effect plus onset and duration of action of inhibitor determines its efficacy. The rate and extent of cellular drug accumulation and efflux of drug from smooth muscle cells plus persistence of drug effects in these cell impact these parameters. We propose possible molecular mechanisms that could account for prolonged action of PDE5 inhibitors including (1) persistence of biochemical effects after inhibitor is cleared from cells, and (2) retention of drug in VSMC beyond plasma clearance. PMID:18418391

  7. An evaluation of the effects of PEO/PEG molecular weights on extruded alumina rods

    NASA Astrophysics Data System (ADS)

    Bolger, Nancy Beth

    1998-12-01

    Alumina rods were piston extruded from bodies containing polyethylene glycols (PEGs) and polyethylene oxides (PEOs) with molecular weights ranging from 1,300 to 3,800,000 g/mol. A blend of aluminas possessing different particle size distributions was evaluated with regard to its extrusion pressure by varying the amount of PEG/PEO addition. Behavior exhibited by the alumina blend was dependent upon the additive that was used. The higher molecular weight binders with average molecular weight of 200,000 g/mol and 3,350,000 g/mol displayed the most severe behaviors of near dilatant and dilatant respectively. Physical properties of the green and fired states, as well as the binder burnout, were investigated with the changing additions. Correlation between the green and fired strengths and the changing molecular weights were examined. The additive present influenced the surface properties of the rods, which affected the green strengths. The highest average molecular weight polyethylene glycols showed higher green strengths, while the lowest green strengths were observed for the high molecular weight polyethylene oxides. Fired strengths generally ranged from approximately 12,000 psi to 16,000 psi for additive batches. Alumina pellets containing twelve separate combinations of polyethylene glycol with polyethylene oxide were dry pressed. Physical properties of the green and fired states were examined. Statistical analysis was performed upon the data and seven combinations of polyethylene glycol with polyethylene oxide were deemed significant. These combinations in conjunction with the same alumina blend were then piston extruded. The addition of polyethylene glycol reduced the near dilatant behavior exhibited by the 200,000 g/mol average molecular weight polyethylene oxide. Dilatant behavior was completely eliminated from the 3,350,000 g/mol average molecular weight polyethylene oxide batches. Physical properties of the green and fired states were again investigated with

  8. Determination of molecular weights of humic substances by analytical (UV scanning) ultracentrifugation

    SciTech Connect

    Reid, P.M.; Wilkinson, A.E.; Tipping, E.; Jones, M.N. Freshwater Biological Association, Ambleside, Cumbria )

    1990-01-01

    Samples of peat humic acid (PHA) and surface water humic (WBHA) and fulvic (WBFA) acids have been extracted from Whitray Beck in North Yorkshire, U.K. The molecular weights of the extracts have been investigated by sedimentation equilibrium using an analytical ultracentrifuge equipped with a UV scanning system. The system allows measurements to be made at low concentrations of humic substances, comparable to those existing in natural humic-rich water. A method is described for correcting UV scanning data for changes in the optical properties of the materials with changing molecular weight. Measurements have also been made on reference samples of Suwannee river humic (SRHA) and fulvic (SRFA) acids from the International Humic Substances Society (IHSS). The weight-average moleuclar weights of the extracted samples range from approximately 2,000 to 17,000 and follow a series PHA > WBHA > WBFA. Apparent specific volumes of these materials were in a range from 0.45 to 0.58 cm{sup 3} g{sup {minus}1} as measured by digital densimetry. Al the samples studied were analysed by gel filtration, but the molecular weights determined by this method based on a globular protein calibration are not in good accord with the absolute determinations by the sedimentation-equilibrium technique. The molecular weight of the SRHA determined by sedimentation equilibrium is in good agreement with that reported by BECKETT (1987) et al., based on flow field-flow fractionation.

  9. An optimal polymerization process for low mean molecular weight HBOC with lower dimer.

    PubMed

    Zhou, Wentao; Li, Shen; Hao, Shasha; Liu, Jiaxin; Wang, Hong; Yang, Chengmin

    2015-06-01

    The new research tried to improve the distribution of molecular weight of Hb-based oxygen carriers (HBOC), a bottleneck of glutaraldehyde (GDA)-polymerization process. The orthogonal experiments were done on the basis of the early study of human placenta Hemoglobin (Hb)-crosslinked-GDA and three factors were selected including the molar ratio of GDA and Hb, Hb concentration, and the rate of the feeding GDA. The optimal match condition of polymerization process prepared for the purpose of lower mean molecular weight, content of super-weight molecule, and the content of dimer. The results showed that the molar ratio of GDA and Hb was the greatest influencing factor on the molecular weight distribution of polymerized-Hb, followed by the Hb concentration, and the last is the rate of feeding GDA. The optimum matching conditions had reached the objective that the mean molecular weight with 155.54 ± 5.79, the content of dimer with 17.23 ± 3.71, and content of super-weight molecule with 0.17 ± 0.09, and the results can be repeated in the 30 times expansion experiments. PMID:25519745

  10. High-molecular-weight polymers for protein crystallization: poly-γ-glutamic acid-based precipitants

    SciTech Connect

    Hu, Ting-Chou; Korczyńska, Justyna; Smith, David K.; Brzozowski, Andrzej Marek

    2008-09-01

    High-molecular-weight poly-γ-glutamic acid-based polymers have been synthesized, tested and adopted for protein crystallization. Protein crystallization has been revolutionized by the introduction of high-throughput technologies, which have led to a speeding up of the process while simultaneously reducing the amount of protein sample necessary. Nonetheless, the chemistry dimension of protein crystallization has remained relatively undeveloped. Most crystallization screens are based on the same set of precipitants. To address this shortcoming, the development of new protein precipitants based on poly-γ-glutamic acid (PGA) polymers with different molecular-weight ranges is reported here: PGA-LM (low molecular weight) of ∼400 kDa and PGA-HM (high molecular weight) of >1000 kDa. It is also demonstrated that protein precipitants can be expanded further to polymers with much higher molecular weight than those that are currently in use. Furthermore, the modification of PGA-like polymers by covalent attachments of glucosamine substantially improved their solubility without affecting their crystallization properties. Some preliminary PGA-based screens are presented here.