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1
Hettiarachchi, Rohan Jagath Kumara. "Venous thromboembolism, cancer and low molecular weight heparin". [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2000. http://dare.uva.nl/document/84386.
Testo completo
2
Matthíasson, Stefán E. "Low molecular weight heparin and dextran in thromboprophylaxis human and experimental studies /". Malmö : Dept. of Surgery, Lund University, Malmö General Hospital, 1994. http://books.google.com/books?id=9OxsAAAAMAAJ.
Testo completo
3
Vecchietti, D. G. "Low Molecular Weight Heparins : in depth structural characterization to understand their different biological properties". Doctoral thesis, Università degli Studi di Milano, 2008. http://hdl.handle.net/2434/59669.
Testo completoAbstract (sommario):
Heparin is a linear, heterogeneous, highly sulfated polysaccharide belonging to the family of glycosaminoglycans, endowed with anticoagulant and antithrombotic properties. Its linear chains are made up of 15-200 disaccharide units of N-sulfated or N-acetylated D-glucosamine linked to hexuronic (glucuronic or iduronic) acid.
Low molecular weight heparins (LMWHs), developed to circumvent some unwanted side effect of unfractionated heparins (UFH), are obtained from UFH by diverse chemical and enzymatic depolymerisation processes. Fragments generated by cleavage of heparin may therefore structurally differ from each other more than the original chains because of the modification induced by the depolymerisation methods and the heterogeneity of the UFH. Only about one-third of heparin chains contains a unique pentasaccharide sequence (AGA*IA), which specifically binds antithrombin (AT) thus promoting the inhibition of certain proteases of the coagulation cascade. Such a sequence, characterized by a central trisulfated glucosamine (A*), is believed to survive the depolymerising procedures used for the preparation of LMWHs.
Functional assays performed in vitro, evaluating plasma protein binding and antiprotease activity AT mediated, showed wide variations among the commercially available LMWHs, indicating that their compositional differences have an important impact on function.
With the aim of contributing to the elucidation of structure-activity relationship of LMWHs, the present work is focusing on the in depth study of the oligosaccharide composition of different LMWH preparations. Three of the most popular commercial preparations Enoxaparin, Dalteparin and Tinzaparin were analysed.
Their compositional differences were determined by analyzing their oligosaccharidic populations by gel permeation chromatography, a very characteristic fingerprint for each sample was revealed.
Affinity chromatography on AT-Sepharose was performed to separate and quantify the high affinity fraction,. Structural characterization of all samples was obtained by 1D and 2D NMR spectroscopy and all molecular weight parameters were evaluated through HP-SEC/TDA. All the HA fractions exhibited a considerably higher molecular weight and a reduced polydispersity with respect to NA fractions.
To deepen the characterization of HA components, HA heparin chains of each LMWH were further fractionated into three subfractions with graded affinity toward AT HA1>HA2>HA3.
All the above fractions were analysed via NMR evaluating the average content of all the monosaccharide components and, in particular, the percentage of A* (N-glucosamine tri-sulfated) and G-A* (disaccharide composed by glucuronic acid and A*) both regarded as markers of heparin active site for AT (AGA*IA).
Selected oligomeric fractions and the HA1, HA2, HA3 fractions were analysed via ESI-TOF (as detector after a SEC chromatography). The molecular weight of all HA subfractions were estimated by two different methods: HP-SEC/ESI-MS and NMR.
The results suggest that neither the molecular weight nor the sulfation degree calculated via NMR exhibited any correlation with the degree of affinity for AT.
By combining information obtained by NMR (G-A* content) and the chain length (calculated by Mw evaluation)the AGA*IA content per chain was approximately calculated pointing out the presence of some chains containing more than an active pentasaccharide (HA1 of enoxaparin and dalteparin).
Preliminary data on biological activity in vitro indicated that the different anti-Xa activities were directly related to the degree of AT affinity and the overall structural considerations.
The present work represents the first insight into the detailed and comparative structural characterization of three commercial LMWHs differing in manufacturing process. Important and characteristic structural parameters were defined, including the precise oligomeric composition, the relative content of AT interacting species, and their molecular weight, together with the relative content of variously substituted monosaccharide components. Further studies are required to unravel the correlation of structural features with LMWH functional properties.
4
Mauron, Thomas. "Influence of low molecular weight heparin and low molecular weight dextran sulfate on the inhibition of coagulation factor XIa by serpins /". Bern : Hämatologisches Zentrallabor der Universität Inselspital, 1998. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
Testo completo
5
Gandara, Esteban. "Is an Intermediate Dose of LMWH Effective for Secondary Prevention of Recurrent Venous Thromboembolism in Pregnant Patients Diagnosed with Deep Vein Thrombosis or Pulmonary Embolism? Design of a Pilot Study". Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23388.
Testo completoAbstract (sommario):
Statement of the problem The primary objective of this thesis was to determine the best study design to evaluate the safety and effectiveness of an intermediate dose of low molecular weight heparin for secondary prevention of pregnancy associated VTE (PAVTE). An RCT was deemed unfeasible,so the use of a single arm study with prior evaluation of feasibility with a pilot study is proposed. // Methods - A systematic review was conducted to evaluate the efficacy of current strategies used for secondary prevention of PAVTE.A survey was used to elicit the non-inferiority margin. // Results - The pooled proportion of recurrent VTE in patients treated with full dose LMWH was 0.012(95% CI 0.006 to 0.02) and the rate of major bleeding was 0.025(95% CI=0.01 to 0.041). The non-inferiority margin was elicited at 2.5%. // Conclusions - Although a randomized controlled trial should be conducted whenever possible, in certain scenarios they are unfeasible. Therefore, an alternative study design should perhaps be used to evaluate the safety and efficacy of therapeutic strategies.
6
Holmström, Margareta. "Clinical aspects on treatment of deep venous thrombosis with a low molecular weight heparin /". Stockholm, 1998. http://diss.kib.ki.se/1998/91-628-2989-0/.
Testo completo
7
Näsström, Birgit. "Lipoprotein lipase in hemodialysis patients and healthy controls : effects of heparin /". Umeå : Univ, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-340.
Testo completo
8
Steward, David W., John B. Bossaer, Brian Odle, Emily Flores e Somi Rikhye. "Prescribing of Low-Molecular-Weight Heparin and Warfarin in Patients with Acute Venous Thromboembolism and Active Cancer". Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/2322.
Testo completoAbstract (sommario):
Background: Malignancy is a significant risk factor for venous thromboembolism (VTE), conferring a 4- to 7-fold increased risk in patients with cancer. Because of its effect on certain tumors, low-molecular-weight heparin (LMWH) has been evaluated as a treatment option for cancer and as an alternative to traditional warfarin therapy in patients with active cancer. LMWH is associated with a reduced recurrence of VTE, fewer adverse bleeding events, and, in some instances, decreased mortality. The American College of Chest Physicians/American Society of Clinical Oncology has recommended LMWH for at least the initial 3 to 6 months when treating VTE in patients with cancer, based on the positive outcomes associated with LMWH.
Objective: The purpose of this study was to evaluate physician prescribing patterns for LMWH or warfarin in patients with acute VTE and active cancer.
Methods: We conducted a retrospective chart review of hospitalized patients at a community teaching hospital with an affiliated regional cancer center located in a rural area of the United States. Patients included in the analysis had an International Classification of Diseases, Ninth Revision code indicative of any cancer type and a concomitant code for any VTE. The primary outcome was the drug prescribed at discharge for the treatment of VTE. Secondary outcomes included specialty of the prescribing physician, adverse bleeding events, and the need for transfusion. VTE treatment regimen was evaluated using the binomial test, and logistic regression analysis was used to determine correlation of the prescriber’s specialty with the patient’s prescribed regimen.
Results: Of 129 patients included in the analysis, 107 (82.9%) were prescribed warfarin compared with 9 (7%) who were prescribed LMWH. Hematologists and oncologists were more likely to prescribe LMWH than general practitioners (odds ratio, 7.8; 95% hazard ratio, 1.5-42). Seven patients had a documented adverse bleeding event and 2 patients required a transfusion. Four of the 7 adverse bleeding events and 1 of the 2 transfusions occurred in the group receiving vitamin K antagonist therapy.
Conclusion: Physicians in our system were significantly more likely to prescribe warfarin for acute treatment of VTE in patients with active cancer—despite consistent evidence and multiple evidence-based guidelines recommending treatment with LMWH in this patient population. This was lower than other observations in Canadian populations but may more accurately represent nonteaching centers in the United States, particularly those in rural areas. Specialists in oncology were significantly more likely to prescribe LMWH than generalists.
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Pranckevičienė, Gabrielė. "Pharmacoepidemiologic assessment of low-molecular-weight heparins utilization in Lithuania and development of pharmacoeconomic model". Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2014~D_20140305_141832-70667.
Testo completoAbstract (sommario):
In recent years, many countries have struggled with the fact that expenditures on health care are growing much faster than the overall level of wealth. Research objectives: 1) to conduct a meta-analysis of heparins by the means of their efficacy, safety parameters and treatment outcomes; 2) to conduct pharmacoepidemiological assessment of long-term heparins utilization in Lithuania; 3) to develop a pharmacoeconomic cost-minimization model for low-molecular-weight heparins based on reference pricing methodology; 4) to investigate heparins prescribing trends and to evaluate heparins prescription adherence to international clinical guidelines at a secondary level clinical hospital. Meta-analysis results showed that low-molecular-weight heparins could be considered interchangeable due to similar therapeutic profiles in some indications. In Lithuania consumption of heparins and corresponding costs were constantly increasing during the period of investigation; therefore it would be relevant to implement modern pharmacoeconomic methodologies to regulate costs. Cost-minimization model suggested that expenditures on this group of medicines could be decreased by nearly 70 percent. Analysis of pharmacoepidemiological study data confirmed that heparins prescription practices at the clinical hospital were insufficiently regulated. In addition this study conducted at the clinical hospital revealed non-compliance of heparins safety monitoring practices with clinical guidelines.Pastaraisiais metais daugelyje šalių sveikatos priežiūros išlaidos augo daug greičiau nei bendras gerovės lygis, todėl yra nuolat diskutuojama, kaip šį išlaidų augimą reikėtų kontroliuoti. Darbo uždaviniai: 1) atlikti heparinų preparatų meta-analizę, palyginant jų efektyvumo ir saugumo parametrus bei gydymo baigtis; 2) atlikti heparinų preparatų ilgalaikio suvartojimo Lietuvoje farmakoepidemiologinį tyrimą; 3) suformuluoti farmakoekonominį kaštų mažinimo sprendimų modelį mažos molekulinės masės heparinų preparatų grupei, remiantis referentinės kainos metodika; 4) ištirti heparinų preparatų skyrimo tendencijas antrinio lygio klinikinėje ligoninėje ir palyginti heparinų preparatų skyrimo atitikimą tarptautinėms gairėms. Meta-analizės rezultatai parodė, jog mažos molekulinės masės heparinai gali būti tarpusavyje pa¬keičiami dėl analogiškų terapinių savybių tam tikrose indikacijose. Heparinų preparatų suvartojimas ir atitinkamos išlaidos tiriamuoju laikotarpiu Lietuvoje nuolat didėjo, todėl būtų aktualu taikyti šiuolaikines farmakoekonomines išlaidų reguliavimo metodikas. Pritaikius kaštų mažinimo modelį heparinų preparatų grupei, būtų galima sumažinti išlaidas šios grupės preparatams beveik 70 procentų. Farmakoepidemiologinio tyrimo rezultatai atskleidė, jog heparinų preparatų skyrimo praktika klinikinėje ligoninėje buvo nepakankamai reglamentuota. Taip pat heparinų preparatų saugumo parametrų stebėjimo praktika ligoninėje neatitiko tarptautinių rekomendacijų.
10
Lima, Juliana Pego. "Development of Nanoparticles as Low Molecular Weight Heparins Carriers for Oral Administration". Master's thesis, Faculdade de Farmácia da Universidade do Porto, 2007. http://hdl.handle.net/10216/7486.
Testo completo
11
Lima, Juliana Pego. "Development of Nanoparticles as Low Molecular Weight Heparins Carriers for Oral Administration". Dissertação, Faculdade de Farmácia da Universidade do Porto, 2007. http://hdl.handle.net/10216/7486.
Testo completo
12
Jeddy, T. A. "Changes following balloon angioplasty of the superficial femoral artery and the effect of low molecular weight heparin : assessment using colourflow doppler ultrasound". Thesis, University of Newcastle Upon Tyne, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246086.
Testo completo
13
Newman, Peter Michael Pathology UNSW. "Antibody and Antigen in Heparin-Induced Thrombocytopenia". Awarded by:University of New South Wales. Pathology, 2000. http://handle.unsw.edu.au/1959.4/17485.
Testo completoAbstract (sommario):
Immune heparin-induced thrombocytopenia (HIT) is a potentially serious complication of heparin therapy and is associated with antibodies directed against a complex of platelet factor 4 (PF4) and heparin. Early diagnosis of HIT is important to reduce morbidity and mortality. I developed an enzyme immunoassay that detects the binding of HIT IgG to PF4-heparin in the fluid phase. This required techniques to purify and biotinylate PF4. The fluid phase assay produces consistently low background and can detect low levels of anti-PF4-heparin. It is suited to testing alternative anticoagulants because, unlike in an ELISA, a clearly defined amount of antigen is available for antibody binding. I was able to detect anti-PF4-heparin IgG in 93% of HIT patients. I also investigated cross-reactivity of anti-PF4-heparin antibodies with PF4 complexed to alternative heparin-like anticoagulants. Low molecular weight heparins cross-reacted with 88% of the sera from HIT patients while half of the HIT sera weakly cross-reacted with PF4-danaparoid (Orgaran). The thrombocytopenia and thrombosis of most of these patients resolved during danaparoid therapy, indicating that detection of low affinity antibodies to PF4-danaparoid by immunoassay may not be an absolute contraindication for danaparoid administration. While HIT patients possess antibodies to PF4-heparin, I observed that HIT antibodies will also bind to PF4 alone adsorbed on polystyrene ELISA wells but not to soluble PF4 in the absence of heparin. Having developed a technique to affinity-purify anti-PF4-heparin HIT IgG, I provide the first estimates of the avidity of HIT IgG. HIT IgG displayed relatively high functional affinity for both PF4-heparin (Kd=7-30nM) and polystyrene adsorbed PF4 alone (Kd=20-70nM). Furthermore, agarose beads coated with PF4 alone were almost as effective as beads coated with PF4 plus heparin in depleting HIT plasmas of anti-PF4-heparin antibodies. I conclude that the HIT antibodies which bind to polystyrene adsorbed PF4 without heparin are largely the same IgG molecules that bind PF4-heparin and thus most HIT antibodies bind epitope(s) on PF4 and not epitope(s) formed by part of a PF4 molecule and part of a heparin molecule. Binding of PF4 to heparin (optimal) or polystyrene/agarose (sub-optimal) promotes recognition of this epitope. Under conditions that are more physiological and sensitive than previous studies, I observed that affinity-purified HIT IgG will cause platelet aggregation upon the addition of heparin. Platelets activated with HIT IgG increased their release and surface expression of PF4. I quantitated the binding of affinity-purified HIT 125I-IgG to platelets as they activate in a plasma milieu. Binding of the HIT IgG was dependent upon heparin and some degree of platelet activation. Blocking the platelet Fc??? receptor-II with the monoclonal antibody IV.3 did not prevent HIT IgG binding to activated platelets. I conclude that anti-PF4-heparin IgG is the only component specific to HIT plasma that is required to induce platelet aggregation. The Fab region of HIT IgG binds to PF4-heparin that is on the surface of activated platelets. I propose that only then does the Fc portion of the bound IgG activate other platelets via the Fc receptor. My data support a dynamic model of platelet activation where released PF4 enhances further antibody binding and more release.
14
James, Stefan. "Coagulation, Inflammation and Myocardial Dysfunction in Unstable Coronary Artery Disease and the Influence of Glycoprotein IIb/IIIa Inhibition and Low Molecular Weight Heparin". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3372.
Testo completo
15
Rivera, Oballe Harry Juan. "Efeito da heparina de baixo peso molecular na perda óssea alveolar em ratos Wistar machos : análises morfométrica e histológica". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/168599.
Testo completoAbstract (sommario):
O objetivo da presente tese foi avaliar os efeitos da heparina de baixo peso molecular (HBPM) na perda óssea alveolar em ratos Wistar. Para a melhor compreensão e entendimento dos efeitos da HBPM se elaborou um único artigo com 40 ratos machos da linhagem Wistar de 60 dias de nascidos, os quais foram dívidos em 4 grupos experimentais previamente randomizados: Grupo Controle (C), Grupos Doença Periodontal (DP), Grupo Heparina (Hp) e Grupo Heparina+Doença Periodontal (Hp+DP) com um período experimental de 60 dias. Um animal foi perdido no período de aclimação, dois animais foram perdidos na primeira de três coletas sanguíneas pré-programadas e um rato foi perdido na colocação da ligadura. Os resultados observados foram analisados são perda óssea alveolar induzida onde houve diferença significava entre os grupos (C) e (DP), entre o grupo (C) e (Hp+DP), entre o grupo (DP) e (Hp) e o grupo (Hp) e (Hp+DP). Foi avaliado perda óssea alveolar não induzida onde não existiu diferença entre os grupos. Foi avaliado o peso do início ao final do período experimental. Foram avaliados o consumo de ração e agua onde não houve diferença significativa entre os grupos. Foram avaliados o número de megacariócitos nos fémures, onde também não existiram diferenças estatísticas. Foram avaliados números de adipócitos no timo, não havendo diferença significativa entre os grupos. Foram avaliados as plaquetas e desvio padrão onde não existiu diferença significativa entre os grupos. Foram avaliados os leucócitos e desvio padrão onde não houve diferença significativa entre os grupos. Posteriormente foi avaliado a porcentagem de linfócitos onde se achou diferença estatisticamente significativa na segunda coleta sanguínea entre o grupo (C) e grupo (Hp+DP) e grupo (Hp) e grupo (Hp+DP). Foi assim que as conclusões deste trabalho foram que o presente estudo mostrou que a HBPM não foi capaz de produzir perda óssea alveolar nos ratos Wistar, mas foi capaz de aumentar a quantidade de leucócitos e linfócitos, indicando a presença de um processo inflamatório.In order to better understand and understand the effects of (LMWH), a single article was elaborated with 40 male rats of the 60 day old Wistar line, which were divided into four previously randomized experimental groups: Control Group (C), Groups Periodontal Disease (PD), Heparin Group (Hp) and Heparin Group + Periodontal Disease (Hp + PD) with an experimental period of 60 days. One animal was lost in the acclimation period, two animals were lost in the first of three preprogrammed blood collections and one mouse was lost in the ligation placement. The observed results were analyzed for induced alveolar bone loss where there was significant difference between groups (C) and (PD), between group (C) and (Hp + PD), between (PD) and (Hp) group and Group (Hp) and (Hp + PD). Uninduced alveolar bone loss was assessed where there was no difference between the groups. The weight of the onset at the end of the experimental period was evaluated. The ration and water consumption were evaluated where there was no significant difference between the groups. The number of megakaryocytes in the femurs was evaluated, in which there were also no statistical differences. Adipocyte numbers were evaluated in the thymus, with no significant difference between the groups. Platelets and standard deviation were evaluated where there was no significant difference between the groups. Leukocytes and standard deviation were evaluated where there was no significant difference between the groups. Later, the percentage of lymphocytes where a statistically significant difference was found in the second blood collection between group (C) and group (Hp + PD) and group (Hp) and group (Hp + PD) was evaluated. Thus the conclusions of this study were that the present study showed that LMWH was not able to produce alveolar bone loss in Wistar rats, but was able to increase the amount of leukocytes and lymphocytes, indicating the presence of a process inflammatory.
16
King, Joseph. "Analysis and Fingerprinting of Glycosaminoglycans". VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/2524.
Testo completoAbstract (sommario):
Heparin is a complex mixture of sulfated polysaccharides derived from animals and one of the oldest drugs in use. While an efficacious anticoagulant, heparin is beset by side effects and pharmacokinetic difficulties. Low molecular weight heparins (LMWH) are made by depolymerizing unfractionated heparin (UFH) and present improvements in these areas. However, they still retain a phenomenally high level of complexity due to their polydispersity and the introduction of non-native structural features. This makes the structural characterization LMWHs a daunting task. This work details the development of a novel capillary electrophoretic (CE) method for fingerprinting LMWHs. Since their complexity normally results in a nearly featureless electropherogram, polyalkylamines were used as a resolving agents to yield highly resolved and reproducible fingerprints characteristic of the LMWH being investigated. Linear polyamines of resolved LMWH in a manner dependent on chain length and charge density, while cyclic polyamines were incapable of resolution. Longer length glycosaminoglycans such as UFH and chondroitin sulfate were not successfully fingerprinted as they lacked run to run consistency. Further investigation into the mode of polyamine binding showed that they bound to LMWH via a two site binding model, indicating the presence of specific sites on LMWH that tightly bind polyamines. Upon the saturation of these sites, the polyamines continue to interact via general electrostatic binding. Pentaethylenehexamine was also able to separate the known contaminant oversulfated chondroitin sulfate from UFH. In July of 2010, the US food and drug administration approved a generic for the widely used LMWH enoxaparin, a questionable move due to the difficulties of proving the equivalence of such a complex mixture. A comparison of the brand and generic batches of enoxaparin using the fingerprinting method revealed striking similarities, bolstering the generic’s claim of equivalency and providing a protocol for the evaluation of other biosimilar LMWHs. This is the first work utilizing CE in developing high resolution fingerprints of LMWH. It presents a noteworthy method for quality assessment of LMWH and provides the basis for designing other small molecule probes for the analysis of complex glycosaminoglycans.
17
Sjögren, Vilhelm. "Oral anticoagulation and stroke risk". Doctoral thesis, Umeå universitet, Institutionen för folkhälsa och klinisk medicin, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-141597.
Testo completoAbstract (sommario):
Background: The risk of ischaemic stroke in patients with atrial fibrillation (AF) and mechanical heart valve (MHV) prostheses can be reduced by oral anticoagulation (OAC), which increases the risk of serious bleeding. The aims of this thesis were [1] to find out how effective and safe warfarin is where treatment quality is high, i.e. Sweden, with proportion of time that patients spend within the therapeutic range (TTR) >70%, [2] whether there is evidence for administering low-molecular-weight heparin (LMWH) during temporary interruptions of OAC (bridging therapy), and whether non-vitamin K-dependent oral anticoagulants (NOACs) as a group, [3] or individually, [4] are more effective and safer than warfarin when used for stroke prevention in patients with AF. Materials and methods: All four studies were retrospective, based on the Swedish anticoagulation register Auricula, and done with merging of data from some or all of the National Patient Register, the Prescribed Drug Register, the Swedish Stroke Register (Riksstroke), and the Cause of Death Register. In studies 2–4, propensity score matching was performed to obtain treatment groups with similar risk profiles. Outcomes were defined as haemorrhages or thromboses requiring specialist care, or death. Haemorrhages were intracranial, gastrointestinal, or other. Thromboses were ischaemic stroke, systemic embolism, myocardial infarction, or venous thromboembolism (VTE). Study 1 described all patients on warfarin during 2006–2011, which was before the introduction of NOACs. Study 2 was a cohort study of all patients who had a planned interruption of warfarin during the same period. Study 3 included all 49,011 patients starting OAC for stroke prevention due to AF between 1 July 2011 and 31 December 2014, and study 4 all 64,382 patients with the same indication between 1 January 2013 and 31 December 2015. Results: Study 1 showed that for the 77,423 patients on warfarin with 217,804 treatment years, TTR was 77.4% for patients with AF, 74.5% with MHV, and 75.9% with VTE. Annual rates of intracranial bleeding were 0.38%, 0.51%, and 0.30%. In study 2, with 14,556 warfarin interruptions, the 30-day risk of a bleeding requiring specialist care was 0.64% for LMWH treated and 0.46% for controls. For patients with VTE as indication for OAC, bleeding rate with LMWH was significantly higher at 0.85% vs. 0.16% (hazard ratio 5.24, 95% confidence interval 1.39–19.77), but with no difference for patients with MHV or AF. The incidence of ischaemic complications was higher in the LMWH bridging group overall and for patients with MHV and AF, but not for patients with VTE. In study 3, for the 12,694 patients starting NOAC (10,392 treatment years) or matched warfarin patients (9,835 treatment years, TTR 70%) due to AF, annual incidence of ischaemic stroke and systemic embolism did not differ between the groups (1.35% vs. 1.58%), but risks of major bleedings and intracranial bleedings were significantly lower: 2.76% vs. 3.61% and 0.40% vs. 0.69%. In study 4, patients on individual NOACs (6,574 dabigatran, 8,323 rivaroxaban, 12,311 apixaban) were compared to 37,174 patients starting warfarin (in total 81,176 treatment years). No NOAC showed any difference in risk of ischaemic stroke or systemic embolism, but there were fewer intracranial bleedings, serious bleedings overall, and deaths for dabigatran and apixaban compared to warfarin. For patients starting rivaroxaban the risk of gastrointestinal bleeding was higher than for matched warfarin counterparts, with no significant differences in other bleeding risks, or mortality. Conclusions: Swedish warfarin treatment shows TTR levels that are high by international standards, correlating to low incidences of ischaemic and haemorrhagic events. LMWH bridging has not been proven beneficial, even for patients with MHV, meaning that bridging in general cannot be recommended. NOACs as a group were safer than high-quality warfarin treatment. Efficacy did not differ, even when comparing individual NOACs to warfarin, but there were fewer bleedings on dabigatran and apixaban. Although not more efficient than warfarin with a high TTR, NOACs should be the recommended first choice for OAC in AF, on the merit of lower bleeding risks.Finansiär: Forskning och Utveckling, Region Västernorrland
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Jernberg, Tomas. "Multi-lead ST-monitoring in the early assessment of patients with suspected or confirmed unstable coronary artery disease". Doctoral thesis, Uppsala University, Department of Medical Sciences, 2000. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-520.
Testo completoAbstract (sommario):
This study evaluated the use of multi-lead ST-monitoring in the early assessment of patients with suspected or confirmed unstable coronary artery disease (UCAD).
At continuous 12-lead ECG (c12ECG), the definition of an ischemic episode as a transient ST-deviation ¡Ý0 for at least 1 minute resulted in a good observer agreement (kappa=0.72) and an acceptable incidence of postural ST-changes.
When c12ECG was performed from admission and for 12 hours in 630 patients with suspected UCAD, 16% had ischemic episodes. At 30 days, patients with episodes had a higher risk of cardiac death or myocardial infarction (MI) (10% vs. 1.5%). In a multivariate analysis, troponin T¡Ý0.10¦Ìg/l and presence of ischemic episodes were independent predictors of cardiac death or MI. When ST-monitoring and troponin T status were combined, patients could be divided into a low-, intermediate-, and high-risk group with 1%, 4% and 12% risk for cardiac death or MI at 30 days of follow up.
As a part of a multicenter trial, including patients with UCAD, 1016 patients underwent ST-monitoring with c12ECG or continuous vectorcardiography (cVCG). Ischemia was detected in 32% and 35%, respectively. When the groups with ischemia were compared, the groups were similar with respect to several clinical variables. Thus, these methods identify the same high-risk population.
Of the 629 patients treated non-invasively with extended treatment of low-molecular- weight heparin (LMWH) or placebo, 34% had ischemic episodes. In this group at 3 months, patients administered LMWH had a significantly lower risk of death, MI, or revascularization than patients treated with placebo (35.2% vs. 53.4%). In patients without transient ischemic episodes, the outcome in the LMWH and placebo group was similar.
Thus, multi-lead monitoring provides important prognostic information early after admission in this population, and seems to identify patients who benefit most from extended antithrombotic treatment.
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RICCITELLI, RICCARDO. "L’utilizzo della Nadroparina Calcica in donne affette da abortività idiopatica ricorrente". Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2005. http://hdl.handle.net/2108/189.
Testo completoAbstract (sommario):
Inherited and acquired thrombophilias are associated with recurrent pregnancy loss(RPL) and venous thromboembolism(VTE).
RPL is a major health problem affecting 1-2% of women at the reproductive age. While chromosomal aberration, endocrinologic dysfunctions and uterine abnormalities are etioloogic factors, a cause of RPL could not be identified.
Inherited and acquired thrombophilias can be found in 50-65% of women with RPL of unknown cause, as well as in women with other vascular pathologies such peeclampsia, intrauterine restriction and placental abruption.
Gestational outcame in woman with inherited thrombphilias who present with RPL is poor with less than 25% of prengnacies resulting in live birth.
The purpose of this study is to verify the safe and efficacy of Nadroparin in RPL.
20
Harrison, Jeffrey. "Deep vein thrombosis after total hip and knee replacement : a review of the incidence, prophylaxis, diagnosis and economic impact of thromboembolic disease in lower limb joint replacement. A comparison of low molecular weight heparin and pneumatic plantar". Thesis, University of Bristol, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311366.
Testo completo
21
Achour, Oussama. "Aide au ciblage du microenvironnement tumoral par le développement d’un nano-système de détection et de traitement des tumeurs avec inhibition ciblée de l’héparanase". Thesis, La Rochelle, 2014. http://www.theses.fr/2014LAROS012/document.
Testo completoAbstract (sommario):
Le microenvironnement des cellules tumorales présente plusieurs particularités comme l'hypoxie, l'acidification du milieu extracellulaire et l'hypersécrétion d'enzymes hydrolytiques. Ces hydrolases, comme la cathepsine D et l'héparanase, interviennent dans les étapes de la progression tumorale et notamment l'angiogenèse. Cette thèse s'intègre dans un projet dont la finalité est de concevoir un nano-objet moléculaire enzymo-sensible qui réagirait d'une manière spécifique aux enzymes hypersécrétées dans le microenvironnement tumoral pour assurer de façon simultanée, une fonction de détection et de ciblage des tumeurs. La première partie de nos travaux a été consacrée à la conception et à la validation d'un lien peptidique intégrable dans l'objet moléculaire, sensible aux formes de la cathepsine D actives du microenvironnement tumoral de cancers mammaires. Cet objectif a été réalisé suite à l'étude cinétique de l'hydrolyse de 5 peptides par la cathepsine D mature et la pro-cathepsine D dans les conditions de pH du microenvironnement tumoral. Nous avons également étudié l'effet de l'hypoxie et de l'acidification du milieu extracellulaire sur la sécrétion des formes actives de la cathepsine D par la lignée tumorale de cancer mammaire MCF-7. Dans une deuxième partie, nous avons travaillé sur l'élaboration d'héparines de bas poids moléculaire pouvant assurer la fonction thérapeutique de l'objet moléculaire grâce à leur activité anti-angiogénique. Nous avons mis au point une méthode innovante pour la dépolymérisation de l'héparine qui consiste en une hydrolyse radicalaire par le péroxyde d'hydrogène assistée par les ultrasons. Cette technique permet la production d'oligosaccharides d'héparines caractérisées par des poids moléculaires et des degrés de sulfatation contrôlés. En fonction des conditions de dépolymérisation par cette technique, les héparines de bas poids moléculaires produites peuvent être utilisées comme anticoagulant ou anti-angiogéniqueTumor microenvironment is characterized by several particularities such as hypoxia, extracellular media acidification and the hyper-secretion of hydrolytic enzymes. These hydrolases, such as cathepsin D and heparanase, are involved in many steps of tumor progression like angiogenesis. This thesis is a part of a project that aims to develop a "smart" molecular nano-object that specifically reacts to hyper-secreted enzymes in the tumor microenvironment for the simultaneous detection and targeting of tumor. The first part of our work concerned the design and the validation of a peptide that is sensitive to active forms of cathepsin D which is a protease, unregulated in many tumors microenvironment such as breast cancers. This objective has been achieved following the kinetic study of the hydrolysis of 5 peptides by mature cathepsin D and procathepsin D in the pH conditions of the tumor microenvironment. On the other hand, we studied the effect of hypoxia and the acidification of the extracellular medium on the secretion of active forms of cathepsin D by the breast cancer cell line MCF-7. In a second part, we worked on the development of low molecular weight heparins that may provide therapeutic function of the molecular object through their anti-angiogenic activity. We have developed an innovative method for the depolymerization of heparin that consists on a radical hydrogen peroxide hydrolysis assisted by ultrasound. This technique allows the production of heparins oligosaccharides characterized by controlled molecular weight and degree of sulfatation. Depending on the depolymerization conditions by this technique, the produced low molecular weight heparins can be used as an anticoagulant or anti-angiogenic
22
Rodriguez, Castro Kryssia Isabel. "Site-specific risk factors for portal vein thrombosis and evaluation of anticoagulation efficacy in patients with cirrhosis". Doctoral thesis, Università degli studi di Padova, 2013. http://hdl.handle.net/11577/3422633.
Testo completoAbstract (sommario):
Advanced liver disease is characterized by profound hemostatic alterations that can lead both to bleeding or to thrombotic complications. While pro-hemorrhagic alterations are present including thrombocytopenia and reduced plasmatic levels of coagulation factors, pro-thrombotic abnormalities such as decrease in anti-coagulant proteins antithrombin, Proteins C and S, increase in prothrombotic Factor VIII, and von Willebrand factor are also present.
The most frequent site of thrombosis in cirrhotic patients is the portal vein, consequence of an interplay of factors including altered hemostasis and venous stasis. The endothelium, the third component of the thrombosis triad, however, probably plays an important role in the genesis of in situ thrombosis within the portal vein. In the present study, endothelium form portal and cava veins were analyzed in cirrhotic patients, and compared to that of non-cirrhotic subjects, in order to determine the possible role of local alterations in the development of thrombosis. The immunofluorescence study of the main endothelial anticoagulant protein, thrombomodulin, revealed decreased presence of this component in the endothelium of the portal vein with respect to the vena cava in cirrhosis patients. On the other hand, the immunohistochemical analysis of pro-coagulant Factor VIII revealed that this endothelial protein is present uninterruptedly lining the lumen of portal vein and vena cava of both cirrhosis patients and non-cirrhotic subjects, without showing any differences between them. Diminished thrombomodulin may hamper the endothelium’s anticoagulant properties, which, in the presence of conserved Factor VIII, may lead to the development of thrombosis.
The thrombosis of the portal vein represents an important milestone in the natural history of patients with cirrhosis, often increasing morbidity before and mortality after liver transplantation. Obtainment of recanalization through anticoagulation is therefore paramount, and in the present study, an analysis was performed regarding factors that may have an impact on efficacy of anticoagulation with low molecular weight heparin in cirrhotic patients with this complication. Anticoagulation with low molecular weight heparin was demonstrated to be a valid strategy for achieving portal vein recanalization, with a response rate of 65.2%, including complete recanalization in 24 of the 46 treated patients, after a mean of 4.5 months (±3.1 months) of anticoagulation. Whereas the hemostatic status of patients did not correlate with the response to anticoagulation, the interval between thrombus onset and start of therapy was the only predictive factor of therapeutic efficacy. Specifically, thrombus age at diagnosis (1.9 ± 1.2 months vs 6.3 ± 4.5 months in the recanalization group and in the non-recanalization group, respectively, p<.001), and the interval between thrombus onset and start of anticoagulation (3.2 ± 1.7 months vs 7.78 ± 4.5 months in the recanalization group and in the non-recanalization group, respectively, p<.002) were the principal determinants of therapeutic efficacy. This underlines the importance of prompt diagnosis and start of therapy to increase the probability of successful anticoagulant therapy.
Although in cirrhosis the low levels of antithrombin, which is necessary for the action of heparins, could theoretically hamper the anticoagulant effect, the clinical efficacy of anticoagulant therapy with low molecular weight heparin has been herein demonstrated.
The anticoagulant effect of low molecular weight heparin was then tested in vitro using the thrombin generation assay, and concentrations within the therapeutic range achieved reduction of endogenous thrombin potential notwithstanding the marked reduction in antithrombin levels that were present in plasma from cirrhotic patients and the low plasma anti-Xa activity determined in vitro. In particular, patients with Child Pugh C cirrhosis were characterized by antithrombin levels which were as low as those of subjects with the prothrombotic condition of genetic antithrombin deficit (42±14% versus 52±4%, respectively, p=.06). At low molecular weight heparin 0.35 UI/mL concentration in vitro, anti-Xa activity was significantly lower in Child Pugh B and Child Pugh C patients as compared to controls (p<0.001), as well as in patients with congenital AT defect as compared to controls (p<0.001). Despite low levels of antithrombin and anti-Xa activity, patients with cirrhosis showed a greater anticoagulant effect of low molecular weight heparin, with a mean endogenous thrombin potential reduction of 72.6±11% (p=0.02 versus controls). This increased susceptibility of cirrhosis patients with advanced stages of the disease may therefore actually warrant dose reduction of anticoagulation.La cirrosi epatica avanzata è caratterizzata da alterazioni emostatiche importanti che possono portare a complicanze emorragiche o trombotiche. Nonostante siano presenti alterazioni pro-emorragiche come trombocitopenia e ridotti livelli dei fattori della coagulazione, sono presenti anche anormalità pro-trombotiche come la diminuzione di proteine anti-coagulanti, quali antitrombina, Proteina C ed S, ed incremento del Fattore VIII e Fattore von Willebrand . Il sito più frequente di trombosi in pazienti cirrotici è la vena porta, risultato di vari fattori quali le alterazioni emostatiche sistemiche così come la stasi venosa locale. Tuttavia, l’endotelio, il terzo componente del triade trombotica, probabilmente gioca un ruolo importante nella genesi della trombosi in situ della vena porta. Nel presente studio, è stato analizzato l’endotelio della vena porta e comparato a quello della vena cava in pazienti cirrotici e non, per determinare il possibile ruolo delle alterazioni locali nello sviluppo della trombosi. Come principale proteina endoteliale anticoagulante, è stata studiata la trombomodulina tramite immunofluorescenza, rivelandone una ridotta presenza nell’endotelio della vena porta rispetto a quello della vena cava nei pazienti cirrotici. D’altro canto, l’analisi immunoistochimica del Fattore VIII, con proprietà pro-coagulanti, ha rivelato che questa proteina endoteliale è presente in maniera continua e costante lungo il lumen della vena porta e della vena cava sia nei pazienti cirrotici che non. La diminuzione della trombomodulina può dannegiare le proprietà anticoagulanti dell’endotelio che, in presenza del Fattore VIII preservato, può portare allo sviluppo della trombosi. La trombosi della vena porta rappresenta una complicanza rilevante nella storia naturale dei pazienti cirrotici, causando frequentemente un aumento della morbilità prima e della mortalità dopo il trapianto epatico. L’ottenimento della ricanalizzazione tramite terapia anticoagulante è perciò importante, e nel presente studio è stata fatta un’analisi dei fattori che possono avere un impatto sull’efficacia della terapia con eparina a basso peso molecolare in pazienti cirrotici con questa complicanza. Si è dimostrato che l’anticoagulazione con eparina a basso peso molecolare è una strategia valida per la ricanalizzazione della vena porta, con un tasso di risposta del 65.2%, includendo ripermeazione completa in 24 dei 46 pazienti trattati, dopo una media di 4.5 mesi (±3.1 mesi) di anticoagulazione. Nonostante lo status emostatico dei pazienti non correlava con la risposta all’anticoagulazione, l’intervallo tra lo sviluppo del trombo e l’inizio della terapia è stato l’unico fattore predittivo dell’efficacia terapeutica. Specificamente, l’età del trombo alla diagnosi (1.9 ± 1.2 mesi vs 6.3 ± 4.5 mesi, rispettivamente, p<.001) e l’intervallo tra lo sviluppo del trombo e l’inizio della terapia anticoagulante (3.2 ± 1.7 mesi vs 7.78 ± 4.5 mesi nel gruppo che ha ottenuto ricanalizzazione e nel gruppo che non ha ottenuto ricanalizzazione, rispettivamente, p<.002) sono stati i principali determinanti dell’efficacia terapeutica. Questo sottolinea l’importanza di una diagnosi precoce e di un opportuno inizio della terapia, per incrementare la probabilità di successo del trattamento anticoagulante. Benché i livelli bassi di antitrombina, necessaria per l’azione dell’eparina, verificatesi in cirrosi possano teoricamente diminuire l’effetto anticoagulante, in questo studio si è dimostrata l’efficacia clinica dell’anticoagulazione con eparina a basso peso molecolare. L’effetto anticoagulante dell’eparina a basso peso molecolare è stato esplorato in vitro utilizzando il test della trombino generazione, e concentrazioni di eparina dentro il range terapeutico sono state in grado di ridurre la generazione della trombina, nonostante la spiccata riduzione nei livelli plasmatici di antitrombina e i bassi livelli di anti-Xa determinati in vitro. In particolare, i pazienti in classe C di Child Pugh si sono caratterizzati da livelli di antitrombina bassi quanto quelli presenti in pazienti con la condizione protrombotica di deficit genetico di questa proteina (42±14% vs 52±4%, rispettivamente, p=.06). Alla concentrazione in vitro di 0.35 UI/mL di eparina a basso peso molecolare, l’attività anti-Xa è stata significativamente più bassa in pazienti in classi di Child Pugh B e C rispetto ai controlli (p<.001), così come in pazienti con difetto genetico dell’antitrombina rispetto ai controlli (p<.001). Nonostante i ridotti livelli di attività anti-Xa, i pazienti cirrotici hanno dimostrato un maggiore effetto anticoagulante dell’eparina a basso peso molecolare, con una riduzione del potenziale endogeno di trombina di 72.6±11% (p=0.02 vs i controlli). Data l’incrementata suscettibilità dei pazienti cirrotici in stadi avanzati della malattia epatica, potrebbe essere necessaria la riduzione della dose di anticoagulazione.
23
Nightingale, Philip D. "Low molecular weight halocarbons in seawater". Thesis, University of East Anglia, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.280971.
Testo completo
24
Hoogland, J. S. "Properties of low molecular weight food surfactants". Thesis, University of Bristol, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333908.
Testo completo
25
Roberts-Thomson, Peter John. "Low molecular weight IgM in health and disease /". Title page, index and abstract only, 1987. http://web4.library.adelaide.edu.au/theses/09MD/09mdr648.pdf.
Testo completo
26
Chen, Qiang. "The major chloroplast low molecular weight heat shock protein". Diss., The University of Arizona, 1992. http://hdl.handle.net/10150/185849.
Testo completoAbstract (sommario):
The goal of this dissertation is to provide information critical for understanding the function of the major chloroplast LMW HSP. The results of this research show that the production of a nuclear-encoded, chloroplast LMW HSP is a highly conserved event in the plant HS response, and that the HSP itself is highly homologous in divergent plant species. Three major conserved regions were identified in the chloroplast LMW HSP. The carboxyl-terminal HS domain of the chloroplast LMW HSP is also found in cytoplasmic LMW HSPs and identifies it as a member of the superfamily of eukaryotic LMW HSPs. The amino-terminal region is unique to the chloroplast LMW HSP and is capable of forming a Met-rich amphipathic α-helix. The chloroplast LMW HSP cannot be detected at normal growth temperatures, but accumulates dramatically in both leaves and roots during HS. The chloroplast LMW HSP is a stable protein with a half-life of approximately 52 h. In the chloroplast, the majority of PsHSP21 is localized in the soluble protein fraction. In its native state, PsHSP21 exists in a 200 kDa particle as is observed for cytoplasmic LMW HSPs. However, unlike the cytoplasmic LMW HSPs, the PsHSP21-containing particles do not aggregate into heat shock granules even under severe, abrupt HS conditions. The formation of the PsHPS21-containing particle can be replicated in isolated chloroplasts, but the chloroplasts must be from heat stressed plants. The protein sequence homology and the similar native structure of the LMW cytoplasmic and chloroplast HSPs suggests they perform similar functions in different cellular compartments. I propose that the 200 kDa particle is the functional form of PsHSP21. Furthermore, the chloroplast LMW HSP performs functions in all types of plastids similar to those of the cytoplasmic LMW HSPs, but with unique substrates within the special environment of plastids. This study provides the first information regarding the expression and structure of the chloroplast LMW HSP. Since the chloroplast contains only a single major LMW HSP, this study also provides the basis for developing a simple model system for studies of the function of all members of the ubiquitous LMW HSP family.
27
Song, Yang. "OXIDATIVE DEPOLYMERIZATION OF LIGNIN TO LOW MOLECULAR WEIGHT AROMATICS". UKnowledge, 2019. https://uknowledge.uky.edu/chemistry_etds/114.
Testo completoAbstract (sommario):
To date, most lignocellulosic biorefinery strategies have focused on optimizing conversion of cellulose to ethanol, leaving lignin as an underutilized biomass constituent. Lignin is engineered by nature with the intent to protect plants from chemical and biological attack; this leaves lignin with high structural irregularity and recalcitrance, rendering conversion of the lignin macromolecule to valuable products particularly challenging. Nevertheless, given that the economics of cellulosic ethanol production are strongly dependent on the value that can be obtained for the lignin co-product, the successful valorization of lignin is a crucial step in the transition towards a bio-based economy.
This thesis focuses on lignin depolymerization using oxidative methods, specifically, the oxidation and cleavage of the β-O-4 linkage. Heterogeneous catalysis in this case is more desirable than homogenous catalysis as the catalyst easily recovered, and it is better suited for industrial applications. Initially, layered double hydroxide (LDH) supported gold nanoparticles were characterized and screened in the oxidation of various lignin model compounds using molecular oxygen, leading to the discovery of an Au/Li-Al LDH heterogeneous catalyst active for oxidative cleavage of the β-O-4 linkage. The Au/Li-Al LDH catalyst was then applied to oxidatively depolymerize Indulin AT kraft lignin and γ-valerolactone (GVL) extracted lignin, high yields of monomers being observed when the oxidized lignins underwent subsequent base-catalyzed hydrolysis. Thereafter, different literature oxidative lignin depolymerization methods were tested on kraft lignin and GVL lignin, and the results compared to the Au/Li-Al LDH catalyst (coupled with hydrolysis) system to determine the most effective oxidative depolymerization method.
28
Rodríguez, Seco Cristina. "Low-Molecular Weight Semiconductors for Organic and Perovskite Solar Cells". Doctoral thesis, Universitat Rovira i Virgili, 2019. http://hdl.handle.net/10803/667660.
Testo completoAbstract (sommario):
Actualment, les fonts d'energia renovables estan atraient molta atenció degut a l'impacte negatiu que els combustibles
fòssils estan causant al planeta. Les tecnologies basades en les cel·les fotovoltaiques són una alternativa sostenible
per cobrir la demanda energètica mundial.
El principal objectiu d'aquest treball és el disseny i la síntesis de noves molècules per tal de reemplaçar els polímers
habitualment utilitzats com a molècules captadores de llum en cel·les solars orgàniques i el spiro-OMeTAD usat com a
transportador de buits (HTM per les sigles en anglès "hole transporting material") en dispositius solars de perovskita.
D'una banda, els polímers són coneguts per ser bons transportadors de buits, posseir una elevada solubilitat i una
bona habilitat per a la formació de capes, però entre els diferents lots existeix una baixa reproductibilitat degut a la
seva síntesi complexa. D'altra banda, el spiro-OMeTAD és la molècula que millor reproductibilitat i eficiència presenta
en cel·les solars de perovskita. No obstant això, la seva síntesi complexa i d’alt cost impedeix la possibilitat d'escalat a
nivell industrial.
Per tal de solucionar aquests problemes, aquesta tesi s'ha enfocat en el disseny, síntesi i caracterització d'un conjunt
de molècules petites de baix pes molecular per a la seva aplicació en aquests dispositius.Actualmente, las fuentes de energía renovables están atrayendo mucha atención debido al impacto negativo que los combustibles fósiles están causando al planeta. Las tecnologías basadas en las celdas fotovoltaicas son una alternativa sostenible para cubrir la demanda energética mundial. El principal objetivo de este trabajo fue el diseño y la síntesis de nuevas moléculas que reemplacen los polímeros comúnmente utilizados como moléculas captadoras de luz en celdas solares orgánicas y el spiro-OMeTAD usado como transportador de huecos (HTM por sus siglas en inglés “hole transporting material”) en dispositivos solares de perovskita. Por una parte, los polímeros son conocidos por ser buenos transportadores de huecos, su alta solubilidad y su favorable habilidad en la formación de capas, pero tienen muy poca reproducibilidad entre distintos lotes. Por otra parte, el spiro-OMeTAD es la molécula que mejor reproducibilidad y eficiencia presenta en celdas solares de perovskita. Sin embargo, su síntesis compleja y de alto coste impide la posibilidad de escalado a nivel industrial. Con el fin de solucionar estos problemas, esta tesis se ha enfocado en el diseño, síntesis y caracterización de un conjunto de moléculas pequeñas de bajo peso molecular para su aplicación en dichos dispositivos
Nowadays, renewable energy sources are attracting a lot of attention due to the undesired environmental impact the fossil fuels are causing to the Earth. Solar cells technologies are a sustainable alternative to the increasing world energy demand. The main aim of this work was to design and synthetize novel molecules that could replace the polymers widely used as absorbers in organic solar cells and spiro-OMeTAD used as a hole transporting material (HTM) in perovskite solar cells. On the one hand, polymers are known for their good hole transporting properties, high solubility and good film forming abilities but they have a poor batch-to-batch reproducibility. Furthermore, spiro-OMeTAD is the best molecule to achieve reproducible and highly efficient perovskite solar cells. However, its complex and expensive synthesis and purification hinder its usage in industrial scale photovoltaics. In order to overcome these problems, the rational design, synthesis and characterization of a variety of small molecules for both applications have been on a focus of this thesis.
29
Cheuk, Sherwin. "Glucose and Glucosamine Derivatives as Novel Low Molecular Weight Gelators". ScholarWorks@UNO, 2008. http://scholarworks.uno.edu/td/868.
Testo completoAbstract (sommario):
Low molecular weight gelators (LMWGs) are small molecules that are capable of entrapping solvents to form a gel in organic solvents or aqueous solution. These compounds rely solely on noncovalent forces to form the fibrous networks necessary to entrap a variety of solvents. The organogels and hydrogels thus formed could have applications in a variety of fields from environmental to biological to medicinal. Carbohydrates are ideal starting materials to synthesize LMWGs, because of their natural abundance, dense chirality, and biocompatibility. D-Glucose is the most common monosaccharide and D-glucosamine is isolated from natural sources, such as crab shells. Several series of compounds were synthesized using compounds 1-3 as the starting materials. These include esters, carbamates, amides, and ureas. The structure and gelation relationship was analyzed to obtain guidelines for designing new LMWGs. Compound 1 is a simple derivative of D-glucose and its terminal alkynyl esters and saturated carbamates are effective gelators. Compound 2 is a simple derivative of D-glucosamine and its amide and urea derivatives are also effective gelators. Compound 3 is formed from the deoxygenation of D-glucose. 1OOHOOCH3OHOPh2OOHOOCH3NH2OPh3OOHOOHOPh The design, synthesis and gelation properties of several classes of sugar based low molecular organo/hydrogelators will be discussed in this thesis in chapters 2, 3, and 4. After obtaining highly effective organo/hydrogelators, potential applications of these novel molecular systems can be explored. Some preliminary study on using one of the gelator in enzyme assay has shown that it is possible to utilize the hydrogels to immobilize enzymes. However, future research can explore further on the applications of these gelators.
30
Williams, Kristopher Aaron. "Synthesis and Characterization of Monosaccharide-derived Low Molecular Weight Gelators". ScholarWorks@UNO, 2011. http://scholarworks.uno.edu/td/135.
Testo completoAbstract (sommario):
Low molecular weight gelators (LMWGs) are interesting materials whose applications are as diverse and wide ranging as their molecular structures. These materials self-assemble through the formation of non-covelent intermolecular forces and interactions to form supramolecular assemblies that trap solvent within their matrices. Because of the non-covalent nature of the forces of self-assembly, the gelation process is typically thermally reversible. In addition, low molecular weight gelators can also be modified to respond to various stimuli, such as change in pH, presence of enzymes or metal cations, or exposure to light. The design of low molecular weight gelators is often difficult, and most new classes of low molecular weight gelators are discovered by serendipity. As such, it is often useful to use structural templates in the design of LMWGs. Biomolecules, such as steroids, amino acids and peptides, and carbohydrates make excellent templates due to their inherent propensity to self assemble. A review of the current literature regarding the use of biomolecules as templates for the design and synthesis of LMWGs will be presented in chapter 1. Our research group has been active in the research of carbohydrate-based LMWGs for several years, and these results are also briefly reviewed in the related chapters. The synthesis and characterization of ester derivatives of D-galactose, D-glucose, and amide derivatives of D-glucosamine will be discussed in chapters 2-4, along with their evaluation for gelation in aqueous and organic solvents, such as hexane, ethanol, water, and aqueous DMSO or ethanol mixtures.
31
Yang, Hao. "Synthesis and characterization of sugar based low molecular weight gelators". ScholarWorks@UNO, 2012. http://scholarworks.uno.edu/td/1496.
Testo completoAbstract (sommario):
Low molecular weight gelators (LMWGs) have gained great attention over the past two decades. These compounds form self-assembled fibrous networks like micelles, cylindrical, sheets, fibers, layers and so on. The fibrous network entraps the solvent and form gel. LMWGs are interesting compounds with many potential applications in material and biomedical sciences.
Many different structures have been found to be good LMWGs. Our interests focus on the carbohydrate based LMWGs. Previously, we have found that several ester derivatives of methyl 4, 6-O-benzylidene-α-D-glucopyranoside are good gelators for organic solvents and aqueous solutions. In this study, in order to understand the structure requirement, we systematically investigated the influence of sugar head groups and the attached hydrophobic tails towards gelation. The design, synthesis and gel properties of esters, amides, ureas, carbamates which derived from sugar head groups show above will be discussed in chapter II, III, IV.
32
Brás, Ana Rita Elias. "Influence of constraining and confinement in the molecular mobility of low molecular weight materials". Doctoral thesis, FCT - UNL, 2009. http://hdl.handle.net/10362/2670.
Testo completoAbstract (sommario):
Dissertation presented to obtain a Ph.D. Degree in Chemical PhysicsDespite the importance that the glassy state has nowadays, the transition from liquid to the glass, glass transition, still remains a matter of debate which constitutes one of the great condensed matter physics challenges. Since this fact is closely related to the cooperativity dynamics, the study of this phenomenon in glass-forming liquids under confinement in the nanometer scale, has recently emerged as a strategy to clarify factors such as the existence of an inherent length scale of the cooperative dynamics that determines the glass transition temperature. In this context, this thesis represents an additional contribution to the study of molecular dynamics of glass-forming liquids under confinement in nanoporous inorganic materials. As target compounds the liquid crystal E7 and the drug Ibuprofen were selected. Since the first exhibit various transitions makes it more sensitive to perturbations and thus appears as the ideal candidate to evaluate confinement effects. The study of ibuprofen is of particular interest because confinement emerges as a method of stabilizing the amorphous phase that is mostly important in pharmaceutical applications. Dielectric Relaxation Spectroscopy(DRS) is the main technique used to obtain detailed information about the molecular mobility in a wide range of frequencies (10-2-109Hz) (Chapter I and II). The first part of the thesis is devoted to the characterization of the two target compounds in the bulk state. The combination of DRS with the specific heat spectroscopy allowed to determine which of the E7 observed relaxation processes (a process in the isotropic phase and two processes in the nematic phase: δ and tumbling) is responsible for the glass transition temperature Tg (tumbling process). Detailed studies of ibuprofen molecular mobility in the liquid, supercooled liquid and glassy states are also presented in this chapter, where four relaxation processes are detected: two secondary processes (γ and β), the cooperative process related to Tg (α ) and the Debye process (D), probably related to the hydrogen bonding dynamics. This study was preceded by an optimization of the conditions to obtain amorphous Ibuprofen which is a crystal in its natural state (Chapter III). In the next chapter (Chapter IV), the molecular dynamics of E7 confined to untreated and phospholipid lecithin treated rigid inorganic membranes with 20 nm pore diameter was evaluated. It was found that both the liquid crystal alignment, as well as the dynamics is influenced by confinement and treatment of the surface pores. Additionally, E7 was further studied confined to the mesoporous materials MCM-41 and SBA-15 type, 100% silica composition and pore size between the 2.8 and 6.8 nm. A multiplicity of relaxation processes was revealed by DRS, including the modes already observed in the bulk E7. In addition, two
Fundação para a Ciência e Tecnologia (FCT),financial support by means of the PhD grant SFRH/BD/23829/2005
33
Gao, Karen Ging. "Photoresist removal using low molecular weight alcohols and IPA-based solutions". Thesis, Georgia Institute of Technology, 2001. http://hdl.handle.net/1853/11875.
Testo completo
34
Gauthier, Elisabeth. "Utilization of low molecular weight substrates by psychrotrophic meat spoilage organisms". Thesis, McGill University, 1990. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=59274.
Testo completoAbstract (sommario):
Four meat spoilage organisms were grown at 4$ sp circ$C for 7 d, in an aqueous extract of meat (Meat Juice Medium), and the levels of various nutrients in the extracts were measured. At an agitation rate of 50 rev$ cdot$min$ sp{-1},$ the four species reached viable counts of 10$ sp8$ Colony Forming Units (CFU)$ cdot$ml$ sp{-1},$ and the order of nutrient utilization was as follows: (1) glucose, (2) gluconate and urea, (3) glycerol, (4) glucose-6-phosphate. Several substrates were still present in the growth medium at the end of the growth period, namely lactate, glucose-6-phosphate and the two unknowns. At a higher agitation rate (100 rev$ cdot$min$ sp{-1}),$ the non-fluorescent pseudomonad reached final counts of ca. 10$ sp{10}$ CFU$ cdot$ml$ sp{-1},$ 2 logs higher than those of the other three organisms present in the mixed culture. The order of nutrient utilization was: (1) glucose, (2) gluconate, urea and glycerol, (3) lactate and glucose-6-phosphate, (4) unknowns 1 and 2. At day 7, none of the nine substrates studied remained in the growth medium.
35
Lo, Wendy. "Thermo-chemical recovery of low molecular weight oligomers from polyethylene waste". Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61313.
Testo completoAbstract (sommario):
This study focused on the chemical recycling of polyethylene using controlled thermo-chemical degradation. Polyethylene was degraded in a stirred, batch reactor under a nitrogen atmosphere. The reaction temperatures that were investigated ranged between 375$ sp circ$C and 421$ sp circ$C. The reaction time ranged between 20 and 50 minutes. Three major products were collected, an insoluble solid residue, a condensable wax that was volatile during the reaction, and a residual wax that was not volatile during the reaction. It was determined that above 409$ sp circ$C, 90% of the original resin weight was converted to both the volatile and residual wax. Both waxes had a final Mn of 400 to 500. Analysis revealed that the volatile wax was a mixture of straight chain hydrocarbons, with 4% of the carbon bonds unsaturated. The residual wax was a mixture of hydrocarbons, both straight and branched components. No liquid product was collected, and gaseous components did not exceed 10% of the original resin weight. It was also determined that silica alumina did not enhance degradation.
36
Cotterill, Sally L. "Purification of a low molecular weight heat shock protein from plants". Thesis, Bangor University, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262239.
Testo completo
37
Danesh, Mesgaran Mohsen. "Ruminal accumulation and fate of low molecular weight peptides in sheep". Thesis, University of Newcastle Upon Tyne, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295475.
Testo completo
38
Crawford, S. M. "Low molecular weight proteinuria and the natural history of multiple myeloma". Thesis, University of Liverpool, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.382055.
Testo completo
39
Parikh, Bhargiv. "Design, Synthesis and Characterization of D-glucosamine Low Molecular Weight Gelators". ScholarWorks@UNO, 2010. http://scholarworks.uno.edu/td/1110.
Testo completoAbstract (sommario):
Low molecular weight gelators (LMWGs) have gained much attention over the last few decades, because of their ability to form supramolecular architectures as well as their many potential applications in biomedical research and as advanced materials. Most of the gelators were discovered through serendipity, and their structural requirements are somewhat ambiguous. This is due, in part, to the fact that the supramolecular gelation phenomenon is not yet fully understood, though many structural classes have been found to be excellent organogelators. Carbohydrates are abundant natural resources that are useful in preparing advanced materials. We have previously showed that monosaccharide derivatives can form effective low molecular weight gelators for both organic solvents and aqueous mixtures. In this research, we have studied the gelation capability of several glucosamine derivatives. Several series of 4,6-O-acetal protected glucosamine derivatives were synthesized and screened for their gelation properties in several solvents.
40
Aktaş, Ece. "Low-Molecular Weight Molecules as Selective Contacts for Perovskite Solar Cells". Doctoral thesis, Universitat Rovira i Virgili, 2021. http://hdl.handle.net/10803/672777.
Testo completoAbstract (sommario):
La tecnologia fotovoltaica és una de les fonts d'energia neta i renovable més prometedores per reduir l'impacte ambiental dels combustibles fòssils en les últimes dècades. en aquest context, les perovskites són un material que ha atret recentment una atenció important a causa de la seva capacitat per aconseguir eficiències de conversió molt elevades. Les capes de càrrega selectiva juguen un paper crucial en el ràpid augment del rendiment del dispositiu i en l'estabilitat de les cel·les solars de perovskita. Recentment, l'aplicació de mono-capes auto-assemblades formades per molècules orgàniques que funcionen com a capes selectives de càrrega en cel·les solars de perovskita ha atret una gran atenció a causa d'avantatges com la rendibilitat, l'estabilitat i l'absència d'additius. L'objectiu d'aquesta tesi és el disseny i la síntesi de noves molècules que formen mono-capes auto-assemblades que funcionin com a capes selectives de forats en cel·les solars de perovskita per aconseguir una eficiència de conversió d'alta d'energia i una vida d'envelliment d'alt rendiment feta a mida.La tecnología fotovoltaica es una de las fuentes de energía limpia y renovable más prometedoras para reducir el impacto ambiental de los combustibles fósiles en las últimas décadas. en este contexto, las *perovskites son un material que ha atraído recientemente una atención importante a causa de su capacidad para conseguir eficiencias de conversión muy elevadas. Las capas de carga selectiva juegan un papel crucial en el rápido aumento del rendimiento del dispositivo y en la estabilidad de las celdas solares de *perovskita. Recientemente, la aplicación de *mono-capes auto-asemejadas formadas por moléculas orgánicas que funcionan como capas selectivas de carga en celdas solares de *perovskita ha atraído una gran atención a causa de ventajas como la rentabilidad, la estabilidad y la ausencia de aditivos. El objetivo de esta tesis es el diseño y la síntesis de nuevas moléculas que forman *mono-capes auto-asemejadas que funcionen como capas selectivas de agujeros en celdas solares de *perovskita para conseguir una eficiencia de conversión de alta de energía y una vida de envejecimiento de alto rendimiento hecha a medida.
Photovoltaic technology is one of the most promising clean and renewable energy sources to reduce the environmental impact of fossil fuels in recent decades. In this context, perovskites are a material that has recently attracted significant attention due to their ability to achieve very high conversion efficiencys. Selective charge layers play a crucial role in rapidly increasing device performance and in the stability of perovskite solar cells. Recently, the application of self-assembly mono-caps made up of organic molecules that function as selective layers of charge in solar perovskite cells has attracted great attention due to advantages such as profitability, stability and the absence of additives. The goal of this thesis is the design and synthesis of new molecules that form self-assembly mono-layers that function as selective layers of holes in solar perovskite cells to achieve high-energy conversion efficiency and a high-performance aging life tailored to size.
41
Funkey, Carolina P. "Abiotic Release of Low Molecular Weight Nitrogen from Effluent Organic Nitrogen". W&M ScholarWorks, 2011. https://scholarworks.wm.edu/etd/1539617906.
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42
Chen, Yuan. "Low-molecular-weight chromium-binding substance advanced studies from aves to human /". Thesis, [Tuscaloosa, Ala. : University of Alabama Libraries], 2009. http://purl.lib.ua.edu/2167.
Testo completo
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Alshahrani, Rasha. "Liquid Organic Electrolytes: Blends of Low Molecular Weight Methoxyoligooxyethylene (MPEGs)/LiTFSI Salt". DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2017. http://digitalcommons.auctr.edu/cauetds/111.
Testo completoAbstract (sommario):
Blends containing methoxyoligooxyethyleneglycol (MPEGs) (MW 350 and 550) and bis(trifluoromethane)sulfonimide lithium (LiTFSI) salt were prepared by solution blending process using tetrahydrofuran (THF) as a solvent. The ionic conductivity of the blends of different compositions were determined at four temperatures i.e. 25°C, 40°C, 60°C and 70°C. A maximum ionic conductivity value of 3.9x10-3 S cm-1 at 25°C was obtained for the blends containing MPEG-350 at an ethylene oxide to lithium salt ratio of 1:10. The ionic conductivity increases with increasing temperature and shows that the ion transport is aided by the segmental motion of the MPEG chains. 7Li NMR spectroscopy was used to study the nature and dynamics of the salt clusters in the blends
44
Hoang, Tiffany Truc. "Speciation and identification of low molecular weight organoselenium metabolites in human urine". Diss., Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/30671.
Testo completo
45
Griffin, Jonathan Hrothgar. "Low molecular weight proteomic analysis of Arabidopsis thaliana and Oryza sativa seeds". Thesis, University of Bristol, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414173.
Testo completo
46
Sivakova, Sona. "Supramolecular Polymers via Nucleobase Directed Self-Assembly of Low-Molecular Weight Monomers". Case Western Reserve University School of Graduate Studies / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=case1112726513.
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47
Verghese, Jenson. "SYNTHESIS AND BIOCHEMICAL STUDIES ON SULFATED MONOMERS OF LOW MOLECULAR WEIGHT LIGNINS". VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1868.
Testo completoAbstract (sommario):
Anticoagulants are used as the first line therapy for management and prevention of thrombotic disorders. Thrombin and factor Xa have been the prime targets for regulation of the coagulation cascade. In this work, a small library of 17 benzofuran derivatives were synthesized and screened against thrombin and factor Xa. The derivatives that displayed inhibitory potential were docked on the exosite-II of factor Xa using a docking protocol that was developed in our research group. These compounds were based on the β-5 structural unit found in the oligomer -'CDSO3‘, which was prepared in our lab and was found to inhibit both thrombin and factor Xa by an exosite-II mediated allosteric disruption of the catalytic triad.The results revealed that these β-5 like derivatives are inhibitory against thrombin and factor Xa, although their potency is weak. Thrombin and factor Xa appear to recognize different structural features suggesting a significant selectivity in recognition. Furthermore, a slight preference for the benzofuran scaffold was observed with factor Xa. Probing the mechanism of inhibition using Michaelis-Menten kinetics reveal that these compounds display uncompetitive inhibition of these proteases and the mechanism of inhibition is allosteric. Docking of these compounds on factor Xa were done using GOLD (Genetic algorithm for ligand docking) and the results, explain the observed inhibition profile. The computed docked poses also give an idea of the residues on the exosite-II of factor Xa critical for inhibition. The molecules studied here are radically different in terms of structure and mechanism of inhibition from any other ligand described in literature. This represents an opportunity to discover novel molecules with a possibly different pharmacological and toxicological profile.
48
Goh, Ching Yong. "Amino acid functionalised calixarenes: crystal growth modifiers and low molecular weight gelators". Thesis, Curtin University, 2012. http://hdl.handle.net/20.500.11937/1894.
Testo completoAbstract (sommario):
A selection of amino acid functionalised calix[4]arenes was studied. Acidic amino acid functionalised calixarenes were investigated as crystal growth modifiers. The self-assembly behaviour of proline functionalised calixarenes were also examined.Calix[4]arenes functionalised at the wide-rim with acidic amino acids were investigated as potential crystal growth modifiers on model mineral systems and were compared with previously investigated narrow-rim analogues. This study found that the wide-rim aspartic acid and glutamic acid functionalised calix[4]arenes had an impact on the morphology of calcium carbonate and barium sulfate. The iminodiacetic acid calix[4]arene was found to have minor impact on the morphology of calcium carbonate.In comparison with the narrow-rim analogues, the wide-rim and narrow-rim aspartic acid calix[4]arenes had similar potency on calcium carbonate while the wide-rim glutamic acid calix[4]arene appeared to be more potent than the narrow-rim calix[4]arene. Calcium carbonate crystallised in the presence of wide-rim aspartic acid and glutamic acid calix[4]arenes and their narrow-rim analogues had stepped edges which resembled calcium carbonate found in biomineral systems (e.g. mollusc shells). Desupersaturation experiments showed the wide-rim aspartic acid calix[4]arene to be a more potent inhibitor of barium sulfate crystallisation than the wide-rim glutamic acid calix[4]arene.An aqueous solution of L-proline calix[4]arene exhibited surfactant-like properties. The self-assembly behaviour of L-proline calix[4]arene in solution was characterised by UV-visible and NMR spectroscopy. The critical aggregation concentration of L-proline calix[4]arene was determined to be 4–9 mM by monitoring a selection of dye compounds using UV-visible spectroscopy. The interaction of L-proline calix[4]arene with small molecules and in the presence of electrolytes was also characterised by NMR spectroscopy. The 1H NMR spectra of L-proline calix[4]arene in the presence of small molecules (tetrahydrofuran, 1-methyl-2-pyrrolidinone, and tert-butyl alcohol) suggested that the calixarene was either acting as a host or selfassembling into larger aggregates. Variable temperature NMR experiments showed that these interactions were thermoreversible.The formation of a hydrogel by proline calix[4]arenes in the presence of electrolytes was a serendipitous discovery. Investigations with selected electrolytes showed that the anion was the dominant factor in determining if a hydrogel formed, with lesser influence from the cation. The thermostability of the calixarene-electrolyte hydrogels tended to follow the Hofmeister series, where more stable hydrogels formed in the presence of anions towards the chaotropic end of the series. A racemic mixture of the proline calixarenes gave a less stable hydrogel compared with hydrogels of the enantiopure compounds. The calixarene-electrolyte hydrogels had a fibrous appearance, as characterised by atomic force microscopy. Some hydrogels collapsed slowly and deposited crystals of sufficient quality for single crystal x-ray crystallography. These structures gave some insights into how intermolecular forces may give rise to the fibrous gel structures; in particular hydrogen bonds between proline moieties, and the inclusion of a proline group into the cavity of a neighbouring calixarene, leading to spiral-like structures. A sarcosine functionalised calix[4]arene also formed hydrogels upon addition of some electrolytes, whereas the proline-functionalised calix[5]arene analogue did not.Since a range of hydrogels have been used as matrices to control crystal growth, a proline calix[4]arene-lithium nitrate hydrogel was used as a potential template for barium sulfate crystallisation. The results suggested that lithium nitrate was the main factor in modification of the barium sulfate morphology. The hydrogel did have a minor impact by slowing the diffusion of sulfate anions into the barium-containing gel phase resulting in smaller particles.The versatility of amino acid functionalised calix[4]arenes has been highlighted here. Wide-rim functionalised acidic amino acid calix[4]arenes were found to be effective crystal growth modifiers; having an impact on the morphology and growth kinetics of model crystallisation systems, calcium carbonate and barium sulfate. Interesting supramolecular chemistry was observed with proline functionalised calix[4]arenes; the proline calixarene interacts with small molecules in solution and either act as a host or self-assembles into large aggregates. The formation of proline calix[4]arene aggregates is interesting as they give rise to hydrogels in the presence of selected electrolytes.
49
Ferrari, Dante F. "Aminolysis kinetics of low molecular weight and polymer-bound anhydride moieties in low and high viscosity media". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq20633.pdf.
Testo completo
50
Lambourne, John Joseph. "Elucidating the role of low molecular weight glutenin subunits in determining wheat quality". Thesis, University of Reading, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.506122.
Testo completo