| 1382651. |
- Stride, A, et al.
(författare)
-
The genetic abnormality in the beta cell determines the response to an oral glucose load
- 2002
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 45:3, s. 427-435
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis. We assessed how the role of genes genetic causation in causing maturity-onset diabetes of the young (MODY) alters the response to an oral glucose tolerance test (OGTT). Methods. We studied OGTT in 362 MODY subjects, from seven European centres; 245 had glucokinase gene mutations and 117 had Hepatocyte Nuclear Factor-1 alpha (HNF-1alpha) gene mutations. Results. BMI and age were similar in the genetically defined groups. Fasting plasma glucose (FPG) was less than 5.5 mmol/l in 2% glucokinase subjects and 46% HNF-1alpha subjects (p < 0.0001). Glucokinase subjects had a higher FPG than HNF-1a subjects ([means +/- SD] 6.8 +/- 0.8 vs 6.0 +/- 1.9 mmol/l, p < 0.0001), a lower 2-h value (8.9 +/- 2.3 vs 11.2 +/- 5.2 mmol/l, p < 0.0001) and a lower OGTT increment (2-h - fasting) (2.1 +/- 2.3 vs 5.2 +/- 3.9 mmol/l, p < 0.0001). The relative proportions classified as diabetic depended on whether fasting (38% vs 22%, glucokinase vs HNF-1alpha) or 2-h values (19% vs 44%) were used. Fasting and 2-h glucose values were not correlated in the glucokinase subjects (r = -0.047, p = 0.65) but were strongly correlated in HNF-1alpha subjects (r = 0.8, p < 0.001). Insulin concentrations were higher in the glucokinase subjects throughout the OGTT. Conclusion/interpretation. The genetic cause of the beta-cell defect results in clear differences in both the fasting glucose and the response to an oral glucose load and this can help diagnostic genetic testing in MODY. OGTT results reflect not only the degree of hyperglycaemia but also the underlying cause.
|
|
| 1382652. |
- Stride, Gail, et al.
(författare)
-
Revisiting the biogeography of Sideroxylon (Sapotaceae) and an evaluation of the taxonomic status of Argania and Spiniluma
- 2014
-
Ingår i: Australian Systematic Botany. - 1030-1887 .- 1446-5701. ; 27:2, s. 104-118
-
Tidskriftsartikel (refereegranskat)abstract
- Biogeography of Sideroxylon (Sapotoideae) and whether the satellite genera Argania and Spiniluma merit recognition are revisited. The hypothesis of an African origin with a subsequent migration to Central America via Europe and the North Atlantic landbridge is challenged. We analysed 58 accessions of trnH-psbA and ITS sequences in a fossil- calibrated, relaxed lognormal clock model with BEAST for phylogenetic and biogeographic inference. Argania spinosa (L.) Skeels from Morocco must be united with Sideroxylon, whereas S. discolor Radcl.-Sm. and S. oxyacanthum Baill. belong to subfamily Chrysophylloideae and may be recognised as Spiniluma. The divergence time estimate suggests that Sideroxylon originated and first diversified in Central America 56.3–52.2 million years ago, contemporaneous with the landbridge, but an archipelago of islands and the Tethys Seaway halted eastward expansion to Africa until c. 20 million years ago, i.e. 25 million years after establishment in Africa. Range expansion of Sideroxylon was therefore not powered by the landbridge, and a long-distance dispersal from Central America to Africa is proposed. The establishment of the Gomphotherium landbridge between Africa and Eurasia at 19 million years ago provided a land-migration route to Europe and Asia, which is reconcilable with the extension of Xantolis into Asia. Sideroxylon has colonised Socotra by over-water dispersal in the Gulf of Aden, Macaronesia, Madagascar and the Mascarene Islands.
|
|
| 1382653. |
- Stridfeldt, Elin, et al.
(författare)
-
Competing Pathways in O-Arylations with Diaryliodonium Salts : Mechanistic Insights
- 2017
-
Ingår i: Chemistry - A European Journal. - : Wiley-VCH Verlagsgesellschaft. - 0947-6539 .- 1521-3765. ; 23:53, s. 13249-13258
-
Tidskriftsartikel (refereegranskat)abstract
- A mechanistic study of arylations of aliphatic alcohols and hydroxide with diaryliodonium salts, to give alkyl aryl ethers and diaryl ethers, has been performed using experimental techniques and DFT calculations. Aryne intermediates have been trapped, and additives to avoid by-product formation originating from arynes have been found. An alcohol oxidation pathway was observed in parallel to arylation; this is suggested to proceed by an intramolecular mechanism. Product formation pathways via ligand coupling and arynes have been compared, and 4-coordinated transition states were found to be favored in reactions with alcohols. Furthermore, a novel, direct nucleophilic substitution pathway has been identified in reactions with electron-deficient diaryliodonium salts.
|
|
| 1382654. |
- Stridfeldt, Elin, 1988-
(författare)
-
Hypervalent Iodine Reagents in Metal-Free Arylations and Vinylations : Investigation of Suitable Coupling Partners and Synthesis of New Reagents
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis concerns the development of metal-free reactions to obtain carbon-heteroatom and carbon-carbon bonds. This is achieved by transferring carbon ligands from hypervalent iodine reagents to suitable nucleophiles.The bulk of the work presented herein concerns arylation of oxygen and nitrogen nucleophiles, using the well-known diaryliodonium salts as aryl sources. In the first project, O-arylation of the oxime ethyl acetohydroxamate was studied. It was found that electron-poor as well as electron-rich aryl moieties could be transferred successfully to this nucleophile. Furthermore, the protocol could be extended to a sequential one-pot synthesis of benzo[b]furans. This method allowed for a fast synthesis of the natural product stemofuran A and formal syntheses of other natural products.In a successive project, O-arylation of hydroxide and aliphatic alkoxides was investigated. It is known that electron-poor aryl moieties can be transferred to these nucleophiles in moderate to high yields. However, combined with more electron-rich diaryliodonium salts, a large amount of side products were formed. These were suppressed upon addition of aryne traps, suggesting that aryne pathways are competing with the desired ligand coupling. It was also observed that secondary alcohols were oxidized to the corresponding ketones. The mechanism for this oxidation was investigated and aryne pathways could be excluded. Instead we suggest that the carbinol hydrogen gets deprotonated via an internal mechanism, after the alkoxide has coordinated to the iodonium salt. Highly sterically congested alkyl aryl ethers could be obtained in high yields by combining tertiary alcohols with ortho-blocked diaryliodonium salts. Next, N-arylation of secondary acyclic amides was studied using acetanilide as the model substrate. This procedure was suitable for transfer of electron-poor as well as ortho-substituted aryl moieties, but attempts to transfer very electron-rich aryl groups were unsuccessful. On the other hand, the amides displayed a complementary reactivity, allowing phenylation of electron-rich amides. In the final project, a one-pot synthesis of the cyclic iodonium reagent vinylbenziodoxolone is presented. These compounds have not been explored as reagents earlier. Initial screenings showed that the vinyl moiety could be transferred to nitrocyclohexane with opposite regioselectivity compared to the acyclic analogue of the reagent.
|
|
| 1382655. |
- Stridfeldt, Elin
(författare)
-
Metal‐Free Arylations of Oxygen and Nitrogen Nucleophiles : Applications of Diaryliodonium Salts
- 2015
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis concerns development of new methods for metal‐free arylations in organic synthesis. The protocols discussed in the thesis are based on a class of hypervalent iodine compounds called diaryliodonium salts. These reagents are known to transfer aryl moieties to suitable nucleophiles.The first part describes O‐arylation of ethyl acetohydroxamate, which serves as a hydroxylamine equivalent. Electron‐rich as well as electron‐poor aryl groups could be transferred from the diaryliodonium salts. The arylation products could then be used as intermediates in a straightforward meta‐free one‐pot synthesis of benzofurans. Using this procedure, various substituted benzofurans were obtained in good yields. Furthermore, this methodology was used to synthesise the natural product Stemofuran A in one single step, starting from commercially available compounds. Three formal syntheses of other bioactive benzofurans were included.The second part describes N‐arylation of secondary acyclic amides. The chemoselectivity was explored with unsymmetric diaryliodonium salts, and aryl moieties with ortho‐substituents were preferably transferred. The protocol was suitable for electron‐deficient as well as highly sterically congested diaryliodonium salts. The transfer of electron‐rich aryl moieties was problematic. However, the reactivity for the amide was complementary to that of the salts and electron‐rich amides were phenylated in high yields. Furthermore, the protocol was compatible with benzamides and amides having sterically hindered acyl groups.Both arylation protocols discussed in this thesis work at ambient temperature and a variety of counter‐ions of the diaryliodonium salts were tolerated.
|
|
| 1382656. |
- Stridfeldt, Elin, et al.
(författare)
-
Synthesis, Characterization and Unusual Reactivity of Vinylbenziodoxolones-Novel Hypervalent Iodine Reagents
- 2016
-
Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 22:45, s. 16066-16070
-
Tidskriftsartikel (refereegranskat)abstract
- A novel type of hypervalent iodine(III) reagents, vinylbenziodoxolones (VBX), has been synthesized in a one-pot reaction from 2-iodobenzoic acid. VBX is bench stable, has been thoroughly characterized and the cyclic structure is supported by X-ray analysis. The reactivity of VBX was investigated in vinylation of nitrocyclohexane, and delivered vinylated products with opposite regioselectivity compared to acyclic vinyl(aryl) iodonium salts. The reagents could become a powerful tool in vinylation reactions under both metal-free and metal-catalyzed conditions.
|
|
| 1382657. |
- Stridfeldt, Fredrik, et al.
(författare)
-
Analyses of single extracellular vesicles from non-small lung cancer cells to reveal effects of epidermal growth factor receptor inhibitor treatments
- 2023
-
Ingår i: Talanta. - : Elsevier BV. - 0039-9140 .- 1873-3573. ; 259
-
Tidskriftsartikel (refereegranskat)abstract
- Precision cancer medicine has changed the treatment landscape of non-small cell lung cancer (NSCLC) as illustrated by the introduction of tyrosine kinase inhibitors (TKIs) towards mutated epidermal growth factor receptor (EGFR). However, as responses to EGFR-TKIs are heterogenous among NSCLC patients, there is a need for ways to early monitor changes in treatment response in a non-invasive way e.g., in patient's blood samples. Recently, extracellular vesicles (EVs) have been identified as a source of tumor biomarkers which could improve on non-invasive liquid biopsy-based diagnosis of cancer. However, the heterogeneity in EVs is high. Putative biomarker candidates may be hidden in the differential expression of membrane proteins in a subset of EVs hard to identify using bulk techniques. Using a fluorescence-based approach, we demonstrate that a single-EV tech-nique can detect alterations in EV surface protein profiles. We analyzed EVs isolated from an EGFR-mutant NSCLC cell line, which is refractory to EGFR-TKIs erlotinib and responsive to osimertinib, before and after treatment with these drugs and after cisplatin chemotherapy. We studied expression level of five proteins; two tetraspanins (CD9, CD81), and three markers of interest in lung cancer (EGFR, programmed death-ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2)). The data reveal alterations induced by the osimertinib treatment compared to the other two treatments. These include the growth of the PD-L1/HER2-positive EV population, with the largest increase in vesicles exclusively expressing one of the two proteins. The expression level per EV decreased for these markers. On the other hand, both the TKIs had a similar effect on the EGFR-positive EV population.
|
|
| 1382658. |
|
|
| 1382659. |
|
|
| 1382660. |
- Stridfeldt, Monika
(författare)
-
La perception du français oral par des apprenants suédois
- 2005
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Swedish learners of French often experience large difficulties in understanding spoken French. Words that the learners know very well when written or when pronounced separately are often hard to recognize in the speech flow. The aim of this study is to examine Swedish learners’ perception of French speech in order to identify the problems.The thesis consists of two parts. The first part provides an introduction to the perception of a second language. It also describes the phonological structures of Swedish and French and gives an overview of studies of the perception of spoken French.The second part of the thesis contains a presentation and an analysis of four perception experiments conducted with Swedish learners of French. The results show that the learners often confuse phonological contrasts that do not exist in Swedish. It is furthermore found that the phonological processes of schwa deletion, liaison, enchaînement and voicing assimilation contribute to the perception problems. However, although liaison may complicate word recognition the results indicate that the so-called potential liaison does so to an even greater extent. In a listening test using nonsense words, the learners seem actually to expect liaison when perceiving a word that can be linked to a following nonsense word. In fact, sequences like un navas and un avas are both perceived as un avas. Paradoxically, liaison thus seems to be most problematic when it does not occur.As to schwa deletion, the results show that word recognition is delayed when the schwa in the first syllable is deleted, as in la s’maine. In addition, the learners make a large number of errors due to schwa deletion. This phonological process sometimes completely prevents word recognition, especially when combined with a voicing assimilation. Schwa deletion thus seems to strongly complicate Swedish learners’ word recognition in spoken French.
|
|
