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Small Alterations (small + alteration)
Selected AbstractsNon-linearity in clinical practiceJOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 2 2003Peter Petros MB BS DMedSc DS FRCOG FRANZCOG CU Abstract The whole spectrum of medicine consists of complex non-linear systems that are balanced and interact with each other. How non-linearity confers stability on a system and explains variation and uncertainty in clinical medicine is discussed. A major theme is that a small alteration in initial conditions may have a major effect on the end result. In the context of non-linearity, it is argued that ,evidence-based medicine' (EBM) as it exists today can only ever be relevant to a small fraction of the domain of medicine, that the ,art of medicine' consists of an intuitive ,tuning in' to these complex systems and as such is not so much an art as an expression of non-linear science. The main cause of iatrogenic disease is interpreted as a failure to understand the complexity of the systems being treated. Case study examples are given and analysed in non-linear terms. It is concluded that good medicine concerns individualized treatment of an individual patient whose body functions are governed by non-linear processes. EBM as it exists today paints with a broad and limited brush, but it does promise a fresh new direction. In this context, we need to expand the spectrum of scientific medicine to include non-linearity, and to look upon the ,art of medicine' as a historical (but unstated) legacy in this domain. [source] Synthesis, Structure, and Optical Properties of Terminally Sulfur-Functionalized Core-Substituted Naphthalene-Bisimide DyesHELVETICA CHIMICA ACTA, Issue 9 2006Alfred B, aszczyk Abstract The synthesis, characterization, and optical properties of a series of new 2,6-disubstituted naphthalene-bisimide dyes as molecular rods comprising terminal AcS groups is reported. The first series of dyes (1,3), comprising phenylhetero (Ph-X) core substituents, cover a broad range of the VIS spectrum, ranging from yellow (2) over red (3) to blue (1). The second series of dyes contains benzylhetero (Bn-X) core substituents (4,7). For the same heteroatom connecting the substituent to the naphthalene core, both series were found to display comparable colors. For the second series, the colors were blue (4), red (5), and violet (6, 7). The Ph-X-substituted dyes 1,3 are nonfluorescent, in contrast to the Bn-X-substituted compounds 4,7. This rich variety of optical features that can be adjusted by rather small alterations of the core substituents makes these structurally very comparable molecular rods ideal candidates for optically triggered molecular-transport investigations. Also, thanks to the terminal AcS groups, these compounds can be placed between nobel-metal electrodes for optically triggered transport experiments. [source] Mutational spectrum of the NF2 gene: a meta-analysis of 12 years of research and diagnostic laboratory findings,,HUMAN MUTATION, Issue 1 2007Iris Ahronowitz Abstract The NF2 tumor suppressor gene on chromosome 22 is a member of the protein 4.1 family of cytoskeletal elements. A number of single- and multiple-tumor phenotypes have been linked to alterations of NF2 since its characterization in 1993. We present a meta-analysis of 967 constitutional and somatic NF2 alterations from 93 published reports, along with 59 additional unpublished events identified in our laboratory and 115 alterations identified in clinical samples submitted to the Massachusetts General Hospital (MGH) Neurogenetics DNA Diagnostic Laboratory. In total, these sources defined 1,070 small genetic changes detected primarily by exon scanning, 42 intragenic changes of one whole exon or larger, and 29 whole gene deletions and gross chromosomal rearrangements. Constitutional single-exon events (N=422) were significantly more likely to be nonsense or splice site changes than somatic events (N=533), which favored frameshift changes (,2 test; P<0.001). Somatic events also differed markedly between tumors of different pathology, most significantly in the tendency of somatic events in meningiomas to lie within the 5, FERM domain of the transcript (Fisher's exact test; P<0.01 in comparison to schwannomas) with a complete absence of mutations in exons 14 and 15. There was no statistically significant difference in mutation type or exon distribution between published constitutional events and those found by the clinical laboratory. Less than 10% of all published and unpublished small alterations are nontruncating (N=63) and these changes are clustered in exons 2 and 3, suggesting that this region may be especially crucial to tumor suppressor activity in the protein. Hum Mutat 28(1), 1,12, 2007. Published 2006 Wiley-Liss, Inc. [source] The Determinants of Foreign Direct Investments: Sensitivity Analyses of Cross-Country RegressionsKYKLOS INTERNATIONAL REVIEW OF SOCIAL SCIENCES, Issue 1 2001Avik Chakrabarti A vast empirical literature has used ad hoc linear cross-country regressions to search for the determinants of FDI. The literature is extensive and controversial. Can policy-makers use this body of research to learn anything that can help them stimulate FDI? The author uses Extreme Bound Analysis (EBA) to examine if any of the conclusions from the existing studies is robust to small changes in the conditioning information set. The EBA upholds the robustness of the correlation between FDI and market-size, as measured by per-capita GDP, but indicates that the relation between FDI and many of the controversial variables (namely, tax, wage, openness, exchange rate, tariff, growth, and trade balance)bare highly sensitive to small alterations in the conditioning information set. The author also studies the distribution of the estimated coefficients of the controversial explanatory variables to rank them in order of their likelihood of their being correlated with FDI. [source] Childhood hyperuricemia and acute renal failure resulting from a missense mutation in the HPRT geneAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2002Tarak Srivastava Abstract A 6-year-old boy was determined to have partial hypoxanthine phosphoribosyl transferase (HPRT) enzyme deficiency without the phenotypic features of Lesch-Nyhan syndrome. He presented with recurrent acute renal failure (ARF) from hyperuricemia. Treatment with allopurinol prevented further attacks of renal failure. T lymphocyte cultures were used to sequence the HPRT cDNA and a novel single nucleotide substitution at codon 65 in exon 3 was found (193C,>,T, 65leu,>,phe). This mutation was confirmed by genomic DNA sequencing and was also detected in his heterozygous, asymptomatic mother and sister. Unlike the cells from patients with classic Lesch-Nyhan syndrome, the in vitro cultures of our patient's T-lymphocytes did not proliferate in the presence of purine analogue 6-thioguanine (TG). This report highlights the unusual occurrence of recurrent ARF in a child with partial HPRT enzyme deficiency. The absence of TG resistance in vitro with this mutation shows that even small alterations in enzyme activity in vivo can result in disease symptoms, in this instance, hyperuricemia sufficient to cause ARF. Atypical HPRT mutations should also be considered in cases of unusual renal failure, because correct diagnosis can allow appropriate treatment, as well as informed genetic counseling. © 2002 Wiley-Liss, Inc. [source] Structure and sugar-specificity of basic winged-bean lectin: structures of new disaccharide complexes and a comparative study with other known disaccharide complexes of the lectinACTA CRYSTALLOGRAPHICA SECTION D, Issue 7 2008Kiran A. Kulkarni Crystal structures of the complexes of basic winged-bean agglutinin with the disaccharides Gal,1-4Gal (galabiose), Gal,1-6Glc (mellibiose) and Gal,1-4Gal,-Et have been determined and the complex with Gal,1-2Gal has been modelled. The interactions of the nonreducing Gal with the lectin at the primary site are the same as those in the known complexes with disaccharides having the ,1,3 linkage. The second residue in Gal,1-4Gal and Gal,1-6Glc forms a water bridge to the lectin, while the ethyl group in Gal,1-4Gal,-Et makes nonpolar interactions. In complexes involving disaccharides with ,1-3 linkages, which form part of the A and B blood-group substances, the second sugar residue forms a direct hydrogen bond to the variable loop in the binding site of the lectin. This in part explains the specificity of the lectin for the blood-group substances and also the higher affinity of ,1,3-linked disaccharides for the lectin compared with disaccharides involving other linkages. Including those reported here, 14 crystal structures involving the lectin, accounting for 54 crystallographically independent subunits, are available. A comparative study of these structures shows that the region involving the curved ,-sheet which nestles the metal ions is relatively rigid. The carbohydrate-binding region is perched on this region. The flat ,-sheet, which is involved in oligomerization and exhibits considerable variability in legume lectins, is relatively flexible. Indeed, the structures of basic winged-bean lectin have been of critical importance in establishing legume lectins as a family of proteins in which small alterations in essentially the same tertiary structure lead to large variations in quaternary association. They have also provided a structural explanation of the blood-group specificity of the lectin. [source] The Role of the Conserved Threonine in P450BM3 Oxygen Activation: Substrate-Determined Hydroxylation Activity of the Thr268Ala MutantCHEMBIOCHEM, Issue 2 2008Max J. Cryle Dr. Abstract The hydroxylation activity of the Thr268Ala mutant of P450BM3 has been shown to occur to varying degrees with small alterations in the structure of a fatty-acid substrate. Ten substrates were investigated, including straight chain, branched chain and cis -cyclopropyl substituted fatty acids with a straight-chain length that varied between 12 and 16 carbon atoms. The efficacy of the hydroxylation activity appeared to be governed by the chain length of the substrate. Substrates possessing 14 to 15 carbons afforded the highest levels of activity, which were comparable with the wild-type enzyme. Outside of this window, straight-chain fatty acids showed reduced activity over the other substrate types. These results provide a cautionary tale concerning the loss of ferryl activity in such cytochrome P450 threonine to alanine mutants, as the nature of the substrate can determine the extent to which hydroxylation chemistry is abolished. [source] | |||||||||||||