Kind Of Polymorphism Research Articles

ECNU-13: A High-Silica Zeolite with Three-Dimensional and High-Connectivity Multi-Pore Structures for Selective Alkene Cracking.

A high-silica zeolite ECNU-13 (Si/Al=23) with a new three-dimensional (3D) pore system and a nanosized morphology has been developed, consisting of multitudes of 10-membered ring (10-R) medium pores and one set of 8-R small pores. A phase-discrimination strategy was proposed to synthesize ECNU-13 by regulating the gel compositions and nucleation processes that were used for preparing 12-R large-pore germanosilicate IM-20 with the known UWY topology. The crystallization was directed towards forming one set of single four-ring (s4r) composite building units together with one set of double four-ring (d4r) rather than two different types of d4r units in IM-20. The electron crystallographic investigations elucidated that the ECNU-13 structure was composed of two kinds of polymorphs as a result of distinct atomic positionings in s4r units. In catalytic cracking of 1-butene, ECNU-13 exhibited high propene selectivity (55.6 %) and propene to ethylene molar ratio (>4.7) superior to well-studied conventional ZSM-5 zeolite catalyst.

ECNU‐13: A High‐Silica Zeolite with Three‐Dimensional and High‐Connectivity Multi‐Pore Structures for Selective Alkene Cracking

AbstractA high‐silica zeolite ECNU‐13 (Si/Al=23) with a new three‐dimensional (3D) pore system and a nanosized morphology has been developed, consisting of multitudes of 10‐membered ring (10‐R) medium pores and one set of 8‐R small pores. A phase‐discrimination strategy was proposed to synthesize ECNU‐13 by regulating the gel compositions and nucleation processes that were used for preparing 12‐R large‐pore germanosilicate IM‐20 with the known UWY topology. The crystallization was directed towards forming one set of single four‐ring (s4r) composite building units together with one set of double four‐ring (d4r) rather than two different types of d4r units in IM‐20. The electron crystallographic investigations elucidated that the ECNU‐13 structure was composed of two kinds of polymorphs as a result of distinct atomic positionings in s4r units. In catalytic cracking of 1‐butene, ECNU‐13 exhibited high propene selectivity (55.6 %) and propene to ethylene molar ratio (>4.7) superior to well‐studied conventional ZSM‐5 zeolite catalyst.

Influence of molecular packing on the color-tunable emissive behavior of viologen derivatives

Color-tunable organic solid-state luminescent materials have received increasing attention owing to their potential applications in displays, imaging, encryption, etc. To provide more information about structure-packing-property relationship of color-tunable organic luminophores, molecules with definite structures and explicit molecular packing are highly desired. In this work, we present an strategy to realize color-tunable luminescence by using the organic molecule 1-(4-carboxyphenyl)-4,4′-bipyridinium (CPB) as building block to construct two kinds of polymorphs by altering molecular conformation and packing modes. The color-tunable emission and relationship between the molecular packing fashion and bulk optical properties are reported. The findings open the opportunity for the development of novel color-tunable luminophores.

Effects of Low-melting-point Fractions of Cocoa Butter on Rice Bran Wax-corn Oil Mixtures: Thermal, Crystallization and Rheological Properties.

The fatty acid compositions, polymorphism, solid fat content (SFC), thermal properties, microstructure and rheological properties of fat blends of rice bran wax and corn oil (RWC) with low-melting-point fractions of cocoa butter (LFCB) in the range of 20-50% were investigated. With the raising content of LFCB, the hardness, SFC, storage modulus (G') and loss modulus (G'') of blend samples increased. The unsaturated fatty acids of blend samples with different LFCB proportion were in the range of 60.42% to 71.25%. Two kinds of polymorphism were observed in blend samples, which were β'-Form and β-Form. During the crystallization process, the rice bran wax was first crystallized, and then induced a part of LFCB formed β'-Form crystals and another LFCB formed the β-Form crystals. The results show that the addition of LFCB could improve the plasticity of fat blends and reduce the difference in properties between them and commercial shortening.

Relationship Between Polymorphisms of Interleukin-1 Receptor Antagonist (IL-1Ra) Genes and Susceptibility to Systemic Lupus Erythematosus in Iranian Population.

Interleukin (IL)-1 has a major role in cell destruction and inflammation. IL-1 receptor antagonist (IL-1RN or IL-1Ra) is a natural anti-inflammatory molecule that blocks IL-1. We intended to determine whether IL-1RN or IL-1Ra variable number tandem repeat (VNTR) polymorphism is associated with susceptibility to systemic lupus erythematosus (SLE) in a series of patients in the Northeastern part of Iran. Genomic DNA was extracted from the whole blood of 104 SLE patients and 209 subjects without SLE as a control group. The control group was matched for age and gender with SLE patients. Then, genomic DNA was genotyped by polymerase chain reaction (PCR) method for a length polymorphism in intron 2 of the IL-1RN gene. Of five alleles, only allele 4 of IL-1RN had a higher frequency in healthy subjects (2.4%) compared to SLE patients (0), with a statistically significant difference (P= 0.03). Eleven kinds of polymorphisms of IL-1RN were found including 1/1, 1/2, 2/2, 3/3, 1/3, 3/5, 2/3, 2/5, 1/5, 4/4 and 1/4 in both groups. In genotype frequency, there was no statistically significant difference regarding gene polymorphism kinds between the two groups (P= 0.29). Alleles 4 of IL-1RN may have a protective role against SLE susceptibility. However, SLE was not associated with any of the 11 kinds of genotype IL1-RN gene polymorphisms studied here.

Different Molecular Interaction between Collagen and α- or β-Chitin in Mechanically Improved Electrospun Composite.

Although collagens from vertebrates are mainly used in regenerative medicine, the most elusive issue in the collagen-based biomedical scaffolds is its insufficient mechanical strength. To solve this problem, electrospun collagen composites with chitins were prepared and molecular interactions which are the cause of the mechanical improvement in the composites were investigated by two-dimensional correlation spectroscopy (2DCOS). The electrospun collagen is composed of two kinds of polymorphs, α- and β-chitin, showing different mechanical enhancement and molecular interactions due to different inherent configurations in the crystal structure, resulting in solvent and polymer susceptibility. The collagen/α-chitin has two distinctive phases in the composite, but β-chitin composite has a relatively homogeneous phase. The β-chitin composite showed better tensile strength with ~41% and ~14% higher strength compared to collagen and α-chitin composites, respectively, due to a favorable secondary interaction, i.e., inter- rather than intra-molecular hydrogen bonds. The revealed molecular interaction indicates that β-chitin prefers to form inter-molecular hydrogen bonds with collagen by rearranging their uncrumpled crystalline regions, unlike α-chitin.

New synonymies, new combinations and lectotype designations for weevils in the tribe Naupactini (Coleoptera: Curculionidae: Entiminae).

We examined the type material of 15 species of Naupactus Dejean and related genera (Curculionidae: Entiminae), most of them described by Alphonse Hustache (Museum National d'Histoire Naturelle, Paris) and Carl Boheman (Naturhistoriska Riksmuseet, Stockholm). The information associated with the types was compared with the original descriptions, and large series of specimens were examined in order to analyze the variation of each species throughout its range (sexual dimorphism, other kinds of polymorphism or geographic variation). Based on the results of this study we establish seven new combinations, one new placement and nine new synonymies, we make 21 lectotype designations and provide three new country and state records. Alceis curtus (Boh.), Lanterius leucophaeus (Boh.), L. sparsus (Boh.), L. sellatus (Boh.), Parapantomorus carinirostris (Hust.), Symmathetes signatus (Blanchard) and Teratopactus acerbus (Boh.) are new combinations and T. sulphureoviridis Hust. is a new placement. The following names are senior synonyms of those between parentheses: Lanterius inermis (Hust.) (syn. Macrostylus ocellatus Lanteri); Naupactus auricinctus Boh. (syn. N. ruficornis Boh.); N. bridgesii G.R. Waterhouse (syn. N. angulithorax Hust.); N. condecoratus Boh. (syn. N. bosqi Hust.); N. cyphoides (Heller) (syn. N. calamuchitanensis Hust., N. viridinitens Hust, N. viridulus Hust.); N. peregrinus (Buchanan) (syn. N. brevicrinitus Hust.); and Trichonaupactus densior Hust. (syn. T. rexus Hust.). For each species we provide the following information: synonyms, available data on type specimens (sex, body length, geographic location, kind of type, and repository), complete geographic distribution, pictures of types or specimens compared with types, an explanation about the reasons that justify the nomenclatural acts.

Pharmaceutical crystallization in Couette-Taylor crystallizer: A case study of polymorphism of amino acid L-glutamic acid

The influence of intensity Taylor vortex flow in Couette-Taylor crystallizer on the crystallization of polymorphic amino acid L-glutamic acid was investigated in cooling crystallization. Here, the L-glutamic acid was chosen as the model crystal product, where it has two kinds of polymorphism including the unstable phase α-form and stable phase β-form crystal. In cooling crystallization, the α-form crystal transformed to the β-form crystal corresponding to the phase transformation of α-form to β-form crystal. The present study found that the selective polymorphism of α-form and β-form crystal as well as the phase transformation significantly depended on the intensity of turbulent Taylor vortex flow in Couette-Taylor crystallizer. Here, the selective β-form nucleation and phase transformation were remarkably promoted as increasing the rotation speed of inner cylinder in Couette-Taylor crystallizer. By comparison with the conventional stirred tank (ST) crystallizer, the Couette-Taylor (CT) crystallizer was at least 2.0 times more effective as regards the selective β-form polymorphism and phase transformation time. The advantage of CT crystallizer over the conventional ST crystallizer was explained in terms of the high shear stress and mass transfer of turbulent Taylor vortex flow in CT crystallizer. Here, the shear stress of Taylor vortex flow in CT crystallizer was at least 23.0 times higher than that of fluid motion in conventional ST crystallizer, whereas the mass transfer of Taylor vortex flow in CT crystallizer was at least 1.2 times higher than that of fluid motion in conventional ST crystallizer. As such, the high turbulent shear stress of Taylor vortex flow was expected to promote the β-form nucleation via the effective molecules alignment, whereas the high mass transfer of Taylor vortex flow facilitated the dissolution rate of α-form and growth rate of β-form crystal, resulting in an acceleration of phase transformation rate.

The association of IL-18 gene promoter polymorphisms and the levels of serum IL-18 on the risk of multiple sclerosis

ObjectivesMultiple sclerosis is an inflammatory condition of the central nervous system whose etiology is influenced by immunologic, genetic, and environmental factors. Aim of the present study was to determine if any relation exists between IL-18 −137C/G and −607C/A gene promoter polymorphisms on the individual susceptibility of multiple sclerosis and also to investigate the possible effect of IL-18 activity regarding this kind of polymorphism and MS. Patients and methods113 patients with clinically definite MS and 135 ethnically-matched controls were participated in this study. IL-18 −137C/G and −607C/A gene promoter polymorphisms were analyzed by Sequence Specific Polymerase Chain Reaction (SS-PCR), while levels of serum IL-18 were measured by Enzyme Linked Immunoassay Assay (ELISA) in patients with MS and healthy controls. ResultsOur results showed that the IL-18 −607AA genotype indicated 6 times higher risk in the development of MS (OR=6.883; 3.17–14.96; p<0.001). According to our findings, smoking seems to be an important confounding factor in MS patients with carrying IL-18 −607 AA and CA+AA genotypes. However, no meaningful association was found with IL-18 −137C/G gene promoter polymorphism. ConclusionIn conclusion, we suggest that IL-18 −607C/A gene promoter polymorphism is a major genetic factor for determining individual susceptibility to MS, where smoking status also increases the risk of MS.

Original article Paraoxonase 1 (PON1) gene -108C&gt;T and p.Q192R polymorphisms and arylesterase activity of the enzyme in patients with dementia

Paraoxonase 1 (PON1) activity was determined using phenylacetate as substrate (arylesterase activity) in 304 individuals with dementia--136 recognised as probable Alzheimer's disease (AD), 64 as dementia of vascular origin (VaD) and 104 as mixed dementia (MD) and in 129 persons without symptoms of dementia and in a good general health. -108C>T polymorphism in the PON1 gene promoter and p.Q192R polymorphism in the coding region were identified. PON1 activity was significantly lower in demented patients as compared with controls particularly in dementia of a neurodegenerative character (AD and MD). The prevalence of PON1-108T allele carriers was significantly higher in the AD group than in controls. The frequencies of the p.Q192R genotypes did not differ significantly between the investigated groups. An association of the rare T-R haplotype with dementia, particularly with dementia of the neurodegenerative type, was found. Multivariate regression analysis showed a significant association of PON1 activity with PON1 -108C>T and p.Q192R polymorphisms. The influence not only of promoter -108C>T, but also of p.Q192R polymorphism on PON1 arylesterase activity was observed. One has to admit that this kind of polymorphism does not preclude interference with the enzyme activity. It could be concluded that the PON1 gene promoter polymorphism plays an additional role in Alzheimer's disease development. It seems however that PON1 activity has a dominating influence on the dementia risk.

Study on the association of p53 codon 72 polymorphisms with risk of gastric cancer in high incidence Hexi area of Gansu Province in China

To investigate the possible association of P53 codon 72 Arg/Pro polymorphisms with risk of gastric cancer in the high incidence Hexi area of Gansu province in China. Blood samples from 140 patients with gastric carcinoma and 125 healthy controls were collected in Hexi area of Gansu province. Polymorphism of P53Arg72Pro was genotyped by PCR-TaqMan. For detection Helicobacter pylori infection, Warhin-Starry staining was used. Three kinds of polymorphisms of P53Arg72Pro were Arg/Arg, Arg/Pro, Pro/Pro. The frequencies in gastric cancer group were 15.7, 60.0, 24.3%, and the frequencies in healthy controls were 25.6, 54.4, 20.0%, respectively. P53 codon 72 Pro carrier genotype (Arg/Pro+Pro/Pro) increased risk of gastric carcinoma with an odds ratio 1.840 (95% CI: 1.006-3.387). Helicobacter pylori infection rate was 68.6% in patients group and 50.4% in healthy controls. Helicobacter pylori infection rate in gastric cancer patients was remarkably higher than that in the controls (OR: 2.147, 95% CI: 1.302-3.541, P=0.003). Stratification analysis showed that P53 codon 72 Pro carrier genotype with Helicobacter pylori infection was significantly higher in cases than that in the controls (OR: 4.182, 95% CI: 1.850-9.454). P53Arg72Pro polymorphisms could be a risk factor for gastric cancer in high incidence Hexi area of Gansu Province in China. P53 codon 72 Pro carrier genotype and Helicobacter pylori positive infection may have a synergistic effect on gastric cancer in high incidence Hexi area of Gansu Province in China.

The effect of multiple weak interactions on the charge transport ability in polymorphs

To get insights of the effect of multiple intermolecular interactions on the charge transport ability of polymorphs, we systematically investigated nine crystals in two kinds of polymorphs within the framework of band model, in which the type and strength of the weak interactions are different. The results show that: (i) the dispersions are relative to the π-stacking area. The bigger area the is, the larger dispersion the is. Thus, it can enhance the charge transport ability. (ii) Hydrogen bonding interactions have a great influence on the dispersion of valence band (VB) rather than conduction band (CB). (iii) When π-stacking and hydrogen bonding interactions coexist in the polymorphs, they enhance the dispersions of CB and restrain that of VB. (iv) When the type of weak interactions increases, the dispersions will be enlarged. Understanding the effect of multiple weak interactions on the polymorphs is a theoretical guide to design novel organic semiconductors with efficient charge transport ability.

Study on the association of COX-2 genetic polymorphisms with risk of gastric cancer in high incidence Hexi area of Gansu province in China

To investigate the possible association of polymorphisms, cyclooxygenase-2 (COX-2) promoter region -899G>C, COX-2 codon 587G>A, with risk of gastric cancer in the high incidence Hexi area of Gansu province in China. Blood samples from 140 patients with gastric carcinoma and 125 normal persons were collected in Hexi area of Gansu province in China. Polymorphisms of COX-2 -899G>A and COX-2 587G>A were genotyped by PCR-TaqMan. For detection Helicobacter pylori infection, Warhin-Starry staining was used. Three kinds of polymorphisms of COX-2 -899G>C were GG, GC and CC. The frequencies in gastric cancer patients were 72.9, 21.4 and 5.7%, and the frequencies in controls were 84.0, 12.8 and 3.2%, respectively. COX-2 -899C carrier (GC + CC) increased risk of gastric carcinoma with an odds ratio 1.950 (95% CI: 1.067-3.586, P=0.029). The genotype of COX-2 587G>A polymorphism were GG, GA and AA. The frequencies in patients group were 86.4, 11.4 and 2.2%, and the frequencies in controls were 89.6, 9.6 and 0.8%, respectively. There was no significant difference between cases and controls in each genotype. Helicobacter pylori infection rate was 68.6% in patients group and 50.4% in healthy controls. Helicobacter pylori infection rate in gastric cancer patients was remarkably higher than that in normal people (OR: 2.147, 95% CI: 1.302-3.541, P=0.003). Stratification analysis was showed that COX-2 -899C carrier genotype with Helicobacter pylori infection was significantly higher in cases than that in healthy controls (OR: 4.000, 95% CI: 1.638-9.770). The polymorphism of COX-2 -899G>C could be a risk factor for gastric cancer in high incidence Hexi area of Gansu Province in China. COX-2 -899C carrier genotype and Helicobacter pylori positive infection may have a synergistic effect on gastric cancer in high incidence Hexi area of Gansu Province in China. However, the polymorphisms of COX-2 587G>A is no association with gastric cancer in the high incidence Hexi area of Gansu Province in China.

Determination of the “Amino Acid Conflicts” and amino acid substitutions in primary structures of 41 human proteins by the proteomic technologies

Proteomic studies of some human tissues and organs (skeletal muscles, myometrium, motor zone of the brain, prostate), and also cultivated myoblasts revealed 41 of 300 identified proteins, in which the present of certain variants of amino acids ("conflicts") was recognized at several positions. Among the 93 registered amino acids "conflicts", seven cases represented the results of the protein polymorphisms caused by corresponding substitution of individual amino acid. Moreover, among prostate proteins the proteomic analysis revealed two isoforms of prostate-specific antigen, formed due to alternative splicing. Thus, our results have shown, that proteomic technologies allow to specify effectively the features of primary structures and to characterize various kinds of polymorphism in many human proteins.

Typed iterators for XML

XML transformations are very sensitive to types: XML types describe the tags and attributes of XML elements as well as the number, kind, and order of their sub-elements. Therefore, operations, even simple ones, that modify these features may affect the types of documents. Operations on XML documents are performed by iterators that, to be useful, need to be typed by a kind of polymorphism that goes beyond what currently exists. For this reason these iterators are not programmed but, rather, hard-coded in the languages. However, this approach soon reaches its limits, as the hard-coded iterators cannot cover fairly standard usage scenarios. As a solution to this problem we propose a generic language to define iterators for XML data. This language can either be used as a compilation target (e.g., for XPATH) or it can be grafted on any statically typed host programming language (as long as this has product types) to endow it with XML processing capabilities. We show that our language mostly offers the required degree of polymorphism, study its formal properties, and show its expressiveness and practical impact by providing several usage examples and encodings.

UGT1As polymorphisms predict toxicity in colorectal cancer patients treated with different recommended doses of irinotecan oriented by UGT1A1*28 polymorphism based on previous phase I study

14511 Background: We have presented at 2006 ASCO annual meeting about a genetic UGT1A1 polymorphism oriented phase (P) I study of Irinotecan and 5’-DFUR for metastatic colorectal cancer (MCRC) to determine the maximum tolerated dose (MTD) and the recommend doses (RD) for each UGT1A1 *1/*1 and *1/*28 genotypes. The RD of biweekly Irinotecan administration was 150 mg/m2 for patients (pts) with wild *1/*1 genotype and 70 mg/m2 of Irinotecan for mutated *1/*28. Now we are carrying out a *28 oriented P II study based on this RD. Here we report the profiles of toxicities in the P II study of irinotecan and 5’-DFUR to analyze other kinds of UGT1As polymorphisms in relation to irinotecan toxicities. Patients &amp; Methods: Eligibility criteria were as follows; histologically proven CRC with unresectable metastatic lesions, PS 0–1, age&lt;76, adequate organ functions, and written informed consent. Twenty one pts with wild type genotype and 9 pts with mutated genotype were enrolled. Irinotecan was infused 150 mg/m2 for pts with *1/*1 genotype and 70 mg/m2 for *1/*28. Hematological and non-hematological toxicities were graded, and UGT1As polymorphisms (UGT1A1*6 and *7, UGT1A7*1*2*3*4, UGT1A9*22) were analyzed. Results: Grade (G)3 &amp; 4 toxicities were observed in 6 of 22 (27%) wild type pts and in 3 of 9 (33%) mutated pts, and in 9 of 31 (29%) all pts. There was no significant difference on the profiles of toxicities between the pts with wild genotype and mutated genotype, irrespective of the difference of the quantity of irinotecan. So, the RD was thought to be adequate. In pts with UGT1A1*6 allele, G3 &amp; 4 toxicities were observed 6/11 (55%), on the other hand 3/20 (15%) in pts without *6 allele (p=0.038). G3 &amp; 4 toxicities were also more frequent in pts with UGT1A7*3 alleles than pts without *3 allele (p&lt;0.10). Conclusions: The profiles of toxicities of pts with *1/*1 or *1/*28 genotypes were similar irrespective of the difference of the quantity of irinotecan. The result indicated that the RD of latest PI for each group was adequate, and this P II study is suitable to analyze other kinds of polymorphisms that have correlation to irinotecan toxicities. UGT1A1*6 and UGT1A7*3 allele will be a novel predictor for toxicity of irinotecan. No significant financial relationships to disclose.

Polymorphisms of interleukin-1R receptor antagonist genes in patients with chronic hepatitis B in Iran

To investigate the relationships between polymorphisms of interleukin-1R receptor antagonist genes and susceptibility to chronic hepatitis B in Iran population. Genomic DNA was extracted from the peripheral blood of 80 patients with chronic hepatitis B (57 males, 23 females) aged 12-77 years (mean 36.1 +/- 13.8 years) and 147 normal controls (96 males, 51 females) aged 6-75 years (mean 41 +/- 18.7 years) who referred to a liver clinic of Tehran and then subjected to polymerase chain reaction (PCR) amplification. PCR products were resolved on a 3% agarose gel and stained with ethidium bromide. Only three of the five kinds of polymorphism (2/2, 2/4, and 4/4) were found in this study. The frequencies of 2/2, 2/4, and 4/4 were 12.5%, 17.5%, 70% respectively in chronic hepatitis B patients and 6.8%, 24.5%, and 68.7% respectively in controls. IL-1 R allele 2 was detected in 30% of chronic hepatitis B patients and in 31.3% of controls, while IL-1 R allele 4 was detected in 87.5% of chronic hepatitis B patients and in 93.2% of controls. The frequency of IL-1R alleles 2 and 4 was detected in 21.25% and 78.75% of the patients and 19.04% and 80.96% of the controls, respectively. Our results suggest that the carriage of IL-1R receptor antagonist alleles 2, 4, 6 may not play any role in the development of HBV infection. Large population-based studies are needed to investigate the role of IL-1 polymorphisms in the pathogenesis of developing chronic hepatitis B.

Polymorphism - prose of Java programmers

In Java programming language as implemented in JDK 5.0 there appear rather advanced kinds of polymorphism, even if they are hidden under different names. The notion of polymorphism unifies many concepts present in typed programming languages, not necessary object-oriented. We briefly define some varieties of polymorphism and trace them in Java. Java shows that industrial programming languages are able to express more abstract patterns using rather involved theoretical means, hence the working programmer has to be better educated in order to understand them, recognize them in different programming languages under different names and superficial syntax, and make good use of them.

HOGG1 SER326CYS genetic polymorphism in a Turkish population

Oxidative DNA damage, caused by either endogenous or exogenous sources of reactive oxygen species (ROS), has been linked to aging, chronic degenerative diseases, inflammatory diseases and cancers. 8-Hydroxydeoxyguanine (8-OHdG) is a major lesion produced by ROS. Among various types of DNA base modifications, 8-OHdG has been the most widely studied and is considered a key biomarker of oxidative DNA damage. Human 8-oxoguanine DNA glycosylase 1 (hOGG1) is a key component of the base excision repair (BER) pathway and catalyzes the removal of 8-OHdG. Ethnic and inter-individual differences in hOGG1 activity and several kinds of polymorphisms at the hOOG1 gene locus have been observed in the different populations studied so far. Since no information is available on the inter-individual variability of the hOGG1 genotype in the Turkish population, we genotyped 206 healthy, unrelated Turkish individuals. The allelic frequencies of the hOGG1 gene in the Turkish population were found to be 0.50, 0.41 and 0.09 (Ser/Ser, Ser/Cys and Cys/Cys, respectively). Our results are similar to those for Caucasians studied previously but are different from Asian populations. It seems that there is a growing need for extensive genotype studies with respect to the hOGG1 gene due to its importance to various types of cancer and to smoking habits.

Active Utilization of Solvent-Mediated Transformation for Exclusive Production of Metastable Polymorph Crystals of AE1-923

A drug substance AE1-923 (4-[[2-[N-(5-Methylfuran-2-sulfonyl)-N-isopropylamino]-5-(trifluoromethyl)phenoxy]methyl]benzoic acid), which was developed for the indications of pollakiuria and pain, was crystallized from the solution prepared with a mixed solvent of ethanol and water. AE1-923 was found to have three kinds of crystal polymorphs in the mixed solvent; namely the unstable A-form, the meta-stable B-form, and the stable C-form. The method of reliable and exclusive production of the meta-stable crystals among the three kinds of crystals was investigated.Three kinds of crystallization operation were attempted. Operation-1 was designed for directly precipitating the B-form crystals by cooling crystallization without precipitating the unstable A-form crystals. However, it was failed by a rapid transformation of polymorph from the B-form to the C-form. Operation-2 was designed for actively utilizing the transformation of polymorph from the A-form crystals to the B-form crystals by cooling crystallization. However, this operation was also failed by the same reason, namely a rapid transformation to the stable C-form. Operation-3 was also designed for actively utilizing the transformation of polymorph by poor solvent crystallization. By Operation-3, each polymorph including the B-form could be exclusively and consecutively produced. From these results, it was concluded that the utilization of the solvent-mediated transformation from the unstable polymorph to the meta-stable polymorph is effective for the production of meta-stable crystals even when three kinds of polymorphs may be simultaneously precipitated.