Low-dimensional hydrogen-bonded structures in the 1:1 and 1:2 proton-transfer compounds of 4,5-dichlorophthalic acid with the aliphatic Lewis bases triethylamine, diethylamine, n-butylamine and piperidine

The structures of proton-transfer compounds of 4,5-dichlorophthalic acid (DCPA) with the aliphatic Lewis bases triethylamine, diethylamine, n-butylamine and piperidine, namely triethylaminium 2-carboxy-4,5-dichlorobenzoate C~6~H~16~N^+^ C~8~H~3~Cl~2~O~4~^-^ (I), diethylaminium 2-carboxy-4,5-dichlorobenzoate C~4~H~12~N^+^ C~8~H~3~Cl~2~O~4~^-^ (II), bis(n-butylaminium) 4,5-dichlorophthalate monohydrate 2(C~4~H~12~N^+^) C~8~H~2~Cl~2~O~4~^2-^ . H~2~O (III) and bis(piperidinium) 4,5-dichlorophthalate monohydrate 2(C~5~H~12~N^+^) C~8~H~2~Cl~2~O~4~^2-^ . H~2~O (IV)have been determined at 200 K. All compounds have hydrogen-bonding associations giving in (I) discrete cation-anion units, linear chains in (II) while (III) and (IV) both have two-dimensional structures. In (I) a discrete cation-anion unit is formed through an asymmetric R2/1(4) N+-H...O,O' hydrogen-bonding association whereas in (II), one-dimensional chains are formed through linear N-H...O associations by both aminium H donors. In compounds (III) and (IV) the primary N-H...O linked cation-anion units are extended into a two-dimensional sheet structure via amide N-H...O(carboxyl) and ...O(carbonyl) interactions. In the 1:1 salts [(I) and (II)], the hydrogen 4,5-dichlorophthalate anions are essentially planar with short intramolecular carboxylic acid O-H...O(carboxyl) hydrogen bonds [O...O, 2.4223(14) and 2.388(2)A respectively]. This work provides a further example of the uncommon zero-dimensional hydrogen-bonded DCPA-Lewis base salt and the one-dimensional chain structure type, while even with the hydrate structures of the 1:2 salts with the primary and secondary amines, the low dimensionality generally associated with 1:1 DCPA salts is also found.

2-(2,4-dinitrobenzyl)pyridinium 2-hydroxy-3,5-dinitrobenzoate

In the structure of the title compound, the salt C12H10N3O4+ C7H3N2O72-, the cations and the anions are linked by a single N+-H...O(carboxyl) hydrogen bond, the discrete cation-anion unit having no intermolecular associations other than weak cation--anion aromatic ring pi--pi interactions [ring centroid separation, 3.7320(14)A] and a number of weak inter-unit aromatic C-H...O contacts.

Guanidinium phenylarsonate-guanidine-water (1/1/2)

In the structure of CH6N3+ C6H6AsO3- . CH5N3 . 2H2O, the phenylarsonate anion gives two R2/2(8) cyclic hydrogen-bonding interactions, one with a guanidinium cation, the other with a guanidine molecule. The anions are also bridged by the water molecules, one of which completes a cyclic R3/5(9) hydrogen-bonding association with the guanidinum cation, conjoint with one of the three R^2^~2~(8) associations about that ion, as well as forming an R1/2(6) cyclic association with the guanidine molecule. The result is a three-dimensional framework structure.

Guanidinium 2-phenylacetate

In the structure of CH6N3+ C8H7O2-, the guanidinium cation gives three cyclic hydrogen-bonding interactions with O acceptors of three independent phenylacetate anions, one R2/2(8) and two R1/2(6), giving one-dimensional columnar structures which extend down the 4~2~ axis in the tetragonal cell. Within these structures there are 86.5A^3^ solvent accessible voids.

Validation of the Algase Wandering Scale (Version 2) in a cross cultural sample

This study examined the psychometric properties of an expanded version of the Algase Wandering Scale (Version 2) (AWS-V2) in a cross-cultural sample. A cross-sectional survey design was used. Study subjects were 172 English-speaking persons with dementia (PWD) from long-term care facilities in the USA, Canada, and Australia. Two or more facility staff rated each subject on the AWS-V2. Demographic and cognitive data (MMSE) were also obtained. Staff provided information on their own knowledge of the subject and of dementia. Separate factor analyses on data from two samples of raters each explained greater than 66% of the variance in AWS-V2 scores and validated four (persistent walking, navigational deficit, eloping behavior, and shadowing) of five factors in the original scale. Items added to create the AWS-V2 strengthened the shadowing subscale, failed to improve the routinized walking subscale, and added a factor, attention shifting as compared to the original AWS. Evidence for validity was found in significant correlations and ANOVAs between the AWS-V2 and most subscales with a single item indicator of wandering and with the MMSE. Evidence of reliability was shown by internal consistency of the AWS-V2 (0.87, 0.88) and its subscales (range 0.88 to 0.66), with Kappa for individual items (17 of 27 greater than 0.4), and ANOVAs comparing ratings across rater groups (nurses, nurse aids, and other staff). Analyses support validity and reliability of the AWS-V2 overall and for persistent walking, spatial disorientation, and eloping behavior subscales. The AWS-V2 and its subscales are an appropriate way to measure wandering as conceptualized within the Need-driven Dementia-compromised Behavior Model in studies of English-speaking subjects. Suggestions for further strengthening the scale and for extending its use to clinical applications are described.

Anhydrous 1:1 proton-transfer compounds of isonipecotamide with picric acid and 3,5-dinitrosalicylic acid: 4-carbamoylpiperidinium 2,4,6-trinitrophenolate and two polymorphs of 4-carbamoylpiperidinium 2-carboxy-4,6-dinitrophenolate

The structures of the anhydrous 1:1 proton-transfer compounds of isonipecotamide (4-carbamoylpiperidine) with picric acid and 3,5-dinitrosalicylic acid, namely 4-carbamoylpiperidinium 2,4,6-trinitrophenolate, C6H13N2O8+ C6H2N3O7- (I) and 4-carbamoylpiperidinium 2-carboxy-4,6-dinitrophenolate, C6H13N2O8+ C7H3N2O7-: two forms, the monoclinic alpha-polymorph (II) and the triclinic beta-polymorph (III) have been determined at 200 K. All compounds form hydrogen-bonded structures, one-dimensional in (II), two-dimensional in (I) and three-dimensional in (III). In (I), the cations form centrosymmetric cyclic head-to-tail hydrogen-bonded homodimers [graph set R2/2(14)] through lateral duplex piperidinium N---H...O(amide) interactions. These dimers are extended into a two-dimensional network structure through further interactions with anion phenolate-O and nitro-O acceptors, including a direct symmetric piperidinium N-H...O(phenol),O(nitro) cation--anion association [graph set R2/1(6)]. The monoclinic polymorph (II) has a similar R2/1(6) cation-anion hydrogen-bonding interaction to (I) but with an additional conjoint symmetrical R1/2(4) interaction as well as head-to-tail piperidinium N-H...O(amide) O hydrogen bonds and amide N-H...O(carboxyl) hydrogen bonds, give a network structure which include large R3/4(20) rings. The hydrogen bonding in the triclinic polymorph (III) is markedly different from that of monoclinic (II). The asymmetric unit contains two independent cation-anion pairs which associate through cyclic piperidinium N-H...O,O'(carboxyl) interactions [graph set R2/1(4)]. The cations also show the zig-zag head-to-tail piperidinium N-H...O(amide) hydrogen-bonded chain substructures found in (II) but in addition feature amide N-H...O(nitro) and O(phenolate) and amide N-H...O(nitro) associations. As well there is a centrosymmetric double-amide N-H...O(carboxyl) bridged bis(cation-anion) ring system [graph set R2/4(8)] in the three-dimensional framework. The structures reported here demonstrate the utility of the isonipecotamide cation as a synthon with previously unrecognized potential for structure assembly applications. Furthermore, the structures of the two polymorphic 3,5-dinitrosalicylic acid salts show an unusual dissimilarity in hydrogen-bonding characteristics, considering that both were obtained from identical solvent systems.

Vibrational spectroscopic characterization of the phosphate mineral hureaulite – (Mn, Fe)5(PO4)2(HPO4)2·4(H2O)

This research was done on hureaulite samples from the Cigana claim, a lithium bearing pegmatite with triphylite and spodumene. The mine is located in Conselheiro Pena, east of Minas Gerais. Chemical analysis was carried out by Electron Microprobe analysis and indicated a manganese rich phase with partial substitution of iron. The calculated chemical formula of the studied sample is: (Mn3.23, Fe1.04, Ca0.19, Mg0.13)(PO4)2.7(HPO4)2.6(OH)4.78. The Raman spectrum of hureaulite is dominated by an intense sharp band at 959 cm−1 assigned to PO stretching vibrations of HPO42− units. The Raman band at 989 cm−1 is assigned to the PO43− stretching vibration. Raman bands at 1007, 1024, 1047, and 1083 cm−1 are attributed to both the HOP and PO antisymmetric stretching vibrations of HPO42− and PO43− units. A set of Raman bands at 531, 543, 564 and 582 cm−1 are assigned to the ν4 bending modes of the HPO42− and PO43− units. Raman bands observed at 414, and 455 cm−1 are attributed to the ν2 HPO42− and PO43− units. The intense A series of Raman and infrared bands in the OH stretching region are assigned to water stretching vibrations. Based upon the position of these bands hydrogen bond distances are calculated. Hydrogen bond distances are short indicating very strong hydrogen bonding in the hureaulite structure. A combination of Raman and infrared spectroscopy enabled aspects of the molecular structure of the mineral hureaulite to be understood.

Expression and prognostic influence of MMP-2, MMP-9 and TIMP-2 in non-small cell lung cancer

Background Matrix metalloproteinases (MMPs) are a family of endopeptidases that digest the extracellular matrix (ECM). Overexpression of different MMPs has been shown to promote tumour cell invasion in vitro. Tissue inhibitors of matrix metalloproteinases (TIMPs) are specific inhibitors of MMPs that also possess growth-promoting properties. Aims To analyse the expression profile of MMP-2, MMP-9 and TIMP-2 in non-small cell lung cancer (NSCLC) and to assess the impact of expression on survival. Methods This is a retrospective study of patients who underwent resection for stage I-IIIa NSCLC with a post-operative survival >60 days. Patient follow up was a minimum of 2 years. Standard ABC immunohistochemistry was performed on 4μm paraffin-embedded sections from the tumour periphery using monoclonal antibodies to MMP-2, MMP-9 and TIMP-2. Results The results of the immunohistochemistry are set out below. marker tumour expression log-rank survival stromal expression log-rank survival MMP-2 9/72 (13%) p=0.10 34/72 (47%) p=0.34 MMP-9 79/152 (52%) p=0.04* 69/152 (45%) p=0.84 TIMP-2 28/90 (31%) p=0.04* 66/90 (73%) p=0.90 Two or more 16/59 (27%) p=0.007* There were no associations between expression and clinicopathological findings for any tumour marker. There was co-expression of MMP-2 and MMP-9 in tumour cells (p=0.01). Conclusions MMP-2, MMP-9 and TIMP-2 are expressed in NSCLC. MMP-9 and TIMP-2 tumour expression correlate with a poor outcome (both p=0.04) and are potential prognostic markers for NSCLC. Cumulative expression of two or more MMPs/TIMPs may also have increased prognostic significance. Proteases and their inhibitors are novel targets for therapeutic intervention and should be evaluated in NSCLC.

Enhancement of 1,2-dehydration of alcohols by alkali cations and protons : a model for dehydration of carbohydrates

We have used electronic structure calculations to investigate the 1,2-dehydration of alcohols as a model for water loss during the pyrolysis of carbohydrates found in biomass. Reaction enthalpies and energy barriers have been calculated for neat alcohols, protonated alcohols and alcohols complexed to alkali metal ions (Li + and Na +). We have estimated pre-exponential A factors in order to obtain gas phase rate constants. For neat alcohols, the barrier to 1,2-dehydration is about 67 kcal mol -1, which is consistent with the limited experimental data. Protonation and metal complexation significantly reduce this activation barrier and thus, facilitate more rapid reaction. With the addition of alkali metals, the rate of dehydration can increase by a factor of 10 8 while addition of a proton can lead to an increase of a factor of 10 23.

Mesenchymal-to-epithelial transition facilitates bladder cancer metastasis : role of fibroblast growth factor receptor-2

Epithelial-to-mesenchymal transition (EMT) increases cell migration and invasion, and facilitates metastasis in multiple carcinoma types, but belies epithelial similarities between primary and secondary tumors. This study addresses the importance of mesenchymal-to-epithelial transition (MET) in the formation of clinically significant metastasis. The previously described bladder carcinoma TSU-Pr1 (T24) progression series of cell lines selected in vivo for increasing metastatic ability following systemic seeding was used in this study. It was found that the more metastatic sublines had acquired epithelial characteristics. Epithelial and mesenchymal phenotypes were confirmed in the TSU-Pr1 series by cytoskeletal and morphologic analysis, and by performance in a panel of in vitro assays. Metastatic ability was examined following inoculation at various sites. Epithelial characteristics associated with dramatically increased bone and soft tissue colonization after intracardiac or intratibial injection. In contrast, the more epithelial sublines showed decreased lung metastases following orthotopic inoculation, supporting the concept that EMT is important for the escape of tumor cells from the primary tumor. We confirmed the overexpression of the IIIc subtype of multiple fibroblast growth factor receptors (FGFR) through the TSU-Pr1 series, and targeted abrogation of FGFR2IIIc reversed the MET and associated functionality in this system and increased survival following in vivo inoculation in severe combined immunodeficient mice. This model is the first to specifically model steps of the latter part of the metastatic cascade in isogenic cell lines, and confirms the suspected role of MET in secondary tumor growth.

Herpes simplex 2 risk among women in a polygynous setting in rural West Africa

OBJECTIVES: To determine risk factors for herpes simplex 2 (HSV2) infection in women in a polygynous rural Gambian population. METHODS: Data from women who participated in a cross-sectional survey of reproductive health were matched to their own and, for women who had been or were married (ever-married), their spouses' data collected in a cross-sectional survey of fertility interests, including information on marital histories. RESULTS: Data were available on 150 never-married and 525 ever-married women. HSV2 prevalence was 16% amongst never-married women and 36% amongst ever-married women. For ever-married women, their own personal characteristics (age, ethnicity and genital cutting status) and events from their husbands' marriage history were important determinants of HSV2 infection. Women whose husbands married for the first time over age 35 were at greater risk than women whose husbands married by age 24 [odds ratio (OR) 2.72, 95% confidence interval (CI) 1.20-6.10]. Women whose husband reported interest in a new marriage were more likely to be HSV2 positive (OR 1.91, 95% CI 1.18-3.09). Women whose husbands were currently monogamous but had had previous marriages (OR 2.76, 95% CI 1.30-5.88) and women in currently polygynous marriages (OR 2.88, 95% CI 1.66-5.01) were three times as likely to be HSV2 positive as women who were their husband's only wife ever. CONCLUSION: Much transmission of HSV2 in this setting occurs within marriage where opportunity for personal protection is limited. High levels of transmission within marriage may undermine the impact of sexual behaviour change programmes aiming to reduce HSV2 and HIV incidence and complicate their evaluation.

The evolutionary history of termites as inferred from 66 mitochondrial genomes

Termites have colonized many habitats and are among the most abundant animals in tropical ecosystems, which they modify considerably through their actions. The timing of their rise in abundance and of the dispersal events that gave rise to modern termite lineages is not well understood. To shed light on termite origins and diversification, we sequenced the mitochondrial genome of 48 termite species and combined them with 18 previously sequenced termite mitochondrial genomes for phylogenetic and molecular clock analyses using multiple fossil calibrations. The 66 genomes represent most major clades of termites. Unlike previous phylogenetic studies based on fewer molecular data, our phylogenetic tree is fully resolved for the lower termites. The phylogenetic positions of Macrotermitinae and Apicotermitinae are also resolved as the basal groups in the higher termites, but in the crown termitid groups, including Termitinae + Syntermitinae + Nasutitermitinae + Cubitermitinae, the position of some nodes remains uncertain. Our molecular clock tree indicates that the lineages leading to termites and Cryptocercus roaches diverged 170 Ma (153-196 Ma 95% confidence interval [CI]), that modern Termitidae arose 54 Ma (46-66 Ma 95% CI), and that the crown termitid group arose 40 Ma (35-49 Ma 95% CI). This indicates that the distribution of basal termite clades was influenced by the final stages of the breakup of Pangaea. Our inference of ancestral geographic ranges shows that the Termitidae, which includes more than 75% of extant termite species, most likely originated in Africa or Asia, and acquired their pantropical distribution after a series of dispersal and subsequent diversification events.

EVERSUN: A phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma

Background We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). Patients and methods A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. Results We recruited 55 eligible participants from September 2010 to August 2012. Demographics: mean age 61, 71% male, favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 80% of participants; 64% received ≥22 weeks of alternating therapy; 78% received ≥22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed with a median progression-free survival of 8 months (95% CI 5–10), and 30 of 55 (55%) had died with a median OS of 17 months (95% CI 12–undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. Conclusions The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment.