The double risk of primitivism

This essay examines the possibilities for practices that appeal to the primitive in the contemporary cultural context. The idea of the primitive is driven by a desire to challenge the limitations of Western culture, while at the same time attracting the charge of promoting Eurocentrism. This essay investigates this double risk and how artists have sought to evade it, confound it, or accentuate it.

Matrix metalloproteinases during wound healing - a double edged sword

The extracellular matrix (ECM) provides a framework for cells and gives skin its tensile strength and elasticity. Loss of its integrity necessitates the clearing of damaged components and the deposition of firstly a provisional matrix and later remodelling of the ECM to support a functionally intact tissue. Matrix metalloproteinases (MMPs) are an important family of enzymes that function in the breakdown of the ECM and modulate the function of many biologically active molecules housed in the ECM. Through their enzymatic actions MMPs play a role in fundamental processes such as immune cell infiltration and ECM remodelling during wound repair. Their tight control is necessary for timely wound healing and excessive MMP activity participates in the development and persistence of chronic wounds, while reduced activity contributes to fibrosis. A number of inhibitors have been designed to target this activity and improve wound healing with limited success. Novel strategies are currently being investigated to improve wound healing by targeting MMP modulating molecules.

Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study) : a multicentre, double-blind, randomised controlled trial

Background Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. Methods Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori, and Pacific Island children aged 1—8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. Eligible children had had at least one pulmonary exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by computer-generated sequence with permuted block design, stratified by study site and exacerbation frequency [1—2 vs ≥3 episodes in the preceding 12 months]) to receive either azithromycin (30 mg/kg) or placebo once a week for up to 24 months. Allocation concealment was achieved by double-sealed, opaque envelopes; participants, caregivers, and study personnel were masked to assignment until after data analysis. The primary outcome was exacerbation (respiratory episodes treated with antibiotics) rate. Analysis of the primary endpoint was by intention to treat. At enrolment and at their final clinic visits, children had deep nasal swabs collected, which we analysed for antibiotic-resistant bacteria. This study is registered with the Australian New Zealand Clinical Trials Registry; ACTRN12610000383066. Findings 45 children were assigned to azithromycin and 44 to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011, thus children received the intervention for 12—24 months. The mean treatment duration was 20·7 months (SD 5·7), with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group. Compared with the placebo group, children receiving azithromycin had significantly lower exacerbation rates (incidence rate ratio 0·50; 95% CI 0·35—0·71; p<0·0001). However, children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving placebo (four of 37, 11%; p=0·002). The most common adverse events were non-pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group) and bronchiectasis-related events (episodes or investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group); however, study drugs were well tolerated with no serious adverse events being attributed to the intervention. Interpretation Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. However, this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria, the clinical consequences of which are uncertain, and will need careful monitoring and further study.

OnLine Ozonolysis Methods for the Determination of Double Bond Position in Unsaturated Lipids

Modern lipidomics relies heavily on mass spectrometry for the structural characterization and quantification of lipids of biological origins. Structural information is gained by tandem mass spectrometry (MS/MS) whereby lipid ions are fragmented to elucidate lipid class, fatty acid chain length, and degree of unsaturation. Unfortunately, however, in most cases double bond position cannot be assigned based on MS/MS data alone and thus significant structural diversity is hidden from such analyses. For this reason, we have developed two online methods for determining double bond position within unsaturated lipids; ozone electrospray ionization mass spectrometry (OzESI-MS) and ozone-induced dissociation (OzID). Both techniques utilize ozone to cleave C-C double bonds that result in chemically induced fragment ions that locate the position(s) of unsaturation

An analogy between the double slit experiment and document ranking

In the last years several works have investigated a formal model for Information Retrieval (IR) based on the mathematical formalism underlying quantum theory. These works have mainly exploited geometric and logical–algebraic features of the quantum formalism, for example entanglement, superposition of states, collapse into basis states, lattice relationships. In this poster I present an analogy between a typical IR scenario and the double slit experiment. This experiment exhibits the presence of interference phenomena between events in a quantum system, causing the Kolmogorovian law of total probability to fail. The analogy allows to put forward the routes for the application of quantum probability theory in IR. However, several questions need still to be addressed; they will be the subject of my PhD research

Rediscovering the double Friedel-Crafts acylation : an expedient entry to phenanthrene-9,10-diones

The double Friedel–Crafts acylation of readily accessible biaryls with oxalyl chloride delivers the respective phenanthrene-9,10-diones, providing an alternative to the traditional methods, which require harsh oxidizing conditions and multistep sequences. This simple method allows the synthesis of various symmetrical and non-symmetrical targets, and is even effective for the synthesis of the parent ring system from (unactivated) biphenyl.

Vibrational spectroscopic study of the sulphate mineral glaucocerinite (Zn,Cu)10Al6(SO4)3(OH)32⋅18H2O – a natural layered double hydroxide

We have studied the molecular structure of the mineral glaucocerinite (Zn,Cu)5Al3(SO4)1.5(OH)16�9(H2O) using a combination of Raman and infrared spectroscopy. The mineral is one of the hydrotalcite supergroup of natural layered double hydroxides. The Raman spectrum is characterised by an intense Raman band at 982 cm�1 with a low intensity band at 1083 cm�1. These bands are attributed to the sulphate symmetric and antisymmetric stretching mode. The infrared spectrum is quite broad with a peak at 1020 cm�1. A series of Raman bands at 546, 584, 602, 625 and 651 cm�1 are assigned to the m4 (SO4)2� bending modes. The observation of multiple bands provides evidence for the reduction in symmetry of the sulphate anion from Td to C2v or even lower symmetry. The Raman band at 762 cm�1 is attributed to a hydroxyl deformation mode associated with AlOH units. Vibrational spectroscopy enables aspects of the molecular structure of glaucocerinite to be determined.

Double trouble — the art of synthesis of chiral dimeric natural products

Double or nothing! Recently the total ynthesis of secalonic acids A and D was reported. This work and other natural product syntheses with a dimerization step as a common feature are featured in this highlight. The significant biological activity of the secalonic acids and the fact that their synthesis has fascinated synthetic chemists for the past forty years make this work a milestone in natural product synthesis.

Elucidation of double bond position in unsaturated lipids by ozone electrospray ionization mass spectrometry

The position(s) of carbon-carbon double bonds within lipids can dramatically affect their structure and reactivity and thus has a direct bearing on biological function. Commonly employed mass spectrometric approaches to the characterization of complex lipids, however, fail to localize sites of unsaturation within the molecular structure and thus cannot distinguish naturally occurring regioisomers. In a recent communication \[Thomas, M. C.; Mitchell, T. W.; Blanksby, S. J. J. Am. Chem. Soc. 2006, 128, 58-59], we have presented a new technique for the elucidation of double bond position in glycerophospholipids using ozone-induced fragmentation within the source of a conventional electrospray ionization mass spectrometer. Here we report the on-line analysis, using ozone electrospray mass spectrometry (OzESI-MS), of a broad range of common unsaturated lipids including acidic and neutral glycerophospholipids, sphingomyelins, and triacylglycerols. All lipids analyzed are found to form a pair of chemically induced fragment ions diagnostic of the position of each double bond(s) regardless of the polarity, the number of charges, or the adduction (e.g., \[M - H](-), \[M - 2H](2-), \[M + H](+), \[M + Na](+), \[M + NH4](+)). The ability of OzESI-MS to distinguish lipids that differ only in the position of the double bonds is demonstrated using the glycerophosphocholine standards, GPCho(9Z-18:1/9Z-18:1) and GPCho(6Z-18:1/6Z-18:1). While these regioisomers cannot be differentiated by their conventional tandem mass spectra, the OzESI-MS spectra reveal abundant fragment ions of distinctive mass-to-charge ratio (m/z). The approach is found to be sufficiently robust to be used in conjunction with the m/z 184 precursor ion scans commonly employed for the identification of phosphocholine-containing lipids in shotgun lipidomic analyses. This tandem OzESI-MS approach was used, in conjunction with conventional tandem mass spectral analysis, for the structural characterization of an unknown sphingolipid in a crude lipid extract obtained from a human lens. The OzESI-MS data confirm the presence of two regioisomers, namely, SM(d18:0/15Z-24:1) and SM(d18:0/17Z-24:1), and suggest the possible presence of a third isomer, SM(d18:0/19Z-24:1), in lower abundance. The data presented herein demonstrate that OzESI-MS is a broadly applicable, on-line approach for structure determination and, when used in conjunction with established tandem mass spectrometric methods, can provide near complete structural characterization of a range of important lipid classes. As such, OzESI-MS may provide important new insight into the molecular diversity of naturally occurring lipids.

Ozone-induced dissociation : Elucidation of double bond position within mass-selected lipid ions

Ions formed from lipids during electrospray ionization of crude lipid extracts have been mass-selected within a quadrupole linear ion trap mass spectrometer and allowed to react with ozone vapor. Gas-phase ion-molecule reactions between unsaturated lipid ions and ozone are found to yield two primary product ions for each carbon-carbon double bond within the molecule. The mass-to-charge ratios of these chemically induced fragments are diagnostic of the position of unsaturation within the precursor ion. This novel analytical technique, dubbed ozone-induced dissociation (OzID), can be applied both in series and in parallel with conventional collision-induced dissociation (CID) to provide near-complete structural assignment of unknown lipids within complex mixtures without prior fractionation or derivatization. In this study, OzID is applied to a suite of complex lipid extracts from sources including human lens, bovine kidney, and commercial olive oil, thus demonstrating the technique to be applicable to a broad range of lipid classes including both neutral and acidic glycerophospholipids, sphingomyelins, and triacylglycerols. Gas-phase ozonolysis reactions are also observed with different types of precursor ions including \[M + H](+), \[M + Li](+), \[M + Na](+), and \[M H](-): in each case yielding fragmentation data that allow double bond position to be unambiguously assigned. Within the human lens lipid extract, three sphingomyelin regioisomers, namely SM(d18:0/15Z-24:1), SM(d18:0/17Z-24:1), and SM(d18:0/19Z-24:1), and a novel phosphatidylethanolamine alkyl ether, GPEtn(11Z-18:1e/9Z18:1), are identified using a combination of CID and OzID. These discoveries demonstrate that lipid identification based on CID alone belies the natural structural diversity in lipid biochemistry and illustrate the potential of OzID as a complementary approach within automated, high-throughput lipid analysis protocols.

Can ginger ameliorate chemotherapy-induced nausea? Protocol of a randomized double blind, placebo-controlled trial

Background Preliminary research shows ginger may be an effective adjuvant treatment for chemotherapy-induced nausea and vomiting but significant limitations need to be addressed before recommendations for clinical practice can be made. Methods/Design In a double–blinded randomised-controlled trial, chemotherapy-naïve patients will be randomly allocated to receive either 1.2 g of a standardised ginger extract or placebo per day. The study medication will be administrated as an adjuvant treatment to standard anti-emetic therapy and will be divided into four capsules per day, to be consumed approximately every 4 hours (300 mg per capsule administered q.i.d) for five days during the first three cycles of chemotherapy. Acute, delayed, and anticipatory symptoms of nausea and vomiting will be assessed over this time frame using a valid and reliable questionnaire, with nausea symptoms being the primary outcome. Quality of life, nutritional status, adverse effects, patient adherence, cancer-related fatigue, and CINV-specific prognostic factors will also be assessed. Discussion Previous trials in this area have noted limitations. These include the inconsistent use of standardized ginger formulations and valid questionnaires, lack of control for anticipatory nausea and prognostic factors that may influence individual CINV response, and the use of suboptimal dosing regimens. This trial is the first to address these issues by incorporating multiple unique additions to the study design including controlling for CINV-specific prognostic factors by recruiting only chemotherapy-naïve patients, implementing a dosing schedule consistent with the pharmacokinetics of oral ginger supplements, and independently analysing ginger supplements before and after recruitment to ensure potency. Our trial will also be the first to assess the effect of ginger supplementation on cancer-related fatigue and nutritional status. Chemotherapy-induced nausea and vomiting are distressing symptoms experienced by oncology patients; this trial will address the significant limitations within the current literature and in doing so, will investigate the effect of ginger supplementation as an adjuvant treatment in modulating nausea and vomiting symptoms. Trial registration

Mass spectrometric study of the dissociation of Group XI metal complexes with fatty acids and glycerolipids : Ag2H+ and Cu2H+ ion formation in the presence of a double bond

Results of mass spectrometric studies are reported for the collisional dissociation of Group XI (Cu, Ag, Au) metal ion complexes with fatty acids (palmitic, oleic, linoleic and a-linolenic) and glycerolipids. Remarkably, the formation of M2H+ ions (M = Cu, Ag) is observed as a dissociation product of the ion complexes containing more than one metal cation and only if the lipid in the complex contains a double bond. Ag2H+ is formed as the main dissociation channel for all three of the fatty acids containing double bonds that were investigated while Cu2H+ is formed with one of the fatty acids and, although abundant, is not the dominant dissociation channel. Also. Cu(I) and Ag(I) ion complexes were observed with glycerolipids (including triacylglycerols and glycerophospholipids) containing either saturated or unsaturated fatty acid substituents. Interestingly. Ag2H+ ion is formed in a major fragmentation channel with the lipids that are able to form the complex with two metal cations (triacylglycerols and glycerophosphoglycerols), while lipids containing a fixed positive charge (glycerophospocholines) complex only with a single metal cation. The formation of Ag2H+ ion is a significant dissociation channel from the complex ion Ag-2(L-H)(+) where L = Glycerophospholipid (GP) (18:1/18:1). Cu(I) also forms complexes of two metal cations with glycerophospholipids but these do not produce Cu2H+ upon dissociation. Rather organic fragments, not containing Cu(I), are formed, perhaps due to different interactions of these metal cations with lipids resulting from the much smaller ionic radius of Cu(I) compared to Ag(I) (C).

Using ambient ozone for assignment of double bond position in unsaturated lipids

Unsaturated lipids deposited onto a range of materials are observed to react with the low concentrations of ozone present in normal laboratory air. Parent lipids and ozonolysis cleavage products are both detected directly from surfaces by desorption electrospray ionisation mass spectrometry (DESI-MS) with the resulting mass spectra providing clear evidence of the double bond position within these molecules. This serendipitous process has been coupled with thin-layer chromatography (TLC) to provide a simple but powerful approach for the detailed structural elucidation of lipids present in complex biological extracts. Lipid extracts from human lens were deposited onto normal phase TLC plates and then developed to separate components according to lipid class. Exposure of the developed plates to laboratory air for ca. 1 h prior to DESI-MS analysis gave rise to ozonolysis products allowing for the unambiguous identification of double bond positions in even low abundant, unsaturated lipids. In particular, the co-localization of intact unsaturated lactosylceramides (LacCer) with products from their oxidative cleavage provide the first evidence for the presence of three isomeric LacCer (d18:0/24:1) species in the ocular lens lipidome, i.e., variants with double bonds at the n-9, n-7 and n-5 positions.

Ozonolysis of phospholipid double bonds during electrospray ionization : A new tool for structure determination

Phospholipids are the key structural component of cell membranes, and recent advances in electrospray ionization mass spectrometry provide for the fast and efficient analysis of these compounds in biological extracts.1-3 The application of electrospray ionization tandem mass spectrometry (ESI-MS/MS) to phospholipid analysis has demonstrated several key advantages over the more traditional chromatographic methods, including speed and greater structural information.4 For example, the ESI-MS/MS spectrum of a typical phospholipidsparticularly in negative ion modesreadily identifies the carbon chain length and the degree of unsaturation of each of the fatty acids esterified to the parent molecule.5 A critical limitation of conventional ESI-MS/MS analysis, however, is the inability to uniquely identify the position of double bonds within the fatty acid chains. This is especially problematic given the importance of double bond position in determining the biological function of lipid classes.6 Previous attempts to identify double bond position in intact phospholipids using mass spectrometry employ either MS3 or offline chemical derivatization.7-11 The former method requires specialized instrumentation and is rarely applied, while the latter methods suffer from complications inherent in sample handling prior to analysis. In this communication we outline a novel on-line approach for the identification of double bond position in intact phospholipids. In our method, the double bond(s) present in unsaturated phospholipids are cleaved by ozonolysis within the ion source of a conventional ESI mass spectrometer to give two chemically induced fragment ions that may be used to unambiguously assign the position of the double bond. This is achieved by using oxygen as the electrospray nebulizing gas in combination with high electrospray voltages to initiate the formation of an ozoneproducing.