Social and Behavioral Sciences Commons^™

Synthesis And Anti-Leukaemic Activity Of Pyrrolo[3,2,1-Hi]Indole-1,2- Diones, Pyrrolo[3,2,1-Ij]Quinoline-1,2-Diones And Other Polycyclic Isatin Derivatives, Lidia Matesic, Julie M. Locke, Kara Vine, Marie Ranson, John B. Bremner, Danielle Skropeta

Danielle Skropeta

To further expand the structure–cytotoxic activity relationships of isatin derivatives and to reduce flexibility in substituent groups at nitrogen, 20 analogues incorporating a ring system between the N1 and C7 atoms of isatin were prepared using a variety of synthetic strategies. This yielded pyrroloindole-, pyrroloquinoline-, pyrroloacridine-, pyrrolophenanthridine- and benzopyrrolophenanthridine-based systems with embedded isatin moieties, the latter possessing a novel carbon skeleton. These compounds were subsequently assessed for their in vitro cytotoxicity against human U937 lymphoma cells, with the brominated pyrroloacridine dione 27 showing the most promising activity (IC50 3.01 μM) after 24 h.

Echo Of A Distant Drum [Episode 1], Siobhan Mchugh

Siobhan McHugh

Episode on the rebellious nature of the Irish in Australia - including Ned Kelly.

Flexibility Revealed By The 1.85 Å Crystal Structure Of The Β Sliding-Clamp Subunit Of Escherichia Coli Dna Polymerase Iii, Aaron J. Oakley, Pavel Prosselkov, Gene Wijffels, Jennifer L. Beck, Matthew Cj Wilce, Nicholas E. Dixon

Professor Nick E Dixon

The subunit of the Escherichia coli replicative DNA polymerase III holoenzyme is the sliding clamp that interacts with the (polymerase) subunit to maintain the high processivity of the enzyme. The protein is a ring-shaped dimer of 40.6 kDa subunits whose structure has previously been determined at a resolution of 2.5 Å [Kong et al. (1992), Cell, 69, 425-437]. Here, the construction of a new plasmid that directs overproduction of to very high levels and a simple procedure for large-scale purification of the protein are described. Crystals grown under slightly modified conditions diffracted to beyond 1.9 Å at 100 K at …

Extracellular Chaperones Modulate The Effects Of Alzheimer's Patient Cerebrospinal Fluid On A Beta(1-42) Toxicity And Uptake , Justin J. Yerbury, Mark R. Wilson

Mark R Wilson

Alzheimer's disease is characterised by the inappropriate death of brain cells and accumulation of the A beta peptide in the brain. Thus, it is possible that there are fundamental differences between Alzheimer's disease patients and healthy individuals in their abilities to clear A beta from brain fluid and to protect neurons from A beta toxicity. In the present study, we examined (1) the cytotoxicity of Alzheimer's disease cerebrospinal fluid (CSF) compared to control CSF, (2) the ability of Alzheimer's disease and control CSF to protect cells from A beta toxicity and to promote cell-mediated clearance of A beta and lastly …

Infrared Spectra Of The Li +_(H 2)N(N=1-3) Cation Complexes, C Emmeluth, B L. J Poad, C D. Thompson, G H. Weddle, E J. Bieske

Berwyck L. J. Poad

The Li+–(H2)n n = 1–3 complexes are investigated through infrared spectra recorded in the H–H stretch region (3980–4120 cm−1) and through ab initio calculations at the MP2∕aug-cc-pVQZ level. The rotationally resolved H–H stretch band of Li+–H2 is centered at 4053.4 cm−1 [a −108 cm−1 shift from the Q1(0) transition of H2]. The spectrum exhibits rotational substructure consistent with the complex possessing a T-shaped equilibrium geometry, with the Li+ ion attached to a slightly perturbed H2 molecule. Around 100 rovibrational transitions belonging to parallel Ka = 0‐0, 1-1, 2-2, and 3-3 subbands are observed. The Ka = 0‐0 and 1-1 transitions …

Infrared Spectra Of Mass-Selected Al+_(Ch4)Nn=1-6clusters, B Poad, C Thompson, E Bieske

Berwyck L. J. Poad

Infrared spectra are recorded for Al⁺–(CH₄)_n n = 1–6 clusters in the CH stretch region (2800–3100 cm⁻¹). The spectra, which are obtained by monitoring photofragmentation in a tandem mass spectrometer, are dominated by a single, narrow band corresponding to the totally symmetric C–H stretching mode of the CH₄ subunits (rendered infrared active through the interaction with the Al⁺ cation). This band shifts progressively to higher wavenumber as the clusters becomes larger, concomitant with a weakening of the intermolecular Al⁺⋯CH₄ bonds. Supporting ab initio calculations for the n = …

Infrared Spectra Of Cl-_(C6h6)Mm=1, 2, Christopher Thompson, Berwyck Poad, Corinna Emmeluth, Evan Bieske

Berwyck L. J. Poad

The Cl^--(C₆H₆)Ar_n n = 0,1,2 and Cl^--(C₆H₆)₂ complexes are investigated using photodissociation infrared spectroscopy in the CH stretch region and through ab initio calculations at the MP2/aug-cc-pVDZ level. The results indicate that Cl^--C₆H₆ possesses a planar structure in which the benzene molecule is attached to the Cl^- anion by a double hydrogen bond. The calculations predict that Cl (C₆H₆)₂ has a C₂ symmetry structure in which the two face-to-face benzene molecules are attached to …

Neuregulin-1 Signalling And Antipsychotic Treatment: Potential Therapeutic Targets In A Schizophrenia Candidate Signalling Pathway, Chao Deng, Bo Pan, Martin Engel, Xu-Feng Huang

Xu-Feng Huang

Identifying the signalling pathways underlying the pathophysiology of schizophrenia is an essential step in the rational development of new antipsychotic drugs for this devastating disease. Evidence from genetic, transgenic and post-mortem studies have strongly supported neuregulin-1 (NRG1)-ErbB4 signalling as a schizophrenia susceptibility pathway. NRG1-ErbB4 signalling plays crucial roles in regulating neurodevelopment and neurotransmission, with implications for the pathophysiology of schizophrenia. Post-mortem studies have demonstrated altered NRG1-ErbB4 signalling in the brain of schizophrenia patients. Antipsychotic drugs have different effects on NRG1-ErbB4 signalling depending on treatment duration. Abnormal behaviours relevant to certain features of schizophrenia are displayed in NRG1/ErbB4 knockout mice or …

Sequential 1,4- And 1,2-Addition Reactions To Α,Β-Unsaturated N-Acyliminium Ions: A New Strategy For The Synthesis Of Spiro And Bridged Heterocycles, Arife Yazici, Stephen G. Pyne

Faculty of Science, Medicine and Health - Papers: part A

Novel bicyclic and tetracyclic spirocycles and tricyclic bridged heterocyclic systems can be readily prepared from sequential 1,4- and 1,2-addition reactions of latent bis-nucleophiles to α,β-unsaturated N-acyliminium ions.

Glutathionylation Potentiates Benign Superoxide Dismutase 1 Variants To The Toxic Forms Associated With Amyotrophic Lateral Sclerosis, Luke Mcalary, Justin J. Yerbury, J. Andrew Aquilina

Faculty of Science, Medicine and Health - Papers: part A

Dissociation of superoxide dismutase 1 dimers is enhanced by glutathionylation, although the dissociation constants reported to date are imprecise. We have quantified the discreet dissociation constants for wild-type superoxide dismutase 1 and six naturally occurring sequence variants, in their unmodified and glutathionylated forms, at the ratios expressed. Unmodified superoxide dismutase 1 variants that shared similar dissociation constants with SOD1WT had disproportionately increased dissociation constants when glutathionylated. This defines a key role for glutathionylation in superoxide dismutase 1 associated familial amyotrophic lateral sclerosis.

Improved Water Vapour Spectroscopy In The 4174-4300 Cm(-1) Region And Its Impact On Sciamachy Hdo/H2o Measurements, R A. Scheepmaker, C Frankenberg, A Galli, A Butz, H Schrijver, N M. Deutscher, D Wunch, T Warneke, S Fally, I Aben

Faculty of Science, Medicine and Health - Papers: part A

The relative abundance of the heavy water isotopologue HDO provides a deeper insight into the atmospheric hydrological cycle. The SCanning Imaging Absorption spectroMeter for Atmospheric CartograpHY (SCIAMACHY) allows for global retrievals of the ratio HDO/H2O in the 2.3 micron wavelength range. However, the spectroscopy of water lines in this region remains a large source of uncertainty for these retrievals. We therefore evaluate and improve the water spectroscopy in the range 4174-4300 cm(-1) and test if this reduces systematic uncertainties in the SCIAMACHY retrievals of HDO/H2O. We use a laboratory spectrum of water vapour to fit line intensity, air broadening and …

Alternative Al Production Methods: Part 1 - A Review Of Indirect Carbothermal Routes, M A. Rhamdhani, M A. Dewan, G A. Brooks, B J. Monaghan, L Prentice

Faculty of Engineering and Information Sciences - Papers: Part A

The production of Al from its ores at present relies on the Bayer (alumina production) and the Hall- Heroult (Al production) process. The cost associated with alumina production and apparent disadvantages of the Hall-Heroult process have led to intensive research to find alternative routes for Al production. The direct carbothermal reduction process has been thoroughly investigated as an alternative technique. Another alternative includes the indirect carbothermal reduction route where alumina (or aluminous ores) is first reduced to intermediate Al compounds before reduced further to Al. The present study reviews and provides systematic thermodynamic analyses of alternative Al production routes. In …

Optimal Design Of An Ultrasmall Soi-Based 1 X 8 Flat-Top Awg By Using An Mmi, Hongqiang Li, Yaoting Bai, Xiaoyi Dong, Enbang Li, Yang Li, Yu Liu, Wenqian Zhou

Faculty of Engineering and Information Sciences - Papers: Part A

Four methods based on a multimode interference (MMI) structure are optimally designed to flatten the spectral response of silicon-on-insulator- (SOI-) based arrayed-waveguide grating (AWG) applied in a demodulation integration microsystem. In the design for each method, SOI is selected as the material, the beam propagation method is used, and the performances (including the 3 dB passband width, the crosstalk, and the insertion loss) of the flat-top AWG are studied. Moreover, the output spectrum responses of AWGs with or without a flattened structure are compared. The results show that low insertion loss, crosstalk, and a flat and efficient spectral response are …

A Simple Model To Extend 1-D Hydraulics To 3-D Hydraulics, Shu-Qing Yang

Faculty of Engineering and Information Sciences - Papers: Part A

the core of fluid mechanics is the study of friction on a solid/liquid interface, the friction force can be divided into skin friction and form drag. Nikuradse's experiments reveal that the friction factor depends on the Reynolds number (Re) and relative roughness (r), this observation implies the co-existence of skin friction and form drag, but the definitions of Re and r given by Nikuradse cannot be linked with the skin friction and form drag, this leads to the invalidity of existing theory to predict the friction factor in a complex flow, like a channel flow with vegetation. To establish a …

Cross-Section Calculations For Positron Scattering From Pyrimidine Over An Energy Range From 0.1 To 10000 Ev, A G. Sanz, M C. Fuss, F Blanco, Z Masin, J D. Gorfinkiel, R P. Mceachran, M J. Brunger, G Garcia

Faculty of Engineering and Information Sciences - Papers: Part A

We report a computational investigation of positron scattering by pyrimidine (C4H4N2) in the gas phase. Integral and differential cross sections have been calculated over a broad energy range by employing two distinct ab initio quantum scattering methods: the R-matrix method and a corrected form of the independent-atom representation, at low and high energies, respectively. Since pyrimidine is a strong polar molecule further dipole-induced excitations have been calculated in the framework of the first Born approximation. Good agreement is found between the different computational models and fair agreement is found with prior experimental results.

Inhibition Of Tnf-Α Production In Lps-Activated Thp-1 Monocytic Cells By The Crude Extracts Of Seven Bhutanese Medicinal Plants, Phurpa Wangchuk, Paul A. Keller, Stephen G. Pyne, Malai Taweechotipatr

Faculty of Science, Medicine and Health - Papers: part A

Ethnopharmacological relevance Seven studied medicinal plants; Aconitum laciniatum, Ajania nubigena, Codonopsis bhutanica, Corydalis crispa, Corydalis dubia, Meconopsis simplicifolia and Pleurospermum amabile, are currently used in the Bhutanese Traditional Medicine (BTM) for the management of different types of disorders including the diseases that bore relevance to various inflammatory conditions.

Aims of the study This study aimed to evaluate the inhibition of TNF-α production in LPS-activated THP-1 monocytic cells by the crude extracts of seven selected Bhutanese medicinal plants. It is expected to; (a) generate a scientific basis for their use in the BTM and (b) form a basis for prioritization of …

Non-Invasive Detection Of Microvascular Changes In A Paediatric And Adolescent Population With Type 1 Diabetes: A Pilot Cross-Sectional Study, Sarah P. M Hosking, Rani Bhatia, Patricia A. Crock, Ian M. R Wright, Marline L. Squance, Glenn Reeves

Faculty of Science, Medicine and Health - Papers: part A

Background: The detection of microvascular damage in type 1 diabetes is difficult and traditional investigations do not detect changes until they are well established. The purpose of this study was to investigate the combined ability of nailfold capillaroscopy, laser Doppler flowmetry, retinal vessel analysis and 24-hr ambulatory blood pressure monitoring to detect early microvascular changes in a paediatric and adolescent population with type 1 diabetes.

Methods: Patients aged between 8 – 18 years with type I diabetes and no other autoimmune conditions were studied. The participants underwent the above cardiac and vascular investigations in a single three-hour session. Standard parameters …

A Joint Theoretical And Experimental Study For Elastic Electron Scattering From 1,4-Dioxane, P Palihawadana, J P. Sullivan, S J. Buckman, Z Masin, J D. Gorfinkiel, F Blanco, G Garcia, M J. Brunger

Faculty of Engineering and Information Sciences - Papers: Part A

We present results of measurements and calculations of elastic electron scattering from 1,4-dioxane in the energy range of 0–1000 eV. Absolute differential and integral elastic cross sections have been measured using a crossed electron-molecule beam spectrometer and the relative flow technique, at four energies in the 10–30 eV range and for scattered electrons in the angular range 20◦–129◦. The measured cross sections are compared with results from R-matrix computations, at the static exchange plus polarization level, calculated at energies between 0–20 eV, and with calculations employing the independent atom model with the screening corrected additivity rule (IAM-SCAR). Those latter computations …

Neuregulin-1 Signalling And Antipsychotic Treatment: Potential Therapeutic Targets In A Schizophrenia Candidate Signalling Pathway, Chao Deng, Bo Pan, Martin Engel, Xu-Feng Huang

Faculty of Science, Medicine and Health - Papers: part A

Identifying the signalling pathways underlying the pathophysiology of schizophrenia is an essential step in the rational development of new antipsychotic drugs for this devastating disease. Evidence from genetic, transgenic and post-mortem studies have strongly supported neuregulin-1 (NRG1)-ErbB4 signalling as a schizophrenia susceptibility pathway. NRG1-ErbB4 signalling plays crucial roles in regulating neurodevelopment and neurotransmission, with implications for the pathophysiology of schizophrenia. Post-mortem studies have demonstrated altered NRG1-ErbB4 signalling in the brain of schizophrenia patients. Antipsychotic drugs have different effects on NRG1-ErbB4 signalling depending on treatment duration. Abnormal behaviours relevant to certain features of schizophrenia are displayed in NRG1/ErbB4 knockout mice or …