Notice of election of B. Nathan and S. Lazarus

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X-ray studies on crystalline complexes involving amino acids and peptides. XXIII. Variability in ionization state, conformation and molecular aggregation in the complexes of succinic acid with DL- and L-lysine

Crystalline complexes of succinic acid with DL- and L-lysine have been prepared and analysed by X-ray diffraction. DL-Lysine complex: C6HIsN202 + 1 2- 1 ~C4H404 .~C4H604, Mr -- 264"2, PI, a = 5"506 (4), =8.070(2), c=14.089(2) A,, a=92.02(1), /3= 100"69 (3), y = 95"85 (3) ~>, Z = 2, Dx = 1"44 g cm -3, R = 0.059 for 2546 observed reflections. Form I of the e-lysine complex: C6HIsN20-, ~ .C4H504, Mr = 264.2, P1, a = 5" 125 (2), b = 8"087 (1), c = 8"689 (1) A,, a = 112.06 (1), /3 = 99.08 (2), y = 93"77(2) °, Z--l, D,,,=1"34(3), Dx=l"34gcm 3 R = 0.033 for 1475 observed reflections. Form II of + I 2- the e-lysine complex: C6H15N202 .,iC4H404 .- 1 I ") 4C4H604.4(C4HsO4""H'"CaH404)" , Mr = 264"2, P1, a = 10.143 (4), b = 10.256 (2), c = 12"916 (3) A,, a = 105.00 (2),/3 = 99-09 (3), y = 92"78 (3)::, Z = 4, Dm= 1"37(4), D,.= 1.38gcm 3, R=0.067 for 2809 observed reflections. The succinic acid molecules in the structures exhibit a variety of ionization states. Two of the lysine conformations found in the complexes have been observed for the first time in crystals containing lysine. Form II of the L-lysine complex is highly pseudosymmetric. In all the complexes, unlike molecules aggregate into separate alternating layers. The basic element of aggregation in the lysine layer in the complexes is an S2-type head-to-tail sequence. This element combines in different ways in the three structures. The basic element of aggre gation in the succinic acid layer in the complexes is a hydrogen-bonded ribbon. The ribbons are interconnected indirectly through amino groups in the lysine layer.

Besides tracking: Simulation of RFID marketing and beyond

This paper asks a new question: how we can use RFID technology in marketing products in supermarkets and how we can measure its performance or ROI (Return-on-Investment). We try to answer the question by proposing a simulation model whereby customers become aware of other customers' real-time shopping behavior and may hence be influenced by their purchases and the levels of purchases. The proposed model is orthogonal to sales model and can have the similar effects: increase in the overall shopping volume. Managers often struggle with the prediction of ROI on purchasing such a technology, this simulation sets to provide them the answers of questions like the percentage of increase in sales given real-time purchase information to other customers. The simulation is also flexible to incorporate any given model of customers' behavior tailored to particular supermarket, settings, events or promotions. The results, although preliminary, are promising to use RFID technology for marketing products in supermarkets and provide several dimensions to look for influencing customers via feedback, real-time marketing, target advertisement and on-demand promotions. Several other parameters have been discussed including the herd behavior, fake customers, privacy, and optimality of sales-price margin and the ROI of investing in RFID technology for marketing purposes. © 2010 Springer Science+Business Media B.V.

A Proof of Convergence of the B-RED and P-RED Algorithms for Random Early Detection

In [8], we recently presented two computationally efficient algorithms named B-RED and P-RED for random early detection. In this letter, we present the mathematical proof of convergence of these algorithms under general conditions to local minima.

Electron energy distributions and transport coefficients in N2 in E times B fields

Using the concept of energy-dependent effective field intensity, electron transport coefficients in nitrogen have been determined in E times B fields (E = electric field intensity, B = magnetic flux density) by the numerical solution of the Boltzmann transport equation for the energy distribution of electrons. It has been observed that as the value of B/p (p = gas pressure) is increased from zero, the perpendicular drift velocity increased linearly at first, reaches a maximum value, and then decreases with increasing B/p. In general, the electron mean energy is found to be a function of Eavet/p( Eavet = averaged effective electric field intensity) only, but the other transport coefficients, such as transverse drift velocity, perpendicular drift velocity, and the Townsend ionization coefficient, are functions of both E/p and B/p.

Titration calorimetric studies to elucidate the specificity of the interactions of polymyxin B with lipopolysaccharides and lipid A

Lipopolysaccharide (LPS), the major cell wall constituent of Gram-negative bacteria, evokes a multitude of biological effects in mammals including pyrogenicity and toxic shock syndrome. Polymyxin B (PmB), a polycationic cyclic peptide, is known to neutralize most of its activities. The nature of the interaction of PmB with LPS and lipid A was investigated by isothermal titration calorimetry. PmB binds to LPS as well as lipid A stoichiometrically and non-co-operatively with micromolar affinity. These interactions are driven primarily by a favourable change in entropy (delta S) and are endothermic in nature. These positive changes in enthalpies decrease with increasing temperature, yielding a heat capacity change, delta Cp, of -2385 J.mol-1.degree-1 for PmB-LPS interactions while the binding of PmB to lipid A displays a delta Cp of -2259 J.mol-1.degree-1. The negative heat capacity changes provide strong evidence for the role of hydrophobic interactions as the driving force for the association of PmB with LPS and lipid A. A correlation of the energetics of these interactions with analyses of the molecular models of PmB suggests that a cluster of solvent-exposed non-polar amino acid side-chains that line one surface of the molecule, together with a ring of positively charged residues on its other surface, are responsible for its strong and stoichiometric binding to LPS.

Elastic modulus of Ti-6Al-4V-xB alloys with B up to 0.55 wt.%

An anomalous variation in the experimental elastic modulus, E, of Ti-6Al-4V-xB (with x up to 0.55 wt.%) is reported. Volume fractions and moduli of the constituent phases were measured using microscopy and nanoindentation,respectively. These were used in simple micromechanical models to examine if the E values could be rationalized. Experimental E values higher than the upper bound estimates suggest complex interplay between microstructural modifications, induced by the addition of B, and properties.

Defects in the IFT-B component IFT172 cause Jeune and Mainzer-Saldino syndromes in humans

Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown roles in human disease. To identify additional IFT-B components defective in ciliopathies, we independently performed different mutation analyses: candidate-based sequencing of all IFT-B-encoding genes in 1,467 individuals with a nephronophthisis-related ciliopathy or whole-exome resequencing in 63 individuals with ATD. We thereby detected biallelic mutations in the IFT-B-encoding gene IFT172 in 12 families. All affected individuals displayed abnormalities of the thorax and/or long bones, as well as renal, hepatic, or retinal involvement, consistent with the diagnosis of ATD or MZSDS. Additionally, cerebellar aplasia or hypoplasia characteristic of Joubert syndrome was present in 2 out of 12 families. Fibroblasts from affected individuals showed disturbed ciliary composition, suggesting alteration of ciliary transport and signaling. Knockdown of ift172 in zebrafish recapitulated the human phenotype and demonstrated a genetic interaction between ift172 and ift80. In summary, we have identified defects in IFT172 as a cause of complex ATD and MZSDS. Our findings link the group of skeletal ciliopathies to an additional IFT-B component, IFT172, similar to what has been shown for IFT-A.

The Mycobacterial MsDps2 Protein Is a Nucleoid-Forming DNA Binding Protein Regulated by Sigma Factors sigma(A) and sigma(B)

The Dps (DNA-binding protein from starved cells) proteins from Mycobacterium smegmatis MsDps1 and MsDps2 are both DNA-binding proteins with some differences. While MsDps1 has two oligomeric states, with one of them responsible for DNA binding, MsDps2 has only one DNA-binding oligomeric state. Both the proteins however, show iron-binding activity. The MsDps1 protein has been shown previously to be induced under conditions of starvation and osmotic stress and is regulated by the extra cellular sigma factors sigma(H) and sigma(F). We show here, that the second Dps homologue in M. smegmatis, namely MsDps2, is purified in a DNA-bound form and exhibits nucleoid-like structures under the atomic force microscope. It appears that the N-terminal sequence of Dps2 plays a role in nucleoid formation. MsDps2, unlike MsDps1, does not show elevated expression in nutritionally starved or stationary phase conditions; rather its promoter is recognized by RNA polymerase containing sigma(A) or sigma(B), under in vitro conditions. We propose that due to the nucleoid-condensing ability, the expression of MsDps2 is tightly regulated inside the cells.

Ratios of T-cell immune-effectors with tumour associated macrophages and PD-1/PD-L1 axis immune-checkpoint molecules, as prognosticators in diffuse large B cell lymphoma: A population-based study

Background Risk-stratification of diffuse large B-cell lymphoma (DLBCL) requires identification of patients with disease that is not cured despite initial R-CHOP. Although the prognostic importance of the tumour microenvironment (TME) is established, the optimal strategy to quantify it is unknown. Methods The relationship between immune-effector and inhibitory (checkpoint) genes was assessed by NanoString™ in 252 paraffin-embedded DLBCL tissues. A model to quantify net anti-tumoural immunity as an outcome predictor was tested in 158 R-CHOP treated patients, and validated in tissue/blood from two independent R-CHOP treated cohorts of 233 and 140 patients respectively. Findings T and NK-cell immune-effector molecule expression correlated with tumour associated macrophage and PD-1/PD-L1 axis markers consistent with malignant B-cells triggering a dynamic checkpoint response to adapt to and evade immune-surveillance. A tree-based survival model was performed to test if immune-effector to checkpoint ratios were prognostic. The CD4*CD8:(CD163/CD68)*PD-L1 ratio was better able to stratify overall survival than any single or combination of immune markers, distinguishing groups with disparate 4-year survivals (92% versus 47%). The immune ratio was independent of and added to the revised international prognostic index (R-IPI) and cell-of-origin (COO). Tissue findings were validated in 233 DLBCL R-CHOP treated patients. Furthermore, within the blood of 140 R-CHOP treated patients immune-effector:checkpoint ratios were associated with differential interim-PET/CT+ve/-ve expression.

Shrinking Violets

Description of the work Shrinking Violets is comprised of two half scale garments in laser cut silk organza, developed with a knotting device to allow for disassembly and reassembly. The first is a jacket in layered red organza including black storm flap details. The second is a vest in jade organza with circles of pink organza attached through a pattern of knots. Research Background This practice-led fashion design research sits within the field of Design for Sustainability (DfS) in fashion that seeks to mitigate the environmental and ethical impacts of fashion consumption and production. The research explores new systems of garment construction for DfS, and examines how these systems may involve ‘designing’ new user interactions with the garments. The garments’ construction system allows them to be disassembled and recycled or reassembled by users to form a new garment. Conventional garment design follows a set process of cutting and construction, with pattern pieces permanently machine-stitched together. Garments typically contain multiple fibre types; for example a jacket may be constructed from a shell of wool/polyester, an acetate lining, fusible interlinings, and plastic buttons. These complex inputs mean that textile recycling is highly labour intensive, first to separate the garment pieces and second to sort the multiple fibre types. This difficulty results in poor quality ‘shoddy’ comprised of many fibre types and unsuitable for new apparel, or in large quantities of recyclable textile waste sent to landfill (Hawley 2011). Design-led approaches that consider the garment’s end of life in the design process are a way of addressing this problem. In Gulich’s (2006) analysis, use of single materials is the most effective way to ensure ease of recycling, with multiple materials that can be detached next in effectiveness. Given the low rate of technological innovation in most apparel manufacturing (Ruiz 2011), a challenge for effective recycling is how to develop new manufacturing methods that allow for garments to be more easily disassembled at end-of-life. Research Contribution This project addresses the research question: How can design for disassembly be considered within the fashion design process? I have employed a practice-led methodology in which my design process leads the research, making use of methods of fashion design practice including garment and construction research, fabric and colour research, textile experimentation, drape, patternmaking, and illustration as well as more recent methods such as laser cutting. Interrogating the traditional approaches to garment construction is necessarily a technical process; however fashion design is as much about the aesthetic and desirability of a garment as it is about the garment’s pragmatics or utility. This requires a balance between the technical demands of designing for disassembly with the aesthetic demands of fashion. This led to the selection of luxurious, semi-transparent fabrics in bold floral colours that could be layered to create multiple visual effects, as well as the experimentation with laser cutting for new forms of finishing and fastening the fabrics together. Shrinking Violets makes two contributions to new knowledge in the area of design for sustainability within fashion. The first is in the technical development of apparel modularity through the system of laser cut holes and knots that also become a patterning device. The second contribution lies in the design of a system for users to engage with the garment through its ability to be easily reconstructed into a new form. Research Significance Shrinking Violets was exhibited at the State Library of Queensland’s Asia Pacific Design Library, 1-5 November 2015, as part of The International Association of Societies of Design Research’s (IASDR) biannual design conference. The work was chosen for display by a panel of experts, based on the criteria of design innovation and contribution to new knowledge in design. References Gulich, B. (2006). Designing textile products that are easy to recycle. In Y. Wang (Ed.), Recycling in Textiles (pp. 25-37). London: Woodhead. Hawley, J. M. (2011). Textile recycling options: exploring what could be. In A. Gwilt & T. Rissanen (Eds.), Shaping Sustainable Fashion: Changing the way we make and use clothes (pp. 143 - 155). London: Earthscan. Ruiz, B. (2014). Global Apparel Manufacturing. Retrieved 10 August 2014, from http://clients1.ibisworld.com/reports/gl/industry/default.aspx?entid=470

A novel DNA intercalator, butylamino-pyrimido[4',5':4,5]selenolo(2,3-b)quinoline, induces cell cycle arrest and apoptosis in leukemic cells

DNA intercalators are one of the most commonly used chemotherapeutic agents. Novel intercalating compounds of pyrimido[4',5':4,5]selenolo(2,3-b)quinoline series having a butylamino or piperazino group at fourth position (BPSQ and PPSQ, respectively) are studied. Our results showed that BPSQ induced cytotoxicity whereas PPSQ was cytostatic. The cytotoxicity induced by BPSQ was concentration- and time-dependent. Cell cycle analysis and tritiated thymidine assay revealed that BPSQ affects the cell cycle progression by arresting at S phase. The absence of p-histone H3 and reduction in the levels of PCNA in the cells treated with BPSQ further confirmed the cell cycle arrest. Further, annexin V staining, DNA fragmentation, nuclear condensation and changes in the expression levels of BCL2/BAD confirmed the activation of apoptosis. Activation of caspase 8 and lack of cleavage of caspase 9, caspase 3 and PARP suggest the possibility of BPSQ triggering extrinsic pathway for induction of apoptosis, which is discussed. Hence, we have identified a novel compound which would have clinical relevance in cancer chemotherapeutics.

Stereoselective Formal Total Synthesis of (-)-Didemniserinolipid B

A formal total synthesis of (-)-didemniserinolipid B from L-(+)-tartaric acid is presented. Key features of the synthesis include construction of the bicyclic acetal core from bisdimethyl amide of tartaric acid and further elaboration by cross metathesis.