Distinct Chains Research Articles

Enantioselective total synthesis of (+)-lyngbyabellin M.

Lyngbyabellin M is a non-ribosomal peptide synthetase/polyketide synthase derived metabolite isolated from the cyanobacterium M. bouillonii displaying thiazole rings and a distinct chlorinated octanoic acid chain. Its absolute configuration was proposed based on the comparison of its spectroscopic data with those of other representatives of this family of marine natural products, as well as degradation and derivatization studies. Here the first total synthesis of (+)-lyngbyabellin M is described based on the coupling of three key intermediates: two chiral thiazole moieties and an anti hydroxycarboxylic acid prepared stereoselectively via a boron enolate mediated aldol reaction directed by Masamune’s chiral auxiliary.

Supply chain structures shaping portfolio of technologies

Purpose – The purpose of this paper is to develop a better understanding of how the supply chain structure (i.e. degree of vertical integration) of a focal organization shapes the breadth of its portfolio of technologies. Design/methodology/approach – In total, three case studies were conducted involving key players in the Australian mass grocery retail sector. Each had a distinct supply chain structure (i.e. totally vertically disintegrated, partially vertically integrated and totally vertically integrated). Each supply chain case study included manufacturers or suppliers, transport and logistics service providers, wholesalers/distributors, as well as the mass grocery retail organizations. Interviews with key personnel from these organizations and other relevant information informed the findings and conclusions. Findings – The information technologies employed by the three focal case organizations and their extended trading partners varied in terms of level, type, complexity and sophistication. The autho...

Simple NMR Experiments Reveal the Influence of Chain Length and Chain Architecture on the Crystalline/Amorphous Interface in Polyethylenes

The distribution of polyethylene (PE) chain segments between the crystalline, noncrystalline, and interfacial morphological regions is an old question that continues to intrigue the polymer science community. Simple solid state NMR experiments described here reveal that even in the case of linear PE, four distinct chain components may be resolved and reliably quantified. The amounts of rigid crystalline chains in all-trans conformations, amorphous chains with increased equilibrium gauche conformer content undergoing essentially isotropic reorientation, mobile all-trans chains (termed mobile trans), and less mobile noncrystalline chains (termed constrained amorphous) can be quantified by simple 13C NMR experiments on solid polymer samples. A version of the EASY background suppression pulse sequence [Jaeger and Hemmann Solid State Nucl. Magn. Reson. 2014, 57–58, 22], modified to eliminate transient Overhauser effects, is used to obtain all of the data in a single experimental acquisition. Using a broad rang...

Abstract P2-16-02: Bi-specific antibodies targeting signaling pathway crosstalk are a new breast cancer immunotherapeutic strategy

Abstract All of the currently approved therapeutic anti-cancer antibodies are monospecific and therefore only capable of interfering with the biological function of a single molecular target. However, breast cancers mostly involve crosstalk of often synergistic signal transduction pathways, and thus, isolated blockade of a single signal transduction pathway is frequently met by escape mechanisms, such as upregulation of redundant pathways, rendering the monospecific immunotherapy less effective. Using chemical biology and molecular biology, Sorrento has developed new approaches to generate IgG-like bi-specific antibodies (BsAbs) targeting either two compensating signal transduction pathways, such as HER family members or a breast cancer specific antigen and an immuno-regulatory molecule such as PDL1 or PD1. The chemical biology method involves specific hetero-dimerization of two half antibody molecules using bio-orthogonal chemistry. The molecular biology approach utilizes phage display by either discovering common light chains for the two relevant antigens in combination with two distinct heavy chains or by selecting dual specific antibodies, namely a single antibody that can recognize two distinct antigens. Progress will be presented on bi-specific as well as dual specific antibodies against Her3 and Her4 as well as immunomodulatory BsAbs with data on in vitro characterization, cell-based functional assays, and in vivo models. Citation Format: Yanliang Zhang, Edwige Gros, Sarabjit Chagar, Jian Cao, Heyue Zhou, Kouros Motamed, Gunnar F Kaufmann, Yanwen Fu. Bi-specific antibodies targeting signaling pathway crosstalk are a new breast cancer immunotherapeutic strategy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-16-02.

Synthesis of borate cross-linked rhamnogalacturonan II.

In the present review, we describe current knowledge about synthesis of borate crosslinked rhamnogalacturonan II (RG-II) and it physiological roles. RG-II is a portion of pectic polysaccharide with high complexity, present in primary cell wall. It is composed of homogalacturonan backbone and four distinct side chains (A–D). Borate forms ester bonds with the apiosyl residues of side chain A of two RG-II monomers to generate borate dimerized RG-II, contributing for the formation of networks of pectic polysaccharides. In plant cell walls, more than 90% of RG-II are dimerized by borate under boron (B) sufficient conditions. Borate crosslinking of RG-II in primary cell walls, to our knowledge, is the only experimentally proven molecular function of B, an essential trace-element. Although abundance of RG-II and B is quite small in cell wall polysaccharides, increasing evidence supports that RG-II and its borate crosslinking are critical for plant growth and development. Significant advancement was made recently on the location and the mechanisms of RG-II synthesis and borate cross-linking. Molecular genetic studies have successfully identified key enzymes for RG-II synthesis and regulators including B transporters required for efficient formation of RG-II crosslinking and consequent normal plant growth. The present article focuses recent advances on (i) RG-II polysaccharide synthesis, (ii) occurrence of borate crosslinking and (iii) B transport for borate supply to RG-II. Molecular mechanisms underlying formation of borate RG-II crosslinking and the physiological impacts are discussed.

Generalized mutual information of quantum critical chains

We study the R\'enyi mutual information $\tilde{I}_n$ of the ground state of different critical quantum chains. The R\'enyi mutual information definition that we use is based on the well established concept of the R\'enyi divergence. We calculate this quantity numerically for several distinct quantum chains having either discrete $Z(Q)$ symmetries (Q-state Potts model with $Q=2,3,4$ and $Z(Q)$ parafermionic models with $Q=5,6,7,8$ and also Ashkin-Teller model with different anisotropies) or the $U(1)$ continuous symmetries(Klein-Gordon field theory, XXZ and spin-1 Fateev-Zamolodchikov quantum chains with different anisotropies). For the spin chains these calculations were done by expressing the ground-state wavefunctions in two special basis. Our results indicate some general behavior for particular ranges of values of the parameter $n$ that defines $\tilde{I}_n$. For a system, with total size $L$ and subsystem sizes $\ell$ and $L-\ell$, the$\tilde{I}_n$ has a logarithmic leading behavior given by $\frac{\tilde{c}_n}{4}\log(\frac{L}{\pi}\sin(\frac{\pi \ell}{L}))$ where the coefficient $\tilde{c}_n$ is linearly dependent on the central charge $c$ of the underlying conformal field theory (CFT) describing the system's critical properties.

Crystal structure of di-methyl-ammonium hydrogen oxalate hemi(oxalic acid).

Single crystals of the title salt, Me2NH2 (+)·HC2O4 (-)·0.5H2C2O4, were isolated as a side product from the reaction involving Me2NH, H2C2O4 and Sn(n-Bu)3Cl in a 1:2 ratio in methanol or by the reaction of the (Me2NH2)2C2O4 salt and Sn(CH3)3Cl in a 2:1 ratio in ethanol. The asymmetric unit comprises a di-methyl-ammonium cation (Me2NH2 (+)), an hydrogenoxalate anion (HC2O4 (-)), and half a mol-ecule of oxalic acid (H2C2O4) situated about an inversion center. From a supra-molecular point of view, the three components inter-act together via hydrogen bonding. The Me2NH2 (+) cations and the HC2O4 (-) anions are in close proximity through bifurcated N-H⋯(O,O) hydrogen bonds, while the HC2O4 (-) anions are organized into infinite chains via O-H⋯O hydrogen bonds, propagating along the a-axis direction. In addition, the oxalic acid (H2C2O4) mol-ecules play the role of connectors between these chains. Both the carbonyl and hydroxyl groups of each diacid are involved in four inter-molecular inter-actions with two Me2NH2 (+) and two HC2O4 (-) ions of four distinct polymeric chains, via two N-H⋯O and two O-H⋯O hydrogen bonds, respectively. The resulting mol-ecular assembly can be viewed as a two-dimensional bilayer-like arrangement lying parallel to (010), and reinforced by a C-H⋯O hydrogen bond.

Disorder from order among anisotropic next-nearest-neighbor Ising spin chains inSrHo2O4

We describe why Ising spin chains with competing interactions in $\rm SrHo_2O_4$ segregate into ordered and disordered ensembles at low temperatures ($T$). Using elastic neutron scattering, magnetization, and specific heat measurements, the two distinct spin chains are inferred to have N\'eel ($\uparrow\downarrow\uparrow\downarrow$) and double-N\'eel ($\uparrow\uparrow\downarrow\downarrow$) ground states respectively. Below $T_\mathrm{N}=0.68(2)$~K, the N\'eel chains develop three dimensional (3D) long range order (LRO), which arrests further thermal equilibration of the double-N\'eel chains so they remain in a disordered incommensurate state for $T$ below $T_\mathrm{S}= 0.52(2)$~K. $\rm SrHo_2O_4$ distills an important feature of incommensurate low dimensional magnetism: kinetically trapped topological defects in a quasi$-d-$dimensional spin system can preclude order in $d+1$ dimensions.

Improving target cell specificity using a novel monovalent bispecific IgG design

Monovalent bispecific IgGs cater to a distinct set of mechanisms of action but are difficult to engineer and manufacture because of complexities associated with correct heavy and light chain pairing. We have created a novel design, “DuetMab,” for efficient production of these molecules. The platform uses knobs-into-holes (KIH) technology for heterodimerization of 2 distinct heavy chains and increases the efficiency of cognate heavy and light chain pairing by replacing the native disulfide bond in one of the CH1-CL interfaces with an engineered disulfide bond. Using two pairs of antibodies, cetuximab (anti-EGFR) and trastuzumab (anti-HER2), and anti-CD40 and anti-CD70 antibodies, we demonstrate that DuetMab antibodies can be produced in a highly purified and active form, and show for the first time that monovalent bispecific IgGs can concurrently bind both antigens on the same cell. This last property compensates for the loss of avidity brought about by monovalency and improves selectivity toward the target cell.

S0520304 ナノ・マイクロ粒子混合系MR流体のMR効果向上と粒子カラム挙動

Magnetorheological (MR) fluids are suspensions of micron-sized magnetic particles dispersed into carrier oils, and behave like a Bingham fluid with magnetic-field responsive yield stress. In this research, bidisperse MR suspensions consisting of micro (6.6 μm) and nano (110 nm) iron particles dispersed into silicone oil were fabricated to investigate the enhancement of the MR effects in close relation to the magnetic field-induced particle cluster structures in the static condition and particle column behavior in the shear flow mode. The static particle cluster structures formed in the suspensions under applied magnetic fields were visualized using an optical microscope in a transmission mode, and the particle column behavior in the shear mode was visualized using a hand-made shear flow device and a digital video system with a micro-lens. The MR effects of the bidispersed MR suspensions changed significantly as a function of the solid fraction of nano-particles. Interestingly, the field-induced shear stress was significantly enhanced when the solid fraction of nano-particles was 25%. As well known, the particle chains formed roughly along to the applied magnetic field were observed for the MR suspension containing the micron-sized iron particles. The enhancement of the MR effects can be attributed to the static formation of distinct and wide particle cluster chains reinforced with nano-particles, and the breaking and reconnection of many thicker particle columns in the shear flow mode.

Bis(methyl)(thia/selena)salen Ag(i) complexes: counter-ion induced structural diversity

The complexation behaviour of bis(methyl)(thia/selena)salen ligands towards Ag(I) ions in the presence of PF6−, ClO4− and NO3− ions, and the self-assembling of the resultant complexes were explored. Changes in counter anion and coordinating sites (S/Se) led to a structural diversity of complexes as determined using single-crystal X-ray diffraction. The crystallographic study of silver complexes 1 and 2 derived from La and Lb, respectively, in the presence of PF6− ions, revealed the formation of 1D coordination polymers. In the cationic polymer 1, the metal center adopts a distorted square pyramidal geometry where the N2S2 donor set of a ligand molecule forms a basal plane while the S atom from another ligand molecule forms an axial bond, which is responsible for the establishment of the coordination polymer. Unlike complex 1 (with a S-ligating site), complex 2 (with a Se-ligating site) is a polymer with a bimetallic unit where the two metal centers (Ag1 and Ag2) differ in their coordination spheres. In the analogous complexes 3 and 4 involving ClO4− as the counter anion, the polymeric frameworks resemble that of 1 but the existence of π–π interactions between the aromatic rings of the two distinct polymeric chains construct a 2D-sheet, while no direct interaction was observed between the polymeric chains in 1 and 2. The presence of NO3− ions yielded the bimetallic metallacycle 5 possessing a center of inversion. The ligand molecules are coordinated in a tridentate mode and the tetrahedral environment around the silver ion was established with the coordination of a nitrate ion.

Modelling, feasibility and performance analyses of a 3-DOF parallel mechanism employed in a rear vehicle suspension

This work deals with a three-degree-of-freedom mechanism for rear independent suspensions, capable to adjust simultaneously the camber, toe and roll angles. Topologically, the mechanism is parallel and asymmetric with three distinct active kinematic chains. In this paper, the kinematic and kinetostatic models are developed. In order to evaluate how promising this mechanism is, two analyses are conducted. First, a performance analysis evaluates the influence of the mechanism actuation on the vehicle dynamic behaviour and, second, a feasibility analysis determines a suitable stroke and the required force/power for the actuators. The obtained results have shown the capability of the mechanism to improve vehicle handling performance, when compared to a car equipped with a conventional suspension system. The evaluation is based on three manoeuvres: a steady-state cornering, a fishhook and a double lane change. Moreover, the mechanism feasibility analysis has shown that the actuator’s stroke, velocity and force can be obtained by using standard hydraulic or eletromechanical actuators.

New iron tetrazolate frameworks: synthesis, temperature effect, thermal behaviour, Mössbauer and magnetic studies.

The exploration of the FeF3/FeF2-Hamtetraz-HF system in dimethylformamide by solvothermal synthesis evidences two isostructural 3D hybrid fluoroferrates. They are prepared from the same starting mixture at two different synthesis temperatures: 120 °C for [Hdma]·(Fe4(II)Fe(III)F8(H2O)2(amtetraz)4) () and 140 °C for [Hdma]1.5·(Fe4.5(II)Fe0.5(III)F7(H2O)(HCOO)(amtetraz)4) (). Both compounds are characterized by single crystal X-ray diffraction, X-ray thermodiffraction, TGA analysis, Mössbauer spectrometry and SQUID magnetometry. They crystallize in the monoclinic system and are built from two distinct chains connected by aminotetrazolate anions. The first chain ∞(Fe(II)FN4) is common to and and can be found in numerous fluorides. In the second chain ∞(Fe3X12) (X = F, N, O), iron cations adopt both valence states Fe(ii)/Fe(iii). The hydrolysis of DMF implies the formation of a [Hdma](+) cation and a (HCOO)(-) anion. The presence of Fe(3+) in both phases is evidenced by (57)Fe Mössbauer spectrometry. The magnetic properties are studied and two transitions from a paramagnetic regime to a long range ordered state below 30 K and 5 K are identified.

Crystal structures and characterization of two one-dimensional coordination polymers containing Ln3+ ions and anthranilate (C7H6NO 2 − ) anions

The syntheses, crystal structures and characterization (IR, TGA/DSC) of the isostructural one-dimensional coordination polymers [Ce(C7H6NO2)3]n (1) and [Pr(C7H6NO2)3]n (2) are described. The metal ions adopt distorted capped square anti-prismatic MO9 coordination geometries. The anthranilate ligands bridge the metal ions in bridging-bidentate (O, μ2-O′) mode to generate [010] chains in the crystal and each ligand features an intramolecular N-H⋯O hydrogen bond. It is notable that two very similar, but crystallographically distinct chains appear in the unit cell. Crystal data: 1, C21H18CeN3O6, Mr = 548.51, monoclinic, P21/c (No. 14), a = 25.0476(10) A, b = 7.4924(2) A, c = 24.6366(7) A, β = 119.424(1)°, V = 4027.1(2) A3, R(F) = 0.037, wR(F2) = 0.068. 2, C21H18N3O6Pr, Mr = 549.29, monoclinic, P21/c (No. 14), a = 25.0077(13) A, b = 7.4497(3) A, c = 24.6063(12) A, β = 119.392(2)°, V = 3994.1(3) A3, R(F) = 0.031, wR(F2) = 0.068.

Ceramide synthases CerS4 and CerS5 are upregulated by 17β-estradiol and GPER1 via AP-1 in human breast cancer cells

Ceramide synthases (CerS) are important enzymes of the sphingolipid pathway, responsible for the production of ceramides with distinct chain lengths. In human breast cancer tissue, we detected a significant increase in CerS4 and CerS6 mRNA in estrogen receptor positive (ER+) cancer tissue. To clarify the molecular mechanism of this upregulation, we cloned CerS2, -4, -5 and CerS6 promoter and 3′-UTR fragments into luciferase reporter gene plasmids and determined luciferase activity in MCF-7 (ERα/β) and MDA-MB-231 (ERβ) cells after 17β-estradiol treatment. Only the activities of CerS4 and CerS5 promoter Luc constructs, as well as CerS2- and CerS5-3′-UTR Luc constructs increased after estradiol treatment in MCF-7 cells, and this could be inhibited by the anti-estrogen fulvestrant. Co-transfection with the G protein-coupled estrogen receptor 1 (GPER1) also enhanced CerS2, CerS4 and CerS6 promoter activity whereas CerS5 promoter activity was inhibited in both cell lines. Promoter deletion and mutation constructs from CerS4 and CerS5 promoters revealed that estradiol and GPER1 mediate their effects on both promoters by activating AP-1, most likely through dimerization of c-Jun and c-Fos. At least we could show, that cell proliferation induced by estradiol could be blocked by co-treatment with Fumonisin B1, indicating that upregulation of CerS in breast cancer cells by estrogen is important for cell proliferation and possibly tumor development. In conclusion, our data highlight transcriptional and posttranscriptional mechanisms regulating CerS expression in human cells which provide the basis for further studies investigating the regulation of CerS expression and ceramide synthesis after diverse stimuli in physiological and pathophysiological processess.

Altered levels of serum sphingomyelin and ceramide containing distinct acyl chains in young obese adults.

Objective:Recent studies indicate that sphingolipids, sphingomyelin (SM) and ceramide (Cer) are associated with the development of metabolic syndrome. However, detailed profiles of serum sphingolipids in the pathogenesis of this syndrome are lacking. Here we have investigated the relationship between the molecular species of sphingolipids in serum and the clinical features of metabolic syndrome, such as obesity, insulin resistance, fatty liver disease and atherogenic dyslipidemia.Subjects:We collected serum from obese (body mass index, BMI⩾35, n=12) and control (BMI=20−22, n=11) volunteers (18−27 years old), measured the levels of molecular species of SM and Cer in the serum by liquid chromatography-mass spectrometry and analyzed the parameters for insulin resistance, liver function and lipid metabolism by biochemical blood test.Results:The SM C18:0 and C24:0 levels were higher, and the C20:0 and C22:0 levels tended to be higher in the obese group than in the control group. SM C18:0, C20:0, C22:0 and C24:0 significantly correlated with the parameters for obesity, insulin resistance, liver function and lipid metabolism, respectively. In addition, some Cer species tended to correlate with these parameters. However, SM species containing unsaturated acyl chains and most of the Cer species were not associated with these parameters.Conclusions:The present results demonstrate that the high levels of serum SM species with distinct saturated acyl chains (C18:0, C20:0, C22:0 and C24:0) closely correlate with the parameters of obesity, insulin resistance, liver function and lipid metabolism, suggesting that these SM species are associated with the development of metabolic syndrome and serve as novel biomarkers of metabolic syndrome and its associated diseases.

Sustainable food procurement in British and Irish zoos

Purpose – The purpose of this paper is to assess the sustainable food procurement (SFP) of members of the British and Irish Association of Zoos and Aquariums (BIAZA). It also considered the inconsistencies between their animal and human food supply chains, as well as between their procurement priorities and practices. Design/methodology/approach – A quantitative, cross-sectional approach was employed, involving the use of a web-based questionnaire to gather data from 41 BIAZA members across 21 indicators of food sustainability. The results were considered within a sustainable supply chain management (SSCM) framework. Findings – There was considerable variation amongst the issues considered by zoos during the SFP process for their animal and human food operations. For both, local expenditure, nutritional content and packaging reduction were some of the highest scoring indicators in practice and as priorities. The overall levels of SFP were found to be equal between the human and animal food supply chains. Significantly low levels of inconsistency were found between the two, practically and in terms of procurement aspirations. Within both supply chains, there was also very few significant gaps between procurement priorities and actions. Originality/value – The originality of this study lies in its comparison of procurement practices and priorities for two contemporaneous but distinct food supply chains. It demonstrates that it is possible to have a high overall degree of consistency between two parallel, but contrasting, supply chains, as well as between procurement priorities and priorities. It will be of use in SSCM, particularly within values-led organisations.

PolyUbiquitin chain linkage topology selects the functions from the underlying binding landscape.

Ubiquitin (Ub) can generate versatile molecular signals and lead to different celluar fates. The functional poly-valence of Ub is believed to be resulted from its ability to form distinct polymerized chains with eight linkage types. To provide a full picture of ubiquitin code, we explore the binding landscape of two free Ub monomers and also the functional landscapes of of all eight linkage types by theoretical modeling. Remarkably, we found that most of the compact structures of covalently connected dimeric Ub chains (diUbs) pre-exist on the binding landscape. These compact functional states were subsequently validated by corresponding linkage models. This leads to the proposal that the folding architecture of Ub monomer has encoded all functional states into its binding landscape, which is further selected by different topologies of polymeric Ub chains. Moreover, our results revealed that covalent linkage leads to symmetry breaking of interfacial interactions. We further propose that topological constraint not only limits the conformational space for effective switching between functional states, but also selects the local interactions for realizing the corresponding biological function. Therefore, the topological constraint provides a way for breaking the binding symmetry and reaching the functional specificity. The simulation results also provide several predictions that qualitatively and quantitatively consistent with experiments. Importantly, the K48 linkage model successfully predicted intermediate states. The resulting multi-state energy landscape was further employed to reconcile the seemingly contradictory experimental data on the conformational equilibrium of K48-diUb. Our results further suggest that hydrophobic interactions are dominant in the functional landscapes of K6-, K11-, K33- and K48 diUbs, while electrostatic interactions play a more important role in the functional landscapes of K27, K29, K63 and linear linkages.

Price competition in duopoly supply chains with stochastic demand

In the literature, substantial researches have been carried out on supply chain coordination. The majority of these studies suggest a mechanism that enforces the supply chain members to follow the strategies that produce the equilibrium of an integrated supply chain. Moreover, most of researches do not consider the competition among supply chains.In this study, we consider an industry consisting of two distinct supply chains which compete with each other over price. Three algorithms are presented to calculate the equilibrium of three possible industry structures. It is assumed that demand is stochastic with additive form whose random component has a uniform distribution. Furthermore, the effect of competition and demand uncertainty intensity on the Nash equilibrium of the structures and supply chains’ profits are discussed in a numerical example.

Quantifying force networks in particulate systems

We present mathematical models based on persistent homology for analyzing force distributions in particulate systems. We define three distinct chain complexes of these distributions: digital, position, and interaction, motivated by different types of data that may be available from experiments and simulations, e.g. digital images, location of the particles, and the forces between the particles, respectively. We describe how algebraic topology, in particular, homology allows one to obtain algebraic representations of the geometry captured by these complexes. For each complex we define an associated force network from which persistent homology is computed. Using numerical data obtained from discrete element simulations of a system of particles undergoing slow compression, we demonstrate how persistent homology can be used to compare the force distributions in different systems, and discuss the differences between the properties of digital, position, and interaction force networks. To conclude, we formulate well-defined measures quantifying differences between force networks corresponding to the different states of a system, and therefore allow to analyze in precise terms dynamical properties of force networks.