A Small Step,a Giant Leap: Somatic Hypermutation of a Single Amino Acid Leads to Anti-La Autoreactivity

The anti-La mab 312B, which was established by hybridoma technology from human-La transgenic mice after adoptive transfer of anti-human La T cells, immunoprecipitates both native eukaryotic human and murine La protein. Therefore, it represents a true anti-La autoantibody. During maturation, the anti-La mab 312B acquired somatic hypermutations (SHMs) which resulted in the replacement of four aa in the complementarity determining regions (CDR) and seven aa in the framework regions. The recombinant derivative of the anti-La mab 312B in which all the SHMs were corrected to the germline sequence failed to recognize the La antigen. We therefore wanted to learn which SHM(s) is (are) responsible for anti-La autoreactivity. Humanization of the 312B ab by grafting its CDR regions to a human Ig backbone confirms that the CDR sequences are mainly responsible for anti-La autoreactivity. Finally, we identified that a single amino acid replacement (D > Y) in the germline sequence of the CDR3 region of the heavy chain of the anti-La mab 312B is sufficient for anti-La autoreactivity.     

Sequence and structure of VH domain from naturally occurring camel heavy chain immunoglobulins lacking light chains

We cloned 17 different PCR fragments encoding V_H genes of camel(Camelus dromedarius). These clones were derived from the camelheavy chain immunoglobulins lacking the light chain counterpartof normal immunoglobulins. Insight into the camel V_H sequencesand structure may help the development of single domain antibodies.The most remarkable difference in the camel V_H, consistent withthe absence of the V_L interaction, is the substitution of theconserved Leu45 by an Arg or Cys. Another noteworthy substitutionis the Leu11 to Ser. This amino acid normally interacts withthe C_H1 domain, a domain missing in the camel heavy chain immunoglobulins.The nature of these substitutions agrees with the increasedsolubility behavior of an isolated camel V_H domain. The V_H domainsof the camels are also characterized by a long CDR3, possiblycompensating for the absence of the V_L contacts with the antigen.The CDR3 lacks the salt bridge between Arg94 and Asp101. However,the frequent occurrence of additional Cys residues in both theCDR1 and CDR3 might lead to the formation of a second internaldisulfide bridge, thereby stabilizing the CDR structure as inthe DAW antibody. Within CDRs of the camel V_H domains we observea broad size distribution and a different amino acid patterncompared with the mouse or human V_H. Therefore the camel hypervariableregions might adopt structures which differ substantially fromthe known canonical structures, thereby increasing the repertoireof the camel antigen binding sites within a V_H.     

Nanobody Paratope Ensembles in Solution Characterized by MD Simulations and NMR

Variable domains of camelid antibodies (so-called nanobodies or V_HH) are the smallest antibody fragments that retain complete functionality and therapeutic potential. Understanding of the nanobody-binding interface has become a pre-requisite for rational antibody design and engineering. The nanobody-binding interface consists of up to three hypervariable loops, known as the CDR loops. Here, we structurally and dynamically characterize the conformational diversity of an anti-GFP-binding nanobody by using molecular dynamics simulations in combination with experimentally derived data from nuclear magnetic resonance (NMR) spectroscopy. The NMR data contain both structural and dynamic information resolved at various timescales, which allows an assessment of the quality of protein MD simulations. Thus, in this study, we compared the ensembles for the anti-GFP-binding nanobody obtained from MD simulations with results from NMR. We find excellent agreement of the NOE-derived distance maps obtained from NMR and MD simulations and observe similar conformational spaces for the simulations with and without NOE time-averaged restraints. We also compare the measured and calculated order parameters and find generally good agreement for the motions observed in the ps–ns timescale, in particular for the CDR3 loop. Understanding of the CDR3 loop dynamics is especially critical for nanobodies, as this loop is typically critical for antigen recognition.     

In situ XAS investigation of the oxidation state and local structure of vanadium in discharged and charged V2O5 aerogel cathodes

We have examined the evolution of the oxidation state and atomic structure of vanadium(V) in discharged and charged nanophase vanadium pentoxide (V₂O₅) aerogel cathodes under in situ conditions using X-ray absorption spectroscopy (XAS). We show that the oxidation state of V in V₂O₅ aerogel cathode heated under vacuum (100 μTorr) at 220 °C for 20.5 h is similar to that of V in a commercially obtained sample of orthorhombic V₂O₅. In addition, lithium (Li) insertion during the first cycle of discharging leads to the reduction of V(V) to V(IV) and V(IV) to V(III) in a manner consistent with the stoichiometry of the sample (i.e. Li_xV₂O₅). Li extraction during charging leads to oxidation of V(III) to V(IV) and then V(IV) to V(V). Furthermore, the oxidation state of V in fully charged cathodes remains unchanged with cycling (upto at least the 16th cycle) from that of V in the control V₂O₅ aerogel cathode. However, the average oxidation state of V in discharged V₂O₅ cathodes increased with cycling. Moreover, the local structure of V in the discharged state has a higher degree of symmetry than that of the fully charged state. A significant change in the structure of the VV correlation of discharged cathodes is observed with cycling indicating the formation of electrochemically irreversible phases.     

Electronic Structure of Unsaturated V2O5(001) and (100) Surfaces: Ab Initio Density Functional Theory Studies

Vanadium oxides based materials are well known to play an active role as catalysts in many chemical processes of technological importance like for example hydrocarbon oxidation reactions or selective catalytic reduction of NO _x in the presence of ammonia. Usually the (010) surface is pointed out as the most important, however one has to underline that other low-indices surfaces are by far less studied. In the present study the electronic structure of V₂O₅(001) and (100) surfaces are determined by ab initio DFT methods using gradient-corrected RPBE exchange-correlation functional. As models of surface sections different embedded V₁₄O₄₅H₂₀, V₁₄O₄₄H₁₈, and V₂₁O₆₅H₂₅ clusters are considered for the (001) surface and V₁₂O₄₀H₂₀, V₁₄O₄₆H₂₂, V₁₆O₅₂H₂₄ for the (100) surface. Detailed analyses of the electronic structure of each cluster are performed using charge density distributions, Mayer bond orders, electrostatic potential maps, character of frontier orbitals, and density of states (total as well as partial, atom projected). Results of the calculations show that overall negative charge of the surface oxygen sites scales with their coordination independent of the surface orientation. Terminal oxygen O(1) is charged the least negatively while doubly coordinated atoms –O(2) and O^e(2) have charge twice as large. This indicates that bridging (for (001) and (100) netplanes) and edging (only for (001) netplane) oxygen sites are more nucleophilic than terminal vanadyl sites, which becomes important in view of the reactivity of the different sites for surface chemical reactions. Vanadium atoms present at these surfaces are positively charged (electrophilic) and may play a role of electron acceptors. The unsaturated surfaces show a strong tendency to surface relaxation that manifest by large relaxation energies.     

Lithium insertion/deinsertion properties of new layered vanadium oxides obtained by oxidation of the precursor H2V3O8

The electrochemical behavior of the three new vanadium oxides M_yH_1−yV₃^VO₈ (M=Li, Na, K; y=0.6-0.9) towards lithium insertion was studied. For each compound, the main insertion phenomena, and the lithium amount which can be inserted, were determined from galvanostatic studies performed at different rates. In order to better explain the differences between the compounds, the galvanostatic intermittent titration technique was used and chronoamperometry experiments were performed. Cyclability studies have shown that the performances of M_0.6H_0.4V₃O₈ (M=Li, K) are not better than those of H₂V₃O₈. On the contrary, Na_0.9H_0.1V₃O₈ presents very interesting lithium insertion properties, with a specific capacity of 215 mAh g⁻¹ in the 1.5-4 V voltage range at C/10, and a capacity loss at the 40th cycle remaining smaller than 2.5%. Na_0.9H_0.1V₃O₈ is therefore a good candidate as positive electrode material for rechargeable lithium batteries.     

VHH Structural Modelling Approaches: A Critical Review

V_HH, i.e., VH domains of camelid single-chain antibodies, are very promising therapeutic agents due to their significant physicochemical advantages compared to classical mammalian antibodies. The number of experimentally solved V_HH structures has significantly improved recently, which is of great help, because it offers the ability to directly work on 3D structures to humanise or improve them. Unfortunately, most V_HHs do not have 3D structures. Thus, it is essential to find alternative ways to get structural information. The methods of structure prediction from the primary amino acid sequence appear essential to bypass this limitation. This review presents the most extensive overview of structure prediction methods applied for the 3D modelling of a given V_HH sequence (a total of 21). Besides the historical overview, it aims at showing how model software programs have been shaping the structural predictions of V_HHs. A brief explanation of each methodology is supplied, and pertinent examples of their usage are provided. Finally, we present a structure prediction case study of a recently solved V_HH structure. According to some recent studies and the present analysis, AlphaFold 2 and NanoNet appear to be the best tools to predict a structural model of V_HH from its sequence.     

NMR studies of poly(2-hydroxy ethyl methacrylate-co-2-vinyl pyridine)

Copolymers of 2-hydroxy ethyl methacrylate-2-vinyl pyridine (H/V) of different composition were synthesized by free radical bulk polymerization using azobisisobutyronitrile (AIBN) as an initiator under nitrogen atmosphere. The copolymer compositions were calculated from ¹H NMR spectra. The reactivity ratios for H/V copolymers obtained from a linear Kelen-Tudos method (KT) and nonlinear error-in-variables method (EVM) are r_H = 0.50 ± 0.10, r_V = 1.04 ± 0.08 and r_H = 0.55, r_V = 1.06 respectively. The complete spectral assignment of methine, methylene, methyl, carbonyl, and aromatic carbon regions in term of compositional and configurational sequences of H/V copolymers were done with the help of ¹³C{¹H} NMR, distortionless enhancement by polarization transfer (DEPT), two-dimensional heteronuclear single quantum coherence (HSQC) along with total correlated spectroscopy (TOCSY). © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Principal hue curves and color difference

The size of perceptual difference of colors (j, k) is scaled as d_jk by selecting a pair of Munsell grays in which the lightness difference matches in size with the color difference. Hence, d is given in terms of Munsell V. The degree of principal hue component α in a color j is scaled as ξ_α(j) by making marks on a line segment and the range of ξ_α is from 0 to 10. By plotting ξ_α(H V/C) on Munsell H‐circle, principal hue curves ξ¯_α(H V/C) are defined, where α = R, Y, G, B, V = 4–7, and C = 2–10. In this process, similar plots of NCS codes (cϕ_α) are used as references. The curves ξ¯_α(H V/C) tell us the appearance of Munsell colors (H V/C) and also enable us to predict color differences. The relationship between d_jk and ΔV = |V_j − V_k|, Δξ¯_α = |ξ¯_α(H_j V_j/C_j) − ξ¯_α(H_k V_k/C_k)| is tested in various ways, e.g., logarithmic, power, Minkowski‐type functions. The best predictor d̃ is given by a simple linear form, d̃ = a_VΔV + {d₀ + Σa_αΔξ¯_α}. For 899 pairs (j, k), 706 differing in H, C and 193 differing in H, V, C, a_V = 0.459, d₀ = 0.610, a_R = 0.199, a_Y = 0.031, a_G = 0.098, a_B = 0.136, and the root‐mean‐squares of (d_jk − d̃_jk) is 0.338 in the matched V‐unit. © 1999 John Wiley & Sons, Inc. Col Res Appl, 24, 266–279, 1999     

A new polymeric chain in the dihydrogendecavanadate(V)–decavanadate(V) [NH2(CH2)4]5[V10O28H2]0.5[V10O28]0.5 obtained by in situ synthesis of the organic cation

A new polymeric compound, [NH₂(CH₂)₄]₅[V₁₀O₂₈H₂]_0.5[V₁₀O₂₈]_0.5, was obtained by in situ synthesis of the organic cation from an aqueous solution of V₂O₅–HCl–NH₂(CH₂)₄NH₂. The crystal structure was solved by single-crystal X-ray diffraction. [NH₂(CH₂)₄]₅[V₁₀O₂₈H₂]_0.5[V₁₀O₂₈]_0.5 consists of dihydrogendecavanadate(V), [H₂V₁₀O₂₈]^4?, and decavanadate(V), [V₁₀O₂₈]^6?, units assembled in one-dimensional arrays by interanionic hydrogen bonds O–H?O and cation-anion N–H?O interactions. The latter involve pyrrolidinium cations, which were obtained in the compound instead of the starting butane-1,4-diamine. Pyrrolidinium cations further connect the polymeric chains into a three-dimensional network. The presence of the two types of units, [H_nV₁₀O₂₈]^(6?n)? with n = 0 and n = 2, in one compound was not yet observed and is herein reported for the first time.     

Catalytic Wet Oxidation of H<Subscript>2</Subscript>S to Sulfur on V/MgO Catalyst

The V/MgO catalysts with different V₂O₅ loadings were prepared by impregnating MgO with aqueous vanadyl sulfate solution. All of the catalysts were characterized by X-ray diffraction (XRD), temperature-programmed reduction (TPR), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). It was observed that the H₂S removal capacity with respect to vanadia content increased up to 6 wt%, and then decreased with further increase in vanadia loading. The prepared catalysts had BET surface areas of 11.3 ~ 95.9 m²/g and surface coverages of V₂O₅ of 0.1 ~ 2.97. The surface coverage calculation of V₂O₅ suggested that a vanadia addition up to a monomolecular layer on MgO support increased the H₂S removal capacity of V/MgO, but the further increase of VO _x surface coverage rather decreased that. Raman spectroscopy showed that the small domains of Mg₃(VO₄)₂ could be present on V/MgO with less than 6 wt% vanadia loading. The crystallites of bulk Mg₃(VO₄)₂ and Mg₂(V₂O₇) became evident on V/MgO catalysts with vanadia loading above 15 wt%, which were confirmed by a XRD. The TPR experiments showed that V/MgO catalysts with the loading below 6 wt% V₂O₅ were more reducible than those above 15 wt% V₂O₅. It indicated that tetrahedrally coordinated V⁵⁺ in well-dispersed Mg₃(VO₄)₂ domains could be the active species in the H₂S wet oxidation. The XPS studies indicated that the H₂S oxidation with V/MgO could proceed from the redox mechanism (V⁵⁺ V⁴⁺) and that V³⁺ formation, deep reduction, was responsible for the deactivation of V/MgO.     

Reactivity of solid BaCe0.9Y0.1O3 towards liquid V2O5

In this work the reactivity in solid BaCe_0.9Y_0.1O_3-δ - liquid V₂O₅ system was investigated in order to evaluate the possibility of composite formation in this system. Impregnation of melted vanadium(V) oxide into solid Y-doped BaCeO₃ was performed in various temperature and time conditions. Due to the relatively high reactivity of components in this system an analysis of the synthesized materials was divided into discussion of the properties of the reactive layer and the inner part. As was shown, decomposition of Y-doped BaCeO₃ in contact with melted vanadium(V) oxide occurs already at temperature 700?°C and results in formation of CeVO₄ as one of the main phases. Moreover, the presence of Ba₈V₇O₂₂ as the intermediate phase was observed. The extension of reaction time and increase of temperature resulted in significant changes in the microstructure and chemical composition of the reactive layer. The incorporation of vanadium into yttrium doped BaCeO₃ structure for inner parts of the synthesized materials was postulated based on the modification of the materials electrical properties and chemical stability towards CO₂ and H₂O. Also, the presence of additional phase in the intergranular voids of doped-BaCeO₃ was suggested.     

Human Antibody Domains and Fragments Targeting Neutrophil Elastase as Candidate Therapeutics for Cancer and Inflammation-Related Diseases

Neutrophil elastase (NE) is a serine protease released during neutrophil maturation. High levels of NE are related to lung tissue damage and poor prognosis in cancer; thus, NE is a potential target for therapeutic immunotherapy for multiple lung diseases and cancers. Here, we isolate and characterize two high-affinity, specific, and noncompetitive anti-NE antibodies Fab 1C10 and V_H 1D1.43 from two large phage-displayed human Fab and V_H libraries. After fusion with human IgG1 Fc, both of them (V_H-Fc 1D1.43 and IgG1 1C10) inhibit NE enzymatic activity with V_H-Fc 1D1.43 showing comparable inhibitory effects to that of the small molecule NE inhibitor SPCK and IgG1 1C10 exhibiting even higher (2.6-fold) activity than SPCK. Their epitopes, as mapped by peptide arrays combined with structural modeling, indicate different mechanisms for blocking NE activity. Both V_H-Fc and IgG1 antibodies block NE uptake by cancer cells and fibroblast differentiation. V_H-Fc 1D1.43 and IgG1 1C10 are promising for the antibody-based immunotherapy of cancer and inflammatory diseases.     

SO2 and NO removal from flue gas over V2O5/AC at lower temperatures — role of V2O5 on SO2 removal

Supporting V₂O₅ onto an activated coke (AC) has been reported to significantly increase the AC's activity in simultaneous SO₂ and NO removal from flue gas. To understand the role of V₂O₅ on SO₂ removal, V₂O₅/AC is studied through SO₂ removal reaction, surface analysis, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) techniques. It is found that the main role of V₂O₅ in SO₂ removal over V₂O₅/AC is to catalyze SO₂ oxidation through a VOSO₄-like intermediate species, which reacts with O₂ to form SO₃ and V₂O₅. The SO₃ formed transfers from the V sites to AC sites and then reacts with H₂O to form H₂SO₄. At low V₂O₅ loadings, a V atom is able to catalyze as many as 8 SO₂ molecules to SO₃. At high V₂O₅ loadings, however, the number of SO₂ molecules catalyzed by a V atom is much less, due possibly to excessive amounts of V₂O₅ sites in comparison to the pores available for SO₃ and H₂SO₄ storage.     

Product of dissolution of V2O5 in the choline chloride–urea deep eutectic solvent

The previously reported high solubility data for V₂O₅ in the deep eutectic solvent of choline chloride and urea (ChCl–urea) is the result of forming [H₂V₁₀O₂₈]^4 − complex anion.Storing this as-prepared solution for about three months at 20 °C, a new compound, [(CH₃)₃N(CH₂)₂OH]₄[H₂V₁₀O₂₈]·2(NH₂)₂CO (1), was obtained. The solid-state structure is assembled of dihydrogendecavanadate(V) anions, choline cations and molecules of urea. The crystal structure is further stabilized by electrostatic interactions and by O–H⋯O and N–H⋯O hydrogen bonds. The ⁵¹V NMR spectroscopy detected the decavanadate anion in the as-prepared solution.     

Hydrothermal synthesis and characterization of a novel two-dimensional framework materials constructed from the polyoxometalates and coordination groups: [As8IIIV14IVO42(CO3)][Cu(en)2]3·10H2O

A new compound [As₈^IIIV₁₄^IVO₄₂(CO₃)][Cu(en)₂]₃·10H₂O (1) has been synthesized from V₂O₅,As₂O₃,CuCl₂·2H₂O, en and H₂C₂O₄·2H₂O in aqueous solution using the hydrothermal method and characterized by single-crystal X-ray diffraction analysis. X-ray crystallography reveals that 1 is a novel two-dimensional framework material constructed from the mixed As/V polyoxometalates and coordination groups.     

Highly hydroxylated carbon fibres as electrode materials of all-vanadium redox flow battery

A highly effective hydroxylated-functionalization of carbon fibres for use as electrodes of all-vanadium redox flow battery (VRFB) was developed. Carbon paper made of carbon fibres was hydroxylated ultrasonically with mixed acids (H₂SO₄/HNO₃, V_H2SO4/V_HNO3 = 3/1) in a Teflon-lined stainless steel autoclave for different time at 80 °C. The structure, composition, and electrochemical properties of the treated samples for positive and negative electrodes of VRFB were characterized with Fourier transformation infrared spectroscopy, thermogravimetric analysis, X-ray photoelectron spectrometry, scanning electron microscopy, X-ray diffraction, cyclic voltammetry, electrochemical impedance spectroscopy, and cell charge and discharge tests. The content of hydroxyl group changes from 3.8% for the untreated sample to 14.3% for the carbon paper treated in mixed acids for 10 h. The highly hydroxylated sample shows its high activity toward the redox reactions of V(II)/V(III) and V(IV)/V(V). The VRFB using the carbon paper treated for 8 h as the electrodes exhibits excellent performance under a current density of 10 mA cm⁻². The average voltage efficiency reaches 91.3%, and the average energy efficiency reaches 75.1%. The mechanisms for the high hydroxylation of the carbon fibres with the mixed acids and the high activity of the treated sample toward the vanadium redoxs are discussed.     

Hydrothermal synthesis,crystal structure and fluorescent properties of a novel 1D polymer: VO2(C7H3O4N)Ag(C10H8N2)·H2O

The hydrothermal synthesis of V₂O₅, AgNO₃, pyridine-2,6-dicarboxylic acid (H₂pdc) and 2,2′-bipyridine (bpy) in water at 160 °C for 4 days yields a novel 1D coordination polymer VO₂(C₇H₃O₄N)Ag(C₁₀H₈N₂)·H₂O (1). Each V center chelates to a tridentate ligand pdc^2? and coordinates to two O atoms, while the square based pyramid conformation of Ag center consists of three O atoms and a bpy molecular. V and Ag polyhedra alternate by either carboxyl or oxo bridges to further form a unique 3d–4d heterometal-based 1D double-chain ribbon.     

Facile hydrothermal synthesis of vanadium oxides nanobelts by ethanol reduction of peroxovanadium complexes

V₃O₇·H₂O and VO₂(B) nanobelts were successfully synthesized by a one-pot hydrothermal approach using peroxovanadium (V) complexes, ethanol and water as the starting materials. Some parameters, such as the ratio of ethanol/water, the reaction temperature and the reaction time, were briefly discussed to reveal the formation of vanadium oxides nanobelts. It was found that the ethanol was oxidized to aldehyde confirmed by the silver mirror reaction and gas chromatography. V₃O₇·H₂O and VO₂(B) nanobelts could be selectively synthesized by controlling the quantity of ethanol. The possible formation mechanism of the synthesis of vanadium oxides nanobelts was proposed. The electrochemical properties of V₃O₇·H₂O and VO₂(B) nanobelts were studied, and they exhibited a high initial discharge capacity of 350 mAh/g and 190 mAh/g, respectively. VO₂(M) nanobelts were prepared by the irreversible transformation of VO₂(B) nanobelts at 700 °C for 2 h under the inert atmosphere. The phase transition properties of VO₂(M) nanobelts were investigated by DSC and variable-temperature IR, which revealed that the as-obtained VO₂(M) nanobelts could be applied to the optical switching devices.     

Homogeneous catalysts of redox reactions based on heteropoly acid solutions. II. Synthesis of catalyst for pilot industrial production of methylethylketone

The homogeneous catalyst used in the 2005–2006 scale-up of the oxidation of n-butylenes into methylethylketone to the industrial level is a chloride-free aqueous solution of palladium complexes in a modified 0.25 M solution of Mo-V-P heteropoly acid with the molecular formula H₁₂P₃Mo₁₈V₇O₈₅ (HPA-7′). Its advantages are increased oxidative capacity in the primary oxidation of n-C₄H₈ and increased thermal stability, which allows quick catalyst regeneration with atmospheric oxygen at 160–170°C. The paper describes the preparation of a pilot lot of the catalyst with a total volume of 50 L; the starting substances were V₂O₅, MoO₃, and H₃PO₄. The key point of the synthesis was dissolving V₂O₅ while stirring in a dilute and cooled H₂O₂ solution. This formed V(V) peroxide complexes, which decompose at elevated temperature to give a 0.0175 M H₆V₁₀O₂₈ solution. This solution was stabilized by adding a calculated amount of H₃PO₄ to give a more stable 0.0125 M H₉PV₁₄O₄₂ solution. Since the H₉PV₁₄O₄₂ solution occupied a large volume, its synthesis was performed three times in a 300-L reactor. In the main 500-L reactor, MoO₃ was dissolved in water with stirring, while adding the remaining portion of H₃PO₄. The resulting mixture was evaporated, gradually introducing all of the previously obtained portions of the dilute H₉PV₁₄O₄₂ solution. The resulting HPA-7′ solution was evaporated to ～100 L and filtered twice, separating the insignificant amount of the precipitate. The filtered solution was again evaporated to 50 L, and a calculated amount of PdCl₂ was added to it while stirring at 70–80°C. A total of 27 lots of the (Pd + 0.25 M HPA-7′) catalyst with a total volume of 1350 L were obtained. All apparatuses of the pilot industrial unit for MEK synthesis were filled with this catalyst.