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Plants often adapt to adverse or stress conditions via differential growth. The trans-Golgi Network (TGN) has been implicated in stress responses, but it is not clear in what capacity it mediates adaptive growth decisions. In this study, we assess the role of the TGN in stress responses by exploring the interactome of the Transport Protein Particle II (TRAPPII) complex, required for TGN structure and function. Together with yeast-two-hybrid screens, this identified shaggy-like kinases (GSK3/AtSKs) as TRAPPII interactors. Kinase assays and pharmacological inhibition providedin vitroandin vivoevidence that AtSKs target the TRAPPII-specific subunit AtTRS120. We identified three GSK3/AtSK phosphorylation sites in AtTRS120. These sites were mutated, and the resulting AtTRS120 phosphovariants subjected to a variety of single and multiple stress conditions. The non-phosphorylatable TRS120 mutant exhibited enhanced adaptation to multiple stress conditions and to osmotic stress whereas the phosphomimetic version was less resilient. This suggests that the TRAPPII phosphostatus mediates adaptive responses to abiotic stress factors. AtSKs are multitaskers that integrate a broad range of signals. Similarly, the TRAPPII interactome is vast and considerably enriched in signaling components. An AtSK-TRAPPII interaction would integrate all levels of cellular organization and instruct the TGN, a central and highly discriminate cellular hub, as to how to mobilize and allocate resources to optimize growth and survival under limiting or adverse conditions.

Supplementary Figure 1. Standard curves for quantification of cellular integrin expression; Supplementary Figure 2. Competition binding to U87MG tumor cell surface integrins; Supplementary Figure 3. Inhibition of tumor cell proliferation. U87MG, A2780 and MB-468 cells were incubated with varying concentrations of 2.5F-Fc-MMAF, and CTRL-Fc-MMAF;Supplementary Figure 4. Growth inhibition of subcutaneous U87MG tumors implanted into Nu/Nu mice; Supplementary Figure 5. Weight monitoring.

N-Chloroamines have recently seen interest as substrates for atom-transfer radical addition (ATRA) reactions with olefins, to form β-chloroamine products, with complete atom incorporation. We report the development of a fully continuous method for N-chloroamine formation and photochemical reaction, utilizing membrane separation to purify the reactive intermediate species. Through detailed reaction optimization, supported by computational studies, we have determined that this type of reaction can be activated by direct substrate irradiation or via a range of triplet sensitizers at different wavelengths (up to 540 nm), allowing access to more favorable and sustainable reaction conditions. A number of substrates were reacted under sensitized or unsensitized conditions and the longer-term stability of the process was demonstrated in a 4.5 h experiment, achieving 94% yield and a throughput of 21.2 g h−1. This study serves to bring N-chloroamines to the fore as ATRA substrates, for implementation in efficient and sustainable synthetic routes.

A procedure for the continuous flow generation of thiomorpholine in a two-step telescoped format was developed. The key step was the photochemical thiol-ene reaction of cysteamine hydrochloride and vinyl chloride as low-cost starting materials. This reaction could be conducted under highly concentrated (4 M) conditions using a low amount (0.1-0.5 mol %) of 9-fluorenone as the photocatalyst, leading to the corresponding half-mustard intermediate in quantitative yield. Thiomorpholine was subsequently obtained by base-mediated cyclization. The robustness of the process was demonstrated by performing the reaction for 7 h (40 min overall residence time), isolating the desired thiomorpholine via distillation.

Whilst allowing for easy access to synthetically versatile motifs and for modification of bioactive molecules, the chemoselective benzylic oxidation reactions of functionalized alkyl arenes remain challenging. Reported in this study is a new non-heme Mn catalyst stabilized by a bipiperidine-based tetradentate ligand, which enables methylene oxidation of benzylic compounds by H

Supramolecular systems hold great potential as ferroelectric materials because they are easy to prepare and do not require toxic and environmentally damaging elements. However, directing the self-assembly process of a supramolecular array to yield polarizable solids is still challenging. Here, we describe induced ferroelectricity in a supramolecular framework of metal-organic cages that are supported by a flexible tripodal ligand (NHCH2 -(3-Py))3 PO (TPPA). Ferroelectric responses on the discrete cage [Cu6 (H2 O)12 (TPPA)8 ](NO3 )12 ⋅ 45H2 O (1) and its 2D-connected framework [{Cu6 Cl4 (H2 O)6 (TPPA)8 }(NO3 )8 ⋅ 60H2 O]n (2) yielded well-resolved rectangular hysteresis loops at room temperature with remnant polarization values of 27.27 and 29.09 μC/cm2 , respectively. Thermal hysteresis measurements (THM) and capacitance-voltage (C-V) plots further corroborate the ferroelectric behavior in these compounds. The polarization in them is due to the displacements of solvated molecules and nitrate ions in the pockets of these frameworks.

Although continuous flow technology can facilitate the scale-up of photochemical processes it is not yet routinely implemented on production scale in the fine chemical industries. This can be attri...

Agitation, which comprises verbal or physical aggression and hyperactivity, is one of the most frequent neuropsychiatric symptoms observed in patients with Alzheimer's disease (AD). It often co-occurs with dysregulated circadian rhythms. Current medications are associated with serious adverse effects, and novel therapeutics are therefore needed. Rodent models can be instrumental to provide a first signal for potential efficacy of novel drug candidates. Longitudinal data assessing the face validity of such models for AD-related agitation are largely missing. We employed telemeterized APPswe mice, a frequently used AD transgenic mouse line overexpressing the human beta-amyloid precursor protein (APP) with the Swedish KM670/671NL mutation, to study the occurrence and progression of changes in reactive aggressive behavior as well as the circadian profile of locomotor activity and body temperature. Analysis was conducted between 5 and 11 months of age, at regular 2-months intervals. The aggressivity of all mice was highest at 5 months and waned with increasing age. APPswe mice were more aggressive than WT at 5 and 7 months of age. The locomotor activity and body temperature of WT mice declined with increasing age, while that of APPswe mice remained rather constant. This genotype difference was solely evident during the active, dark phase. APPswe mice did not display a phase shift of their circadian rhythms. We conclude that the APPswe mouse line can recapitulate some of the behavioral disturbances observed in AD, including an agitation-relevant phenotype characterized by active phase hyperactivity and aggressivity. It does not recapitulate the nighttime disturbances (also characterized by hyperactivity) and the shift of circadian rhythms observed in AD patients. Therefore, the APPswe strain could be used at specific ages to model a subset of agitation-relevant behavioral problems and to test the modulatory effects of drugs.

The covalent coupling of porphine molecules on Au(111) is studied by scanning probe microscopy experiments and density functional theory. At sufficient temperatures, dehydrogenative C–C coupling of...

Recent advances in cell-free protein synthesis have enabled the folding and assembly of full-length antibodies at high titers with extracts from prokaryotic cells. Coupled with the facile engineering of the E. coli translation machinery, E. coli based in vitro protein synthesis reactions have emerged as a leading source of IgG molecules with non-natural amino acids incorporated at specific locations for producing homogeneous antibody drug conjugates. While this has been demonstrated with extract produced in batch fermentation mode, continuous extract fermentation would facilitate supplying material for large-scale manufacturing of protein therapeutics. To accomplish this, the IgG-folding chaperones DsbC and FkpA, and orthogonal tRNA for non-natural amino acid production were integrated onto the chromosome with high strength constitutive promoters. This enabled co-expression of all three factors at a consistently high level in the extract strain for the duration of a five-day continuous fermentation. Cell-free protein synthesis reactions with extract produced from cells grown continuously yielded titers of IgG containing non-natural amino acids above those from extract produced in batch fermentations. In addition, the quality of the synthesized IgGs and the potency of ADC produced with continuously fermented extract were indistinguishable from those produced with batch extract. These experiments demonstrate that continuous fermentation of E. coli to produce extract for cell-free protein synthesis is feasible and helps unlock the potential for cell-free protein synthesis as a platform for biopharmaceutical production.

A simple reordering of the reaction sequence allowed the improved synthesis of EIDD‐2801, an antiviral drug with promising activity against the SARS‐CoV‐2 virus, starting from uridine. Compared to the original route, the yield was enhanced from 17 % to 61 %, and fewer isolation/purification steps were needed. In addition, a continuous flow procedure for the final acetonide deprotection was developed, which proved to be favorable toward selectivity and reproducibility., An improved protocol was developed for the synthesis of EIDD‐2801, which is currently in Phase II clinical trials for the treatment of COVID‐19. The process employs uridine as starting material and proceeds through triazolation, one‐pot acetonide protection/esterification and telescoped hydroxyamination/continuous flow acetonide deprotection.John Wiley & Sons, Ltd.

A simple reordering of the reaction sequence allowed the improved synthesis of EIDD-2801, an antiviral with promising activity against the SARS-CoV-2 virus, starting from uridine. Compared to the original route, the yield was enhanced from 17% to 61%, and fewer isolation/purification steps were needed. In addition, a continuous flow procedure for the final acetonide deprotection was developed, which proved to be favorable toward selectivity and reproducibility.

A large-pore version of Mg-CUK-1, a water-stable metal-organic framework (MOF) with 1-D channels, was synthesized in basic water. Mg-CUK-1L has a BET surface area of 2896 m2 g-1 and shows stark selectivity for CO2 sorption over N2, O2, H2, and CH4. It displays reversible, multistep gated sorption of CO2 below 0.33 atm. The dehydrated single-crystal structure of Mg-CUK-1L confirms retention of the open-channel structure. The MOF can be loaded with organic molecules by immersion in hot melts, providing single crystals suitable for X-ray diffraction. trans-Azobenzene fills the channels in a 2 × 2 arrangement. Solid-state UV-vis spectroscopy reveals that azobenzene molecules undergo reversible trans-cis isomerization, despite being close-packed; this surprising result is confirmed by DFT-simulated UV-vis spectra.

Designing molecular crystals with switchable dipoles for ferroelectric applications is challenging and often serendipitous. Herein, we show a systematic approach toward hierarchical 1D, 2D and 3D frameworks that are assembled through successive linkage of metal-organic cages [Cu6 (H2 O)12 (TPTA)8 ]12+ with chloride ions. Their ferroelectric properties are due to the displacement of channel-bound nitrate counterions and solvated water molecules relative to the framework of cages. Ferroelectric measurements of crystals of discrete and 1D-framework assemblies showed axial ferroelectric anisotropy with high remnant polarisation. Both, the reversible formation of cage-connected networks and the observation of ferroelectric anisotropic behaviour are rare among metal-ligand cage assemblies.

Keggin-type polyoxometalates (POM) immobilized on alkylaminophosphazene (RPN)-functionalized silica (POM/RPN-SiO2) are new effective single-site solid catalysts for oxidative desulfurization (ODS) of diesel fuel under mild conditions in a biphasic system composed of a benzothiophene-containing model diesel fuel (heptane) and aqueous 30% H2O2. The catalytic activity of POM/RPN-SiO2 was found to be influenced by the choice of POM and the amine R group in RPN, decreasing in the order PMo > PW > SiW and Bz > iBu > iPr, respectively. The most effective catalyst, PMo/BzPN-SiO2 (PMo = PMo12O403−), exhibited 100% removal of dibenzothiophene from model diesel fuel at 60 °C and ambient pressure and could be reused without loss of activity. This catalyst outperforms other recently reported heterogeneous catalysts for ODS in similar systems. 13C, 29Si and 31P MAS NMR, FTIR, SEM, BET and elemental analysis were used to characterize the structure of surface phosphazene and POM species in the new catalysts.

PCM-101 is a phosphine coordination material comprised of tris(p-carboxylato)triphenylphosphine and secondary pillaring groups coordinated to [M3 (OH)]5+ nodes (M=Co, Ni). PCM-101 has a unique topology in which R3 P: sites are arranged directly trans to one another, with a P⋅⋅⋅P separation distance dictated by the pillars. Post-synthetic coordination of soft metals to the P: sites proceeds at room temperature to provide X-ray quality crystals that permit full structural resolution. Addition of AuCl groups forces a large distortion of the parent framework. In contrast, CuBr undergoes insertion directly between the trans-P sites to form dimers that mimic solution-phase complexes, but that are geometrically strained due to steric pressure exerted by the MOF scaffold. The metalated materials are active in heterogeneous hydroaddition catalysis under mild conditions, yielding different major products compared to their molecular counterparts.

Two isostructural lanthanide-based metal - organic frameworks, {[Ln(C16H12N2O4)(CHO2)(OH2)·2(C5H11NO)]}n, Ln = Yb (1) and Tm (2), and a cadmium(II) coordination polymer,{[Cd2(C16H12N2O4)(NO3)·4(C3H7NO)]}n, were synthesized by the combination of the respective metal nitrate and 2,2′-diamino-trans 4,4′-stilbenedicarboxylate (C16H12N2O4) under solvothermal conditions [C5H11NO = diethylformamide and C3H7NO = dimethylformamide]. Their structures were determined by X-ray single crystal analysis, X-ray powder diffraction, Fourier transformed infrared spectroscopy, elemental analysis, thermogravimetric analysis and solid state photoluminescence spectroscopy. Both lanthanide structures are infinite three-dimensional non-penetrating networks with extremely large diamond shape accessible channels of cross-sectional dimensions [30 A x 12 A] and with the amino-functional groups projecting into the channels. The cadmium-based structure is a one-dimensional coordination polymer with both the carboxylate and the amino groups coordinating the cadmium atoms, which resulted in a large increase in the rigidity of the ligand. Ligand-based fluorescence was exhibited by all three networks, with the cadmium based structure showing the highest intensity and longest fluorescence radiative lifetime.

Diethylamine is the smallest and simplest molecule that features a supramolecular helix as its lowest energy aggregate. Structural studies and large scale sampling simulations show that the helical arrangement is more stable than cyclic structures, which are the dominant species for other small hydrogen bonding molecules.

Malaria, one of the most common vector borne human diseases, is a major world health issue. In 2015 alone, more than 200 million people were infected with malaria, out of which, 429 000 died. Even though artemisinin-based combination therapies (ACT) are highly effective at treating malaria infections, novel efforts toward development of vaccines to prevent transmission are still needed. Pfs25, a postfertilization stage parasite surface antigen, is a leading transmission-blocking vaccine (TBV) candidate. It is postulated that Pfs25 anchors to the cell membrane using a glycosylphosphatidylinositol (GPI) linker, which itself possesses pro-inflammatory properties. In this study, Escherichia coli derived extract (XtractCF+TM) was used in cell free protein synthesis [CFPS] to successfully express >200 mg/L of recombinant Pfs25 with a C-terminal non-natural amino acid (nnAA), namely, p-azidomethyl phenylalanine (pAMF), which possesses a reactive azide group. Thereafter, a unique conjugate vaccine (CV), namely, Pfs25-GPI was generated with dibenzocyclooctyne (DBCO) derivatized glycan core of malaria GPI using a simple but highly efficient copper free click chemistry reaction. In mice immunized with Pfs25 or Pfs25-GPI, the Pfs25-GPI group showed significantly higher titers compared to the Pfs25 group. Moreover, only purified IgGs from Pfs25-GPI group were able to significantly block transmission of parasites to mosquitoes, as judged by a standard membrane feeding assay [SMFA]. To our knowledge, this is the first report of the generation of a CV using Pfs25 and malaria specific GPI where the GPI is shown to enhance the ability of Pfs25 to elicit transmission blocking antibodies.

Tethering complexes mediate the initial, specific contact between donor and acceptor membranes. This review focuses on the modularity and function of multisubunit tethering complexes (MTCs) in higher plants. One emphasis is on molecular interactions of plant MTCs. Here, a number of insights have been gained concerning interactions between different tethering complexes, and between tethers and microtubule-associated proteins. The roles of tethering complexes in abiotic stress responses appear indirect, but in the context of biotic stress responses it has been suggested that some tethers are direct targets of pathogen effectors or virulence factors. In light of the central roles tethering complexes play in plant development, an emerging concept is that tethers may be co-opted for plant adaptive responses.

Amber codon suppression for the insertion of non-natural amino acids (nnAAs) is limited by competition with release factor 1 (RF1). Here we describe the genome engineering of a RF1 mutant strain that enhances suppression efficiency during cell-free protein synthesis, without significantly impacting cell growth during biomass production. Specifically, an out membrane protease (OmpT) cleavage site was engineered into the switch loop of RF1, which enables its conditional inactivation during cell lysis. This facilitates extract production without additional processing steps, resulting in a scaleable extract production process. The RF1 mutant extract allows nnAA incorporation at previously intractable sites of an IgG1 and at multiple sites in the same polypeptide chain. Conjugation of cytotoxic agents to these nnAAs, yields homogeneous antibody drug conjugates (ADCs) that can be optimized for conjugation site, drug to antibody ratio (DAR) and linker-warheads designed for efficient tumor killing. This platform provides the means to generate therapeutic ADCs inaccessible by other methods that are efficient in their cytotoxin delivery to tumor with reduced dose-limiting toxicities and thus have the potential for better clinical impact.

Supramolecular ferroelectrics have emerged as an exciting topic of research for both fundamental understanding and practical applications in the areas of energy and electronics. Here, we describe the synthesis of two metallo-cavitands [{M4L8(H2O)8}⊃9(H2O)]·(NO3)8·x(H2O) [MNi2+ (1) or Co2+ (2)] and demonstrate solid-state host–guest behavior and ferroelectricity in the presence of various hydrated alkali metal cations (Hy-A) in their intrinsic voids. Due to the confinement effects of the cavitands, the degree of hydration observed for these alkali metal ions is on the upper side; in particular, the K+, Rb+ and Cs+ ions show high hydration numbers of 8, 9 and 10, respectively. Ferroelectric studies on 1, [Hy-A]⊂1 and [Hy-A]⊂2 assemblies show remnant polarization (Pr) values ranging from 27 to 30 μC cm−2 with concomitant variations in the coercive field (Ec) values at a lower frequency of 0.1 Hz. The observed features for the P–E loop characteristics of all the assemblies are reminiscent of triglycine sulphate (TGS) and certain other supramolecular ferroelectrics. Interestingly, ferroelectric fatigue measurements on all these systems show sizable variations as the cavitands with hard Li+ ions exhibiting the maximum (fatigue) tolerance and the ones with higher polarizable Cs+ ions show a reduction in Pr values up to 35%, after 105 switching cycles. The results signify the effect of encapsulated guest molecules in altering the polarization attributes (Pr, Ec and fatigue tolerance) via host–guest interactions.

Transport Protein Particle II (TRAPPII) is essential for exocytosis, endocytosis, protein sorting and cytokinesis. In spite of a considerable understanding of its biological role, little information is known about Arabidopsis TRAPPII complex topology and molecular function. In this study, independent proteomic approaches initiated with TRAPP components or Rab-A GTPase variants converge on the TRAPPII complex. We show that the Arabidopsis genome encodes the full complement of 13 TRAPPC subunits, including four previously unidentified components. A dimerization model is proposed to account for binary interactions between TRAPPII subunits. Preferential binding to dominant negative (GDP-bound) versus wild-type or constitutively active (GTP-bound) RAB-A2a variants discriminates between TRAPPII and TRAPPIII subunits and shows that Arabidopsis complexes differ from yeast but resemble metazoan TRAPP complexes. Analyzes of Rab-A mutant variants in trappii backgrounds provide genetic evidence that TRAPPII functions upstream of RAB-A2a, allowing us to propose that TRAPPII is likely to behave as a guanine nucleotide exchange factor (GEF) for the RAB-A2a GTPase. GEFs catalyze exchange of GDP for GTP; the GTP-bound, activated, Rab then recruits a diverse local network of Rab effectors to specify membrane identity in subsequent vesicle fusion events. Understanding GEF-Rab interactions will be crucial to unravel the co-ordination of plant membrane traffic.

Trimethylaluminum finds widespread applications in chemical and materials synthesis, most prominently in its partially hydrolyzed form of methylalumoxane (MAO), which is used as a cocatalyst in the polymerization of olefins. This work investigates the sequential reactions of trimethylaluminum with hexaprotic phosphazenes (RNH)6P3N3 (=XH6) equipped with substituents R of varied steric bulk including tert-butyl (1H6), cyclohexyl (2H6), isopropyl (3H6), isobutyl (4H6), ethyl (5H6), propyl (6H6), methyl (7H6), and benzyl (8H6). Similar to MAO, the resulting complexes of polyanionic phosphazenates [XH n] n-6 accommodate multinuclear arrays of [AlMe2]+ and [AlMe]2+. Reactions were monitored by 31P NMR spectroscopy, and structures were determined by single-crystal X-ray diffraction. They included 1H4(AlMe2)2, 1H3(AlMe2)3, 2H3(AlMe2)3, 3(AlMe2)4AlMe, 4H(AlMe2)5, 4(AlMe2)6, {5H(AlMe2)4}2AlMe, 5(AlMe2)6, 6(AlMe2)6, {7(AlMe2)4AlMe}2, and 8(AlMe2)6. The study shows that subtle variations of the steric properties of the R groups influence the reaction pathways, levels of aggregation, and fluxional behavior. While [AlMe2]+ is the primary product of the metalation, [AlMe]2+ is utilized to alleviate overcrowding or to aid aggregation. At the later stages of metalation, [AlMe2]+ groups start to scramble around congested sites. The ligands proved to be very robust and extremely flexible, offering a unique platform to study complex multinuclear metal arrangements.

Nach dem Beschluss des Gemeinsamen Bundesausschusses (G-BA) vom 17.12.2015 wird das gesetzliche Qualitatssicherungsverfahren zum 1.1.2017 mit der fallbezogenen Dokumentation postoperativer Wundinfektionen beginnen.

Antibody drug conjugates (ADCs) harness the target specificity of a monoclonal antibody (mAb) and the high cytotoxicity of a small molecule, enabling improved delivery of a potent antitumor agent compared to traditional chemotherapy for cancer therapy. Only two ADCs have been marketed, both of which are produced via nonsite-specific conjugation of the cytotoxic drug to either interchain cysteine (Adcetris) or lysine (Kadcyla). A growing body of evidence suggests that site-specific ADCs, because of their payload homogeneity, will improve pharmacokinetics and have wider therapeutic windows when compared to heterogeneous ADCs. Previously, we have demonstrated the use of a cell free expression system (Xpress CF+) for rapid production of site-specific ADCs. Here we report the generation of a variety of ADCs via conjugation between a site-specific incorporated non-natural amino acid (nnAA), para-azidomethyl-l-phenylalanine (pAMF), and dibenzocyclooctyl-(polyethylene glycol)4 (DBCO-(PEG)4) linked payloads using ...

Antibody–drug conjugates (ADC) have generated significant interest as targeted therapeutics for cancer treatment, demonstrating improved clinical efficacy and safety compared with systemic chemotherapy. To extend this concept to other tumor-targeting proteins, we conjugated the tubulin inhibitor monomethyl-auristatin-F (MMAF) to 2.5F–Fc, a fusion protein composed of a human Fc domain and a cystine knot (knottin) miniprotein engineered to bind with high affinity to tumor-associated integrin receptors. The broad expression of integrins (including αvβ3, αvβ5, and α5β1) on tumor cells and their vasculature makes 2.5F-Fc an attractive tumor-targeting protein for drug delivery. We show that 2.5F-Fc can be expressed by cell-free protein synthesis, during which a non-natural amino acid was introduced into the Fc domain and subsequently used for site-specific conjugation of MMAF through a noncleavable linker. The resulting knottin–Fc–drug conjugate (KFDC), termed 2.5F-Fc-MMAF, had approximately 2 drugs attached per KFDC. 2.5F–Fc–MMAF inhibited proliferation in human glioblastoma (U87MG), ovarian (A2780), and breast (MB-468) cancer cells to a greater extent than 2.5F–Fc or MMAF alone or added in combination. As a single agent, 2.5F–Fc–MMAF was effective at inducing regression and prolonged survival in U87MG tumor xenograft models when administered at 10 mg/kg two times per week. In comparison, tumors treated with 2.5F–Fc or MMAF were nonresponsive, and treatment with a nontargeted control, CTRL–Fc–MMAF, showed a modest but not significant therapeutic effect. These studies provide proof-of-concept for further development of KFDCs as alternatives to ADCs for tumor targeting and drug delivery applications. Mol Cancer Ther; 15(6); 1291–300. ©2016 AACR.

Metal–organic frameworks (MOFs) are typically crystalline microporous materials with metal ions of usually one oxidation state (although mixed-valence MOFs have been reported) and one type of co-ordination structure. Here, a microporous mixed-valence Cu(I,II)-MOF featuring a unique network of distinct Cu(I) and Cu(II) coordination sites is prepared by solvothermal reduction of HKUST-1. Like HKUST-1, this compound is assembled solely from Cu ions and benzene 1,3,5-tricarboxylate (BTC) ligands. The new MOF exhibits dual micropore size distribution and shows superior water stability compared to HKUST-1.

Sudan virus (SUDV) and Ebola viruses (EBOV) are both members of the Ebolavirus genus and have been sources of epidemics and outbreaks for several decades. We present here the generation and characterization of cross-reactive antibodies to both SUDV and EBOV, which were produced in a cell-free system and protective against SUDV in mice. A non-human primate, cynomolgus macaque, was immunized with viral-replicon particles expressing the glycoprotein of SUDV-Boniface (8A). Two separate antibody fragment phage display libraries were constructed after four immunogen injections. Both libraries were screened first against the SUDV and a second library was cross-selected against EBOV-Kikwit. Sequencing of 288 selected clones from the two distinct libraries identified 58 clones with distinct VH and VL sequences. Many of these clones were cross-reactive to EBOV and SUDV and able to neutralize SUDV. Three of these recombinant antibodies (X10B1, X10F3, and X10H2) were produced in the scFv-Fc format utilizing a cell-free production system. Mice that were challenged with SUDV-Boniface receiving 100µg of the X10B1/X10H2 scFv-Fc combination 6 and 48-h post-exposure demonstrated partial protection individually and complete protection as a combination. The data herein suggests these antibodies may be promising candidates for further therapeutic development.

Charge-neutral chiral hosts are attractive due to their ability to recognize a wide range of guest functionalities and support enantioselective processes. However, reports on such charge-neutral cages are very scarce in the literature. Here, we report an enantiomeric pair of tetrahedral Pd(ii) cages built from chiral tris(imido)phosphate trianions and oxalate linkers, which exhibit enantioselective separation capabilities for epichlorohydrin, β-butyrolactone, and 3-methyl- and 3-ethyl cyclopentanone.

Alkylaminophosphazenes (RPN) are efficient and tuneable phase-transfer agents for environmentally benign biphasic oxidation with hydrogen peroxide catalysed by polyoxometalates (POMs). Substituent groups on the phosphazene ring can be varied to modify the phase-transfer efficiency of RPN for use in water–organic two-phase systems. Active phosphazene–polyoxometalate aggregates that self-assemble in situ from RPN and Keggin POMs, such as PMo12O403− and PW12O403−, were found to be efficient and recyclable catalysts for the oxidation of benzothiophenes and the epoxidation of alkenes with hydrogen peroxide. Lipophilic phosphazene cations present in these aggregates render the POM soluble in organic media. Catalyst activity in the biphasic oxidation with H2O2 varies with the RPN substituent alkylamino groups with respect to the solvent system used. The activity decreases in the series of POMs: PMo12O403−>PW12O403−≫SiW12O404− irrespective of the solvent system used.

Polyisobutylene (PIB) oligomer-bound amines render Keggin polyoxometalates (POM) heptane soluble, making them efficient and recyclable catalysts for environmentally benign biphasic oxidations with hydrogen peroxide. This is illustrated using both oxidative desulfurization and alkene epoxidation reactions that can be efficiently carried out in a heptane–water two-phase system occurring through facile phase transfer of POM by the amine terminated PIB oligomer.

Structural transformations of supramolecular assemblies play an important role in the synthesis of complex metal-organic materials. Nonetheless, more than often little is known of the assembly pathways that lead to the final product. Herein, we describe the conversion of cubic metal-organic polyhedra to connected-cage networks of varying topologies. The neutral cubic cage assembly of formula {Pd₃[PO(NiPr)₃]}₈(PZDC)₁₂ has been synthesized from {Pd₃[(NiPr)₃PO](OAc)₂(OH)}₂·2(CH₃)₂SO and 2,5-pyrazenedicarboxilic acid (PZDC-2H). This 42-component self-assembly is the largest known among the neutral cages with Pd(II) ions. The cage contains twenty-four vacant carboxylate O-sites at the PZDC ligands that are available for further coordination. Post-assembly reactions of the cubic cage with Fe(II) and Zn(II) ions produced cage-connected networks of dia and qtz topologies, respectively. During these reactions, the discrete cubic cage transforms into a network of tetrahedral cages that are bridged by the 3d metal-ions. The robustness of the [Pd₃{[PO(NiPr)₃}]³+ molecular building units made it possible to map the post-assembly reactions in detail, which revealed a variety of intermediate 1D and 2D cage-networks. Such step-by-step mapping of the transformation of discrete cages to cage-connected frameworks is unprecedented in the chemistry of coordination driven assemblies.

PCM-22, a metal-organic framework material comprising triphenylphosphine and Ln3+ ions (Ln = Pr–Yb), exhibits solid-state luminescence at room temperature. Mixed-metal versions of PCM-22 that contain controlled amounts of Eu3+, Gd3+, and Tb3+ function as highly sensitive, broad-scope solid-state sensors that can rapidly identify unknown solvents by providing a unique “eight-factor” fingerprint. The sensors allow for immediate solvent identification via color changes that are obvious to the naked eye and also permit quantitative chemical analysis by uncomplicated spectrophotometry. These same materials achieve quantitative detection of H2O in D2O from 10 to 120,000 ppm. The detection of trace H2O is also demonstrated in a range of common solvents, including those incompatible with conventional laboratory titration methods. A series of luminescent phosphine coordination materials show diverse sensing capabilities. These solid-state sensor materials can detect trace H2O impurities in D2O from 10 to 120,000 ppm and can rapidly identify unknown solvents.

Within Western scholarship, recent democratic theory has been dominated by notions of deliberation, compromise, and consensus. A challenge to these notions emerged out of a small but important paradigm of social and political theory, one that conceptually re-prioritized the political ideal of agon. Engaging with the contributions of political theorist Chantal Mouffe as an exemplar of agonal theory, this chapter aims to demonstrate that both the analytic foundations and normative commitments of her writings concurrently imply and depend upon a considerably more robust notion of the social than that which she utilizes. Drawing on the classical sociological perspectives of Ferdinand Tonnies and Georg Simmel, this chapter puts forth just such a robust account, suggesting a complementary vocabulary through which to explore the hitherto occluded social dimensions of agonal democratic theory.

Metal-doped polyoxotitanium cages are a developing class of inorganic compounds which can be regarded as nano- and sub-nano sized molecular relatives of metal-doped titania nanoparticles. These species can serve as models for the ways in which dopant metal ions can be incorporated into metal-doped titania (TiO2 ), a technologically important class of photocatalytic materials with broad applications in devices and pollution control. In this study a series of cobalt(II)-containing cages in the size range ca. 0.7-1.3 nm have been synthesized and structurally characterized, allowing a coherent study of the factors affecting the band gaps in well-defined metal-doped model systems. Band structure calculations are consistent with experimental UV/Vis measurements of the Tix Oy absorption edges in these species and reveal that molecular dipole moment can have a profound effect on the band gap. The observation of a dipole-induced band-gap decrease mechanism provides a potentially general design strategy for the formation of low band-gap inorganic cages.

Typically, metal–organic frameworks (MOFs) exhibit ordered micropores (