Conjugated rod-coil diblock copolymers self-assemble due to a balance of liquid crystalline (rod-rod) and enthalpic (rod-coil) interactions. Previous work has shown that while classical block copolymers self-assemble into a wide variety of nanostructures, when rod-rod interactions dominate self-assembly in rod-coil block copolymers, lamellar structures are preferred. Here, it is demonstrated that other, potentially more useful, nanostructures can be formed when these two interactions are more closely balanced. In particular, hexagonally packed polylactide (PLA) cylinders embedded in a semiconducting poly(3-alkylthiophene) (P3AT) matrix can be formed. This microstructure has been long-sought as it provides an opportunity to incorporate additional functionalities into a majority phase nanostructured conjugated polymer, for example in organic photovoltaic applications. Previous efforts to generate this phase in polythiophene-based block copolymers have failed due to the high driving force for P3AT crystallization. Here, we demonstrate that careful design of the P3AT moiety allows for a balance between crystallization and microphase separation due to chemical dissimilarity between copolymer blocks. In addition to hexagonally packed cylinders, P3AT-PLA block copolymers form nanostructures with long-range order at all block copolymer compositions. Importantly, the conjugated moiety of the P3AT-PLA block copolymers retains the crystalline packing structure and characteristic high time-of-flight charge transport of the homopolymer polythiophene (μ(h) ~10(-4) cm(2) V(-1) s(-1)) in the confined geometry of the block copolymer domains.

Development of a Plasmodium falciparum (Pf) transmission blocking vaccine (TBV) has the potential to significantly impact malaria control. Antibodies elicited against sexual stage proteins in the human bloodstream are taken up with the blood meal of the mosquitoes and inactivate parasite development in the mosquito. In a phase 1 trial, a leading TBV identified as Pfs25-EPA/Alhydrogel appeared safe and immunogenic, however, the level of Pfs25-specific antibodies were likely too low for an effective vaccine. Pfs230, a 230-kDa sexual stage protein expressed in gametocytes is an alternative vaccine candidate. A unique 6-cysteine-rich domain structure within Pfs230 have thwarted its recombinant expression and characterization for clinical evaluation for nearly a quarter of a century. Here, we report on the identification, biochemical, biophysical, and immunological characterization of recombinant Pfs230 domains. Rabbit antibodies generated against recombinant Pfs230 domains blocked mosquito transmission of a laboratory strain and two field isolates using an ex vivo assay. A planned clinical trial of the Pfs230 vaccine is a significant step toward the potential development of a transmission blocking vaccine to eliminate malaria.Development of a malaria vaccine that effectively protects against parasite infection of both the natural host, Anopheles mosquitoes, and its secondary host, man, would effectively disrupt transmission and clinical disease. The most well known investigational vaccine against Plasmodium falciparum malaria that recently received a positive scientific opinion from the Committee for Medicinal Products for Human Use of the European Medicines Agency in July 2015, is identified as RTS,S (Mosquirix TM ). This vaccine targets the circumsporozoite protein that is present on the surface of the sporozoite, the parasite stage that infects man (1). RTS,S, a virus like-particle-based vaccine, is protective against clinical disease in about 30% of the young children who participated in a phase 3 trial (1, 2).Efforts toward development of a vaccine to disrupt parasite infection of the mosquito host, also identified as a transmission blocking vaccine have to date only been able to evaluate a sexual stage-specific protein, Pfs25, 2 which is a 25-kDa protein expressed on the zygote and ookinete surfaces. A phase 1 study demonstrated that human antibodies raised against a recombinant Pfs25 (Pfs25H) protein formulated in Montanide ISA 51, a water-in-oil adjuvant formulation, were biologically active in an ex vivo feeding assay (3), however, this formulation was not deemed suitable for a public health vaccine. More recently, in preclinical studies, Pfs25H has been shown to have enhanced immunogenic properties when chemically conjugated to a carrier molecule such as Neisseria meningitis outer membrane protein complex (4), or Pseudomonas aeruginosa ExoProtein A (EPA) (5, 6). In particular, the chemically conjugated Pfs25-EPA has the biophysical features of a nanoparticle with a diameter of about 25 m in solution, simil...

Citation for published item:furkh rdtD wF nd ted D eF nd xov kD wF nd i elD eF nd o¤ %t hovskyD uF nd tell iD pF nd rirs h D eF nd r likD wF @PHIHA 9gon ept of mole ul r h rge stor ge diele tri l yer for org ni thinE(lm memory tr nsistorsF9D edv n ed m teri lsFD PP @PQAF ppF PSPSEPSPVF Further information on publisher's website:httpXGGdxFdoiForgGIHFIHHPG dm FPHIHHHHQH Publisher's copyright statement: his is the epted version of the following rti leX furkh rdtD wF nd ted D eF nd xov kD wF nd i elD eF nd o¤ %t hovskyD uF nd tell iD pF nd rirs h D eF nd r likD wF @PHIHA 9gon ept of mole ul r h rge stor ge diele tri l yer for org ni thinE(lm memory tr nsistorsF9D edv n ed m teri lsFD PP @PQAF ppF PSPSEPSPVD whi h h s een pu lished in (n l form t httpXGGdxFdoiForgGIHFIHHPG dm FPHIHHHHQHF his rti le m y e used for nonE ommer i l purposes in ord n e ith ileyE gr erms nd gonditions for selfE r hivingFAdditional information:Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. In this work we report on a novel concept of an electrically programmable selfassembled molecular gate dielectric layer for OTFTs (see figure 1a) that can be reversibly charged and discharged and retains these digital states even when the supply voltage is removed. Due to the small thickness of the dielectric stack (app. 5.7 nm), the memory transistors operate with very small program and erase voltages of ± 2 V. Despite the extremely small dielectric thickness, the retention time is already promising (~6 hours with a read voltage of -750 mV applied continuously). The dielectric is a mixed monolayer of aliphatic and C 60 -functionalized phosphonic acid molecules (app. 2.1 nm thickness) on a patterned and plasma-oxidized aluminum gate electrode on a glass substrate. The aluminum oxide (AlO x ) contributes with a thickness of 3.6 nm to the dielectric layer stack 6 . As the aliphatic component, n-octadecylphosphonic acid 1 was chosen, which has already shown excellent insulating characteristics as the gate dielectric 6 . As the charge storage component, the C 60 -derivative 2 was synthesized to take advantage of the strong acceptor properties and reversible redox behavior of C 60 (Figure 1b and Supplementary Information SI-1) and of the self-assembly properties induced by the C 18 -aliphatic tail with phosphonic acid anchor group.Mixed self-assembled monolayers of 1 and 2 were created by a simple "one pot" solution content) have a relatively small memory ratio of 2.5 (see Section I in Figure 3b), the devices

No abstract

On the way towards wide-spread flexible large-area electronics, several features are of particular interest. With focus on low-cost applications, the manufacturing requires high throughput, preferably realized by simple methods on large-area flexible substrates, for example spin coating, [1,2] inkjet-printing [3][4][5] or roll-to-roll techniques.[6] In view of mobile applications with low power consumption, complementary logic circuit designs are beneficial; these require p-channel and n-channel field-effect transistors with large, balanced mobilities and good air stability. For low-temperature-processed p-channel transistors with mobility greater than 1 cm 2

Proteins Pfs230 and Pfs48/45 are Plasmodium falciparum transmission-blocking (TB) vaccine candidates that form a membrane-bound protein complex on gametes. The biological role of Pfs230 or the Pfs230-Pfs48/45 complex remains poorly understood. Here, we present the crystal structure of recombinant Pfs230 domain 1 (Pfs230D1M), a 6-cysteine domain, in complex with the Fab fragment of a TB monoclonal antibody (mAb) 4F12. We observed the arrangement of Pfs230 on the surface of macrogametes differed from that on microgametes, and that Pfs230, with no known membrane anchor, may exist on the membrane surface in the absence of Pfs48/45. 4F12 appears to sterically interfere with Pfs230 function. Combining mAbs against different epitopes of Pfs230D1 or of Pfs230D1 and Pfs48/45, significantly increased TB activity. These studies elucidate a mechanism of action of the Pfs230D1 vaccine, model the functional activity induced by a polyclonal antibody response and support the development of TB vaccines targeting Pfs230D1 and Pfs230D1-Pfs48/45.

Transmission-blocking vaccines are based on eliciting antibody responses in the vertebrate host that disrupt parasite development in the mosquito vector and prevent malaria transmission. The surface protein Pfs47 is present in Plasmodium falciparum gametocytes and female gametes. The potential of Pfs47 as a vaccine target was evaluated. Soluble full-length recombinant protein, consisting of three domains, was expressed in E. coli as a thioredoxin fusion (T-Pfs47). The protein was immunogenic, and polyclonal and monoclonal antibodies (mAb) were obtained, but they did not confer transmission blocking activity (TBA). All fourteen mAb targeted either domains 1 or 3, but not domain 2 (D2), and immune reactivity to D2 was also very low in polyclonal mouse IgG after T-Pfs47 immunization. Disruption of the predicted disulfide bond in D2, by replacing cysteines for alanines (C230A and C260A), allowed expression of recombinant D2 protein in E. coli. A combination of mAbs targeting D2, and deletion proteins from this domain, allowed us to map a central 52 amino acid (aa) region where antibody binding confers strong TBA (78-99%). This 52 aa antigen is immunogenic and well conserved, with only seven haplotypes world-wide that share 96–98% identity. Neither human complement nor the mosquito complement-like system are required for the observed TBA. A dramatic reduction in ookinete numbers and ookinete-specific transcripts was observed, suggesting that the antibodies are interacting with female gametocytes and preventing fertilization.

fThe extended rod-like Plasmodium falciparum circumsporozoite protein (CSP) is comprised of three primary domains: a charged N terminus that binds heparan sulfate proteoglycans, a central NANP repeat domain, and a C terminus containing a thrombospondin-like type I repeat (TSR) domain. Only the last two domains are incorporated in RTS,S, the leading malaria vaccine in phase 3 trials that, to date, protects about 50% of vaccinated children against clinical disease. A seroepidemiological study indicated that the N-terminal domain might improve the efficacy of a new CSP vaccine. Using a panel of CSP-specific monoclonal antibodies, well-characterized recombinant CSPs, label-free quantitative proteomics, and in vitro inhibition of sporozoite invasion, we show that native CSP is N-terminally processed in the mosquito host and undergoes a reversible conformational change to mask some epitopes in the N-and C-terminal domains until the sporozoite interacts with the liver hepatocyte. Our findings show the importance of understanding processing and the biophysical change in conformation, possibly due to a mechanical or molecular signal, and may aid in the development of a new CSP vaccine.T he development of a vaccine to aid in the control of malaria is critical, as Plasmodium falciparum has evolved resistance to all antimalarial drugs deployed so far, including artemisinin (1). The leading malaria vaccine (RTS,S), currently in phase 3 trials, contains a formulated virus-like particle that encompasses the central and carboxyl-terminal domains of the circumsporozoite protein (CSP) fused to the hepatitis B virus surface antigen (2) and protects approximately 30% to 50% of infants or children from clinical disease for a limited duration (3, 4). Naturally derived human antibodies against a portion of the N-terminal region, including region 1, are associated with a reduced risk of disease (5), providing a basis to design new CSP vaccines. This N-terminal region of the CSP is absent from RTS,S.The importance of understanding protein structure because of its impact on the induction of broadly neutralizing antibodies and subsequent vaccine design continues to be revealed in the HIV arena (6, 7). In malaria, the importance of protein conformation for the induction of neutralizing antibodies was recently shown in vivo for an orthologue of the leading asexual-stage malaria vaccine antigen apical membrane antigen-1 (AMA-1). Only a recombinant AMA-1 forming a stable complex with a constrained synthetic rhoptry neck protein-2 peptide induced protective antibodies in vivo against a lethal blood-stage challenge malaria parasite infection (8). When developing a novel CSP vaccine, these more recent developments need to be considered with regard to the potential for changes within the CSP, such as through in vivo processing or conformational changes (9, 10) in a protein with a known extended rod-like structure (11), that could mask the adhesion domains located at the N-and C-terminal domains (9).To address these questions, a panel of CSP-speci...