Materials science and genetic engineering have joined forces over the last three decades in the development of so-called protein-based polymers. These are proteins, typically with repetitive amino ...acid sequences, that have such physical properties that they can be used as functional materials. Well-known natural examples are collagen, silk, and elastin, but also artificial sequences have been devised. These proteins can be produced in a suitable host via recombinant DNA technology, and it is this inherent control over monomer sequence and molecular size that renders this class of polymers of particular interest to the fields of nanomaterials and biomedical research. Traditionally, Escherichia coli has been the main workhorse for the production of these polymers, but the methylotrophic yeast Pichia pastoris is finding increased use in view of the often high yields and potential bioprocessing benefits. We here provide an overview of protein-based polymers produced in P. pastoris. We summarize their physicochemical properties, briefly note possible applications, and detail their biosynthesis. Some challenges that may be faced when using P. pastoris for polymer production are identified: (i) low yields and poor process control in shake flask cultures; i.e., the need for bioreactors, (ii) proteolytic degradation, and (iii) self-assembly in vivo. Strategies to overcome these challenges are discussed, which we anticipate will be of interest also to readers involved in protein expression in P. pastoris in general.
Electron-electron interactions can render an otherwise conducting material insulating, with the insulator-metal phase transition in correlated-electron materials being the canonical macroscopic ...manifestation of the competition between charge-carrier itinerancy and localization. The transition can arise from underlying microscopic interactions among the charge, lattice, orbital and spin degrees of freedom, the complexity of which leads to multiple phase-transition pathways. For example, in many transition metal oxides, the insulator-metal transition has been achieved with external stimuli, including temperature, light, electric field, mechanical strain or magnetic field. Vanadium dioxide is particularly intriguing because both the lattice and on-site Coulomb repulsion contribute to the insulator-to-metal transition at 340 K (ref. 8). Thus, although the precise microscopic origin of the phase transition remains elusive, vanadium dioxide serves as a testbed for correlated-electron phase-transition dynamics. Here we report the observation of an insulator-metal transition in vanadium dioxide induced by a terahertz electric field. This is achieved using metamaterial-enhanced picosecond, high-field terahertz pulses to reduce the Coulomb-induced potential barrier for carrier transport. A nonlinear metamaterial response is observed through the phase transition, demonstrating that high-field terahertz pulses provide alternative pathways to induce collective electronic and structural rearrangements. The metamaterial resonators play a dual role, providing sub-wavelength field enhancement that locally drives the nonlinear response, and global sensitivity to the local changes, thereby enabling macroscopic observation of the dynamics. This methodology provides a powerful platform to investigate low-energy dynamics in condensed matter and, further, demonstrates that integration of metamaterials with complex matter is a viable pathway to realize functional nonlinear electromagnetic composites.
This paper is both a review of some recent developments in the utilization of magnetism for applications to logic and memory and a description of some new innovations in nanomagnetics and ...spintronics. Nanomagnetics is primarily based on the magnetic interactions, while spintronics is primarily concerned with devices that utilize spin polarized currents. With the end of complementary metal-oxide-semiconductor (CMOS) in sight, nanomagnetics can provide a new paradigm for information process using the principles of magnetic quantum cellular automata (MQCA). This paper will review and describe these principles and then introduce a new nonlithographic method of producing reconfigurable arrays of MQCAs and/or storage bits that can be configured electrically. Furthermore, this paper will provide a brief description of magnetoresistive random access memory (MRAM), the first mainstream spintronic nonvolatile random access memory and project how far its successor spin transfer torque random access memory (STT-RAM) can go to provide a truly universal memory that can in principle replace most, if not all, semiconductor memories in the near future. For completeness, a description of an all-metal logic architecture based on magnetoresistive structures (transpinnor) will be described as well as some approaches to logic using magnetic tunnel junctions (MTJs).
CoFe2O4 (CFO)–BiFeO3 (BFO) nanocomposites are an intriguing option for future memory and logic technologies due to the magnetoelectric properties of the system. However, these nanocomposites form ...with CFO pillars randomly located within a BFO matrix, making implementation in devices difficult. To overcome this, we present a technique to produce patterned nanocomposites through self-assembly. CFO islands are patterned on Nb-doped SrTiO3 to direct the self-assembly of epitaxial CFO–BFO nanocomposites, producing square arrays of CFO pillars.
The disease-causing blood-stage of the Plasmodium falciparum lifecycle begins with invasion of human erythrocytes by merozoites. Many vaccine candidates with key roles in binding to the erythrocyte ...surface and entry are secreted from the large bulb-like rhoptry organelles at the apical tip of the merozoite. Here we identify an essential role for the conserved protein P. falciparum Cytosolically Exposed Rhoptry Leaflet Interacting protein 1 (PfCERLI1) in rhoptry function. We show that PfCERLI1 localises to the cytosolic face of the rhoptry bulb membrane and knockdown of PfCERLI1 inhibits merozoite invasion. While schizogony and merozoite organelle biogenesis appear normal, biochemical techniques and semi-quantitative super-resolution microscopy show that PfCERLI1 knockdown prevents secretion of key rhoptry antigens that coordinate merozoite invasion. PfCERLI1 is a rhoptry associated protein identified to have a direct role in function of this essential merozoite invasion organelle, which has broader implications for understanding apicomplexan invasion biology.
We studied shear-induced fracture and self-healing of well-defined transient polymer networks formed by telechelic polypeptides, with nodes formed by collagen-like triple helices. When these gels are ...sheared at a rate that is higher than the inverse relaxation time of the nodes, fracture occurs at a critical stress which increases logarithmically with increasing shear rate. When a constant stress is applied, fracture occurs after a delay time that decreases exponentially with increasing stress. These observations indicate that fracture in these systems is due to stress-activated rupture of triple-helical junctions. After rupture, the physical gels heal completely.
Strongly correlated oxides that undergo a metal‐insulator transition (MIT) are a subject of great current interest for their potential application to future electronics as switches and sensors. ...Recent advances in thin film technology have opened up new avenues to tailor MIT for novel devices beyond conventional CMOS scaling. Here, dimensional‐crossover‐driven MITs are demonstrated in high‐quality epitaxial SrVO3 (SVO) thin films grown by a pulsed electron‐beam deposition technique. Thick SVO films (∼25 nm) exhibit metallic behavior with the electrical resistivity following the T2 law corresponding to a Fermi liquid system. A temperature driven MIT is induced in SVO ultrathin films with thicknesses below 6.5 nm. The transition temperature TMIT is at 50 K for the 6.5 nm film, 120 K for the 5.7 nm film and 205 K for the 3 nm film. The emergence of the observed MIT can be attributed to the dimensional crossover from a three‐dimensional metal to a two‐dimensional Mott insulator, as the resulting reduction in the effective bandwidth W opens a band gap at the Fermi level. The magneto‐transport study of the SVO ultrathin films also confirm the observed MIT is due to the electron‐electron interactions other than disorder‐induced localization.
A metal‐insulator transition (MIT) induced in high‐quality epitaxial SrVO3 (SVO) ultrathin films with thicknesses less than 6.5 nm (ca.17 monolayers) is demonstrated. It is shown that the emergence of the MIT is due to dimensional cross‐over from a three‐dimensional metal to a two‐dimensional Mott insulator, and any competing effects like Anderson localization are small and do not significantly contribute to the transport. Here, the first transport study to show this crossover is presented, and earlier photoemission results are confirmed.
Artificial 3-dimensional (3D) cell culture systems, which mimic the extracellular matrix (ECM), hold great potential as models to study cellular processes under controlled conditions. The natural ECM ...is a 3D structure composed of a fibrous hydrogel that provides both mechanical and biochemical cues to instruct cell behavior. Here we present an ECM-mimicking genetically engineered protein-based hydrogel as a 3D cell culture system that combines several key features: (1) Mild and straightforward encapsulation meters (1) ease of ut I am not so sure.encapsulation of the cells, without the need of an external crosslinker. (2) Supramolecular assembly resulting in a fibrous architecture that recapitulates some of the unique mechanical characteristics of the ECM, i.e. strain-stiffening and self-healing behavior. (3) A modular approach allowing controlled incorporation of the biochemical cue density (integrin binding RGD domains). We tested the gels by encapsulating MG-63 osteoblastic cells and found that encapsulated cells not only respond to higher RGD density, but also to overall gel concentration. Cells in 1% and 2% (weight fraction) protein gels showed spreading and proliferation, provided a relative RGD density of at least 50%. In contrast, in 4% gels very little spreading and proliferation occurred, even for a relative RGD density of 100%. The independent control over both mechanical and biochemical cues obtained in this modular approach renders our hydrogels suitable to study cellular responses under highly defined conditions.
Severe hypoglycemia is a complication of insulin therapy and a continuing barrier to achieving glycemic targets at every age. Glucagon, a drug that has been on the market for several decades, is an ...effective treatment for severe hypoglycemia, but is underutilized. The emotional impact of severe hypoglycemia and the emergency use of glucagon is not clear. This study aimed to understand current perceptions of glucagon from both the perspective of people with T1D and people likely to aid in an emergency situation. All participants were recruited from T1D Exchange Glu (www.myglu.org), an online community for individuals living with T1D. The current study conducted interviews with people with T1D (n=9, average age 44.7 years) and caregivers (n=8, average age 37.8 years) of minors with T1D. Interviews were recorded, transcribed, and thematically analyzed. Participants described experiences and emotions surrounding severe hypoglycemia, importance of specific glucagon characteristics, and priorities during severe hypoglycemia. Participants expressed on a 1-10 scale the importance of glucagon’s time to recovery (average: 8.56), mode of administration (average: 8.56), cost (average: 5.67), and not requiring refrigeration (average: 9.56). Themes among participants with T1D included feelings of distress, fear, and helplessness; common caregiver themes included feeling intimidated by the administration of glucagon. People with T1D discussed how they make decisions during a hypoglycemic emergency and rely on others for decision-making. Participants described their ideal glucagon and emphasized how fast glucagon needs to be, the desire for minimal side effects, and different administration types. These results provide insight into the real-world impact of diabetes on both persons with T1D and their caregivers and highlight the attitudes about severe hypoglycemia and emergency treatment with glucagon.
Disclosure
A. Hughes: None. J. Bispham: None. L. Fuller: None. W. Wolf: None. S.A. Fitch: Employee; Self; Zealand Pharma A/S. S.A. Weinzimer: Consultant; Spouse/Partner; Tandem Diabetes Care. Consultant; Self; Zealand Pharma A/S. Speaker’s Bureau; Self; Insulet Corporation.
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