Recombinant production of interleukin-1 receptor antagonist in fusion to albumin binding domain with potential affinity to human serum albumin.

Background and purpose: Anakinra must be injected daily due to its short half-life and this leads to lower patient compliance. Therefore, the aim of this study was to produce an interleukin-1 receptor antagonist (IL-1Ra) with albumin binding domain (ABD) as a novel fusion protein and evaluate its binding ability to albumin and its biological effects. Experimental approach: The three-dimensional structure of IL-1Ra-ABD was predicted by MODELLER software and its interaction with IL-1R was evaluated by the HADDOCK server. The expression of IL-1Ra-ABD was performed in E. coli in fusion with intein 1 of pTWIN1 in soluble form and then purified. The affinity of IL-1Ra-ABD to human serum albumin (HSA) was determined on native-PAGE, and its release percent toward time was evaluated. Moreover, an MTT assay was used to determine the antagonizing properties of recombinant IL-1Ra-ABD against IL-1ß in A375 and HEK293 cell lines. Findings/Results: The stable complex of IL-1Ra-ABD with IL-1R established the absence of steric hindrance due to the addition of ABD to IL-1Ra. The expression induction of intein 1-IL-1Ra-ABD using 0.1 mM IPTG at 15 °C, and its cleavage represented bands approximately in 50 and 23 kDa. Furthermore, about 78% of IL-1Ra-ABD was attached to the HSA after 2 h of incubation, and the MTT assay showed no significant differences between the effects of IL-1Ra-ABD and native IL-1Ra in cell survival. Conclusions and implications: The production of soluble IL-1Ra-ABD with no significant differences in IL-1Ra antagonizing effects was successfully performed. IL-1Ra-ABD showed suitable interaction with HSA and was released over time. However, the half-life of IL-1Ra-ABD in vivo must be determined in the subsequent investigations.

Direct observation of a magnetic-field-induced Wigner crystal.

Wigner predicted that when the Coulomb interactions between electrons become much stronger than their kinetic energy, electrons crystallize into a closely packed lattice1. A variety of two-dimensional systems have shown evidence for Wigner crystals2-11 (WCs). However, a spontaneously formed classical or quantum WC has never been directly visualized. Neither the identification of the WC symmetry nor direct investigation of its melting has been accomplished. Here we use high-resolution scanning tunnelling microscopy measurements to directly image a magnetic-field-induced electron WC in Bernal-stacked bilayer graphene and examine its structural properties as a function of electron density, magnetic field and temperature. At high fields and the lowest temperature, we observe a triangular lattice electron WC in the lowest Landau level. The WC possesses the expected lattice constant and is robust between filling factor ν ≈ 0.13 and ν ≈ 0.38 except near fillings where it competes with fractional quantum Hall states. Increasing the density or temperature results in the melting of the WC into a liquid phase that is isotropic but has a modulated structure characterized by the Bragg wavevector of the WC. At low magnetic fields, the WC unexpectedly transitions into an anisotropic stripe phase, which has been commonly anticipated to form in higher Landau levels. Analysis of individual lattice sites shows signatures that may be related to the quantum zero-point motion of electrons in the WC lattice.

Developing a surface acoustic wave-induced microfluidic cell lysis device for point-of-care DNA amplification.

We developed a microchip device using surface acoustic waves (SAW) and sharp-edge glass microparticles to rapidly lyse low-level cell samples. This microchip features a 13-finger pair interdigital transducer (IDT) with a 30-degree focused angle, creating high-intensity acoustic beams converging 6 mm away at a 16 MHz frequency. Cell lysis is achieved through centrifugal forces acting on Candida albicans cells and glass particles within the focal area. To optimize this SAW-induced streaming, we conducted 42 pilot experiments, varying electrical power, droplet volume, glass particle size, concentration, and lysis time, resulting in optimal conditions: an electrical signal of 2.5 W, a 20 µL sample volume, glass particle size below 10 µm, concentration of 0.2 µg, and a 5-min lysis period. We successfully amplified DNA target fragments directly from the lysate, demonstrating an efficient microchip-based cell lysis method. When combined with an isothermal amplification technique, this technology holds promise for rapid point-of-care (POC) applications.

Quantum textures of the many-body wavefunctions in magic-angle graphene.

Interactions among electrons create novel many-body quantum phases of matter with wavefunctions that reflect electronic correlation effects, broken symmetries and collective excitations. Many quantum phases have been discovered in magic-angle twisted bilayer graphene (MATBG), including correlated insulating1, unconventional superconducting2-5 and magnetic topological6-9 phases. The lack of microscopic information10,11 of possible broken symmetries has hampered our understanding of these phases12-17. Here we use high-resolution scanning tunnelling microscopy to study the wavefunctions of the correlated phases in MATBG. The squares of the wavefunctions of gapped phases, including those of the correlated insulating, pseudogap and superconducting phases, show distinct broken-symmetry patterns with a √3 × âˆš3 super-periodicity on the graphene atomic lattice that has a complex spatial dependence on the moiré scale. We introduce a symmetry-based analysis using a set of complex-valued local order parameters, which show intricate textures that distinguish the various correlated phases. We compare the observed quantum textures of the correlated insulators at fillings of ±2 electrons per moiré unit cell to those expected for proposed theoretical ground states. In typical MATBG devices, these textures closely match those of the proposed incommensurate Kekulé spiral order15, whereas in ultralow-strain samples, our data have local symmetries like those of a time-reversal symmetric intervalley coherent phase12. Moreover, the superconducting state of MATBG shows strong signatures of intervalley coherence, only distinguishable from those of the insulator with our phase-sensitive measurements.

Hunting for Majoranas.

Over the past decade, there have been considerable efforts to observe non-abelian quasiparticles in novel quantum materials and devices. These efforts are motivated by the goals of demonstrating quantum statistics of quasiparticles beyond those of fermions and bosons and of establishing the underlying science for the creation of topologically protected quantum bits. In this Review, we focus on efforts to create topological superconducting phases that host Majorana zero modes. We consider the lessons learned from existing experimental efforts, which are motivating both improvements to present platforms and the exploration of new approaches. Although the experimental detection of non-abelian quasiparticles remains challenging, the knowledge gained thus far and the opportunities ahead offer high potential for discovery and advances in this exciting area of quantum physics.

A biological and a mathematical model of SLE treated by mesenchymal stem cells covering all the stages of the disease.

In this study, we proposed a biological model explaining the progress of autoimmune activation along different stages of systemic lupus erythematosus (SLE). For any upcoming stage of SLE, any new component is introduced, when it is added to the model. Particularly, the interaction of mesenchymal stem cells, with the components of the model, is specified in a way that both the inflammatory and anti-inflammatory functions of these cells would be covered. The biological model is then recapitulated to a model with less complexity that explains the main features of the problem. Later, a 7th-order mathematical model for SLE is proposed, based on this simplified model. Finally, the range of validity of the proposed mathematical model was assessed. For this purpose, we simulated the model and analyzed the simulation results in case of some known behaviors of the disease, such as tolerance breach, the appearance of systemic inflammation, development of clinical signs, and occurrence of flares and improvements. The model was able to reproduce these events, qualitatively.

Kratom-induced common bile duct dilation.

Kratom is an herb with opioid-like properties that has become readily available in the United States and is being used for self-management of pain and opioid withdrawal. We present a case of common bile duct dilation secondary to use of kratom. Our suspicion is that the mu-opioid agonism associated with kratom use resulted in effects similar to what might be seen in opiate-induced biliary ductal dilation.

Spectroscopy of Twisted Bilayer Graphene Correlated Insulators.

We analytically compute the scanning tunneling microscopy (STM) signatures of integer-filled correlated ground states of the magic angle twisted bilayer graphene (TBG) narrow bands. After experimentally validating the strong-coupling approach at ±4 electrons/moiré unit cell, we consider the spatial features of the STM signal for 14 different many-body correlated states and assess the possibility of Kekulé distortion (KD) emerging at the graphene lattice scale. Remarkably, we find that coupling the two opposite graphene valleys in the intervalley-coherent (IVC) TBG insulators does not always result in KD. As an example, we show that the Kramers IVC state and its nonchiral U(4) rotations do not exhibit any KD, while the time-reversal-symmetric IVC state does. Our results, obtained over a large range of energies and model parameters, show that the STM signal and Chern number of a state can be used to uniquely determine the nature of the TBG ground state.

Catalogue of flat-band stoichiometric materials.

Topological electronic flattened bands near or at the Fermi level are a promising route towards unconventional superconductivity and correlated insulating states. However, the related experiments are mostly limited to engineered materials, such as moiré systems1-3. Here we present a catalogue of the naturally occuring three-dimensional stoichiometric materials with flat bands around the Fermi level. We consider 55,206 materials from the Inorganic Crystal Structure Database catalogued using the Topological Quantum Chemistry website4,5, which provides their structural parameters, space group, band structure, density of states and topological characterization. We combine several direct signatures and properties of band flatness with a high-throughput analysis of all crystal structures. In particular, we identify materials hosting line-graph or bipartite sublattices-in either two or three dimensions-that probably lead to flat bands. From this trove of information, we create the Materials Flatband Database website, a powerful search engine for future theoretical and experimental studies. We use the database to extract a curated list of 2,379 high-quality flat-band materials, from which we identify 345 promising candidates that potentially host flat bands with charge centres that are not strongly localized on the atomic sites. We showcase five representative materials and provide a theoretical explanation for the origin of their flat bands close to the Fermi energy using the S-matrix method introduced in a parallel work6.

Study of the Demographic and Clinical Profile in a Neurocutaneous Rare Disease: A Cross-Sectional Study.

OBJECTIVE: Neurofibromatosis is one of the most common dominantly inherited genetic disorders. This study aimed to study the demographic and clinical profile of neurofibromatosis patients. METHODS: This study is cross-sectional conducted in 2020 on the population of patients with neurofibromatosis. Patients who are members of the Neurofibromatosis Association answered the online demographic and clinical information questionnaire. RESULTS: 446 patients with neurofibromatosis participated in this study with a mean age of 33.39 plus or minus 12.87 years. 297 patients (66.6%) were women and 378 (84.8%) patients had type 1 neurofibromatosis. The disease visibility was reported to be moderate in 254 patients (54.9%) and the severity of the disease was mild in 238 (53.4%) patients. The type of neurofibromatosis was not significantly related to gender, age groups, parental education, and ethnicity. The relationship between severity and age (p is equal to less than 0.001) and gender (p is equal to 0.042) was significant and the relationship between visibility and age (p is equal to less than 0.001) was significant but despite the fact that the disease was more visible in men than women, it was not significantly related to gender. CONCLUSIONS: The study results showed that the most common complication in the study population was Cafe au lait spot. In addition, visibility and severity of the disease were mild and moderate, respectively. Keyword: Neurofibromatosis, Demographic information, Clinical Information.

Visualizing broken symmetry and topological defects in a quantum Hall ferromagnet.

The interaction between electrons in graphene under high magnetic fields drives the formation of a rich set of quantum Hall ferromagnetic (QHFM) phases with broken spin or valley symmetry. Visualizing atomic-scale electronic wave functions with scanning tunneling spectroscopy (STS), we resolved microscopic signatures of valley ordering in QHFM phases and spectral features of fractional quantum Hall phases of graphene. At charge neutrality, we observed a field-tuned continuous quantum phase transition from a valley-polarized state to an intervalley coherent state, with a Kekulé distortion of its electronic density. Mapping the valley texture extracted from STS measurements of the Kekulé phase, we could visualize valley skyrmion excitations localized near charged defects. Our techniques can be applied to examine valley-ordered phases and their topological excitations in a wide range of materials.

Evidence for unconventional superconductivity in twisted bilayer graphene.

The emergence of superconductivity and correlated insulators in magic-angle twisted bilayer graphene (MATBG) has raised the intriguing possibility that its pairing mechanism is distinct from that of conventional superconductors1-4, as described by the Bardeen-Cooper-Schrieffer (BCS) theory. However, recent studies have shown that superconductivity persists even when Coulomb interactions are partially screened5,6. This suggests that pairing in MATBG might be conventional in nature and a consequence of the large density of states of its flat bands. Here we combine tunnelling and Andreev reflection spectroscopy with a scanning tunnelling microscope to observe several key experimental signatures of unconventional superconductivity in MATBG. We show that the tunnelling spectra below the transition temperature Tc are inconsistent with those of a conventional s-wave superconductor, but rather resemble those of a nodal superconductor with an anisotropic pairing mechanism. We observe a large discrepancy between the tunnelling gap ΔT, which far exceeds the mean-field BCS ratio (with 2ΔT/kBTc ~ 25), and the gap ΔAR extracted from Andreev reflection spectroscopy (2ΔAR/kBTc ~ 6). The tunnelling gap persists even when superconductivity is suppressed, indicating its emergence from a pseudogap phase. Moreover, the pseudogap and superconductivity are both absent when MATBG is aligned with hexagonal boron nitride. These findings and other observations reported here provide a preponderance of evidence for a non-BCS mechanism for superconductivity in MATBG.

Spectroscopy of a tunable moiré system with a correlated and topological flat band.

Moiré superlattices created by the twisted stacking of two-dimensional crystals can host electronic bands with flat energy dispersion in which enhanced interactions promote correlated electron states. The twisted double bilayer graphene (TDBG), where two Bernal bilayer graphene are stacked with a twist angle, is such a moiré system with tunable flat bands. Here, we use gate-tuned scanning tunneling spectroscopy to directly demonstrate the tunability of the band structure of TDBG with an electric field and to show spectroscopic signatures of electronic correlations and topology for its flat band. Our spectroscopic experiments are in agreement with a continuum model of TDBG band structure and reveal signatures of a correlated insulator gap at partial filling of its isolated flat band. The topological properties of this flat band are probed with the application of a magnetic field, which leads to valley polarization and the splitting of Chern bands with a large effective g-factor.

Tuning interactions between spins in a superconductor.

Novel many-body and topological electronic phases can be created in assemblies of interacting spins coupled to a superconductor, such as one-dimensional topological superconductors with Majorana zero modes (MZMs) at their ends. Understanding and controlling interactions between spins and the emergent band structure of the in-gap Yu-Shiba-Rusinov (YSR) states they induce in a superconductor are fundamental for engineering such phases. Here, by precisely positioning magnetic adatoms with a scanning tunneling microscope (STM), we demonstrate both the tunability of exchange interaction between spins and precise control of the hybridization of YSR states they induce on the surface of a bismuth (Bi) thin film that is made superconducting with the proximity effect. In this platform, depending on the separation of spins, the interplay among Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction, spin-orbit coupling, and surface magnetic anisotropy stabilizes different types of spin alignments. Using high-resolution STM spectroscopy at millikelvin temperatures, we probe these spin alignments through monitoring the spin-induced YSR states and their energy splitting. Such measurements also reveal a quantum phase transition between the ground states with different electron number parity for a pair of spins in a superconductor tuned by their separation. Experiments on larger assemblies show that spin-spin interactions can be mediated in a superconductor over long distances. Our results show that controlling hybridization of the YSR states in this platform provides the possibility of engineering the band structure of such states for creating topological phases.

Strongly correlated Chern insulators in magic-angle twisted bilayer graphene.

Interactions between electrons and the topology of their energy bands can create unusual quantum phases of matter. Most topological electronic phases appear in systems with weak electron-electron interactions. The instances in which topological phases emerge only as a result of strong interactions are rare and mostly limited to those realized in intense magnetic fields1. The discovery of flat electronic bands with topological character in magic-angle twisted bilayer graphene (MATBG) has created a unique opportunity to search for strongly correlated topological phases2-9. Here we introduce a local spectroscopic technique using a scanning tunnelling microscope to detect a sequence of topological insulators in MATBG with Chern numbers C = ±1, ±2 and ±3, which form near filling factors of ±3, ±2 and ±1 electrons per moiré unit cell, respectively, and are stabilized by modest magnetic fields. One of the phases detected here (C = +1) was previously observed when the sublattice symmetry of MATBG was intentionally broken by a hexagonal boron nitride substrate, with interactions having a secondary role9. We demonstrate that strong electron-electron interactions alone can produce not only the previously observed phase, but also other unexpected Chern insulating phases in MATBG. The full sequence of phases that we observe can be understood by postulating that strong correlations favour breaking time-reversal symmetry to form Chern insulators that are stabilized by weak magnetic fields. Our findings illustrate that many-body correlations can create topological phases in moiré systems beyond those anticipated from weakly interacting models.

Observation of backscattering induced by magnetism in a topological edge state.

The boundary modes of topological insulators are protected by the symmetries of the nontrivial bulk electronic states. Unless these symmetries are broken, they can give rise to novel phenomena, such as the quantum spin Hall effect in one-dimensional (1D) topological edge states, where quasiparticle backscattering is suppressed by time-reversal symmetry (TRS). Here, we investigate the properties of the 1D topological edge state of bismuth in the absence of TRS, where backscattering is predicted to occur. Using spectroscopic imaging and spin-polarized measurements with a scanning tunneling microscope, we compared quasiparticle interference (QPI) occurring in the edge state of a pristine bismuth bilayer with that occurring in the edge state of a bilayer, which is terminated by ferromagnetic iron clusters that break TRS. Our experiments on the decorated bilayer edge reveal an additional QPI branch, which can be associated with spin-flip scattering across the Brioullin zone center between time-reversal band partners. The observed QPI characteristics exactly match with theoretical expectations for a topological edge state, having one Kramer's pair of bands. Together, our results provide further evidence for the nontrivial nature of bismuth and in particular, demonstrate backscattering inside a helical topological edge state induced by broken TRS through local magnetism.

Cascade of electronic transitions in magic-angle twisted bilayer graphene.

Magic-angle twisted bilayer graphene exhibits a variety of electronic states, including correlated insulators1-3, superconductors2-4 and topological phases3,5,6. Understanding the microscopic mechanisms responsible for these phases requires determination of the interplay between electron-electron interactions and quantum degeneracy (the latter is due to spin and valley degrees of freedom). Signatures of strong electron-electron correlations have been observed at partial fillings of the flat electronic bands in recent spectroscopic measurements7-10, and transport experiments have shown changes in the Landau level degeneracy at fillings corresponding to an integer number of electrons per moiré unit cell2-4. However, the interplay between interaction effects and the degeneracy of the system is currently unclear. Here we report a cascade of transitions in the spectroscopic properties of magic-angle twisted bilayer graphene as a function of electron filling, determined using high-resolution scanning tunnelling microscopy. We find distinct changes in the chemical potential and a rearrangement of the low-energy excitations at each integer filling of the moiré flat bands. These spectroscopic features are a direct consequence of Coulomb interactions, which split the degenerate flat bands into Hubbard sub-bands. We find these interactions, the strength of which we can extract experimentally, to be surprisingly sensitive to the presence of a perpendicular magnetic field, which strongly modifies the spectroscopic transitions. The cascade of transitions that we report here characterizes the correlated high-temperature parent phase11,12 from which various insulating and superconducting ground-state phases emerge at low temperatures in magic-angle twisted bilayer graphene.

A modular ultra-high vacuum millikelvin scanning tunneling microscope.

We describe the design, construction, and performance of an ultra-high vacuum (UHV) scanning tunneling microscope (STM) capable of imaging at dilution-refrigerator temperatures and equipped with a vector magnet. The primary objective of our design is to achieve a high level of modularity by partitioning the STM system into a set of easily separable, interchangeable components. This naturally segregates the UHV needs of STM instrumentation from the typically non-UHV construction of a dilution refrigerator, facilitating the usage of non-UHV materials while maintaining a fully bakeable UHV chamber that houses the STM. The modular design also permits speedy removal of the microscope head from the rest of the system, allowing for repairs, modifications, and even replacement of the entire microscope head to be made at any time without warming the cryostat or compromising the vacuum. Without using cryogenic filters, we measured an electron temperature of 184 mK on a superconducting Al(100) single crystal.