Quantum fluctuations drive nonmonotonic correlations in a qubit lattice.

Fluctuations may induce the degradation of order by overcoming ordering interactions, consequently leading to an increase of entropy. This is particularly evident in magnetic systems characterized by nontrivial, constrained disorder, where thermal or quantum fluctuations can yield counterintuitive forms of ordering. Using the proven efficiency of quantum annealers as programmable spin system simulators, we present a study based on entropy postulates and experiments on a platform of programmable superconducting qubits to show that a low level of uncertainty can promote ordering in a system impacted by both thermal and quantum fluctuations. A set of experiments is proposed on a lattice of interacting qubits arranged in a triangular geometry with precisely controlled disorder, effective temperature, and quantum fluctuations. Our results demonstrate the creation of ordered ferrimagnetic and layered anisotropic disordered phases, displaying characteristics akin to the elegant order-by-disorder phenomenon. Extensive experimental evidence is provided for the role of quantum fluctuations in lowering the total energy of the system by increasing entropy and defect clustering. Our thorough and comprehensive application of an intentionally introduced noise on a quantum platform provides insight into the dynamics of defects and fluctuations in quantum devices, which may help to reduce the cost associated with quantum processing.

Next-generation sequencing in dermatology.

Over the past decade, Next-Generation Sequencing (NGS) has advanced our understanding, diagnosis, and management of several areas within dermatology. NGS has emerged as a powerful tool for diagnosing genetic diseases of the skin, improving upon traditional PCR-based techniques limited by significant genetic heterogeneity associated with these disorders. Epidermolysis bullosa and ichthyosis are two of the most extensively studied genetic diseases of the skin, with a well-characterized spectrum of genetic changes occurring in these conditions. NGS has also played a critical role in expanding the mutational landscape of cutaneous squamous cell carcinoma, enhancing our understanding of its molecular pathogenesis. Similarly, genetic testing has greatly benefited melanoma diagnosis and treatment, primarily due to the high prevalence of BRAF hot spot mutations and other well-characterized genetic alterations. Additionally, NGS provides a valuable tool for measuring tumor mutational burden, which can aid in management of melanoma. Lastly, NGS demonstrates promise in improving the sensitivity of diagnosing cutaneous T-cell lymphoma. This article provides a comprehensive summary of NGS applications in the diagnosis and management of genodermatoses, cutaneous squamous cell carcinoma, melanoma, and cutaneous T-cell lymphoma, highlighting the impact of NGS on the field of dermatology.

Quantum critical dynamics in a 5,000-qubit programmable spin glass.

Experiments on disordered alloys1-3 suggest that spin glasses can be brought into low-energy states faster by annealing quantum fluctuations than by conventional thermal annealing. Owing to the importance of spin glasses as a paradigmatic computational testbed, reproducing this phenomenon in a programmable system has remained a central challenge in quantum optimization4-13. Here we achieve this goal by realizing quantum-critical spin-glass dynamics on thousands of qubits with a superconducting quantum annealer. We first demonstrate quantitative agreement between quantum annealing and time evolution of the Schrödinger equation in small spin glasses. We then measure dynamics in three-dimensional spin glasses on thousands of qubits, for which classical simulation of many-body quantum dynamics is intractable. We extract critical exponents that clearly distinguish quantum annealing from the slower stochastic dynamics of analogous Monte Carlo algorithms, providing both theoretical and experimental support for large-scale quantum simulation and a scaling advantage in energy optimization.

Nodular melanoma in an African American Japanese male.

Nodular melanoma (NM) is the third most common subtype of melanoma among African Americans trailing behind acral lentiginous melanoma and superficial spreading melanoma. This case of NM in an African American Japanese male was selected due to the rare occurrence of NM in people of color.

Kagome qubit ice.

Topological phases of spin liquids with constrained disorder can host a kinetics of fractionalized excitations. However, spin-liquid phases with distinct kinetic regimes have proven difficult to observe experimentally. Here we present a realization of kagome spin ice in the superconducting qubits of a quantum annealer, and use it to demonstrate a field-induced kinetic crossover between spin-liquid phases. Employing fine control over local magnetic fields, we show evidence of both the Ice-I phase and an unconventional field-induced Ice-II phase. In the latter, a charge-ordered yet spin-disordered topological phase, the kinetics proceeds via pair creation and annihilation of strongly correlated, charge conserving, fractionalized excitations. As these kinetic regimes have resisted characterization in other artificial spin ice realizations, our results demonstrate the utility of quantum-driven kinetics in advancing the study of topological phases of spin liquids.

Increasing dominance of Indian Ocean variability impacts Australian wheat yields.

The relationships between crop productivity and climate variability drivers are often assumed to be stationary over time. However, this may not be true in a warming climate. Here we use a crop model and a machine learning algorithm to demonstrate the changing impacts of climate drivers on wheat productivity in Australia. We find that, from the end of the nineteenth century to the 1980s, wheat productivity was mainly subject to the impacts of the El Niño Southern Oscillation. Since the 1990s, the impacts from the El Niño Southern Oscillation have been decreasing, but those from the Indian Ocean Dipole have been increasing. The warming climate has brought more occurrences of positive Indian Ocean Dipole events, resulting in severe yield reductions in recent decades. Our findings highlight the need to adapt seasonal forecasting to the changing impacts of climate variability to inform the management of climate-induced yield losses.

Qubit spin ice.

Artificial spin ices are frustrated spin systems that can be engineered, in which fine tuning of geometry and topology has allowed the design and characterization of exotic emergent phenomena at the constituent level. Here, we report a realization of spin ice in a lattice of superconducting qubits. Unlike conventional artificial spin ice, our system is disordered by both quantum and thermal fluctuations. The ground state is classically described by the ice rule, and we achieved control over a fragile degeneracy point, leading to a Coulomb phase. The ability to pin individual spins allows us to demonstrate Gauss's law for emergent effective monopoles in two dimensions. The demonstrated qubit control lays the groundwork for potential future study of topologically protected artificial quantum spin liquids.

Scaling advantage over path-integral Monte Carlo in quantum simulation of geometrically frustrated magnets.

The promise of quantum computing lies in harnessing programmable quantum devices for practical applications such as efficient simulation of quantum materials and condensed matter systems. One important task is the simulation of geometrically frustrated magnets in which topological phenomena can emerge from competition between quantum and thermal fluctuations. Here we report on experimental observations of equilibration in such simulations, measured on up to 1440 qubits with microsecond resolution. By initializing the system in a state with topological obstruction, we observe quantum annealing (QA) equilibration timescales in excess of one microsecond. Measurements indicate a dynamical advantage in the quantum simulation compared with spatially local update dynamics of path-integral Monte Carlo (PIMC). The advantage increases with both system size and inverse temperature, exceeding a million-fold speedup over an efficient CPU implementation. PIMC is a leading classical method for such simulations, and a scaling advantage of this type was recently shown to be impossible in certain restricted settings. This is therefore an important piece of experimental evidence that PIMC does not simulate QA dynamics even for sign-problem-free Hamiltonians, and that near-term quantum devices can be used to accelerate computational tasks of practical relevance.

Onset of frontal fibrosing alopecia during inhibition of Th1/17 Pathways with ustekinumab.

The mechanism underlying frontal fibrosing alopecia (FFA) is unknown, but proposed mechanisms share commonality of T cell-mediated destruction of the hair follicle bulge. IL-12 and IL-23 are key cytokines involved in CD4 T cell differentiation towards Th1 and Th17 phenotypes. We present a 62-year-old woman who developed persistent FFA while on ustekinumab for treatment of preexisting psoriasis. This case presents evidence against Th1 and Th17 pathways as essential to pathogenesis in FFA. This case also suggests that IL-12 and IL-23 inhibition is ineffective for this form of scarring alopecia.

Observation of topological phenomena in a programmable lattice of 1,800 qubits.

The work of Berezinskii, Kosterlitz and Thouless in the 1970s1,2 revealed exotic phases of matter governed by the topological properties of low-dimensional materials such as thin films of superfluids and superconductors. A hallmark of this phenomenon is the appearance and interaction of vortices and antivortices in an angular degree of freedom-typified by the classical XY model-owing to thermal fluctuations. In the two-dimensional Ising model this angular degree of freedom is absent in the classical case, but with the addition of a transverse field it can emerge from the interplay between frustration and quantum fluctuations. Consequently, a Kosterlitz-Thouless phase transition has been predicted in the quantum system-the two-dimensional transverse-field Ising model-by theory and simulation3-5. Here we demonstrate a large-scale quantum simulation of this phenomenon in a network of 1,800 in situ programmable superconducting niobium flux qubits whose pairwise couplings are arranged in a fully frustrated square-octagonal lattice. Essential to the critical behaviour, we observe the emergence of a complex order parameter with continuous rotational symmetry, and the onset of quasi-long-range order as the system approaches a critical temperature. We describe and use a simple approach to statistical estimation with an annealing-based quantum processor that performs Monte Carlo sampling in a chain of reverse quantum annealing protocols. Observations are consistent with classical simulations across a range of Hamiltonian parameters. We anticipate that our approach of using a quantum processor as a programmable magnetic lattice will find widespread use in the simulation and development of exotic materials.

Reversible Regulation of Promoter and Enhancer Histone Landscape by DNA Methylation in Mouse Embryonic Stem Cells.

DNA methylation is one of a number of modes of epigenetic gene regulation. Here, we profile the DNA methylome, transcriptome, and global occupancy of histone modifications (H3K4me1, H3K4me3, H3K27me3, and H3K27ac) in a series of mouse embryonic stem cells (mESCs) with varying DNA methylation levels to study the effects of DNA methylation on deposition of histone modifications. We find that genome-wide DNA demethylation alters occupancy of histone modifications at both promoters and enhancers. This is reversed upon remethylation by Dnmt expression. DNA methylation promotes H3K27me3 deposition at bivalent promoters, while opposing H3K27me3 at silent promoters. DNA methylation also reversibly regulates H3K27ac and H3K27me3 at previously identified tissue-specific enhancers. These effects require DNMT catalytic activity. Collectively, our data show that DNA methylation is essential and instructive for deposition of specific histone modifications across regulatory regions, which together influences gene expression patterns in mESCs.

Revisiting the electrochemical impedance spectroscopy of magnesium with online inductively coupled plasma atomic emission spectroscopy.

The electrochemical impedance of reactive metals such as magnesium is often complicated by an obvious inductive loop with decreasing frequency of the AC polarising signal. The characterisation and ensuing explanation of this phenomenon has been lacking in the literature to date, being either ignored or speculated. Herein, we couple electrochemical impedance spectroscopy (EIS) with online atomic emission spectroelectrochemistry (AESEC) to simultaneously measure Mg-ion concentration and electrochemical impedance spectra during Mg corrosion, in real time. It is revealed that Mg dissolution occurs via Mg(2+) , and that corrosion is activated, as measured by AC frequencies less than approximately 1 Hz approaching DC conditions. The result of this is a higher rate of Mg(2+) dissolution, as the voltage excitation becomes slow enough to enable all Mg(2+) -enabling processes to adjust in real time. The manifestation of this in EIS data is an inductive loop. The rationalisation of such EIS behaviour, as it relates to Mg, is revealed for the first time by using concurrent AESEC.

Protein complex prediction with RNSC.

Graph theory analysis of biological networks, such as protein-protein interactions (PPIs), gene regulatory, metabolic, etc., has identified a strong relationship between topology of these networks and the underlying cellular function and biological processes (Sharan et al. Mol Syst Biol 3:88, 2007). We focus on PPI networks, in which nodes correspond to proteins and edges represent interactions among the proteins. The size of these networks is ever growing, and thus efficient identification of various network motifs and dense sub-networks has become necessary. Predicting highly connected sub-graphs in a PPI network is important to biologists as it may help to identify biologically meaningful protein complexes, and with further integrative analysis may lead to identifying dynamic assembly of individual subunits in these complexes. In this chapter, we describe one method for predicting protein complexes in two steps. The first step is to partition the nodes of a PPI network (i.e. proteins) into highly connected groups or clusters using the Restricted Neighbourhood Search Clustering algorithm. This provides a set of clusters that represent candidate complexes. The second step of the method is to filter the candidate complexes based on three criteria: minimum cluster size, minimum interaction density, and minimum functional homogeneity, which reflects the extent to which the proteins of the candidate cluster operate in the same functional group. Candidate complexes passing all three criteria are then put forward as predicted protein complexes. The effectiveness of this method is investigated in the previous studies (King et al. Bioinformatics 20:3013-3020, 2004; Brohee and van Helden BMC Bioinformatics 7:488, 2006; and Moschopoulos et al. BMC Bioinformatics 10(Suppl 6):S11, 2009).

Generation of oxygen gradients in microfluidic devices for cell culture using spatially confined chemical reactions.

This paper reports a microfluidic device capable of generating oxygen gradients for cell culture using spatially confined chemical reactions with minimal chemical consumption. The microfluidic cell culture device is constructed by single-layer polydimethylsiloxane (PDMS) microfluidic channels, in which the cells can be easily observed by microscopes. The device can control the oxygen gradients without the utilization of bulky pressurized gas cylinders, direct addition of oxygen scavenging agents, or tedious gas interconnections and sophisticated flow control. In addition, due to the efficient transportation of oxygen within the device using the spatially confined chemical reactions, the microfluidic cell culture device can be directly used in conventional cell incubators without altering their gaseous compositions. The oxygen gradients generated in the device are numerically simulated and experimentally characterized using an oxygen-sensitive fluorescence dye. In this paper, carcinomic human alveolar basal epithelial (A549) cells have been cultured in the microfluidic device with a growth medium and an anti-cancer drug (Tirapazamine, TPZ) under various oxygen gradients. The cell experiment results successfully demonstrate the hyperoxia-induced cell death and hypoxia-induced cytotoxicity of TPZ. In addition, the results confirm the great cell compatibility and stable oxygen gradient generation of the developed device. Consequently, the microfluidic cell culture device developed in this paper is promising to be exploited in biological labs with minimal instrumentation to study cellular responses under various oxygen gradients.