Accurately computing the electronic properties of a quantum ring.

A promising approach to study condensed-matter systems is to simulate them on an engineered quantum platform1-4. However, the accuracy needed to outperform classical methods has not been achieved so far. Here, using 18 superconducting qubits, we provide an experimental blueprint for an accurate condensed-matter simulator and demonstrate how to investigate fundamental electronic properties. We benchmark the underlying method by reconstructing the single-particle band structure of a one-dimensional wire. We demonstrate nearly complete mitigation of decoherence and readout errors, and measure the energy eigenvalues of this wire with an error of approximately 0.01 rad, whereas typical energy scales are of the order of 1 rad. Insight into the fidelity of this algorithm is gained by highlighting the robust properties of a Fourier transform, including the ability to resolve eigenenergies with a statistical uncertainty of 10-4 rad. We also synthesize magnetic flux and disordered local potentials, which are two key tenets of a condensed-matter system. When sweeping the magnetic flux we observe avoided level crossings in the spectrum, providing a detailed fingerprint of the spatial distribution of local disorder. By combining these methods we reconstruct electronic properties of the eigenstates, observing persistent currents and a strong suppression of conductance with added disorder. Our work describes an accurate method for quantum simulation5,6 and paves the way to study new quantum materials with superconducting qubits.

Noise-resilient edge modes on a chain of superconducting qubits.

Inherent symmetry of a quantum system may protect its otherwise fragile states. Leveraging such protection requires testing its robustness against uncontrolled environmental interactions. Using 47 superconducting qubits, we implement the one-dimensional kicked Ising model, which exhibits nonlocal Majorana edge modes (MEMs) with [Formula: see text] parity symmetry. We find that any multiqubit Pauli operator overlapping with the MEMs exhibits a uniform late-time decay rate comparable to single-qubit relaxation rates, irrespective of its size or composition. This characteristic allows us to accurately reconstruct the exponentially localized spatial profiles of the MEMs. Furthermore, the MEMs are found to be resilient against certain symmetry-breaking noise owing to a prethermalization mechanism. Our work elucidates the complex interplay between noise and symmetry-protected edge modes in a solid-state environment.

Realizing topologically ordered states on a quantum processor.

The discovery of topological order has revised the understanding of quantum matter and provided the theoretical foundation for many quantum error­correcting codes. Realizing topologically ordered states has proven to be challenging in both condensed matter and synthetic quantum systems. We prepared the ground state of the toric code Hamiltonian using an efficient quantum circuit on a superconducting quantum processor. We measured a topological entanglement entropy near the expected value of ­ln2 and simulated anyon interferometry to extract the braiding statistics of the emergent excitations. Furthermore, we investigated key aspects of the surface code, including logical state injection and the decay of the nonlocal order parameter. Our results demonstrate the potential for quantum processors to provide insights into topological quantum matter and quantum error correction.

Control of lymphopoiesis by p50csk, a regulatory protein tyrosine kinase.

The csk gene encodes a nonreceptor protein tyrosine kinase that acts in part by regulating the activity of src-family protein tyrosine kinases. Since the src-family kinases p56lck and p59fyn play pivotal roles during lymphocyte development, it seemed plausible that p50csk might contribute to these regulatory circuits. Using a gene targeting approach, mouse embryonic stem cell lines lacking functional csk genes were generated. These csknull embryonic stem cells proved capable of contributing to many adult tissues, notably heart and brain. However, although csknull progenitors colonized the developing thymus, T and B cell differentiation were both blocked at very early stages. This represented a relatively selective interdiction of lymphocyte maturation, since csknull hematopoietic progenitors supported the development of normal-appearing MAC-1+ blood leukocytes, and the successful maturation of granulocyte/macrophage-colony-forming units from fetal liver progenitors. We conclude that p50csk regulates normal lymphocyte differentiation, but that it almost certainly does so by acting on targets other than p56lck and p59fyn.

TACI-Ig prevents the development of airway hyperresponsiveness in a murine model of asthma.

BACKGROUND: Increased levels of serum IgE are associated with greater asthma prevalence and disease severity. IgE depletion using an anti-IgE monoclonal antibody has met with success in the treatment of moderate-to-severe and severe persistent allergic asthma. OBJECTIVE: To test whether B cell-targeted therapy is a more effective treatment for airway hyperresponsiveness (AHR) in a murine model compared with IgE-depletion. METHODS: We delivered soluble mTACI-Ig, a receptor for the B cell survival factors BLyS (B Lymphocyte Stimulator) and APRIL (A PRoliferation-Inducing Ligand), or anti-IgE to allergen-sensitized mice before airway challenge with allergen. RESULTS: mTACI-Ig treatment reduced circulating mature B cell levels in the blood, while anti-IgE treatment had no effect on B cell counts. Both mTACI-Ig and anti-IgE decreased the levels of total and allergen-specific IgE in the serum. Histopathologic analysis of lungs showed a reduction in disease severity scores for both treatment groups, but results were more pronounced in mTACI-Ig-treated mice. Neutrophil and eosinophil numbers in the bronchoalveolar lavage (BAL) were significantly reduced following mTACI-Ig treatment, but not after anti-IgE delivery. BLyS and APRIL blockade also resulted in a significant decrease in IL-4 and eotaxin mRNA and IL-4 and KC protein levels in total lung homogenates and BAL fluid, respectively. Finally, mTACI-Ig treatment was more effective than anti-IgE treatment in reducing AHR to inhaled antigen. CONCLUSIONS: Our data demonstrate that delivery of mTACI-Ig is a more effective treatment than anti-IgE mAb in a murine model of AHR.

Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals.

5-Hydroxymethylcytosine (5hmC) is a recently characterized epigenetic mark that is particularly abundant in brain tissue and that regulates gene transcription. We have recently begun to understand the important role of 5hmC in brain development, plasticity and disease, but there are currently little data on 5hmC alterations in psychiatric illnesses. Here we report what we believe to be the first genome-wide analysis of 5hmC in the depressed brain. Using AbaSI sequencing, we investigated 5hmC in the prefrontal cortex of depressed (N=19) and psychiatrically healthy controls (N=19). Consistent with previous global 5hmC analyses in other phenotypes, and likely owing to the inter-individual variability in 5hmC content, the distribution of 5hmC across chromosomes and genomic features was not different between groups. We did, however, find 550 CpGs with suggestive evidence of differential hydroxymethylation. Of these, we validated CpGs in the gene body of myosin XVI (MYO16) and insulin-degrading enzyme using targeted oxidative bisulfite sequencing. Furthermore, the enrichment of 5hmC was also associated with changes in the expression of these two genes in depressed suicides. Together, our results present a novel mechanism linking increased 5hmC to depression and provide a framework for future research in this field.

Rhizobium etli CE3 carries vir gene homologs on a self-transmissible plasmid.

RosR is a transcriptional regulator important for determining cell-surface characteristics and nodulation competitiveness in Rhizobium etli CE3. We identified a 15-kb region that contains genes with similarity to members of the virB, virC, virG, and virE operons of Agrobacterium tumefaciens and demonstrated that RosR directly regulates one operon in this region. These genes were located on plasmid pa of R. etli CE3, which is self-transmissible between R. etli and A. tumefaciens.

Ethylene oxide neurotoxicity: report of four cases and review of the literature.

Four workers were exposed to ethylene oxide gas. Acute encephalopathy occurred in one, and peripheral neuropathy in three, two of whom were symptomatic. Nerve conduction velocity studies were abnormal in three, including the asymptomatic patient. Decreasing the amount of exposure resulted in relief of symptoms. The abnormal nerve conduction studies did not change in two patients who continued to work at a lower level of exposure, whereas the conduction abnormalities improved in the patient who was removed from exposure.

Arm-diaphragm synkinesis: electrodiagnostic studies of aberrant regeneration of phrenic motor neurons.

Arm-diaphragm synkinesis may occur after injury to the proximal portion of the brachial plexus or cervical nerve roots. Regenerating axons of phrenic motor neurons are misdirected to supply limb muscles. Electrodiagnostic investigations of three patients with symptoms referable to upper brachial plexus or cervical roots revealed motor units in either biceps or triceps muscles that discharged during inspiration. These units did not fire during forced or passive expiration or Valsalva maneuver. Activation of these units could not be achieved by volitional contraction of the appropriate arm muscles. The synkinetic motor units were of increased amplitude and duration. Some units contained late components that demonstrated jitter and blocking, as is characteristic of reinnervated motor units. The unwary electromyographer may misinterpret these synkinetic units as incomplete muscle relaxation or some form of abnormal repetitive discharge. Correct identification of these units provides objective evidence of antecedent nerve root or brachial plexus injury.

Peripheral neuropathy in epileptic patients.

The prevalence of peripheral neuropathy in 186 epileptic patients was 16.7%. The neuropathy was characterized by stocking hypesthesia and reduced Achilles reflexes, and it occurred with all anticonvulsant agents. Electrophysiologic tests indicated slowing of peroneal and sural nerve conduction velocity and prolongation or absence of H reflexes and F responses. The prevalence of neuropathy was not greater in patients receiving phenytoin, and there was no relationship between clinical or electrical abnormalities and blood levels or duration of treatment for either phenytoin or phenobarbital. We did not find a specific relationship between phenytoin usage and peripheral neuropathy in epileptic patients.

Sarcoidosis of the peripheral nervous system.

The clinical and electrophysiologic data of four new patients with sarcoidosis involving the peripheral nerves are presented and the subject is reviewed. Two had a symmetric polyneuropathy and two had polyradiculopathy. These plus the few cases in the literature indicate that the findings on electromyography are most consistent with axonal neuropathy, in a multifocal pattern. Needle electrolyography was more useful than nerve conduction studies in identifying lesions.

Paraplegia due to ossification of ligamenta flava in X-linked hypophosphatemia. A case report.

STUDY DESIGN: Spinal canal decompression at the most prominent of multiple posterior calcified thoracic lesions in a case of X-linked hypophosphatemia was undertaken for treatment and diagnosis purposes, as well as to assess possible nature of the pathophysiology underlying the presenting deficits. OBJECTIVES: To discuss the clinical assessment diagnostic and treatment aspects of this rare coincidence of ossification of ligamenta flava in the patient with the skeletal deformities of X-linked hypophosphatemia. SUMMARY OF BACKGROUND DATA: The patient with the stigmata and chemical findings of an X-linked hypophosphatemia presented with paraplegia and multiple calcified posterior spinal thoracic lesions. This was studied with magnetic resonance imaging and electrophysiologic studies of the spinal sensory pathways of the legs. These data constituted the preoperative information required to assess later results of surgical intervention. METHODS: Presurgical clinical, imaging and electrophysiologic studies and laboratory and pathologic investigations of the surgical specimens. RESULTS: Resolution of the paraplegia with walking and return to work in a physically demanding job for the last 4 or 5 years of postoperative follow-up after surgical decompression of the spinal cord only at the worst and highest of the effected spinal levels. CONCLUSION: The coincidence of X-linked hypophosphatemia and ossification of ligamenta flava has been reported only in two or three cases in the literature. Removal of the offending ossifying lesion is known to result in resolution of the clinical deficits but similar lesions at other spinal levels are suspected of producing recurrences. The return of function and of the corresponding electrophysiologic correlates indicate a neurono-apractic nature of the neurologic symptoms.

Insomnia and its treatment. When are hypnotics justified?

Symptomatic treatment of transient insomnias is advisable, for without treatment these sleep disorders may become persistent. The drugs of choice are the benzodiazepine hypnotics, which have minimal side effects when used for short periods in properly selected patients. The three such drugs currently available in the United States differ enough in half-life, absorption rate, and potential for drug interactions that they cannot be used interchangeably. A sound selection matches the drug's characteristics with the patient's needs. Transient insomnias must be differentiated from persistent insomnias, which are more resistant to treatment. Hypnotic agents not only are more likely to be ineffective against persistent insomnias but also have greater potential for exacerbating a sleep-related breathing disorder, producing a drug-dependent insomnia, or contributing to drug misuse.

The Carotenoid Hydrocarbons of Euglena gracilis and Derived Mutants.

An examination of the carotene fractions extracted from Euglena gracilis Z and pressure-bleached Euglena mutants PR-1, PR-2, PR-3, and PR-4 revealed phytoene in mutants PR-1, PR-2, and PR-3. Photosynthetic E. gracilis Z cultured at different light intensities showed no detectable phytoene, nor was phytoene found in mutant PR-4. However, dark-cultured E. gracilis Z yielded readily assayable amounts of phytoene. With the exception of PR-4, in which no C(40) carotenoids were detected, the following carotenes were identified in all from their mass spectra: phytoene, phytofluene, zeta-carotene, beta-zeacarotene, and beta-carotene. Of these, phytoene and beta-zeacarotene had not previously been unequivocally identified in Euglena.

Identification and distribution of the costimulatory receptor CD28 in the mouse.

T cell activation requires Ag-specific stimulation mediated by the TCR as well as an additional stimulus provided by Ag presenting cells. On human T cells, it has been shown that antibodies to the Ag CD28 can provide a potent amplification signal for cytokine production and proliferation. Here we describe the production of a mAb to the murine homologue of CD28, and the use of this antibody to examine the function and distribution of CD28 in the mouse. Anti-murine CD28 synergizes with TCR-mediated signals to greatly enhance lymphokine production and proliferation of T cells, and the CD28 signal is not blocked by cyclosporin A. In the peripheral lymphoid organs and in the blood of the mouse, all CD4+ and CD8+ T cells express CD28. In the thymus, CD28 expression is highest on immature CD3-, CD8+ and CD4+8+ cells, and on CD4-8- cells that express alpha beta and tau delta TCR. The level of CD28 on mature CD4+ and CD8+ alpha beta TCR+ thymocytes is two- to fourfold lower than on the immature cells. The potent costimulatory function of CD28 on mature T cells, together with the high level of expression on CD4+8+ thymocytes, suggest that this costimulatory receptor might play an important role in T cell development and activation.

CD28-mediated costimulation is necessary for optimal proliferation of murine NK cells.

CD28, a cell surface molecule expressed on all murine T cells, plays a critical role in T cell activation. We show here that NK-1.1+ cells, a subpopulation of SCID splenocytes, and IL-2-activated NK cells express CD28, although at lower levels than alpha beta T cells. Optimal proliferation of highly purified asialo GM1+ NK cells from the SCID spleen was observed in response to stimulation with IL-2 and PMA, together with anti-CD28 or L-B7+ cells. Thus, in addition to IL-2, murine NK cells require CD28-mediated costimulatory signals for optimal proliferation. IL-2-activated NK cells produced enhanced levels of IFN-gamma and TNF in response to stimulation with anti-CD28 and PMA. On the other hand, we were unable to demonstrate that CD28 signaling had any effect on NK-mediated cytotoxicity. We conclude that the CD28 costimulatory pathway is functional in NK cells and plays an important role in their proliferation and cytokine production.

Isolated mechanical lesions of the sural nerve.

One case of compression neuropathy and one case of iatrogenic stretch injury to the sural nerve were demonstrated with electrophysiologic (EP) testing. Isolated mechanical injuries to the sural nerve may occur more frequently than is generally realized, and EP studies can greatly aid in the diagnosis of these injuries, thus avoiding the necessity for neuroradiologic investigations.

The murine homologue of the T lymphocyte antigen CD28. Molecular cloning and cell surface expression.

The human T lymphocyte Ag CD28 (Tp44) is a homodimeric glycoprotein expressed on the surface of a majority of human peripheral T cells and thymocytes. Although exposure of T cells to anti-CD28 mAb does not activate T cells, stimulation of CD28 can synergize with signals transmitted through the TCR or other stimuli to augment proliferation and lymphokine production. We have used a portion of the human CD28 cDNA to isolate a homologous murine cDNA from an EL4 T lymphoma library. The murine clone has 61% nucleotide identity with the human cDNA. Both human and murine sequences exhibit homology with members of the Ig supergene family and CTLA-4, a T cell specific murine gene. Many characteristics of the human CD28 molecule are conserved within the putative murine CD28 polypeptide. The murine cDNA sequence encodes a polypeptide of 218 amino acids that has 68% identity with the human sequence. Both the murine and human molecules are integral membrane glycoproteins with hydrophobic signal peptide sequences and transmembrane region. All five potential N-linked glycosylation sites are conserved and six of the seven cysteine residues of the mouse protein are found in the human CD28 polypeptide. The murine cDNA is encoded by a single copy nonrearranging gene whose expression at the mRNA level is restricted to T cells. A rabbit antiserum was raised against a synthetic peptide corresponding to a hydrophilic portion of the translated murine cDNA sequence. This antiserum identifies an 80-kDa homodimer consisting of disulfide-bonded subunits of 40 kDa that is expressed on splenic T cells, thymocytes, and several T cell tumors, but not on B cells. deglycosylation studies indicate that four of the five N-linked glycosylation sites are used and that the mature core protein has a molecular mass of 25 kDa, close to that predicted by the cDNA sequence. Transfection of the murine cDNA into Chinese hamster ovary cells resulted in the expression of an 80-kDa dimeric molecule that was immunoprecipitated by the antipeptide antiserum. Taken together, these data provide strong support that we have identified the murine homologue of CD28.

Handcuff neuropathy revisited.

Peripheral nerve injury due to handcuff placement has been reported in the past, always involving the superficial radial nerve, and sometimes involving other peripheral nerves at the wrist. We present two unusual cases in which the ulnar nerves were affected, but the radial nerves were normal or only minimally affected. This serves to emphasize a broader clinical spectrum of handcuff injury. Significant disability may result. These cases also involve alcohol intoxication, which may predispose patients to this type of injury because of overly aggressive application of restraints motivated by the patients' bellicose behavior.