Dynamics of magnetization at infinite temperature in a Heisenberg spin chain.

Understanding universal aspects of quantum dynamics is an unresolved problem in statistical mechanics. In particular, the spin dynamics of the one-dimensional Heisenberg model were conjectured as to belong to the Kardar-Parisi-Zhang (KPZ) universality class based on the scaling of the infinite-temperature spin-spin correlation function. In a chain of 46 superconducting qubits, we studied the probability distribution of the magnetization transferred across the chain's center, [Formula: see text]. The first two moments of [Formula: see text] show superdiffusive behavior, a hallmark of KPZ universality. However, the third and fourth moments ruled out the KPZ conjecture and allow for evaluating other theories. Our results highlight the importance of studying higher moments in determining dynamic universality classes and provide insights into universal behavior in quantum systems.

Stable quantum-correlated many-body states through engineered dissipation.

Engineered dissipative reservoirs have the potential to steer many-body quantum systems toward correlated steady states useful for quantum simulation of high-temperature superconductivity or quantum magnetism. Using up to 49 superconducting qubits, we prepared low-energy states of the transverse-field Ising model through coupling to dissipative auxiliary qubits. In one dimension, we observed long-range quantum correlations and a ground-state fidelity of 0.86 for 18 qubits at the critical point. In two dimensions, we found mutual information that extends beyond nearest neighbors. Lastly, by coupling the system to auxiliaries emulating reservoirs with different chemical potentials, we explored transport in the quantum Heisenberg model. Our results establish engineered dissipation as a scalable alternative to unitary evolution for preparing entangled many-body states on noisy quantum processors.

Single-photon detection using high-temperature superconductors.

The detection of individual quanta of light is important for quantum communication, fluorescence lifetime imaging, remote sensing and more. Due to their high detection efficiency, exceptional signal-to-noise ratio and fast recovery times, superconducting-nanowire single-photon detectors (SNSPDs) have become a critical component in these applications. However, the operation of conventional SNSPDs requires costly cryocoolers. Here we report the fabrication of two types of high-temperature superconducting nanowires. We observe linear scaling of the photon count rate on the radiation power at the telecommunications wavelength of 1.5 µm and thereby reveal single-photon operation. SNSPDs made from thin flakes of Bi2Sr2CaCu2O8+δ exhibit a single-photon response up to 25 K, and for SNSPDs from La1.55Sr0.45CuO4/La2CuO4 bilayer films, this response is observed up to 8 K. While the underlying detection mechanism is not fully understood yet, our work expands the family of materials for SNSPD technology beyond the liquid helium temperature limit and suggests that even higher operation temperatures may be reached using other high-temperature superconductors.

Disappearance of superconductivity due to vanishing coupling in the overdoped Bi[Formula: see text]Sr[Formula: see text]CaCu[Formula: see text]O[Formula: see text].

In cuprate superconductors, superconductivity is accompanied by a plethora of orders and phenomena that complicate our understanding of superconductivity in these materials. Prominent in the underdoped regime, these orders weaken or vanish with overdoping. Here, we approach the superconducting phase from the more conventional overdoped side. We present angle-resolved photoemission spectroscopy studies of Bi[Formula: see text]Sr[Formula: see text]CaCu[Formula: see text]O[Formula: see text], cleaved and annealed in ozone to increase the doping all the way to the non-superconducting phase. We show that the mass renormalization in the antinodal region of the Fermi surface that possibly reflects the pairing, weakens with doping and completely disappears precisely where superconductivity disappears. This is the evidence that in the overdoped regime, superconductivity is determined primarily by the coupling strength. A doping dependence and an abrupt disappearance above the transition temperature eliminate phononic mechanism of the observed renormalization and identify the onset of spin-fluctuations as its likely origin.

Phase diagram of Bi2Sr2CaCu2O8+δ revisited.

In cuprate superconductors, the doping of carriers into the parent Mott insulator induces superconductivity and various other phases whose characteristic temperatures are typically plotted versus the doping level p. In most materials, p cannot be determined from the chemical composition, but it is derived from the superconducting transition temperature, Tc, using the assumption that the Tc dependence on doping is universal. Here, we present angle-resolved photoemission studies of Bi2Sr2CaCu2O8+δ, cleaved and annealed in vacuum or in ozone to reduce or increase the doping from the initial value corresponding to Tc = 91 K. We show that p can be determined from the underlying Fermi surfaces and that in-situ annealing allows mapping of a wide doping regime, covering the superconducting dome and the non-superconducting phase on the overdoped side. Our results show a surprisingly smooth dependence of the inferred Fermi surface with doping. In the highly overdoped regime, the superconducting gap approaches the value of 2Δ0 = (4 ± 1)kBTc.

CD1d-dependent immune suppression mediated by regulatory B cells through modulations of iNKT cells.

Regulatory B cells (Breg) express high levels of CD1d that presents lipid antigens to invariant natural killer T (iNKT) cells. The function of CD1d in Breg biology and iNKT cell activity during inflammation remains unclear. Here we show, using chimeric mice, cell depletion and adoptive cell transfer, that CD1d-lipid presentation by Bregs induces iNKT cells to secrete interferon (IFN)-γ to contribute, partially, to the downregulation of T helper (Th)1 and Th17-adaptive immune responses and ameliorate experimental arthritis. Mice lacking CD1d-expressing B cells develop exacerbated disease compared to wild-type mice, and fail to respond to treatment with the prototypical iNKT cell agonist α-galactosylceramide. The absence of lipid presentation by B cells alters iNKT cell activation with disruption of metabolism regulation and cytokine responses. Thus, we identify a mechanism by which Bregs restrain excessive inflammation via lipid presentation.

Measurement of circulating transcripts and gene cluster analysis predicts and defines therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) is an effective method for treating neuroendocrine tumors (NETs). It is limited, however, in the prediction of individual tumor response and the precise and early identification of changes in tumor size. Currently, response prediction is based on somatostatin receptor expression and efficacy by morphological imaging and/or chromogranin A (CgA) measurement. The aim of this study was to assess the accuracy of circulating NET transcripts as a measure of PRRT efficacy, and moreover to identify prognostic gene clusters in pretreatment blood that could be interpolated with relevant clinical features in order to define a biological index for the tumor and a predictive quotient for PRRT efficacy. METHODS: NET patients (n = 54), M: F 37:17, median age 66, bronchial: n = 13, GEP-NET: n = 35, CUP: n = 6 were treated with (177)Lu-based-PRRT (cumulative activity: 6.5-27.8 GBq, median 18.5). At baseline: 47/54 low-grade (G1/G2; bronchial typical/atypical), 31/49 (18)FDG positive and 39/54 progressive. Disease status was assessed by RECIST1.1. Transcripts were measured by real-time quantitative reverse transcription PCR (qRT-PCR) and multianalyte algorithmic analysis (NETest); CgA by enzyme-linked immunosorbent assay (ELISA). Gene cluster (GC) derivations: regulatory network, protein:protein interactome analyses. STATISTICAL ANALYSES: chi-square, non-parametric measurements, multiple regression, receiver operating characteristic and Kaplan-Meier survival. RESULTS: The disease control rate was 72 %. Median PFS was not achieved (follow-up: 1-33 months, median: 16). Only grading was associated with response (p < 0.01). At baseline, 94 % of patients were NETest-positive, while CgA was elevated in 59 %. NETest accurately (89 %, χ(2) = 27.4; p = 1.2 × 10(-7)) correlated with treatment response, while CgA was 24 % accurate. Gene cluster expression (growth-factor signalome and metabolome) had an AUC of 0.74 ± 0.08 (z-statistic = 2.92, p < 0.004) for predicting response (76 % accuracy). Combination with grading reached an AUC: 0.90 ± 0.07, irrespective of tumor origin. Circulating transcripts correlated accurately (94 %) with PRRT responders (SD+PR+CR; 97 %) vs. non-responders (91 %). CONCLUSIONS: Blood NET transcript levels and the predictive quotient (circulating gene clusters+grading) accurately predicted PRRT efficacy. CgA was non-informative.

The clinical utility of a novel blood-based multi-transcriptome assay for the diagnosis of neuroendocrine tumors of the gastrointestinal tract.

OBJECTIVES: Current monoanalyte blood-based biomarkers for the diagnosis and follow-up of neuroendocrine tumors (NETs) do not achieve satisfactory metrics of sensitivity and specificity. We report the sensitivity and selectivity of the PCR-based test, the NETest, to detect tumors with reference to other benign and malignant gastrointestinal diseases. METHODS: A total of 179 cases (gastrointestinal tumors: n=81; pancreatic disease: n=98) were prospectively collected and assessed using the NETest or chromogranin A (CgA) to determine metrics for detecting small intestinal and pancreatic NETs. RESULTS: For intestinal carcinoids, the accuracy of the NETest was 93% (all NETs positive and 3 (12%) colorectal tumors were positive). CgA was positive in 80%, but 29% (n=7) of colorectal cancers were CgA positive. For pancreatic disease, the NETest accuracy was 94% (96% NETs positive, 2 (6%) of intraductal papillary mucinous neoplasms (IPMNs) were positive). The accuracy of CgA was 56% (29% of pancreatic NETs were CgA positive). Overall, the NETest was significantly more sensitive than CgA for the detection of small intestinal (area under the curve 0.98 vs. 0.75 P<0.0001) and pancreatic NETs (0.94 vs. 0.52, P<0.0001). NETest scores were elevated (P<0.05) in extensive disease and were more accurate (76-80%) than CgA levels (20-32%). The metrics of the multianalyte NETest met the performance criteria proposed by the National Institutes of Health for biomarkers, whereas CgA measurement did not. CONCLUSIONS: This study demonstrates that a blood-based multianalyte NET gene transcript measurement of well-differentiated small intestinal and pancreatic neuroendocrine tumor disease is sensitive and specific and outperforms the current monoanalyte diagnostic strategy of plasma CgA measurement.

Gene transcript analysis blood values correlate with 68Ga-DOTA-somatostatin analog (SSA) PET/CT imaging in neuroendocrine tumors and can define disease status.

PURPOSE: Precise determination of neuroendocrine tumor (NET) disease status and response to therapy remains a rate-limiting concern for disease management. This reflects limitations in biomarker specificity and resolution capacity of imaging. In order to evaluate biomarker precision and identify if combinatorial blood molecular markers and imaging could provide added diagnostic value, we assessed the concordance between (68)Ga-somatostatin analog (SSA) positron emission tomography (PET), circulating NET gene transcripts (NETest), chromogranin A (CgA), and Ki-67 in NETs. METHODS: We utilized two independent patient groups with positive (68)Ga-SSA PET: data set 1 ((68)Ga-SSA PETs undertaken for peptide receptor radionuclide therapy (PRRT), as primary or salvage treatment, n = 27) and data set 2 ((68)Ga-SSA PETs performed in patients referred for initial disease staging or restaging after various therapies, n = 22). We examined the maximum standardized uptake value (SUVmax), circulating gene transcripts, CgA levels, and baseline Ki-67. Regression analyses, generalized linear modeling, and receiver-operating characteristic (ROC) analyses were undertaken to determine the strength of the relationships. RESULTS: SUVmax measured in two centers were mathematically evaluated (regression modeling) and determined to be comparable. Of 49 patients, 47 (96 %) exhibited a positive NETest. Twenty-six (54 %) had elevated CgA (χ(2) = 20.1, p < 2.5×10(-6)). The majority (78 %) had Ki-67 < 20 %. Gene transcript scores were predictive of imaging with >95 % concordance and significantly correlated with SUVmax (R (2) = 0.31, root-mean-square error = 9.4). The genes MORF4L2 and somatostatin receptors SSTR1, 3, and 5 exhibited the highest correlation with SUVmax. Progressive disease was identified by elevated levels of a quotient of MORF4L2 expression and SUVmax [ROC-derived AUC (R (2) = 0.7, p < 0.05)]. No statistical relationship was identified between CgA and Ki-67 and no relationship with imaging parameters was evident. CONCLUSION: (68)Ga-SSA PET imaging parameters (SUVmax) correlated with a circulating NET transcript signature. Disease status could be predicted by an elevated quotient of gene expression (MORF4L2) and SUVmax. These observations provide the basis for further exploration of strategies that combine imaging parameters and disease-specific molecular data for the improvement of NET management.

Design and performance of an ultra-high vacuum scanning tunneling microscope operating at dilution refrigerator temperatures and high magnetic fields.

We describe the construction and performance of a scanning tunneling microscope capable of taking maps of the tunneling density of states with sub-atomic spatial resolution at dilution refrigerator temperatures and high (14 T) magnetic fields. The fully ultra-high vacuum system features visual access to a two-sample microscope stage at the end of a bottom-loading dilution refrigerator, which facilitates the transfer of in situ prepared tips and samples. The two-sample stage enables location of the best area of the sample under study and extends the experiment lifetime. The successful thermal anchoring of the microscope, described in detail, is confirmed through a base temperature reading of 20 mK, along with a measured electron temperature of 250 mK. Atomically resolved images, along with complementary vibration measurements, are presented to confirm the effectiveness of the vibration isolation scheme in this instrument. Finally, we demonstrate that the microscope is capable of the same level of performance as typical machines with more modest refrigeration by measuring spectroscopic maps at base temperature both at zero field and in an applied magnetic field.

Experimental substantiation for the use of mexidol and 3-hydroxypyridine fumarate in chronic myocardial injury.

We studied the cardioprotective properties of mexidol and 3-hydroxypyridine fumarate in rat model of chronic myocardial injury. We found that 3-hydroxypyridine fumarate (25 mg/kg) produced more pronounced antioxidant and cardioprotective effects than mexidol (25 mg/kg).

[The character of the morphological changes of the mucous membrane of the large intestine and the genetic polymorphism of IL-1RA, IL-1B, IL-4 TNFA in patient with irritable bowel syndrome].

UNLABELLED: The aim of this study was to evaluate the presence or absence of a relationship between the variants of the course of IBS and their association with genetic polymorphisms of genes and intergenic interaction of cytokines. MATERIALS AND METHODS: The sample consisted of 81 patients, the diagnosis was verified according to the criteria of the Rome III, were isolated psychopathological, morphological complications, extra-intestinal symptoms. Polymorphism genotyping IL-1Ra, IL-b, IL-4, TNFa performed by PCR. Statistical treatment are a non-parametric analysis of multiple comparisons, hierarchical log-linear analysis. It is found out the relation between the clinical variants with morphological changes of the mucous membrane of the large intestine, the association between gender characteristics of patients with IBS is established and with genetic polymorphisms of cytokines.

[Efficacy of combined administration of ridostin and oseltamivir (tamiflu) for therapy and prophylaxis of experimental infection induced by influenza virus A (H5N1) in mice].

AIM: Study of possibility of treatment-prophylaxis effect increase during combined administration of ridostin and tamiflu in experiments in mice infected with highly pathogenic influenza virus strain A/chicken/Kurgan/05/2005 (H5N1). MATERIALS AND METHODS: Balb/c line mice infected intranasally with influenza virus at 100 and 10 LD50 doses received ridostin and tamiflu as monopreparation or the combined variant before or after the infection. The mice were observed for 16 days, lethality rate, protection coefficient and average life span were evaluated. Virus concentration in lungs was determined by using titration in MDCK cell line. RESULTS: Combined administration ofridostin and tamiflu after the infection increased survivability of the animals when compared with the control group, and reduced influenza virus concentration in lungs. CONCLUSION: Treatment effect during combined administration of ridostin and tamiflu after influenza virus infection increased.

[The application of xMAP technology in genetic typing of measles virus].

The genetic typing of measles virus in clinical samples using xMAP technology was applied. The study provided the calculation and application of specific oligonucleotide probes of genotypes D4, D6 and D7 of measles virus. The strain HobO96 genotype A of measles virus as a check sample was used. The technical approaches to the optimization of preparatory work organization and to the process of identification of measles virus genotypes are described. The presence of genotypes D4, D6 and D7 in clinical samples is proved by the sequence analysis. The genetic typing effectiveness of technique of DNA hybridization using xMAP technology on the instrumental base BioPlex (BioRad, USA) is demonstrated.

[Evaluation of immunogenicity and safety of 2 immunizations with allantoic intranasal live influenza vaccine Ultragrivac].

AIM: Evaluate reactogenicity, safety and immunogenicity in phase 2 clinical trials of 2 immunization schedules with Ultragrivac--an allantoic intranasal life influenza vaccine based on A/17/ duck/Potsdam/86/92 [17/H5] reassortant strain. MATERIALS AND METHODS: 4 groups of volunteers participated in the study: group 1--40 individuals were vaccinated twice with a 10 day interval; group 2--40 individuals were vaccinated twice with a 21 day interval; group 3 (control)--10 individuals received placebo twice with a 10 day interval; group 4 (control)--10 individuals received placebo twice with a 21 day interval. Local (secretory IgA), cellular and humoral immune response were evaluated. Humoral immunity was evaluated by the intensity of increase of geometric mean antibody titers against 2 influenza virus strains A/17/duck/Potsdam/86/92 [17/H5] and A/chicken/Suzdalka/Nov-1 1/2005 (H5N1), and by the level of significant (4 times or more) antibody seroconversions after the vaccination. RESULTS: After the use of Ultragrivac the level of secretory IgA in the nasal cavity of vaccinated volunteers in the groups with revaccination intervals of 10 and 21 days increased significantly. The second immunization with 10 or 21 day intervals significantly increased postvaccinal humoral immune response. Humoral immune response induction after 2 vaccinations with 10 day interval was no less effective than with 21 day interval. CONCLUSION: Ultragrivac allantoic intranasal live influenza vaccine is areactogenic, harmless for vaccinated individuals, safe for those around, and has immunogenic properties against not only homologous virus A(H5N2), but also against influenza strain A(H5N1).

[Studies of properties of pandemic influenza virus A/H1N1 circulated in Russian Federation in 2009 - 2010].

AIM: Studies of cultural, virologic, antigenic properties of 89 samples of pandemic influenza A(H1N1) 2009 virus isolated in Russian Federation from May 2009 to March 2010. MATERIALS AND METHODS: Properties of isolated samples were compared with those of the reference strain A/ California/04/2009 (H1N1). RESULTS: Studies of biological properties and analysis of genome nucleotide sequences of the isolated samples showed that those strains are closely related to the reference strain. CONCLUSION: Monitoring of genetic, virologic and antigenic properties of pandemic influenza A(H1N1) 2009 virus isolates carried out from May 2009 to March 2010 did not reveal significant changes in the abovementioned properties of the virus or emergence of mutations that can lead to such changes.

[In vitro and in vivo efficacy of Ingavirin against strains of pandemic influenza virus A(H1N1/09)v].

AIM: To study efficacy of Ingavirin in vitro and in vivo against strains of pandemic influenza virus A(H1N1/09)v and influenza virus A(H5N1) and A(H3N2). MATERIALS AND METHODS: Changes in hemagglutinating and cytopathic activity of influenza virus strains A(H1N1/09)v, A(H5N1) and A(H3N2) during their incubation in the presence of Ingavirin or Remantadin on MDCK cell culture were studied. In mice infected by influenza strains A(H1N1/09)v and A(H3N2) and orally treated with Ingavirin, Tamiflu or Remantadin virus titers in lungs were measured. RESULTS: There was decrease in hemagglutinating and cytopathic activity of influenza virus strains after incubation with Ingavirin in vitro. Ingavirin effectively inhibited reproduction of influenza virus strains A(H1N1/09)v and A(H3N2) in lungs of infected mice. Titers of these strains in lung homogenates decreased when Ingavirin was orally administered to infected mice. CONCLUSION: Strains of influenza virus A(H1N1/09)v were susceptible to Ingavirin and Tamiflu but resistant to Remantadin. Reference strains of A(H5N1) and A(H3N2) were susceptible to Ingavirin, Tamiflu and Remantadin.

[Study of efficacy of anaferon pediatric in mice infected by pandemic influenza virus A(H1N1/09)v].

AIM: To study efficacy of anaferon pediatric in mice infected by pandemic influenza virus A(H1N1/09)v. MATERIALS AND METHODS: Influenza virus strain A/California/07/2009 (H1N1)v was used. Three groups of BALB/c mice intranasally inoculated with influenza virus were studied. First group received solution of Anaferon pediatric during 5 days before and 8 days after inoculation, 2nd group received Tamiflu during 5 days after inoculation. Distilled water was administered orally to mice from control group. RESULTS: It was shown that Anaferon pediatric used as preventive and treatment agent in mice intranasally inoculated with 100% infectious dose of influenza virus strain A/ California/07/2009 (H1N1)v had antiviral effect, which expressed in 10-fold decreased reproduction of influenza virus in lungs of infected mice compared to control group measured 4, 6, and 8 days after inoculation. CONCLUSION: Use of anaferon pediatric before and after inoculation with influenza virus A(H1N1/09)v was not less effective than use of Tamiflu after inoculation.

[Pandemic influenza virus A (H1N1) in Amur region in autumn 2009].

AIM: Isolation and study of molecular genetic characteristics of pandemic influenza virus A (H1N1) circulated in Amur region in autumn 2009 as well as testing of serum samples taken from citizens of this region during November- December 2009 in order to measure levels of antibodies to socially significant serotypes of influenza A virus. MATERIALS AND METHODS: Strain of pandemic influenza virus A/Blagoveschensk/01/2009 (H1N1) was isolated on MDCK cell culture and nucleotide sequences of all eight segments of viral genome were determined. Five hundred seventy-six serum samples taken in Amur region in autumn 2009 were tested by hemagglutination inhibition assay. RESULTS: Nucleotide sequence of A/Blagovechensk/01/2009 (H1N1) strain was 99.7% identical to reference influenza virus strain A/California/04/2009. Diagnostically significant titers of antibodies to pandemic influenza virus were observed in 46.3% of persons younger 30 years old and in 20.1% older persons. Antibodies to seasonal influenza virus H1N1 and H3N2 were detected in 39.5 and 29.8% of persons respectively. CONCLUSION: Final seroepidemiological picture of distribution of pandemic virus in Amur region matches with the one for seasonal influenza virus A (H1N1): > 60% of seropositive persons were registered in age group < 18 years old, and this proportion increases with increasing age.

[Study of antiviral activity of extracts obtained from basidial fungi against influenza viruses of different subtypes in experiments in vitro and in vivo].

AIM: To study antiviral activity of extracts obtained from basidial fungi against influenza viruses of different subtypes. MATERIALS AND METHODS: Antiviral activity of extracts obtained from basidial fungi against influenza virus A/chicken/Kurgan/05/2005 (H5N1) was determined in in vitro experiments. Changes in infectiousness of pandemic influenza virus A/Moscow/226/2009 (HIN1)v caused by extracts of basidial fungi was studied in experiments in vitro and in vivo. RESULTS: Seventy water extracts of basidial fungi were studied, of which 10 were able to inhibit infectiousness of influenza virus strain A/ chicken/Kurgan/05/2005 (H5N1) in MDCK cell culture. Also, several studied extracts decreased infectiousness of pandemic influenza virus strain A/ Moscow/226/2009 (H1N1)v in MDCK cells and inhibit its reproduction in lungs of infected mice. CONCLUSION: High antiviral activity of extracts obtained from basidial fungi against influenza viruses opens perspectives for development of drugs with preventive and treatment effects.