Correlations between biomarkers of senescent cell accumulation at the systemic, tissue and cellular levels in elderly patients.

The aim of the study was to investigate the relationship between established clinical systemic biomarkers of ageing and the development of age-associated diseases and senescent cell biomarkers at tissue and cellular levels. Thirty-eight patients (mean age 70 ± 4.9 years) who were assessed for traditional risk factors for cardiovascular diseases were included. From all patients we obtained biomaterials (peripheral blood, skin, subcutaneous fatty tissue) and isolated different cell types (peripheral blood mononuclear cells (PBMC), fibroblasts (FB) and mesenchymal stem/stromal cells (MSC)). Isolated cells were analyzed using several senescent cells biomarkers such as telomere length and telomerase activity, proliferation rate, cell cycle inhibitor expression (p16 and p21), b-galactosidase activity, gH2AX expression. CD34+ cell content in peripheral blood was determined by flow cytometry. Systemic senescent cell-associated factors (insulin-like growth factor 1 (IGF-1), fibroblast growth factor 21 (FGF-21), osteoprogerin, ferritin, soluble vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule 1 (ICAM-1)) in peripheral blood as well as senescence-associated secretory phenotype (SASP) components in MSC and FB secretome were evaluated by ELISA. Skin and adipose tissue biopsy samples were analyzed histologically to assess senescent cell markers. A strong significant association of tissue p16 expression with age (r = 0.600, p < 0.001), pulse wave velocity (PWV) (r = 0.394, p = 0.015), vascular cell adhesion molecule (VCAM-1) content (r = 0.312, p = 0.006) in the systemic blood stream and p16 mRNA level in the blood mononuclear cells (MNCs) (r = 0.380, p = 0.046) were confirmed by correlation analysis. Statistically significant correlations were found with indicators of FBs and MSCs proliferation in culture and acquisition of SASP by the cells. Thus, p16 expression in tissues correlated significantly with interleukin-6 (IL-6) (r = 0.485, p < 0.05) and monocyte chemoattractant protein type 1 (MCP-1) (r = 0.372, p < 0.05) secretion by isolated cells. The results of regression analysis confirmed that, regardless of age, the expression of p16 was associated with the proliferation of isolated cells and IL-6 within SASP. Based on these findings, two models have been proposed to predict the level of p16 expression in tissues from the levels of other markers of senescent cell accumulation determined by non-invasive methods and available in clinical practice.

Indoor radon exposure and its correlation with the radiometric map of uranium in Sweden.

Indoor radon concentrations are controlled by both human factors and geological factors. It is important to separate the anthropogenic and geogenic contributions. We show that there is a positive correlation between the radiometric map of uranium in the ground and the measured radon in the household in Sweden. A map of gamma radiation is used to obtain an equivalent uranium concentration (ppm eU) for each postcode area. The aggregated uranium content is compared to the yearly average indoor radon concentration for different types of houses. Interestingly, modern households show reduced radon concentrations even in postcode areas with high average uranium concentrations. This shows that modern construction is effective at reducing the correlation with background uranium concentrations and minimizing the health risk associated with radon exposure. These correlations and predictive housing parameters could assist in monitoring higher risk areas.

Urine TERT promoter mutations-based tumor DNA detection in patients with bladder cancer: A pilot study.

Telomerase reverse transcriptase (TERT) promoter mutations are the most frequent genetic events in bladder cancer (BC). The aim of the present pilot study was to evaluate the diagnostic potential of urine TERT promoter mutations-based liquid biopsy in patients with an ongoing oncological process, as well as in post-resection patients at risk of BC recurrence. A total of 60 patients were enrolled, of whom 27 patients had histologically proven BC; 23 had no signs of BC (control group); and 10 patients underwent transurethral malignancy resection 3-6 months prior to urine donation ('second look' group). Urine TERT promoter mutations were detected using Droplet Digital PCR. Receiver operating characteristic curve analysis revealed significant diagnostic power of the present approach (area under the curve: -0.768). At the cut-off value of tumor DNA fraction 0.34%, the sensitivity and specificity were 55.56 and 100%, respectively. In the positive samples, tumor DNA fraction varied significantly from 0.59 to 48.77%. In the 'second look' group, tumor DNA was detected in 4/10 patients, highlighting the possibility of BC recurrence with its fraction ranging only from 0.90 to 6.61%. Therefore, urine TERT promoter mutations-based liquid biopsy appears to be a promising tool for BC diagnosis and surveillance. The main study will include recruitment of additional patients, extension of the mutation panel, prolonged follow-up of the post-resection patients, as well as screening of industrial workers exposed to specific carcinogens.

Thermal magnetic fluctuations of a ferroelectric quantum critical point.

Entanglement of two different quantum orders is of an interest of the modern condensed matter physics. One of the examples is the dynamical multiferroicity, where fluctuations of electric dipoles lead to magnetization. We investigate this effect at finite temperature and demonstrate an elevated magnetic response of a ferroelectric near the ferroelectric quantum critical point (FE QCP). We calculate the magnetic susceptibility of a bulk sample on the paraelectric side of the FE QCP at finite temperature and find enhanced magnetic susceptibility near the FE QCP. We propose quantum paraelectric strontium titanate as a candidate material to search for dynamic multiferroicity. We estimate the magnitude of the magnetic susceptibility for this material and find that it is detectable experimentally.

Proximity-Induced Odd-Frequency Superconductivity in a Topological Insulator.

At an interface between a topological insulator (TI) and a conventional superconductor (SC), superconductivity has been predicted to change dramatically and exhibit novel correlations. In particular, the induced superconductivity by an s-wave SC in a TI can develop an order parameter with a p-wave component. Here we present experimental evidence for an unexpected proximity-induced novel superconducting state in a thin layer of the prototypical TI, Bi_{2}Se_{3} proximity coupled to Nb. From depth-resolved magnetic field measurements below the superconducting transition temperature of Nb, we observe a local enhancement of the magnetic field in Bi_{2}Se_{3} that exceeds the externally applied field, thus supporting the existence of an intrinsic paramagnetic Meissner effect arising from an odd-frequency superconducting state. Our experimental results are complemented by theoretical calculations supporting the appearance of such a component at the interface which extends into the TI. This state is topologically distinct from the conventional Bardeen-Cooper-Schrieffer state it originates from. To the best of our knowledge, these findings present a first observation of bulk odd-frequency superconductivity in a TI. We thus reaffirm the potential of the TI-SC interface as a versatile platform to produce novel superconducting states.

Ubiquity of Superconducting Domes in the Bardeen-Cooper-Schrieffer Theory with Finite-Range Potentials.

Based on recent progress in mathematical physics, we present a reliable method to analytically solve the linearized Bardeen-Cooper-Schrieffer (BCS) gap equation for a large class of finite-range interaction potentials leading to s-wave superconductivity. With this analysis, we demonstrate that the monotonic growth of the superconducting critical temperature T_{c} with the carrier density n predicted by standard BCS theory, is an artifact of the simplifying assumption that the interaction is quasilocal. In contrast, we show that any well-defined nonlocal potential leads to a "superconducting dome," i.e., a nonmonotonic T_{c}(n) exhibiting a maximum value at finite doping and going to zero for large n. This proves that, contrary to conventional wisdom, the presence of a superconducting dome is not necessarily an indication of competing orders, nor of exotic superconductivity.

Multiferroic quantum criticality.

The zero-temperature limit of a continuous phase transition is marked by a quantum critical point, which can generate physical effects that extend to elevated temperatures. Magnetic quantum criticality is now well established, and has been explored in systems ranging from heavy fermion metals to quantum Ising materials. Ferroelectric quantum critical behaviour has also been recently demonstrated, motivating a flurry of research investigating its consequences. Here, we introduce the concept of multiferroic quantum criticality, in which both magnetic and ferroelectric quantum criticality occur in the same system. We develop the phenomenology of multiferroic quantum criticality and describe the associated experimental signatures, such as phase stability and modified scaling relations of observables. We propose several material systems that could be tuned to multiferroic quantum criticality utilizing alloying and strain as control parameters. We hope that these results stimulate exploration of the interplay between different kinds of quantum critical behaviours.

Direct comparison of QIAamp DSP Virus Kit and QIAamp Circulating Nucleic Acid Kit regarding cell-free fetal DNA isolation from maternal peripheral blood.

BACKGROUND: Blood of pregnant women contains cell-free fetal DNA (cffDNA), which is widely used in non-invasive prenatal diagnosis. The modern laboratory equipment market provides huge variety of commercial kits for isolation of circulating nucleic acids, but unfortunately none of them are standardized for isolation of cffDNA, which is a crucial step for success of subsequent analysis. AIM: To compare DSPVK and CNAK in terms of cffDNA, cell-free total DNA (cftDNA) yield and resulting cffDNA fraction, as well as to try to explain the possible difference between the efficacy of these kits. METHODS: Peripheral blood samples were collected from 18 healthy pregnant women (6th-14th week of pregnancy) and from 12 healthy unpregnant subjects. cftDNA was isolated using QIAamp Circulating Nucleic Acid Kit (CNAK) (Qiagen, Germany) and QIAamp DSP Virus Kit (DSPVK) (Qiagen, Germany) from 1 ml of plasma of each sample. Methylation-sensitive restriction was carried out to isolate cffDNA. Yield of cffDNA and cftDNA was quantified using digital PCR. To explain the difference in resulting efficacy of these two kits PCR inhibitors analysis was performed, as well as the optimal plasma input for DSPVK was investigated. RESULTS: Yield of cffDNA using CNAK was statistically significantly higher than using DSPVK (167.62 (125.34-192.47) vs 52.88 (35.48-125.42) GEq/mL, p < 0.001). The same applies to cftDNA yield, CNAK appears to be statistically significantly superior to DSPVK (743.42 (455.02-898.33) vs 371.07 (294.37-509.89) GEq/mL, p < 0.001). cffDNA fraction using CNAK was also higher than using DSVPK (24.75 (14.5-31.53) vs 14.20 (6.88-25.83) %, p = 0.586), although the difference was not statistically significant due to inconsistency of DSPVK results from sample to sample. PCR inhibitors analysis uncovered increased amount of PCR inhibitors in CNAK cftDNA solution, compared to DSPVK (p = 0.002). Usage of 0.5 mL of plasma for cftDNA extraction with DSPVK over 1 mL demonstrates almost 1.8 times higher cftDNA output (p = 0.028), which suggests that this kit is not so viable for volumes of plasma larger than 0.5 mL. CONCLUSIONS: We recommend CNAK over DSPVK for quantitative analysis of cffDNA. Nevertheless, DSPVK is definitely suitable for qualitative analysis as well as for research with limited budget, since it is almost 3 times cheaper than CNAK.

Conformational fingerprint of blood and tissue ACEs: Personalized approach.

BACKGROUND: The pattern of binding of monoclonal antibodies (mAbs) to 18 epitopes on human angiotensin I-converting enzyme (ACE)-"conformational fingerprint of ACE"-is a sensitive marker of subtle conformational changes of ACE due to mutations, different glycosylation in various cells, the presence of ACE inhibitors and specific effectors, etc. METHODOLOGY/PRINCIPAL FINDINGS: We described in detail the methodology of the conformational fingerprinting of human blood and tissue ACEs that allows detecting differences in surface topography of ACE from different tissues, as well detecting inter-individual differences. Besides, we compared the sensitivity of the detection of ACE inhibitors in the patient's plasma using conformational fingerprinting of ACE (with only 2 mAbs to ACE, 1G12 and 9B9) and already accepted kinetic assay and demonstrated that the mAbs-based assay is an order of magnitude more sensitive. This approach is also very effective in detection of known (like bilirubin and lysozyme) and still unknown ACE effectors/inhibitors which nature and set could vary in different tissues or different patients. CONCLUSIONS/SIGNIFICANCE: Phenotyping of ACE (and conformational fingerprinting of ACE as a part of this novel approach for characterization of ACE) in individuals really became informative and clinically relevant. Appreciation (and counting on) of inter-individual differences in ACE conformation and accompanying effectors make the application of this approach for future personalized medicine with ACE inhibitors more accurate. This (or similar) methodology can be applied to any enzyme/protein for which there is a number of mAbs to its different epitopes.

Theory of combustion in disordered media.

The conventional theory of combustion describes systems where all of the parameters are spatially homogeneous. On the other hand, combustion in disordered explosives has long been known to occur after local regions of the material, called hot spots, are ignited. In this article we show that a system of randomly distributed hot spots exhibits a dynamic phase transition, which, depending on parameters of the system, can be either first or second order. These two regimes are separated by a tricritical point. We also show that on the qualitative level the phase diagram of the system is universal. It is valid in two and three dimensions, in the cases when the hot spots interact either by heat or sound waves, and in a broad range of microscopic disorder models.

Invariance of Topological Indices Under Hilbert Space Truncation.

We show that the topological index of a wave function, computed in the space of twisted boundary phases, is preserved under Hilbert space truncation, provided the truncated state remains normalizable. If truncation affects the boundary condition of the resulting state, the invariant index may acquire a different physical interpretation. If the index is symmetry protected, the truncation should preserve the protecting symmetry. We discuss implications of this invariance using paradigmatic integer and fractional Chern insulators, Z_{2} topological insulators, and spin-1 Affleck-Kennedy-Lieb-Tasaki and Heisenberg chains, as well as its relation with the notion of bulk entanglement. As a possible application, we propose a partial quantum tomography scheme from which the topological index of a generic multicomponent wave function can be extracted by measuring only a small subset of wave function components, equivalent to the measurement of a bulk entanglement topological index.

Data Mining for Three-Dimensional Organic Dirac Materials: Focus on Space Group 19.

We combined the group theory and data mining approach within the Organic Materials Database that leads to the prediction of stable Dirac-point nodes within the electronic band structure of three-dimensional organic crystals. We find a particular space group P212121 (#19) that is conducive to the Dirac nodes formation. We prove that nodes are a consequence of the orthorhombic crystal structure. Within the electronic band structure, two different kinds of nodes can be distinguished: 8-fold degenerate Dirac nodes protected by the crystalline symmetry and 4-fold degenerate Dirac nodes protected by band topology. Mining the Organic Materials Database, we present band structure calculations and symmetry analysis for 6 previously synthesized organic materials. In all these materials, the Dirac nodes are well separated within the energy and located near the Fermi surface, which opens up a possibility for their direct experimental observation.

Theory of deflagration in disordered media.

The conventional theory of burning works well in the case of uniform media where all system parameters are spatially independent. We develop a theory of burning in disordered media. In this case, rare regions (hot spots) where the burning process is more effective than on average may control the heat propagation in an explosive sample. We show that most predictions of the theory of burning are quite different from the conventional case. In particular, we show that a system of randomly distributed hot spots exhibits a dynamic phase transition, which is similar to the percolation transition. Depending on parameters of the system the phase transition can be either first or second order. These two regimes are separated by a tricritical point. The above results may be applicable to dynamics of any overheated disordered system with a first order phase transition.

Scanning Tunneling Microscopy Observation of Phonon Condensate.

Using quantum tunneling of electrons into vibrating surface atoms, phonon oscillations can be observed on the atomic scale. Phonon interference patterns with unusually large signal amplitudes have been revealed by scanning tunneling microscopy in intercalated van der Waals heterostructures. Our results show that the effective radius of these phonon quasi-bound states, the real-space distribution of phonon standing wave amplitudes, the scattering phase shifts, and the nonlinear intermode coupling strongly depend on the presence of defect-induced scattering resonance. The observed coherence of these quasi-bound states most likely arises from phase- and frequency-synchronized dynamics of all phonon modes, and indicates the formation of many-body condensate of optical phonons around resonant defects. We found that increasing the strength of the scattering resonance causes the increase of the condensate droplet radius without affecting the condensate fraction inside it. The condensate can be observed at room temperature.

Organic materials database: An open-access online database for data mining.

We present an organic materials database (OMDB) hosting thousands of Kohn-Sham electronic band structures, which is freely accessible online at http://omdb.diracmaterials.org. The OMDB focus lies on electronic structure, density of states and other properties for purely organic and organometallic compounds that are known to date. The electronic band structures are calculated using density functional theory for the crystal structures contained in the Crystallography Open Database. The OMDB web interface allows users to retrieve materials with specified target properties using non-trivial queries about their electronic structure. We illustrate the use of the OMDB and how it can become an organic part of search and prediction of novel functional materials via data mining techniques. As a specific example, we provide data mining results for metals and semiconductors, which are known to be rare in the class of organic materials.

Faraday Rotation Due to Surface States in the Topological Insulator (Bi1-xSbx)2Te3.

Using magneto-infrared spectroscopy, we have explored the charge dynamics of (Bi,Sb)2Te3 thin films on InP substrates. From the magneto-transmission data we extracted three distinct cyclotron resonance (CR) energies that are all apparent in the broad band Faraday rotation (FR) spectra. This comprehensive FR-CR data set has allowed us to isolate the response of the bulk states from the intrinsic surface states associated with both the top and bottom surfaces of the film. The FR data uncovered that electron- and hole-type Dirac Fermions reside on opposite surfaces of our films, which paves the way for observing many exotic quantum phenomena in topological insulators.

Erratum: Quantum Critical Origin of the Superconducting Dome in SrTiO_{3} [Phys. Rev. Lett. 115, 247002 (2015)].

This corrects the article DOI: 10.1103/PhysRevLett.115.247002.

Dynamical Quantum Phase Transitions: Role of Topological Nodes in Wave Function Overlaps.

A sudden quantum quench of a Bloch band from one topological phase toward another has been shown to exhibit an intimate connection with the notion of a dynamical quantum phase transition (DQPT), where the returning probability of the quenched state to the initial state-i.e., the Loschmidt echo-vanishes at critical times {t^{*}}. Analytical results to date are limited to two-band models, leaving the exact relation between topology and DQPT unclear. In this Letter, we show that, for a general multiband system, a robust DQPT relies on the existence of nodes (i.e., zeros) in the wave function overlap between the initial band and the postquench energy eigenstates. These nodes are topologically protected if the two participating wave functions have distinctive topological indices. We demonstrate these ideas in detail for both one and two spatial dimensions using a three-band generalized Hofstadter model. We also discuss possible experimental observations.

General Conditions for Proximity-Induced Odd-Frequency Superconductivity in Two-Dimensional Electronic Systems.

We obtain the general conditions for the emergence of odd-frequency superconducting pairing in a two-dimensional (2D) electronic system proximity coupled to a superconductor, making minimal assumptions about both the 2D system and the superconductor. Using our general results we show that a simple heterostructure formed by a monolayer of a group VI transition metal dichalcogenide, such as molybdenum disulfide, and an s-wave superconductor with Rashba spin-orbit coupling exhibits odd-frequency superconducting pairing. Our results allow the identification of a new class of systems among van der Waals heterostructures in which odd-frequency superconductivity should be present.

Dual nature of magnetic dopants and competing trends in topological insulators.

Topological insulators interacting with magnetic impurities have been reported to host several unconventional effects. These phenomena are described within the framework of gapping Dirac quasiparticles due to broken time-reversal symmetry. However, the overwhelming majority of studies demonstrate the presence of a finite density of states near the Dirac point even once topological insulators become magnetic. Here, we map the response of topological states to magnetic impurities at the atomic scale. We demonstrate that magnetic order and gapless states can coexist. We show how this is the result of the delicate balance between two opposite trends, that is, gap opening and emergence of a Dirac node impurity band, both induced by the magnetic dopants. Our results evidence a more intricate and rich scenario with respect to the once generally assumed, showing how different electronic and magnetic states may be generated and controlled in this fascinating class of materials.