Quantum measurement enables single biomarker sensitivity in flow cytometry.

We present the first unambiguous experimental method enabling single-fluorophore sensitivity in a flow cytometer using quantum properties of single-photon emitters. We use a quantum measurement based on the second-order coherence function to prove that the optical signal is produced by individual biomarkers traversing the interrogation volume of the flow cytometer from the first principles. This observation enables the use of the quantum toolbox for rapid detection, enumeration, and sorting of single fluorophores in large cell populations as well as a 'photons-to-moles' calibration of this measurement modality.

[DNA Phenotyping of Remains from Elite Burials of the Khazar Period of Southern Russia].

Ancient DNA analyses help to solve the problems related to the genogeographic origin and migration patterns of populations. The Khazar Khaganate is a subject of controversy among researchers. Its complex historical development, lack of a sufficient number of artistic and written sources, the disappearance of representatives of Khazar culture leaves open the question of the appearance of the Khazars. DNA phenotyping of bone remains from elite burials of the Khazar period of Southern Russia was carried out with respect to eye color, hair color, skin color, and AB0 blood groups. Eight out of 10 individuals had brown eyes, dark hair (to varying degrees), and a predominantly dark skin during their lifetime. Individuals from two burials had gray-blue eyes, and one individual had blond hair. The most probable AB0 blood group was identified in eight people, of which five blood group 0 (I) group, four had blood group A (II), and one had blood group B (III). The allele frequency distribution was assessed for ten population-specific autosomal markers and suggested high heterogeneity for the ethnogeographic origin of the Khazars examined. The results are evidence for ethnocultural, genetic, and phenotypic diversity of the Khazar Khaganate.

[Universal Panel of Insertion/Deletion Polymorphisms and Biochip-Based Kit ChipID106 for Genetic Personal Identification].

A panel of 106 insertion/deletion (InDel) polymorphisms and a method of their genotyping on biochips were proposed as a new approach to genetic personal identification. Short lengths and low mutation rates are basic properties of InDel markers, which thus have significant advantages over short tandem repeats (STRs) widely used in forensics. The allele frequency distributions of all known InDel polymorphisms were studied in the five largest world populations (European, East Asian, South Asian, African, and American). Markers were selected to meet the following criteria: the minor allele frequency (MAF) is higher than 0.30; the physical distance between markers is greater than 3 Mb; there are no polymorphisms, tandem repeats, and palindromes in the flanking sequences; the AT/GC ratio is close to 1. A panel of 106 polymorphisms was thus formed; the average MAF was estimated at 0.396 in the five populations. The method developed for panel genotyping included one-step multiplex PCR and subsequent hybridization on a biological microarray. The average amplicon length was 72 bp. A sample of 201 residents of Moscow and St. Petersburg was tested to determine the main characteristics of the panel: the random matching probability (MP) was 1.89x 10^(-43) and the combined probability of paternity exclusion (CPE) was 0.99999999063. The method provides an alternative to molecular genetic personal identification based on the STR length variations.

[Review of the possible impact of 100% juices on nutritional quality, risk of obesity and type 2 diabetes mellitus].

Studies show that fruit juices are a source of macro- and micronutrients. Despite the fact that modern technologies for the industrial processing of fruits into juice are aimed at preserving the bioactive compounds of the original raw materials, juices are the subject of controversy due to the presence of free sugars and less dietary fiber than in fresh fruits. The purpose of the work was to systematize the available studies on the effect of 100% juices on nutrition quality, obesity and type 2 diabetes mellitus. Material and methods. Systematic search in PubMed, Google Scholar, eLIBRARY databases in accordance with the inclusion criteria: the study examined 100% fruit or vegetable juices, the article was in Russian or English in a peer-reviewed journal, the subjects (in the case of clinical studies) were people aged 1 to 18 years and older. 98 sources were analyzed based on the title of the article, of which 35 did not relate to juices. 63 sources were analyzed based on their abstracts, of which 28 were included in the main study. Results. According to the results of the literature analysis, it follows that moderate consumption of 100% juices not only does not have negative effects on human health, but, on the contrary improve the health of the organism. In particular, its intake helps lower blood pressure and the content of highly sensitive C-reactive protein, thereby reducing the risk of cardiovascular diseases. Juices enrich the daily diet due to the macro- and micronutrients they contain, which improves the quality of nutrition in general. Researches prove that there is no correlation between moderate juice consumption and type 2 diabetes onset. The glycemic index of the juices is low or medium, which distinguishes them from standard soft drinks containing sugar. The consumption of juices (100-500 ml/day) does not increase the risk of obesity in adults and children. Conclusion. Negative effects, such as weight gain and an increased risk of diabetic diseases, can only be observed with excessive consumption of juices.

[Comparative analysis of the total content of polyphenols in some types of industrial juice products].

Fruits are the most important source of polyphenols, substances that have a positive effect on human health. Modern technologies for the industrial processing of fruits into juice are aimed at preserving the useful components of the raw material in it. The issue of the content of polyphenols in industrial juice products, and, especially, changes in their concentration over time, is important for understanding the nutritional value of juice products and requires further study. The purpose of the work is to study the total content of polyphenols depending on the type of juice products and the time elapsed since the product was manufactured. Material and methods. The total content of polyphenols in terms of gallic acid was determined by the Folin-Ciocalteu method in four popular types of juice products (orange, grapefruit and apple juice, cherry nectar), various brands and with different production dates. The results of the determination in 60 product samples selected from Russian retail chains were analyzed. Results. Polyphenols are found in all types of products in significant amounts: in orange juices from 678 to 870 mg/kg, in grapefruit juices from 447 to 798 mg/kg, in apple juices from 264 to 1320 mg/kg, in cherry nectars from 696 to 1090 mg/kg. The highest average content was found in cherry nectars (859±106 mg/kg), followed by orange (781±54 mg/kg) and grapefruit juices (634±91 mg/kg). In apple juices, there is a significant variation in the content of polyphenols depending on the method of juice production - the highest content of polyphenols was found in straight-pressed apple juices (1119±124 mg/kg). The content of polyphenols in products stored for six months or more does not show any significant differences from the content in fresher products, which suggests a consistently high content of polyphenols in juice products throughout the entire shelf life. Conclusion. The study showed the presence of high concentrations of common polyphenols in juice products. The dependence of total polyphenol content on the time elapsed since the production of juice product was not found. Juice products of industrial production can make a significant contribution to the intake of polyphenols in the human body.

[A Biochip for Genotyping Polymorphisms Associated with Eye, Hair, Skin Color, AB0 Blood Group, Sex, Y Chromosome Core Haplogroup, and Its Application to Study the Slavic Population].

This paper presents a method for genotyping a panel of 60 single nucleotide polymorphisms (SNPs) using single-stage PCR followed by hybridization on a hydrogel biochip. The pool of analyzed polymorphisms consists of 41 SNPs included in the HIrisPlex-S panel, 4 SNPs of the AB0 gene (261G>Del, 297A>G, 657C>T, 681G>A), markers of the AMELX and AMELY genes, and 14 SNP markers of the Y chromosome haplogroups: B (M60), C (M130), D (CTS3946), E (M5388), G (P257), H (M2920), I (U179), J (M304), L (M185), N (M231), O (M175), Q (M1105), R (P224) and T (M272). These genetic data allow one to predict the phenotype of the desired person according to the characteristics of eye, hair, skin color, AB0 blood group, sex, and genogeographic origin in the male line. The setting protocol is simplified as much as possible to facilitate the introduction of the method into practice. The distribution of allele frequencies of the studied polymorphisms, as well as AB0 blood groups among the Slavs (N = 482), originating mainly from central Russia, was established.

Structure Investigations of Islands with Atomic-Scale Boron-Carbon Bilayers in Heavily Boron-Doped Diamond Single Crystal: Origin of Stepwise Tensile Stress.

The detailed studies of the surface structure of synthetic boron-doped diamond single crystals using both conventional X-ray and synchrotron nano- and microbeam diffraction, as well as atomic force microscopy and micro-Raman spectroscopy, were carried out to clarify the recently discovered features in them. The arbitrary shaped islands towering above the (111) diamond surface are formed at the final stage of the crystal growth. Their lateral dimensions are from several to tens of microns and their height is from 0.5 to 3 µm. The highly nonequilibrium conditions of crystal growth enhance the boron solubility and, therefore, lead to an increase of the boron concentrations in the islands on the surface up to 1022 cm-3, eventually generating significant stresses in them. The stress in the islands is found to be the volumetric tensile stress. This conclusion is based on the stepwise shift of the diamond Raman peak toward lower frequencies from 1328 to 1300 cm-1 in various islands and on the observation of the shift of three low-intensity reflections at 2-theta Bragg angles of 41.468°, 41.940° and 42.413° in the X-ray diffractogram to the left relative to the (111) diamond reflection at 2theta = 43.93°. We believe that the origin of the stepwise tensile stress is a discrete change in the distances between boron-carbon layers with the step of 6.18 Å. This supposition explains also the stepwise (step of 5 cm-1) behavior of the diamond Raman peak shift. Two approaches based on the combined application of Raman scattering and X-ray diffraction data allowed determination of the values of stresses both in lateral and normal directions. The maximum tensile stress in the direction normal to the surface reaches 63.6 GPa, close to the fracture limit of diamond, equal to 90 GPa along the [111] crystallographic direction. The presented experimental results unambiguously confirm our previously proposed structural model of the boron-doped diamond containing two-dimensional boron-carbon nanosheets and bilayers.

Practical quantum-enhanced receivers for classical communication.

Communication is an integral part of human life. Today, optical pulses are the preferred information carriers for long-distance communication. The exponential growth in data leads to a "capacity crunch" in the underlying physical systems. One of the possible methods to deter the exponential growth of physical resources for communication is to use quantum, rather than classical measurement at the receiver. Quantum measurement improves the energy efficiency of optical communication protocols by enabling discrimination of optical coherent states with the discrimination error rate below the shot-noise limit. In this review article, the authors focus on quantum receivers that can be practically implemented at the current state of technology, first and foremost displacement-based receivers. The authors present the experimentalist view on the progress in quantum-enhanced receivers and discuss their potential.

Experimental demonstration of the near-quantum optimal receiver.

We implement the cyclic quantum receiver based on the theoretical proposal of Roy Bondurant and demonstrate experimentally below the shot-noise limit (SNL) discrimination of quadrature phase-shift keying signals (PSK). We also experimentally test the receiver generalized for longer communication alphabet lengths and coherent frequency shift keying (CFSK) encoding. Using off-the-shelf components, we obtain state discrimination error rates that are 3 dB and 4.6 dB below the SNLs of ideal classical receivers for quadrature PSK and CFSK encodings, respectively. The receiver unconditionally surpasses the SNL for M=8 PSK and CFSK. This receiver can be used for the simple and robust practical implementation of quantum-enhanced optical communication.

Electromagnetically induced transparency in inhomogeneously broadened solid media.

We study, theoretically and experimentally, electromagnetically induced transparency (EIT) in two different solid-state systems. Unlike many implementations in homogeneously broadened media, these systems exhibit inhomogeneous broadening of their optical and spin transitions typical of solid-state materials. We observe EIT lineshapes typical of atomic gases, including a crossover into the regime of Autler-Townes splitting, but with the substitution of the inhomogeneous widths for the homogeneous values. We obtain quantitative agreement between experiment and theory for the width of the transparency feature over a range of optical powers and inhomogeneous linewidths. We discuss regimes over which analytical and numerical treatments capture the behavior. As solid-state systems become increasingly important for scalable and integratable quantum optical and photonic devices, it is vital to understand the effects of the inhomogeneous broadening that is ubiquitous in these systems. The treatment presented here can be applied to a variety of systems, as exemplified by the common scaling of experimental results from two different systems.

Refraction and ultra-small-angle scattering of X-rays in a single-crystal diamond compound refractive lens.

In this work a double-crystal setup is employed to study compound refractive lenses made of single-crystal diamond. The point spread function of the lens is calculated taking into account the lens transmission, the wavefront aberrations, and the ultra-small-angle broadening of the X-ray beam. It is shown that, similarly to the wavefront aberrations, the ultra-small-angle scattering effects can significantly reduce the intensity gain and increase the focal spot size. The suggested approach can be particularly useful for the characterization of refractive X-ray lenses composed of many tens of unit lenses.

Comparative Study of Novel Fluorescent Cyanine Nucleotides: Hybridization Analysis of Labeled PCR Products Using a Biochip.

This study investigated the synthesis and substrate properties of Cy5-labeled dUTP derivatives with different substituents, linkers between the dye unit and pyrimidine heterocycle and fluorophore charges. Fluorescently labeled nucleoside triphosphates were studied as substrates using multiplex PCR with Taq and Vent (exo-) DNA polymerases, the typical representatives of the A and B polymerase families. The efficiency of nucleotide incorporation during PCR was assessed with a multi-parameter hybridization analysis using a diagnostic DNA microarray. The hybridization analysis indirectly estimates the incorporation efficiency of dye-labeled nucleotides in multiplex PCR. Our results demonstrated higher efficiencies of substrates with electrically neutral dyes than electropositive and electronegative Cy5 residues.

Formation of Boron-Carbon Nanosheets and Bilayers in Boron-Doped Diamond: Origin of Metallicity and Superconductivity.

The insufficient data on a structure of the boron-doped diamond (BDD) has frustrated efforts to fully understand the fascinating electronic properties of this material and how they evolve with doping. We have employed X-ray diffraction and Raman scattering for detailed study of the large-sized BDD single crystals. We demonstrate a formation of boron-carbon (B-C) nanosheets and bilayers in BDD with increasing boron concentration. An incorporation of two boron atoms in the diamond unit cell plays a key role for the B-C nanosheets and bilayer formation. Evidence for these B-C bilayers which are parallel to {111} planes is provided by the observation of high-order, super-lattice reflections in X-ray diffraction and Laue patterns. B-C nanosheets and bilayers minimize the strain energy and affect the electronic structure of BDD. A new shallow acceptor level associated with B-C nanosheets at ~37 meV and the spin-orbit splitting of the valence band of ~6 meV are observed in electronic Raman scattering. We identified that the superconducting transitions occur in the (111) BDD surfaces only. We believe that the origin of Mott and superconducting transitions is associated with the two-dimensional (2D) misfit layer structure of BDD. A model for the BDD crystal structure, based on X-ray and Raman data, is proposed and confirmed by density functional theoretical calculation.

Positive operator-valued measure reconstruction of a beam-splitter tree-based photon-number-resolving detector.

Here we present a reconstruction of the positive operator-value measurement of a photon-number-resolving detector comprised of three 50∶50 beam-splitters in a tree configuration, terminated with four single-photon avalanche detectors. The four detectors' outputs are processed by an electronic board that discriminates detected photon number states from 0 to 4 and implements a "smart counting" routine to compensate for dead time issues at high count rates.

[An experience with neuroprotective therapy of primary open-angle glaucoma based on the use of different dosage forms of Mexidol]. / Opyt neiroprotektornoi terapii pervichnoi otkrytougol'noi glaukomy na osnove primeneniya razlichnykh form Meksidola.

UNLABELLED: Aim - to develop an algorithm to guide neuroprotective therapy in railway workers undergoing long-term follow-up for primary open-angle glaucoma (POAG) judging from the efficacy of sequential administration of intravenous dosage form of Mexidol and oral tablets. MATERIAL AND METHODS: All sorts of JSC Russian Railways employees with stage I-III POAG and well-controlled intraocular pressure were enrolled. Mexidol was first to be administered intravenously by a dropper in a day hospital (250 mg daily for 5 days) and then taken orally at home (125 mg t.i.d. for 3 months). A comprehensive ophthalmic examination with high-technology control was performed in all patients at their first, second, and third follow-up visits. RESULTS: Data from 58 patients (96 eyes) were analyzed. Statistically significant improvements in perimetry and optical coherence tomography results were only obtained at a third visit, i.e. at the end of the course of Mexidol tablets. The treatment effect was most pronounced in stage I-II patients. CONCLUSION: The results suggest that combination therapy with intravenous and oral Mexidol received sequentially as well as long-term (3-month) administration of Mexidol tablets can both be recommended in POAG patients. It has been also found that neuroprotective therapy with Mexidol performs best for early stages of the disease.

FGFR3 and TP53 mutations in a prospective cohort of Belarusian bladder cancer patients.

AIM: The aim of this study was to determine the frequencies of FGFR3 and TP53 mutations in a prospective cohort of 150 bladder cancer patients and to assess the relationship between their mutational status and clinicopathological variables. MATERIALS AND METHODS: The FGFR3 and TP53 mutations were detected by the SNaPshot method and PCR-single-strand conformational polymorphism analysis followed by DNA sequencing. RESULTS: The activating FGFR3 mutations were found in 71 (47.3%) whereas TP53 mutations were observed in 31 (20.7%) urothelial carcinomas. FGFR3-mutant tumors significantly correlated with lower tumor stage and grade, papillary form of bladder cancer and the absence of metastases while TP53-mutant tumors were strongly associated with higher tumor stage and grade as well as the presence of metastasis. We also found significant inverse correlation between FGFR3 mutations and TP53 alterations in urothelial carcinomas (p=0.03). Four possible genotypes were observed in the whole studied cohort, namely FGFR3mut/TP53wt (41.3%), FGFR3wt/TP53wt (38%), FGFR3wt/TP53mut (14.7%), and FGFR3mut/TP53mut (6%). Tumors with FGFR3wt/TP53wt genotype comprised the subgroup, in which all stages and grades were equally distributed. CONCLUSIONS: Our findings confirm the alternative role of FGFR3 and TP53 mutations in the development of bladder cancer. Together these two genetic markers are attributed to 62% of the tumors studied. Tumors with both wild type genes included urothelial carcinomas of all stages and grades and may develop through another genetic pathway. To elucidate complete molecular profile of bladder tumors further additional studies are needed.

All-diamond optical assemblies for a beam-multiplexing X-ray monochromator at the Linac Coherent Light Source.

A double-crystal diamond (111) monochromator recently implemented at the Linac Coherent Light Source (LCLS) enables splitting of the primary X-ray beam into a pink (transmitted) and a monochromatic (reflected) branch. The first monochromator crystal, with a thickness of ∼100 µm, provides sufficient X-ray transmittance to enable simultaneous operation of two beamlines. This article reports the design, fabrication and X-ray characterization of the first and second (300 µm-thick) crystals utilized in the monochromator and the optical assemblies holding these crystals. Each crystal plate has a region of about 5 × 2 mm with low defect concentration, sufficient for use in X-ray optics at the LCLS. The optical assemblies holding the crystals were designed to provide mounting on a rigid substrate and to minimize mounting-induced crystal strain. The induced strain was evaluated using double-crystal X-ray topography and was found to be small over the 5 × 2 mm working regions of the crystals.

Storage and retrieval of collective excitations on a long-lived spin transition in a rare-earth ion-doped crystal.

Robust, long-lived optical quantum memories are important components of many quantum information and communication protocols. We demonstrate coherent generation, storage, and retrieval of excitations on a long-lived spin transition via spontaneous Raman scattering in a rare-earth ion-doped crystal. We further study the time dynamics of the optical correlations in this system. This is the first demonstration of its kind in a solid and an enabling step toward realizing a solid-state quantum repeater.

Hybrid diamond-silicon angular-dispersive x-ray monochromator with 0.25-meV energy bandwidth and high spectral efficiency.

We report on the design, implementation, and performance of an x-ray monochromator with ultra-high energy resolution (ΔE/E ≃ 2.7 × 10(-8)) and high spectral efficiency using x rays with photon energies E ≃ 9.13 keV. The operating principle of the monochromator is based on the phenomenon of angular dispersion in Bragg back-diffraction. The optical scheme of the monochromator is a modification of a scheme reported earlier [Shvyd'ko et al., Phys. Rev. A 84, 053823 (2011)], where a collimator/wavelength selector Si crystal was replaced with a 100-µm-thick type IIa diamond crystal. This modification provides a very-small-energy bandwidth ΔE ≃ 0.25 meV, a 3-fold increase in the aperture of the accepted beam, a reduction in the cumulative angular dispersion rate of x rays emanating from the monochromator for better focusing on a sample, a sufficient angular acceptance matching the angular divergence of an undulator source (≈ 10 µrad), and an improved throughput due to low x-ray absorption in the thin diamond crystal. The measured spectral efficiency of the monochromator was ≈ 65% with an aperture of 0.3 × 1 mm(2). The performance parameters of the monochromator are suitable for inelastic x-ray spectroscopy with an absolute energy resolution ΔE < 1 meV.

Ancilla-assisted calibration of a measuring apparatus.

A quantum measurement can be described by a set of matrices, one for each possible outcome, which represents the positive operator-valued measure (POVM) of the sensor. Efficient protocols of POVM extraction for arbitrary sensors are required. We present the first experimental POVM reconstruction that takes explicit advantage of a quantum resource, i.e., nonclassical correlations with an ancillary state. A POVM of a photon-number-resolving detector is reconstructed by using strong quantum correlations of twin beams generated by parametric down-conversion. Our reconstruction method is more statistically robust than POVM reconstruction methods that use classical input states.