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This review examines the evolution of the radionuclide diagnosis of HER2-positive breast cancer using various compounds as a targeting module in clinical practice: from full-length antibodies to a new group of small synthetic proteins called alternative scaffold proteins. This topic is of especial relevance today in view of the problems attendant to the detection of breast cancer with HER2/neu overexpression, which, in most cases, introduce errors in the treatment of patients. The results of clinical studies of radiopharmaceuticals based on affibody molecules, ADAPTs, and DARPins for SPECT and PET have demonstrated good tolerability of the compounds, their rapid excretion from the body, and the possibility to differentiate tumor sites depending on the HER2/neu status. This indicates that targeted radionuclide diagnosis holds promise and the need to continue research in this direction.

Introduction. Overexpression of Her2/neu is detected in 15–20 % of patients with breast cancer and associated with an aggressive form of disease and low overall and disease-free survival rates. Currently, immunohistochemical studies (IHC) and methods of in situ hybridization are used to assess Her2/neu status. One of significant drawbacks of this detection is the impossibility of simultaneous assessment of the receptor status of the primary tumor and metastatic sites. The increasing popularity of radionuclide methods using recombinant proteins as a targeting module have already demonstrated their effectiveness in solving this question at the initial stages of clinical research.The purpose of this study is to demonstrate a clinical case of assessing the extent of breast cancer in a patient with overexpression of Her2/neu using a radiopharmaceutical based on targeted protein molecules labeled with technetium-99m.Description of the clinical case. A patient diagnosed with stage IIIA right breast cancer (T2N2M0), multicentric growth and metastases in right axillary and subclavian lymph nodes at the diagnostic stage was injected intravenously with 99mTc-ADAPT6 radiopharmaceutical. The drug was prepared in the Department of Nuclear Medicine of Research Cancer Institute (Tomsk) immediately before its administration. Planar scintigraphy and singlephoton emission tomography of the chest organs were performed 2 hours after injection of 99mTc-ADAPT6 radiopharmaceutical. In addition to the previously described tumors, 3 foci of hyperfixation of the tracer in the projection of the 5th rib on the right along the middle-clavicular line, as well as in the projection of the 8 and 9 thoracic vertebrae (Th VIII, IX) were found. Computed tomography of the chest organs and bone scintigraphy with 99mTc-pyrophosphate showed no metastases in the 5th rib on the right and Th VIII, IX. Magnetic resonance imaging of the thoracic spine revealed 2 metastatic foci in Th VIII, IX. Planar scintigraphy with 99mTc-pyrophosphate and CT performed 6 months after injection of 99mTc-ADAPT6 revealed previously described foci in the projection of the thoracic spine (Th VIII, IX) and 5 ribs on the right along the mid-clavicular line. Conclusion. The results demonstrated during the study suggest that 99mTc-ADAPT6 is a promising tracer for molecular imaging of tumor foci with overexpression of the Her2/neu receptor in breast cancer patients.

The aim of this work was to continue the monitoring of the H2O maser emission in IRAS 16293–2422 to detect superflares. We have been observing H2O maser emission at a wavelength of 1.35 cm towards the source IRAS 16293–2422 since 1999. The observations have been carried out with the 22-m radio telescope of the Pushchino Radio Astronomy Observatory (Russia). In 2007–2018, we also conducted several sessions of observations in OH lines at a wavelength of 18 cm in both circular polarizations with the Nançay Radio Telescope (France). Between 1997 and 2021, we observed three cycles of high activity of the H2O maser with a period of 8 yr. This variability could be related to the changing activity of the protostar in the tight binary system of IRAS 16293–2422 in the process of its formation. This variability could be related to an increase in the activity of the tight binary protostar IRAS 16293–2422 A, first seen in 2002. The H2O maser variation in flux density and radial velocity suggests that disturbances are propagating through organized structures in the form of chains ∼3.5 au long, with monotonic velocity gradients in the direction of propagation. The 18-cm OH emission in the main and satellite lines is thermal.

The aim of the study was to identify the most informative prognostic parameters that allow assessing the status of the epidermal growth factor receptor Her2/neu in the primary tumor in breast cancer patients using the radiopharmaceutical «99mTc-ADAPT6». Material and methods. The study included 15 patients with breast cancer (T1-4N0-2M0) before the system therapy. Eight patients were found to overexpress Her2/neu in the primary breast tumor, in 7 cases the expression of the marker was not diagnosed. Morphological and immunohistochemical studies were performed in all cases. All patients are undergoing a radionuclide study using the radiopharmaceutical «99mTc-ADAPT6» at a dosage of protein 500 μg. Results. Patients with Her2-positive breast tumors showed a significantly higher accumulation of «99mTc-ADAPT6» in primary tumor (p

The conditions for carrying out molecular dynamics calculations of adsorption isotherms of gases and vapors in micropores of active carbons providing a quantitative coincidence of the calculated and experimental isotherms are considered.

Background. The main purpose of the Her2/neu status determination in clinical practice is to determine the indications for the appointment of targeted therapy. The main methods for detecting the Her2/neu status are the immunohistochemical method (IHC) and the fluorescence in situ hybridization (FISH); however, despite their widespread use, they have a number of significant disadvantages. Over the past few years, radionuclide diagnostics using a new class of alternative scaffold proteins that meet all the requirements for optimal delivery of radionuclides to tumor cells has become widespread. Aim. To study the possibility of clinical use of a radiopharmaceutical based on technetium-99m-labeled target molecules for the diagnosis of breast cancer with the Her2/neu overexpression in humans. Materials and methods. The study included 11 patients with breast cancer (T1–4N0–2M0) before systemic therapy: 5 with Her2/neu overexpression; expression of the marker was not detected in 6. In all cases, morphologicaland immunohistochemical studies were performed. In case of Her2/neu 2+, FISH analysis was performed. The radiopharmaceutical was prepared immediately before administration, after which it was slowly injected intravenously into the patient. Scintigraphic studies in the “WholeBody” mode and SPECT of the chest organs were performed 2, 4, 6 and 24 hours after injection. Results. Radiochemical yield, radiochemical purity and activity before administration were (80 ± 4)%, (98 ± 1)% and (434 ± 19.5) MBq, respectively. The greatest uptake by normal organs was observed at a time interval of 6 hours in the kidneys and at a moderate activity in the liver and lungs at the same time interval. The organ with the highest absorbed dose was the kidneys; significant accumulation was also detected in the adrenal glands, gallbladder, liver, pancreas and spleen. The smallest accu mulation of the studied drug was observed in the brain (0.001 ± 0.000) mGy and skin (0.001 ± 0.000) mGy. The effective dose was (0.009 ± 0.002) mGy. The difference between tumors with positive and negative Her2-neu expression was found at all time points. In this case, the best indicator was determined after 2 hours of drug injection (р < 0.05). Conclusion. Based on the results obtained, it can be indicated that the investigated radiopharmaceutical can be considered as a new additional method for the diagnosis of Her2-positive breast tumors.

The monitoring results of the OH maser source in W75 N in the main line at 1665 MHz performed in 2007–2020 using the Nancay Radio Telescope (France) are presented. Generally, the maser in 2007–2009 is characterized by a high activity. During the monitoring, time variations of the Stokes parameters were found for all spectral features in the radial velocity range from –1 to 14 km/s. We found that its positional angle $$\chi $$ and the degree of linear polarization $${{m}_{{\text{L}}}}$$ , as well as the degree of circular polarization $${{m}_{{\text{C}}}}$$ of most features, change with time according to certain regularities, not chaotically. Or they can change very weakly and there is a correlation with the variability of the flux density. In this case, the radial velocities of the features change very little. It is shown that the main feature at 12 km/s during 50 years since the discovery of the OH maser in W75 N had two maxima of activity with an interval of about 30 years between them. The identification of spectral features in the 1665 MHz line with maser spots on VLBA maps has been carried out. We showed that a strong flare of the main features in 2007–2009 occurred in the VLA 2 source. During this flare, small changes in the angle $$\chi $$ and significant changes in the degree of both linear and circular polarization of features at 1.75, 2.1, and 3.05 km/s were observed. For the 0.65 km/s feature, significant changes in all emission parameters were observed. The emission in the 1612 MHz satellite line is broadband. The broadening of the line to 1.9 km/s indicates that, in addition to thermal motion of matter, there is also turbulent motion of matter in the medium.

Due to the need to develop technologies for nonregenerative adsorptive separation of ethane, propane, and butane from mixtures (1–5%) with natural gas, the molecular dynamics method was used to calculate the dependence of the adsorbed amounts and separation coefficients of the components of binary mixtures of methane with ethane, propane, and butane on the composition of mixtures, temperature, and pressure.

We present the results of our observations of the star-forming region located in the Perseus arm and associated with the Sharpless nebula S231 in the lines of H2O at a wavelength of 1.35 cm and OH at a wavelength of 18 cm obtained with the Pushchino 22-m radio telescope (Russia) and the Nancay Large Radio Telescope (France), respectively. We provide a catalog of H2O maser spectra in the period from March 2003 to March 2020. The variability of the integrated flux that we have calculated based on the monitoring by Felli et al. (1987–2007) and our monitoring (2003–2020) has a quasi-cyclic pattern with a cycle duration from 4.3 to 7.7 yr. Flares of maser emission of both single and several features occurred in each activity cycle. The mean rise and decay times of the flare emission were $$0.30 \pm 0.02$$ and $$0.35 \pm 0.02$$ yr, respectively. The observed radial velocity drift and jumps of the H2O emission features can be a consequence of the impact of shocks emerging as the protostar activity rises on them. The complex pattern of variability shows that the H2O masing medium is fragmented and small-scale turbulent motions of matter can occur in it. We have observed the OH maser emission in the 1665 and 1667 MHz main lines and the 1720 MHz satellite line. A large number of OH emission features and their variability have been detected. We have found one Zeeman pair at ‒9.2 km/s with a small splitting, with the longitudinal magnetic field in the period 2008–2020 having decreased monotonically from 0.24 to 0.10 mG. For the three most intense features we have calculated the degrees of linear polarization and position angles. A correlation between the H2O and OH maser activities has been found.

As an addition to previously obtained data, it has been shown that the adsorption isotherms calculated by the molecular dynamics method for components of light hydrocarbon mixtures in micropores of active carbons and on graphene surfaces are quantitatively described by equations of lattice models with well-coordinated equation parameters.

We present the observation results of the star forming region NGC 2071 in the 1.35-cm H2O line and 18-cm OH lines obtained with the 22-m radio telescope in Pushchino (Russia) and the large radio telescope in Nancay (France), respectively. The catalog of H2O maser emission spectra from December 2010 to January 2020 is given. The total flux variability for the entire monitoring period (1979–2020) has two activity cycles of close duration (approximately 20 years), which were accompanied by strong flares at intervals of one to four years. It is shown that the medium for the generation of H2O maser emission is greatly fragmented and contains small-scale turbulent motions of matter. The observed drift and radial velocity jumps of the H2O emission features can be a consequence of the complex, inhomogeneous structure of the maser emission regions. OH emission in the 1665 and 1667 MHz main lines and in the 1612 MHz satellite line in the radial velocity range of 7–12 km/s is broadband. The ratio of intensities differs from equilibrium. The substantiation of the observed ratio between the intensities of this emission and absorption in the 1720 MHz line is given. OH maser emission was observed in 2007 in the left circular polarization in the 1667 MHz line at 13.02 and 13.55 km/s with a flux density of ~0.3 Jy and a width of ~0.25 km/s for each of the velocities.

Purpose: Evaluation of a radiopharmaceutical based on 99mTc-labeled targeted molecules DARPin9_29 for radionuclide diagnostics of malignancies with Her2/neu overexpression. Material and methods: The DARPin9_29 sequence was amplified from the plasmid pET-DARP-6HIS for the DARPin9_29-His6 gene expression in E. coli cells. The eluent of 99mTcO4– (400–500 μl, 4 GBq) was added to the kit and incubated at a temperature of 100 °C for 20 minutes. After incubation, 40 μl of tricarbonyl technetium was added to 168 μg of DARPin9_29 in 100 μl of PBS (sodium phosphate buffer), followed by incubation at 40 °C for 60 minutes. The radiochemical yield and purity were determined by thin layer radiochromatography, the purification was performed using NAP-5 cleansing columns (GE Healthcare). Cell lines with different levels of Her2/neu expression were used: SKOV-3> BT474 >> DU-145 for the determination of the radiopharmaceutical specificity. Her2/neu expressing cell line SKOV-3 was used for in vitro study. The study was conducted 6 hours after the administration of the drug. Results: The radiochemical yield was 72 ± 8 %, the radiochemical purity after purification was 98.7 ± 1.0 %. The stability in PBS (phosphate buffered saline) solution after 1 hour was 99.8 ± 0.2; after 3 hours – 98.2 ± 0.1. In vitro studies showed that the accumulation of explored compound was directly proportional to the level of Her2/neu expression in cells, while blocking the receptors with an excess of unlabeled protein showed a significant reduction in binding in the group of cells. Data on biodistribution and SPECT/CT in the body of the animal BALB/c nu/nu demonstrated rapid removal of the compound from the blood stream and high accumulation in the liver, kidney and bladder 6 hours after the introduction of the radiopharmaceutical. Conclusion: The studies demonstrated high radiochemical yields and purity, as well as stability of the studied compound. The results of in vitro and in vivo analysis showed the specificity and affinity of the radiopharmaceutical to the Her2/neu receptor on the surface of tumor cells. The high accumulation of the drug in the liver and kidneys, detected in in vivo studies, is probably due to the lipophilicity of the 99mTc(CO)3-histidine tag and indicates the limitation of its further clinical use in assessing the condition of the above organs, which will require additional diagnostic methods, as well as possible modification chemical structure.

It has been demonstrated that adsorption isotherms on microporous activated carbons calculated by the method of molecular dynamics at temperatures higher than critical for adsorbents quantitatively coincide with experimental isotherms at calculations in micropores of finite sizes, with the micropore width being chosen in accordance with the theory of micropore volume filling and properly selected force field.

The structure and evolution of powerful H2O maser flares in the source IRAS 18316–0602 are studied using the results of observations on the 22-m radio telescope of the Pushchino Radio Astronomy Observatory. The main origin of the last powerful, short-term flare in 2017 may be the superposition of two maser condensations with very similar radial velocities along the line of sight. All powerful flares occurring in IRAS 18316–0602 since 2002 can be associated with a cluster of maser condensations whose radial velocities are in the interval 41.0–43.5 km/s. It is suggested that this may be related to turbulent, possibly vortical, motions of material in this region.

Based on a numerical experiment, it is proven that the Dubinin theory of micropore filling can be extended to adsorption equilibria at supercritical temperatures. The temperature dependences of the main parameters of the theory are refined.

A molecular dynamic experiment is carried out for analyzing the isotherms of adsorption on a graphene surface at temperatures below and above the critical values for adsorptives. It is shown that the monomolecular isotherms of gas adsorption on the flat carbon surfaces can be described using the set of equations of the lattice model and the equations of the theory of the volume filling of micropores (TVFM). The obtained results are compared with the experimental data on adsorption in micropores of active carbons. When describing the isotherms of polymolecular adsorption with the use of the BET and the Aranovich equations, the filling of each layer is analyzed.

It is shown that an earlier-suggested method of computing isotherms of adsorption of vapor mixtures in a sample pore of active carbon using molecular dynamics can be applied for quantitative computation of adsorption isotherms of components of binary gas mixtures at temperatures higher than critical. It is shown that computed adsorption isotherms of mixture components in micropores and on graphene surfaces are quantitatively described by equations of the lattice model.

The targeted delivery of radionuclides to tumours holds great promise for diagnosis and treatment of malignant neoplasms. The development of scaffold proteins has significantly simplified the design of targeting agents with desirable properties. This review comprehensively describes the key aspects of the design of radionuclide compounds, including classification of radionuclides, methodology for their attachment to targeting agents and characteristics of these agents that affect their behaviour in the body. Various targeting molecules are compared in terms of their ability to specifically find malignant foci in the body. The most recent achievements of cancer theranostics that aim at increasing the selectivity of antitumour effect are described, such as the fusion of targeting scaffold proteins with the albumin-binding domain and pretargeting. Special attention is paid to the creation of targeted radionanomaterials. Advantages and disadvantages of different strategies are analyzed and approaches for improving the delivery to tumours and for minimizing the undesirable impact on healthy organs and tissues are proposed. Particular emphasis is placed on the results of studies published in 2020–2021 that have not yet been covered by reviews. The bibliography includes 191 references.

The study of the country’s food security can be approached from different angles, but the analysis of agricultural production is paramount since significant volumes of domestic production are the key to the country’s independence from external sources. In the course of the study, such general scientific methods as analysis, synthesis and historical are used, as well as statistical methods, in particular: graphical, tabular, coefficient. During the elaboration of the selected issues, the following results were achieved. First, in 2015 compared with 1990, an increase in such a strategic product as grain in 10 out of 15 Post-Soviet countries and a decrease in meat production (in 11 out of 15 republics) and milk (in 9 out of 15 republics) are observed. Second, the self-sufficiency ratio indicates that 80% of the Post-Soviet countries provide themselves with grain in 2015. For meat and milk, the situation is depressing, only 13% of countries provide themselves with meat and 27%—with milk. Third, the former republics of the Soviet Union compensate for the missing volume of domestic production of milk and meat by imports which make them dependent on fluctuations in world prices and market conditions. The analysis of the level of agricultural production and the value of the coefficient of self-sufficiency in grain, milk and meat in the Post-Soviet countries allows us to conclude that production volumes are increasing, there are no threats to food security in relation to the grain market, but such threats for the meat and milk markets exist.

Russian abstract: Актуальность темы обусловлена важным значением мониторинга индикаторов региональных рынков труда для обеспечения необходимых условий сбалансированного социально-экономического развития страны. Сильная межрегиональная дифференциация заработной платы, наряду с также очень значительной ее дифференциацией по видам экономической деятельности является важнейшим фактором перемещения экономически активного населения между регионами страны в условиях недостаточности трудовых ресурсов на макроуровне. В статье отражены результаты оценки степени межрегиональной дифференциации значений среднемесячной номинальной начисленной заработной платы работников организаций в регионах России. Оценка произведена с помощью коэффициента размаха, децильного коэффициента дифференциации и коэффициента вариации. Выявлена устойчивая тенденция снижения значений коэффициента размаха и децильного коэффициента дифференциации в период 2000-2018 гг., что отнесено к позитивным процессам на региональных рынках труда. Сделан вывод об уменьшении неравенства российских регионов по уровню средней номинальной заработной платы. Установлено, что совокупность регионов страны стала более однородной за исследуемый временной интервал по заданному признаку. Проведено сопоставление динамике значений коэффициентов с общеэкономической динамикой. Выдвинута гипотеза взаимосвязи динамики валового регионального продукта и изменения однородности массива регионов по уровню среднемесячной номинальной начисленной заработной платы работников организаций, которая предложена в качестве исходного положения для дальнейших исследований. Для повышения эффективности мониторинга реализации Стратегии пространственного развития предложено учитывать динамику значений децильного коэффициента дифференциации, коэффициента вариации, а также коэффициента размаха (разброса) российских регионов, городских агломераций, макрорегионов и федеральных округов по уровню среднемесячной номинальной начисленной заработной платы работников организаций. English abstract: The relevance of the topic is due to the importance of monitoring indicators of regional labor markets to ensure the necessary conditions for a balanced socio-economic development of the country. Strong interregional differentiation of wages, along with its very significant differentiation by type of economic activity, is the most important factor in the movement of economically active population between regions of the country in conditions of insufficient labor resources at the macro level. The article reflects the results of assessing the degree of interregional differentiation for the average monthly nominal accrued wages of employees of organizations in the regions of Russia. The assessment was made using the amplitude coefficient, decile coefficient of differentiation and coefficient of variation. A steady tendency towards a decrease in the magnitude of the coefficient of magnitude and decile coefficient of differentiation in the period 2000-2018 is revealed, which is attributed to positive processes in regional labor markets. It is concluded that the inequality of the Russian regions is reduced in terms of the average nominal wage. It has been established that the totality of the country's regions has become more homogeneous over the studied time interval for a given attribute. The coefficient values dynamics is compared with the general economic dynamics. A hypothesis has been put forward on the relationship between the dynamics of the gross regional product and changes in the homogeneity of the array of regions in terms of the average monthly nominal accrued wages of employees of organizations, which is proposed as a starting point for further research. To increase the effectiveness of monitoring the implementation of the Spatial Development Strategy, it is proposed to take into account the dynamics of the values of the decile coefficient of differentiation, the coefficient of variation, as well as the span (spread) coefficient of the Russian regions, city agglomerations, macro-regions and federal districts according to the average monthly nominal salary of employees of organizations.

We consider our variants of applying a molecular dynamics method to quantitatively calculate adsorption isotherms of gases and vapor and their mixtures on microporous active coals in a wide temperature range (lower and higher than the critical one for adsorptives) and the dependence of adsorbate densities on the width of slit-like micropores.

The possibility of describing isotherms of gas adsorption on flat carbon surfaces by means of lattice model equations and equations of the theory of micropore volume filling has been demonstrated. The obtained results have been compared to data on the adsorption in micropores of active carbon.

Results of monitoring hydroxyl and water masers in the star-forming region S128 are presented. A large number of emission features in the 1665 MHz OH line have been detected in both circular polarizations. In spite of the strong variability of the flux density in the main 1665 MHz line, the radial velocities of the features remained constant. Zeeman splitting of the 1720MHz line equal to 0.86 km/s was detected, corresponding to a longitudinal magnetic field of 3.6 mG. The variability of the H2O emission has a cyclic character with a quasi-period of 4–14 yrs. The evolution of individual features confirms that the H2O sources A and B are associated with an ionization front between two colliding CO clouds, and shows that the activity was transferred from maser B to maser A in 1999–2001.

Molecular-dynamics calculations confirmed the applicability of the equations of the theory of volume filling of micropores and the lattice model for describing the isotherm of adsorption onto active carbons in a wide range of temperatures below and above the critical values.

The results of monitoring the H2O maser observed toward the region GH2O 092.67+03.07 (IRAS 21078+5211) located in the Giant Molecular Cloud Cygnus OB7 are presented. The observations were carried out with the 22-m radio telescope of the Pushchino Radio Astronomy Observatory in 2006–2017. Strong flares of the H2O maser emission with flux densities up to 19 800 Jy were detected. The flares exhibited both global (over the source) and local characters. All the flares were accompanied by strong variations in the H2O spectra within the corresponding radial-velocity ranges. Individual H2O components form both compact clusters and chains 1–2-AU long. Analysis of the variations of the fluxes, radial velocities, and line shapes of features during the flares showed that the medium may be strongly fragmented, with small-scale turbulent motions taking place in the H2Omaser region.

The results of a study of the maser source IRAS 18316−0602 in the H2O line at λ = 1.35 cm are reported. The observations were carried out on the 22-m radio telescope of the Pushchino Radio Astronomy Observatory (Russia) from June 2002 until March 2017. Three superflares were detected, in 2002, 2010, and 2016, with peak flux densities of >3400, 19 000, and 46 000 Jy, respectively. An analysis of these superflares is presented. The flares took place during periods of high maser activity in a narrow interval of radial velocities (40.5–42.5 km/s), and could be associated with the passage of a strong shock. The emission of three groups of features at radial velocities of about 41, 42, and 43 km/s dominated during themonitoring. The flare in 2016 was accompanied by a considerable increase in the flux densities of several features with velocities of 35–56 km/s.

The methods of describing absolute adsorption isotherms of binary nonelectrolyte solutions components on macro- and microporous adsorbents have been considered within the framework of the lattice model.

Different ways to theoretically calculate the temperature dependence of the adsorption isotherms of individual substances on activated charcoals in a wide range of temperatures below and above critical temperatures are examined.

A quantitative topological analysis of supramolecular structures in ethanol solutions with methanol, propanol, water, benzene, and hexane is performed by the MDGT method previously proposed by the authors. The method is based on a combination of molecular dynamics calculations and the graph theory, which enables the recognition and memorization of supramolecular structures observed in each snapshot of the molecular dynamic trajectory, the averaging of data for any number of these snapshots. Thus, the averaged concentrations of associates (dimers, trimers, etc.) are represented and then the concentrations and characteristics of isomers (e.g., chains, branched chains, rings, etc.), bond lengths, angles, etc. are determined in each group of associates.

Methods for describing adsorption isotherms and the thermodynamic characteristics of adsorption of methane, ethylene, propane, and butane on active carbons are considered in a wide range of temperatures below and above the critical ones.

In connection with the problem of adsorption accumulation of methane, the methods of quantum chemistry and molecular dynamics are used to study in detail the dependence of methane density at the limiting fillings on the width of slit-shaped active carbon micropores and on the nanotube diameter. It is shown that adsorption energy, density, and, therefore, the limiting adsorption of methane are maximum at the given micropore volume at a pore width of 1–1.1 nm and nanotube diameter of 1.6 nm.