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We experimentally demonstrate the generation of polarization-squeezed light in a short piece of solid-core chalcogenide (ChG) (As 2 S 3 ) fiber via the Kerr effect for femtosecond pulses at 1.56 µm. Directly measured squeezing of -2.8 dB is obtained in a setup without active stabilization. Numerical simulations are in good agreement with the experimental results and indicate that the measured squeezing in our setup is mainly limited by the losses in the detection system rather than by the fiber properties.

This article provides a comprehensive overview of the applications of methods of machine learning (ML) and artificial intelligence (AI) in ambient ionization mass spectrometry (AIMS). AIMS has emerged as a powerful analytical tool in recent years, allowing for rapid and sensitive analysis of various samples without the need for extensive sample preparation. The integration of ML/AI algorithms with AIMS has further expanded its capabilities, enabling enhanced data analysis. This review discusses ML/AI algorithms applicable to the AIMS data and highlights the key advancements and potential benefits of utilizing ML/AI in the field of mass spectrometry, with a focus on the AIMS community., (© 2024 John Wiley & Sons Ltd.)

Ambient ionization mass spectrometry was proved to be a powerful tool for oncological surgery. Still, it remains a translational technique on the way from laboratory to clinic. Brain surgery is the most sensitive to resection accuracy field since the balance between completeness of resection and minimization of nerve fiber damage determines patient outcome and quality of life. In this review, we summarize efforts made to develop various intraoperative support techniques for oncological neurosurgery and discuss difficulties arising on the way to clinical implementation of mass spectrometry-guided brain surgery., (© 2024 John Wiley & Sons Ltd.)

One of the prime applications of squeezed light is enhancing the sensitivity of an interferometer below the quantum shot-noise limit, but so far, no such experimental demonstration was reported when using the optical Kerr effect. In prior setups involving Kerr-squeezed light, the role of the interferometer was merely to characterize the noise pattern. The lack of such a demonstration was largely due to the cumbersome tilting of the squeezed ellipse in phase space. Here, we present the first experimental observation of phase-sensitivity enhancement in an interferometer using Kerr squeezing., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Rapid and reliable methods for detecting tumor margins are crucial for neuro-oncology. Several mass spectrometry-based methods have been recently proposed to address this problem. Inline Cartridge Extraction (ICE) demonstrates the potential for clinical application, based on ex-vivo analysis of dissected tissues, but requires time-consuming steps to avoid cross-contamination. In this work, a method of incorporating a disposable electrospray emitter into the ICE cartridge by PEEK sleeves melting is developed. It reduces total analysis time and improves throughput. The proposed setup also improves the robustness of the ICE molecular profiling as demonstrated with human glial tumor samples in that stability and reproducibility of the spectra were increased.

Bright squeezed light can be generated in optical fibers utilizing the Kerr effect for ultrashort laser pulses. However, pulse propagation in a fiber is subject to nonconservative effects that deteriorate the squeezing. Here, we analyze two-mode polarization squeezing, which is SU(2)-invariant, robust against technical perturbations, and can be generated in a polarization-maintaining fiber. We perform a rigorous numerical optimization of the process and the pulse parameters using our advanced model of quantum pulse evolution in the fiber that includes various nonconservative effects and real fiber data. Numerical results are consistent with experimental results.

Rapid microwave sintering of different oxide ceramics with heating rates up to 300 °C/min and zero hold time has been implemented using a 24 GHz gyrotron-based system for high-temperature processing of materials. The design of the system, principle of operation, and process control are described. Particular attention is given to the design of thermal insulation assemblies and the implementation of temperature measurement in an environment with intense electromagnetic fields. A description of an optical system for dilatometry and temperature measurement is presented. The interrelation between the automatically regulated output power of the gyrotron and the microwave power absorbed volumetrically in the sample is analyzed on the basis of energy balance considerations. The analysis is illustrated by considering examples of rapid sintering processes with ZnO-based and BaTiO 3 ceramic samples making use of direct and susceptor-assisted microwave heating. It is demonstrated that an increase in the volumetrically absorbed power leads to the development of a controlled thermal instability, which results in a lower temperature of the densification onset.

Ex-vivo molecular profiling has recently emerged as a promising method for intraoperative tissue identification, especially in neurosurgery. The short-term storage of resected samples at room temperature is proposed to have negligible influence on the lipid molecular profiles. However, a detailed investigation of short-term molecular profile stability is required to implement molecular profiling in a clinic. This study evaluates the effect of storage media, temperature, and washing solution to determine conditions that provide stable and reproducible molecular profiles, with the help of ambient ionization mass spectrometry using rat cerebral cortex as model brain tissue samples. Utilizing normal saline for sample storage and washing media shows a positive effect on the reproducibility of the spectra; however, the refrigeration shows a negligible effect on the spectral similarity. Thus, it was demonstrated that up to hour-long storage in normal saline, even at room temperature, ensures the acquisition of representative molecular profiles using ambient ionization mass spectrometry.

In this article, results are presented of experiments on depositing charged particles, which imitate the levitating dust on the Moon, on stainless steel. Ensembles of particles are created above the surface of laboratory regolith whose composition and particle size distribution imitate the dust that covers the Moon's surface. Under the action of the gyrotron radiation on regolith, non-linear physical-chemical processes develop (breakdown, chain plasmachemical reactions, and particle scattering by the Coulomb mechanism), which lead to the appearance of a levitating cloud of particles. The simulation experiment is based on the similarity between the processes that develop in the laboratory experiments with regolith and the processes that occur on the Moon during its bombardment by micrometeorites. The effect of the levitating cloud on stainless steel plates is studied and it is shown that regolith particles in the shape of spheroids of different sizes are deposited on the surface of the plates. The dimensions of the deposited particles and the density of their placement depend on the quality of treatment of the plate surface. It is shown that the laboratory-produced dusty plasma can be used in simulation experiments to study the modification of surfaces of different materials for space technology., Competing Interests: The authors declare no conflicts of interest.

Tumor cell percentage (TCP) is an essential characteristic of biopsy samples that directly affects the sensitivity of molecular testing in clinical practice. Apart from clarifying diagnoses, rapid evaluation of TCP combined with various neuronavigation systems can be used to support decision making in neurosurgery. It is known that ambient mass spectrometry makes it possible to rapidly distinguish healthy from malignant tissues. In connection with this, here we demonstrate the possibility of using non-imaging ambient mass spectrometry to evaluate TCP in glial tumor tissues with a high degree of confidence. Molecular profiles of histologically annotated human glioblastoma tissue samples were obtained using the inline cartridge extraction ambient mass spectrometry approach. XGBoost regressors were trained to evaluate tumor cell percentage. Using cross-validation, it was estimated that the TCP was determined by the regressors with a precision of approximately 90% using only low-resolution data. This result demonstrates that ambient mass spectrometry provides an accurate method todetermine TCP in dissected tissues even without implementing mass spectrometry imaging. The application of such techniques offers the possibility to automate routine tissue screening and TCP evaluation to boost the throughput of pathology laboratories. Rapid estimation of tumor cell percentage during neurosurgery.

Summary: Mass spectrometry (MS) methods are widely used for the analysis of biological and medical samples. Recently developed methods, such as DESI, REIMS and NESI allow fast analyses without sample preparation at the cost of higher variability of spectra. In biology and medicine, MS profiles are often used with machine learning (classification, regression, etc.) algorithms and statistical analysis, which are sensitive to outliers and intraclass variability. Here, we present spectra similarity matrix (SSM) Display software, a tool for fast visual outlier detection and variance estimation in mass spectrometric profiles. The tool speeds up the process of manual spectra inspection, improves accuracy and explainability of outlier detection, and decreases the requirements to the operator experience. It was shown that the batch effect could be revealed through SSM analysis and that the SSM calculation can also be used for tuning novel ion sources concerning the quality of obtained mass spectra., Availability and Implementation: Source code, example datasets, binaries and other information are available at https://github.com/EvgenyZhvansky/R_matrix., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Recently, mass-spectrometry methods show its utility in tumor boundary location. The effect of differences between research and clinical protocols such as low- and high-resolution measurements and sample storage have to be understood and taken into account to transfer methods from bench to bedside. In this study, we demonstrate a simple way to compare mass spectra obtained by different experimental protocols, assess its quality, and check for the presence of outliers and batch effect in the dataset. We compare the mass spectra of both fresh and frozen-thawed astrocytic brain tumor samples obtained with the inline cartridge extraction prior to electrospray ionization. Our results reveal the importance of both positive and negative ion mode mass spectrometry for getting reliable information about sample diversity. We show that positive mode highlights the difference between protocols of mass spectra measurement, such as fresh and frozen-thawed samples, whereas negative mode better characterizes the histological difference between samples. We also show how the use of similarity spectrum matrix helps to identify the proper choice of the measurement parameters, so data collection would be kept reliable, and analysis would be correct and meaningful., (© 2020 John Wiley & Sons, Ltd.)

In this work, we demonstrate a new approach for interactively assessing hyperspectral data spatial structures for heterogeneity using mass spectrometry imaging. This approach is based on the visualization of the cosine distance as the similarity levels between mass spectra of a chosen region and the rest of the image (sample). The applicability of the method is demonstrated on a set of mass spectrometry images of frontal mouse brain slices. Selection of the reference pixel of the mass spectrometric image and a further view of the corresponding cosine distance map helps to prepare supporting vectors for further analysis, select features, and carry out biological interpretation of different tissues in the mass spectrometry context with or without histological annotation. Visual inspection of the similarity maps reveals the spatial distribution of features in tissue samples, which can serve as the molecular histological annotation of a slide.

Significant metabolism alteration is accompanying the cell malignization process. Energy metabolism disturbance leads to the activation of de novo synthesis and beta-oxidation processes of lipids and fatty acids in a cancer cell, which becomes an indicator of pathological processes inside the cell. The majority of studies dealing with lipid metabolism alterations in glial tumors are performed using the cell lines in vitro or animal models. However, such conditions do not entirely represent the physiological conditions of cell growth or possible cells natural variability. This work presents the results of the data obtained by applying ambient mass spectrometry to human glioblastoma multiform tissues. By analyzing a relatively large cohort of primary and secondary glioblastoma samples, we identify the alterations in cells lipid composition, which accompanied the development of grade IV brain tumors. We demonstrate that primary glioblastomas, as well as ones developed from astrocytomas, are enriched with mono- and diunsaturated phosphatidylcholines (PC 26:1, 30:2, 32:1, 32:2, 34:1, 34:2). Simultaneously, the saturated and polyunsaturated phosphatidylcholines and phosphatidylethanolamines decrease. These alterations are obviously linked to the availability of the polyunsaturated fatty acids and activation of the de novo lipid synthesis and beta-oxidation pathways under the anaerobic conditions in the tumor core.

Objective: The aim: The purpose of the present research was to study the results of coronary artery bypass graft (CABG) surgery depending on the degree of left ventricular ejection fraction (LVEF) reduction with the aim to identify additional echocardiographic predictors of the early postoperative period., Patients and Methods: Materials and methods: Were fixed, the results of CABG in 97 patients operated on in the "Bikard" private clinic from March 2016 to December 2018 were the material of the research. All patients underwent CABG surgery under cardiopulmonary bypass and cardioplegia, and in the preoperative period underwent echocardiographic examination according to the standard technique on the Vivid 7 machine. Patients, in dependent of the LVEF, were divided into 3 groups: group 1 35 people (LVEF < 40%), group 2 32 people ( 40% < LVEF < 50%), group 3 30 people (LVEF > 50%)., Results: Results: Our studies showed that the most important echocardiographic predictors of a complicated development of the disease in the early postoperative period, in addition to LVEF of the heart, can be the size of the left ventricle and left atrial, the presence and severity of mitral regurgitation and diastolic dysfunction of the left ventricle of the heart., Conclusion: Conclusions: Comprehensive measurement of these echocardiographic parameters will allow more accurately predict the results of coronary artery bypass grafting in the early postoperative period.

Express MS identification of biological tissues has become a much more accessible research method due to the application of direct specimen ionization at atmospheric pressure. In contrast to traditional methods of analysis employing GC-MS methods for determining the molecular composition of the analyzed objects it eliminates the influence of mutual ion suppression. Despite significant progress in the field of direct MS of biological tissues, the question of mass spectrometric profile attribution to a certain type of tissue still remains open. The use of modern machine learning methods and protocols (e.g., "random forests") enables us to trace possible relationships between the components of the sample MS profile and the result of brain tumor tissue classification (astrocytoma or glioblastoma). It has been shown that the most pronounced differences in the mass spectrometric profiles of these tumors are due to their lipid composition. Detection of statistically significant differences in lipid profiles of astrocytoma and glioblastoma may be used to perform an express test during surgery and inform the neurosurgeon what type of malignant tissue he is working with. The ability to accurately determine the boundaries of the neoplastic growth significantly improves the quality of both surgical intervention and postoperative rehabilitation, as well as the duration and quality of life of patients.

RNA polymerase/promoter recognition represents a basic problem of molecular biology. Decades-long efforts were made in the area, and yet certain challenges persist. The usage of certain most suitable model subjects is pivotal for the research. System of T7 bacteriophage RNA-polymerase/T7 native promoter represents an exceptional example for the purpose. Moreover, it has been studied the most and successfully applied to aims of biotechnology and bioengineering. Both structural simplicity and high specificity of this molecular duo are the reason for this. Despite highly similar sequences of distinct T7 native promoters, the T7 RNA-polymerase enzyme is capable of binding respective promoter in a highly specific and adjustable manner. One explanation here is that the process relies primarily on DNA physical properties rather than nucleotide sequence. Here, we address the issue by analyzing massive data recently published by Komura and colleagues. This initial study employed Next Generation Sequencing (NGS) in order to quantify activity of promoter variants including ones with multiple substitutions. As a result of our work substantial bias in simultaneous occurrence of single-nucleotide sequence alterations was found: the highest rate of co-occurrence was evidenced within specificity loop of binding region while the lowest - in initiation region of promoter. If both location and a kind of nucleotides involved in replacement (both initial and resulting) are taken into consideration, one can easily note that N to A substitutions are most preferred ones across the whole 19 b.p.-long sequence. At the same time, N to C are tolerated only at crucial position in recognition loop of binding region, and N to G are uniformly least tolerable. Later in this work the complete set of variants was split into groups with mutations (1) exclusively in binding region; (2) exclusively in melting region; (3) in both regions. Among these three groups second comprises extremely few variants (at triple-digit rate lesser than in two other groups, 46 versus over one and six thousand). Yet these are all promoter with substantial to high activity. This group two appeared heterogenous by primary sequence; indeed, upon further subdivision into above versus below average activity subgroups first one was found to comprise promoters with negligible conservation at - 2 position of melting region; the second was hardly conserved in this region at all. This draws our attention to perfect consensus sequence of class III T7 promoter with - 2 nucleotide randomized (all four are present by one to several copies in the previously published source dataset), the picture becomes even more pronounced. We therefore suggest that mutations at the position therefore do not cause significant changes in terms of promoter activity. At the same time, such modifications dramatically change DNA physical properties which were calculated in our study (namely electrostatic potential and propensity to bend). One possible suggestion here is that - 2 nucleotide might function as a generic switch; if so, substitution - 2A to - 2T has important regulatory consequences. The fact that that - 2 b.p. is the most evidently different nucleotide between class II versus class III promoters of T7 genome and that it also distinguishes the class III promoter in T7 genome versus promoters of its relative but reproductively isolated bacteriophage T3. In other words, it appears feasible that mutation at - 2 nucleotide does not impede promoter activity yet alter its physical properties thus affecting differential RNA polymerase/promoter interaction.

The development of perspective diagnostic techniques in medicine requires efficient high-throughput biological sample analysis methods. Here, we present an inline cartridge extraction that facilitates the screening rate of mass spectrometry shotgun lipidomic analysis of tissue samples. We illustrate the method by its application to tumor tissue identification in neurosurgery. In perspective, this high-performance method provides new possibilities for the investigation of cancer pathogenesis and metabolic disorders.

A novel X-ray gas monitor (XGM) has been developed which allows the measurement of absolute photon pulse energy and photon beam position at all existing and upcoming free-electron lasers (FELs) over a broad spectral range covering vacuum ultraviolet (VUV), extreme ultraviolet (EUV) and soft and hard X-rays. The XGM covers a wide dynamic range from spontaneous undulator radiation to FEL radiation and provides a temporal resolution of better than 200 ns. The XGM consists of two X-ray gas-monitor detectors (XGMDs) and two huge-aperture open electron multipliers (HAMPs). The HAMP enhances the detection efficiency of the XGM for low-intensity radiation down to 10 5 photons per pulse and for FEL radiation in the hard X-ray spectral range, while the XGMD operates in higher-intensity regimes. The relative standard uncertainty for measurements of the absolute photon pulse energy is well below 10%, and down to 1% for measurements of relative pulse-to-pulse intensity on pulses with more than 10 10 photons per pulse. The accuracy of beam-position monitoring in the vertical and horizontal directions is of the order of 10 µm., (open access.)

X-ray gas monitors (XGMs) are operated at the European XFEL for non-invasive single-shot pulse energy measurements and average beam position monitoring. They are used for tuning and maintaining the self-amplified spontaneous emission (SASE) operation and for sorting single-shot experimental data according to the pulse-resolved energy monitor data. The XGMs were developed at DESY based on the specific requirements for the European XFEL. In total, six XGM units are continuously in operation. Here, the main principle and experimental setup of an XGM are summarized, and the locations of the six XGMs at the facility are shown. Pulse energy measurements at 0.134 nm wavelength are presented, exceeding 1 mJ obtained with an absolute measurement uncertainty of 7-10%; correlations between different XGMs are shown, from which a SASE1 beamline transmission of 97% is deduced. Additionally, simultaneous position measurements close to the undulator and at the end of the tunnel are shown, along with the correlation of beam position data simultaneously acquired by an XGM and an imager.

The majority of research in the biomedical sciences is carried out with the highest resolution accessible to the scientist, but, in the clinic, cost constraints necessitate the use of low-resolution devices. Here, we compare high- and low-resolution direct mass spectrometry profiling data and propose a simple pre-processing technique that makes high-resolution data suitable for the development of classification and regression techniques applicable to low-resolution data, while retaining high accuracy of analysis. This work demonstrates an approach to de-noising spectra to make the same representation for both high- and low-resolution spectra. This approach uses noise threshold detection based on the Tversky index, which compares spectra with different resolutions, and minimizes the percentage of resolution-specific peaks. The presented method provides an avenue for the development of analytical algorithms using high-resolution mass spectrometry data, while applying these algorithms in the clinic using low-resolution mass spectrometers., (© 2019 Published by Elsevier B.V. on behalf of The Association for Mass Spectrometry: Applications to the Clinical Lab (MSACL).)

In this work, we demonstrate a new approach for assessing the stability and reproducibility of mass spectra obtained via ambient ionization methods. This method is suitable for both comparing experiments during which only one mass spectrum is measured and for evaluating the internal homogeneity of mass spectra collected over a period of time. The approach uses Pearson's r coefficient and the cosine measure to compare the spectra. It is based on the visualization of dissimilarities between measurements, thus leading to the analysis of dissimilarity patterns. The cosine measure and correlations are compared to obtain better metrics for spectra homogeneity. The method filters out unreliable scans to prevent the analyzed sample from being wrongly characterized. The applicability of the method is demonstrated on a set of brain tumor samples. The developed method could be employed in neurosurgical applications, where mass spectrometry is used to monitor the intraoperative tumor border.

The relation between the processes of replication and transcription has been actively studied over several decades, but detailed mechanisms for their interaction have not been established reliably. Among the initiating transcription promoters of bacteria and bacteriophages, there are both promoters having an additional function of the secondary origin of replication (OR) and promoters not participating in this process. In this paper, we describe the stability of DNA by Stress-Induced Duplex Destabilization (SIDD) profiles for a complete set of promoters and the primary OR of the bacteriophage T7 genome. It has been shown that, among the native T7 promoters, only those that have an additional function of secondary OR are characterized by high destabilization. These include the phiOL and phiOR promoters adjoining the 5' and 3' terminal repeats of bacteriophage T7, and of six other T7 group phages. In each case, these two promoters are located in the regions of DNA with high destabilization of the duplex. Additionally, the genomes of seven representatives of the T7 group without annotated phiOL and phiOR have been considered. For three of them, high peaks of SIDD profiles have been found near the ends of the genomic DNA that may be due to the presence of similar phiOL and phiOR promoters. Probably, such promoters can be found in the genomes of other bacteriophages. Thus, for the promoters of bacteriophages, we have a confirmation of the relationship of SIDD as a DNA duplex parameter and the DNA replication initiation on promoters, serving as secondary OR.

Bioelectrochemical systems such as microbial fuel cells (MFCs) are promising new technologies for efficient removal of organic compounds from industrial wastewaters, including that generated from swine farming. We inoculated two pairs of laboratory-scale MFCs with sludge granules from a beer wastewater-treating anaerobic digester (IGBS) or from sludge taken from the bottom of a tank receiving swine wastewater (SS). The SS-inoculated MFC outperformed the IGBS-inoculated MFC with regard to COD and VFA removal and electricity production. Using a metagenomic approach, we describe the microbial diversity of the MFC planktonic and anodic communities derived from the different inocula. Proteobacteria (mostly Deltaproteobacteria) became the predominant phylum in both MFC anodic communities with amplification of the electrogenic genus Geobacter being the most pronounced. Eight dominant and three minor species of Geobacter were found in both MFC anodic communities. The anodic communities of the SS-inoculated MFCs had a higher proportion of Clostridium and Bacteroides relative to those of the IGBS-inoculated MFCs, which were enriched with Pelobacter . The archaeal populations of the SS- and IGBS-inoculated MFCs were dominated by Methanosarcina barkeri and Methanothermobacter thermautotrophicus , respectively. Our results show a long-term influence of inoculum type on the performance and microbial community composition of swine wastewater-treating MFCs.

Motivation: Bacterial luciferases are heterodimeric enzymes that catalyze a chemical reaction, so called bioluminescence, which causes light emission in bacteria. Bioluminescence is vastly used as a reporter system in research tools and commercial developments. However, the details of the mechanisms that stabilize and transform the reaction intermediates as well as differences in the enzymatic kinetics amongst different bacterial luciferases remain to be elucidated., Results: Amino acid sequences alignments for 21 bacterial luciferases (both α- and β-subunits) were analyzed. For α-subunit, containing the enzyme active center, 48 polymorphic amino acid positions were identified. According to them, the sequences fell into two distinct groups known as slow and fast based on the decay rate of the bioluminescence reaction. The differences in the enzyme active site induced by structural polymorphism are analyzed., Availability and Implementation: Three-dimensional models of Photobacterium leiognathi luciferase and Vibrio harveyi luciferase (with reconstructed mobile loop) are freely available at PMDB database: PM0080525 and PM0080526, respectively., Contact: adeeva@sfu-kras.ruSupplementary information: Supplementary data are available at Bioinformatics online., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The results of a study of ultra-rapid (flash) sintering of oxide ceramic materials under microwave heating with high absorbed power per unit volume of material (10-500 W/cm³) are presented. Ceramic samples of various compositions-Al₂O₃; Y₂O₃; MgAl₂O₄; and Yb(LaO)₂O₃-were sintered using a 24 GHz gyrotron system to a density above 0.98-0.99 of the theoretical value in 0.5-5 min without isothermal hold. An analysis of the experimental data (microwave power; heating and cooling rates) along with microstructure characterization provided an insight into the mechanism of flash sintering. Flash sintering occurs when the processing conditions-including the temperature of the sample; the properties of thermal insulation; and the intensity of microwave radiation-facilitate the development of thermal runaway due to an Arrhenius-type dependency of the material's effective conductivity on temperature. The proper control over the thermal runaway effect is provided by fast regulation of the microwave power. The elevated concentration of defects and impurities in the boundary regions of the grains leads to localized preferential absorption of microwave radiation and results in grain boundary softening/pre-melting. The rapid densification of the granular medium with a reduced viscosity of the grain boundary phase occurs via rotation and sliding of the grains which accommodate their shape due to fast diffusion mass transport through the (quasi-)liquid phase. The same mechanism based on a thermal runaway under volumetric heating can be relevant for the effect of flash sintering of various oxide ceramics under a dc/ac voltage applied to the sample.

A gas monitor detector was implemented and characterized at the Soft X-ray Research (SXR) instrument to measure the average, absolute and pulse-resolved photon flux of the LCLS beam in the energy range between 280 and 2000 eV. The detector is placed after the monochromator and addresses the need to provide reliable absolute pulse energy as well as pulse-resolved measurements for the various experiments at this instrument. This detector provides a reliable non-invasive measurement for determining flux levels on the samples in the downstream experimental chamber and for optimizing signal levels of secondary detectors and for the essential need of data normalization. The design, integration into the instrument and operation are described, and examples of its performance are given.

This paper reports novel measurements of x-ray optical radiation on an absolute scale from the intense and ultra-short radiation generated in the soft x-ray regime of a free electron laser. We give a brief description of the detection principle for radiation measurements which was specifically adapted for this photon energy range. We present data characterizing the soft x-ray instrument at the Linac Coherent Light Source (LCLS) with respect to the radiant power output and transmission by using an absolute detector temporarily placed at the downstream end of the instrument. This provides an estimation of the reflectivity of all x-ray optical elements in the beamline and provides the absolute photon number per bandwidth per pulse. This parameter is important for many experiments that need to understand the trade-offs between high energy resolution and high flux, such as experiments focused on studying materials via resonant processes. Furthermore, the results are compared with the LCLS diagnostic gas detectors to test the limits of linearity, and observations are reported on radiation contamination from spontaneous undulator radiation and higher harmonic content.

The entire T7 bacteriophage genome contains 39937 base pairs (Database NCBI RefSeq N1001604). Here, electrostatic potential distribution around double helical T7 DNA was calculated by Coulomb method using the computer program of Sorokin A.A. (lptolik@gmail.com). Electrostatic profiles of 17 promoters recognized by T7 phage-specific RNA polymerase were analyzed. It was shown that electrostatic profiles of all T7 RNA polymerase-specific promoters can be characterized by distinctive motifs which are specific for each promoter class. Comparative analysis of electrostatic profiles of native T7 promoters of different classes demonstrates that T7 RNA polymerase can differentiate them due to their electrostatic features.

We have observed the simultaneous inner-shell absorption of two extreme-ultraviolet photons by a Xe atom in an experiment performed at the short-wavelength free electron laser facility FLASH. Photoelectron spectroscopy permitted us to unambiguously identify a feature resulting from the ionization of a single electron of the 4d subshell of Xe by two photons each of energy (93±1)  eV. The feature's intensity has a quadratic dependence on the pulse energy. The results are discussed and interpreted within the framework of recent results of ion spectroscopy experiments of Xe obtained at ultrahigh irradiance in the extreme-ultraviolet regime.

The distribution of the electrostatic potential of T7 bacteriophage genome has been calculated. Promoter sites were localized in the electrostatic profile of T7-DNA. The electrostatic patterns of sigma70-specific promoters interacting with Escherichia coli RNA-polymerase were analyzed and compared with their functional behavior. Some specific electrostatic motifs were found in the upstream region of the promoters that may be involved in the differential recognition of promoter DNA by RNA-polymerase.

Exceptional behavior of light-matter interaction in the extreme ultraviolet is demonstrated. The photoionization of different rare gases was compared at the free-electron laser in Hamburg, FLASH, by applying ion spectroscopy at the wavelength of 13.7 nm and irradiance levels of thousands of terawatts per square centimeter. In the case of xenon, the degree of nonlinear photoionization was found to be significantly higher than for neon, argon, and krypton. This target specific behavior cannot be explained by the standard theories developed for optical strong-field phenomena. We suspect that the collective giant 4d resonance of xenon is the driving force behind the effect that arises in this spectral range.

The temporal coherence properties of soft x-ray free electron laser pulses at FLASH are measured at 23.9 nm by interfering two time-delayed partial beams directly on a CCD camera. The partial beams are obtained by wave front beam splitting in an autocorrelator operating at photon energies from h nu = 30 to 200 eV. At zero delay a visibility of (0.63+/- 0.04) is measured. The delay of one partial beam reveals a coherence time of 6 fs at 23.9 nm. The visibility further displays a non-monotonic decay, which can be rationalized by the presence of multiple pulse structure.

In the spectral range of the extreme ultraviolet at a wavelength of 13.3 nm, we have studied the photoionization of xenon at ultrahigh intensities. For our ion mass-to-charge spectroscopy experiments, irradiance levels from 10(12) to 10(16) W cm(-2) were achieved at the new free-electron laser in Hamburg FLASH by strong beam focusing with the aid of a spherical multilayer mirror. Ion charges up to Xe21+ were observed and investigated as a function of irradiance. Our surprising results are discussed in terms of a perturbative and nonperturbative description.

The oligonucleotide composition of the E. coli genome and its sigma70-specific promoters has been analyzed. The promoter DNA was shown to contain mainly AT-rich hexanucleotides having functionally important physical properties such as the ability to form easily melting sites and induce the bending of the double helix. A comparative analysis of the electrostatic characteristics of hexanucleotides within the whole sequence of the E. coli genome and its promoter regions was made. Hexanucleotides possessing a more electronegative surrounding were found to predominate in the nucleotide sequence of the promoter DNA.

Electrostatic profiles for sigma70-specific promoters of T4 bacteriophage and four consensus-like synthetic promoters have been calculated. It was shown that the promoters can be classified according to the presence of some specific electrostatic elements located in the far upstream region of their DNAs. A correlation between the electrostatic elements specific for promoters and their functional behaviour was established. A general scheme of promotor activity regulation through electrostatic interactions between the upstream region of promoter DNA and the RNA-polymerase a-subunit was suggested.

A comparative analysis of electrostatic patterns for 359 sigma70-specific promoters and 359 nonpromoter regions on electrostatic map of Escherichia coli genome was carried out. It was found that DNA is not a uniformly charged molecule. There are some local inhomogeneities in its electrostatic profile which correlate with promoter sequences. Electrostatic patterns of promoter DNAs can be specified due to the presence of some distinctive motifs which differ for different promoter groups and may be involved as signal elements in differential recognition of various promoters by the enzyme. Some specific electrostatic elements which are responsible for modulating promoter activities due to ADP-ribosylation of RNA polymerase alpha-subunit were found in far upstream regions of T4 phage early promoters and E. coli ribosomal promoters.

Distribution of electrostatic potential of the complete sequence of E. coli genome was calculated. Comparative analysis of electrostatic patterns for 359 promoter and nonpromoter nucleotide sequences was carried out. It is found that nonpromoter regions are characterized by more homogeneous distribution of electrostatic potential with no common specific elements. Electrostatic patterns of promoter DNAs can be specified due to the presence of some distinctive motifs which may be involved as promoter signal elements in RNA-polymerase-promoter recognition.

The distribution of electrostatic potential of the complete sequence of the E. coli genome was calculated. It was found that DNA is not a uniformly charged molecule. There are some local inhomogeneities in its electrostatic profile, which correlate with the position of promoters in the genome. Electrostatic patterns of promoter DNAs can be specified due to the presence of some distinctive motifs, which may be involved as promoter signal elements in RNA-polymerase-promoter recognition.

A comparative analysis of electrostatic potential distribution for "early" T4 phage promoters was undertaken. The data obtained indicate that there are some particular elements in the patterns of electrostatic potential distribution of promoter DNA specific for promoter groups differing by their functional response to ADP-ribosylation of the alpha-subunit as well as to rpoB403- or rpoB409 mutationals of the beta-subunit of RNA-polymerase.

Comparative analysis of electrostatic potential distribution for "early" T4 phage promoters was undertaken, along with calculation of topography of electrostatic potential around the native and ADP-ribosylated C-terminal domain of RNA polymerase alpha-subunit. The data obtained indicate that there is specific difference in the patterns of electrostatic potential distribution in far upstream regions of T4 promoters differing by their response to ADP-ribosylation of RNA polymerase. A specific change in profiles of electrostatic potential distribution for the native and ADP-ribosylated forms of RNA polymerase alpha-subunit was observed suggesting that this factor may be responsible for modulating T4 promoter activities in response to the enzyme modification.

Distribution of electrostatic potential of DNA fragments was evaluated. A method for calculation of electrostatic potential distribution based on Coulomb's law is proposed for long DNA fragments (approximately 1000 nucleotide pairs). For short DNA sequences, this technique provides a good correlation with the results obtained using Poisson-Boltzmann equation thus justifying its application in comparative studies for long DNA fragments. Calculation was performed for several DNA fragments from E. coli and bacteriophage T7 genomes containing promoter and nonpromoter regions. The results obtained indicate that coding regions are characterized by more homogeneous distribution of electrostatic potential whereas local inhomogeneity of DNA electrostatic profile is typical for promoter regions. The possible role of electrostatic interactions in RNA polymerase-promoter recognition is discussed.

The dynamics of cardiomyocyte spontaneous beatings with fractal dimension calculation was studied. It was shown that isolated single cardiomyocyte beats stochastically, but when a number of cells synchronized a significant changes in the dynamics appear: deterministic chaos could be detected. Several reasons are discussed as a possible explanation of such a behavior: the effect of system volume increasing and specific influence of gap-junctions on the rhythm formation.