Hengzongshu/ArticleAgent huggingface dataset:
Recombinant human interferon alpha-2b (rIFN) is widely used for the treatment of both viral and oncological diseases. The short half-life and toxicity of rIFN are a serious limitation for the use of rIFN in therapy. In this regard, the development of a less toxic rIFN with a longer half-life is an important goal of medical biotechnology. Currently, there are two main modifications of long-acting rIFN - pegylated rIFN and rIFN genetically fused with albumin. The use of human apolipoprotein A-I (apoA-I) as a protector protein seems also promising, since apoA-I has a long half-life in the body, is not immunogenic, is capable of natural formation of lipoprotein complexes, and allows improve the pharmacokinetics of therapeutic proteins fused with it.

In this work, a recombinant strain of Pichia pastoris X33, producing a chimeric protein consist of rIFN, fused with human apoA-I through a flexible linker, was obtained. The IFN and apoA-I genes were optimized for expression in P. pastoris. The cultivation of a yeast strain producing a chimeric cytokine was carried out in an orbital shaker. The protein yield was 30 mg/L. The chimera was purified by reversed phase chromatography. The purity of the final preparation of the chimera was about 90%. The primary structure of the chimera was confirmed by MALDI-TOF.

The chimeric cytokine exhibited high specific antiviral activity comparable to that of rIFN and equal to 1.6 × 108 IU/mg. The chimera showed a 1.8-fold longer half-life in comparison with rIFN аfter a single subcutaneous injection in mice.
Purpose Electron paramagnetic resonance (EPR) imaging in the spectral‐spatial domain with application of soluble paramagnetic probes provides an opportunity for spatially resolved functional measurements of living objects. The purpose of this study was to develop EPR methods for visualization of oxygenation and acidosis of ischemic myocardium. Methods EPR oxygen measurements were performed using isotopically substituted 2 H, 15 N‐dicarboxyproxyl. The radical has an EPR line width of 320 mG and oxygen‐induced line broadening of 0.53 mG/mm Hg, providing oxygen sensitivity down to 5 μM. pH measurements were performed using previously developed pH‐sensitive imidazoline nitroxide. The radical has an EPR spectrum with pH‐dependable hyperfine splitting, pK = 6.6, providing pH sensitivity of approximately 0.05 U in the physiological range. Results EPR imaging of isolated and perfused rat hearts was performed in the two‐dimensional + spectral domain. The spatial resolution of the measurements was about 1.4 mm. Marked tissue hypoxia was observed in the ischemic area of the heart after occlusion of the left anterior descending coronary artery. Tissue oxygenation was partly restored upon reperfusion. EPR mapping of myocardial pH indicated acidosis of the ischemic area down to pH 6.7–6.8. Conclusion This study demonstrates the capability of low‐field EPR and the nitroxide spin probes for mapping of myocardial oxygenation and pH. The developed approaches might be used for noninvasive investigation of microenvironment on living objects. Magn Reson Med 76:350–358, 2016. © 2015 Wiley Periodicals, Inc.
MicroRNAs (miRNA) are short 21-23nt RNAs capable of inhibiting translation of complementary target messenger RNAs. Almost half of D. melanogaster miRNA genes are grouped in genomic clusters. The peculiarities of the expression of clustered miRNAs were studied using publicly available libraries of sequenced small RNAs from different Drosophila tissues. We have shown that although miRNAs from almost all clusters have similar tissue expression profiles (coordinated clusters), some clusters contain miRNAs with uncoordinated expression profiles. The predicted transcription start sites (TSSs) of such clusters are located upstream of the first miRNA, but no TSSs are found within the clusters. The expression profiles of miR and miR* sequences in uncoordinated clustered miRNAs do not correlate while their profiles from the coordinated clustered miRNAs are similar. The presence of exclusively upstream promoters in miRNA clusters containing uncoordinated miRNAs means that the clusters are transcribed as single transcription units. The difference of tissue expression profiles of uncoordinated miRNAs and the corresponding miRs* suggests a post-transcriptional regulation of their processing or stability.
Dilated cardiomyopathy (DCM) is a complex, etiologically heterogeneous myocardial disease, which is one of the main causes of heart failure and heart transplantation. In 2016, experts from the European working group proposed a new definition of cardiomyopathy, which includes intermediate variants with a change in phenotype in carriers of mutations from subclinical form to the full manifestations of the disease. The classification of DCM was supplemented with intermediate phenotypes with the inclusion of a hypokinetic form with reduced contractile function without ventricular dilatation and variants with predominant dilation or arrhythmogenicity. Pathological architectonics of DCM consists of many genetic determinants that interact with numerous environmental factors. Clinical manifestations depend not only on the malignancy and penetrance of the gene mutation, but also on a number of other causes — epigenomic factors, age, toxic effects, environmental aggressiveness, pregnancy, and the effects of other acquired diseases. The article summarizes the current epidemiological data and ideas about specific molecular changes with an unfavorable prognosis. For clarity, we present clinical observations of familial DCM with mutations in the RBM20 and LMNA genes.
Recently, the observation of a high-frequency private allele, the 9-repeat allele at microsatellite D9S1120, in all sampled Native American and Western Beringian populations has been interpreted as evidence that all modern Native Americans descend primarily from a single founding population. However, this inference assumed that all copies of the 9-repeat allele were identical by descent and that the geographic distribution of this allele had not been influenced by natural selection. To investigate whether these assumptions are satisfied, we genotyped 34 single nucleotide polymorphisms across ∼500 kilobases (kb) around D9S1120 in 21 Native American and Western Beringian populations and 54 other worldwide populations. All chromosomes with the 9-repeat allele share the same haplotypic background in the vicinity of D9S1120, suggesting that all sampled copies of the 9-repeat allele are identical by descent. Ninety-one percent of these chromosomes share the same 76.26 kb haplotype, which we call the "American Modal Haplotype" (AMH). Three observations lead us to conclude that the high frequency and widespread distribution of the 9-repeat allele are unlikely to be the result of positive selection: 1) aside from its association with the 9-repeat allele, the AMH does not have a high frequency in the Americas, 2) the AMH is not unusually long for its frequency compared with other haplotypes in the Americas, and 3) in Latin American mestizo populations, the proportion of Native American ancestry at D9S1120 is not unusual compared with that observed at other genomewide microsatellites. Using a new method for estimating the time to the most recent common ancestor (MRCA) of all sampled copies of an allele on the basis of an estimate of the length of the genealogy descended from the MRCA, we calculate the mean time to the MRCA of the 9-repeat allele to be between 7,325 and 39,900 years, depending on the demographic model used. The results support the hypothesis that all modern Native Americans and Western Beringians trace a large portion of their ancestry to a single founding population that may have been isolated from other Asian populations prior to expanding into the Americas.
This article describes an energy increase of the pulses generated from all-fiber Erbium master oscillator with a ring hybrid cavity.The energy is significantly increased up to 3.5 nJ with a cavity lengthening with a stable highly chirped dissipative soliton (HCDS) generation regime.Pump direction change leads to a generation of noise-like pulses with 5.5 nJ energy.
Violations of CPT symmetry and Lorentz invariance are searched for by studying interference effects in B^{0} mixing and in B_{s}^{0} mixing. Samples of B^{0}→J/ψK_{S}^{0} and B_{s}^{0}→J/ψK^{+}K^{-} decays are recorded by the LHCb detector in proton-proton collisions at center-of-mass energies of 7 and 8 TeV, corresponding to an integrated luminosity of 3 fb^{-1}. No periodic variations of the particle-antiparticle mass differences are found, consistent with Lorentz invariance and CPT symmetry. Results are expressed in terms of the standard model extension parameter Δa_{μ} with precisions of O(10^{-15}) and O(10^{-14}) GeV for the B^{0} and B_{s}^{0} systems, respectively. With no assumption on Lorentz (non)invariance, the CPT-violating parameter z in the B_{s}^{0} system is measured for the first time and found to be Re(z)=-0.022±0.033±0.005 and Im(z)=0.004±0.011±0.002, where the first uncertainties are statistical and the second systematic.
Many studies have shown that dichlorodiphenyltrichloroethane (DDT) exposure raises breast cancer risk. Another insecticide with similar properties is endosulfan, which has been actively used in agriculture after DDT prohibition. Previously, we have identified some estradiol-, progesterone-, and testosterone-sensitive microRNAs (miRNAs, miRs). Because DDT and endosulfan have estrogenic, antiandrogenic, and antiprogesterone properties, we hypothesized that these miRNAs are affected by the insecticides. We quantified relative levels of miRNAs and expression levels of their target genes in breast cancer MCF-7 cells treated with p,p'-DDT, o,p'-DDT, or endosulfan. We also quantified miR-19b expression, which, as previously shown, is regulated by estrogen. Here, we observed that miR-19b expression increased in response not only to estradiol but also to testosterone and progesterone. Treatment of MCF-7 cells with p,p'-DDT or endosulfan decreased the protein levels of apoptosis regulators TP53INP1 and APAF1. In cells treated with o,p'-DDT, the TP53INP1 amount decreased after 24 h of incubation, but increased after 48 h of incubation with insecticide. OXTR expression, which is known to be associated with breast carcinogenesis, significantly diminished under the exposure of all insecticides. In cells treated with p,p'-DDT or o,p'-DDT, the observed changes were accompanied by alterations of the levels of hormone-responsive miRNAs: miR-324, miR-190a, miR-190b, miR-27a, miR-193b, and miR-19b.
Age-related macular degeneration (AMD), a neurodegenerative and vascular retinal disease, is the leading cause of blindness in the developed world. Accumulating evidence suggests that alterations in the expression of a small heat shock protein (αB-crystallin) are involved in the pathogeneses of AMD. Here we demonstrate that senescence-accelerated OXYS rats—an animal model of the dry form of AMD—develop spontaneous retinopathy against the background of reduced expression of αB-crystallin in the retina at the early preclinical stages of retinopathy (age 20 days) as well as at 4 and 24 months of age, during the progressive stage of the disease. The level of αA-crystallin expression in the retina of OXYS rats at all the ages examined was no different from that in disease-free Wistar rats. Treatment with the mitochondria-targeted antioxidant SkQ1 (plastoquinonyl-decyltriphenylphosphonium) from 1.5 to 4 months of age, 250 nmol/kg, increased the level of αB-crystallin expression in the retina of OXYS rats. SkQ1 slowed the development of retinopathy and reduced histological aberrations in retinal pigment epithelium cells. SkQ1 also attenuated neurodegenerative changes in the photoreceptors and facilitated circulation in choroid blood vessels in the retina of OXYS rats; this improvement was probably linked with the restoration of αB-crystallin expression.
The Toarcian Oceanic Anoxic Event (T-OAE, c . 182 Ma) represents a major perturbation of the carbon cycle marked by widespread black shale deposition. Consequently, the onset of the T-OAE has been linked to the combined effects of global warming, high productivity, basin restriction and salinity stratification. However, the processes that led to termination of the event remain elusive.

Here, we present palynological data from Arctic Siberia (Russia), the Viking Corridor (offshore Norway) and the Yorkshire Coast (UK), all spanning the upper Pliensbachian – upper Toarcian stages. Rather than a ‘dinoflagellate cyst black-out’, as recorded in T-OAE strata of NW Europe, both the Arctic and Viking Corridor records show high abundance and dinoflagellate diversity throughout the T-OAE interval as calibrated by C-isotope records. Significantly, in the Arctic Sea and Viking Corridor, numerous species of the Parvocysta and Phallocysta suites make their first appearance in the lower Toarcian Falciferum Zone much earlier than in Europe, where these key dinoflagellate species appeared suddenly during the Bifrons Zone.

Our results indicate migrations of Arctic dinoflagellate species, driven by relative sea-level rise in the Viking Corridor and the establishment of a S-directed circulation from the Arctic Sea into the Tethys Ocean. The results support oceanographic models, but are at odds with some interpretations based on geochemical proxies. The migration of Arctic dinoflagellate species coincides with the end of the T-OAE and marks the arrival of oxygenated, low-salinity Arctic waters, triggering a regime change from persistent euxinia to more dynamic oxygen conditions.
$s$-channel discontinuity of the quark-quark scattering amplitude with gluon quantum numbers in the $t$ channel and a negative signature is calculated in the Regge kinematical region in the two-loop approximation. Using this discontinuity and assuming that the Regge asymptotic behavior is given by the Reggeized gluon contribution, we calculate the gluon trajectory in the two-loop approximation. Remarkable cancellations lead to the independence of the trajectory on properties of the scattered quarks, confirming the gluon Reggeization.
Features of the formation of supersonic underexpanded jets in condensation, as well as measurements in such jets by electron-beam and molecular-beam methods are considered.

The examples which compare the traditional method of mass spectrometry with ionization and a new method ionization by high-voltage electron beam with the subsequent transport of ions to the mass spectrometer detector with its own turned-off ionization block illustrate changes in the detected clusters.

It is shown that the clusters in the flow can change both the geometry and the structure of the supersonic jets. It is determined that the readings of the mass analyzer used as a detector of a narrowly directed molecular beam depend to a large extent on the size of the clusters and the value of the detector’s solid angle.
. Analysing the genesis of Quaternary sediments is important for understanding the glaciation history and development of marine sediments in the northern part of Western Siberia. The problem is relevant since there is no consistent concept of the Quaternary sediment genesis in the north of Western Siberia. The formation of sediments is associated with marine, glacial and interglacial sedimentation conditions. The research objective is to identify the persistent features characterising the conditions of sedimentation and relief formation using the Nadym River basin as an example. The best method for studying this problem is a comprehensive analysis of the lithological, chronostratigraphic, petrographic and geomorphological studies of the Quaternary sediment upper strata. This study provides data from the analysis of the basic characteristics of quartz grains at the site. The rounding and morphology of the quartz grains provide evidence of possible glacial processing of some of the site strata. A petrographic study of selected boulder samples was performed. Some of them, by the shape and presence of striation, can be attributed to ice basins. The first use of a detailed digital elevation model applied to the study area made it possible to identify specific relief forms that could very likely be created during glaciations. Based on the analysis, we propose to consider the vast lake alluvial plains in the Nadym River basin as periglacial regions. This idea lays the lithological framework for understanding the reasons for the formation of the modern landscape structure. The materials and descriptions provided are of interest to researchers of Quaternary sediments, topography, vegetation and soil cover, particularly researchers engaged in revising the history of the natural environment development in the north of Western Siberia.
One of the core symptoms of major depression in human is anhedonia.For that reason, one of the main requirements towards experimental depression models is that they be able to demonstrate anhedonia in animals, that have been exposed to stressful events, and other behavioral changes attributable to a depression-like state.However, the results presented in the literature are contradictory: sweet solution intake, which is considered as a parameter of hedonic/anhedonic behavior in animals, responds quite differently to stressful situations in that it is either unaffected or increased or decreased.

Different experimental designs used for the study of anhedonia in male mice exposed to chronic social defeat stress were tried to understand the reasons for so contradictory responses.Anhedonia appears as an abrupt reduction in sweet solution consumption in stressed animals and by failure to attain recovery after deprivation.However, it was also demonstrated that sucrose solution intake and preference strongly depend on the experimental context; that the possible critical factor may be prior acquaintance with the hedonic stimulus -or the lack whereof.

Analysis of literature data and ours allowed us to conclude that the lack of a significant decrease in sweet solution intake in stressed animals is no evidence of lack of depression.Furthermore this decrease is evidence of anhedonia only provided other symptoms of depression are present.Hedonic consumable intake can be decreased over various diseases, in particular, a high level of anxiety, pathological aggression or depression.
In modern conditions of a high level of uncertainty in the development of science, engineering and technology in economic sectors, it is necessary to learn how to manage this long-term process purposefully, which is possible through forecasting tools, for example, foresight methodology. This is especially true for agriculture, and in particular for the crop sector, where the level of uncertainty is much higher than in other sectors due to work with living organisms and the impact on the results of production of natural and climatic conditions.

The consistent use of foresight tools made it possible to develop a Strategy for the scientific and technological development of the crop industry for the Novosibirsk region, the algorithm of which is presented in this article.

The main feature of the Strategy will be the identification of promising areas of scientific and technological development depending on the natural and agricultural zoning of the region, which allows one to take into account the specifics of different regions of the Novosibirsk region to build a more accurate and high-quality forecast.
In his De communi mathematica scientia Iamblichus famously distinguishes two orders of initiation within the Pythagorean School. Clement of Alexandria as a 'Neopythagorean Philosopher' is relatively badly served.

The goal of the Pythagoreans consists not in abstaining from doing certain important things, but rather in abstention from harmful and useless things in order to attain to a better performance in those which are really vital. Thus, Pythagoras discoursed about sciences with those inclined to philosophy, while the rest received ethical maxims in a 'symbolic' manner.

Clement, however, does not want to know about any schism: this twofold education is considered by him a well-designed technique, which gradually leads the students to the 'revealed knowledge, reserved for the elite'. His distinction between fundamental belief and the highest faith, on the one hand, and the scientific knowledge and gnosis , on the other, became fundamental for the later Christian theory of knowledge.
Axionlike particles (ALPs) are predicted in many extensions of the standard model, and their masses can naturally be well below the electroweak scale. In the presence of couplings to electroweak bosons, these particles could be emitted in flavor-changing B meson decays. We report herein a search for an ALP, a, in the reaction B^{±}→K^{±}a, a→γγ using data collected by the BABAR experiment at SLAC. No significant signal is observed, and 90% confidence level upper limits on the ALP coupling to electroweak bosons are derived as a function of ALP mass, improving current constraints by several orders of magnitude in the range 0.175 GeV
Composite Sn + C electrodes were sputtered using an electric arc method. As a result, materials representing spherical tin nanoparticles packed in a carbon matrix were synthesized. The carbon matrix reliably separates the nanoparticles, preventing them from contacting and coagulating, which preserves their size. The structure of the material was studied in detail by transmission electron microscopy. The sizes of tin nanoparticles were described by a log-normal distribution, and the average size depended on the pressure of the buffer gas. The carbon structure was studied by Raman spectroscopy. It is established that tin and carbon structures are related to each other, and the processes of condensation of tin vapor and agglomeration of the carbon structure affect each other.
The Kamchatka Peninsula is one of the most tectonically active regions in the world, where intensive and diverse modern volcanic activity takes place. In the recent decade, substantial progress in the investigation of deep structures beneath Kamchatka has been achieved owing to numerous tomography studies based on seismological data provided by permanent stations and temporary networks deployed in some key areas.

The goal of this review is summarizing and systematizing dozens of separate multiscale geophysical studies in Kamchatka and constructing an integral model of volcano-feeding systems. An important part of this review contains the description of results of various seismic studies related to the Klyuchevskoy group volcanoes. The results of the regional-scale seismic tomography reveal the existence of the Pacific slab window. Middle-scale tomography studies have found traces of an ascending hot mantle flow. Seismic models of the entire crust in the area of the Klyuchevskoy group were used to identify different mechanisms of magmatic feeding. The data of local networks deployed on several volcanoes of Kamchatka were used to image the magma sources in the upper crust.

The comparison of the results for the Kamchatka volcanoes with tomography models of several other volcanoes of the world allowed determining some common features and differences in feeding active magmatic systems.
The evolution of mechanical properties of Russian steel St3 subjected to cyclic elasto-plastic deformation is analyzed under a broad spectrum of loading conditions. This particular material is chosen due to its wide use in industrial facilities operating in Arctic and Russian North.

Basic state parameters are determined, including the true strains, secant and tangent moduli, heat generation due to plastic dissipation, thus characterizing the evolution of the thermo-mechanical state. The temporal evolution of kinetic parameters during each loading block provides insights into the hardening and damage accumulation.

These data form an experimental basis for development, calibration, and validation of new material models. The main effects are identified and discussed, and the modelling approaches are assessed.