Energetic Electron Precipitation Driven by Electromagnetic Ion Cyclotron Waves from ELFIN's Low Altitude Perspective.

We review comprehensive observations of electromagnetic ion cyclotron (EMIC) wave-driven energetic electron precipitation using data collected by the energetic electron detector on the Electron Losses and Fields InvestigatioN (ELFIN) mission, two polar-orbiting low-altitude spinning CubeSats, measuring 50-5000 keV electrons with good pitch-angle and energy resolution. EMIC wave-driven precipitation exhibits a distinct signature in energy-spectrograms of the precipitating-to-trapped flux ratio: peaks at >0.5 MeV which are abrupt (bursty) (lasting ∼17 s, or ΔL∼0.56) with significant substructure (occasionally down to sub-second timescale). We attribute the bursty nature of the precipitation to the spatial extent and structuredness of the wave field at the equator. Multiple ELFIN passes over the same MLT sector allow us to study the spatial and temporal evolution of the EMIC wave - electron interaction region. Case studies employing conjugate ground-based or equatorial observations of the EMIC waves reveal that the energy of moderate and strong precipitation at ELFIN approximately agrees with theoretical expectations for cyclotron resonant interactions in a cold plasma. Using multiple years of ELFIN data uniformly distributed in local time, we assemble a statistical database of ∼50 events of strong EMIC wave-driven precipitation. Most reside at L∼5-7 at dusk, while a smaller subset exists at L∼8-12 at post-midnight. The energies of the peak-precipitation ratio and of the half-peak precipitation ratio (our proxy for the minimum resonance energy) exhibit an L-shell dependence in good agreement with theoretical estimates based on prior statistical observations of EMIC wave power spectra. The precipitation ratio's spectral shape for the most intense events has an exponential falloff away from the peak (i.e., on either side of ∼1.45 MeV). It too agrees well with quasi-linear diffusion theory based on prior statistics of wave spectra. It should be noted though that this diffusive treatment likely includes effects from nonlinear resonant interactions (especially at high energies) and nonresonant effects from sharp wave packet edges (at low energies). Sub-MeV electron precipitation observed concurrently with strong EMIC wave-driven >1 MeV precipitation has a spectral shape that is consistent with efficient pitch-angle scattering down to ∼ 200-300 keV by much less intense higher frequency EMIC waves at dusk (where such waves are most frequent). At ∼100 keV, whistler-mode chorus may be implicated in concurrent precipitation. These results confirm the critical role of EMIC waves in driving relativistic electron losses. Nonlinear effects may abound and require further investigation.

The ELFIN Mission.

The Electron Loss and Fields Investigation with a Spatio-Temporal Ambiguity-Resolving option (ELFIN-STAR, or heretoforth simply: ELFIN) mission comprises two identical 3-Unit (3U) CubeSats on a polar (∼93∘ inclination), nearly circular, low-Earth (∼450 km altitude) orbit. Launched on September 15, 2018, ELFIN is expected to have a >2.5 year lifetime. Its primary science objective is to resolve the mechanism of storm-time relativistic electron precipitation, for which electromagnetic ion cyclotron (EMIC) waves are a prime candidate. From its ionospheric vantage point, ELFIN uses its unique pitch-angle-resolving capability to determine whether measured relativistic electron pitch-angle and energy spectra within the loss cone bear the characteristic signatures of scattering by EMIC waves or whether such scattering may be due to other processes. Pairing identical ELFIN satellites with slowly-variable along-track separation allows disambiguation of spatial and temporal evolution of the precipitation over minutes-to-tens-of-minutes timescales, faster than the orbit period of a single low-altitude satellite (Torbit ∼ 90 min). Each satellite carries an energetic particle detector for electrons (EPDE) that measures 50 keV to 5 MeV electrons with Δ E/E < 40% and a fluxgate magnetometer (FGM) on a ∼72 cm boom that measures magnetic field waves (e.g., EMIC waves) in the range from DC to 5 Hz Nyquist (nominally) with <0.3 nT/sqrt(Hz) noise at 1 Hz. The spinning satellites (Tspin ∼ 3 s) are equipped with magnetorquers (air coils) that permit spin-up or -down and reorientation maneuvers. Using those, the spin axis is placed normal to the orbit plane (nominally), allowing full pitch-angle resolution twice per spin. An energetic particle detector for ions (EPDI) measures 250 keV - 5 MeV ions, addressing secondary science. Funded initially by CalSpace and the University Nanosat Program, ELFIN was selected for flight with joint support from NSF and NASA between 2014 and 2018 and launched by the ELaNa XVIII program on a Delta II rocket (with IceSatII as the primary). Mission operations are currently funded by NASA. Working under experienced UCLA mentors, with advice from The Aerospace Corporation and NASA personnel, more than 250 undergraduates have matured the ELFIN implementation strategy; developed the instruments, satellite, and ground systems and operate the two satellites. ELFIN's already high potential for cutting-edge science return is compounded by concurrent equatorial Heliophysics missions (THEMIS, Arase, Van Allen Probes, MMS) and ground stations. ELFIN's integrated data analysis approach, rapid dissemination strategies via the SPace Environment Data Analysis System (SPEDAS), and data coordination with the Heliophysics/Geospace System Observatory (H/GSO) optimize science yield, enabling the widest community benefits. Several storm-time events have already been captured and are presented herein to demonstrate ELFIN's data analysis methods and potential. These form the basis of on-going studies to resolve the primary mission science objective. Broad energy precipitation events, precipitation bands, and microbursts, clearly seen both at dawn and dusk, extend from tens of keV to >1 MeV. This broad energy range of precipitation indicates that multiple waves are providing scattering concurrently. Many observed events show significant backscattered fluxes, which in the past were hard to resolve by equatorial spacecraft or non-pitch-angle-resolving ionospheric missions. These observations suggest that the ionosphere plays a significant role in modifying magnetospheric electron fluxes and wave-particle interactions. Routine data captures starting in February 2020 and lasting for at least another year, approximately the remainder of the mission lifetime, are expected to provide a very rich dataset to address questions even beyond the primary mission science objective.

Carcinogenesis Associated with Human Papillomavirus Infection. Mechanisms and Potential for Immunotherapy.

Human papillomavirus (HPV) infection is responsible for approximately 5% of all cancers and is associated with 30% of all pathogen-related cancers. Cervical cancer is the third most common cancer in women worldwide; about 70% of cervical cancer cases are caused by the high-risk HPVs (HR HPVs) of genotypes 16 and 18. HPV infection occurs mainly through sexual contact; however, viral transmission via horizontal and vertical pathways is also possible. After HPV infection of basal keratinocytes or ecto-endocervical transition zone cells, viral DNA persists in the episomal form. In most cases, infected cells are eliminated by the immune system. Occasionally, elimination fails, and HPV infection becomes chronic. Replication of HPVs in dividing epithelial cells is accompanied by increased expression of the E6 and E7 oncoproteins. These oncoproteins are responsible for genomic instability, disruption of the cell cycle, cell proliferation, immortalization, and malignant transformation of HPV-infected cells. Besides, E6 and E7 oncoproteins induce immunosuppression, preventing the detection of HPV-infected and transformed cells by the immune system. HPV integration into the genome of the host cell leads to the upregulation of E6 and E7 expression and contributes to HPV-associated malignization. Prophylactic HPV vaccines can prevent over 80% of HPV-associated anogenital cancers. The vaccine elicits immune response that prevents initial infection with a given HPV type but does not eliminate persistent virus once infection has occurred and does not prevent development of the HPV-associated neoplasias, which necessitates the development of therapeutic vaccines to treat chronic HPV infections and HPV-associated malignancies.

Therapeutic Vaccines Against Human Papilloma Viruses: Achievements and Prospects.

Human papillomaviruses of high carcinogenic risk (HR HPVs) are major etiological agents of malignant diseases of the cervix, vulva, penis, anal canal, larynx, head, and neck. Prophylactic vaccination against HPV, which mainly covers girls and women under 25, does not prevent vertical and horizontal HPV transmission in infants and children and does not have a therapeutic effect. As a result, a significant proportion of the population is not protected from the HPV infection and development of HPV-associated neoplastic transformation and cancer, which indicates the need for development and introduction of therapeutic HPV vaccines. Unlike prophylactic vaccines aimed at the formation of virus-neutralizing antibodies, therapeutic vaccines elicit cellular immune response leading to the elimination of infected and malignant cells expressing viral proteins. The ideal targets for vaccine immunotherapy are highly conserved HR HPV oncoproteins E6 and E7 expressed in precancerous and tumor tissues. Here, we describe expression of these proteins during different stages of HPV infection, their antigenic and immunogenic properties, and T-cell epitopes, the response to which correlates with natural regression of HPV-induced neoplastic changes. The review describes patterns of E6 and E7 oncoproteins presentation to the immune system as components of candidate vaccines along with the results of the most promising preclinical trials and animal models used in these trials. Special attention is paid to vaccine candidates which have shown efficacy in clinical trials in patients with HPV-associated neoplastic changes.

Characteristics of the Flank Magnetopause: THEMIS Observations.

The terrestrial magnetopause is the boundary that shields the Earth's magnetosphere on one side from the shocked solar wind and its embedded interplanetary magnetic field on the other side. In this paper, we show observations from two of the Time History of Events and Macroscales Interactions during Substorms (THEMIS) satellites, comparing dayside magnetopause crossings with flank crossings near the terminator. Macroscopic properties such as current sheet thickness, motion, and current density are examined for a large number of magnetopause crossings. The results show that the flank magnetopause is typically thicker than the dayside magnetopause and has a lower current density. Consistent with earlier results from Cluster observations, we also find a persistent dawn-dusk asymmetry with a thicker and more dynamic magnetopause at dawn than at dusk.

Magnetotail Fast Flow Occurrence Rate and Dawn-Dusk Asymmetry at XGSM ∼ -60 RE.

As a direct result of magnetic reconnection, plasma sheet fast flows act as primary transporter of mass, flux, and energy in the Earth's magnetotail. During the last decades, these flows were mainly studied within XGSM>-60RE , as observations near or beyond lunar orbit were limited. By using 5 years (2011-2015) of ARTEMIS (Acceleration, Reconnection, Turbulence, and Electrodynamics of the Moons Interaction with the Sun) data, we statistically investigate earthward and tailward flows at around 60 RE downtail. A significant fraction of fast flows is directed earthward, comprising 43% (vx >400 km/s) to 56% (vx >100 km/s) of all observed flows. This suggests that near-Earth and midtail reconnection are equally probable of occurring on either side of the ARTEMIS downtail distance. For fast convective flows (v⊥x >400 km/s), this fraction of earthward flows is reduced to about 29%, which is in line with reconnection as source of these flows and a downtail decreasing Alfvén velocity. More than 60% of tailward convective flows occur in the dusk sector (as opposed to the dawn sector), while earthward convective flows are nearly symmetrically distributed between the two sectors for low AL (>-400 nT) and asymmetrically distributed toward the dusk sector for high AL (<-400 nT). This indicates that the dawn-dusk asymmetry is more pronounced closer to Earth and moves farther downtail during high geomagnetic activity. This is consistent with similar observations pointing to the asymmetric nature of tail reconnection as the origin of the dawn-dusk asymmetry of flows and other related observables. We infer that near-Earth reconnection is preferentially located at dusk, whereas midtail reconnection (X >- 60RE ) is likely symmetric across the tail during weak substorms and asymmetric toward the dusk sector for strong substorms, as the dawn-dusk asymmetric nature of reconnection onset in the near-Earth region progresses downtail.

Green Tea Extract Increases the Expression of Genes Responsible for Regulation of Calcium Balance in Rat Slow-Twitch Muscles under Conditions of Exhausting Exercise.

We studied the role of calcium-regulating structures of slow- (m. soleus, SOL) and fast-twitch (m. extensor digitorum longus, EDL) skeletal muscles of rats during adaptation to exhausting physical activity and the possibility of modulating this adaptation with decaffeinated green tea extract. It was established that EDL adaptation is mainly aimed at Са2+ elimination from the sarcoplasm by Са-ATPase and its retention in the reticulum by calsequestrin. Administration of green tea extract increased endurance due to involvement of slow-twitch muscles whose adaptation is associated with enhanced expression of all the studied genes responsible for the regulation of Ca2+ balance.

[DNA methylation level and telomere length as a basis for the biological aging clock model construction].

Aging is a process that depends on a variety of both external and internal factors. The biological age of a person determines body deterioration and the risk of age-related diseases. Currently, as indicators of biological age are considered different characteristics including average length of telomeres in cells and the level DNA methylation. We propose to combine the two approaches to create a model to assess the biological age of the person. Application of qPCR to determina the length of telomeres and MS-HRM for analysis of DNA methylation will help us to determine the parameters of interest quickly when using a minimum set of equipment.

[Selection of reference genes for transcription analysis for myocarditis studies].

Myocarditis is defined as myocardial inflammation, followed by cardiomyocyte necrosis. Diagnostics of myocarditis is based on unsafe and complicated method of endomyocardial biopsy (EMB). Development of myocarditis might alter gene expression not only in cardiac but in peripheral blood cells (PBC) as well. So, transcription profiles can be considered as possible biomarkers for the given pathology. At the moment, there are no reference genes defined for expression analysis in myocarditis studies. In this study, we analyzed mRNA content of six housekeeping genes in EMB and PBC samples. An algorithm for processing qPCR results obtained under the limited amount of sample is proposed. Set of GAPDH and HPRT1 genes has been selected for normalization of gene expression profiles in cardiac tissue and blood cells under the studies of myocarditis.

Electromagnetic energy conversion at reconnection fronts.

Earth's magnetotail contains magnetic energy derived from the kinetic energy of the solar wind. Conversion of that energy back to particle energy ultimately powers Earth's auroras, heats the magnetospheric plasma, and energizes the Van Allen radiation belts. Where and how such electromagnetic energy conversion occurs has been unclear. Using a conjunction between eight spacecraft, we show that this conversion takes place within fronts of recently reconnected magnetic flux, predominantly at 1- to 10-electron inertial length scale, intense electrical current sheets (tens to hundreds of nanoamperes per square meter). Launched continually during intervals of geomagnetic activity, these reconnection outflow flux fronts convert ~10 to 100 gigawatts per square Earth radius of power, consistent with local magnetic flux transport, and a few times 10(15) joules of magnetic energy, consistent with global magnetotail flux reduction.

[Telomere length in the population of long-lived persons of North-West region of Russia].

Interdisciplinary study of telomere length, polymorphism of genes of renin-angiotensin (ACE) and serotonin (5HTR2A and 5HTTPR) systems in population of aged and old inhabitants of the North-West of Russia was conducted, in their relations to data from clinical and geriatric anamnesis, and psychological functioning. Regular link between telomere length and respondent's age was demonstrated in subgroups of old respondents and long-livers, by method of factor analysis.

Anomalous scaling, nonlocality, and anisotropy in a model of the passively advected vector field.

A model of the passive vector quantity advected by the Gaussian velocity field with the covariance approximately delta(t-t('))|x-x(')|(epsilon) is studied; the effects of pressure and large-scale anisotropy are discussed. The inertial-range behavior of the pair correlation function is described by an infinite family of scaling exponents, which satisfy exact transcendental equations derived explicitly in d dimensions by means of the functional techniques. The exponents are organized in a hierarchical order according to their degree of anisotropy, with the spectrum unbounded from above and the leading (minimal) exponent coming from the isotropic sector. This picture extends to higher-order correlation functions. Like in the scalar model, the second-order structure function appears nonanomalous and is described by the simple dimensional exponent: S2 approximately r(2-epsilon). For the higher-order structure functions, S(2n)approximately r(n(2-epsilon)+ delta(n)), the anomalous scaling behavior is established as a consequence of the existence in the corresponding operator product expansions of "dangerous" composite operators, whose negative critical dimensions determine the anomalous exponents delta(n)<0. A close formal resemblance of the model with the stirred Navier-Stokes equation reveals itself in the mixing of relevant operators and is the main motivation of the paper. Using the renormalization group, the anomalous exponents are calculated in the O(epsilon) approximation, in large d dimensions, for the even structure functions up to the twelfth order.

[Treatment of acute complicated abscess of the lungs]. / Lechenie ostrykh oslozhnennykh abstsessov legkikh.

Results of examination and treatment of 194 patients with acute complicated abscesses of the lungs were analyzed. The main pathogenic agent of this pathology is gram-negative microorganisms and anaerobic neclostridial flora. Methods of bacterioscopy and gas-liquid chromatography were used for its verification. It was noted that the basis of medical tactics in complicated abscesses of the lungs is the rational antibiotic therapy in combination with parasurgical methods of treatment. Surgical methods are indicated in gangrening abscess, pulmonary hemorrhage, non-effective complex therapy.