Amplification of Frequency-Modulated Similariton Pulses in Length-Inhomogeneous Active Fibers

The possibility of an effective gain of the self-similar frequency-modulated (FM) wave packets is studied in the lengthinhomogeneous active fibers. The dynamics of parabolic pulses with the constant chirp has been considered. The optimal profile for the change of the group-velocity dispersion corresponding to the optimal similariton pulse amplification has been obtained. It is shown that the use of FM pulses in the active (gain) and length-inhomogeneous optical fibers with the normal group-velocity dispersion can provide subpicosecond optical pulse amplification up to the energies higher than 1 nJ

Multi-Omics Studies towards Novel Modulators of Influenza A Virus-Host Interaction

Human influenza A viruses (IAVs) cause global pandemics and epidemics. These viruses evolve rapidly, making current treatment options ineffective. To identify novel modulators of IAV-host interactions, we re-analyzed our recent transcriptomics, metabolomics, proteomics, phosphoproteomics, and genomics/virtual ligand screening data. We identified 713 potential modulators targeting 199 cellular and two viral proteins. Anti-influenza activity for 48 of them has been reported previously, whereas the antiviral efficacy of the 665 remains unknown. Studying anti-influenza efficacy and immuno/neuro-modulating properties of these compounds and their combinations as well as potential viral and host resistance to them may lead to the discovery of novel modulators of IAV-host interactions, which might be more effective than the currently available anti-influenza therapeutics

A RAS-independent biomarker panel to reliably predict response to MEK inhibition in colorectal cancer

BACKGROUND: In colorectal cancer (CRC), mutations of genes associated with the TGF-β/BMP signaling pathway, particularly affecting SMAD4, are known to correlate with decreased overall survival and it is assumed that this signaling axis plays a key role in chemoresistance. METHODS: Using CRISPR technology on syngeneic patient-derived organoids (PDOs), we investigated the role of a loss-of-function of SMAD4 in sensitivity to MEK-inhibitors. CRISPR-engineered SMAD4(R361H) PDOs were subjected to drug screening, RNA-Sequencing, and multiplex protein profiling (DigiWest(R)). Initial observations were validated on an additional set of 62 PDOs with known mutational status. RESULTS: We show that loss-of-function of SMAD4 renders PDOs sensitive to MEK-inhibitors. Multiomics analyses indicate that disruption of the BMP branch within the TGF-β/BMP pathway is the pivotal mechanism of increased drug sensitivity. Further investigation led to the identification of the SFAB-signature (SMAD4, FBXW7, ARID1A, or BMPR2), coherently predicting sensitivity towards MEK-inhibitors, independent of both RAS and BRAF status. CONCLUSION: We identified a novel mutational signature that reliably predicts sensitivity towards MEK-inhibitors, regardless of the RAS and BRAF status. This finding poses a significant step towards better-tailored cancer therapies guided by the use of molecular biomarkers

Genome-Wide Analysis of Evolutionary Markers of Human Influenza A(H1N1)pdm09 and A(H3N2) Viruses May Guide Selection of Vaccine Strain Candidates

Here we analyzed whole-genome sequences of 3,969 influenza A(H1N1)pdm09 and 4,774 A(H3N2) strains that circulated during 2009-2015 in the world. The analysis revealed changes at 481 and 533 amino acid sites in proteins of influenza A(H1N1)pdm09 and A(H3N2) strains, respectively. Many of these changes were introduced as a result of random drift. However, there were 61 and 68 changes that were present in relatively large number of A(H1N1)pdm09 and A(H3N2) strains, respectively, that circulated during relatively long time. We named these amino acid substitutions evolutionary markers, as they seemed to contain valuable information regarding the viral evolution. Interestingly, influenza A(H1N1)pdm09 and A(H3N2) viruses acquired non-overlapping sets of evolutionary markers. We next analyzed these characteristic markers in vaccine strains recommended by the World Health Organization for the past five years. Our analysis revealed that vaccine strains carried only few evolutionary markers at antigenic sites of viral hem agglutinin (HA) and neuraminidase (NA). The absence of these markers at antigenic sites could affect the recognition of HA and NA by human antibodies generated in response to vaccinations. This could, in part, explain moderate efficacy of influenza vaccines during 2009-2014. Finally, we identified influenza A(H1N1)pdm09 and A(H3N2) strains, which contain all the evolutionary markers of influenza A strains circulated in 2015, and which could be used as vaccine candidates for the 2015/2016 season. Thus, genome-wide analysis of evolutionary markers of influenza A(H1N1)pdm09 and A(H3N2) viruses may guide selection of vaccine strain candidates.Peer reviewe

2-циклоалкилимино-5-(4-нитрофенил)-1,3,4-тиадиазины, обладающие биологической активностью против вирусов оспы

Изобретение относится к новым 2-циклоалкилимино-5-(4-нитрофенил)-1,3,4-тиадиазинам общей формулы I: где пиперидино; пирролидино; метилпиперазино; гексаметиленимино, которые обладают биологической активностью против вирусов оспы. Технический результат - получены новые биологически активные соединения, обладающие противовирусным действием, в частности в отношении вирусов оспы. 1 н.п. ф-лы, 1 табл. Изобретение относится к области биологически активных соединений, касается разработки новых производных 1,3,4-тиадиазинов, и предназначено для лечения и профилактики заболеваний, вызываемых патогенными для человека и животных вирусами, а также вирусом оспавакцины (лечение поствакцинальных осложнений)

СЕРОТИПЫ STREPTOCOCCUS PNEUMONIAE, ВЫЗЫВАЮЩИХ ВЕДУЩИЕ НОЗОЛОГИЧЕСКИЕ ФОРМЫ ПНЕВМОКОККОВЫХ ИНФЕКЦИЙ

First in Russia prospective non-interventional hospital-based study on Streptococcus pneumoniae serotypes causing meningitis and acute otitis media (AOM) in children and community-acquired pneumonia (CAP) in children and adults, as well as serotype coverage by pneumococcal conjugate vaccines (PCV’s) of different composition has been conducted. Serotypes 19F, 14 and serogroup 6 are the leading in meningitis; serotype coverage is 70,6% for PCV7, and 76,5% – for PCV10 and PCV13. Among S. pneumoniae serotypes causing AOM 19F, 3, 23F and serogroup 6 have been the most prevalent in Saint Petersburg. PCV7 and PCV10 provide equal serotypes coverage in AOM – 63,2% among children 0–2 years old, and 32,5% among children 5–17 years old. PCV13 covers up to 79% of serotypes in infants. In CAP PCV7 and PCV10 provide 57,1% serotype coverage in children and 56,1% – in adults. Serotype coverage in CAP for PCV13 has been 14,3% and 34,5% higher for children and adults, correspondingly. Obtained data supports PCV inclusion in children immunization program in Saint Petersburg, whereas PCV13 provides the broadest serotype coverage. In the course PCV’s implementation continued pneumococcal infection surveillance is advisable.Впервые в России в проспективном неинтервенционном госпитальном эпидемиологическом исследовании изучен серотиповой состав Streptococcus pneumoniae, вызывающих менингиты, внебольничную пневмонию и острый средний отит (ОСО), а также охват циркулирующих серотипов пневмококковыми конъюгированными вакцинами (ПКВ) различного состава. К ведущим серотипам S. pneumoniae, вызывающим у детей гнойный менингит, относятся 19F, 14 и серогруппа 6. Охват серотипов S. pneumoniae, вызывающих гнойный менингит для ПКВ7, составляет 70,6%, а для ПКВ10 и ПКВ13 – 76,5%. Ведущими серотипами пневмококков, вызывающих ОСО, в Санкт-Петербурге являются серотипы 19F, 3, 23F и серогруппа 6. Охват серотипов для ПКВ7 и ПКВ10 одинаков и составляет 63,2% для детей в возрасте 0–2 лет и 32,5% для детей в возрасте 5–17 лет. Для ПКВ13 эти показатели составляют соответственно 79% и 55%. При внебольничной пневмонии ПКВ7 и ПКВ10 обеспечивали одинаковый охват: 57,1% у детей и 56,1% у взрослых. Для ПКВ13 эти показатели были на 14,3% больше у детей и на 34,5% у взрослых. Полученные данные обосновывают целесообразность применения пневмококковых конъюгированных вакцин для массовой иммунизации детей в Санкт-Петербурге, при этом ПКВ13 обеспечивает наибольший охват серотипов S. pneumoniae, вызывающих основные пневмококковые заболевания. Для оценки эффективности вакцинации целесообразно продолжить эпидемиологическое наблюдение за пневмококковыми инфекциями после проведения массовой иммунизации ПКВ13