High-order alloharmonics produced by nonperiodic drivers

High-order harmonics are ubiquitous in nature and present in electromagnetic, acoustic, and gravitational waves. They are generated by periodic nonlinear processes or periodic high-frequency pulses. However, this periodicity is often inexact, such as that in chirped (frequency-swept) optical waveforms or interactions with nonstationary matter -- for instance, reflection from accelerating mirrors. Spectra observed in such cases contain complicated sets of harmonic-like fringes. We encountered such fringes in our experiment on coherent extreme ultraviolet generation via BISER, and could not interpret them using currently available knowledge. Here, we present a comprehensive theory based on interference of harmonics with different orders fully explaining the formation of these fringes, which we call alloharmonics. Like atomic spectra, the complex alloharmonic spectra depend on several integer numbers and bear a unique imprint of the emission process, which the theory can decipher, avoiding confusion or misinterpretation. We also demonstrate the alloharmonics in simulations of gravitational waves emitted by binary black hole mergers. Further, we predict the presence of alloharmonics in the radio spectra of pulsars and in optical frequency combs, and propose their use for measurement of extremely small accelerations necessary for testing gravity theories. The alloharmonics phenomenon generalizes classical harmonics and is critical in research fields such as laser mode locking, frequency comb generation, attosecond pulse generation, pulsar studies, and future gravitational wave spectroscopy.Comment: 29 pages, 9 figures, 3 table

A Functional Role for 4qA/B in the Structural Rearrangement of the 4q35 Region and in the Regulation of FRG1 and ANT1 in Facioscapulohumeral Dystrophy

The number of D4Z4 repeats in the subtelomeric region of chromosome 4q is strongly reduced in patients with Facio-Scapulo-Humeral Dystrophy (FSHD). We performed chromosome conformation capture (3C) analysis to document the interactions taking place among different 4q35 markers. We found that the reduced number of D4Z4 repeats in FSHD myoblasts was associated with a global alteration of the three-dimensional structure of the 4q35 region. Indeed, differently from normal myoblasts, the 4qA/B marker interacted directly with the promoters of the FRG1 and ANT1 genes in FSHD cells. Along with the presence of a newly identified transcriptional enhancer within the 4qA allele, our demonstration of an interaction occurring between chromosomal segments located megabases away on the same chromosome 4q allows to revisit the possible mechanisms leading to FSHD

DUX4c Is Up-Regulated in FSHD. It Induces the MYF5 Protein and Human Myoblast Proliferation

Facioscapulohumeral muscular dystrophy (FSHD) is a dominant disease linked to contractions of the D4Z4 repeat array in 4q35. We have previously identified a double homeobox gene (DUX4) within each D4Z4 unit that encodes a transcription factor expressed in FSHD but not control myoblasts. DUX4 and its target genes contribute to the global dysregulation of gene expression observed in FSHD. We have now characterized the homologous DUX4c gene mapped 42 kb centromeric of the D4Z4 repeat array. It encodes a 47-kDa protein with a double homeodomain identical to DUX4 but divergent in the carboxyl-terminal region. DUX4c was detected in primary myoblast extracts by Western blot with a specific antiserum, and was induced upon differentiation. The protein was increased about 2-fold in FSHD versus control myotubes but reached 2-10-fold induction in FSHD muscle biopsies. We have shown by Western blot and by a DNA-binding assay that DUX4c over-expression induced the MYF5 myogenic regulator and its DNA-binding activity. DUX4c might stabilize the MYF5 protein as we detected their interaction by co-immunoprecipitation. In keeping with the known role of Myf5 in myoblast accumulation during mouse muscle regeneration DUX4c over-expression activated proliferation of human primary myoblasts and inhibited their differentiation. Altogether, these results suggested that DUX4c could be involved in muscle regeneration and that changes in its expression could contribute to the FSHD pathology

Femtosecond laser driven high-flux highly collimated MeV-proton beam

金沢大学先端科学・社会共創推進機構Highlly collimated energetic protons whose energies are up to 4 MeV are generated by an intense femtosecond Titanium Sappheire laser pulse interacting with a 7.5, 12.5, and 25 μm-thick Polyimide tape target and 5 μm-thick copper target. We find no clear difference on the proton spectra from 7.5, 12.5, and 25 μm Polyimide tape target. The highest conversion efficiency from laser energy into protons of ∼3% is observed with a 7.5 μm thick Polyimide target. The quality of the proton beam is good enough to obtain a clear projection image of a mesh having 10 μm line and space structure, installed into the passage of the beam. We obtain clear vertical lines on the proton intensity profiles from the copper target, which are considered to be transferred from the surface of the copper target. From it, we can restrict the size of the proton emitting region to be ∼20μm. © 2008 American Institute of Physics.Embargo Period 12 month

Remodeling of the chromatin structure of the facioscapulohumeral muscular dystrophy (FSHD) locus and upregulation of FSHD-related gene 1 (FRG1) expression during human myogenic differentiation

<p>Abstract</p> <p>Background</p> <p>Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder associated with the partial deletion of integral numbers of 3.3 kb D4Z4 DNA repeats within the subtelomere of chromosome 4q. A number of candidate FSHD genes, adenine nucleotide translocator 1 gene (<it>ANT1</it>), FSHD-related gene 1 (<it>FRG1</it>), <it>FRG2 </it>and <it>DUX4c</it>, upstream of the D4Z4 array (FSHD locus), and double homeobox chromosome 4 (<it>DUX4</it>) within the repeat itself, are upregulated in some patients, thus suggesting an underlying perturbation of the chromatin structure. Furthermore, a mouse model overexpressing <it>FRG1 </it>has been generated, displaying skeletal muscle defects.</p> <p>Results</p> <p>In the context of myogenic differentiation, we compared the chromatin structure and tridimensional interaction of the D4Z4 array and <it>FRG1 </it>gene promoter, and <it>FRG1 </it>expression, in control and FSHD cells. The <it>FRG1 </it>gene was prematurely expressed during FSHD myoblast differentiation, thus suggesting that the number of D4Z4 repeats in the array may affect the correct timing of <it>FRG1 </it>expression. Using chromosome conformation capture (3C) technology, we revealed that the <it>FRG1 </it>promoter and D4Z4 array physically interacted. Furthermore, this chromatin structure underwent dynamic changes during myogenic differentiation that led to the loosening of the <it>FRG1</it>/4q-D4Z4 array loop in myotubes. The <it>FRG1 </it>promoter in both normal and FSHD myoblasts was characterized by H3K27 trimethylation and Polycomb repressor complex binding, but these repression signs were replaced by H3K4 trimethylation during differentiation. The D4Z4 sequences behaved similarly, with H3K27 trimethylation and Polycomb binding being lost upon myogenic differentiation.</p> <p>Conclusion</p> <p>We propose a model in which the D4Z4 array may play a critical chromatin function as an orchestrator of <it>in cis </it>chromatin loops, thus suggesting that this repeat may play a role in coordinating gene expression.</p

The recombinant fusion protein CFP10–ESAT6–dIFN has protective effect against tuberculosis in guinea pigs

Development of effective vaccine candidates against tuberculosis (TB) is currently the most important challenge in the prevention of this disease since the BCG vaccine fails to guarantee a lifelong protection, while any other approved vaccine with better efficiency is still absent. The protective effect of the recombinant fusion protein CFP10–ESAT6–dIFN produced in a prokaryotic expression system (Escherichia coli) has been assessed in a guinea pig model of acute TB. The tested antigen comprises the Mycobacterium tuberculosis (Mtb) proteins ESAT6 and CFP10 as well as modified human γ-interferon (dIFN) for boosting the immune response. Double intradermal immunization of guinea pigs with the tested fusion protein (2 × 0.5 µg) induces a protective effect against subsequent Mtb infection. The immunized guinea pigs do not develop the symptoms of acute TB and their body weight gain was five times more as compared with the non-immunized infected guinea pigs. The animal group immunized with this dose of antigen displays the minimum morphological changes in the internal organs and insignificant inflammatory lesions in the liver tissue, which complies with a decrease in the bacterial load in the spleen and average Mtb counts in macrophages

Опыт применения фокусированного ультразвукового исследования сердца у пациентов с COVID-19 в Prone-позиции

Aim of the study. To study the experience of using focused transthoracic echocardiography in patients with COVID-19 in prone position (fEchoPr) in intensive care units (ICU).Materials and methods. The retrospective observational study included 53 patients (period from 15 April to 31 December 2020). Inclusion criteria: confirmed diagnosis of COVID-19, availability of fEchoPr data, outcome certainty (discharge/death). We analyzed electronic medical records. The fEchoPr was performed in patients in the prone position with a bolster under the left side of the chest and left arm raised (‘swimmer’s position’). We assessed the systolic function of the right ventricle (RV) (tricuspid annular plane systolic excursion (TAPSE)), RV size, RV/LV ratio, systolic function of the left ventricle (LV) (left ventricular outflow tract velocity time integral. (LVOT VTI)), and pulmonary hypertension (PH) (tricuspid regurgitation peak gradient (PGTR). Depending on the results, the patients were divided into 2 groups: informative (+fEchoPr) and non-informative (–fEchoPr) examinations.Results. There was no statistically significant difference in the groups (+fEcho n = 35 vs –fEcho n = 18) by age (65.6 ± 15.3 vs 60.2 ± 15.8, p &gt; 0.05), by gender (male: 23 (65.7%) vs 14 (77.8%), p &gt; 0.05), by body mass index (31.3 ± 5.3 kg/m 2 vs 29.5 ± 5.4 kg/m2 , p &gt; 0.05), by mechanical ventilation support (24 (68.6%) vs 17 (94.4%), p = 0.074), by NEWS scale indicators (6.9 ± 3.7 vs 8.5 ± 3.5 points), by mortality (82.8% vs 94.4%, p &gt; 0.05). Correlation analysis revealed a moderate inverse relationship between being on mechanical ventilation and the informative value of the study (Spearman's r = −0.30 at p = 0.033). In the +fEchoPr group, the correct measurement of TAPSE and RV/LV was carried out in 100%: a decrease in RV systolic function was recorded in 5 patients (14%), expansion of the RV in 13 patients (37%). Signs of PH were detected in 11 patients (31%), PGTR could not be measured in 10 patients (28%). LV systolic dysfunction was detected in 7 patients (20%). No pathology was detected in 16 patients (46%). One patient was diagnosed with infective endocarditis of native mitral valve, which was later confirmed by autopsy.Conclusion. In 66% of cases, fEchoPr examinations were informative, especially in terms of assessing the state of the right heart. fEchoPr examination is an affordable, valid and reproducible method to assess and monitor the state of the heart in ICU patients.Цель исследования: изучение опыта применения фокусированного трансторакального эхокардиографического исследования в Prone-позиции (фЭхоPr) в отделениях реанимации и интенсивной терапии (ОРИТ) у пациентов с COVID-19.Материал и методы. В ретроспективное наблюдательное исследование включено 53 пациента (период 15.04–31.12.20). Критерии включения: подтвержденный диагноз COVID-19, наличие данных фЭхоPr, определенность исхода (выписка/смерть). Анализировались электронные истории болезни. фЭхоPr выполнялось в положении пациента на животе с валиком под левой частью грудной клетки и поднятой левой рукой (“поза пловца”). Проводилась оценка систолической функции правого желудочка (ПЖ) (измерение экскурсии фиброзного кольца трикуспидального клапана (TAPSE)), размера ПЖ, систолической функции левого желудочка (ЛЖ) (измерение интеграла линейной скорости кровотока в выходном тракте ЛЖ (VTIвтлж)), параметра ПЖ/ЛЖ, легочной гипертензии (ЛГ) (измерение пикового градиента трикуспидальной регургитации (PGTR)). В зависимости от результатов пациенты были разделены на 2 группы: информативные (+фЭхоPr) и неинформативные (−фЭхоPr) исследования.Результаты. Не выявлено статистически значимой разницы в группах (+фЭхоPr n = 35 vs -фЭхоPr n = 18) по возрасту (65,6 ± 15,3 года vs 60,2 ± 15,8 года, р &gt; 0,05), полу (муж.: 23 (65,7%) vs 14 (77,8%), р &gt; 0,05), индексу массы тела (31,3 ± 5,3 кг/м 2 vs 29,5 ± 5,4 кг/м2 , р &gt; 0,05), нахождению на искусственной вентиляции легких (ИВЛ) (24 (68,6%) vs 17 (94,4%), р = 0,074), показателям шкалы NEWS (6,9 ± 3,7 vs 8,5 ± 3,5 балла), летальности (82,8% vs 94,4%, р &gt; 0,05). Корреляционный анализ выявил умеренную обратную связь между нахождением на ИВЛ и информативностью исследования (r-Спирмена = −0,30 при р = 0,033). В группе +фЭхоPr корректное измерение TAPSE и ПЖ/ЛЖ проведено в 100%: снижение систолической функции ПЖ зафиксировано у 5 (14%), расширение ПЖ у 13 (37%) пациентов. Признаки ЛГ выявлены у 11 (31%), измерить PGTR не удалось у 10 (28%) человек. Систолическая дисфункция ЛЖ выявлена у 7 (20%). Не было выявлено патологии у 16 (46%) пациентов. У одного пациента диагностирован инфекционный эндокардит нативного митрального клапана, подтвердившийся при проведении аутопсии.Заключение. В 66% случаев проведение фЭхоPr было информативным, особенно в части оценки состояния правых отделов сердца. фЭхоPr – доступный, валидный и воспроизводимый метод оценки и мониторинга состояния сердца у пациентов в ОРИТ

Information Modeling Technology for Interaction with Cyberspace

В работе рассматриваются возможности технологий информационного моделирования объектов и территорий для прогнозирования последствий чрезвычайных ситуаций. На примере студенческих проектов представлен результат цифровых моделей. Предложено создание реестра заготовок BIM-моделей для дальнейшей аналитики влияния объектов недвижимости на инфраструктуру города через использование возможностей киберпространства.The paper considers the possibilities of information modeling technologies of objects and territories for the prediction of the consequences of emergencies. The result of digital models is presented on the example of student projects. It is proposed to create a register of BIM-models blanks for further analysis of the impact of real estate objects on the infrastructure of the city through the use of cyberspace capabilities

Technopark Project As A Component Part of Innovative Scenario of Territorial Development

В статье рассказывается о наиболее эффективных приемах, используемых при разработке технопарков, которые были выведены при помощи анализа зарубежного и отечественного опыта по созданию подобных проектов, а также собственной работы авторов над созданием технопарка, в рамках проектного обучения. Представленные материалы могут быть использованы для развития территорий и стимулирования инноваций в производстве.The article describes the most effective techniques used in the development of technoparks, which were derived by analyzing foreign and domestic experience in creating such projects, as well as the authors' own work on creating a technopark, as part of project-based learning. The presented materials can be used for the development of territories and stimulation of innovations in production