Beam coupling in hybrid photorefractive inorganic-cholesteric liquid crystal cells: impact of optical rotation

We develop a theoretical model to describe two-beam energy exchange in a hybrid photorefractive inorganic-cholesteric cell. A cholesteric layer is placed between two inorganic substrates. One of the substrates is photorefractive (Ce:SBN). Weak and strong light beams are incident on the hybrid cell. The interfering light beams induce a periodic space-charge field in the photorefractive window. This penetrates into the cholesteric liquid crystal (LC), inducing a diffraction grating written on the LC director. In the theory, the flexoelectric mechanism for electric field-director coupling is more important than the LC static dielectric anisotropy coupling. The LC optics is described in the Bragg regime. Each beam induces two circular polarized waves propagating in the cholesteric cell with different velocities. The model thus includes optical rotation in the cholesteric LC. The incident light beam wavelength can fall above, below, or inside the cholesteric gap. The theory calculates the energy gain of the weak beam, as a result of its interaction with the pump beam within the diffraction grating. Theoretical results for exponential gain coefficients are compared with experimental results for hybrid cells filled with cholesteric mixture BL038/CB15 at different concentrations of chiral agent CB15. Reconciliation between theory and experiment requires the inclusion of a phenomenological multiplier in the magnitude of the director grating. This multiplier is cubic in the space-charge field, and we provide a justification of the q-dependence of the multiplier. Within this paradigm, we are able to fit theory to experimental data for cholesteric mixtures with different spectral position of cholesteric gap relative to the wavelength of incident beams, subject to the use of some fitting parameters

ДОСЛІДЖЕННЯ ЕЛЕМЕНТНОГО СКЛАДУ ГРУШІ ЗВИЧАЙНОЇ ЛИСТЯ СОРТУ НОЯБРСЬКА

Introduction. Mineral elements are enzyme cofactors, constituents of vitamins, hormones, all body cells and tissues, they are essential for its normal metabolism: homeostasis support, progress of biochemical, enzymatic, plastic, hormonal, regulatory and metabolic processes, being a necessary and vital part of human diet. Their deficiency, excess or imbalance in the body may cause certain diseases, syndromes, disorders or pathological states. The object of the study were pear leaves of Noiabrska cultivar, collected in Ivano-Frankivsk region in August 2018. Pears of this cultivar are widely cultivated on the territory of Ukraine in private households or farms, especially in Western and Transdniester regions. The aim of the study – research on the qualitative composition and quantitative content of mineral elements in pear leaves of Noiabrska cultivar. Research Methods. The element composition of pear leaves of Noiabrska cultivar was studied using atomic-absorption spectrometry at the department of analytical chemistry of the State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine. Results and Discussion. The obtained results of experimental research carried out show the presence of 19 mineral elements in pear leaves of Noiabrska cultivar. K (2185 mg/100 g), Ca (1140 mg/100 g), Mg (380 mg/100 g), P (85 mg/100 g), Si (76 mg/100 g) and Al (62 mg/100 g) were accumulated in the highest amount in the plant material, while Cu (0.23 mg/100 g), Ni (0.11 mg/100 g) and Mo (0.047 mg/100 g) – in the lowest. The content of heavy metals was within the limits of permissible concentration. Conclusions. 19 mineral elements were identified in pear leaves of Noiabrska cultivar, and their content was determined by the means of atomic-absorption spectrometry. The received experimental data will be used in further work at predictive modeling of pharmacological activity of the plant material studied, medicinal agents on its basis, as well as at standardization and development of quality control methods for the plant material.Вступление. Минеральные элементы являются кофакторами ферментов, составными частями витаминов, гормонов, всех клеток и тканей организма, они необходимы для его нормальной жизнедеятельности: поддержания гомеостаза, протекания биохимических, ферментативных, пластических, гормональных, регуляторных и обменных процессов, являются обязательной и незаменимой частью рациона питания. Их дефицит, избыток или дисбаланс в организме может вызвать определенные заболевания, синдромы, нарушения или патологические состояния. Объектом исследования были груши обыкновенной листья сорта Ноябрьская, заготовленные в Ивано-Франковской области в августе 2018 г. Груша обыкновенная данного сорта широко культивируется на территории Украины в частных и фермерских хозяйствах, особенно в западных регионах и Приднестровье. Цель исследования – изучить качественный состав и количественное содержание минеральных элементов в груши обыкновенной листьях сорта Ноябрьская. Методы исследования. Элементный состав определяли методом атомно-абсорбционной спектрометрии на базе отдела аналитической химии ГНУ НТК “Институт монокристаллов” НАН Украины. Результаты и обсуждение. Полученные результаты проведенных экспериментальных исследований свидетельствуют о наличии в груши обыкновенной листьях сорта Ноябрьская 19 минеральных элементов. В наибольшем количестве в сырье накапливались K (2185 мг/100 г), Ca (1140 мг/100 г), Mg (380 мг/100 г), P (85 мг/100 г), Si (76 мг/100 г) и Al (62 мг/100 г), в наименьшем – Cu (0,23 мг/100 г), Ni (0,11 мг/100 г) и Mo (0,047 мг/100 г). Содержание тяжелых металлов находилось в пределах допустимых концентраций. Выводы. Методом атомно-абсорбционной спектрометрии в груши обыкновенной листьях сорта Ноябрьская идентифицировано и определено количественное содержание 19 минеральных элементов. Полученные экспериментальные данные будут использованы в дальнейшей работе при прогнозировании фармакологической активности исследуемого сырья, лекарственных средств на его основе, а также с целью стандартизации и разработки методов контроля качества сырья.Вступ. Мінеральні елементи є кофакторами ферментів, складовими частинами вітамінів, гормонів, усіх клітин і тканин організму, вони необхідні для його нормальної життєдіяльності: підтримки гомеостазу, перебігу біохімічних, ферментативних, пластичних, гормональних, регуляторних та обмінних процесів, є обов’язковою і незамінною частиною раціону харчування. Їх дефіцит, надлишок чи дисбаланс в організмі може спричинити певні захворювання, синдроми, порушення або патологічні стани. Об’єктом дослідження були груші звичайної листя сорту Ноябрська, заготовлені в Івано-Франківській області в серпні 2018 р. Груша звичайна даного сорту широко культивується на території України у приватних і фермерських господарствах, особливо в західних регіонах та Придністров’ї. Мета дослідження – вивчити якісний склад та кількісний вміст мінеральних елементів у груші звичайної листі сорту Ноябрська. Методи дослідження. Елементний склад груші звичайної листя сорту Ноябрська изначали методом атомно-абсорбційної спектрометрії на базі відділу аналітичної хімії ДНУ НТК “Інститут монокристалів” НАН України. Результати й обговорення. Одержані результати проведених експериментальних досліджень свідчать про наявність у груші звичайної листі сорту Ноябрська 19 мінеральних елементів. У найбільшій кількості в сировині накопичувалися K (2185 мг/100 г), Ca (1140 мг/100 г), Mg (380 мг/100 г), P (85 мг/100 г), Si (76 мг/100 г) і Al (62 мг/100 г), у найменшій – Cu (0,23 мг/100 г), Ni (0,11 мг/100 г) та Mo (0,047 мг/100 г). Вміст важких металів перебував у межах допустимих концентрацій. Висновки. Методом атомно-абсорбційної спектрометрії у груші звичайної листі сорту Ноябрська ідентифіковано та визначено кількісний вміст 19 мінеральних елементів. Одержані експериментальні дані буде використано в подальшій роботі при прогнозуванні фармакологічної активності досліджуваної сировини, лікарських засобів на її основі, а також з метою стандартизації та розробки методів контролю якості сировини

Estimating initial viral levels during simian immunodeficiency virus/human immunodeficiency virus reactivation from latency

Human immunodeficiency virus (HIV) viremia rebounds rapidly after treatment interruption, and a variety of strategies are being explored to reduce or control viral reactivation posttreatment. This viral rebound arises from reactivation of individual latently infected cells, which spread during ongoing rounds of productive infection. The level of virus produced by the initial individual reactivating cells is not known, although it may have major implications for the ability of different immune interventions to control viral rebound. Here we use data from both HIV and simian immunodeficiency virus (SIV) treatment interruption studies to estimate the initial viral load postinterruption and thereby the initial individual reactivation event. Using a barcoded virus (SIVmac239M) to track reactivation from individual latent cells, we use the observed viral growth rates and frequency of reactivation to model the dynamics of reactivation to estimate that a single reactivated latent cell can produce an average viral load equivalent to ~0.1 to 0.5 viral RNA (vRNA) copies/ml. Modeling of treatment interruption in HIV suggests an initial viral load equivalent of ~0.6 to 1 vRNA copies/ml. These low viral loads immediately following latent cell reactivation provide a window of opportunity for viral control by host immunity, before further replication allows viral spread. This work shows the initial levels of viral production that must be controlled in order to successfully suppress HIV reactivation following treatment interruption

Balancing Statistical Power and Risk in HIV Cure Clinical Trial Design

Background. Analytical treatment interruptions (ATI) are pauses of antiretroviral therapy (ART) in the context of human immunodeficiency virus (HIV) cure trials. They are the gold standard in determining if interventions being tested can achieve sustained virological control in the absence of ART. However, withholding ART comes with risks and discomforts to trial participant. We used mathematical models to explore how ATI study design can be improved to maximize statistical power, while minimizing risks to participants. Methods. Using previously observed dynamics of time to viral rebound (TVR) post-ATI, we modelled estimates for optimal sample size, frequency, and ATI duration required to detect a significant difference in the TVR between control and intervention groups. Groups were compared using a log-rank test, and analytical and stochastic techniques. Results. In placebo-controlled TVR studies, 120 participants are required in each arm to detect 30% difference in frequency of viral reactivation at 80% power. There was little statistical advantage to measuring viral load more frequently than weekly, or interrupting ART beyond 5 weeks in a TVR study. Conclusions. Current TVR HIV cure studies are underpowered to detect statistically significant changes in frequency of viral reactivation. Alternate study designs can improve the statistical power of ATI trials

Time-to-infection by Plasmodium falciparum is largely determined by random factors

BACKGROUND: The identification of protective immune responses to P. falciparum infection is an important goal for the development of a vaccine for malaria. This requires the identification of susceptible and resistant individuals, so that their immune responses may be studied. Time-to-infection studies are one method for identifying putative susceptible individuals (infected early) versus resistant individuals (infected late). However, the timing of infection is dependent on random factors, such as whether the subject was bitten by an infected mosquito, as well as individual factors, such as their level of immunity. It is important to understand how much of the observed variation in infection is simply due to chance. METHODS: We analyse previously published data from a treatment-time-to-infection study of 201 individuals aged 0.5 to 78 years living in Western Kenya. We use a mathematical modelling approach to investigate the role of immunity versus random factors in determining time-to-infection in this cohort. We extend this analysis using a modelling approach to understand what factors might increase or decrease the utility of these studies for identifying susceptible and resistant individuals. RESULTS: We find that, under most circumstances, the observed distribution of time-to-infection is consistent with this simply being a random process. We find that age, method for detection of infection (PCR versus microscopy), and underlying force of infection are all factors in determining whether time-to-infection is a useful correlate of immunity. CONCLUSIONS: Many epidemiological studies of P. falciparum infection assume that the observed variation in infection outcomes, such as time-to-infection or presence or absence of infection, is determined by host resistance or susceptibility. However, under most circumstances, this distribution appears largely due to the random timing of infection, particularly in children. More direct measurements, such as parasite growth rate, may be more useful than time-to-infection in segregating patients based on their level of immunity

The Dynamics of Naturally Acquired Immunity to Plasmodium falciparum Infection

Severe malaria occurs predominantly in young children and immunity to clinical disease is associated with cumulative exposure in holoendemic settings. The relative contribution of immunity against various stages of the parasite life cycle that results in controlling infection and limiting disease is not well understood. Here we analyse the dynamics of Plasmodium falciparum malaria infection after treatment in a cohort of 197 healthy study participants of different ages in order to model naturally acquired immunity. We find that both delayed time-to-infection and reductions in asymptomatic parasitaemias in older age groups can be explained by immunity that reduces the growth of blood stage as opposed to liver stage parasites. We found that this mechanism would require at least two components - a rapidly acting strain-specific component, as well as a slowly acquired cross-reactive or general immunity to all strains. Analysis and modelling of malaria infection dynamics and naturally acquired immunity with age provides important insights into what mechanisms of immune control may be harnessed by malaria vaccine strategists

Timing of initiation of anti-retroviral therapy predicts post-treatment control of SIV replication

One approach to ‘functional cure’ of HIV infection is to induce durable control of HIV replication after the interruption of antiretroviral therapy (ART). However, the major factors that determine the viral ‘setpoint’ level after treatment interruption are not well understood. Here we combine data on ART interruption following SIV infection for 124 total animals from 10 independent studies across 3 institutional cohorts to understand the dynamics and predictors of post-treatment viral control. We find that the timing of treatment initiation is an important determinant of both the peak and early setpoint viral levels after treatment interruption. During the first 3 weeks of infection, every day of delay in treatment initiation is associated with a 0.22 log10 copies/ml decrease in post-rebound peak and setpoint viral levels. However, delay in initiation of ART beyond 3 weeks of infection is associated with higher postrebound setpoint viral levels. For animals treated beyond 3 weeks post-infection, viral load at ART initiation was the primary predictor of post-rebound setpoint viral levels. Potential alternative predictors of post-rebound setpoint viral loads including cell-associated DNA or RNA, time from treatment interruption to rebound, and pre-interruption CD8+ T cell responses were also examined in the studies where these data were available. This analysis suggests that optimal timing of treatment initiation may be an important determinant of posttreatment control of HIV

Preferential selection of viral escape mutants by CD8+ T cell 'sieving' of SIV reactivation from latency

HIV rapidly rebounds after interruption of antiretroviral therapy (ART). HIV-specific CD8+ T cells may act to prevent early events in viral reactivation. However, the presence of viral immune escape mutations may limit the effect of CD8+ T cells on viral rebound. Here, we studied the impact of CD8 immune pressure on post-treatment rebound of barcoded SIVmac293M in 14 Mamu-A*01 positive rhesus macaques that initiated ART on day 14, and subsequently underwent two analytic treatment interruptions (ATIs). Rebound following the first ATI (seven months after ART initiation) was dominated by virus that retained the wildtype sequence at the Mamu-A*01 restricted Tat-SL8 epitope. By the end of the two-month treatment interruption, the replicating virus was predominantly escaped at the Tat-SL8 epitope. Animals reinitiated ART for 3 months prior to a second treatment interruption. Time-torebound and viral reactivation rate were significantly slower during the second treatment interruption compared to the first. Tat-SL8 escape mutants dominated early rebound during the second treatment interruption, despite the dominance of wild-type virus in the proviral reservoir. Furthermore, the escape mutations detected early in the second treatment interruption were well predicted by those replicating at the end of the first, indicating that escape mutant virus in the second interruption originated from the latent reservoir as opposed to evolving de novo post rebound. SL8-specific CD8+ T cell levels in blood prior to the second interruption were marginally, but significantly, higher (median 0.73% vs 0.60%, p = 0.016). CD8+ T cell depletion approximately 95 days after the second treatment interruption led to the reappearance of wild-type virus. This work suggests that CD8+ T cells can actively suppress the rebound of wild-type virus, leading to the dominance of escape mutant virus after treatment interruption