Optimal seasonal schedule for the production of isoprene, a highly volatile biogenic VOC.

The leaves of many trees emit volatile organic compounds (abbreviated as BVOCs), which protect them from various damages, such as herbivory, pathogens, and heat stress. For example, isoprene is highly volatile and is known to enhance the resistance to heat stress. In this study, we analyze the optimal seasonal schedule for producing isoprene in leaves to mitigate damage. We assume that photosynthetic rate, heat stress, and the stress-suppressing effect of isoprene may vary throughout the season. We seek the seasonal schedule of isoprene production that maximizes the total net photosynthesis using Pontryagin's maximum principle. The isoprene production rate is determined by the changing balance between the cost and benefit of enhanced leaf protection over time. If heat stress peaks in midsummer, isoprene production can reach its highest levels during the summer. However, if a large portion of leaves is lost due to heat stress in a short period, the optimal schedule involves peaking isoprene production after the peak of heat stress. Both high photosynthetic rate and high isoprene volatility in midsummer make the peak of isoprene production in spring. These results can be clearly understood by distinguishing immediate impacts and the impacts of future expectations.

Viral rebound occurrence immediately after drug discontinuation involving neither drug resistance nor latent reservoir.

Some viruses exhibit "rebound" when the administration of antiviral drugs is discontinued. Viral rebound caused by resistance mutations or latent reservoirs has been studied mathematically. In this study, we investigated the viral rebound due to other causes. Since immunity is weaker during antiviral treatment than without the treatment, drug discontinuation may lead to an increase in the viral load. We analyzed the dynamics of the number of virus-infected cells, cytotoxic T lymphocytes, and memory cells and identified the conditions under which the viral load increased upon drug discontinuation. If drug is administered for an extended period, a viral rebound occurs when the ratio of viral growth rate in the absence to that in the presence of the antiviral drug exceeds the "rebound threshold." We analyzed how the rebound threshold depended on the patient's conditions and the type of treatment. Mathematical and numerical analyses revealed that rebound after discontinuation was more likely to occur when the drug effectively reduced viral proliferation, drug discontinuation was delayed, and the processes activating immune responses directly were stronger than those occurring indirectly through immune memory formation. We discussed additional reasons for drugs to cause viral rebound more likely.

Multiple colonies of cancer involved in mutual suppression with the immune system.

We study the effects of the immune system on multiple cancer colonies. When cancer cells proliferate, cytotoxic T lymphocytes (CTLs) reactive to the cancer-specific antigens are activated, suppressing the growth of cancer colonies. The immune reaction activated by a large cancer colony may suppress and eliminate smaller colonies. However, cancer cells mitigate immune reactions by slowing down the activation of CTLs in dendritic cells with regulatory T cells and by inactivating CTLs attacking cancer cells with immune checkpoints. If cancer cells strongly suppress the immune reaction, the system may become bistable, where both the cancer-dominated and immunity-dominated states are locally stable. We study several models differing in the distance between colonies and the migration speeds of CTLs and regulatory T cells. We examine how the domains of attraction for multiple equilibria change with parameters. Nonlinear cancer-immunity dynamics may produce a sharp transition from a state with a small number of colonies and strong immunity to one with many colonies and weak immunity, resulting in the rapid emergence of many cancer colonies in the same organ or metastatic sites.

Temporal Pattern of the Emergence of a Mutant Virus Escaping Cross-Immunity and Stochastic Extinction Within a Host.

A high mutation rate of the RNA virus results in the emergence of novel mutants that may escape the immunity activated by the original (wild-type) strain. However, many of them go extinct because of the stochasticity due to the small initial number of infected cells. In a previous paper, we studied the probability of escaping stochastic extinction when the novel mutant has a faster rate of infection and when it is resistant to a drug that suppresses the wild-type virus. In this study, we examine the effect of escaping the immune reaction of the host. Based on a continuous-time branching process with time-dependent rates, we conclude the chance for a mutant strain to be established [Formula: see text] decreases with time [Formula: see text] since the wild-type infection when the mutant is produced. The number of novel mutants that can escape extinction risk has a peak soon after the wild-type infection. The number of novel escape mutations produced per patient in the early phase of host infection is small both for very strong and very weak immune responses, and it attains its maximum value when immune activity is of an intermediate strength.

Cosmetic effects of red-light reflection by ultramarine blue pigment.

OBJECTIVE: Inorganic pigments used as colouring agents in cosmetics (especially foundations) have many advantages over organic pigments, such as better opacity, weather and chemical resistance and lower cost. However, the types used in cosmetics are very limited, with various kinds of red, yellow and black iron oxide along with white titanium dioxide being the main materials. Ultramarine blue (UB) as a blue pigment and chromium oxide as a green pigment are also sometimes used in cosmetics. In this study, we focus once again on UB and reexamine the possibility of expanding the colour gamut using UB instead of black pigment and creating other optical cosmetic effects. METHODS: The effects of using UB were measured using spectroscopic instruments to determine the colour parameters when applied on artificial skin. The appearance of the product when applied to the human face was also verified both in terms of human appearance evaluation by an expert (esthetician) and numerical evaluation using imaging spectrometer measurements. RESULTS: The verified results showed that, at least in the colour range targeting Asian people, UB could not create a new colour gamut, but it was clear that UB could impart an optical effect that produced a beautiful skin effect on the face. This was remarkable both in the evaluation of human appearance and in the spectral measurement results, which confirmed the phenomenon "red-light makes skin look beautiful," which has been variously reported since the 2000s, using a different approach. CONCLUSION: We have discovered a new possibility that UB, widely recognized as a pigment, is involved not only in colour tone but also in optical effects that contribute to the goal of beautiful skin, i.e. hiding skin wrinkles, eliminating unevenness of colour and improving skin homogeneity.

OBJECTIF: Les pigments inorganiques utilisés comme colorants dans les cosmétiques (en particulier les fonds de teint) présentent de nombreux avantages par rapport aux pigments organiques, comme une meilleure opacité, une meilleure résistance aux conditions météorologiques et aux produits chimiques, et un moindre coût. Cependant, les types utilisés dans les cosmétiques sont très limités, avec différents oxydes de fer rouge, jaune et noir, et le dioxyde de titane blanc comme principal matériau. Le bleu ultramarin (BU) comme pigment bleu et l'oxyde de chrome comme pigment vert sont aussi parfois utilisés dans les cosmétiques. Dans cette étude, nous nous concentrons à nouveau sur le BU et réexaminons la possibilité d'étendre la gamme de couleurs en utilisant le BU au lieu du pigment noir et en créant d'autres effets cosmétiques optiques. MÉTHODES: Les effets de l'utilisation du BU ont été mesurés à l'aide d'instruments spectroscopiques pour déterminer les paramètres de couleur lors de l'application sur une peau artificielle. L'aspect du produit appliqué sur le visage humain a également été vérifié à la fois en termes d'évaluation de l'apparence humaine par un expert (esthéticien) et d'évaluation numérique à l'aide de mesures par spectromètre d'imagerie. RÉSULTATS: Les résultats vérifiés ont montré que, au moins dans la gamme de couleurs ciblant les Asiatiques, le BU ne pouvait pas créer une nouvelle gamme de couleurs, mais il était clair que le BU pouvait donner un effet optique qui produit une apparence soignée de la peau du visage. Ceci était remarquable tant dans l'évaluation humaine de l'apparence que dans les résultats de mesure spectrale, qui ont confirmé le phénomène selon lequel « la lumière rouge rend la peau belle ¼, qui a été rapporté de diverses manières depuis les années 2000, en utilisant une approche différente. CONCLUSION: Nous avons découvert qu'il est possible que le BU, largement reconnu comme pigment, joue un rôle non seulement dans le teint, mais également dans les effets optiques qui contribuent à l'objectif d'une belle peau, c'est-à-dire cacher les rides, uniformiser la couleur du teint et améliorer l'homogénéité de la peau.

Waves of infection emerging from coupled social and epidemiological dynamics.

The coronavirus (SARS-CoV-2) exhibited waves of infection in 2020 and 2021 in Japan. The number of infected had multiple distinct peaks at intervals of several months. One possible process causing these waves of infection is people switching their activities in response to the prevalence of infection. In this paper, we present a simple model for the coupling of social and epidemiological dynamics. The assumptions are as follows. Each person switches between active and restrained states. Active people move more often to crowded areas, interact with each other, and suffer a higher rate of infection than people in the restrained state. The rate of transition from restrained to active states is enhanced by the fraction of currently active people (conformity), whereas the rate of backward transition is enhanced by the abundance of infected people (risk avoidance). The model may show transient or sustained oscillations, initial-condition dependence, and various bifurcations. The infection is maintained at a low level if the recovery rate is between the maximum and minimum levels of the force of infection. In addition, waves of infection may emerge instead of converging to the stationary abundance of infected people if both conformity and risk avoidance of people are strong.

Escaping stochastic extinction of mutant virus: Temporal pattern of emergence of drug resistance within a host.

After infecting a host, a viral strain may increase rapidly within the body and produce mutants with a faster proliferation rate than the virus itself. However, most of the mutants become extinct because of the stochasticity caused by the small number of infected cells. In addition, the mean growth rate of a mutant strain decreases with time because the number of susceptible target cells is reduced by the original strain. In this study, we calculated the fraction of mutants that can escape stochastic extinction, based on a continuous-time branching process with a time-dependent growth rate. We analyzed two cases differing in the mode of viral transmission: (1) an infected cell transmits the virus through cell-to-cell contact with a susceptible target cell; (2) an infected cell releases numerous free viral particles that subsequently infect susceptible target cells. The chance for a mutant strain to be established decreases with time after infection of the original type, and it may oscillate before convergence at the stationary value. We then calculated the probability of escaping stochastic extinction for a drug-resistant mutant when a patient received an antiviral drug that suppressed the original strain. Combining the rate of mutant production from the original strain and the chance of escaping stochastic extinction, the number of emerging drug-resistant mutations may have two peaks: one soon after the infection of the original type and the second at the start of antiviral drug administration.

Identification of biaryl sulfone derivatives as antagonists of the histamine H3 receptor: discovery of (R)-1-(2-(4'-(3-methoxypropylsulfonyl)biphenyl-4-yl)ethyl)-2-methylpyrrolidine (APD916).

The design of a new clinical candidate histamine-H(3) receptor antagonist for the potential treatment of excessive daytime sleepiness (EDS) is described. Phenethyl-R-2-methylpyrrolidine containing biphenylsulfonamide compounds were modified by replacement of the sulfonamide linkage with a sulfone. One compound from this series, 2j (APD916) increased wakefulness in rodents as measured by polysomnography with a duration of effect consistent with its pharmacokinetic properties. The identification of a suitable salt form of 2j allowed it to be selected for further development.

Design and evaluation of novel biphenyl sulfonamide derivatives with potent histamine H(3) receptor inverse agonist activity.

Antagonism of the histamine-H(3) receptor is one tactic being explored to increase wakefulness for the treatment of disorders such as excessive daytime sleepiness (EDS) as well as other sleep or cognitive disorders. Phenethyl-R-2-methylpyrrolidine containing biphenylsulfonamide compounds were shown to be potent and selective antagonists of the H(3) receptor. Several of these compounds demonstrated in vivo activity in a rat model of (R)-alpha-methyl histamine (RAMH) induced dipsogenia, and one compound (4e) provided an increase in wakefulness in rats as measured by polysomnographic methods. However, more detailed analysis of the PK/PD relationship suggested the presence of a common active metabolite which may preclude this series of compounds from further development.

Novel H3 receptor antagonists with improved pharmacokinetic profiles.

A new series of H(3) antagonists derived from the natural product Conessine are presented. Several compounds from these new series retain the potency and selectivity of earlier diamine based analogs while exhibiting improved PK characteristics. One compound (3u) demonstrated functional antagonism of the H(3) receptor in an in vivo pharmacological model.

A new family of H3 receptor antagonists based on the natural product Conessine.

A new family of Histamine H(3) receptor antagonists (5a-t) has been prepared based on the structure of the natural product Conessine, a known H(3) antagonist. Several members of the new series are highly potent and selective binders of rat and human H(3) receptors and display inverse agonism at the human H(3) receptor. Compound 5n exhibited promising rat pharmacokinetic properties and demonstrated functional antagonism of the H(3) receptor in an in-vivo pharmacological model.

An 8pi electron electrocyclization leading to a 9,19-methano-bridged analogue of 1 alpha,25-dihydroxyvitamin D3.

[reaction: see text] Lindlar semihydrogenation of a vitamin D type trienyne leads spontaneously to 9 alpha,19-methano-1 alpha,25-dihydroxyvitamin D3. The intermediate tetraene resulting from the reduction undergoes a rapid, stereoselective 8pi electron electrocyclization affording a novel steroid containing a linearly fused ABC (six-eight-six) 1,3,5-cyclooctatriene carbon framework.