Self-Consistent Extraction of Spectroscopic Bounds on Light New Physics.

Fundamental physical constants are determined from a collection of precision measurements of elementary particles, atoms, and molecules. This is usually done under the assumption of the standard model (SM) of particle physics. Allowing for light new physics (NP) beyond the SM modifies the extraction of fundamental physical constants. Consequently, setting NP bounds using these data, and at the same time assuming the Committee on Data of the International Science Council recommended values for the fundamental physical constants, is not reliable. As we show in this Letter, both SM and NP parameters can be simultaneously determined in a consistent way from a global fit. For light vectors with QED-like couplings, such as the dark photon, we provide a prescription that recovers the degeneracy with the photon in the massless limit and requires calculations only at leading order in the small new physics couplings. At present, the data show tensions partially related to the proton charge radius determination. We show that these can be alleviated by including contributions from a light scalar with flavor nonuniversal couplings.

New physics searches at kaon and hyperon factories.

Rare meson decays are among the most sensitive probes of both heavy and light new physics. Among them, new physics searches using kaons benefit from their small total decay widths and the availability of very large datasets. On the other hand, useful complementary information is provided by hyperon decay measurements. We summarize the relevant phenomenological models and the status of the searches in a comprehensive list of kaon and hyperon decay channels. We identify new search strategies for under-explored signatures, and demonstrate that the improved sensitivities from current and next-generation experiments could lead to a qualitative leap in the exploration of light dark sectors.

Erratum to: Anomaly free Froggatt-Nielsen models of flavor.

[This corrects the article DOI: 10.1007/JHEP10(2019)188.].

Synergistic and antagonistic effects of immunomodulatory drugs on the action of antifungals against Candida glabrata and Saccharomyces cerevisiae.

Candidemia and other forms of invasive fungal infections caused by Candida glabrata and to a lesser extent Saccharomyces cerevisiae are a serious health problem, especially if their steadily rising resistance to the limited range of antifungal drugs is taken into consideration. Various drug combinations are an attractive solution to the resistance problem, and some drug combinations are already common in the clinical environment due to the nature of diseases or therapies. We tested a few of the common antifungal-immunomodulatory drug combinations and evaluated their effect on selected strains of C. glabrata and S. cerevisiae. The combinations were performed using the checkerboard microdilution assay and interpreted using the Loewe additivity model and a model based on the Bliss independence criterion. A synergistic interaction was confirmed between calcineurin inhibitors (Fk506 and cyclosporine A) and antifungals (fluconazole, itraconazole, and amphotericin B). A new antagonistic interaction between mycophenolic acid (MPA) and azole antifungals was discovered in non-resistant strains. A possible mechanism that explains this is induction of the Cdr1 efflux pump by MPA in C. glabrata ATCC 2001. The Pdr1 regulatory cascade plays a role in overall resistance to fluconazole, but it is not essential for the antagonistic interaction. This was confirmed by the Cgpdr1Δ mutant still displaying the antagonistic interaction between the drugs, although at lower concentrations of fluconazole. This antagonism calls into question the use of simultaneous therapy with MPA and azoles in the clinical environment.

Quorum-sensing in yeast and its potential in wine making.

This mini-review synthesises the present knowledge of microbial quorum-sensing, with a specific focus on quorum-sensing in yeast, and especially in wine yeast. In vine and wine ecosystems, yeast co-interact with a large variety of microorganisms, thereby affecting the fermentation process and, consequently, the flavour of the wine. The precise connections between microbial interactions and quorum-sensing remain unclear, but we describe here how and when some species start to produce quorum-sensing molecules to synchronously adapt their collective behaviour to new conditions. In Saccharomyces cerevisiae, the quorum-sensing molecules were identified as 2-phenylethanol and tryptophol. However, it was recently shown that also a quorum-sensing molecule formerly identified only in Candida albicans, tyrosol, appears to be regulated in S. cerevisiae according to cell density. This review describes the methods for detection and quantification of those quorum-sensing molecules, their underlying mechanisms of action, and their genetic background. It also examines the external stimuli that evoke the quorum-sensing mechanism in the wine-processing environment. The review closes with insight into the biotechnological applications that are already making use of the advantages of quorum-sensing systems and indicates the important questions that still need to be addressed in future research into quorum-sensing.

Probiotic yeast Saccharomyces boulardii (nom. nud.) modulates adhesive properties of Candida glabrata.

Following the widespread use of immunosuppressive therapy together with broad-spectrum antimycotic therapy, the frequency of mucosal and systemic infections caused by the pathogenic yeast Candida glabrata has increased in the past decades. Due to the resistance of C. glabrata to existing azole drugs, it is very important to look for new strategies helping the treatment of such fungal diseases. In this study, we investigated the effect of the probiotic yeast Saccharomyces boulardii (nom. nud.) on C. glabrata adhesion at different temperatures, pH values, and in the presence of fluconazole, itraconazole and amphotericin B. We also studied the adhesion of C. glabrata co-culture with Candida krusei, Saccharomyces cerevisiae, two bacterial probiotics Lactobacillus rhamnosus and Lactobacillus casei The method used to assess adhesion was crystal violet staining. Our results showed that despite the nonadhesiveness of S. boulardii cells, this probiotic significantly affected the adherence ability of C. glabrata This effect was highly dependent on C. glabrata strain and was either antagonistic or synergistic. Regarding the extrinsic factors, temperature did not indicate any significant influence on this S. boulardii modulatory effect, while at high pH and at increased concentrations of antimycotics, S. boulardii did not manage to repress the adhesion of C. glabrata strains. The experiments of C. glabrata co-cultures with other species showed that the adhesiveness of two separate cultures could not be used to predict the adhesiveness of their co-culture.

Quorum-Sensing Kinetics in Saccharomyces cerevisiae: A Symphony of ARO Genes and Aromatic Alcohols.

The kinetics of quorum sensing in Saccharomyces cerevisiae were studied using a mini-fermentation platform. The quorum-sensing molecules were monitored using our previous HPLC approach that is here supported by quantitative real-time PCR analysis of the quorum-sensing genes. We thus initially confirm correlations between peak production rates of the monitored quorum-sensing molecules 2-phenylethanol, tryptophol, and tyrosol and peak expression of the genes responsible for their synthesis: ARO8, ARO9, and ARO10. This confirms the accuracy of our previously implemented kinetic model, thus favoring its use in further studies in this field. We also show that the quorum-sensing kinetics are precisely dependent on the population growth phase and that tyrosol production is also regulated by cell concentration, which has not been reported previously. Additionally, we show that during wine fermentation, ethanol stress reduces the production of 2-phenylethanol, tryptophol, and tyrosol, which opens new challenges in the control of wine fermentation.

Exclusive window onto Higgs Yukawa couplings.

We show that both flavor-conserving and flavor-violating Yukawa couplings of the Higgs boson to first- and second-generation quarks can be probed by measuring rare decays of the form h→MV, where M denotes a vector meson and V indicates either γ, W or Z. We calculate the branching ratios for these processes in both the standard model and its possible extensions. We discuss the experimental prospects for their observation. The possibility of accessing these Higgs couplings appears to be unique to the high-luminosity LHC and future hadron colliders, providing further motivation for those machines.

Evaluation of toxic endpoints for a set of cosmetic ingredients with CAESAR models.

The randomly selected set of 558 chemicals from Cosmetic inventory was studied with internet accessible program package CAESAR. Four toxic endpoints were considered: mutagenicity, carcinogenicity, developmental toxicity and skin sensitization. The CAESAR program provides beside the predictions comprehensive information on applicability domain and the similarity between the considered compound and the compounds from model's training set. This information was used to implement for clustering and classification of chemicals. As the technique the Self Organizing Maps was applied. This technique also enables us to define to each cluster the cluster indicator, i.e., the characteristic compound, which is considered as a representative for a cluster.

The influence of serial repitching of Saccharomyces pastorianus on its karyotype and protein profile during the fermentation of gluten-free buckwheat and quinoa wort.

Gluten-free beer-like beverages from malted buckwheat and quinoa are somehow close to their commercial production, but rather high expenses are expected due to the relatively high price of grain, some technological adaptations of process and the need for external enzyme supplementation during mashing. One of the common and efficient cost reduction measures in the industrial scale is serial repitching of the yeast biomass, which has not been studied for the buckwheat and quinoa wort fermentation before. In that manner we have monitored possible changes in yeast's proteins and chromosomal DNA during eleven serial repitchings of the yeast Saccharomyces pastorianus strain TUM 34/70 for fermentation of the barley, buckwheat and quinoa wort. Karyotypes showed changes in regard to the raw materials used and many responsible candidate proteins are suggested which could cause these differences. Different relative expressions of some protein bands were also linked to the proteins involved in yeast stress response and proteins involved in fermentation performance. Results suggest that serial repitching of the strain TUM 34/70 seems suitable for the production of gluten-free beer-like beverages from buckwheat and quinoa.

Monitoring of quorum-sensing molecules during minifermentation studies in wine yeast.

At high cell density or under low nutrient conditions, yeasts collectively adapt their metabolism by secreting aromatic alcohols in what is known as quorum sensing. However, the mechanisms and role of quorum sensing in yeast are poorly understood, and the methodology behind this process is not well established. This paper describes an effective approach to study quorum sensing in yeast fermentations. The separation, detection, and quantification of the putative quorum-sensing molecules 2-phenylethanol, tryptophol, and tyrosol have been optimized on a simple HPLC-based system. With the use of a phenyl HPLC column and a fluorescence detector, the sensitivity of the system was significantly increased. This allowed extraction and concentration procedures to be eliminated and the process to be scaled down to 2 mL minifermentations. Additionally, an innovative method for rapid viable-cell counting is presented. This study forms the basis for detailed studies in kinetics and regulation of quorum sensing in yeast fermentation.

Implications of lepton flavor universality violations in B decays.

Present measurements of b→cτν and b→uτν transitions differ from the standard model predictions of lepton flavor universality by almost 4σ. We examine new physics interpretations of this anomaly. An effective field theory analysis shows that minimal flavor violating models are not preferred as an explanation, but are also not yet excluded. Allowing for general flavor violation, right-right vector and right-left scalar quark currents are identified as viable candidates. We discuss explicit examples of two Higgs doublet models, leptoquarks as well as quark and lepton compositeness. Finally, implications for LHC searches and future measurements at the (super-)B factories are presented.

Astrophysics-independent bounds on the annual modulation of dark matter signals.

We show how constraints on the time integrated event rate from a given dark matter (DM) direct detection experiment can be used to bound the amplitude of the annual modulation signal in another experiment. The method requires only mild assumptions about the properties of the local DM distribution: that it is temporally stable on the scale of months and spatially homogeneous on the ecliptic. We apply the method to the annual modulation signal in DAMA/LIBRA, which we compare to the bounds derived from XENON10, XENON100, cryogenic DM search, and SIMPLE data. Assuming a DM mass of 10 GeV, we show that under the above assumptions about the DM halo, a DM interpretation of the DAMA/LIBRA signal is excluded for several classes of models: at 6.3σ (4.6σ) for elastic isospin conserving (violating) spin-independent interactions, and at 4.9σ for elastic spin-dependent interactions on protons.

Forward-backward asymmetry in tt production from flavor symmetries.

We show that the forward-backward asymmetry in top quark pair production can be enhanced by fields that transform nontrivially under the flavor group and satisfy minimal flavor violation, while at the same time the constraints from associated effects on the dσ(tt)/dM(tt) distribution, dijet resonance searches, same-sign top-pair production, and other phenomenology are satisfied. We work out two examples in detail: one where a scalar color antisextet field that is also an antisextet of SU(3)(U) enhances the forward-backward asymmetry and one where the enhancement arises from a vector color octet field that is also an octet of SU(3)(U).

Artificial neural networks to evaluate the boron concentration decreasing profile in blood-BPA samples of BNCT patients.

For the prediction of decay concentration profiles of the p-boronophenylalanine (BPA) in blood during BNCT treatment, a method is suggested based on Kohonen neural networks. The results of a model trained with the concentration profiles from the literature are described. The prediction of the model was validated by the leave-one-out method. Its robustness shows that it is mostly independent on small variations. The ability to fit retrospective experimental data shows an uncertainty lower than the two compartment model used previously.

Linear vs. Non-linear Modelling. Case study: modelling of binding affinity of inhibitors to Trypsin.

On the set of 53 trypsin inhibitors the affinity to the covalent bound ligands is modeled using linear (MLR) and non-linear (ANN) methods. Each compound is represented by 343 chemical descriptors. The hypothesis was that linear models are not sufficiently flexible to yield the best model, because in MLR (multiple regression analysis) the number of variables (descriptors) is limited by the number of objects in the training set. On the other hand the CP-ANN (counter-propagation-artificial neural network) is not limited by this restriction and can thus involve larger number of variables than there are compounds in the training set. Both methods are applied on the same division of 53 compounds on the training, test, and validation sets. In a systematic GA (genetic algorithm) search the MLR models containing all possible forms of linear polynomials, i.e., from 3 to 25 variables were scanned and no better model that one obtained by the CP-ANN model was found.

The effect of fungicides on yeast communities associated with grape berries.

The influence of three commonly used fungicides (iprodione, pyrimethanil and fludioxonil plus cyprodinil) on the density and diversity of yeast populations present on grape berries was evaluated. At the time of harvest, the fungicide residues on grapes were below the maximum permitted levels. In general, larger yeast counts were found on the treated grapes than on the control samples. Among 23 species identified, Cryptococcus magnus, Rhodotorula glutinis and Sporidiobolus pararoseus dominated on sound grape berries. The results showed that the tested fungicides had only a minor impact on the composition of grape berry communities in comparison with the effect of weather conditions and the mode of grape berry sampling. Halo assays using filter discs loaded with fungicides were used as in vitro tests of the sensitivity of grape berry isolates. The fungicide containing pyrimethanil suppressed the growth of all basidiomycetous yeast species, while the sporadically occurring fermentative yeasts were unaffected. Fungicides with fludioxonil plus cyprodinil and iprodione as active substances showed specificity for certain species. Our results suggest that after the safety interval, the presence of fungicides has a minor impact on the composition of grape berry communities, although at the time of fungicide applications, the yeast species composition changes.

Invasive growth of Saccharomyces cerevisiae depends on environmental triggers: a quantitative model.

In this contribution, the influence of various physicochemical factors on Saccharomyces cerevisiae invasive growth is examined quantitatively. Agar-invasion assays are generally applied for in vitro studies on S. cerevisiae invasiveness, the phenomenon observed as a putative virulence trait in this clinically more and more concerning yeast. However, qualitative agar-invasion assays, used until now, strongly limit the feasibility and interpretation of analyses and therefore needed to be improved. Besides, knowledge in this field concerning the physiology of invasive growth, influenced by stress conditions related to the human alimentary tract and food, is poor and should be expanded. For this purpose, a quantitative agar-invasion assay, presented in our previous work, was applied in this contribution to clarify the significance of the stress factors controlling the adhesion and invasion of the yeast in greater detail. Ten virulent and non-virulent S. cerevisiae strains were assayed at various temperatures, pH values, nutrient starvation, modified atmosphere, and different concentrations of NaCl, CaCl2 and preservatives. With the use of specific parameters, like a relative invasion, eight invasive growth models were hypothesized, which enabled intelligible interpretation of the results. A strong preference for invasive growth (meaning high relative invasion) was observed when the strains were grown on nitrogen- and glucose-depleted media. A significant increase in the invasion of the strains was also determined at temperatures typical for human fever (37-39 degrees C). On the other hand, a strong repressive effect on invasion was found in the presence of salts, anoxia and some preservatives.

Implications of the dimuon CP asymmetry in B(d,s) decays.

The D0 Collaboration reported a 3.2σ deviation from the standard model (SM) prediction in the like-sign dimuon asymmetry. Assuming that new physics contributes only to B(d,s) mixing, we show that the data can be analyzed without using the theoretical calculation of ΔΓ(s), allowing for robust interpretations. We find that this framework gives a good fit to all measurements, including the recent CDF Collaboration S(ψϕ) result. The data allow universal new physics with similar contributions relative to the SM in the B(d) and B(s) systems, but favors a larger deviation in B(s) than in B(d) mixing. The general minimal flavor violation framework with flavor diagonal CP violating phases can account for the former case and remarkably even for the latter case. This observation makes it simpler to speculate about which extensions with general flavor structure may also fit the data.