Jet quenching in hot strongly coupled gauge theories simplified

Theoretical studies of jet stopping in strongly-coupled QCD-like plasmas have used gauge-gravity duality to find that the maximum stopping distance scales like E^{1/3} for large jet energies E. In recent work studying jets that are created by finite-size sources in the gauge theory, we found an additional scale: the typical (as opposed to maximum) jet stopping distance scales like (EL)^{1/4}, where L is the size of the space-time region where the jet is created. In this paper, we show that the results of our previous, somewhat involved computation in the gravity dual, and the (EL)^{1/4} scale in particular, can be very easily reproduced and understood in terms of the distance that high-energy particles travel in AdS_5-Schwarzschild space before falling into the black brane. We also investigate how stopping distances depend on the conformal dimension of the source operator used to create the jet.Comment: 30 pages, 10 figure

Planets in Mean-Motion Resonances and the System Around HD45364

In some planetary systems, the orbital periods of two of its members present a commensurability, usually known by mean-motion resonance. These resonances greatly enhance the mutual gravitational influence of the planets. As a consequence, these systems present uncommon behaviors, and their motions need to be studied with specific methods. Some features are unique and allow us a better understanding and characterization of these systems. Moreover, mean-motion resonances are a result of an early migration of the orbits in an accretion disk, so it is possible to derive constraints on their formation. Here we review the dynamics of a pair of resonant planets and explain how their orbits evolve in time. We apply our results to the HD 45365 planetary system.Comment: invited review, 17 pages, 6 figure

Positive feedback induces switch between distributive and processive phosphorylation of Hog1

Cellular decision making often builds on ultrasensitive MAPK pathways. The phosphorylation mechanism of MAP kinase has so far been described as either distributive or processive, with distributive mechanisms generating ultrasensitivity in theoretical analyses. However, the in vivo mechanism of MAP kinase phosphorylation and its activation dynamics remain unclear. Here, we characterize the regulation of the MAP kinase Hog1 in Saccharomyces cerevisiae via topologically different ODE models, parameterized on multimodal activation data. Interestingly, our best fitting model switches between distributive and processive phosphorylation behavior regulated via a positive feedback loop composed of an affinity and a catalytic component targeting the MAP kinase-kinase Pbs2. Indeed, we show that Hog1 directly phosphorylates Pbs2 on serine 248 (S248), that cells expressing a non-phosphorylatable (S248A) or phosphomimetic (S248E) mutant show behavior that is consistent with simulations of disrupted or constitutively active affinity feedback and that Pbs2-S248E shows significantly increased affinity to Hog1 in vitro. Simulations further suggest that this mixed Hog1 activation mechanism is required for full sensitivity to stimuli and to ensure robustness to different perturbations.© 2023. The Author(s)

Protein crystals in adenovirus type 5-infected cells: requirements for intranuclear crystallogenesis, structural and functional analysis

Intranuclear crystalline inclusions have been observed in the nucleus of epithelial cells infected with Adenovirus serotype 5 (Ad5) at late steps of the virus life cycle. Using immuno-electron microscopy and confocal microscopy of cells infected with various Ad5 recombinants modified in their penton base or fiber domains, we found that these inclusions represented crystals of penton capsomers, the heteromeric capsid protein formed of penton base and fiber subunits. The occurrence of protein crystals within the nucleus of infected cells required the integrity of the fiber knob and part of the shaft domain. In the knob domain, the region overlapping residues 489–492 in the FG loop was found to be essential for crystal formation. In the shaft, a large deletion of repeats 4 to 16 had no detrimental effect on crystal inclusions, whereas deletion of repeats 8 to 21 abolished crystal formation without altering the level of fiber protein expression. This suggested a crucial role of the five penultimate repeats in the crystallisation process. Chimeric pentons made of Ad5 penton base and fiber domains from different serotypes were analyzed with respect to crystal formation. No crystal was found when fiber consisted of shaft (S) from Ad5 and knob (K) from Ad3 (heterotypic S5-K3 fiber), but occurred with homotypic S3K3 fiber. However, less regular crystals were observed with homotypic S35-K35 fiber. TB5, a monoclonal antibody directed against the Ad5 fiber knob was found by immunofluorescence microscopy to react with high efficiency with the intranuclear protein crystals in situ. Data obtained with Ad fiber mutants indicated that the absence of crystalline inclusions correlated with a lower infectivity and/or lower yields of virus progeny, suggesting that the protein crystals might be involved in virion assembly. Thus, we propose that TB5 staining of Ad-infected 293 cells can be used as a prognostic assay for the viability and productivity of fiber-modified Ad5 vectors

Recreational Physical Activity as an Independent Predictor of Multivariable Cardiovascular Disease Risk

The role of physical activity in preventing CVD has been highlighted by Professor Jerry Morris in the 1950’s. We report outcome of a 15-year prospective study with the aim to identify whether physical activity showed cardiovascular benefit independent of common risk factors and of central obesity. Baseline data of 8662 subjects, with no previous history of heart disease, diabetes or stroke, were obtained from an age- and gender- stratified sample of adults in Australian capital cities and were linked with the National Death Index to determine the causes of death of 610 subjects who had died to 31 December 2004. The study consisted of 4175 males (age 42.3±13.1 years) and 4487 females (age 42.8±13.2 years). Fasting serum lipid levels, systolic and diastolic blood pressure and smoking habits at baseline were recorded. The Framingham Risk Scores of 15-year mortality due to CHD and CVD were calculated using established equations. Subjects were also asked if they engaged in vigorous exercise, less vigorous exercise or walk for recreation and exercise in the past 2 weeks. Subjects in the high recreational physical activity category were 0.16 (0.06–0.43; p<0.001) and 0.12 (0.03–0.48; p = 0.003) times as likely as subjects in the low category for CVD and CHD mortality respectively. After adjusting for both the Framingham Risk Score and central obesity (Waist circumference to Hip circumference Ratio), those in the high recreational physical activity group were 0.35 (0.13–0.98) times less likely compared to the low category for CVD mortality. Recreational physical activity independently predicted reduced cardiovascular mortality over fifteen years. A public health focus on increased physical activity and preventing obesity is required to reduce the risk of CVD and CHD

The specificity and patterns of staining in human cells and tissues of p16INK4a antibodies demonstrate variant antigen binding

The validity of the identification and classification of human cancer using antibodies to detect biomarker proteins depends upon antibody specificity. Antibodies that bind to the tumour-suppressor protein p16INK4a are widely used for cancer diagnosis and research. In this study we examined the specificity of four commercially available anti-p16INK4a antibodies in four immunological applications. The antibodies H-156 and JC8 detected the same 16 kDa protein in western blot and immunoprecipitation tests, whereas the antibody F-12 did not detect any protein in western blot analysis or capture a protein that could be recognised by the H-156 antibody. In immunocytochemistry tests, the antibodies JC8 and H-156 detected a predominately cytoplasmic localised antigen, whose signal was depleted in p16INK4a siRNA experiments. F-12, in contrast, detected a predominately nuclear located antigen and there was no noticeable reduction in this signal after siRNA knockdown. Furthermore in immunohistochemistry tests, F-12 generated a different pattern of staining compared to the JC8 and E6H4 antibodies. These results demonstrate that three out of four commercially available p16INK4a antibodies are specific to, and indicate a mainly cytoplasmic localisation for, the p16INK4a protein. The F-12 antibody, which has been widely used in previous studies, gave different results to the other antibodies and did not demonstrate specificity to human p16INK4a. This work emphasizes the importance of the validation of commercial antibodies, aside to the previously reported use, for the full verification of immunoreaction specificity

The identification of informative genes from multiple datasets with increasing complexity

Background In microarray data analysis, factors such as data quality, biological variation, and the increasingly multi-layered nature of more complex biological systems complicates the modelling of regulatory networks that can represent and capture the interactions among genes. We believe that the use of multiple datasets derived from related biological systems leads to more robust models. Therefore, we developed a novel framework for modelling regulatory networks that involves training and evaluation on independent datasets. Our approach includes the following steps: (1) ordering the datasets based on their level of noise and informativeness; (2) selection of a Bayesian classifier with an appropriate level of complexity by evaluation of predictive performance on independent data sets; (3) comparing the different gene selections and the influence of increasing the model complexity; (4) functional analysis of the informative genes. Results In this paper, we identify the most appropriate model complexity using cross-validation and independent test set validation for predicting gene expression in three published datasets related to myogenesis and muscle differentiation. Furthermore, we demonstrate that models trained on simpler datasets can be used to identify interactions among genes and select the most informative. We also show that these models can explain the myogenesis-related genes (genes of interest) significantly better than others (P < 0.004) since the improvement in their rankings is much more pronounced. Finally, after further evaluating our results on synthetic datasets, we show that our approach outperforms a concordance method by Lai et al. in identifying informative genes from multiple datasets with increasing complexity whilst additionally modelling the interaction between genes. Conclusions We show that Bayesian networks derived from simpler controlled systems have better performance than those trained on datasets from more complex biological systems. Further, we present that highly predictive and consistent genes, from the pool of differentially expressed genes, across independent datasets are more likely to be fundamentally involved in the biological process under study. We conclude that networks trained on simpler controlled systems, such as in vitro experiments, can be used to model and capture interactions among genes in more complex datasets, such as in vivo experiments, where these interactions would otherwise be concealed by a multitude of other ongoing events

Infant Botulism

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66984/2/10.1177_000992289303201105.pd