Limitation of Trypanosoma brucei parasitaemia results from a combination of density-dependent parasite differentiation and parasite killing by the host immune response

In the bloodstream of its mammalian host, the "slender" form of Trypanosoma brucei replicates extracellularly, producing a parasitaemia. At high density, the level of parasitaemia is limited at a sublethal level by differentiation to the non-replicative "stumpy" form and by the host immune response. Here, we derive continuous time equations to model the time-course, cell types and level of trypanosome parasitaemia, and compare the best fits with experimental data. The best fits that were obtained favour a model in which both density-dependent trypanosome differentiation and host immune response have a role in limiting the increase of parasites, much poorer fits being obtained when differentiation and immune response are considered independently of one another. Best fits also favour a model in which the slender-to-stumpy differentiation progresses in a manner that is essentially independent of the cell cycle. Finally, these models also make the prediction that the density-dependent trypanosome differentiation mechanism can give rise to oscillations in parasitaemia level. These oscillations are independent of the immune system and are not due to antigenic variation

Vibrational overtone initiated unimolecular dissociation of HOCH_2OOH and HOCD_2OOH: Evidence for mode selective behavior

The vibrational overtone induced unimolecular dissociation of HMHP (HOCH2OOH) and HMHP-d2 (HOCD2OOH) into OH and HOCH2O (HOCD2O) fragments is investigated in the region of the 4nuOH and 5nuOH bands. The unimolecular dissociation rates in the threshold region, corresponding to the 4nuOH band, exhibit measurable differences associated with excitation of the OH stretch of the alcohol versus the peroxide functional group, with the higher energy alcohol OH stretching state exhibiting a slower dissociation rate compared to the lower energy peroxide OH stretch in both HMHP and HMHP-d2. Predictions using the Rice–Ramsperger–Kassel–Marcus theory give rates that are in reasonably good agreement with the measured dissociation rate for the alcohol OH stretch but considerably differ from the measured rates for the peroxide OH stretch in both isotopomers. The present results are interpreted as suggesting that the extent of intramolecular vibrational energy redistribution (IVR) is different for the two OH stretching states associated with the two functional groups in HMHP, with IVR being substantially less complete for the peroxide OH stretch. Analysis of the OH fragment product state distributions in conjunction with phase-space theory simulation gives a D0 value of 38±0.7 kcal/mole for breaking the peroxide bond in HMHP

The Nikolaevskiy equation with dispersion

The Nikolaevskiy equation was originally proposed as a model for seismic waves and is also a model for a wide variety of systems incorporating a neutral, Goldstone mode, including electroconvection and reaction-diffusion systems. It is known to exhibit chaotic dynamics at the onset of pattern formation, at least when the dispersive terms in the equation are suppressed, as is commonly the practice in previous analyses. In this paper, the effects of reinstating the dispersive terms are examined. It is shown that such terms can stabilise some of the spatially periodic traveling waves; this allows us to study the loss of stability and transition to chaos of the waves. The secondary stability diagram (Busse balloon) for the traveling waves can be remarkably complicated.Comment: 24 pages; accepted for publication in Phys. Rev.

The Consequences of Choking in Sport: A Constructive or Destructive Experience?

Through an empirical phenomenological methodology, the study examined the short- and long-term consequences of choking in sport. Eleven intermediate golfers (10 male, 1 female; age 23–50 years, M = 34.6, SD = 8.9) with handicaps of 6–18 (M = 10.91, SD = 3.98) completed phenomenological interviews that explored the perceived psychological impact of their choking episode(s). While the reported short-term consequences were negative (i.e., collapse in performance standards, limited attention/emotional control, and negative affect), most participants thought the long-term impact of choking was constructive, for it encouraged adversity-related growth. However, a small number of golfers identified the long-term consequences as highly destructive, including a loss of self-confidence, withdrawal from the sport, and, in 1 case, lowered self-worth. The findings of the study extend the choking literature by informing strategies that can be used to encourage constructive, rather than destructive, consequences from any choking episode that athletes may experience

Mononuclear cell transcriptome changes associated with dimethyl fumarate in MS.

ObjectiveTo identify short-term changes in gene expression in peripheral blood mononuclear cells (PBMCs) associated with treatment response to dimethyl fumarate (DMF, Tecfidera) in patients with relapsing-remitting MS (RRMS).MethodsBlood samples were collected from 24 patients with RRMS (median Expanded Disability Status Scale score, 2.0; range 1-7) at baseline, 6 weeks, and 15 months after the initiation of treatment with DMF (BG-12; Tecfidera). Seven healthy controls were also recruited, and blood samples were collected over the same time intervals. PBMCs were extracted from blood samples and sequenced using next-generation RNA sequencing. Treatment responders were defined using the composite outcome measure "no evidence of disease activity" (NEDA-4). Time-course and cross-sectional differential expression analyses were performed to identify transcriptomic markers of treatment response.ResultsTreatment responders (NEDA-4 positive, 8/24) over the 15-month period had 478 differentially expressed genes (DEGs) 6 weeks after the start of treatment. These were enriched for nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and inhibition of nuclear factor κB (NFκB) pathway transcripts. For patients who showed signs of disease activity, there were no DEGs at 6 weeks relative to their (untreated) baseline. Contrasting transcriptomes expressed at 6 weeks with those at 15 months of treatment, 0 and 1,264 DEGs were found in the responder and nonresponder groups, respectively. Transcripts in the nonresponder group (NEDA-4 negative, 18/24) were enriched for T-cell signaling genes.ConclusionShort-term PBMC transcriptome changes reflecting activation of the Nrf2 and inhibition of NFκB pathways distinguish patients who subsequently show a medium-term treatment response with DMF. Relative stabilization of gene expression patterns may accompany treatment-associated suppression of disease activity

Subject-Specific Lesion Generation and Pseudo-Healthy Synthesis for Multiple Sclerosis Brain Images

Understanding the intensity characteristics of brain lesions is key for defining image-based biomarkers in neurological studies and for predicting disease burden and outcome. In this work, we present a novel foreground-based generative method for modelling the local lesion characteristics that can both generate synthetic lesions on healthy images and synthesize subject-specific pseudo-healthy images from pathological images. Furthermore, the proposed method can be used as a data augmentation module to generate synthetic images for training brain image segmentation networks. Experiments on multiple sclerosis (MS) brain images acquired on magnetic resonance imaging (MRI) demonstrate that the proposed method can generate highly realistic pseudo-healthy and pseudo-pathological brain images. Data augmentation using the synthetic images improves the brain image segmentation performance compared to traditional data augmentation methods as well as a recent lesion-aware data augmentation technique, CarveMix. The code will be released at https://github.com/dogabasaran/lesion-synthesis.Comment: 13 pages, 6 figures, 2022 MICCAI SASHIMI (Simulation and Synthesis in Medical Imaging) Workshop pape

Demonstrating an absolute quantum advantage in direct absorption measurement

Engineering apparatus that harness quantum theory promises to offer practical advantages over current technology. A fundamentally more powerful prospect is that such quantum technologies could out-perform any future iteration of their classical counterparts, no matter how well the attributes of those classical strategies can be improved. Here, for optical direct absorption measurement, we experimentally demonstrate such an instance of an absolute advantage per photon probe that is exposed to the absorbative sample. We use correlated intensity measurements of spontaneous parametric downconversion using a commercially available air-cooled CCD, a new estimator for data analysis and a high heralding efficiency photon-pair source. We show this enables improvement in the precision of measurement, per photon probe, beyond what is achievable with an ideal coherent state (a perfect laser) detected with 100% efficient and noiseless detection. We see this absolute improvement for up to 50% absorption, with a maximum observed factor of improvement of 1.46. This equates to around 32% reduction in the total number of photons traversing an optical sample, compared to any future direct optical absorption measurement using classical light

The silicon trypanosome

African trypanosomes have emerged as promising unicellular model organisms for the next generation of systems biology. They offer unique advantages, due to their relative simplicity, the availability of all standard genomics techniques and a long history of quantitative research. Reproducible cultivation methods exist for morphologically and physiologically distinct life-cycle stages. The genome has been sequenced, and microarrays, RNA-interference and high-accuracy metabolomics are available. Furthermore, the availability of extensive kinetic data on all glycolytic enzymes has led to the early development of a complete, experiment-based dynamic model of an important biochemical pathway. Here we describe the achievements of trypanosome systems biology so far and outline the necessary steps towards the ambitious aim of creating a , a comprehensive, experiment-based, multi-scale mathematical model of trypanosome physiology. We expect that, in the long run, the quantitative modelling enabled by the Silicon Trypanosome will play a key role in selecting the most suitable targets for developing new anti-parasite drugs

Dehydration Reduces Posterior Leg and Trunk Flexibility and Increases Stiffness in Male Collegiate Age Runners

Dehydration reduces flexibility and increases stiffness in male collegiate age runners. Dehydration has been shown to negatively affect collagen in vitro; however the literature lacks works exploring the in vivo effects of dehydration on collagenous tissue. This study addresses this gap in the literature, by exploring the effects of dehydration on the muscles and connective tissues of the posterior leg. It was hypothesized that when dehydrated, the collagen within these tissues would become stiffer, decreasing flexibility and increasing stiffness. A cross-over cohort design was conducted to evaluate nineteen male collegiate runners. Each subject attended three sessions: baseline, dehydration and euhydration. The order of testing was randomly assigned and the PI was blinded throughout. Mean sit and reach (MSnR), mean terminal straight leg raise (MTSLR) and mean posterior leg stiffness (MPLS) scores for each testing condition were analyzed using a repeated measures ANOVA. Dehydrated, subjects demonstrated statistically significant decreases in MSnR scores, p\u3c0.001, d=0.469 (MSnR dehydrated 26.83 ± 7.53 cm and MSnR euhydrated 30.36 ± 7.53 cm) and MTSLR, p\u3c0.001, d=1.068 (MTSLR dehydrated 51.38 ± 9.39 and MTSLR euhydrated 60.58 ± 7.74), with a concurrent increase in MPLS, p=0.005, d=1.023 (MPLS dehydrated 0.899 ± 0.357 and MPLS euhydrated 0.508 ± 0.409), as compared to when they were euhydrated. The large effect size for MPLS and MTSLR and moderate for MSnR indicates that when dehydrated subjects became stiffer and has less flexibility as compared to when they are euhydrated. These changes may impede performance and increase the risk of injury in dehydrated individuals