A kinetic model describing the processivity of Myosin-V

The precise details of how myosin-V coordinates the biochemical reactions and mechanical motions of its two head elements to engineer effective processive molecular motion along actin filaments remain unresolved. We compare a quantitative kinetic model of the myosin-V walk, consisting of five basic states augmented by two further states to allow for futile hydrolysis and detachments, with experimental results for run lengths, velocities, and dwell times and their dependence on bulk nucleotide concentrations and external loads in both directions. The model reveals how myosin-V can use the internal strain in the molecule to synchronize the motion of the head elements. Estimates for the rate constants in the reaction cycle and the internal strain energy are obtained by a computational comparison scheme involving an extensive exploration of the large parameter space. This scheme exploits the fact that we have obtained analytic results for our reaction network, e.g., for the velocity but also the run length, diffusion constant, and fraction of backward steps. The agreement with experiment is often reasonable but some open problems are highlighted, in particular the inability of such a general model to reproduce the reported dependence of run length on ADP concentration. The novel way that our approach explores parameter space means that any confirmed discrepancies should give new insights into the reaction network model

Truncating the Y-Axis: Threat or Menace?

Bar charts with y-axes that don't begin at zero can visually exaggerate effect sizes. However, advice for whether or not to truncate the y-axis can be equivocal for other visualization types. In this paper we present examples of visualizations where this y-axis truncation can be beneficial as well as harmful, depending on the communicative and analytic intent. We also present the results of a series of crowd-sourced experiments in which we examine how y-axis truncation impacts subjective effect size across visualization types, and we explore alternative designs that more directly alert viewers to this truncation. We find that the subjective impact of axis truncation is persistent across visualizations designs, even for designs with explicit visual cues that indicate truncation has taken place. We suggest that designers consider the scale of the meaningful effect sizes and variation they intend to communicate, regardless of the visual encoding

Percent Fat Mass Increases with Recovery, But Does Not Vary According to Dietary Therapy in Young Malian Children Treated for Moderate Acute Malnutrition.

BackgroundModerate acute malnutrition (MAM) affects 34.1 million children globally. Treatment effectiveness is generally determined by the amount and rate of weight gain. Body composition (BC) assessment provides more detailed information on nutritional stores and the type of tissue accrual than traditional weight measurements alone.ObjectiveThe aim of this study was to compare the change in percentage fat mass (%FM) and other BC parameters among young Malian children with MAM according to receipt of 1 of 4 dietary supplements, and recovery status at the end of the 12-wk intervention period.MethodsBC was assessed using the deuterium oxide dilution method in a subgroup of 286 children aged 6-35 mo who participated in a 12-wk community-based, cluster-randomized effectiveness trial of 4 dietary supplements for the treatment of MAM: 1) lipid-based, ready-to-use supplementary food (RUSF); 2) special corn-soy blend "plus plus" (CSB++); 3) locally processed, fortified flour (MI); or 4) locally milled flours plus oil, sugar, and micronutrient powder (LMF). Multivariate linear regression modeling was used to evaluate change in BC parameters by treatment group and recovery status.ResultsMean ± SD %FM at baseline was 28.6% ± 5.32%. Change in %FM did not vary between groups. Children who received RUSF vs. MI gained more (mean; 95% CI) weight (1.43; 1.13, 1.74 kg compared with 0.84; 0.66, 1.03 kg; P = 0.02), FM (0.70; 0.45, 0.96 kg compared with 0.20; 0.05, 0.36 kg; P = 0.01), and weight-for-length z score (1.23; 0.79, 1.54 compared with 0.49; 0.34, 0.71; P = 0.03). Children who recovered from MAM exhibited greater increases in all BC parameters, including %FM, than children who did not recover.ConclusionsIn this study population, children had higher than expected %FM at baseline. There were no differences in %FM change between groups. International BC reference data are needed to assess the utility of BC assessment in community-based management of acute malnutrition programs. This trial was registered at clinicaltrials.gov as NCT01015950

Optic Nerve Head Quantification in Idiopathic Intracranial Hypertension by Spectral Domain OCT

Objective: To evaluate 3D spectral domain optical coherence tomography (SDOCT) volume scans as a tool for quantification of optic nerve head (ONH) volume as a potential marker for treatment effectiveness and disease progression in idiopathic intracranial hypertension (IIH). Design and Patients: Cross-sectional pilot trial comparing 19 IIH patients and controls matched for gender, age and body mass index. Each participant underwent SDOCT. A custom segmentation algorithm was developed to quantify ONH volume (ONHV) and height (ONHH) in 3D volume scans. Results:Whereas peripapillary retinal nerve fiber layer thickness did not show differences between controls and IIH patients, the newly developed 3D parameters ONHV and ONHH were able to discriminate between controls, treated and untreated patients. Both ONHV and ONHH measures were related to levels of intracranial pressure (ICP). Conclusion: Our findings suggest 3D ONH measures as assessed by SDOCT as potential diagnostic and progression markers in IIH and other disorders with increased ICP. SDOCT may promise a fast and easy diagnostic alternative to repeated lumba

Spectral Theory for Perturbed Krein Laplacians in Nonsmooth Domains

We study spectral properties for $H_{K,\Omega}$, the Krein--von Neumann extension of the perturbed Laplacian $-\Delta+V$ defined on $C^\infty_0(\Omega)$, where $V$ is measurable, bounded and nonnegative, in a bounded open set $\Omega\subset\mathbb{R}^n$ belonging to a class of nonsmooth domains which contains all convex domains, along with all domains of class $C^{1,r}$, $r>1/2$. In particular, in the aforementioned context we establish the Weyl asymptotic formula #\{j\in\mathbb{N} | \lambda_{K,\Omega,j}\leq\lambda\} = (2\pi)^{-n} v_n |\Omega| \lambda^{n/2}+O\big(\lambda^{(n-(1/2))/2}\big) {as} \lambda\to\infty, where $v_n=\pi^{n/2}/ \Gamma((n/2)+1)$ denotes the volume of the unit ball in $\mathbb{R}^n$, and $\lambda_{K,\Omega,j}$, $j\in\mathbb{N}$, are the non-zero eigenvalues of $H_{K,\Omega}$, listed in increasing order according to their multiplicities. We prove this formula by showing that the perturbed Krein Laplacian (i.e., the Krein--von Neumann extension of $-\Delta+V$ defined on $C^\infty_0(\Omega)$) is spectrally equivalent to the buckling of a clamped plate problem, and using an abstract result of Kozlov from the mid 1980's. Our work builds on that of Grubb in the early 1980's, who has considered similar issues for elliptic operators in smooth domains, and shows that the question posed by Alonso and Simon in 1980 pertaining to the validity of the above Weyl asymptotic formula continues to have an affirmative answer in this nonsmooth setting.Comment: 60 page

A Survey on the Krein-von Neumann Extension, the corresponding Abstract Buckling Problem, and Weyl-Type Spectral Asymptotics for Perturbed Krein Laplacians in Nonsmooth Domains

In the first (and abstract) part of this survey we prove the unitary equivalence of the inverse of the Krein--von Neumann extension (on the orthogonal complement of its kernel) of a densely defined, closed, strictly positive operator, $S\geq \varepsilon I_{\mathcal{H}}$ for some $\varepsilon >0$ in a Hilbert space $\mathcal{H}$ to an abstract buckling problem operator. This establishes the Krein extension as a natural object in elasticity theory (in analogy to the Friedrichs extension, which found natural applications in quantum mechanics, elasticity, etc.). In the second, and principal part of this survey, we study spectral properties for $H_{K,\Omega}$, the Krein--von Neumann extension of the perturbed Laplacian $-\Delta+V$ (in short, the perturbed Krein Laplacian) defined on $C^\infty_0(\Omega)$, where $V$ is measurable, bounded and nonnegative, in a bounded open set $\Omega\subset\mathbb{R}^n$ belonging to a class of nonsmooth domains which contains all convex domains, along with all domains of class $C^{1,r}$, $r>1/2$.Comment: 68 pages. arXiv admin note: extreme text overlap with arXiv:0907.144

Children with Moderate Acute Malnutrition with No Access to Supplementary Feeding Programmes Experience High Rates of Deterioration and No Improvement: Results from a Prospective Cohort Study in Rural Ethiopia

Background: Children with moderate acute malnutrition (MAM) have an increased risk of mortality, infections and impaired physical and cognitive development compared to well-nourished children. In parts of Ethiopia not considered chronically food insecure there are no supplementary feeding programmes (SFPs) for treating MAM. The short-term outcomes of children who have MAM in such areas are not currently described, and there remains an urgent need for evidence-based policy recommendations. Methods: We defined MAM as mid-upper arm circumference (MUAC) of ≥11.0cm and <12.5cm with no bilateral pitting oedema to include Ethiopian government and World Health Organisation cut-offs. We prospectively surveyed 884 children aged 6–59 months living with MAM in a rural area of Ethiopia not eligible for a supplementary feeding programme. Weekly home visits were made for seven months (28 weeks), covering the end of peak malnutrition through to the post-harvest period (the most food secure window), collecting anthropometric, socio-demographic and food security data. Results: By the end of the study follow up, 32.5% (287/884) remained with MAM, 9.3% (82/884) experienced at least one episode of SAM (MUAC <11cm and/or bilateral pitting oedema), and 0.9% (8/884) died. Only 54.2% of the children recovered with no episode of SAM by the end of the study. Of those who developed SAM half still had MAM at the end of the follow up period. The median (interquartile range) time to recovery was 9 (4–15) weeks. Children with the lowest MUAC at enrolment had a significantly higher risk of remaining with MAM and a lower chance of recovering. Conclusions: Children with MAM during the post-harvest season in an area not eligible for SFP experience an extremely high incidence of SAM and a low recovery rate. Not having a targeted nutrition-specific intervention to address MAM in this context places children with MAM at excessive risk of adverse outcomes. Further preventive and curative approaches should urgently be considered

Measures in Visualization Space

Postponed access: the file will be available after 2021-08-12Measurement is an integral part of modern science, providing the fundamental means for evaluation, comparison, and prediction. In the context of visualization, several different types of measures have been proposed, ranging from approaches that evaluate particular aspects of visualization techniques, their perceptual characteristics, and even economic factors. Furthermore, there are approaches that attempt to provide means for measuring general properties of the visualization process as a whole. Measures can be quantitative or qualitative, and one of the primary goals is to provide objective means for reasoning about visualizations and their effectiveness. As such, they play a central role in the development of scientific theories for visualization. In this chapter, we provide an overview of the current state of the art, survey and classify different types of visualization measures, characterize their strengths and drawbacks, and provide an outline of open challenges for future research.acceptedVersio