Adaptive Out-Orientations with Applications

We give simple algorithms for maintaining edge-orientations of a fully-dynamic graph, such that the out-degree of each vertex is bounded. On one hand, we show how to orient the edges such that the out-degree of each vertex is proportional to the arboricity $\alpha$ of the graph, in a worst-case update time of $O(\log^2 n \log \alpha)$. On the other hand, motivated by applications in dynamic maximal matching, we obtain a different trade-off, namely the improved worst case update time of $O(\log n \log \alpha)$ for the problem of maintaining an edge-orientation with at most $O(\alpha + \log n)$ out-edges per vertex. Since our algorithms have update times with worst-case guarantees, the number of changes to the solution (i.e. the recourse) is naturally limited. Our algorithms make choices based entirely on local information, which makes them automatically adaptive to the current arboricity of the graph. In other words, they are arboricity-oblivious, while they are arboricity-sensitive. This both simplifies and improves upon previous work, by having fewer assumptions or better asymptotic guarantees. As a consequence, one obtains an algorithm with improved efficiency for maintaining a $(1+\varepsilon)$ approximation of the maximum subgraph density, and an algorithm for dynamic maximal matching whose worst-case update time is guaranteed to be upper bounded by $O(\alpha + \log n\log \alpha)$, where $\alpha$ is the arboricity at the time of the update

Counterflow dielectrophoresis for trypanosome enrichment and detection in blood

Human African trypanosomiasis or sleeping sickness is a deadly disease endemic in sub-Saharan Africa, caused by single-celled protozoan parasites. Although it has been targeted for elimination by 2020, this will only be realized if diagnosis can be improved to enable identification and treatment of afflicted patients. Existing techniques of detection are restricted by their limited field-applicability, sensitivity and capacity for automation. Microfluidic-based technologies offer the potential for highly sensitive automated devices that could achieve detection at the lowest levels of parasitemia and consequently help in the elimination programme. In this work we implement an electrokinetic technique for the separation of trypanosomes from both mouse and human blood. This technique utilises differences in polarisability between the blood cells and trypanosomes to achieve separation through opposed bi-directional movement (cell counterflow). We combine this enrichment technique with an automated image analysis detection algorithm, negating the need for a human operator

Capsaicin-sensitive cutaneous primary afferents convey electrically induced itch in humans

Specially designed transcutaneous electrical stimulation paradigms can be used to provoke experimental itch. However, it is unclear which primary afferent fibers are activated and whether they represent pathophysiologically relevant, C-fiber mediated itch. Since low-threshold mechano-receptors have recently been implicated in pruriception we aimed to characterize the peripheral primary afferent subpopulation conveying electrically evoked itch in humans (50 Hz stimulation, 100 μs square pulses, stimulus-response function to graded stimulus intensity). In 10 healthy male volunteers a placebo-controlled, 24-h 8% topical capsaicin-induced defunctionalization of capsaicin-sensitive (transient receptor potential V1-positive, ‘TRPV1’+) cutaneous fibers was performed. Histaminergic itch (1% solution introduced by a prick test lancet) was provoked as a positive control condition. Capsaicin pretreatment induced profound loss of warmth and heat pain sensitivity (pain threshold and supra-threshold ratings) as assessed by quantitative sensory testing, indicative of efficient TRPV1-fiber defunctionalization (all outcomes: P 0.0001). The topical capsaicin robustly, and with similar efficaciousness, inhibited itch intensity evoked by electrical stimulation and histamine (−89 ± 4.1% and −78 ± 4.9%, respectively, both: P 0.0001 compared to the placebo patch area). The predominant primary afferent substrate for electrically evoked itch in humans, using the presently applied stimulation paradigm, is concluded to be capsaicin-sensitive polymodal C-fibers.FSW - Self-regulation models for health behavior and psychopathology - ou

The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer

BACKGROUND: Prostate cancer is thought to be the most heritable cancer, although little is known about how this genetic contribution varies across age. METHODS: To address this question, we undertook the world's largest prospective study in the Nordic Twin Study of Cancer cohort, including 18,680 monozygotic and 30,054 dizygotic same sex male twin pairs. We incorporated time-to-event analyses to estimate the risk concordance and heritability while accounting for censoring and competing risks of death, essential sources of biases that have not been accounted for in previous twin studies modeling cancer risk and liability. RESULTS: The cumulative risk of prostate cancer was similar to that of the background population. The cumulative risk for twins whose co-twin was diagnosed with prostate cancer was greater for MZ than for DZ twins across all ages. Among concordantly affected pairs, the time between diagnoses was significantly shorter for MZ than DZ pairs (median 3.8 versus 6.5 years, respectively). Genetic differences contributed substantially to variation in both the risk and the liability (heritability=58% (95% CI 52%–63%) of developing prostate cancer. The relative contribution of genetic factors was constant across age through late life with substantial genetic heterogeneity even when diagnosis and screening procedures vary. CONCLUSIONS: Results from the population based twin cohort, indicate a greater genetic contribution to the risk of developing prostate cancer when addressing sources of bias. The role of genetic factors is consistently high across age IMPACT: Findings impact the search for genetic and epigenetic markers and frame prevention efforts

Public awareness and support for use of wastewater for SARS-CoV-2 monitoring: A community survey in Louisville, Kentucky

The majority of sewer systems in the United States and other countries, are operated by public utilities. In the absence of any regulation, public perception of monitoring wastewater for population health biomarkers is an important consideration for a public utility commission when allocating resources for this purpose. In August 2021, we conducted a survey as part of an ongoing COVID-19 community prevalence study in Louisville/Jefferson County, KY. The survey comprised of seven questions about awareness of and privacy concerns and was sent to 32,000 households randomly distributed within the county. A total of 1,220 sampled adults participated in the probability sample, and 981 were used in analysis. A total of 2,444 adults additionally responded in the convenience sample, and 1,751 were used in analysis. The samples were weighted to produce estimates representative of all adults in the county. Public awareness of tracking COVID-19 virus in the sewers was low. Opinions about how data from this activity are shared strongly supported public disclosure of monitoring results. Responses showed more support for measuring the largest areas (\u3e30,000 to 50,000 households) typically representing population levels found in a community or regional wastewater treatment plant. Those who had a history of COVID-19 infection were more likely to support highly localized monitoring. Understanding wastewater surveillance strategies and thresholds of privacy concerns requires in-depth, comprehensive analysis of public opinion for continued success and efficacy of public health monitoring

Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism

Interactions between host and gut microbial communities are modulated by diets and play pivotal roles in immunological homeostasis and health. We show that exchanging the protein source in a high fat, high sugar, westernized diet from casein to whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath is sufficient to reverse western diet-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22 °C) and at thermoneutrality (T30 °C). Concomitant with microbiota changes, mice fed the Methylococcus-based western diet exhibit improved glucose regulation, reduced body and liver fat, and diminished hepatic immune infiltration. Intake of the Methylococcu-based diet markedly boosts Parabacteroides abundances in a manner depending on adaptive immunity, and upregulates triple positive (Foxp3+RORγt+IL-17+) regulatory T cells in the small and large intestine. Collectively, these data point to the potential for leveraging the use of McB lysates to improve immunometabolic homeostasis.publishedVersio

FlexOracle: predicting flexible hinges by identification of stable domains

<p>Abstract</p> <p>Background</p> <p>Protein motions play an essential role in catalysis and protein-ligand interactions, but are difficult to observe directly. A substantial fraction of protein motions involve hinge bending. For these proteins, the accurate identification of flexible hinges connecting rigid domains would provide significant insight into motion. Programs such as GNM and FIRST have made global flexibility predictions available at low computational cost, but are not designed specifically for finding hinge points.</p> <p>Results</p> <p>Here we present the novel FlexOracle hinge prediction approach based on the ideas that energetic interactions are stronger <it>within </it>structural domains than <it>between </it>them, and that fragments generated by cleaving the protein at the hinge site are independently stable. We implement this as a tool within the Database of Macromolecular Motions, MolMovDB.org. For a given structure, we generate pairs of fragments based on scanning all possible cleavage points on the protein chain, compute the energy of the fragments compared with the undivided protein, and predict hinges where this quantity is minimal. We present three specific implementations of this approach. In the first, we consider only pairs of fragments generated by cutting at a <it>single </it>location on the protein chain and then use a standard molecular mechanics force field to calculate the enthalpies of the two fragments. In the second, we generate fragments in the same way but instead compute their free energies using a knowledge based force field. In the third, we generate fragment pairs by cutting at <it>two </it>points on the protein chain and then calculate their free energies.</p> <p>Conclusion</p> <p>Quantitative results demonstrate our method's ability to predict known hinges from the Database of Macromolecular Motions.</p