Collective decision-making on triadic graphs

Many real-world networks exhibit community structures and non-trivial clustering associated with the occurrence of a considerable number of triangular subgraphs known as triadic motifs. Triads are a set of distinct triangles that do not share an edge with any other triangle in the network. Network motifs are subgraphs that occur significantly more often compared to random topologies. Two prominent examples, the feedforward loop and the feedback loop, occur in various real-world networks such as gene-regulatory networks, food webs or neuronal networks. However, as triangular connections are also prevalent in communication topologies of complex collective systems, it is worthwhile investigating the influence of triadic motifs on the collective decision-making dynamics. To this end, we generate networks called Triadic Graphs (TGs) exclusively from distinct triadic motifs. We then apply TGs as underlying topologies of systems with collective dynamics inspired from locust marching bands. We demonstrate that the motif type constituting the networks can have a paramount influence on group decision-making that cannot be explained solely in terms of the degree distribution. We find that, in contrast to the feedback loop, when the feedforward loop is the dominant subgraph, the resulting network is hierarchical and inhibits coherent behavior

A cross-center smoothness prior for variational Bayesian brain tissue segmentation

Suppose one is faced with the challenge of tissue segmentation in MR images, without annotators at their center to provide labeled training data. One option is to go to another medical center for a trained classifier. Sadly, tissue classifiers do not generalize well across centers due to voxel intensity shifts caused by center-specific acquisition protocols. However, certain aspects of segmentations, such as spatial smoothness, remain relatively consistent and can be learned separately. Here we present a smoothness prior that is fit to segmentations produced at another medical center. This informative prior is presented to an unsupervised Bayesian model. The model clusters the voxel intensities, such that it produces segmentations that are similarly smooth to those of the other medical center. In addition, the unsupervised Bayesian model is extended to a semi-supervised variant, which needs no visual interpretation of clusters into tissues.Comment: 12 pages, 2 figures, 1 table. Accepted to the International Conference on Information Processing in Medical Imaging (2019

Evidence for Superfluidity of Ultracold Fermions in an Optical Lattice

The study of superfluid fermion pairs in a periodic potential has important ramifications for understanding superconductivity in crystalline materials. Using cold atomic gases, various condensed matter models can be studied in a highly controllable environment. Weakly repulsive fermions in an optical lattice could undergo d-wave pairing at low temperatures, a possible mechanism for high temperature superconductivity in the cuprates. The lattice potential could also strongly increase the critical temperature for s-wave superfluidity. Recent experimental advances in the bulk include the observation of fermion pair condensates and high-temperature superfluidity. Experiments with fermions and bosonic bound pairs in optical lattices have been reported, but have not yet addressed superfluid behavior. Here we show that when a condensate of fermionic atom pairs was released from an optical lattice, distinct interference peaks appear, implying long range order, a property of a superfluid. Conceptually, this implies that strong s-wave pairing and superfluidity have now been established in a lattice potential, where the transport of atoms occurs by quantum mechanical tunneling and not by simple propagation. These observations were made for unitarity limited interactions on both sides of a Feshbach resonance. For larger lattice depths, the coherence was lost in a reversible manner, possibly due to a superfluid to insulator transition. Such strongly interacting fermions in an optical lattice can be used to study a new class of Hamiltonians with interband and atom-molecule couplings.Comment: accepted for publication in Natur

The epidemiology of kidney disease in people of African ancestry with HIV in the UK

Background: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality globally. The risk of CKD is increased in people of African ancestry and with Human Immunodeficiency Virus (HIV) infection. Methods: We conducted a cross-sectional study investigating the relationship between region of ancestry (East, Central, South or West Africa) and kidney disease in people of sub-Saharan African ancestry with HIV in the UK between May 2018 and February 2020. The primary outcome was renal impairment (estimated glomerular filtration rate [eGFR] of 50 mg/mmol), and biopsy-confirmed HIV-associated nephropathy (HIVAN), focal segmental glomerulosclerosis (FSGS) or arterionephrosclerosis. Multivariable robust Poisson regression estimated the effect of region of African ancestry on kidney disease outcomes. Findings: Of the 2468 participants (mean age 48.1 [SD 9.8] years, 62% female), 193 had renal impairment, 87 stage 5 CKD, 126 proteinuria, and 43 HIVAN/FSGS or arterionephrosclerosis. After adjusting for demographic characteristics, HIV and several CKD risk factors and with East African ancestry as referent, West African ancestry was associated with renal impairment (prevalence ratio [PR] 2.06 [95% CI 1.40–3.04]) and stage 5 CKD (PR 2.23 [1.23–4.04]), but not with proteinuria (PR 1.27 [0.78–2.05]). West African ancestry (as compared to East/South African ancestry) was also strongly associated with a diagnosis of HIVAN/FSGS or arterionephrosclerosis on kidney biopsy (PR 6.44 [2.42–17.14]). Interpretation: Our results indicate that people of West African ancestry with HIV are at increased risk of kidney disease. Although we cannot rule out the possibility of residual confounding, geographical region of origin appears to be a strong independent risk factor for CKD as the association did not appear to be explained by several demographic, HIV or renal risk factors

Repulsively bound atom pairs in an optical lattice

Throughout physics, stable composite objects are usually formed via attractive forces, which allow the constituents to lower their energy by binding together. Repulsive forces separate particles in free space. However, in a structured environment such as a periodic potential and in the absence of dissipation, stable composite objects can exist even for repulsive interactions. Here we report on the first observation of such an exotic bound state, comprised of a pair of ultracold atoms in an optical lattice. Consistent with our theoretical analysis, these repulsively bound pairs exhibit long lifetimes, even under collisions with one another. Signatures of the pairs are also recognised in the characteristic momentum distribution and through spectroscopic measurements. There is no analogue in traditional condensed matter systems of such repulsively bound pairs, due to the presence of strong decay channels. These results exemplify on a new level the strong correspondence between the optical lattice physics of ultracold bosonic atoms and the Bose-Hubbard model, a correspondence which is vital for future applications of these systems to the study of strongly correlated condensed matter systems and to quantum information.Comment: 5 pages, 4 figure

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

Circulating microRNA's as a diagnostic tool for hepatocellular carcinoma in a hyper endemic HIV setting, KwaZulu-Natal, South Africa: a case control study protocol focusing on viral etiology.

BACKGROUND: A wide range of studies has investigated the diagnostic proficiency of extracellular microRNAs (miRNAs) in hepatocellular cancer (HCC). HCC is expected to increase in Sub-Saharan Africa (SSA), due to endemic levels of viral infection (HBV/HIV), ageing and changing lifestyles. This unique aetiological background provides an opportunity for investigating potentially novel circulating miRNAs as biomarkers for HCC in a prospective study in South Africa. METHODS: This study will recruit HCC patients from two South African cancer hospitals, situated in Durban and Pietermaritzburg in the province of KwaZulu-Natal. These cases will include both HBV mono-infected and HBV/HIV co-infected HCC cases. The control group will consist of two (2) age and sex-matched healthy population controls per HCC case randomly selected from a Durban based laboratory. The controls will exclude patients if they have any evidence of chronic liver disease. A standardised reporting approach will be adopted to detect, quantify and normalize the level of circulating miRNAs in the blood sera of HCC cases and their controls. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) will be employed to quantity extracellular miRNAs. Differences in concentration of relevant miRNA by case/control status will be assessed using the Wilcoxon rank-sum (Mann-Whitney U) test. Adjustment for multiple testing (Bonferroni correction), receiver operating curves (ROC) and optimal breakpoint analyses will be employed to identify potential thresholds for the differentiation of miRNA levels of HCC cases and their controls. DISCUSSION: Although there is a growing base of literature regarding the role of circulating miRNAs as biomarkers, this promising field remains a 'work in progress'. The aetiology of HBV infection in HCC is well understood, as well as it's role in miRNA deregulation, however, the mediating role of HIV infection is unknown. HCC incidence in SSA, including South Africa, is expected to increase significantly in the next decade. A combination of factors, therefore, offers a unique opportunity to identify candidate circulating miRNAs as potential biomarkers for HBV/HIV infected HCC

Balance between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in the cervical mucus plug estimated by determination of free non-complexed TIMP

<p>Abstract</p> <p>Background</p> <p>The cervical mucus plug (CMP) is a semi-solid structure with antibacterial properties positioned in the cervical canal during pregnancy. The CMP contains high concentrations of matrix metalloproteinase 8 and 9 (MMP-8, MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1). This indicates a potential to degrade extracellular matrix components depending on the balance between free non-complexed inhibitors and active enzymes.</p> <p>Methods</p> <p>Thirty-two CMPs collected during active labor at term were analyzed. Twelve CMPs were separated into a cellular and an extracellular/fluid phase and analyzed by gelatin and reverse zymography to reveal MMP and TIMP location. Twenty samples were homogenized, extracted and studied by the TIMP activity assay based on gelatin zymography. Enzyme-linked immunosorbent assay (ELISA) was used to determine TIMP-1, MMP-8 and MMP-9 protein concentrations, and gelatin and reverse zymography used to identify gelatinases and TIMPs, respectively. The Western blotting technique was applied for semi-quantification of alpha2-macroglobulin. An ELISA activity assay was used to detect MMP-8 and MMP-9 activity.</p> <p>Results</p> <p>ProMMP-2, proMMP-9, TIMP-1 and TIMP-2 were almost exclusively located in the fluid phase compared to the cellular phase of the CMP. All the extracted samples contained MMP-8, MMP-9, TIMP-1, TIMP-2 and alpha2-macroglobulin. Free non-complexed TIMP was detected in all the samples analyzed by the TIMP activity assay and was associated with TIMP-1 protein (R = 0.71, p < 0.001) and with the TIMP/MMP molar ratio (1.7 (1.1–2.5) (mean (95% confidence interval)) (R = 0.65, p = 0.002). The ELISA activity assay showed no activity from MMP-8 or MMP-9.</p> <p>Conclusion</p> <p>Due to their extracellular location, potential proteolytic activity from neutrophil-derived MMPs in the CMP could exert a biological impact on cervical dilatation and fetal membrane rupture at term. The functional TIMP activity assay, revealing excess non-complexed TIMP, and a molar inhibitor/enzyme ratio above unity, indicate that refined MMP control prevents CMP-originated proteolytic activity in the surrounding tissue.</p