pinecone/core-2020-05-10-deduplication huggingface dataset:
The high bone mass phenotype is characterised by a combined cortical and trabecular bone phenotype: Findings from a pQCT case–control study

AbstractHigh bone mass (HBM), detected in 0.2% of DXA scans, is characterised by a mild skeletal dysplasia largely unexplained by known genetic mutations. We conducted the first systematic assessment of the skeletal phenotype in unexplained HBM using pQCT in our unique HBM population identified from screening routine UK NHS DXA scans.pQCT measurements from the mid and distal tibia and radius in 98 HBM cases were compared with (i) 65 family controls (constituting unaffected relatives and spouses), and (ii) 692 general population controls.HBM cases had substantially greater trabecular density at the distal tibia (340 [320, 359] mg/cm3), compared to both family (294 [276, 312]) and population controls (290 [281, 299]) (p<0.001 for both, adjusted for age, gender, weight, height, alcohol, smoking, malignancy, menopause, steroid and estrogen replacement use). Similar results were obtained at the distal radius. Greater cortical bone mineral density (cBMD) was observed in HBM cases, both at the midtibia and radius (adjusted p<0.001). Total bone area (TBA) was higher in HBM cases, at the distal and mid tibia and radius (adjusted p<0.05 versus family controls), suggesting greater periosteal apposition. Cortical thickness was increased at the mid tibia and radius (adjusted p<0.001), implying reduced endosteal expansion. Together, these changes resulted in greater predicted cortical strength (strength strain index [SSI]) in both tibia and radius (p<0.001). We then examined relationships with age; tibial cBMD remained constant with increasing age amongst HBM cases (adjusted β −0.01 [−0.02, 0.01], p=0.41), but declined in family controls (−0.05 [−0.03, −0.07], p<0.001) interaction p=0.002; age-related changes in tibial trabecular BMD, CBA and SSI were also divergent. In contrast, at the radius HBM cases and controls showed parallel age-related declines in cBMD and trabecular BMD.HBM is characterised by increased trabecular BMD and by alterations in cortical bone density and structure, leading to substantial increments in predicted cortical bone strength. In contrast to the radius, neither trabecular nor cortical BMD declined with age in the tibia of HBM cases, suggesting attenuation of age-related bone loss in weight-bearing limbs contributes to the observed bone phenotype
Biomolecule Association Rates Do Not Provide a Complete Description of Bond Formation

AbstractThe efficiency of many cell-surface receptors is dependent on the rate of binding soluble or surface-attached ligands. Much effort was exerted to measure association rates between soluble molecules (three-dimensional kon) and, more recently, between surface-attached molecules (two-dimensional [2D] kon). According to a generally accepted assumption, the probability of bond formation between receptors and ligands is proportional to the first power of encounter duration. Here we provide new experimental evidence and review published data demonstrating that this simple assumption is not always warranted. Using as a model system the (2D) interaction between ICAM-1-coated surfaces and flowing microspheres coated with specific anti-ICAM-1 antibodies, we show that the probability of bond formation may scale as a power of encounter duration that is significantly higher than 1. Further, we show that experimental data may be accounted for by modeling ligand-receptor interaction as a displacement along a single path of a rough energy landscape. Under a wide range of conditions, the probability that an encounter of duration t resulted in bond formation varied as erfc[(t0/t)1/2], where t0 was on the order of 10 ms. We conclude that the minimum contact time for bond formation may be a useful parameter to describe a ligand-receptor interaction, in addition to conventional association rates
A non-human hepadnaviral adjuvant for hepatitis C virus-based genetic vaccines

AbstractHuman hepatitis B virus (HBV) core antigen (HBcAg) can act as an adjuvant in hepatitis C virus (HCV)-based DNA vaccines. Since two billion people are, or have been, in contact with HBV, one may question the use of human HBV sequences as adjuvant. We herein evaluated non-human stork hepatitis B virus core gene-sequences from stork as DNA vaccine adjuvants. Full-length and fragmented stork HBcAg gene-sequences were added to an HCV non-structural (NS) 3/4A gene (NS3/4A-stork-HBcAg). This resulted in an enhanced priming of HCV-specific IFN-γ and IL-2 responses in both wild-type (wt)- and NS3/4A-transgenic (Tg) mice, the latter with dysfunctional NS3/4A-specific T cells. The NS3/4A-stork-HBcAg vaccine primed NS3/4A-specific T cells in hepatitis B e antigen (HBeAg)-Tg mice with dysfunctional T cells to HBcAg and HBeAg. Repeated immunizations boosted expansion of IFN-γ and IL-2-producing NS3/4A-specific T cells in wt- and NS3/4A-Tg mice. Importantly, NS3/4A-stork-HBcAg-DNA induced in vivo long-term functional memory T cell responses, whose maintenance required CD4+ T cells. Thus, avian HBcAg gene-sequences from stork can effectively act as a DNA vaccine adjuvant. This technology can most likely be universally expanded to other genetic vaccine antigens, as this completely avoids the use of sequences from a human virus where a pre-existing immunity may interfere with its adjuvant effect
Hybrid Simulators for Product Service-Systems – Innovation Potential Demonstrated on Urban Bike Mobility

AbstractOne major goal of the Rethinking Prototyping project is to bring scientists from different domains like engineering and arts to explore collaboratively new approaches of development and testing of Product Service Systems (PSS). PSS combine products, services, and infrastructure to fulfil individual customer needs. Therefore, the development of PSS is an extension of traditional engineering design process, which mainly refers to purely tangible products or intangible services into an integrated development process of products and services.The basis is a new technology called Smart Hybrid Prototyping (SHP), a joint development by Fraunhofer IPK and the TU Berlin. SHP is an innovative technology for a multimodal interdisciplinary evaluation of virtual prototypes in early development stages. It is based upon methods of Mixed Reality extended by modern industrial technologies to allow natural interaction with virtual prototypes of mechanical or mechatronic systems. It serves as a bridge between physical reality and digital virtuality.The use cases in this paper are based on urban bike mobility. Therefore, three concepts have been worked out to specify main requirements for an urban hybrid bike simulator. The first use case is from the perspective of a bicycle rental, where rental services for the users can be developed, validated, and optimized. The second use case provides the integration of mobile devices like smartphones and tablets for the development and validation of mobile services for bicyclists. The third use case is oriented on development and validation of new bicycles and urban mobility concepts like e-bikes, pedelecs, tripelecs and sharing services. Based on these generic use cases the requirements on a hybrid bicycle simulator were derived.Why a bicycle simulator? Well, we are firmly convinced that the future of urban mobility is determined from trends such as ecological rethinking and the desire for sports and healthy life. Furthermore, it is one of the most competitive and agile markets using most innovative materials and manufacturing technologies
Functional phage display of leech-derived tryptase inhibitor (LDTI): construction of a library and selection of thrombin inhibitors11Enzymes: thrombin (EC 3.4.21.5); trypsin (EC 3.4.21.4); plasma kallikrein (EC 3.4.21.34); factor Xa (EC 3.4.21.6); plasmin (EC 3.4.21.7); neutrophil elastase (EC 3.4.21.37).

AbstractThe recombinant phage antibody system pCANTAB 5E has been used to display functionally active leech-derived tryptase inhibitor (LDTI) on the tip of the filamentous M13 phage. A limited combinatorial library of 5.2×104 mutants was created with a synthetic LDTI gene, using a degenerated oligonucleotide and the pCANTAB 5E phagemid. The mutations were restricted to the P1–P4′ positions of the reactive site. Fusion phages and appropriate host strains containing the phagemids were selected after binding to thrombin and DNA sequencing. The variants LDTI-2T (K8R, I9V, S10, K11W, P12A), LDTI-5T (K8R, I9V, S10, K11S, P12L) and LDTI-10T (K8R, I9L, S10, K11D, P12I) were produced with a Saccharomyces cerevisiae expression system. The new inhibitors, LDTI-2T and -5T, prolong the blood clotting time, inhibit thrombin (Ki 302 nM and 28 nM) and trypsin (Ki 6.4 nM and 2.1 nM) but not factor Xa, plasma kallikrein or neutrophil elastase. The variant LDTI-10T binds to thrombin but does not inhibit it. The relevant reactive site sequences of the thrombin inhibiting variants showed a strong preference for arginine in position P1 (K8R) and for valine in P1′ (I9V). The data indicate further that LDTI-5T might be a model candidate for generation of active-site directed thrombin inhibitors and that LDTI in general may be useful to generate specific inhibitors suitable for a better understanding of enzyme-inhibitor interactions
Challenges in Risk Assessment: Quantitative Risk Assessment

AbstractThe process of risk analysis consists out of three components, risk assessment, risk management and risk communication. These components are internationally well spread by Codex Alimentarius Commission as being the basis for setting science based standards, criteria on food safety hazards, e.g. setting maximum limits of mycotoxins in foodstuffs. However, the technical component risk assessment is hard to elaborate and to understand. Key in a risk assessment is the translation of biological or chemical pathways into a mathematical framework. Within the International Training Program ‘ITP food safety, quality assurance and risk analysis’ of Ghent University, department of Food Safety and Food Quality, we developed for low and middle income countries and emerging countries a training module on risk assessment. In where (semi-) quantitative probabilistic risk assessment calculations or qualitative risk rankings are trained for both microbial and chemical food safety hazards along the agro-food chain. This presentation will explain these methodologies demonstrated with examples from former ITP trainees
Detecting induced star-like minors in polynomial time

AbstractThe Induced Minor problem is to test whether a graph G contains a graph H as an induced minor, i.e., if G can be modified into H by a sequence of vertex deletions and edge contractions. When H is fixed, i.e., not part of the input, this problem is denoted H-Induced Minor. We provide polynomial-time algorithms for this problem in the case that the fixed target graph has a star-like structure. In particular, we show polynomial-time solvability for all forests H on at most seven vertices except for one such case
Generalized μ–τ symmetry and discrete subgroups of O(3)

AbstractThe generalized μ–τ interchange symmetry in the leptonic mixing matrix U corresponds to the relations: |Uμi|=|Uτi| with i=1,2,3. It predicts maximal atmospheric mixing and maximal Dirac CP violation given θ13≠0. We show that the generalized μ–τ symmetry can arise if the charged lepton and neutrino mass matrices are invariant under specific residual symmetries contained in the finite discrete subgroups of O(3). The groups A4, S4 and A5 are the only such groups which can entirely fix U at the leading order. The neutrinos can be (a) non-degenerate or (b) partially degenerate depending on the choice of their residual symmetries. One obtains either vanishing or very large θ13 in case of (a) while only A5 can provide θ13 close to its experimental value in the case (b). We provide an explicit model based on A5 and discuss a class of perturbations which can generate fully realistic neutrino masses and mixing maintaining the generalized μ–τ symmetry in U. Our approach provides generalization of some of the ideas proposed earlier in order to obtain the predictions, θ23=π/4 and δCP=±π/2
SoLid: Search for Oscillations with Lithium-6 Detector at the SCK-CEN BR2 reactor

AbstractSterile neutrinos have been considered as a possible explanation for the recent reactor and Gallium anomalies arising from reanalysis of reactor flux and calibration data of previous neutrino experiments. A way to test this hypothesis is to look for distortions of the anti-neutrino energy caused by oscillation from active to sterile neutrino at close stand-off (∼6–8m) of a compact reactor core. Due to the low rate of anti-neutrino interactions the main challenge in such measurement is to control the high level of gamma rays and neutron background.The SoLid experiment is a proposal to search for active-to-sterile anti-neutrino oscillation at very short baseline of the SCK•CEN BR2 research reactor.This experiment uses a novel approach to detect anti-neutrino with a highly segmented detector based on Lithium-6. With the combination of high granularity, high neutron-gamma discrimination using 6LiF:ZnS(Ag) and precise localization of the Inverse Beta Decay products, a better experimental sensitivity can be achieved compared to other state-of-the-art technology. This compact system requires minimum passive shielding allowing for very close stand off to the reactor. The experimental set up of the SoLid experiment and the BR2 reactor will be presented. The new principle of neutrino detection and the detector design with expected performance will be described. The expected sensitivity to new oscillations of the SoLid detector as well as the first measurements made with the 8 kg prototype detector deployed at the BR2 reactor in 2013–2014 will be reported
Overcoming Chemical, Biological, and Computational Challenges in the Development of Inhibitors Targeting Protein-Protein Interactions

Protein-protein interactions (PPIs) underlie the majority of biological processes, signaling, and disease. Approaches to modulate PPIs with small molecules have therefore attracted increasing interest over the past decade. However, there are a number of challenges inherent in developing small-molecule PPI inhibitors that have prevented these approaches from reaching their full potential. From target validation to small-molecule screening and lead optimization, identifying therapeutically relevant PPIs that can be successfully modulated by small molecules is not a simple task. Following the recent review by Arkin et al., which summarized the lessons learnt from prior successes, we focus in this article on the specific challenges of developing PPI inhibitors and detail the recent advances in chemistry, biology, and computation that facilitate overcoming them. We conclude by providing a perspective on the field and outlining four innovations that we see as key enabling steps for successful development of small-molecule inhibitors targeting PPIs
On isometric full embeddings of symplectic dual polar spaces into Hermitian dual polar spaces

AbstractLet n⩾2, let K,K′ be fields such that K′ is a quadratic Galois-extension of K and let θ denote the unique nontrivial element in Gal(K′/K). Suppose the symplectic dual polar space DW(2n-1,K) is fully and isometrically embedded into the Hermitian dual polar space DH(2n-1,K′,θ). We prove that the projective embedding of DW(2n-1,K) induced by the Grassmann-embedding of DH(2n-1,K′,θ) is isomorphic to the Grassmann-embedding of DW(2n-1,K). We also prove that if n is even, then the set of points of DH(2n-1,K′,θ) at distance at most n2-1 from DW(2n-1,K) is a hyperplane of DH(2n-1,K′,θ) which arises from the Grassmann-embedding of DH(2n-1,K′,θ)
Arene ruthenium dithiolato–carborane complexes for boron neutron capture therapy (BNCT)

AbstractWe report the effect of low-energy thermal neutron irradiation on the antiproliferative activities of a highly hydrophobic organometallic arene ruthenium dithiolato–carborane complex [Ru(p-cymene) (1,2-dicarba-closo-dodecarborane-1,2-dithiolato)] (1), and of its formulation in Pluronic® triblock copolymer P123 core–shell micelles (RuMs). Complex 1 was highly active, with and without neutron irradiation, towards human ovarian cancer cells (A2780; IC50 0.14 μM and 0.17 μM, respectively) and cisplatin-resistant human ovarian cancer cells (A2780cisR; IC50 0.05 and 0.13 μM, respectively). Complex 1 was particularly sensitive to neutron irradiation in A2780cisR cells (2.6 × more potent after irradiation compared to non-irradiation). Although less potent, the encapsulated complex 1 as RuMs nanoparticles resulted in higher cellular accumulation (2.5×), and was sensitive to neutron irradiation in A2780 cells (1.4× more potent upon irradiation compared to non-irradiation)
Improved light-cone sum rules for the electromagnetic form factors of the nucleon

AbstractWe calculate the electromagnetic form factors of the nucleon within the light-cone sum rule approach. In comparison to previous work [Phys. Rev. D 65 (2002) 074011] we suggest to use a pure isospin-1/2 interpolating field for the nucleon, since the Chernyak–Zhitnitsky current leads to numerically large, unphysical, isospin violating contributions. The leading-order sum rules are derived for the form factors and the results are confronted with the experimental data. Our approach tends to favor the nucleon distribution amplitudes that are not far from the asymptotic shape
Thermophysical Properties of Silicon Dioxide (SiO2) in Ethylene Glycol/Water Mixture for Proton Exchange Membrane Fuel Cell Cooling Application

AbstractPolymer Electrolyte Membrane Fuel Cells (PEMFC) operation is sensitive to micro electrochemical changes and can only tolerate a small temperature variation for optimal power generation. An effective cooling system is needed to comply with this condition. Nanofluids are perceived as a potential coolant for thermal management in PEMFC application that allows for more compact design. The dispersion of nanofluid in water-ethylene glycol base fluid enhances the thermal conductivity for improved heat transfer. The thermal conductivity, viscosity and electrical conductivity of different Silicon Dioxide (SiO2) concentrations diluted in Ethylene Glycol/Water (EG/W) mixtures of 40EG, 50EG and 60EG are reported. However, the electrical conductivity would contribute to electrical leakage and is a limiting factor for fuel cell operation. Highest value of thermal conductivity recorded is the dispersion of nanofluid in 40EG whereas the viscosity of SiO2 is the highest in 60EG dilution. Electrical conductivity is recorded the highest in EG/W 40:60% with 0.5% of SiO2. However, the electrical conductivity would contribute to electrical leakage and is a limiting factor for fuel cell operation
Neutron-19C scattering: Emergence of universal properties in a finite range potential

AbstractThe low-energy properties of the elastic s-wave scattering for the n-19C are studied near the critical condition for the occurrence of an excited Efimov state in n–n-18C. It is established to which extent the universal scaling laws, strictly valid in the zero-range limit, survive when finite range potentials are considered. By fixing the two-neutrons separation energy in 20C with available experimental data, it is studied the scaling of the real (δ0R) and imaginary parts of the s-wave phase-shift with the variation of the n-18C binding energy. We obtain some universal characteristics given by the pole-position of kcot⁡(δ0R) and effective-range parameters. By increasing the n-18C binding energy, it was verified that the excited state of 20C goes to a virtual state, resembling the neutron–deuteron behavior in the triton. It is confirmed that the analytical structure of the unitary cut is not affected by the range of the potential or mass asymmetry of the three-body system
An improved multiple model particle filtering approach for manoeuvring target tracking using airborne GMTI with geographic information

AbstractThis paper proposes a ground vehicle tracking method using an airborne ground moving target indicator radar where the surrounding geographic information is considered to determine vehicle's movement type as well as constrain its positions. Multiple state models corresponding to different movement modes are applied to represent the vehicle's behaviour in different terrain conditions. Based on geographic conditions and multiple state models, a constrained variable structure multiple model particle filter algorithm is proposed. Compared with the traditional multiple model particle filtering schemes, the proposed algorithm utilises a particle swarm optimisation technique which generates more effective particles and generated particles are constrained into the feasible geographic region. Numerical simulation results in a realistic environment show that the proposed method achieves better tracking performance compared with current state-of-the-art ones for manoeuvring vehicle tracking
4-coloring H-free graphs when H is small

AbstractThe k-Coloring problem is to test whether a graph can be colored with at most k colors such that no two adjacent vertices receive the same color. If a graph G does not contain a graph H as an induced subgraph, then G is called H-free. For any fixed graph H on at most six vertices, it is known that 3-Coloring is polynomial-time solvable on H-free graphs whenever H is a linear forest, and NP-complete otherwise. By solving the missing case P2+P3, we prove the same result for 4-Coloring provided that H is a fixed graph on at most five vertices
A non-trivial zero length limit of the Nambu–Goto string

AbstractWe show that a Nambu–Goto string has a nontrivial zero length limit which corresponds to a massless particle with extrinsic curvature. The system has the set of six first class constraints, which restrict the phase space variables so that the spin vanishes. Upon quantization, we obtain six conditions on the state, which can be represented as a wave function of position coordinates, xμ, and velocities, qμ. We have found a wave function ψ(x,q) that turns out to be a general solution of the corresponding system of six differential equations, if the dimensionality of spacetime is eight. Although classically the system is just a point particle with vanishing extrinsic curvature and spin, the quantized system is not trivial, because it is consistent in eight, but not in arbitrary, dimensions