Memoryless Routing in Convex Subdivisions: Random Walks are Optimal

A memoryless routing algorithm is one in which the decision about the next edge on the route to a vertex t for a packet currently located at vertex v is made based only on the coordinates of v, t, and the neighbourhood, N(v), of v. The current paper explores the limitations of such algorithms by showing that, for any (randomized) memoryless routing algorithm A, there exists a convex subdivision on which A takes Omega(n^2) expected time to route a message between some pair of vertices. Since this lower bound is matched by a random walk, this result implies that the geometric information available in convex subdivisions is not helpful for this class of routing algorithms. The current paper also shows the existence of triangulations for which the Random-Compass algorithm proposed by Bose etal (2002,2004) requires 2^{\Omega(n)} time to route between some pair of vertices.Comment: 11 pages, 6 figure

Scalable Similarity Search for Molecular Descriptors

Similarity search over chemical compound databases is a fundamental task in the discovery and design of novel drug-like molecules. Such databases often encode molecules as non-negative integer vectors, called molecular descriptors, which represent rich information on various molecular properties. While there exist efficient indexing structures for searching databases of binary vectors, solutions for more general integer vectors are in their infancy. In this paper we present a time- and space- efficient index for the problem that we call the succinct intervals-splitting tree algorithm for molecular descriptors (SITAd). Our approach extends efficient methods for binary-vector databases, and uses ideas from succinct data structures. Our experiments, on a large database of over 40 million compounds, show SITAd significantly outperforms alternative approaches in practice.Comment: To be appeared in the Proceedings of SISAP'1

Assessing the Impact of Loyalty Program on Consumer Purchasing Behavior in Fine-Dining Restaurant

This study explores the influence of loyalty program on customer purchasing behavior in fine-dining restaurant. It examines the factors that motivate customers to enroll on the program and loyalty rewards customers’ prefer. Questionnaires were administered to 172 guests to solicit views on how loyalty programs impact on their purchasing behavior. The respondents were selected at random upon request to answer the questionnaires. Data was analyzed using SPSS version 16. The findings revealed that members of the loyalty programs showed positive attitude towards patronizing other restaurant products thereby increasing sales margin of the restaurants. Majority of the customers expressed the desire for immediate rewards such as discount. Food quality emerged as the major motivational factor to enroll on loyalty programs followed by environment and brand. The study concludes that, loyalty programs that are designed to match the target groups influence consumer-purchasing decision. The implication is that restaurant managers should continue to seek customers’ views on loyalty rewards as customers’ expectations change overtime. Furthermore, food quality should not be overlooked as customers begin to consider it as a motivational factor to enroll on loyalty programs in fine-dining restaurants. Keywords: Loyalty programs, Consumer Behavior, Fine-Dining Restauran

CO₂ gasification of bio-char derived from conventional and microwave pyrolysis

Thermal-chemical processing of biomass is expected to provide renewable and clean energy and fuels in the future. Due to the nature of endothermic reactions, microwave and conventional heating have been applied to this technology. However, more studies need to be carried out to clarify the difference between these two heating technologies. In this work, we investigated two bio-char samples produced from conventional pyrolysis of wood biomass (yield of bio-char: 38.48 and 59.70 wt.%, respectively) and one bio-char produced from microwave pyrolysis with a yield of 45.16 wt.% from the same biomass sample at different process conditions. Various methodologies have been used to characterise the bio-chars. CO₂ gasification of bio-char has also been studied using a thermogravimetric analyser (TGA) and a fixed-bed reaction system. The results show that volatile and carbon contents of the bio-char derived from microwave pyrolysis were between the two conventional bio-chars. However, the microwave bio-char is more reactive for CO₂ gasification, as more CO was released during TGA experiments, and the CO release peak was narrower compared with the CO₂ gasification of the conventional bio-chars. It is suggested that the conventional bio-char is less reactive due to the presence of more secondary chars which are produced from secondary reactions of volatiles during the conventional biomass pyrolysis. While the microwave pyrolysis generates more uniform bio-chars with less secondary char, and therefore, has advantages of producing bio-char for downstream char gasification

Multi-Resolution Sensitivity Analysis of Model of Immune Response to Helicobacter pylori Infection via Spatio-Temporal Metamodeling

Computational immunology studies the interactions between the components of the immune system that includes the interplay between regulatory and inflammatory elements. It provides a solid framework that aids the conversion of pre-clinical and clinical data into mathematical equations to enable modeling and in silico experimentation. The modeling-driven insights shed lights on some of the most pressing immunological questions and aid the design of fruitful validation experiments. A typical system of equations, mapping the interaction among various immunological entities and a pathogen, consists of a high-dimensional input parameter space that could drive the stochastic system outputs in unpredictable directions. In this paper, we perform spatio-temporal metamodel-based sensitivity analysis of immune response to Helicobacter pylori infection using the computational model developed by the ENteric Immune SImulator (ENISI). We propose a two-stage metamodel-based procedure to obtain the estimates of the Sobol' total and first-order indices for each input parameter, for quantifying their time-varying impacts on each output of interest. In particular, we fully reuse and exploit information from an existing simulated dataset, develop a novel sampling design for constructing the two-stage metamodels, and perform metamodel-based sensitivity analysis. The proposed procedure is scalable, easily interpretable, and adaptable to any multi-input multi-output complex systems of equations with a high-dimensional input parameter space

Machine vision-assisted analysis of structure-localization relationships in a combinatorial library of prospective bioimaging probes

With a combinatorial library of bioimaging probes, it is now possible to use machine vision to analyze the contribution of different building blocks of the molecules to their cell-associated visual signals. For this purpose, cell-permeant, fluorescent styryl molecules were synthesized by condensation of 168 aldehyde with 8 pyridinium/quinolinium building blocks. Images of cells incubated with fluorescent molecules were acquired with a high content screening instrument. Chemical and image feature analysis revealed how variation in one or the other building block of the styryl molecules led to variations in the molecules' visual signals. Across each pair of probes in the library, chemical similarity was significantly associated with spectral and total signal intensity similarity. However, chemical similarity was much less associated with similarity in subcellular probe fluorescence patterns. Quantitative analysis and visual inspection of pairs of images acquired from pairs of styryl isomers confirm that many closely-related probes exhibit different subcellular localization patterns. Therefore, idiosyncratic interactions between styryl molecules and specific cellular components greatly contribute to the subcellular distribution of the styryl probes' fluorescence signal. These results demonstrate how machine vision and cheminformatics can be combined to analyze the targeting properties of bioimaging probes, using large image data sets acquired with automated screening systems. © 2009 International Society for Advancement of CytometryPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63004/1/20713_ftp.pd

Abundant sub-micron grains revealed in newly discovered extreme debris discs

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this record DATA AVAILABILITY: The VISIR data used in this paper are publicly available at ESO Archive (http://archive.eso.org/eso/eso_archive_main. html).Extreme debris discs (EDDs) are bright and warm circumstellar dusty structures around main sequence stars. They may represent the outcome of giant collisions occuring in the terrestrial region between large planetesimals or planetary bodies, and thus provide a rare opportunity to peer into the aftermaths of these events. Here, we report on results of a mini-survey we conducted with the aim to increase the number of known EDDs, investigate the presence of solid-state features around 10 μm in eight EDDs, and classify them into the silica or silicate dominated groups. We identify four new EDDs and derive their fundamental properties. For these, and for four other previously known discs, we study the spectral energy distribution around 10 μm by means of VLT/VISIR photometryin three narrow-band filters and conclude that all eight objects likely exhibit solid-state emission features from sub-micron grains. We find that four discs probably belong to the silicate dominated subgroup. Considering the age distribution of the entire EDD sample, we find that their incidence begins to decrease only after 300 Myr, suggesting that the earlier common picture that these objects are related to the formation of rocky planets may not be exclusive, and that other processes may be involved for older objects (≳100 Myr). Because most of the older EDD systems have wide, eccentric companions, we suggest that binarity may play a role in triggering late giant collisions.Hungarian National Research, Development and Innovation OfficeHungarian National Research, Development and Innovation OfficeBolyai+Royal SocietyNASANASAHungarian Academy of Science

Novel fibronectin mutations and expansion of the phenotype in spondylometaphyseal dysplasia with “corner fractures”

Heterozygous pathogenic variants in the FN1 gene, encoding fibronectin (FN), have recently been shown to be associated with a skeletal disorder in some individuals affected by spondylometaphyseal dysplasia with “corner fractures” (SMD-CF). The most striking feature characterizing SMD-CF is irregularly shaped metaphyses giving the appearance of “corner fractures”. An array of secondary features, including developmental coxa vara, ovoid vertebral bodies and severe scoliosis, may also be present. FN is an important extra cellular matrix component for bone and cartilage development. Here we report five patients affected by this subtype of SMD-CF caused by five novel FN1 missense mutations: p.Cys123Tyr, p.Cys169Tyr, p.Cys213Tyr, p.Cys231Trp and p.Cys258Tyr. All individuals shared a substitution of a cysteine residue, disrupting disulfide bonds in the FN type-I assembly domains located in the N-terminal assembly region. The abnormal metaphyseal ossification and “corner fracture” appearances were the most remarkable clinical feature in these patients. In addition, generalized skeletal fragility with low-trauma bilateral femoral fractures was identified in one patient. Interestingly, the distal femoral changes in this patient healed with skeletal maturation. Our report expands the phenotypic and genetic spectrum of the FN1-related SMD-CF and emphasizes the importance of FN in bone formation and possibly also in the maintenance of bone strength.Peer reviewe

A potent antimalarial benzoxaborole targets a Plasmodium falciparum cleavage and polyadenylation specificity factor homologue.

Benzoxaboroles are effective against bacterial, fungal and protozoan pathogens. We report potent activity of the benzoxaborole AN3661 against Plasmodium falciparum laboratory-adapted strains (mean IC50 32 nM), Ugandan field isolates (mean ex vivo IC50 64 nM), and murine P. berghei and P. falciparum infections (day 4 ED90 0.34 and 0.57 mg kg-1, respectively). Multiple P. falciparum lines selected in vitro for resistance to AN3661 harboured point mutations in pfcpsf3, which encodes a homologue of mammalian cleavage and polyadenylation specificity factor subunit 3 (CPSF-73 or CPSF3). CRISPR-Cas9-mediated introduction of pfcpsf3 mutations into parental lines recapitulated AN3661 resistance. PfCPSF3 homology models placed these mutations in the active site, where AN3661 is predicted to bind. Transcripts for three trophozoite-expressed genes were lost in AN3661-treated trophozoites, which was not observed in parasites selected or engineered for AN3661 resistance. Our results identify the pre-mRNA processing factor PfCPSF3 as a promising antimalarial drug target