Profile-Based Optimal Matchings in the Student-Project Allocation Problem

In the Student/Project Allocation problem (spa) we seek to assign students to individual or group projects offered by lecturers. Students provide a list of projects they find acceptable in order of preference. Each student can be assigned to at most one project and there are constraints on the maximum number of students that can be assigned to each project and lecturer. We seek matchings of students to projects that are optimal with respect to profile, which is a vector whose rth component indicates how many students have their rth-choice project. We present an efficient algorithm for finding agreedy maximum matching in the spa context – this is a maximum matching whose profile is lexicographically maximum. We then show how to adapt this algorithm to find a generous maximum matching – this is a matching whose reverse profile is lexicographically minimum. Our algorithms involve finding optimal flows in networks. We demonstrate how this approach can allow for additional constraints, such as lecturer lower quotas, to be handled flexibly

Physiological Indicators for User Trust in Machine Learning with Influence Enhanced Fact-Checking

© IFIP International Federation for Information Processing 2019. Trustworthy Machine Learning (ML) is one of significant challenges of “black-box” ML for its wide impact on practical applications. This paper investigates the effects of presentation of influence of training data points on machine learning predictions to boost user trust. A framework of fact-checking for boosting user trust is proposed in a predictive decision making scenario to allow users to interactively check the training data points with different influences on the prediction by using parallel coordinates based visualization. This work also investigates the feasibility of physiological signals such as Galvanic Skin Response (GSR) and Blood Volume Pulse (BVP) as indicators for user trust in predictive decision making. A user study found that the presentation of influences of training data points significantly increases the user trust in predictions, but only for training data points with higher influence values under the high model performance condition, where users can justify their actions with more similar facts to the testing data point. The physiological signal analysis showed that GSR and BVP features correlate to user trust under different influence and model performance conditions. These findings suggest that physiological indicators can be integrated into the user interface of AI applications to automatically communicate user trust variations in predictive decision making

Multiple Levels of Synergistic Collaboration in Termite Lignocellulose Digestion

In addition to evolving eusocial lifestyles, two equally fascinating aspects of termite biology are their mutualistic relationships with gut symbionts and their use of lignocellulose as a primary nutrition source. Termites are also considered excellent model systems for studying the production of bioethanol and renewable bioenergy from 2nd generation (non-food) feedstocks. While the idea that gut symbionts are the sole contributors to termite lignocellulose digestion has remained popular and compelling, in recent years host contributions to the digestion process have become increasingly apparent. However, the degree to which host and symbiont, and host enzymes, collaborate in lignocellulose digestion remain poorly understood. Also, how digestive enzymes specifically collaborate (i.e., in additive or synergistic ways) is largely unknown. In the present study we undertook translational-genomic studies to gain unprecedented insights into digestion by the lower termite Reticulitermes flavipes and its symbiotic gut flora. We used a combination of native gut tissue preparations and recombinant enzymes derived from the host gut transcriptome to identify synergistic collaborations between host and symbiont, and also among enzymes produced exclusively by the host termite. Our findings provide important new evidence of synergistic collaboration among enzymes in the release of fermentable monosaccharides from wood lignocellulose. These monosaccharides (glucose and pentoses) are highly relevant to 2nd-generation bioethanol production. We also show that, although significant digestion capabilities occur in host termite tissues, catalytic tradeoffs exist that apparently favor mutualism with symbiotic lignocellulose-digesting microbes. These findings contribute important new insights towards the development of termite-derived biofuel processing biotechnologies and shed new light on selective forces that likely favored symbiosis and, subsequently, group living in primitive termites and their cockroach ancestors

Antibody-Dependent Cell-Mediated Cytotoxicity Epitopes on the Hemagglutinin Head Region of Pandemic H1N1 Influenza Virus Play Detrimental Roles in H1N1-Infected Mice

Engaging the antibody-dependent cell-mediated cytotoxicity (ADCC) for killing of virus-infected cells and secretion of antiviral cytokines and chemokines was incorporated as one of the important features in the design of universal influenza vaccines. However, investigation of the ADCC epitopes on the highly immunogenic influenza hemagglutinin (HA) head region has been rarely reported. In this study, we determined the ADCC and antiviral activities of two putative ADCC epitopes, designated E1 and E2, on the HA head of a pandemic H1N1 influenza virus in vitro and in a lethal mouse model. Our data demonstrated that sera from the E1-vaccinated mice could induce high ADCC activities. Importantly, the induction of ADCC response modestly decreased viral load in the lungs of H1N1-infected mice. However, the elevated ADCC significantly increased mouse alveolar damage and mortality than that of the PBS-vaccinated group (P < 0.0001). The phenotype was potentially due to an exaggerated inflammatory cell infiltration triggered by ADCC, as an upregulated release of cytotoxic granules (perforin) was observed in the lung tissue of E1-vaccinated mice after H1N1 influenza virus challenge. Overall, our data suggested that ADCC elicited by certain domains of HA head region might have a detrimental rather than protective effect during influenza virus infection. Thus, future design of universal influenza vaccine shall strike a balance between the induction of protective immunity and potential side effects of ADCC.published_or_final_versio

Three-dimensional femtosecond laser nanolithography of crystals

Nanostructuring hard optical crystals has so far been exclusively feasible at their surface, as stress induced crack formation and propagation has rendered high precision volume processes ineffective. We show that the inner chemical etching reactivity of a crystal can be enhanced at the nanoscale by more than five orders of magnitude by means of direct laser writing. The process allows to produce cm-scale arbitrary three-dimensional nanostructures with 100 nm feature sizes inside large crystals in absence of brittle fracture. To showcase the unique potential of the technique, we fabricate photonic structures such as sub-wavelength diffraction gratings and nanostructured optical waveguides capable of sustaining sub-wavelength propagating modes inside yttrium aluminum garnet crystals. This technique could enable the transfer of concepts from nanophotonics to the fields of solid state lasers and crystal optics.Comment: Submitted Manuscript and Supplementary Informatio

Design, synthesis and biological characterization of novel inhibitors of CD38

Human CD38 is a novel multi-functional protein that acts not only as an antigen for B-lymphocyte activation, but also as an enzyme catalyzing the synthesis of a Ca 2+ messenger molecule, cyclic ADP-ribose, from NAD +. It is well established that this novel Ca 2+ signaling enzyme is responsible for regulating a wide range of physiological functions. Based on the crystal structure of the CD38/NAD + complex, we synthesized a series of simplified N-substituted nicotinamide derivatives (Compound1-14). A number of these compounds exhibited moderate inhibition of the NAD + utilizing activity of CD38, with Compound4 showing the highest potency. The crystal structure of CD38/Compound4 complex and computer simulation of Compound7 docking to CD38 show a significant role of the nicotinamide moiety and the distal aromatic group of the compounds for substrate recognition by the active site of CD38. Biologically, we showed that both Compounds4 and 7 effectively relaxed the agonist-induced contraction of muscle preparations from rats and guinea pigs. This study is a rational design of inhibitors for CD38 that exhibit important physiological effects, and can serve as a model for future drug development. © 2011 The Royal Society of Chemistry.postprin

Sybil tolerance and probabilistic databases to compute web services trust

© Springer International Publishing Switzerland 2015. This paper discusses how Sybil attacks can undermine trust management systems and how to respond to these attacks using advanced techniques such as credibility and probabilistic databases. In such attacks end-users have purposely different identities and hence, can provide inconsistent ratings over the same Web Services. Many existing approaches rely on arbitrary choices to filter out Sybil users and reduce their attack capabilities. However this turns out inefficient. Our approach relies on non-Sybil credible users who provide consistent ratings over Web services and hence, can be trusted. To establish these ratings and debunk Sybil users techniques such as fuzzy-clustering, graph search, and probabilistic databases are adopted. A series of experiments are carried out to demonstrate robustness of our trust approach in presence of Sybil attacks

Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes

Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human and equine subjects by examining the contractile responses of biopsied muscle strips exposed to caffeine, a potent RYR1 agonist. However, this test is not widely available and, due to its invasive nature, is potentially less suitable for valuable animals in training or in the human paediatric setting. Furthermore, increasingly, RYR1 gene polymorphisms (of unknown pathogenicity and significance) are being identified through next generation sequencing projects. Consequently, we have investigated a less invasive test that can be used to study calcium homeostasis in cultured, skin-derived fibroblasts that are converted to the muscle lineage by viral transduction with a MyoD (myogenic differentiation 1) transgene. Similar models have been utilised to examine calcium homeostasis in human patient cells, however, to date, there has been no detailed assessment of the cells’ calcium homeostasis, and in particular, the responses to agonists and antagonists of RYR1. Here we describe experiments conducted to assess calcium handling of the cells and examine responses to treatment with dantrolene, a drug commonly used for prophylaxis of recurrent exertional rhabdomyolysis in horses and malignant hyperthermia in humans