Conditional Hardness of Earth Mover Distance

The Earth Mover Distance (EMD) between two sets of points A, B subseteq R^d with |A| = |B| is the minimum total Euclidean distance of any perfect matching between A and B. One of its generalizations is asymmetric EMD, which is the minimum total Euclidean distance of any matching of size |A| between sets of points A,B subseteq R^d with |A| <= |B|. The problems of computing EMD and asymmetric EMD are well-studied and have many applications in computer science, some of which also ask for the EMD-optimal matching itself. Unfortunately, all known algorithms require at least quadratic time to compute EMD exactly. Approximation algorithms with nearly linear time complexity in n are known (even for finding approximately optimal matchings), but suffer from exponential dependence on the dimension. In this paper we show that significant improvements in exact and approximate algorithms for EMD would contradict conjectures in fine-grained complexity. In particular, we prove the following results: - Under the Orthogonal Vectors Conjecture, there is some c>0 such that EMD in Omega(c^{log^* n}) dimensions cannot be computed in truly subquadratic time. - Under the Hitting Set Conjecture, for every delta>0, no truly subquadratic time algorithm can find a (1 + 1/n^delta)-approximate EMD matching in omega(log n) dimensions. - Under the Hitting Set Conjecture, for every eta = 1/omega(log n), no truly subquadratic time algorithm can find a (1 + eta)-approximate asymmetric EMD matching in omega(log n) dimensions

An Investigation of Neural Stimulation Efficiency With Gaussian Waveforms

Objective: Previous computational studies predict that Gaussian shaped waveforms use the least energy to activate nerves. The primary goal of this study was to examine the claimed potential of up to 60% energy savings with these waveforms over a range of phase widths (50- $200~\mu \text{s}$ ) in an animal model. Methods: The common peroneal nerve of anaesthetized rats was stimulated via monopolar and bipolar electrodes with single stimuli. The isometric peak twitch force of the extensor digitorum longus muscle was recorded to indicate the extent of neural activation. The energy consumption, charge injection and maximum instantaneous power values required to reach 50% neural activation were compared between Gaussian pulses and standard rectangular stimuli. Results: Energy savings in the 50- $200~\mu \text{s}$ range of phase widths did not exceed 17% and were accompanied by significant increases in maximum instantaneous power of 110-200%. Charge efficiency was found to be increased over the whole range of tested phase widths with Gaussian compared to rectangular pulses and reached up to 55% at 1ms phase width. Conclusion: These findings challenge the claims of up to 60% energy savings with Gaussian like stimulation waveforms. The moderate energy savings achieved with the novel waveform are accompanied with considerable increases in maximal instantaneous power. Larger power sources would therefore be required, and this opposes the trend for implant miniaturization. Significance: This is the first study to comprehensively investigate stimulation efficiency of Gaussian waveforms. It sheds new light on the practical potential of such stimulation waveforms

The Effect of Sub-Threshold Pre-Pulses on Neural Activation Depends on Electrode Configuration

IEEE Objective: Published research on nerve stimulation with sub-threshold conditioning pre-pulses is contradictory. Like most early research on electrical stimulation (ES), the pioneer work on the use of pre-pulses was modelled and measured only for monopolar electrodes. However, many contemporary ES applications, including miniaturized neuromodulation implants, known as electroceuticals, operate in bipolar mode. Methods: We compared depolarizing (DPPs) and hyperpolarizing (HPPs) pre-pulses on neural excitability in rat nerve with monopolar and bipolar electrodes. The rat common peroneal nerve was stimulated with biphasic stimuli with and without ramp and square DPPs or HPPs of 1, 5 and 10ms duration and 10% - 20% of the amplitude of the following pulse. Results: The effects were opposite for the monopolar and bipolar configurations. With monopolar electrodes DPPs increased the amplitude required to activate 50% of the motoneuron pool (between 0.7% and 10.3%) and HPPs decreased the threshold (between 1.7% and 4.7%). With bipolar electrodes both pre-pulse types had the opposite effect: DPPs decreased thresholds (between 1.8% and 5.5%) whereas HPPs increased thresholds (between 0.5% and 4.1%). Electroneurograms from the stimulated nerve revealed spatial and temporal differences in action potential generation for monopolar and bipolar electrodes. In bipolar biphasic stimulation, excitation first occurred at the return electrode as a response to the transition between the cathodic and anodic phase. Conclusion: These data help to resolve the contradictions in the published data over two decades. Significance: They also show that fundamental research carried out in monopolar configuration is not directly applicable to contemporary bipolar ES applications

ULearn: personalized medical learning on the web for patient empowerment

Health literacy constitutes an important step towards patient empowerment and the Web is presently the biggest repository of medical information and, thus, the biggest medical resource to be used in the learning process. However, at present, web medical information is mainly accessed through generic search engines that do not take into account the user specific needs and starting knowledge and so they are not able to support learning activities tailored to the specific user requirements. This work presents “ULearn” a meta engine that supports access, understanding and learning on the Web in the medical domain based on specific user requirements and knowledge levels towards what we call “balanced learning”. Balanced learning allows users to perform learning activities based on specific user requirements (understanding, deepening, widening and exploring) towards his/her empowerment. We have designed and developed ULearn to suggest search keywords correlated to the different user requirements and we have carried out some preliminary experiments to evaluate the effectiveness of the provided information

Optimal strategies for electrical stimulation with implantable neuromodulation devices

Electrical stimulation (ES) is a neuromodulation technique that uses electrical pulses to modulate the activity of excitable cells to provide a therapeutic effect. Many past and present ES applications use rectangular current waveforms that have been well studied and are easy to generate. However, an extensive body of scientific literature describes different stimulation waveforms and their potential benefits. A key measure of stimulation performance is the amplitude required to reach a certain percentual threshold of activation, as it directly influences important ES parameters such as energy consumption per pulse and charge density. The research summarized in this thesis was conducted to re-examine some of the most-commonly suggested ES waveform variations in a rodent in-vivo nerve-muscle preparation. A key feature of our experimental model is the ability to test stimulation with both principal electrode configurations, monopolar and bipolar, under computer control and in randomized order. Among the rectangular stimulation waveforms, we investigated the effect of interphase gaps (IPGs), asymmetric charge balanced pulses, and subthreshold conditioning pre-pulses. For all these rectangular waveforms, we surprisingly observed opposite effects in the monopolar compared to the bipolar stimulation electrode configuration. The rationale for this consistent observation was identified by analyzing electroneurograms (ENGs) of the stimulated nerve. In the monopolar configuration, biphasic pulses first evoked compound action potentials (eCAPs) as a response to the first field transition. In the bipolar electrode configuration, that is the mode in which many contemporary ES devices, including the envisioned miniaturized electroceuticals, operate, eCAPs were first elicited at the return electrode in response to the middle field transition of biphasic pulses. As all rectangular waveform variations achieve their effect by modulating the amplitude and timing of cathodic (excitatory) and anodic (inhibitory) field transitions, the inverted current profile at the bipolar return electrode explains these observed opposite effects. Further we investigated the claimed benefits of non-rectangular, Gaussian stimulation waveforms in our animal model. In our study only moderate energy savings of up to 17% were observed, a finding that is surprising in light of the predicted range of benefits of up to 60% energy savings with this novel waveform in question. Additionally, we identified a major disadvantage in terms of substantially increased maximum instantaneous power requirements with Gaussian compared to rectangular stimuli. We examined physiological changes in fast twitch muscle following motor nerve injury, and optimal stimulation strategies for activation of denervated muscle. While a high frequency doublet has previously been identified to enhance stimulation efficiency of healthy fast twitch muscle, an effect that has been termed “doublet effect”, we here show that this benefit is gradually lost in muscle during denervation. Lastly, the effect of long duration stimulation pulses, that are required to activate denervated muscle, on nerve is examined. We show that these long pulses can activate nerves up to three times when the three field transition within the biphasic pulses are separated by more than (i.e., when the phase width is above) the refractory period of that nerve. This observation challenges state-of-the-art computational models of extracellular nerve stimulation that do not seem to predict such multiple activations. Further, an undesired up to threefold co-activation of innervated structures nearby the denervated stimulation target warrants further research to study whether these co-activations can be lessened with alternative stimulation waveforms such as ramped sawtooth pulses

Personality and local brain structure: Their shared genetic basis and reproducibility

Local cortical architecture is highly heritable and distinct genes are associated with specific cortical regions. Total surface area has been shown to be genetically correlated with complex cognitive capacities, suggesting cortical brain structure is a viable endophenotype linking genes to behavior. However, to what extend local brain structure has a genetic association with cognitive and emotional functioning is incompletely understood. Here, we study the genetic correlation between personality traits and local cortical structure in a large-scale twin sample (Human Connectome Project, n ​= ​1102, 22-37y) and we evaluated whether observed associations reflect generalizable relationships between personality and local brain structure two independent age-matched samples (Brain Genomics Superstructure Project: n ​= ​925, age ​= ​19-35y, enhanced Nathan Kline Institute dataset: n ​= ​209, age: 19-39y). We found a genetic overlap between personality traits and local cortical structure in 10 of 18 observed phenotypic associations in predominantly frontal cortices. However, we only observed evidence in favor of replication for the negative association between surface area in medial prefrontal cortex and Neuroticism in both replication samples. Quantitative functional decoding indicated this region is implicated in emotional and socio-cognitive functional processes. In sum, our observations suggest that associations between local brain structure and personality are, in part, under genetic control. However, associations are weak and only the relation between frontal surface area and Neuroticism was consistently observed across three independent samples of young adults

Immune responses to gp82 provide protection against mucosal Trypanosoma cruzi infection

The potential use of the Trypanosoma cruzi metacyclic trypomastigote (MT) stage-specific molecule glycoprotein-82 (gp82) as a vaccine target has not been fully explored. We show that the opsonization of T. cruzi MT with gp82-specific antibody prior to mucosal challenge significantly reduces parasite infectivity. In addition, we investigated the immune responses as well as the systemic and mucosal protective immunity induced by intranasal CpG-adjuvanted gp82 vaccination. Spleen cells from mice immunized with CpG-gp82 proliferated and secreted IFN-γ in a dose-dependent manner in response to in vitro stimulation with gp82 and parasite lysate. More importantly, these CpG-gp82-immunized mice were significantly protected from a biologically relevant oral parasite challenge.Saint Louis University Department of Molecular MicrobiologyUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Microbiologia, Imunologia e ParasitologiaUNIFESP, EPM, Depto. de Microbiologia, Imunologia e ParasitologiaSciEL

Screening of the quantum-confined Stark effect in AlN/GaN nanowire superlattices by Germanium doping

We report on electrostatic screening of polarization-induced internal electric fields in AlN/GaN nanowire heterostructures with Germanium-doped GaN nanodiscs embedded between AlN barriers. The incorporation of Germanium at concentrations above $10^{20}\,\text{cm}^{-3}$ shifts the photoluminescence emission energy of GaN nanodiscs to higher energies accompanied by a decrease of the photoluminescence decay time. At the same time, the thickness-dependent shift in emission energy is significantly reduced. In spite of the high donor concentration a degradation of the photoluminescence properties is not observed.Comment: Manuscript including Supplemental material (15 pages, 5 figures

Neurotransmitter transporter/receptor co-expression shares organizational traits with brain structure and function

The relationship between brain areas based on neurotransmitter receptor and transporter molecule expression patterns may provide a link between brain structure and its function. Here, we studied the organization of the receptome, a measure of regional neurotransmitter receptor/transporter molecule (NTRM) similarity, derived from in vivo PET imaging studies of 19 different receptors and transporters. Nonlinear dimensionality reduction revealed three main spatial gradients of receptor similarity in the cortex. The first gradient differentiated the somato-motor network from the remaining cortex. The second gradient spanned between temporo-occipital and frontal anchors, differentiating visual and limbic networks from attention and control networks, and the third receptome gradient was anchored between the occipital and temporal cortices. In subcortical structures, the receptome delineated a striato-thalamic axis, separating functional communities. Moreover, we observed similar organizational principles underlying receptome differentiation in cortex and subcortex, indicating a link between subcortical and cortical NTRM patterning. Overall, we found that the cortical receptome shared key organizational traits with brain structure and function. Node-level correspondence of receptor similarity to functional, microstructural, and diffusion MRI-based measures decreased along a primary-to-transmodal gradient. Compared to primary and paralimbic regions, we observed higher receptomic diversification in unimodal and heteromodal regions, possibly supporting functional flexibility. In sum, we show how receptor similarity may form an additional organizational layer of human brain architecture, bridging brain structure and function