QuMinS: fast and scalable querying, mining and summarizing multi-modal databases

Given a large image set, in which very few images have labels, how to guess labels for the remaining majority? How to spot images that need brand new labels different from the predefined ones? How to summarize these data to route the user’s attention to what really matters? Here we answer all these questions. Specifically, we propose QuMinS, a fast, scalable solution to two problems: (i) Low-labor labeling (LLL) – given an image set, very few images have labels, find the most appropriate labels for the rest; and (ii) Mining and attention routing – in the same setting, find clusters, the top-'N IND.O' outlier images, and the 'N IND.R' images that best represent the data. Experiments on satellite images spanning up to 2.25 GB show that, contrasting to the state-of-the-art labeling techniques, QuMinS scales linearly on the data size, being up to 40 times faster than top competitors (GCap), still achieving better or equal accuracy, it spots images that potentially require unpredicted labels, and it works even with tiny initial label sets, i.e., nearly five examples. We also report a case study of our method’s practical usage to show that QuMinS is a viable tool for automatic coffee crop detection from remote sensing images.

Sulforaphane as a multifunctional neuroprotective molecule to prevent and slow down the progression of Alzheimer’s disease

Oxidative stress has been implicated in the pathogenesis of a number of diseases including neurodegenerative disorders, cancer, ischemia, etc. Alzheimer’s disease (AD) is histopathologically characterized by the presence of extracellular senile plaque (SP), predominantly consisting of fibrillar amyloid-peptide (Aβ), intracellular neurofibrillary tangles (NFTs), composed of hyperphosphorylated tau protein, and cell loss in the selected regions of the brain. However, the pathogenesis of AD remains largely unknown, but a number of hypothesis were proposed for AD mechanisms, which include: the amyloid cascade, excitotoxicity, oxidative stress and inflammation hypothesis, and all of them are based, to some extent on the role of A. Accumulated evidence indicates that the increased levels of ROS may act as important mediators of synaptic loss and eventually promote formation of neurofibrillary tangles and senile plaques. Therefore a vicious circle between ROS and Aaccumulation may accelerate progression of AD. For these reasons, growing attention has focused on oxidative mechanism of Atoxicity as well as the search for novel neuroprotective agents. A strategy to prevent the oxidative stress in neurons may be the use of chemopreventive agents as inducers of antioxidant and phase 2 enzymes. Sulforaphane (SF), derived from corresponding glucoraphanin, glucosinolate found in abundance in cruciferous vegetables, has recently gained attention as a potential neuroprotective compound inducer of antioxidant phase 2 enzymes. Consistent with this evidence, the study is aimed at identifying the SF ability to prevent and counteract the oxidative damage inducted by oligomers of Aβ (1-42) in terms of impairment in the intracellular redox state and cellular death in differentiated human neuroblastoma and microglia primary cultures. In addition we will evaluated the mechanism underlying the SF neuroprotection activity.

Fast and accurate numerical solutions in some problems of particle and radiation transport: synthetic acceleration for the method of short characteristics, Doppler-broadened scattering kernel, remote sensing of the cryosphere

The aim of this work is to present various aspects of numerical simulation of particle and radiation transport for industrial and environmental protection applications, to enable the analysis of complex physical processes in a fast, reliable, and efficient way. In the first part we deal with speed-up of numerical simulation of neutron transport for nuclear reactor core analysis. The convergence properties of the source iteration scheme of the Method of Characteristics applied to be heterogeneous structured geometries has been enhanced by means of Boundary Projection Acceleration, enabling the study of 2D and 3D geometries with transport theory without spatial homogenization. The computational performances have been verified with the C5G7 2D and 3D benchmarks, showing a sensible reduction of iterations and CPU time. The second part is devoted to the study of temperature-dependent elastic scattering of neutrons for heavy isotopes near to the thermal zone. A numerical computation of the Doppler convolution of the elastic scattering kernel based on the gas model is presented, for a general energy dependent cross section and scattering law in the center of mass system. The range of integration has been optimized employing a numerical cutoff, allowing a faster numerical evaluation of the convolution integral. Legendre moments of the transfer kernel are subsequently obtained by direct quadrature and a numerical analysis of the convergence is presented. In the third part we focus our attention to remote sensing applications of radiative transfer employed to investigate the Earth's cryosphere. The photon transport equation is applied to simulate reflectivity of glaciers varying the age of the layer of snow or ice, its thickness, the presence or not other underlying layers, the degree of dust included in the snow, creating a framework able to decipher spectral signals collected by orbiting detectors.

Prediction of dental implant torque with a fast and automatic finite element analysis: a pilot study

Despite its importance, implant removal torque can be assessed at present only after implantation. This paper presents a new technique to help clinicians preoperatively evaluate implant stability.

Identification of speeded and slowed familiar melodies by younger, middle-aged, and older musicians and nonmusicians

There is a range of tempos within which listeners can identify familiar tunes (around 0.8 to 6.0 notes/s). Faster and slower tunes are difficult to identify. The authors assessed fast and slow melody-identification thresholds for 80 listeners ages 17–79 years with expertise varying from musically untrained to professional. On fast-to-slow (FS) trials the tune started at a very fast tempo and slowed until the listener identified it. Slow-to-fast (SF) trials started slow and accelerated. Tunes either retained their natural rhythms or were stylized isochronous versions. Increased expertise led to better performance for both FS and SF thresholds (r = .45). Performance declined uniformly across the 62-year age range in the FS condition (r = .27). SF performance was unaffected by age. Although early encoding processes may slow with age, expertise has a greater effect. Musical expertise involves perceptual learning with melodies at a wide range of tempos.

Mice with a targeted disruption of the Fgfrl1 gene die at birth due to alterations in the diaphragm

FGFRL1 is a recently discovered member of the fibroblast growth factor receptor family that is lacking the intracellular tyrosine kinase domain. To elucidate the function of the novel receptor, we created mice with a targeted disruption of the Fgfrl1 gene. These mice develop normally until term, but die within a few minutes after birth due to respiratory failure. The respiratory problems are explained by a significant reduction in the size of the diaphragm muscle, which is not sufficient to inflate the lungs after birth. The remaining portion of the diaphragm muscle appears to be well developed and innervated. It consists of differentiated myofibers with nuclei at the periphery. Fast and slow muscle fibers occur in normal proportions. The myogenic regulatory factors MyoD, Myf5, myogenin and Mrf4 and the myocyte enhancer factors Mef2A, Mef2B, Mef2C and Mef2D are expressed at normal levels. Experiments with a cell culture model involving C2C12 myoblasts show that Fgfrl1 is expressed during the late stages of myotube formation. Other skeletal muscles do not appear to be affected in the Fgfrl1 deficient mice. Thus, Fgfrl1 plays a critical role in the development of the diaphragm.

Development and Validation of a Fast and Homogeneous Cell-Based Fluorescence Screening Assay for Divalent Metal Transporter 1 (DMT1/SLC11A2) Using the FLIPR Tetra.

Divalent metal ion transporter 1 (DMT1) is a proton-coupled Fe(2+) transporter that is essential for iron uptake in enterocytes and for transferrin-associated endosomal iron transport in many other cell types. DMT1 dysfunction is associated with several diseases such as iron overload disorders and neurodegenerative diseases. The main objective of the present work is to develop and validate a fluorescence-based screening assay for DMT1 modulators. We found that Fe(2+) or Cd(2+) influx could be reliably monitored in calcium 5-loaded DMT1-expressing HEK293 cells using the FLIPR Tetra fluorescence microplate reader. DMT1-mediated metal transport shows saturation kinetics depending on the extracellular substrate concentration, with a K0.5 value of 1.4 µM and 3.5 µM for Fe(2+) and Cd(2+), respectively. In addition, Cd(2+) was used as a substrate for DMT1, and we find a Ki value of 2.1 µM for a compound (2-(3-carbamimidoylsulfanylmethyl-benzyl)-isothiourea) belonging to the benzylisothioureas family, which has been identified as a DMT1 inhibitor. The optimized screening method using this compound as a reference demonstrated a Z' factor of 0.51. In summary, we developed and validated a sensitive and reproducible cell-based fluorescence assay suitable for the identification of compounds that specifically modulate DMT1 transport activity.

Interlinked dual-time feedback loops can enhance robustness to stochasticity and persistence of memory.

Multiple interlinked positive feedback loops shape the stimulus responses of various biochemical systems, such as the cell cycle or intracellular Ca2+ release. Recent studies with simplified models have identified two advantages of coupling fast and slow feedback loops. This dual-time structure enables a fast response while enhancing resistances of responses and bistability to stimulus noise. We now find that (1) the dual-time structure similarly confers resistance to internal noise due to molecule number fluctuations, and (2) model variants with altered coupling, which better represent some specific biochemical systems, share all the above advantages. We also develop a similar bistable model with coupling of a fast autoactivation loop to a slow loop. This model's topology was suggested by positive feedback proposed to play a role in long-term synaptic potentiation (LTP). The advantages of fast response and noise resistance are also present in this autoactivation model. Empirically, LTP develops resistance to reversal over approximately 1h . The model suggests this resistance may result from increased amounts of synaptic kinases involved in positive feedback.

Convergent and divergent modulatory pathways in {\it Aplysia\/}: Cellular and network studies

Neuromodulation is essential to many functions of the nervous system. In the simple gastropod mollusk Aplysia californica, neuromodulation of the circuits for the defensive withdrawal reflexes has been associated with several forms of learning. In the present work, the neurotransmitters and neural circuitry which contribute to the modulation of the tail-siphon withdrawal reflex were examined.^ A recently-identified neuropeptide transmitter, buccalin A was found to modulate the biophysical properties of the sensory neurons that mediate the reflex. The actions of buccalin A on the sensory neurons were compared with those of the well-characterized modulatory transmitter serotonin, and convergence and divergence in the actions of these two transmitters were evaluated. Buccalin A dramatically increased the excitability of sensory neurons and occluded further enhancement of excitability by serotonin. Buccalin A produced no significant change in spike duration, and it did not block serotonin-induced spike broadening. Voltage-clamp analysis revealed the currents that may be involved in the effects on spike duration and excitability. Buccalin A decreased an outward current similar to the S-K$\sp+$ current (I$\sb{\rm K,S}$). Buccalin A appeared to occlude further modulation of I$\sb{\rm K,S}$ by serotonin, but did not block serotonin-induced modulation of the voltage-dependent delayed rectifier K$\sp+$ current (I$\sb{\rm K,V}$). These results suggest that buccalin A converges on some, but not all, of the same subcellular modulatory pathways as serotonin.^ In order to begin to understand neuromodulation in a more physiological context for the tail-siphon withdrawal reflex, the modulatory circuitry for the tail-withdrawal circuit was examined. Mechanoafferent neurons in the J cluster of the cerebral ganglion were identified as elements of a modulatory circuit for the reflex. Excitatory and inhibitory connections were observed between the J cells and the pleural sensory neurons, the tail motor neurons, and several classes of interneurons for the tail-siphon withdrawal circuit. The J cells produced both fast and slow PSPs in these neurons. Of particular interest was the ability of the J cells to produce slow EPSPs in the pleural sensory neurons. These slow EPSPs were associated with an increase in the excitability of the sensory neurons. The J cells appear to mediate both sensory and modulatory inputs to the circuit for the tail-siphon withdrawal reflex from the anterior part of the animal. ^

Sedimentary Metal Bioavailability Determined By the Digestive Constraints of Marine Deposit Feeders: Gut Retention Time and Dissolved Amino Acids

Contaminant metals bound to sediments are subject to considerable solubilization during passage of the sediments through the digestive systems of deposit feeders. We examined the kinetics of this process, using digestive fluids extracted from deposit feeders Arenicola marina and Parastichopus californicus and then incubated with contaminated sediments. Kinetics are complex, with solubilization followed occasionally by readsorption onto the sediment. In general, solubilization kinetics are biphasic, with an initial rapid step followed by a slower reaction. For many sediment-organism combinations, the reaction will not reach a steady state or equilibrium within the gut retention time (GRT) of the organisms, suggesting that metal bioavailability in sediments is a time-dependent parameter. Experiments with commercial protein solutions mimic the kinetic patterns observed with digestive fluids, which corroborates our previous study that complexation by dissolved amino acids (AA) in digestive fluids leads to metal solubilization (Chen & Mayer 1998b; Environ Sci Technol 32:770-778). The relative importance of the fast and slow reactions appears to depend on the ratio of ligands in gut fluids to the amount of bound metal in sediments. High ligand to solid metal ratios result in more metals released in fast reactions and thus higher lability of sedimentary metals. Multiple extractions of a sediment with digestive fluid of A. marina confirm the potential importance of incomplete reactions within a single deposit-feeding event, and make clear that bioavailability to a single animal is Likely different from that to a community of organisms. The complex kinetic patterns lead to the counterintuitive prediction that toxification of digestive enzymes by solubilized metals will occur more readily in species that dissolve less metals.

Development of a method for fast and automatic radiocarbon measurement of aerosol samples by online coupling of an elemental analyzer with a MICADAS AMS

A fast and automatic method for radiocarbon analysis of aerosol samples is presented. This type of analysis requires high number of sample measurements of low carbon masses, but accepts precisions lower than for carbon dating analysis. The method is based on online Trapping CO2 and coupling an elemental analyzer with a MICADAS AMS by means of a gas interface. It gives similar results to a previously validated reference method for the same set of samples. This method is fast and automatic and typically provides uncertainties of 1.5–5% for representative aerosol samples. It proves to be robust and reliable and allows for overnight and unattended measurements. A constant and cross contamination correction is included, which indicates a constant contamination of 1.4 ± 0.2 μg C with 70 ± 7 pMC and a cross contamination of (0.2 ± 0.1)% from the previous sample. A Real-time online coupling version of the method was also investigated. It shows promising results for standard materials with slightly higher uncertainties than the Trapping online approach.