199 research outputs found
Forward-Start Options in the Barndorff-Nielsen-Shephard Model
We derive a semi-analytical formula for pricing forward-start options in the Barndorff-Nielsen- Shephard model. In terms of computational time, this formula is equivalent to one-dimensional integration
BlinkML: Efficient Maximum Likelihood Estimation with Probabilistic Guarantees
The rising volume of datasets has made training machine learning (ML) models
a major computational cost in the enterprise. Given the iterative nature of
model and parameter tuning, many analysts use a small sample of their entire
data during their initial stage of analysis to make quick decisions (e.g., what
features or hyperparameters to use) and use the entire dataset only in later
stages (i.e., when they have converged to a specific model). This sampling,
however, is performed in an ad-hoc fashion. Most practitioners cannot precisely
capture the effect of sampling on the quality of their model, and eventually on
their decision-making process during the tuning phase. Moreover, without
systematic support for sampling operators, many optimizations and reuse
opportunities are lost.
In this paper, we introduce BlinkML, a system for fast, quality-guaranteed ML
training. BlinkML allows users to make error-computation tradeoffs: instead of
training a model on their full data (i.e., full model), BlinkML can quickly
train an approximate model with quality guarantees using a sample. The quality
guarantees ensure that, with high probability, the approximate model makes the
same predictions as the full model. BlinkML currently supports any ML model
that relies on maximum likelihood estimation (MLE), which includes Generalized
Linear Models (e.g., linear regression, logistic regression, max entropy
classifier, Poisson regression) as well as PPCA (Probabilistic Principal
Component Analysis). Our experiments show that BlinkML can speed up the
training of large-scale ML tasks by 6.26x-629x while guaranteeing the same
predictions, with 95% probability, as the full model.Comment: 22 pages, SIGMOD 201
Trans synaptic assemblies link synaptic vesicles and neuroreceptors
Synaptic transmission is characterized by fast, tightly coupled processes and complex signaling pathways that require a precise protein organization, such as the previously reported nanodomain colocalization of pre and postsynaptic proteins. Here, we used cryo electron tomography to visualize synaptic complexes together with their native environment comprising interacting proteins and lipids on a 2 to 4 nm scale. Using template free detection and classification, we showed that tripartite trans synaptic assemblies subcolumns link synaptic vesicles to postsynaptic receptors and established that a particular displacement between directly interacting complexes characterizes subcolumns. Furthermore, we obtained de novo average structures of ionotropic glutamate receptors in their physiological composition, embedded in plasma membrane. These data support the hypothesis that synaptic function is carried by precisely organized trans synaptic units. It provides a framework for further exploration of synaptic and other large molecular assemblies that link different cells or cellular regions and may require weak or transient interactions to exert their functio
Cuticular chemoprofile of the fruit fly drosophila subobscura (diptera, drosophilidae)
In insects, cuticular hydrocarbon (CHC) profile is involved in many important biological functions and may vary in different conditions. Among fruit fly species, Drosophila subobscura is one of the most frequently used in genetic, ecological and evolutionary research, because of its rich chromosomal polymorphism, specific behavioral repertoires and habitat preferences. In this work, we identified and quantified cuticular chemoprofile of D. subobscura. Using gas chromatography (GC) and gas chromatography coupled with mass spectrometry (GC-MS), 25 chemical compounds were found in males and 23 compounds were found in females. Further, ANOVA confirmed significant sexual dimorphism in cuticular chemoprofile amounts. Knowledge of cuticular chemistry could contribute to further research in D. subobscura, starting from behavioral, up to ecological, since this species is recognized as an important model system for the study and monitoring of global climate changes
Giant magnetic enhancement in Fe/Pd films and its influence on the magnetic interlayer coupling
The magnetic properties of thin Pd fcc(001) films with embedded monolayers of
Fe are investigated by means of first principles density functional theory. The
induced spin polarization in Pd is calculated and analyzed in terms of quantum
interference within the Fe/Pd/Fe bilayer system. An investigation of the
magnetic enhancement effects on the spin polarization is carried out and its
consequences for the magnetic interlayer coupling are discussed. In contrast to
{\it e.g.} the Co/Cu fcc(001) system we find a large effect on the magnetic
interlayer coupling due to magnetic enhancement in the spacer material. In the
case of a single embedded Fe monolayer we find aninduced Pd magnetization
decaying with distance from the magnetic layer as ~ with
. For the bilayer system we find a giant magnetic
enhancement (GME) that oscillates strongly due to interference effects. This
results in a strongly modified magnetic interlayer coupling, both in phase and
magnitude, which may not be described in the pure
Ruderman-Kittel-Kasuya-Yoshida (RKKY) picture. No anti-ferromagnetic coupling
was found and by comparison with magnetically constrained calculations we show
that the overall ferromagnetic coupling can be understood from the strong
polarization of the Pd spacer
Synucleins Have Multiple Effects on Presynaptic Architecture
Synucleins ( a , b , g -synuclein) are abundant presynaptic proteins, with a -synuclein linked to the pathogenesis of Parkinson’s disease. Vargas et al. investigate the effects of deleting synucleins and overexpressing mutated a -synuclein on synapse architecture using electron microscopy. They find that synucleins regulate presynaptic terminal size and synaptic vesicle distribution
3-D Ultrastructure of O. tauri: Electron Cryotomography of an Entire Eukaryotic Cell
The hallmark of eukaryotic cells is their segregation of key biological functions into discrete, membrane-bound organelles. Creating accurate models of their ultrastructural complexity has been difficult in part because of the limited resolution of light microscopy and the artifact-prone nature of conventional electron microscopy. Here we explored the potential of the emerging technology electron cryotomography to produce three-dimensional images of an entire eukaryotic cell in a near-native state. Ostreococcus tauri was chosen as the specimen because as a unicellular picoplankton with just one copy of each organelle, it is the smallest known eukaryote and was therefore likely to yield the highest resolution images. Whole cells were imaged at various stages of the cell cycle, yielding 3-D reconstructions of complete chloroplasts, mitochondria, endoplasmic reticula, Golgi bodies, peroxisomes, microtubules, and putative ribosome distributions in-situ. Surprisingly, the nucleus was seen to open long before mitosis, and while one microtubule (or two in some predivisional cells) was consistently present, no mitotic spindle was ever observed, prompting speculation that a single microtubule might be sufficient to segregate multiple chromosomes
Cryo-electron tomography of cells: connecting structure and function
Cryo-electron tomography (cryo-ET) allows the visualization of cellular structures under close-to-life conditions and at molecular resolution. While it is inherently a static approach, yielding structural information about supramolecular organization at a certain time point, it can nevertheless provide insights into function of the structures imaged, in particular, when supplemented by other approaches. Here, we review the use of experimental methods that supplement cryo-ET imaging of whole cells. These include genetic and pharmacological manipulations, as well as correlative light microscopy and cryo-ET. While these methods have mostly been used to detect and identify structures visualized in cryo-ET or to assist the search for a feature of interest, we expect that in the future they will play a more important role in the functional interpretation of cryo-tomograms
Glycolysis downregulation is a hallmark of HIV-1 latency and sensitizes infected cells to oxidative stress
HIV-1 infects lymphoid and myeloid cells, which can harbor a latent proviral reservoir responsible for maintaining lifelong infection. Glycolytic metabolism has been identified as a determinant of susceptibility to HIV-1 infection, but its role in the development and maintenance of HIV-1 latency has not been elucidated. By combining transcriptomic, proteomic, and metabolomic analyses, we here show that transition to latent HIV-1 infection downregulates glycolysis, while viral reactivation by conventional stimuli reverts this effect. Decreased glycolytic output in latently infected cells is associated with downregulation of NAD+/NADH. Consequently, infected cells rely on the parallel pentose phosphate pathway and its main product, NADPH, fueling antioxidant pathways maintaining HIV-1 latency. Of note, blocking NADPH downstream effectors, thioredoxin and glutathione, favors HIV-1 reactivation from latency in lymphoid and myeloid cellular models. This provides a “shock and kill effect” decreasing proviral DNA in cells from people living with HIV/AIDS. Overall, our data show that downmodulation of glycolysis is a metabolic signature of HIV-1 latency that can be exploited to target latently infected cells with eradication strategies
- …