When Causal Intervention Meets Adversarial Examples and Image Masking for Deep Neural Networks

Discovering and exploiting the causality in deep neural networks (DNNs) are crucial challenges for understanding and reasoning causal effects (CE) on an explainable visual model. "Intervention" has been widely used for recognizing a causal relation ontologically. In this paper, we propose a causal inference framework for visual reasoning via do-calculus. To study the intervention effects on pixel-level features for causal reasoning, we introduce pixel-wise masking and adversarial perturbation. In our framework, CE is calculated using features in a latent space and perturbed prediction from a DNN-based model. We further provide the first look into the characteristics of discovered CE of adversarially perturbed images generated by gradient-based methods \footnote{~~https://github.com/jjaacckkyy63/Causal-Intervention-AE-wAdvImg}. Experimental results show that CE is a competitive and robust index for understanding DNNs when compared with conventional methods such as class-activation mappings (CAMs) on the Chest X-Ray-14 dataset for human-interpretable feature(s) (e.g., symptom) reasoning. Moreover, CE holds promises for detecting adversarial examples as it possesses distinct characteristics in the presence of adversarial perturbations.Comment: Noted our camera-ready version has changed the title. "When Causal Intervention Meets Adversarial Examples and Image Masking for Deep Neural Networks" as the v3 official paper title in IEEE Proceeding. Please use it in your formal reference. Accepted at IEEE ICIP 2019. Pytorch code has released on https://github.com/jjaacckkyy63/Causal-Intervention-AE-wAdvIm

Power-dependent internal loss in Josephson bifurcation amplifiers

We have studied nonlinear superconducting resonators: lambda/2 coplanar-waveguide (CPW) resonators with Josephson junctions (JJs) placed in the middle and lambda/4 CPW resonators terminated by JJs, which can be used for the qubit readout as "bifurcation amplifiers." The nonlinearity of the resonators arises from the Josephson junctions, and because of the nonlinearity, the resonators with appropriate parameters are expected to show a hysteretic response to the frequency sweep, or "bifurcation," when they are driven with a sufficiently large power. We designed and fabricated resonators whose resonant frequencies were around 10 GHz. We characterized the resonators at low temperatures, T<0.05 K, and confirmed that they indeed exhibited hysteresis. The sizes of the hysteresis, however, are sometimes considerably smaller than the predictions based on the loaded quality factor in the weak drive regime. When the discrepancy appears, it is mostly explained by taking into account the internal loss, which often increases in our resonators with increasing drive power in the relevant power range. As a possible origin of the power-dependent loss, the quasiparticle channel of conductance of the JJs is discussed.Comment: 8 pages, 9 figure

A Systematic Study of the Vibrational Free Energies of Polypeptides in Folded and Random States

AbstractMolecular vibrations, especially low frequency motions, may be used as an indication of the rigidity or the flatness of the protein folding energy landscape. We have studied the vibrational properties of native folded as well as random coil structures of more than 60 polypeptides. The picture we obtain allows us to perceive how and why the energy landscape progressively rigidifies while still allowing potential flexibility. Compared with random coil structures, both α-helices and β-hairpins are vibrationally more flexible. The vibrational properties of loop structures are similar to those of the corresponding random coil structures. Inclusion of an α-helix tends to rigidify peptides and so-called building blocks of the structure, whereas the addition of a β-structure has less effect. When small building blocks coalesce to form larger domains, the protein rigidifies. However, some folded native conformations are still found to be vibrationally more flexible than random coil structures, for example, β2-microglobulin and the SH3 domain. Vibrational free energy contributes significantly to the thermodynamics of protein folding and affects the distribution of the conformational substates. We found a weak correlation between the vibrational folding energy and the protein size, consistent with both previous experimental estimates and theoretical partition of the heat capacity change in protein folding

Imaginary polarization as a way to surmount the sign problem in ab initio calculations of spin-imbalanced Fermi gases

From ultracold atoms to quantum chromodynamics, reliable ab initio studies of strongly interacting fermions require numerical methods, typically in some form of quantum Monte Carlo calculation. Unfortunately, (non)relativistic systems at finite density (spin polarization) generally have a sign problem, such that those ab initio calculations are impractical. It is well-known, however, that in the relativistic case imaginary chemical potentials solve this problem, assuming the data can be analytically continued to the real axis. Is this feasible for nonrelativistic systems? Are the interesting features of the phase diagram accessible in this manner? By introducing complex chemical potentials, for real total particle number and imaginary polarization, the sign problem is avoided in the nonrelativistic case. To give a first answer to the above questions, we perform a mean-field study of the finite-temperature phase diagram of spin-1/2 fermions with imaginary polarization.Comment: 5 pages, 2 figures; published versio

A Microcantilever-based Gas Flow Sensor for Flow Rate and Direction Detection

The purpose of this paper is to apply characteristics of residual stress that causes cantilever beams to bend for manufacturing a micro-structured gas flow sensor. This study uses a silicon wafer deposited silicon nitride layers, reassembled the gas flow sensor with four cantilever beams that perpendicular to each other and manufactured piezoresistive structure on each micro-cantilever by MEMS technologies, respectively. When the cantilever beams are formed after etching the silicon wafer, it bends up a little due to the released residual stress induced in the previous fabrication process. As air flows through the sensor upstream and downstream beam deformation was made, thus the airflow direction can be determined through comparing the resistance variation between different cantilever beams. The flow rate can also be measured by calculating the total resistance variations on the four cantilevers.Comment: Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/handle/2042/16838

Metabolic regulation of functional decline during in vitro expansion of human mesenchymal stem cells

Human mesenchymal stem cells (hMSCs) isolated from various adult tissues are primary candidates in cell therapy and being tested in clinical trials for a wide range of diseases. The pro-regenerative and therapeutic properties of hMSCs are largely attributed to their trophic effects that coordinately modulate the progression of inflammation and enhance the endogenous tissue repair by host progenitor cells. However, immediately after isolation and upon culture expansion, hMSCs lose their in vivo quiescent state and start to accumulate genetic and phenotypic changes that significantly alter their phenotypic properties with reduced clonogenic population and therapeutic potential [1]. The culture-induced changes lead to both cellular senescence and metabolic alteration, resulting in reduced therapeutic outcome in various disease models. Since clinical application requires defined cellular properties and large-scale production of hMSCs, preserving cellular homeostasis during hMSCs in vitro expansion is a major barrier for hMSCs-based therapy and production. Once viewed as a mere consequence of the state of a cell, metabolism is now known to play active roles in regulating cellular events that govern stem cell phenotype and age-related functional properties during in vitro culture. Replicative passaging of hMSCs leads to cellular senescence following with insufficient energy production, decline of stemness and functional properties. Here, we report that energy metabolism in regulating hMSC aging-related properties due to in vitro replicative culture expansion in 2D planner or spinner flask bioreactor. hMSCs under in vitro culture up to 15 passages exhibited higher senescence with significant morphological alteration. 13C-glucose-based GC-MS metabolomics analysis suggested that metabolically heterogeneity at low passage hMSCs population while metabolic shift from glycolysis towards OXPHOS at high passage hMSCs. Rapid production of energy required for maintaining cellular properties of hMSCs alters mitochondrial function and leads to breakdown of cellular homeostasis with metabolic and redox imbalance. The alteration of metabolic profile and disruption of cellular homeostasis results in the replicative senescence and decline of therapeutic potentials of hMSCs. Understanding of hMSCs aging during in vitro culture expansion provides the insight of metabolic regulation for stem cell fate and engineering aspects for preserving and rejuvenating hMSCs functions via 3D culture or restore of metabolic balance [2]. Please click Additional Files below to see the full abstract

Metabolism Regulation Of Phenotypic And Therapeutic Properties Of Human Mesenchymal Stem Cells

Introduction Human mesenchymal stem cells (hMSCs) isolated from various adult tissues are primary candidates in cell therapy and tissue regeneration. The pro-regenerative properties of hMSCs are largely attributed to their trophic effects by the release of factors that coordinately modulate the progression of inflammation and enhance the endogenous tissue repair by host progenitor cells. However, immediately after isolation and upon culture expansion, hMSCs acquire and accumulate genetic and phenotypic changes that significantly alter their phenotypic properties with reduced clonogenic and therapeutic potential. The culture-induced changes are not only correlated with reduced clonogenicity and proliferation but also with reduced therapeutic outcome in various disease models. Thus, preserving hMSC therapeutic potency following in vitro expansion is an important goal in hMSC application. Once viewed as a mere consequence of the state of a cell, metabolism is now known to play active roles in regulating cellular events that govern stem cell phenotype and functional properties. Our long term objective is to understand the role of energy metabolism in regulating hMSC cell fate with ultimate goals of developing metabolic strategies to augment hMSCs therapeutic properties. Results Our recent studies show that hMSCs have heterogeneity at the level of primary energy metabolism [1] and possess metabolic plasticity to reconfigure their metabolic network in their reacquisition of stem cell primitive properties and immune-modulatory property [2]. First, 13C-glucose-based metabolomics analysis suggested that hMSC are metabolically heterogeneous and that clonogenic subpopulation of hMSCs enriched in low density culture (100 cells/cm2) possesses a metabolic phenotype that differs from that of hMSCs in high-density (3,000 cells/cm2) in their levels of glycolysis metabolism and pentose phosphate pathway (PPP). Metabolic inhibition studies revealed that glycolysis and PPP play active roles in maintaining hMSCs clonogenicity by regulating ATP generation, maintaining cellular redox state, and scavenging exogenous reactive oxygen species [1]. Second, we showed that hMSCs possess metabolic plasticity and effectively reconfigure their metabolism during 3D aggregation culture, and that this metabolic reconfiguration plays a central role in their reacquisition of primitive phenotypic properties [2]. Specifically, aggregate formation of hMSCs remodeled their mitochondrial network with reduced mitochondrial membrane potential, resulting in metabolic reconfiguration with reduced mitochondrial citric acid cycle (TCA cycle) activity, increased aerobic glycolysis, and anaplerotic flux. The effects of metabolic reconfiguration on stem cell gene expression and secretory function was recapitulated in the gain- and loss-of-function experiments using small molecule metabolic modulators, confirming its functional role in regulating hMSC properties. Finally, we showed that hMSC immuno-activation in response to interferon-γ (IFN-γ) treatment is associated with metabolic reconfiguration towards increased aerobic glycolysis, characterized by increased glucose consumption and upregulation of glycolysis-related genes and enzymes. We further demonstrated that both glucose deprivation and glycolysis inhibition were sufficient to abolish the secretion of indoleamine 2,3-dioxygenase (IDO) a critical anti-inflammatory cytokine secreted by hMSCs, suggesting the central role of aerobic glycolysis in regulating hMSC immunomodulatory properties. Conclusions Together, the results revealed the mechanistic connection between metabolic regulation and hMSC therapeutic phenotype, and demonstrated the regulation of metabolism as a strategy in potentiating hMSCs properties for cell therapy. In the presentation, the implication of these findings in hMSC bioprocessing and therapeutic application will be discussed. References [1]. Liu, Y., N. Munoz, B.A. Bunnell, T.M. Logan, and T. Ma, Density-Dependent Metabolic Heterogeneity in Human Mesenchymal Stem Cells. Stem Cells, 2015. 33(11): p. 3368-81. [2]. Liu, Y., N. Munoz, A.C. Tsai, B.A. Bunnell, T.M. Logan, and T. Ma, Metabolic Reconfiguration Supports Reacquisition of Primitive Phenotype in Human Mesenchymal Stem Cell Aggregates. Stem Cells, 2016. August 2016, (Accepted

Locating a scatterer in the active volcanic area of Southern Peru from ambient noise cross-correlation

We report on a strong scatterer of seismic energy in the 5–10 s period range located in the volcanic arc of Southern Peru. It is superficially like an active noise source in that it produces a continuous signal that arrives earlier than the inter-station surface wave in the noise cross-correlations. However, it is clearly determined to be a scatterer based on the coda arrivals observed in the cross-correlations, and the fact that it scatters waves from earthquake sources. We model the scatterer as a cylinder approximately 5 km in diameter with a shear wave velocity 30 per cent lower than the background velocity. It is likely to exist at the depth of 5–10 km, and is located at 71.6°W/16.1°S with an error of 10 km, which is near the inactive volcano Nevado Chachani and the active volcano El Misti which recently erupted in 1985

Evidence for non-self-similarity of microearthquakes recorded at a Taiwan borehole seismometer array

We investigate the relationship between seismic moment M0 and source duration tw of microearthquakes by using high-quality seismic data recorded with a vertical borehole array installed in central Taiwan. We apply a waveform cross-correlation method to the three-component records and identify several event clusters with high waveform similarity, with event magnitudes ranging from 0.3 to 2.0. Three clusters—Clusters A, B and C—contain 11, 8 and 6 events with similar waveforms, respectively. To determine how M0 scales with tw, we remove path effects by using a path-averaged Q. The results indicate a nearly constant tw for events within each cluster, regardless of M0, with mean values of tw being 0.058, 0.056 and 0.034 s for Clusters A, B and C, respectively. Constant tw, independent of M0, violates the commonly used scaling relation tw∝M1/30tw∝M01/3. This constant duration may arise either because all events in a cluster are hosted on the same isolated seismogenic patch, or because the events are driven by external factors of constant duration, such as fluid injections into the fault zone. It may also be related to the earthquake nucleation size