Monitoring of gene knockouts: genome-wide profiling of conditionally essential genes

Monitoring of gene knockouts is a new microarray-based genetic technique used for genome-wide identification of conditionally essential genes in bacteri

Non-alcoholic fatty liver diseases: update on the challenge of diagnosis and treatment

The prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to be 25-30% of the population, and is the most common cause of elevated liver enzymes in Korea. NAFLD is a “hot potato” for pharmaceutical companies. Many clinical trials are underway to develop a first-in-class drug to treat NAFLD. However, there are several challenging issues regarding the diagnosis of NAFLD. Currently, liver biopsy is the gold standard method for the diagnosis of NAFLD and steatohepatitis. Ideally, globally recognized standards for histological diagnosis and methods to optimize observer agreement on biopsy interpretation should be developed. Liver biopsy is the best method rather than a perfect one. Recently, multi-parametric magnetic resonance imagery can estimate the amount of intrahepatic fat successfully and is widely used in clinical trials. But no diagnostic method can discriminate between steatohepatitis and simple steatosis. The other unresolved issue in regard to NAFLD is the absence of satisfactory treatment options. Vitamin E and obeticholic acid have shown protective effects in randomized controlled trials, but this drug has not been approved for use in Korea. This study will provide a description of diagnostic methods and treatments that are currently recommended for NAFLD

Explaining Convolutional Neural Networks through Attribution-Based Input Sampling and Block-Wise Feature Aggregation

As an emerging field in Machine Learning, Explainable AI (XAI) has been offering remarkable performance in interpreting the decisions made by Convolutional Neural Networks (CNNs). To achieve visual explanations for CNNs, methods based on class activation mapping and randomized input sampling have gained great popularity. However, the attribution methods based on these techniques provide lower resolution and blurry explanation maps that limit their explanation power. To circumvent this issue, visualization based on various layers is sought. In this work, we collect visualization maps from multiple layers of the model based on an attribution-based input sampling technique and aggregate them to reach a fine-grained and complete explanation. We also propose a layer selection strategy that applies to the whole family of CNN-based models, based on which our extraction framework is applied to visualize the last layers of each convolutional block of the model. Moreover, we perform an empirical analysis of the efficacy of derived lower-level information to enhance the represented attributions. Comprehensive experiments conducted on shallow and deep models trained on natural and industrial datasets, using both ground-truth and model-truth based evaluation metrics validate our proposed algorithm by meeting or outperforming the state-of-the-art methods in terms of explanation ability and visual quality, demonstrating that our method shows stability regardless of the size of objects or instances to be explained.Comment: 9 pages, 9 figures, Accepted at the Thirty-Fifth AAAI Conference on Artificial Intelligence (AAAI-21

Nucleotide Biosynthesis Is Critical for Growth of Bacteria in Human Blood

Proliferation of bacterial pathogens in blood represents one of the most dangerous stages of infection. Growth in blood serum depends on the ability of a pathogen to adjust metabolism to match the availability of nutrients. Although certain nutrients are scarce in blood and need to be de novo synthesized by proliferating bacteria, it is unclear which metabolic pathways are critical for bacterial growth in blood. In this study, we identified metabolic functions that are essential specifically for bacterial growth in the bloodstream. We used two principally different but complementing techniques to comprehensively identify genes that are required for the growth of Escherichia coli in human serum. A microarray-based and a dye-based mutant screening approach were independently used to screen a library of 3,985 single-gene deletion mutants in all non-essential genes of E. coli (Keio collection). A majority of the mutants identified consistently by both approaches carried a deletion of a gene involved in either the purine or pyrimidine nucleotide biosynthetic pathway and showed a 20- to 1,000-fold drop in viable cell counts as compared to wild-type E. coli after 24 h of growth in human serum. This suggests that the scarcity of nucleotide precursors, but not other nutrients, is the key limitation for bacterial growth in serum. Inactivation of nucleotide biosynthesis genes in another Gram-negative pathogen, Salmonella enterica, and in the Gram-positive pathogen Bacillus anthracis, prevented their growth in human serum. The growth of the mutants could be rescued by genetic complementation or by addition of appropriate nucleotide bases to human serum. Furthermore, the virulence of the B. anthracis purE mutant, defective in purine biosynthesis, was dramatically attenuated in a murine model of bacteremia. Our data indicate that de novo nucleotide biosynthesis represents the single most critical metabolic function for bacterial growth in blood and reveal the corresponding enzymes as putative antibiotic targets for the treatment of bloodstream infections

Current fluctuations in a single tunnel junction

We study noise spectra of currents through a tunnel junction in weak tunneling limit. We introduce effective capacitance to take into account the interaction effect and explicitly incorporate the electromagnetic environment of the junction into the formulation. We study the effect of charging energy and macroscopic environment on noise spectra. We calculate current fluctuations at tunneling barrier and fluctuations measured at leads. It is shown that two fluctuations have different noise spectra and the relation between them is nontrivial. We provide an explanation for the origin of the difference. Experimental implications are discussed.Comment: 25 pages, Revtex 3.

Study of B meson decays to three-body charmless hadronic final states

We report results of a study of charmless B meson decays to three-body KPiPi, KKPi and KKK final states. Measurements of branching fractions for B decays to K+0Pi+Pi-, K+K+K-, K0K+K-, KsKsK+ and KsKsKs final states are presented. The decays B0=>K0K+K-, B+=>KsKsK+ and B0=>KsKsKs are observed for the first time. We also report evidence for B+=>K+K-Pi+ decay. For the three-body final states K0K+K-, KsKsPi+, K+K+Pi- and K-Pi+Pi+ 90% confidence level upper limits are reported. Finally, we discuss the possibility of using the three-body B0=>KsK+K- decay for CP violation studies. The results are obtained with a 78 fb^-1 data sample collected at the Y(4S) resonance by the Belle detector operating at the KEKB asymmetric energy e+e- collider.Comment: 15 pages, 6 figures. To be submitted to PR

Observation of Radiative Decay D0→ϕγD^0 \to \phi \gamma

We report the observation of the decay $D^{0} \to \phi \gamma$ with a statistical significance of $5.4\sigma$ in 78.1 \ifb of data collected by the Belle experiment at the KEKB $e^+ e^-$ collider. This is the first observation of a flavor-changing radiative decay of a charmed meson. The Cabibbo- and color-suppressed decays $D^0 \to \phi \pi^0$, $\phi \eta$ are also observed for the first time. We measure branching fractions \br(D^{0} \to \phi \gamma) = [ 2.60^{+0.70}_{-0.61} \stat {}^{+0.15}_{-0.17} \syst ] \times 10^{-5}, \br(D^{0} \to \phi \pi^{0}) = [ 8.01 \pm 0.26 \stat \pm 0.47 \syst ] \times 10^{-4}, and \br(D^{0} \to \phi \eta) = [ 1.48 \pm 0.47 \stat \pm 0.09 \syst ] \times 10^{-4}.Comment: 9 pages, 4 figures, Belle Preprint 2003-24, KEK Preprint 2003-75, updated version of BELLE-CONF-0346 (contributed paper to the XXI International Symposium on Lepton and Photon Interactions at High Energies,Fermilab Aug 11-16,2003). to appear in Phys. Rev. Let

Measurement of branching fraction ratios and CP asymmetries in B±→DCPK±B^{\pm} \to D_{CP}K^{\pm}

We report results on the decay $B^{-} \to D_{CP}K^{-}$ and its charge conjugate using a data sample of 85.4 million $B\bar{B}$ pairs recorded at the $\Upsilon(4S)$ resonance with the Belle detector at the KEKB asymmetric $e^{+}e^{-}$ storage ring. Ratios of branching fractions of Cabibbo-suppressed to Cabibbo-favored processes are determined to be ${\cal B}(B^- \to D^0 K^-)/{\cal B}(B^- \to D^0 \pi^-)= 0.077 \pm 0.005(stat) \pm 0.006(sys)$, ${\cal B}(B^- \to D_1 K^-)/{\cal B}(B^- \to D_1 \pi^-) = 0.093 \pm 0.018(stat) \pm 0.008(sys)$ and ${\cal B}(B^- \to D_2 K^-)/{\cal B}(B^- \to D_2 \pi^-) = 0.108 \pm 0.019(stat) \pm 0.007(sys)$ where the indices 1 and 2 represent the CP=+1 and CP=$-$1 eigenstates of the $D^{0}-\bar{D^{0}}$ system, respectively. We find the partial-rate charge asymmetries for $B^{-} \to D_{CP}K^{-}$ to be ${\cal{A}}_1 = 0.06 \pm 0.19(stat) \pm 0.04(sys)$ and ${\cal{A}}_2 = -0.19 \pm 0.17(stat) \pm 0.05(sys)$.Comment: 10 pages, 3 figures, submitted to Physical Review

Search for Direct CP Violation in B -> K pi Decays

We search for direct CP violation in flavor specific B -> K pi decays by measuring the rate asymmetry between charge conjugate modes. The search is performed on a data sample of 11.1 million B B bar events recorded on the Upsilon(4S) resonance by the Belle experiment at KEKB. We measure 90% confidence intervals in the partial rate asymmetry A_CP of -0.25 < A_CP(K-/+ pi+/-) < 0.37, -0.40 < A_CP(K-/+ pi^0) < 0.36, and -0.53 < A_CP(K^0 pi-/+) < 0.82. By combining the K-/+ pi+/- and K-/+ pi^0 final states, we conclude that -0.22 < A_CP[K-/+(pi+/- + pi^0)] < 0.25 at the 90% confidence level.Comment: Submitted to PRD Rapid Communication

Observation of Large CP Violation in the Neutral B Meson System

We present a measurement of the Standard Model CP violation parameter sin 2phi_1 based on a 29.1 fb^{-1} data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. One neutral B meson is fully reconstructed as a J/psi Ks, psi(2S) Ks, chi_c1 Ks, eta_c Ks, J/psi K_L or J/psi K^{*0} decay and the flavor of the accompanying B meson is identified from its decay products. From the asymmetry in the distribution of the time intervals between the two B meson decay points, we determine sin 2phi_1 = 0.99 +- 0.14(stat) +- 0.06(syst). We conclude that we have observed CP violation in the neutral B meson system.Comment: 4 figures, to appear in Phys. Rev. Letter