Draft crystal structure of the vault shell at 9-A resolution.

Vaults are the largest known cytoplasmic ribonucleoprotein structures and may function in innate immunity. The vault shell self-assembles from 96 copies of major vault protein and encapsulates two other proteins and a small RNA. We crystallized rat liver vaults and several recombinant vaults, all among the largest non-icosahedral particles to have been crystallized. The best crystals thus far were formed from empty vaults built from a cysteine-tag construct of major vault protein (termed cpMVP vaults), diffracting to about 9-A resolution. The asymmetric unit contains a half vault of molecular mass 4.65 MDa. X-ray phasing was initiated by molecular replacement, using density from cryo-electron microscopy (cryo-EM). Phases were improved by density modification, including concentric 24- and 48-fold rotational symmetry averaging. From this, the continuous cryo-EM electron density separated into domain-like blocks. A draft atomic model of cpMVP was fit to this improved density from 15 domain models. Three domains were adapted from a nuclear magnetic resonance substructure. Nine domain models originated in ab initio tertiary structure prediction. Three C-terminal domains were built by fitting poly-alanine to the electron density. Locations of loops in this model provide sites to test vault functions and to exploit vaults as nanocapsules

Excess Observed in CDF Bs0→μ+μ−B^0_s \to \mu^{+} \mu^{-} and SUSY at the LHC

The recent excess observed by CDF in $B^0_s \to \mu^{+} \mu^{-}$ is interpreted in terms of a possible supersymmetric origin. An analysis is given of the parameter space of mSUGRA and non-universal SUGRA models under the combined constraints from LHC-7 with 165 pb$^{-1}$ of integrated luminosity, under the new XENON-100 limits on the neutralino-proton spin independent cross section and under the CDF $B^0_s \to \mu^{+} \mu^{-}$ 90% C.L. limit reported to arise from an excess number of dimuon events. It is found that the predicted value of the branching ratio $B^0_s \to \mu^{+} \mu^{-}$ consistent with all the constraints contains the following set of NLSPs: chargino, stau, stop or CP odd (even) Higgs. The lower bounds of sparticles, including those from the LHC, XENON and CDF $B^0_s\to \mu^+\mu^-$ constraint, are exhibited and the shift in the allowed range of sparticle masses arising solely due to the extra constraint from the CDF result is given. It is pointed out that the two sided CDF 90% C.L. limit puts upper bounds on sparticle masses. An analysis of possible signatures for early discovery at the LHC is carried out corresponding to the signal region in $B^0_s \to \mu^{+} \mu^{-}$. Implications of GUT-scale non-universalities in the gaugino and Higgs sectors are discussed. If the excess seen by the CDF Collaboration is supported by further data from LHCb or D0, this new result could be a harbinger for the discovery of supersymmetry.Comment: References added, text update

Weakly supervised deep learning for the detection of domain generation algorithms

Domain generation algorithms (DGAs) have become commonplace in malware that seeks to establish command and control communication between an infected machine and the botmaster. DGAs dynamically and consistently generate large volumes of malicious domain names, only a few of which are registered by the botmaster, within a short time window around their generation time, and subsequently resolved when the malware on the infected machine tries to access them. Deep neural networks that can classify domain names as benign or malicious are of great interest in the real-time defense against DGAs. In contrast with traditional machine learning models, deep networks do not rely on human engineered features. Instead, they can learn features automatically from data, provided that they are supplied with sufficiently large amounts of suitable training data. Obtaining cleanly labeled ground truth data is difficult and time consuming. Heuristically labeled data could potentially provide a source of training data for weakly supervised training of DGA detectors. We propose a set of heuristics for automatically labeling domain names monitored in real traffic, and then train and evaluate classifiers with the proposed heuristically labeled dataset. We show through experiments on a dataset with 50 million domain names that such heuristically labeled data is very useful in practice to improve the predictive accuracy of deep learning-based DGA classifiers, and that these deep neural networks significantly outperform a random forest classifier with human engineered features

A Compact Microchip-Based Atomic Clock Based on Ultracold Trapped Rb Atoms

We propose a compact atomic clock based on ultracold Rb atoms that are magnetically trapped near the surface of an atom microchip. An interrogation scheme that combines electromagnetically-induced transparency (EIT) with Ramsey's method of separated oscillatory fields can achieve atomic shot-noise level performance of 10^{-13}/sqrt(tau) for 10^6 atoms. The EIT signal can be detected with a heterodyne technique that provides noiseless gain; with this technique the optical phase shift of a 100 pW probe beam can be detected at the photon shot-noise level. Numerical calculations of the density matrix equations are used to identify realistic operating parameters at which AC Stark shifts are eliminated. By considering fluctuations in these parameters, we estimate that AC Stark shifts can be canceled to a level better than 2*10^{-14}. An overview of the apparatus is presented with estimates of duty cycle and power consumption.Comment: 15 pages, 11 figures, 5 table

A Mesoscopic Resonating Valence Bond system on a triple dot

We introduce a mesoscopic pendulum from a triple dot. The pendulum is fastened through a singly-occupied dot (spin qubit). Two other strongly capacitively islands form a double-dot charge qubit with one electron in excess oscillating between the two low-energy charge states (1,0) and (0,1); this embodies the weight of the pendulum. The triple dot is placed between two superconducting leads as shown in Fig. 1. Under well-defined conditions, the main proximity effect stems from the injection of resonating singlet (valence) bonds on the triple dot. This gives rise to a Josephson current that is charge- and spin-dependent. Consequences in a SQUID-geometry are carefully investigated.Comment: final version to appear in PR

Exchange Interaction Between Three and Four Coupled Quantum Dots: Theory and Applications to Quantum Computing

Several prominent proposals have suggested that spins of localized electrons could serve as quantum computer qubits. The exchange interaction has been invoked as a means of implementing two qubit gates. In this paper, we analyze the strength and form of the exchange interaction under relevant conditions. We find that, when several spins are engaged in mutual interactions, the quantitative strengths or even qualitative forms of the interactions can change. It is shown that the changes can be dramatic within a Heitler-London model. Hund-Mulliken calculations are also presented, and support the qualititative conclusions from the Heitler-London model. The effects need to be considered in spin-based quantum computer designs, either as a source of gate error to be overcome or a new interaction to be exploited.Comment: 16 pages, 16 figures. v3: Added Hund-Mulliken calculations in 3-dots case. A few small corrections. This version submitted to PR

Sex differences in plasma clozapine and norclozapine concentrations in clinical practice and in relation to body mass index and plasma glucose concentrations: a retrospective survey

Background Clozapine is widely prescribed and, although effective, can cause weight gain and dysglycemia. The dysmetabolic effects of clozapine are thought to be more prevalent in women with this gender on average attaining 17 % higher plasma clozapine concentrations than men. Methods We investigated the relationship between dose, body mass index (BMI), plasma glucose concentration, and plasma clozapine and N-desmethylclozapine (norclozapine) concentrations in 100 individuals with a severe enduring mental illness. Results Mean (10th/90th percentile) plasma clozapine concentrations were higher for women [0.49 (0.27–0.79) mg/L] compared with men [0.44 (0.26–0.70) mg/L] (F = 2.2; p = 0.035). There was no significant gender difference in the prescribed clozapine dose. BMI was significantly higher in women [mean (95 % CI) = 34.5 (26.0–45.3)] for females compared with 32.5 (25.2–41.0) for males. Overall, BMI increased by 0.7 kg/m 2 over a mean follow-up period of 210 days. A lower proportion, 41 % of women had a fasting blood glucose ≤6.0 mmol/L (<6.0 mmol/L is defined by the International Diabetes Federation as normal glucose handling), compared with 88 % of men (χ2  = 18.6, p < 0.0001). Conclusions We have shown that mean BMI and blood glucose concentrations are higher in women prescribed clozapine than in men. Women also tended to attain higher plasma clozapine concentrations than men. The higher BMI and blood glucose in women may relate to higher tissue exposure to clozapine, as a consequence of sex differences in drug metabolism