Private Multiplicative Weights Beyond Linear Queries

A wide variety of fundamental data analyses in machine learning, such as linear and logistic regression, require minimizing a convex function defined by the data. Since the data may contain sensitive information about individuals, and these analyses can leak that sensitive information, it is important to be able to solve convex minimization in a privacy-preserving way. A series of recent results show how to accurately solve a single convex minimization problem in a differentially private manner. However, the same data is often analyzed repeatedly, and little is known about solving multiple convex minimization problems with differential privacy. For simpler data analyses, such as linear queries, there are remarkable differentially private algorithms such as the private multiplicative weights mechanism (Hardt and Rothblum, FOCS 2010) that accurately answer exponentially many distinct queries. In this work, we extend these results to the case of convex minimization and show how to give accurate and differentially private solutions to *exponentially many* convex minimization problems on a sensitive dataset

Co-registration of Sequential Multidetector Computed Tomography Studies for the Evaluation of Surgical Instrumentation following Resection of Spinal Tumors

Surgical resection of spinal tumors involves complex reconstructive procedures. The stability and integrity of the surgical construct are evaluated with multidetector computed tomography (MDCT). As coregistration, or fusion, of different imaging modalities, especially positron emission tomography/computed tomography (PET/CT), is common practice, we sought to determine if this technique could be applied to sequential, postoperative MDCT studies of the spine. Herein, we demonstrate that by utilizing the Hermes workstation, co-registration of MDCT spine studies can be performed. This technique allows sequential MDCT examinations of the post-operative spine to be viewed together as one study and may aid in evaluation of the position and integrity of the surgical construct over time. Further study and refinement of this technique will be necessary before clinical implementation

Black Holes in the Universe: Generalized Lemaitre-Tolman-Bondi Solutions

We present new exact solutions {which presumably describe} black holes in the background of a spatially flat, pressureless dark matter (DM)-, or dark matter plus dark energy (DM+DE)-, or quintom-dominated universe. These solutions generalize Lemaitre-Tolman-Bondi metrics. For a DM- or (DM+DE)-dominated universe, the area of the black hole apparent horizon (AH) decreases with the expansion of the universe while that of the cosmic AH increases. However, for a quintom-dominated universe, the black hole AH first shrinks and then expands, while the cosmic AH first expands and then shrinks. A (DM+DE)-dominated universe containing a black hole will evolve to the Schwarzschild-de Sitter solution with both AHs approaching constant size. In a quintom-dominated universe, the black hole and cosmic AHs will coincide at a certain time, after which the singularity becomes naked, violating Cosmic Censorship.Comment: 13 pages, 4 figure

Compositional Proteomics: Effects of Spatial Constraints on Protein Quantification Utilizing Isobaric Tags.

Mass spectrometry (MS) has become an accessible tool for whole proteome quantitation with the ability to characterize protein expression across thousands of proteins within a single experiment. A subset of MS quantification methods (e.g., SILAC and label-free) monitor the relative intensity of intact peptides, where thousands of measurements can be made from a single mass spectrum. An alternative approach, isobaric labeling, enables precise quantification of multiple samples simultaneously through unique and sample specific mass reporter ions. Consequently, in a single scan, the quantitative signal comes from a limited number of spectral features (≤11). The signal observed for these features is constrained by automatic gain control, forcing codependence of concurrent signals. The study of constrained outcomes primarily belongs to the field of compositional data analysis. We show experimentally that isobaric tag proteomics data are inherently compositional and highlight the implications for data analysis and interpretation. We present a new statistical model and accompanying software that improves estimation accuracy and the ability to detect changes in protein abundance. Finally, we demonstrate a unique compositional effect on proteins with infinite changes. We conclude that many infinite changes will appear small and that the magnitude of these estimates is highly dependent on experimental design

Cosmological expansion and local physics

The interplay between cosmological expansion and local attraction in a gravitationally bound system is revisited in various regimes. First, weakly gravitating Newtonian systems are considered, followed by various exact solutions describing a relativistic central object embedded in a Friedmann universe. It is shown that the ``all or nothing'' behaviour recently discovered (i.e., weakly coupled systems are comoving while strongly coupled ones resist the cosmic expansion) is limited to the de Sitter background. New exact solutions are presented which describe black holes perfectly comoving with a generic Friedmann universe. The possibility of violating cosmic censorship for a black hole approaching the Big Rip is also discussed.Comment: 17 pages, LaTeX, to appear in Phys. Rev.

EXMOTIF: efficient structured motif extraction

BACKGROUND: Extracting motifs from sequences is a mainstay of bioinformatics. We look at the problem of mining structured motifs, which allow variable length gaps between simple motif components. We propose an efficient algorithm, called EXMOTIF, that given some sequence(s), and a structured motif template, extracts all frequent structured motifs that have quorum q. Potential applications of our method include the extraction of single/composite regulatory binding sites in DNA sequences. RESULTS: EXMOTIF is efficient in terms of both time and space and is shown empirically to outperform RISO, a state-of-the-art algorithm. It is also successful in finding potential single/composite transcription factor binding sites. CONCLUSION: EXMOTIF is a useful and efficient tool in discovering structured motifs, especially in DNA sequences. The algorithm is available as open-source at:

MGP Panel is a comprehensive targeted genomics panel for molecular profiling of multiple myeloma patients

PURPOSE: We designed a comprehensive multiple myeloma (MM) targeted sequencing panel to identify common genomic abnormalities in a single assay and validated it against known standards. EXPERIMENTAL DESIGN: The panel comprised 228 genes/exons for mutations, 6 regions for translocations, and 56 regions for copy number abnormalities (CNAs). Toward panel validation, targeted sequencing was conducted on 233 patient samples and further validated using clinical fluorescence in situ hybridization (FISH) (translocations), multiplex ligation probe analysis (MLPA) (CNAs), whole genome sequencing (WGS) (CNAs, mutations, translocations) or droplet digital PCR (ddPCR) of known standards (mutations). RESULTS: Canonical IgH translocations were detected in 43.2% of patients by sequencing, and aligned with FISH except for one patient. CNAs determined by sequencing and MLPA for 22 regions were comparable in 103 samples and concordance between platforms was R2=0.969. VAFs for 74 mutations were compared between sequencing and ddPCR with concordance of R2=0.9849. CONCLUSIONS: In summary, we have developed a targeted sequencing panel that is as robust or superior to FISH and WGS. This molecular panel is cost effective, comprehensive, clinically actionable and can be routinely deployed to assist risk stratification at diagnosis or post-treatment to guide sequencing of therapies

A structural comparison of human serum transferrin and human lactoferrin

The transferrins are a family of proteins that bind free iron in the blood and bodily fluids. Serum transferrins function to deliver iron to cells via a receptor-mediated endocytotic process as well as to remove toxic free iron from the blood and to provide an anti-bacterial, low-iron environment. Lactoferrins (found in bodily secretions such as milk) are only known to have an anti-bacterial function, via their ability to tightly bind free iron even at low pH, and have no known transport function. Though these proteins keep the level of free iron low, pathogenic bacteria are able to thrive by obtaining iron from their host via expression of outer membrane proteins that can bind to and remove iron from host proteins, including both serum transferrin and lactoferrin. Furthermore, even though human serum transferrin and lactoferrin are quite similar in sequence and structure, and coordinate iron in the same manner, they differ in their affinities for iron as well as their receptor binding properties: the human transferrin receptor only binds serum transferrin, and two distinct bacterial transport systems are used to capture iron from serum transferrin and lactoferrin. Comparison of the recently solved crystal structure of iron-free human serum transferrin to that of human lactoferrin provides insight into these differences

Human PAPS Synthase Isoforms Are Dynamically Regulated Enzymes with Access to Nucleus and Cytoplasm

In higher eukaryotes, PAPS synthases are the only enzymes producing the essential sulphate-donor 3′-phospho-adenosine-5′-phosphosulphate (PAPS). Recently, PAPS synthases have been associated with several genetic diseases and retroviral infection. To improve our understanding of their pathobiological functions, we analysed the intracellular localisation of the two human PAPS synthases, PAPSS1 and PAPSS2. For both enzymes, we observed pronounced heterogeneity in their subcellular localisation. PAPSS1 was predominantly nuclear, whereas PAPSS2 localised mainly within the cytoplasm. Treatment with the nuclear export inhibitor leptomycin B had little effect on their localisation. However, a mutagenesis screen revealed an Arg-Arg motif at the kinase interface exhibiting export activity. Notably, both isoforms contain a conserved N-terminal basic Lys-Lys-Xaa-Lys motif indispensable for their nuclear localisation. This nuclear localisation signal was more efficient in PAPSS1 than in PAPSS2. The activities of the identified localisation signals were confirmed by microinjection studies. Collectively, we describe unusual localisation signals of both PAPS synthase isoforms, mobile enzymes capable of executing their function in the cytoplasm as well as in the nucleus