(Clemson University) While the world admires the beauty and fragrance of flowers, most of us are missing out on the extraordinary processes these seemingly delicate life forms are carrying out every moment of the day. Matthew Koski, an assistant professor at Clemson, is not only paying attention, he is advancing his research with a three-year, $455,000 grant from the NSF for a study of flower adaptations titled 'Modifying the floral microenvironment: elevational divergence in floral thermoregulatory mechanisms.'

Pathogenic bacteria of the genera Mycobacterium and Corynebacterium cause severe human diseases such as tuberculosis (Mycobacterium tuberculosis) and diphtheria (Corynebacterium diphtheriae). The cells of these species are surrounded by protective cell walls rich in long-chain mycolic acids. These fatty acids are conjugated to the disaccharide trehalose on the cytoplasmic side of the bacterial cell membrane. They are then transported across the membrane to the periplasm where they act as donors for other reactions. We have previously shown that transient acetylation of the glycolipid trehalose monohydroxycorynomycolate (hTMCM) enables its efficient transport to the periplasm in Corynebacterium glutamicum and that acetylation is mediated by the membrane protein TmaT. Here, we show that a putative methyltransferase, encoded at the same genetic locus as TmaT, is also required for optimal hTMCM transport. Deletion of the C. glutamicum gene NCgl2764 (Rv0224c in M. tuberculosis) abolished acetyltrehalose monocorynomycolate (AcTMCM) synthesis, leading to accumulation of hTMCM in the inner membrane and delaying its conversion to trehalose dihydroxycorynomycolate (h2TDCM). Complementation with NCgl2764 normalized turnover of hTMCM to h2TDCM. In contrast, complementation with NCgl2764 derivatives mutated at residues essential for methyltransferase activity failed to rectify the defect, suggesting that NCgl2764/Rv0224c encodes a methyltransferase, designated here as MtrP. Comprehensive analyses of the individual mtrP and tmaT mutants and of a double mutant revealed strikingly similar changes across several lipid classes compared with WT bacteria. These findings indicate that both MtrP and TmaT have nonredundant roles in regulating AcTMCM synthesis, revealing additional complexity in the regulation of trehalose mycolate transport in the Corynebacterineae.

The millions of customers, the short deadline: how the public service's digital revolution will start.

Deanna L. Davis
Apr 1, 2020; 61:505-522
Research Articles

11 March 2020

This article provides an introduction to Fourier transform-based mass spectrometry (FTMS). The key performance characteristics of FTMS, mass accuracy and resolution, are presented in the view of how they impact the interpretation of measurements in proteomic applications. The theory and principles of operation of two types of mass analyzer, Fourier transform ion cyclotron resonance and Orbitrap, are described. Major benefits as well as limitations of FTMS technology are discussed in the context of practical sample analysis, and illustrated with examples included as figures in this text and in the accompanying slide set. Comparisons highlighting the performance differences between the two mass analyzers are made where deemed useful in assisting the user with choosing the most appropriate technology for his/her application. Recent developments of these high-performing mass spectrometers are mentioned to provide a future outlook.

11 March 2020

Primitive sterol evolution plays an important role in fossil record interpretation and offers potential therapeutic avenues for human disease resulting from nematode infections. Recognizing that C4-methyl stenol products [8(14)-lophenol] can be synthesized in bacteria while C4-methyl stanol products (dinosterol) can be synthesized in dinoflagellates and preserved as sterane biomarkers in ancient sedimentary rock is key to eukaryotic sterol evolution. In this regard, nematodes have been proposed to convert dietary cholesterol to 8(14)-lophenol by a secondary metabolism pathway that could involve sterol C4 methylation analogous to the C2 methylation of hopanoids (radicle-type mechanism) or C24 methylation of sterols (carbocation-type mechanism). Here, we characterized dichotomous cholesterol metabolic pathways in Caenorhabditis elegans that generate 3-oxo sterol intermediates in separate paths to lophanol (4-methyl stanol) and 8(14)-lophenol (4-methyl stenol). We uncovered alternate C3-sterol oxidation and ⁷ desaturation steps that regulate sterol flux from which branching metabolite networks arise, while lophanol/8(14)-lophenol formation is shown to be dependent on a sterol C4α-methyltransferse (4-SMT) that requires 3-oxo sterol substrates and catalyzes a newly discovered 3-keto-enol tautomerism mechanism linked to S-adenosyl-l-methionine-dependent methylation. Alignment-specific substrate-binding domains similarly conserved in 4-SMT and 24-SMT enzymes, despite minimal amino acid sequence identity, suggests divergence from a common, primordial ancestor in the evolution of methyl sterols. The combination of these results provides evolutionary leads to sterol diversity and points to cryptic C4-methyl steroidogenic pathways of targeted convergence that mediate lineage-specific adaptations.­­

Myelin is a unique lipid-rich membrane structure that accelerates neurotransmission and supports neuronal function. Sphingolipids are critical myelin components. Yet sphingolipid content and synthesis have not been well characterized in oligodendrocytes, the myelin-producing cells of the CNS. Here, using quantitative real-time PCR, LC-MS/MS-based lipid analysis, and biochemical assays, we examined sphingolipid synthesis during the peak period of myelination in the postnatal rat brain. Importantly, we characterized sphingolipid production in isolated oligodendrocytes. We analyzed sphingolipid distribution and levels of critical enzymes and regulators in the sphingolipid biosynthetic pathway, with focus on the serine palmitoyltransferase (SPT) complex, the rate-limiting step in this pathway. During myelination, levels of the major SPT subunits increased and oligodendrocyte maturation was accompanied by extensive alterations in the composition of the SPT complex. These included changes in the relative levels of two alternative catalytic subunits, SPTLC2 and -3, in the relative levels of isoforms of the small subunits, ssSPTa and -b, and in the isoform distribution of the SPT regulators, the ORMDLs. Myelination progression was accompanied by distinct changes in both the nature of the sphingoid backbone and the N-acyl chains incorporated into sphingolipids. We conclude that the distribution of these changes among sphingolipid family members is indicative of a selective channeling of the ceramide backbone toward specific downstream metabolic pathways during myelination. Our findings provide insights into myelin production in oligodendrocytes and suggest how dysregulation of the biosynthesis of this highly specialized membrane could contribute to demyelinating diseases.

If your business key column is a name literal, like " business key "n, a syntax error occurs when that variable name does not follow standard SAS naming conventions.

In SAS Data Integration Studio, the columns that you select to include in the target table in a Business Rules transformation appear in the Selected columns area in a random order. Th

Pathogenic bacteria of the genera Mycobacterium and Corynebacterium cause severe human diseases such as tuberculosis (Mycobacterium tuberculosis) and diphtheria (Corynebacterium diphtheriae). The cells of these species are surrounded by protective cell walls rich in long-chain mycolic acids. These fatty acids are conjugated to the disaccharide trehalose on the cytoplasmic side of the bacterial cell membrane. They are then transported across the membrane to the periplasm where they act as donors for other reactions. We have previously shown that transient acetylation of the glycolipid trehalose monohydroxycorynomycolate (hTMCM) enables its efficient transport to the periplasm in Corynebacterium glutamicum and that acetylation is mediated by the membrane protein TmaT. Here, we show that a putative methyltransferase, encoded at the same genetic locus as TmaT, is also required for optimal hTMCM transport. Deletion of the C. glutamicum gene NCgl2764 (Rv0224c in M. tuberculosis) abolished acetyltrehalose monocorynomycolate (AcTMCM) synthesis, leading to accumulation of hTMCM in the inner membrane and delaying its conversion to trehalose dihydroxycorynomycolate (h2TDCM). Complementation with NCgl2764 normalized turnover of hTMCM to h2TDCM. In contrast, complementation with NCgl2764 derivatives mutated at residues essential for methyltransferase activity failed to rectify the defect, suggesting that NCgl2764/Rv0224c encodes a methyltransferase, designated here as MtrP. Comprehensive analyses of the individual mtrP and tmaT mutants and of a double mutant revealed strikingly similar changes across several lipid classes compared with WT bacteria. These findings indicate that both MtrP and TmaT have nonredundant roles in regulating AcTMCM synthesis, revealing additional complexity in the regulation of trehalose mycolate transport in the Corynebacterineae.

Heme-regulatory motifs (HRMs) are present in many proteins that are involved in diverse biological functions. The C-terminal tail region of human heme oxygenase-2 (HO2) contains two HRMs whose cysteine residues form a disulfide bond; when reduced, these cysteines are available to bind Fe3+-heme. Heme binding to the HRMs occurs independently of the HO2 catalytic active site in the core of the protein, where heme binds with high affinity and is degraded to biliverdin. Here, we describe the reversible, protein-mediated transfer of heme between the HRMs and the HO2 core. Using hydrogen-deuterium exchange (HDX)-MS to monitor the dynamics of HO2 with and without Fe3+-heme bound to the HRMs and to the core, we detected conformational changes in the catalytic core only in one state of the catalytic cycle—when Fe3+-heme is bound to the HRMs and the core is in the apo state. These conformational changes were consistent with transfer of heme between binding sites. Indeed, we observed that HRM-bound Fe3+-heme is transferred to the apo-core either upon independent expression of the core and of a construct spanning the HRM-containing tail or after a single turnover of heme at the core. Moreover, we observed transfer of heme from the core to the HRMs and equilibration of heme between the core and HRMs. We therefore propose an Fe3+-heme transfer model in which HRM-bound heme is readily transferred to the catalytic site for degradation to facilitate turnover but can also equilibrate between the sites to maintain heme homeostasis.

Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans. This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder. The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown. Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80–2.50 Å resolution. These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis. Together with molecular dynamics simulations, the structures also revealed how FUT8 dimerization plays an important role in defining the acceptor substrate-binding site. Collectively, this information significantly builds on our understanding of the core fucosylation process.

Andrew S. Kimball
Sep 1, 2017; 66:2459-2471
Immunology and Transplantation

11 March 2020

The University of Kentucky has landed a commitment from former Wake Forest big man Olivier Sarr, one of the top transfers ahead of the 2020 season.

Dentists who have had a dental plan payment check lost in the mail could consider a way to receive safe and secure payment through electronic funds transfer payments.

OBJECTIVE

We conducted an open-label, phase I study using autologous umbilical cord blood (UCB) infusion to ameliorate type 1 diabetes (T1D). Having previously reported on the first 15 patients reaching 1 year of follow-up, herein we report on the complete cohort after 2 years of follow-up.

Every business begun before the Internet now faces the same challenge: How to transform to compete in a digital economy? This is the leadership challenge examined by BRITE founder and Columbia Business School faculty member David Rogers in his newest book, The Digital Transformation Playbook (April 5, 2016; Columbia Business School Publishing). In the book, […]

We all understand that digital media, data, and analytics are driving transformations in society and business. Most marketers are now armed with case studies of what can be done differently, but many are still challenged with how to truly develop new ideas and execute new strategies to grow their business. Mitch Joel, President of Mirum […]

What if you could repay loans through volunteering and mentorship instead of money? Activist Angie Murimirwa shares how a game-changing economic tool known as "social interest" is reinvigorating sub-Saharan communities once trapped in cycles of poverty. Join her as she explains how this approach to lending is creating opportunities for thousands of African women and girls -- and shows why this model can be replicated anywhere with lasting effects.

Sam Houston State has announced the addition of two transfer wide receivers, former Howard standout Jequez Ezzard and Harvard grad transfer Cody Chrest, for their final seasons of eligibility this year. The 5-foot-9, 190-pound Ezzard, from College Park, Georgia, gives the Southland Conference program one of the top big-play pass catchers in the FCS. The 6-foot, 190-pound Chrest, from Houston, broke out last season with 45 receptions and 706 receiving yards, Harvard's team highs.

City planning -- Remote sensing.

Biodiversity -- Climatic factors.

Paris : V.A. Delahaye, 1880.

London (46 Pall Mall) : Pub.d by R. Bowyer & M. Parkes, 1st Jan.y 1830.

England : London County Council, Public Assistance Department, 1935.

Leith, 2019

Oregon State basketball player Destiny Slocum has opted to enter the transfer portal for her final season of eligibility. Slocum, a 5-foot-7 guard, averaged a team-best 14.9 points and had 4.7 assists a game this past season with the Beavers, who finished the season ranked No. 14 with a 23-9 record. In a statement released by the university on Thursday, Slocum thanked everyone who supported her in the decision.

The Tennessee Lady Vols have added forward-center Keyen Green as a graduate transfer from Liberty. Coach Kellie Harper announced Wednesday that Green has signed a scholarship for the upcoming season. The 6-foot-1 Green spent the past four seasons at Liberty and graduated in May 2019.

LEXINGTON, Ky. (AP) -- Sophomore guards Jazmine Massengill and Robyn Benton transferred to Kentucky from Southeastern Conference rivals Wednesday.

Maori Davenport, who drew national attention over an eligibility dispute during her senior year of high school, is transferring to Georgia after playing sparingly in her lone season at Rutgers. Lady Bulldogs coach Joni Taylor announced Davenport's decision Wednesday. The 6-foot-4 center from Troy, Alabama will have to sit out a season under NCAA transfer rules before she is eligible to join Georgia in 2021-22.

Baylor has signed a transfer point guard for the third year in a row, and this one can play multiple seasons with the Lady Bears. Jaden Owens is transferring from UCLA after signing a national letter of intent with Baylor, which had graduate transfers at point guard each of the past two seasons. The Texas native just completed her freshman season with the Bruins and has three seasons of eligibility remaining.

François Bachoc, José Betancourt, Reinhard Furrer, Thierry Klein.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 1962--2008.

Abstract:
The asymptotic analysis of covariance parameter estimation of Gaussian processes has been subject to intensive investigation. However, this asymptotic analysis is very scarce for non-Gaussian processes. In this paper, we study a class of non-Gaussian processes obtained by regular non-linear transformations of Gaussian processes. We provide the increasing-domain asymptotic properties of the (Gaussian) maximum likelihood and cross validation estimators of the covariance parameters of a non-Gaussian process of this class. We show that these estimators are consistent and asymptotically normal, although they are defined as if the process was Gaussian. They do not need to model or estimate the non-linear transformation. Our results can thus be interpreted as a robustness of (Gaussian) maximum likelihood and cross validation towards non-Gaussianity. Our proofs rely on two technical results that are of independent interest for the increasing-domain asymptotic literature of spatial processes. First, we show that, under mild assumptions, coefficients of inverses of large covariance matrices decay at an inverse polynomial rate as a function of the corresponding observation location distances. Second, we provide a general central limit theorem for quadratic forms obtained from transformed Gaussian processes. Finally, our asymptotic results are illustrated by numerical simulations.

Daniel R. Kowal, Antonio Canale.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 1744--1772.

Abstract:
We propose a simple yet powerful framework for modeling integer-valued data, such as counts, scores, and rounded data. The data-generating process is defined by Simultaneously Transforming and Rounding (STAR) a continuous-valued process, which produces a flexible family of integer-valued distributions capable of modeling zero-inflation, bounded or censored data, and over- or underdispersion. The transformation is modeled as unknown for greater distributional flexibility, while the rounding operation ensures a coherent integer-valued data-generating process. An efficient MCMC algorithm is developed for posterior inference and provides a mechanism for adaptation of successful Bayesian models and algorithms for continuous data to the integer-valued data setting. Using the STAR framework, we design a new Bayesian Additive Regression Tree model for integer-valued data, which demonstrates impressive predictive distribution accuracy for both synthetic data and a large healthcare utilization dataset. For interpretable regression-based inference, we develop a STAR additive model, which offers greater flexibility and scalability than existing integer-valued models. The STAR additive model is applied to study the recent decline in Amazon river dolphins.

Benjamin Colling, Ingrid Van Keilegom.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 769--800.

Abstract:
Consider the following semiparametric transformation model $Lambda_{ heta }(Y)=m(X)+varepsilon $, where $X$ is a $d$-dimensional covariate, $Y$ is a univariate response variable and $varepsilon $ is an error term with zero mean and independent of $X$. We assume that $m$ is an unknown regression function and that ${Lambda _{ heta }: heta inTheta }$ is a parametric family of strictly increasing functions. Our goal is to develop two new estimators of the transformation parameter $ heta $. The main idea of these two estimators is to minimize, with respect to $ heta $, the $L_{2}$-distance between the transformation $Lambda _{ heta }$ and one of its fully nonparametric estimators. We consider in particular the nonparametric estimator based on the least-absolute deviation loss constructed in Colling and Van Keilegom (2019). We establish the consistency and the asymptotic normality of the two proposed estimators of $ heta $. We also carry out a simulation study to illustrate and compare the performance of our new parametric estimators to that of the profile likelihood estimator constructed in Linton et al. (2008).

The wavelet scattering transform is an invariant and stable signal representation suitable for many signal processing and machine learning applications. We present the Kymatio software package, an easy-to-use, high-performance Python implementation of the scattering transform in 1D, 2D, and 3D that is compatible with modern deep learning frameworks, including PyTorch and TensorFlow/Keras. The transforms are implemented on both CPUs and GPUs, the latter offering a significant speedup over the former. The package also has a small memory footprint. Source code, documentation, and examples are available under a BSD license at https://www.kymat.io.

Datasets in sleep science present challenges for machine learning algorithms due to differences in recording setups across clinics. We investigate two deep transfer learning strategies for overcoming the channel mismatch problem for cases where two datasets do not contain exactly the same setup leading to degraded performance in single-EEG models. Specifically, we train a baseline model on multivariate polysomnography data and subsequently replace the first two layers to prepare the architecture for single-channel electroencephalography data. Using a fine-tuning strategy, our model yields similar performance to the baseline model (F1=0.682 and F1=0.694, respectively), and was significantly better than a comparable single-channel model. Our results are promising for researchers working with small databases who wish to use deep learning models pre-trained on larger databases.

Recent advancements in diagnostic learning and development of gesture-based human machine interfaces have driven surface electromyography (sEMG) towards significant importance. Analysis of hand gestures requires an accurate assessment of sEMG signals. The proposed work presents a novel sequential master-slave architecture consisting of deep neural networks (DNNs) for classification of signs from the Indian sign language using signals recorded from multiple sEMG channels. The performance of the master-slave network is augmented by leveraging additional synthetic feature data generated by long short term memory networks. Performance of the proposed network is compared to that of a conventional DNN prior to and after the addition of synthetic data. Up to 14% improvement is observed in the conventional DNN and up to 9% improvement in master-slave network on addition of synthetic data with an average accuracy value of 93.5% asserting the suitability of the proposed approach.

Edgar Dobriban, William Leeb, Amit Singer.

Source: The Annals of Statistics, Volume 48, Number 1, 491--513.

Abstract:
We consider the linearly transformed spiked model , where the observations $Y_{i}$ are noisy linear transforms of unobserved signals of interest $X_{i}$: egin{equation*}Y_{i}=A_{i}X_{i}+varepsilon_{i},end{equation*} for $i=1,ldots ,n$. The transform matrices $A_{i}$ are also observed. We model the unobserved signals (or regression coefficients) $X_{i}$ as vectors lying on an unknown low-dimensional space. Given only $Y_{i}$ and $A_{i}$ how should we predict or recover their values? The naive approach of performing regression for each observation separately is inaccurate due to the large noise level. Instead, we develop optimal methods for predicting $X_{i}$ by “borrowing strength” across the different samples. Our linear empirical Bayes methods scale to large datasets and rely on weak moment assumptions. We show that this model has wide-ranging applications in signal processing, deconvolution, cryo-electron microscopy, and missing data with noise. For missing data, we show in simulations that our methods are more robust to noise and to unequal sampling than well-known matrix completion methods.

Michael Jauch, Peter D. Hoff, David B. Dunson.

Source: Bernoulli, Volume 26, Number 2, 1560--1586.

Abstract:
Random orthogonal matrices play an important role in probability and statistics, arising in multivariate analysis, directional statistics, and models of physical systems, among other areas. Calculations involving random orthogonal matrices are complicated by their constrained support. Accordingly, we parametrize the Stiefel and Grassmann manifolds, represented as subsets of orthogonal matrices, in terms of Euclidean parameters using the Cayley transform. We derive the necessary Jacobian terms for change of variables formulas. Given a density defined on the Stiefel or Grassmann manifold, these allow us to specify the corresponding density for the Euclidean parameters, and vice versa. As an application, we present a Markov chain Monte Carlo approach to simulating from distributions on the Stiefel and Grassmann manifolds. Finally, we establish that the Euclidean parameters corresponding to a uniform orthogonal matrix can be approximated asymptotically by independent normals. This result contributes to the growing literature on normal approximations to the entries of random orthogonal matrices or transformations thereof.