Developing surrogate markers for predicting antibiotic resistance "hot spots" in rivers where limited data are available

Pinpointing environmental antibiotic resistance (AR) hot spots in low-and middle-income countries (LMICs) is hindered by a lack of available and comparable AR monitoring data relevant to such settings. Addressing this problem, we performed a comprehensive spatial and seasonal assessment of water quality and AR conditions in a Malaysian river catchment to identify potential "simple"surrogates that mirror elevated AR. We screened for resistant coliforms, 22 antibiotics, 287 AR genes and integrons, and routine water quality parameters, covering absolute concentrations and mass loadings. To understand relationships, we introduced standardized "effect sizes"(Cohen's D) for AR monitoring to improve comparability of field studies. Overall, water quality generally declined and environmental AR levels increased as one moved down the catchment without major seasonal variations, except total antibiotic concentrations that were higher in the dry season (Cohen's D > 0.8, P < 0.05). Among simple surrogates, dissolved oxygen (DO) most strongly correlated (inversely) with total AR gene concentrations (Spearman's ρ 0.81, P < 0.05). We suspect this results from minimally treated sewage inputs, which also contain AR bacteria and genes, depleting DO in the most impacted reaches. Thus, although DO is not a measure of AR, lower DO levels reflect wastewater inputs, flagging possible AR hot spots. DO measurement is inexpensive, already monitored in many catchments, and exists in many numerical water quality models (e.g., oxygen sag curves). Therefore, we propose combining DO data and prospective modeling to guide local interventions, especially in LMIC rivers with limited data

Effects of Dietary Distillers Dried Grains with Solubles and Soybean Meal on Extruded Pellet Characteristics and Growth Responses of Juvenile Yellow Perch

A 126-d feeding trial was performed to investigate graded combinations of distillers dried grains with solubles (DDGS) and soybean meal (SBM) in diets formulated for yellow perch Perca flavescens. Six experimental diets contained DDGS and SBM at 0 and 31.5% (dry matter basis), respectively (0/31.5 diet), 10 and 26% (10/26), 20 and 20.5% (20/20.5), 30 and 15% (30/15), 40 and 9.5% (40/9.5), and 50 and 4% (50/4) to obtain similar levels of crude protein (mean ± SE = 30.1 ± 0.2%), crude lipid (16.7 ± 0.7%), and digestible energy (13.5 ± 0.2 kJ/g). Fourteen fish (initial individual weight = 19.1 ± 0.5 g) were randomly selected and stocked into each of twenty-four 110-L tanks (4 replicate tanks/diet). Common biological and mechanical filter systems were used to recirculate the water and maintain similar water quality. Fish that received the 40/9.5 diet exhibited the highest apparent absolute weight gain and percent weight gain, while fish that were fed the 10/26, 20/20.5, 30/15, and 40/9.5 diets exhibited similar absolute weight gain. Fish that were given the 20/20.5, 30/15, and 40/9.5 diets also exhibited similar percent weight gain. Fulton’s condition factor and apparent protein digestibility were significantly lower and higher, respectively, for fish that received the 50/4 diet than for all other treatment groups. Crude protein and crude lipid levels in muscle samples did not significantly differ among treatment groups. Results indicated that yellow perch can utilize DDGS plus SBM at a combined inclusion level of up to 49.5% without negative effects on growth. The mechanical strength and color of the extruded pellets were related to the level of DDGS plus SBM in the feed blends. Hepatosomatic indices were correlated with pellet color, while protein digestibility decreased with increasing pellet strength

Robertson Intelligent States

Diagonalization of uncertainty matrix and minimization of Robertson inequality for n observables are considered. It is proved that for even n this relation is minimized in states which are eigenstates of n/2 independent complex linear combinations of the observables. In case of canonical observables this eigenvalue condition is also necessary. Such minimizing states are called Robertson intelligent states (RIS). The group related coherent states (CS) with maximal symmetry (for semisimple Lie groups) are particular case of RIS for the quadratures of Weyl generators. Explicit constructions of RIS are considered for operators of su(1,1), su(2), h_N and sp(N,R) algebras. Unlike the group related CS, RIS can exhibit strong squeezing of group generators. Multimode squared amplitude squeezed states are naturally introduced as sp(N,R) RIS. It is shown that the uncertainty matrices for quadratures of q-deformed boson operators a_{q,j} (q > 0) and of any k power of a_j = a_{1,j} are positive definite and can be diagonalized by symplectic linear transformations. PACS numbers: 03.65.Fd, 42.50.DvComment: 23 pages, LaTex. Minor changes in text and references. Accepted in J. Phys.

Barut-Girardello coherent states for u(p,q) and sp(N,R) and their macroscopic superpositions

The Barut-Girardello coherent states (BG CS) representation is extended to the noncompact algebras u(p,q) and sp(N,R) in (reducible) quadratic boson realizations. The sp(N,R) BG CS take the form of multimode ordinary Schr\"odinger cat states. Macroscopic superpositions of 2^{n-1} sp(N,R) CS (2^n canonical CS, n=1,2,...) are pointed out which are overcomplete in the N-mode Hilbert space and the relation between the canonical CS and the u(p,q) BG-type CS representations is established. The sets of u(p,q) and sp(N,R) BG CS and their discrete superpositions contain many states studied in quantum optics (even and odd N-mode CS, pair CS) and provide an approach to quadrature squeezing, alternative to that of intelligent states. New subsets of weakly and strongly nonclassical states are pointed out and their statistical properties (first- and second-order squeezing, photon number distributions) are discussed. For specific values of the angle parameters and small amplitude of the canonical CS components these states approaches multimode Fock states with one, two or three bosons/photons. It is shown that eigenstates of a squared non-Hermitian operator A^2 (generalized cat states) can exhibit squeezing of the quadratures of A.Comment: 29 pages, LaTex, 5 figures. Improvements in text, corrections in some formulas. To appear in J. Phys. A, v. 3

A Hidden Markov Model for Copy Number Variant prediction from whole genome resequencing data

Motivation: Copy Number Variants (CNVs) are important genetic factors for studying human diseases. While high-throughput whole genome re-sequencing provides multiple lines of evidence for detecting CNVs, computational algorithms need to be tailored for different type or size of CNVs under different experimental designs. Results: To achieve optimal power and resolution of detecting CNVs at low depth of coverage, we implemented a Hidden Markov Model that integrates both depth of coverage and mate-pair relationship. The novelty of our algorithm is that we infer the likelihood of carrying a deletion jointly from multiple mate pairs in a region without the requirement of a single mate pairs being obvious outliers. By integrating all useful information in a comprehensive model, our method is able to detect medium-size deletions (200-2000bp) at low depth (<10× per sample). We applied the method to simulated data and demonstrate the power of detecting medium-size deletions is close to theoretical values. Availability: A program implemented in Java, Zinfandel, is available at http://www.cs.columbia.edu/~itsik/zinfandel

Two-photon parametric pumping versus two-photon absorption: A quantum jump approach

Published versio

Clinical relevance of heparin-PF4 complex antibody in DVT after total joint replacement

<p>Abstract</p> <p>Background</p> <p>Antibodies to the heparin-platelet factor-4 (HPF-4) complex (HIT antibodies) have been observed in patients with heparin-induced thrombocytopenia (HIT). These antibodies are thought to be involved in thrombosis through activation of platelet/endothelial cells. This prospective study was conducted to determine the incidence of post-operative HIT antibodies to assess the associated risk of deep vein thrombosis (DVT) in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA).</p> <p>Methods</p> <p>We studied 104 patients who underwent unilateral primary TKA (n = 44) and primary THA (n = 60) with short-duration prophylaxis (1–2 days of a fixed dose of unfractionated heparin). HIT antibodies were assayed using a sandwich-type ELISA before the operation and after heparin treatment (post-operative day 7).</p> <p>Results</p> <p>In the clinical outcome, the incidence of symptomatic DVT was 15.4% (16/104, TKA; 10, THA 6) and pulmonary embolism (PE) was not observed. The total seroconversion rate of HIT antibodies at post-operative day 7 was 34.6% (36/104). Among 36 seroconverted patients, 11 (30.6%) developed symptomatic DVT and 5 out of 68 of the non-seroconverted patients (7.4%) developed symptomatic DVT. The incidence for DVT was significantly higher in the seroconverted patients compared with that of the non-seroconverted patients (odds ratio 5.5, 95%CI: 1.7–17.6 <it>p </it>= 0.0028). Furthermore, in the patients with symptomatic DVT, the titer of HIT antibodies at post-operative day 7 was significantly higher compared with those without symptomatic DVT.</p> <p>Conclusion</p> <p>Our data therefore suggest that seroconversion for HIT antibodies generated by heparin is associated with a risk of DVT in patients undergoing total joint replacement.</p

Chemoproteomics reveals Toll-like receptor fatty acylation

Partial funding for Open Access provided by The Ohio State University Open Access Fund.Background: Palmitoylation is a 16-carbon lipid post-translational modification that increases protein hydrophobicity. This form of protein fatty acylation is emerging as a critical regulatory modification for multiple aspects of cellular interactions and signaling. Despite recent advances in the development of chemical tools for the rapid identification and visualization of palmitoylated proteins, the palmitoyl proteome has not been fully defined. Here we sought to identify and compare the palmitoylated proteins in murine fibroblasts and dendritic cells. Results: A total of 563 putative palmitoylation substrates were identified, more than 200 of which have not been previously suggested to be palmitoylated in past proteomic studies. Here we validate the palmitoylation of several new proteins including Toll-like receptors (TLRs) 2, 5 and 10, CD80, CD86, and NEDD4. Palmitoylation of TLR2, which was uniquely identified in dendritic cells, was mapped to a transmembrane domain-proximal cysteine. Inhibition of TLR2 S-palmitoylation pharmacologically or by cysteine mutagenesis led to decreased cell surface expression and a decreased inflammatory response to microbial ligands. Conclusions: This work identifies many fatty acylated proteins involved in fundamental cellular processes as well as cell type-specific functions, highlighting the value of examining the palmitoyl proteomes of multiple cell types. Spalmitoylation of TLR2 is a previously unknown immunoregulatory mechanism that represents an entirely novel avenue for modulation of TLR2 inflammatory activity.This work was supported by funding from the NIH/NIAID (grant R00AI095348 to J.S.Y.), the NIH/NIGMS (R01GM087544 to HCH), and the Ohio State University Public Health Preparedness for Infectious Diseases (PHPID) program. NMC is supported by the Ohio State University Systems and Integrative Biology Training Program (NIH/NIGMS grant T32GM068412). BWZ is a fellow of the National Science Foundation Graduate Research Fellowship Program (DGE-0937362)

Superhard Phases of Simple Substances and Binary Compounds of the B-C-N-O System: from Diamond to the Latest Results (a Review)

The basic known and hypothetic one- and two-element phases of the B-C-N-O system (both superhard phases having diamond and boron structures and precursors to synthesize them) are described. The attention has been given to the structure, basic mechanical properties, and methods to identify and characterize the materials. For some phases that have been recently described in the literature the synthesis conditions at high pressures and temperatures are indicated.Comment: Review on superhard B-C-N-O phase

The birth of a human-specific neural gene by incomplete duplication and gene fusion

Background: Gene innovation by duplication is a fundamental evolutionary process but is difficult to study in humans due to the large size, high sequence identity, and mosaic nature of segmental duplication blocks. The human-specific gene hydrocephalus-inducing 2, HYDIN2, was generated by a 364 kbp duplication of 79 internal exons of the large ciliary gene HYDIN from chromosome 16q22.2 to chromosome 1q21.1. Because the HYDIN2 locus lacks the ancestral promoter and seven terminal exons of the progenitor gene, we sought to characterize transcription at this locus by coupling reverse transcription polymerase chain reaction and long-read sequencing. Results: 5' RACE indicates a transcription start site for HYDIN2 outside of the duplication and we observe fusion transcripts spanning both the 5' and 3' breakpoints. We observe extensive splicing diversity leading to the formation of altered open reading frames (ORFs) that appear to be under relaxed selection. We show that HYDIN2 adopted a new promoter that drives an altered pattern of expression, with highest levels in neural tissues. We estimate that the HYDIN duplication occurred ~3.2 million years ago and find that it is nearly fixed (99.9%) for diploid copy number in contemporary humans. Examination of 73 chromosome 1q21 rearrangement patients reveals that HYDIN2 is deleted or duplicated in most cases. Conclusions: Together, these data support a model of rapid gene innovation by fusion of incomplete segmental duplications, altered tissue expression, and potential subfunctionalization or neofunctionalization of HYDIN2 early in the evolution of the Homo lineage