bluuebunny/crossref_metadata_2025 huggingface dataset:
Database-driven Multi Locus Sequence Typing (MLST) of bacterial
pathogens
Authors: Chan Man-Suen , Maiden Martin C. J. , Spratt Brian G.
Published: July 2002

Motivation: Multi Locus Sequence Typing (MLST) is a newly developed typing method for bacteria based on the sequence determination of internal fragments of seven house-keeping genes. It has proved useful in characterizing and monitoring disease-causing and antibiotic resistant lineages of bacteria. The strength of this approach is that unlike data obtained using most other typing methods, sequence data are unambiguous, can be held on a central database and be queried through a web server.

Results: A database-driven software system (mlstdb) has been developed, which is used by public health laboratories and researchers globally to query their nucleotide sequence data against centrally held databases over the internet. The mlstdb system consists of a set of perl scripts for defining the database tables and generating the database management interface and dynamic web pages for querying the databases.

Availability: http://www.mlst.net.

Contact: mchan@molbiol.ox.ac.uk

* To whom correspondence should be addressed.

2 Present address: Department of Paediatrics, The Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.

3 Present address: Department of Infectious Disease Epidemiology, Imperial College School of Medicine, University of London, St Mary’s Campus, Norfolk Place, London W2 1PG, UK.
A Java applet for visualizing protein–protein interaction
Authors: Mrowka Ralf
Published: July 2002

Summary: A web applet for browsing protein–protein interactions was implemented. It enables the display of interaction relationships, based upon neighboring distance and biological function.

Availability: The Java applet is available at http://www.charite.de/bioinformatics

Contact: Mrowka@rz.hu-berlin.de
TreeWiz: interactive exploration of huge trees
Authors: Rost Ursula , Bornberg-Bauer Erich
Published: July 2002

Motivation: The rapidly increasing amount and disparity of biological data requires interpretation at many levels of description. Human judgement and intuition are important because not all data can be automatically and comprehensively analyzed. Visualization of trees and substructures corresponding to certain features are often used to analyze phylogenies or taxonomies. Unfortunately, most existing tools do not cope with the size of current datasets, the required functionality, or both.

Results: We introduce a program for visualization of huge trees and also for the interactive exploration of their content. We have developed a range of new schemes which are tailored for biological problems. Users can get an overview, zoom in, filter out data and retrieve details from standard databases such as SWISS-PROT. Furthermore, it is possible to analyze the relationship between chosen leaf sets that are specified by common features on a second level of representation. On a PC (with ≈ 512 MB RAM), trees of up to several tens of thousands of leaves can be loaded and both rapidly and interactively explored. We demonstrate the use of this program for the analysis of the SYSTERS data set (which contains hierarchically clustered protein sequences) to which PFAM domains were added as features.

Availability: TreeWiz is written in JAVA and is free for academic use. The full application as well as a restricted applet version can be found on the web-page http://www.eml.org/english/staff/homes/ulla/rost.html.

Contact: Ursula.Rost@eml.villa-bosch.de

* To whom correspondence should be addressed.
A Bayesian framework for combining gene
predictions
Authors: Pavlović Vladimir , Garg Ashutosh , Kasif Simon
Published: July 2002

Motivation: Gene identification and gene discovery in new genomic sequences is one of the most timely computational questions addressed by bioinformatics scientists. This computational research has resulted in several systems that have been used successfully in many whole-genome analysis projects. As the number of such systems grows the need for a rigorous way to combine the predictions becomes more essential.

Results: In this paper we provide a Bayesian network framework for combining gene predictions from multiple systems. The framework allows us to treat the problem as combining the advice of multiple experts. Previous work in the area used relatively simple ideas such as majority voting. We introduce, for the first time, the use of hidden input/output Markov models for combining gene predictions. We apply the framework to the analysis of the Adh region in Drosophila that has been carefully studied in the context of gene finding and used as a basis for the GASP competition. The main challenge in combination of gene prediction programs is the fact that the systems are relying on similar features such as cod on usage and as a result the predictions are often correlated. We show that our approach is promising to improve the prediction accuracy and provides a systematic and flexible framework for incorporating multiple sources of evidence into gene prediction systems.

Availability: Software can be made available on request from the authors.

Contact: vladimir@bu.edu

* Part of this research was presented at Computational Genomics 2000, Baltimore, MD, November 2000. Portions of this research were conducted at Compaq Computer Corporation, Cambridge Research Laboratory, Cambridge, MA.
OligoArray: genome-scale oligonucleotide design for microarrays
Authors: Rouillard Jean-Marie , Herbert Christopher J. , Zuker Michael
Published: July 2002

Summary: OligoArray is a program that computes gene specific and secondary structure free oligonucleotides for genome-scale oligonucleotide microarray construction or other applications.

Availability: The program code is distributed under the GNU General Public License and is freely available for non-profit use via request from the authors.

Contact: jean-marie.rouillard@cgm.cnrs-gif.fr

Supplementary information: http://berry.engin.umich.edu/oligoarray
Distribution patterns of over-represented k-mers
in non-coding yeast DNA
Authors: Hampson Steven , Kibler Dennis , Baldi Pierre
Published: July 2002

Motivation: Over-represented k-mers in genomic DNA regions are often of particular biological interest. For example, over-represented k-mers in co-regulated families of genes are associated with the DNA binding sites of transcription factors. To measure over-representation, we introduce a statistical background model based on single-mismatches, and apply it to the pooled 500 bp ORF Upstream Regions (USRs) of yeast. More importantly, we investigate the context and spatial distribution of over-represented k-mers in yeast USRs.

Results: Single and double-stranded spatial distributions of most over-represented k-mers are highly non-random, and predominantly cluster into a small number of classes that are robust with respect to over-representation measures. Specifically, we show that the three most common distribution patterns can be related to DNA structure, function, and evolution and correspond to: (a) homologous ORF clusters associated with sharply localized distributions; (b) regulatory elements associated with a symmetric broad hill-shaped distribution in the 50–200 bp USR; and (c) runs of As, Ts, and ATs associated with a broad hill-shaped distribution also in the 50–200 bp USR, with extreme structural properties. Analysis of over-representation, homology, localization, and DNA structure are essential components of a general data-mining approach to finding biologically important k-mers in raw genomic DNA and understanding the ‘lexicon’ of regulatory regions.

Contact: hampson@ics.uci.edu; kibler@ics.uci.edu; pfbaldi@ics.uci.edu

* To whom correspondence should be addressed. Also at Department of Biological Chemistry, College of Medicine.
Cell cycle‐dependent recruitment of HDAC‐1 correlates with deacetylation of histone H4 on an Rb–E2F target promoter
Authors: Ferreira Roger , Naguibneva Irina , Mathieu Marion , Ait‐Si‐Ali Slimane , Robin Philippe , Pritchard Linda L , Harel‐Bellan Annick
Published: July 2002

The transcription factor E2F, which is a key element in the control of cell proliferation, is repressed by Rb and other pocket proteins in growth‐arrested differentiating cells, as well as in proliferating cells when they progress through early G1. It is not known whether similar mechanisms are operative in the two situations. A body of data suggests that E2F repression by pocket proteins involves class I histone deacetylases (HDACs). It has been hypothesized that these enzymes are recruited to E2F target promoters where they deacetylate histones. Here we have tested this hypothesis directly by using formaldehyde cross‐linked chromatin immunoprecipitation (XChIP) assays to evaluate HDAC association in living cells. Our data show that a histone deacetylase, HDAC‐1, is stably bound to an E2F target promoter during early G1 in proliferating cells and released at the G1–S transition. In addition, our results reveal an inverse correlation between HDAC‐1 recruitment and histone H4 acetylation on specific lysines.
Comparative in-vitro activity of levofloxacin against isolates of bacteria from adult patients with community-acquired lower respiratory tract infections
Authors: Casellas J. M. , Gilardoni M. , Tomè G. , Goldberg M. , Ivanovic S. , Orduna M. , Dolmann A. , Ascoli M. , Ariza H. , Montero J. M.
Published: July 2002

This study was conducted to evaluate the activity of levofloxacin in comparison with a range of antibacterial agents against recent isolates obtained consecutively from patients with community-acquired pneumonia (CAP) or acute exacerbation of chronic bronchitis (AECB) during the period 1995 to 1996. Susceptibility testing was carried out by either microdilution or the Etest, and interpreted according to NCCLS breakpoints. The activity of levofloxacin was compared with that of amoxycillin, amoxycillin–clavulanate, cefuroxime, cefixime, erythromycin, roxithromycin, clarithromycin, azithromycin, ofloxacin and ciprofloxacin. Clinically significant numbers of bacteria were recovered from 31 CAP and 94 AECB specimens. The predominant bacterial species in the CAP specimens were Streptococcus pneumoniae (21 isolates) and Haemophilus influenzae (four isolates). The AECB isolates mainly consisted of S. pneumoniae (38%), Moraxella catarrhalis (26%), H. influenzae (19%) and Pseudomonas aeruginosa (10%). The overall percentage susceptible of the isolates for each antibiotic was: amoxycillin, 64%; amoxycillin–clavulanate, 89%; cefuroxime, 87%; cefixime, 78%; erythromycin, 85%; roxithromycin, 87%; clarithromycin, 87%; azithromycin, 85%; ofloxacin, 95%; ciprofloxacin, 95%; and levofloxacin, 97%. The activities of levofloxacin and the other agents were also compared against 40 S. pneumoniae isolates, of which 20 were penicillin-non- susceptible, recovered from CAP and AECB specimens during the period 1994 to 1996. These strains were all susceptible to levofloxacin, but only 50% were susceptible to ciprofloxacin and 80% to ofloxacin. Twenty M. catarrhalis, 20 H. influenzae and 20 methicillin-susceptible S. aureus isolates were also all susceptible to levofloxacin. Furthermore, 20 community-acquired P. aeruginosa isolates showed similar percentage susceptible rates to levofloxacin and ciprofloxacin. These in-vitro results suggest that levofloxacin may be useful in the treatment of community-acquired lower respiratory tract infections.
Bactericidal activity of levofloxacin against Streptococcus pneumoniae in an in-vitro model simulating serum pharmacokinetic parameters
Authors: Shah P. M. , Schwärzel R.
Published: July 2002

The objective of the current study was to evaluate the bactericidal activity of levofloxacin against Streptococcus pneumoniae at concentrations equivalent to those present in serum after a po dosage of 500 mg. Nine S. pneumoniae strains (one penicillin G-resistant, one penicillin G-intermediate resistant, and two penicillin G- and cefotaxime-resistant) were exposed to a levofloxacin concentration of 6 mg/L diluted at a terminal half-life ( t½ ) of 8 h. Surviving S. pneumoniae (cfu/mL) were quantified up to 24 h by the membrane filtration method. Levofloxacin was rapidly bactericidal and reduced the quantity of inoculum to below the detection level of 10 cfu/mL within 2.5–5.15 h, irrespective of susceptibility to penicillin G or cefotaxime. No viable S. pneumoniae could be detected at the end of the observation period (24 h). All strains except one (strain 17134) had an MIC < 1.0 mg/L, and the minimum bactericidal concentrations (MBCs) were, at the most, one dilution higher than the respective MICs. The inoculum was high, ranging from 2.9 × 10 5 to 7.5 × 10 6 cfu/mL. The time required to achieve 99% death ranged from 0.9 to 3.1 h, and was longest for strain 17134 which had an MIC of 1.0 mg/L and an MBC of 2.0 mg/L. A 99.9% reduction in inoculum was achieved within 1.5–4.15 h. At a serum concentration achievable after a single po dosage of 500 mg, levofloxacin showed rapid and complete bactericidal activity against the S. pneumoniae strains tested.
The ethylene–receptor family from
Arabidopsis
: structure and function
Authors: Bleecker Anthony B. , Esch Jeffrey J. , Hall Anne E. , Rodríguez Fernando I. , Binder Brad M.
Published: July 2002

The gaseous hormone ethylene regulates many aspects of plant growth and development. Ethylene is perceived by a family of high–affinity receptors typified by the ETR1 protein from
Arabidopsis
. The
ETR1
gene codes for a protein, which contains a hydrophobic N–terminal domain that binds ethylene and a C–terminal domain that is related in sequence to histidine kinase–response regulator two–component signal transducers found in bacteria. A structural model for the ethylene binding domain is presented in which a Cu(I) ion is coordinated within membrane–spanning α–helices of the hydrophobic domain. It is proposed that binding of ethylene to the transition metal would induce a conformational change in the sensor domain that would be propagated to the cytoplasmic transmitter domain of the protein. A total of four additional genes that are related in sequence to
ETR1
have been identified in
Arabidopsis
. Specific missense mutations in any one of the five genes leads to ethylene insensitivity
in planta
. Models for signal transduction that can account for the genetic dominance of these mutations are discussed.
Ageing and immortality
Authors: Rose Michael R. , Mueller Laurence D.
Published: July 2002

The concept of the force of natural selection was developed to explain the evolution of ageing. After ageing, however, comes a period in which mortality rates plateau and some individual organisms could, in theory, live forever. This late–life immortality has no presently agreed upon explanation. Two main theories have been offered. The first is heterogeneity within ageing cohorts, such that only extremely robust individuals survive ageing. This theory can be tested by comparisons of more and less robust cohorts. It can also be tested by fitting survival data to its models. The second theory is that late–life plateaus in mortality reflect the inevitable late–life plateau in the force of natural selection. This theory can be tested by changing the force of natural selection in evolving laboratory populations, particularly the age at which the force plateaus. This area of research has great potential for elucidating the overall structure of life–history evolution, particularly the interrelationship between the three life–history phases of development, ageing and immortality.
Pseudosubstrate regulation of the SCFβ-TrCP ubiquitin ligase by hnRNP-U
Authors: Davis Matti , Hatzubai Ada , Andersen Jens S. , Ben-Shushan Etti , Fisher Gregory Zvi , Yaron Avraham , Bauskin Asne , Mercurio Frank , Mann Matthias , Ben-Neriah Yinon
Published: July 2002

β-TrCP/E3RS (E3RS) is the F-box protein that functions as the receptor subunit of the SCFβ-TrCP ubiquitin ligase (E3). Surprisingly, although its two recognized substrates, IκBα and β-catenin, are present in the cytoplasm, we have found that E3RS is located predominantly in the nucleus. Here we report the isolation of the major E3RS-associated protein, hnRNP-U, an abundant nuclear phosphoprotein. This protein occupies E3RS in a specific and stoichiometric manner, stabilizes the E3 component, and is likely responsible for its nuclear localization. hnRNP-U binding was abolished by competition with a pIκBα peptide, or by a specific point mutation in the E3RS WD region, indicating an E3–substrate-type interaction. However, unlike pIκBα, which is targeted by SCFβ-TrCP for degradation, the E3-bound hnRNP-U is stable and is, therefore, a pseudosubstrate. Consequently, hnRNP-U engages a highly neddylated active SCFβ-TrCP, which dissociates in the presence of a high-affinity substrate, resulting in ubiquitination of the latter. Our study points to a novel regulatory mechanism, which secures the localization, stability, substrate binding threshold, and efficacy of a specific protein-ubiquitin ligase.
Substrate recognition by the Cdc20 and Cdh1 components of the anaphase-promoting complex
Authors: Pfleger Cathie M. , Lee Ethan , Kirschner Marc W.
Published: July 2002

The specificity of ubiquitin-mediated protein degradation with regards to the selection of substrates to be polyubiquitinated has only been determined rather recently. Substrate targeting by the N-end rule and HECT (homology to E6AP carboxylterminus) domain ubiquitin ligases occurs through substrate-specific binding domains. In contrast, the SCF complex recruits substrates through a substrate adaptor protein, the F-box subunit. Despite evidence showing that Cdc20 and Cdh1 bind and activate the anaphase-promoting complex (APC) in a substrate-specific manner, there is no evidence that the activating protein and substrate interact directly; hence, no clear model exists for the mechanism of APC activation or recruitment of substrates. We show here that the activators Cdc20 and Cdh1 can associate with substrates via their N termini. In the absence of APC, Cdc20 and Cdh1 bind substrates reflecting Cdc20–APC and Cdh1–APC specificity. The N termini of Cdc20 and Cdh1 provide specificity functionally, as demonstrated by the generation of active chimeras that display the specificity corresponding to their N termini. Thus, Cdc20 and Cdh1 act as both substrate recognition and activating modules for APC.
Identification and purification of two distinct complexes containing the five RAD51 paralogs
Authors: Masson Jean-Yves , Tarsounas Madalena C. , Stasiak Alicja Z. , Stasiak Andrzej , Shah Rajvee , McIlwraith Michael J. , Benson Fiona E. , West Stephen C.
Published: July 2002

Cells defective in any of the RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) are sensitive to DNA cross-linking agents and to ionizing radiation. Because the paralogs are required for the assembly of DNA damage-induced RAD51 foci, and mutant cell lines are defective in homologous recombination and show genomic instability, their defect is thought to be caused by an inability to promote efficient recombinational repair. Here, we show that the five paralogs exist in two distinct complexes in human cells: one contains RAD51B, RAD51C, RAD51D, and XRCC2 (defined as BCDX2), whereas the other consists of RAD51C with XRCC3. Both protein complexes have been purified to homogeneity and their biochemical properties investigated. BCDX2 binds single-stranded DNA and single-stranded gaps in duplex DNA, in accord with the proposal that the paralogs play an early (pre-RAD51) role in recombinational repair. Moreover, BCDX2 complex binds specifically to nicks in duplex DNA. We suggest that the extreme sensitivity of paralog-defective cell lines to cross-linking agents is owing to defects in the processing of incised cross links and the consequential failure to initiate recombinational repair at these sites.
Toward a Cytological Characterization of the Rice Genome
Authors: Cheng Zhukuan , Buell C. Robin , Wing Rod A. , Gu Minghong , Jiang Jiming
Published: July 2002

Rice (Oryza sativa L.) will be the first major crop, as well as the first monocot plant species, to be completely sequenced. Integration of DNA sequence-based maps with cytological maps will be essential to fully characterize the rice genome. We have isolated a set of 24 chromosomal arm-specific bacterial artificial chromosomes to facilitate rice chromosome identification. A standardized rice karyotype was constructed using meiotic pachytene chromosomes ofO. sativa spp. japonica rice var. Nipponbare. This karyotype is anchored by centromere-specific and chromosomal arm-specific cytological landmarks and is fully integrated with the most saturated rice genetic linkage maps in which Nipponbare was used as one of the mapping parents. An ideogram depicting the distribution of heterochromatin in the rice genome was developed based on the patterns of 4',6-diamidino-2-phenylindole staining of the Nipponbare pachytene chromosomes. The majority of the heterochromatin is distributed in the pericentric regions with some rice chromosomes containing a significantly higher proportion of heterochromatin than other chromosomes. We showed that pachytene chromosome-based fluorescence in situ hybridization analysis is the most effective approach to integrate DNA sequences with euchromatic and heterochromatic features.
Differential Divergence of Three Human Pseudoautosomal Genes and Their Mouse Homologs: Implications for Sex Chromosome Evolution
Authors: Gianfrancesco Fernando , Sanges Remo , Esposito Teresa , Tempesta Sergio , Rao Ercole , Rappold Gudrun , Archidiacono Nicoletta , Graves Jennifer A.M. , Forabosco Antonino , D'Urso Michele
Published: July 2002

The human pseudoautosomal region 1 (PAR1) is essential for meiotic pairing and recombination, and its deletion causes male sterility. Comparative studies of human and mouse pseudoautosomal genes are valuable in charting the evolution of this interesting region, but have been limited by the paucity of genes conserved between the two species. We have cloned a novel human PAR1 gene, DHRSXY, encoding an oxidoreductase of the short-chain dehydrogenase/reductase family, and isolated a mouse ortholog Dhrsxy. We also searched for mouse homologs of recently reported PGPL and TRAMP genes that flank it within PAR1. We recovered a highly conserved mouse ortholog of PGPL by cross-hybridization, but found no mouse homolog of TRAMP. Like Csf2ra and Il3ra, both mouse homologs are autosomal; Pgpl on chromosome 5, andDhrsxy subtelomeric on chromosome 4. TRAMP, like the human genes within or near PAR1, is probably very divergent or absent in the mouse genome. We interpret the rapid divergence and loss of pseudoautosomal genes in terms of a model of selection for the concentration of repetitive recombinogenic sequences that predispose to high recombination and translocation.

[The sequence data described in this paper have been submitted to the EMBL data library under accession nos. AJ293620, AJ296079, and AJ293619.]
Generation and Comparative Analysis of ∼3.3 Mb of Mouse Genomic Sequence Orthologous to the Region of Human Chromosome 7q11.23 Implicated in Williams Syndrome
Authors: DeSilva Udaya , Elnitski Laura , Idol Jacquelyn R. , Doyle Johannah L. , Gan Weiniu , Thomas James W. , Schwartz Scott , Dietrich Nicole L. , Beckstrom-Sternberg Stephen M. , McDowell Jennifer C. , Blakesley Robert W. , Bouffard Gerard G. , Thomas Pamela J. , Touchman Jeffrey W. , Miller Webb , Green Eric D.
Published: July 2002

Williams syndrome is a complex developmental disorder that results from the heterozygous deletion of a ∼1.6-Mb segment of human chromosome 7q11.23. These deletions are mediated by large (∼300 kb) duplicated blocks of DNA of near-identical sequence. Previously, we showed that the orthologous region of the mouse genome is devoid of such duplicated segments. Here, we extend our studies to include the generation of ∼3.3 Mb of genomic sequence from the mouse Williams syndrome region, of which just over 1.4 Mb is finished to high accuracy. Comparative analyses of the mouse and human sequences within and immediately flanking the interval commonly deleted in Williams syndrome have facilitated the identification of nine previously unreported genes, provided detailed sequence-based information regarding 30 genes residing in the region, and revealed a number of potentially interesting conserved noncoding sequences. Finally, to facilitate comparative sequence analysis, we implemented several enhancements to the program PipMaker, including the addition of links from annotated features within a generated percent-identity plot to specific records in public databases. Taken together, the results reported here provide an important comparative sequence resource that should catalyze additional studies of Williams syndrome, including those that aim to characterize genes within the commonly deleted interval and to develop mouse models of the disorder.

[The sequence data described in this paper have been submitted to GenBank under accession nos. AF267747, AF289666,AF289667, AF289664, AF289665, AC091250, AC079938, AC084109, AC024607,AC074359, AC024608, AC083858, AC083948, AC084162, AC087420, AC083890,AC080158, AC084402, AC083889, AC083857, and AC079872.]
Toward genomic identification of β‐barrel membrane proteins: Composition and architecture of known structures
Authors: Wimley William C.
Published: July 2002

The amino acid composition and architecture of all β‐barrel membrane proteins of known three‐dimensional structure have been examined to generate information that will be useful in identifying β‐barrels in genome databases. The database consists of 15 nonredundant structures, including several novel, recent structures. Known structures include monomeric, dimeric, and trimeric β‐barrels with between 8 and 22 membrane‐spanning β‐strands each. For this analysis the membrane‐interacting surfaces of the β‐barrels were identified with an experimentally derived, whole‐residue hydrophobicity scale, and then the barrels were aligned normal to the bilayer and the position of the bilayer midplane was determined for each protein from the hydrophobicity profile. The abundance of each amino acid, relative to the genomic abundance, was calculated for the barrel exterior and interior. The architecture and diversity of known β‐barrels was also examined. For example, the distribution of rise‐per‐residue values perpendicular to the bilayer plane was found to be 2.7 ± 0.25 Å per residue, or about 10 ± 1 residues across the membrane. Also, as noted by other authors, nearly every known membrane‐spanning β‐barrel strand was found to have a short loop of seven residues or less connecting it to at least one adjacent strand. Using this information we have begun to generate rapid screening algorithms for the identification of β‐barrel membrane proteins in genomic databases. Application of one algorithm to the genomes ofEscherichia coliandPseudomonas aeruginosaconfirms its ability to identify β‐barrels, and reveals dozens of unidentified open reading frames that potentially code for β‐barrel outer membrane proteins.
Crystal structure of the Yersinia pestis GTPase activator YopE
Authors: Evdokimov Artem G. , Tropea Joseph E. , Routzahn Karen M. , Waugh David S.
Published: July 2002

Yersinia pestis, the causative agent of bubonic plague, evades the immune response of the infected organism by using a type III (contact‐dependent) secretion system to deliver effector proteins into the cytosol of mammalian cells, where they interfere with signaling pathways that regulate inflammation and cytoskeleton dynamics. The cytotoxic effector YopE functions as a potent GTPase‐activating protein (GAP) for Rho family GTP‐binding proteins, including RhoA, Rac1, and Cdc42. Down‐regulation of these molecular switches results in the loss of cell motility and inhibition of phagocytosis, enabling Y. pestis to thrive on the surface of macrophages. We have determined the crystal structure of the GAP domain of YopE (YopEGAP; residues 90–219) at 2.2‐Å resolution. Apart from the fact that it is composed almost entirely of α‐helices, YopEGAP shows no obvious structural similarity with eukaryotic RhoGAP domains. Moreover, unlike the catalytically equivalent arginine fingers of the eukaryotic GAPs, which are invariably contained within flexible loops, the critical arginine in YopEGAP (Arg144) is part of an α‐helix. The structure of YopEGAP is strikingly similar to the GAP domains from Pseudomonas aeruginosa (ExoSGAP) and Salmonella enterica (SptPGAP), despite the fact that the three amino acid sequences are not highly conserved. A comparison of the YopEGAP structure with those of the Rac1‐ExoSGAP and Rac1‐SptP complexes indicates that few, if any, significant conformational changes occur in YopEGAP when it interacts with its G protein targets. The structure of YopEGAP may provide an avenue for the development of novel therapeutic agents to combat plague.
Plumb line and the shape of the earth
Authors: Mohazzabi Pirooz , James Mark C.
Published: July 2002

The equation for plumb line deviation currently presented in textbooks ignores the effect of earth’s flattening on the direction of true gravitational acceleration and is incorrect by nearly a factor of 2. The correct equation is consistent with the shape and dimensions of the earth with a very high degree of accuracy. The simple treatment of the problem uses Newton’s second law in an inertial reference system and is suitable for introductory physics courses.
An ensemble source spectra model for merchant ship-radiated noise
Authors: Wales Stephen C. , Heitmeyer Richard M.
Published: July 2002

This paper presents an evaluation of the classical model for determining an ensemble of the broadband source spectra of the sound generated by individual ships and proposes an alternate model to overcome the deficiencies in the classical model. The classical model, proposed by Ross [Mechanics of Underwater Noise (Pergamon, New York, 1976)] postulates that the source spectrum for an individual ship is proportional to a baseline spectrum with the constant of proportionality determined by a power-law relationship on the ship speed and length. The model evaluation, conducted on an ensemble of 54 source spectra over a 30–1200-Hz to 1200-Hz frequency band, shows that this assumption yields large rms errors in the broadband source level for the individual ships and significantly overestimates the variability in the source level across the ensemble of source spectra. These deficiencies are a consequence of the negligible correlation between the source level and the ship speed and the source level and the ship length. The alternate model proposed here represents the individual ship spectra by a modified rational spectrum where the poles and zeros are restricted to the real axis and the exponents of the terms are not restricted to integer values. An evaluation of this model on the source spectra ensemble indicates that the rms errors are significantly less than those obtained with any model where the frequency dependence is represented by a single baseline spectrum. Furthermore, at high frequencies (400 to 1200 Hz), a single-term rational spectrum model is sufficient to describe the frequency dependence and, at the low frequencies (30 to 400 Hz), there is only a modest reduction in the rms error for a higher order model. Finally, a joint probability density on the two parameters of the single term model based on the measured histograms of these parameters is proposed. This probability density provides a mechanism for generating an ensemble of ship spectra.
An interpretation of the MBSL temperatures deduced from metal atom emission
Authors: Bernstein Lawrence S.
Published: July 2002

Recent MBSL observations [McNamara et al., Univ. of Illinois (private communication)] of metal atom emission from a variety of metal carbonyls seeded into Ar display similar peak emission temperatures of approximately 5000 K. Additionally, metal ion emission lines have not been detected. These observations can be interpreted to mean that the peak emission temperature is also the peak collapse temperature. The same conclusion was previously reported based on the same 5000 K temperature observed for C2 MBSL. However, it was argued [Bernstein et al., J. Phys. Chem. 100, 6612 (1996)] that the chemistry giving rise to C2 emission turns on and off in a narrow temperature window around 5000 K. Thus it was concluded that C2 emission is not a useful thermometer for higher collapse temperatures which may be attained in MBSL. It is argued that a similar situation exists for the metal atom emission chemistry. Detailed calculations based on a coupled chemical–hydrodynamic collapse model support this hypothesis. The lack of observed metal atom ion lines is attributed to the absence of sufficiently strong lines in the observational spectral window of the experiments.
Viscosity measurement with laser-generated and detected shear waves
Authors: Costley R. Daniel , Shah Vimal V. , Winstead Christopher B. , Singh J. P. , Balasubramaniam Krishnan
Published: July 2002

A technique is described in which laser-generated shear waves can be used to measure the viscosity of liquids. The technique involves measuring the shear wave reflection coefficient at a solid–liquid interface. To accommodate this procedure, a wedge was designed to launch laser-generated shear waves into the material at nearly normal incidence to the solid–liquid interface. The reflected laser-generated shear waves are detected at a second interface with a laser interferometer. The angle of incidence at this second interface is at an angle greater than the critical angle. The purpose of this arrangement is to maximize the out-of-plane displacement at this second interface so that detection with the interferometer can be more easily accomplished. Calculations that support the design of the wedge and experiment are outlined and experimental results are presented and discussed. This technique would be most applicable in those situations in which conventional techniques are not suitable, such as those involving high temperature and hostile environments.
Evoked otoacoustic emissions arise by two fundamentally different mechanisms: A taxonomy for mammalian OAEs
Authors: Shera Christopher A. , Guinan John J.
Published: July 2002

Otoacoustic emissions (OAEs) of all types are widely assumed to arise by a common mechanism: nonlinear electromechanical distortion within the cochlea. In this view, both stimulus-frequency (SFOAEs) and distortion-product emissions (DPOAEs) arise because nonlinearities in the mechanics act as “sources” of backward-traveling waves. This unified picture is tested by analyzing measurements of emission phase using a simple phenomenological description of the nonlinear re-emission process. The analysis framework is independent of the detailed form of the emission sources and the nonlinearities that produce them. The analysis demonstrates that the common assumption that SFOAEs originate by nonlinear distortion requires that SFOAE phase be essentially independent of frequency, in striking contradiction with experiment. This contradiction implies that evoked otoacoustic emissions arise by two fundamentally different mechanisms within the cochlea. These two mechanisms (linear reflection versus nonlinear distortion) are described and two broad classes of emissions—reflection-source and distortion- source emissions—are distinguished based on the mechanisms of their generation. The implications of this OAE taxonomy for the measurement, interpretation, and clinical use of otoacoustic emissions as noninvasive probes of cochlear function are discussed.
The precedence effect
Authors: Litovsky Ruth Y. , Colburn H. Steven , Yost William A. , Guzman Sandra J.
Published: July 2002

In a reverberant environment, sounds reach the ears through several paths. Although the direct sound is followed by multiple reflections, which would be audible in isolation, the first-arriving wavefront dominates many aspects of perception. The “precedence effect” refers to a group of phenomena that are thought to be involved in resolving competition for perception and localization between a direct sound and a reflection. This article is divided into five major sections. First, it begins with a review of recent work on psychoacoustics, which divides the phenomena into measurements of fusion, localization dominance, and discrimination suppression. Second, buildup of precedence and breakdown of precedence are discussed. Third measurements in several animal species, developmental changes in humans, and animal studies are described. Fourth, recent physiological measurements that might be helpful in providing a fuller understanding of precedence effects are reviewed. Fifth, a number of psychophysical models are described which illustrate fundamentally different approaches and have distinct advantages and disadvantages. The purpose of this review is to provide a framework within which to describe the effects of precedence and to help in the integration of data from both psychophysical and physiological experiments. It is probably only through the combined efforts of these fields that a full theory of precedence will evolve and useful models will be developed.
Chemical preparation and crystal data for four new condensed phosphates
Authors: Sbai Kacem , Atibi Azzeddine , El Kababi Khadija , Belaaouad Said
Published: July 2002

Methods of chemical preparation and crystallographic data are reported for four new condensed phosphates: one hydrated cyclotriphosphate MnAg4(P3O9)2·6H2O and three long-chain polyphosphates: MnAg2(PO3)4, NiAg4(PO3)6 and NiNa4(PO3)6. Two of these new condensed phosphates, associated with manganese, belong to previously investigated structure types.
Precision patient education using a “flipped classroom” approach
Authors: Schuller Bradley W , Burch Christina , Casterton Theresa , Crowther Catie , Fowler Jordan , Stenmark Matthew H
Published: April 2022

Objectives

To improve patient education delivered over telemedicine by using a “flipped classroom”‐inspired approach.

Methods

A “flipped classroom” is an education strategy used to engage active learning by sending students home with lecture material and reserving classroom time for collaborative learning. To adapt this approach for use in radiation oncology patient education, three pieces of written education material were created: introduction to radiation oncology, treatment planning scan, and treatment delivery. An automated system was created to deliver precisely timed emails at three time points ahead of appointments. Appointment time was then used for collaborative learning with our staff. As a primary endpoint, email engagement metrics were tracked via the automated system. Secondarily, enrolled patients were surveyed to assess level of understanding (before vs. after intervention), anxiety (before vs. after intervention), and satisfaction. Additionally, email delivery timing, clarity, relevance, and patient support were evaluated. Data analyses test the impact of active learning against our existing education approaches.

Results

Overall, 77.1% of the emails were opened, and of those, patients accessed 72.2% of the education material. Patients re‐read the education material 4.6 times on average. Active learning increased patient understanding regarding the purpose of the treatment planning scan (p = 0.031) and increased patient understanding of what to expect during daily radiation treatments (p = 0.0078). Patients reported reduced anxiety (p = 0.031) and high scores for satisfaction, timing, clarity, relevance, and overall support.

Conclusions

Patient engagement with the education material was high, and they continued to access it many times. Active learning enhances patient comprehension of complex treatment information leading to decreased anxiety. Furthermore, this technique can be incorporated into existing telemedicine with basic technology.
Treatment with Exogenously Added Catalase Alters CD8 T Cell Memory Differentiation and Function
Authors: Aksoylar Halil‐Ibrahim , Patsoukis Nikolaos
Published: April 2022

Cell‐based immunotherapy is a promising approach to cancer treatment. However, the metabolically hostile tumor microenvironment (TME) poses a major barrier to this therapeutic approach. Metabolic reprogramming may enhance T cell effector function and support longevity and persistence within the TME. Metabolic processes lead reactive oxygen species (ROS) production, which are mandatory mediators of signaling and immune cell functions, but detrimental when present in excess. Catalase (CAT) is an intracellular antioxidant enzyme that scavenges hydrogen peroxide (H2O2), a central ROS member with a plethora of biological effects. H2O2 is produced intracellularly and extracellularly, diffusing freely between the two compartments. In this study, it is found that scavenging extracellular H2O2 by CAT supplementation has a major impact on the cell redox state, decreased intracellular ROS, but enhanced activation and altered memory differentiation. Under in vitro chronic activation conditions, CAT treatment favors CD8 T cells with less exhausted phenotype, increased activation and memory markers, and high bioenergetic capacity. Under in vitro acute activation conditions, CAT treatment selectively prevents differentiation transition from the stem cell memory/naive (TSCM/TN)‐ to the central memory (TCM)‐like phenotype, while enhancing activation and polyfunctionality. The study highlights the critical role of H2O2 as a “hidden player” in T cell fitness and memory differentiation.
Mechano‐Responsive Leapfrog Micelles Enable Interactive Apoptotic and Ferroptotic Cancer Therapy
Authors: Li Yao , Qin Yan , Shang Yaqi , Li Yaru , Liu Fang , Luo Jiajia , Zhu Jundong , Guo Xuliang , Wang Zheng , Zhao Yanjun
Published: April 2022

The combination of apoptosis and ferroptosis is highly appealing in addressing the tumor heterogeneity‐induced therapy resistance. Reactive oxygen species (ROS)‐based cancer nanomedicine can assemble multiple cell death modalities in a single platform, but the potency of ferroptosis induction is limited. Here, a novel mechano‐responsive polymeric micellar system for selective ferroptosis boosting and ROS therapy sensitization is reported. The mechanophore, ferrocene (Fc) is the key to such design, and the ultrasound can speed up the dissociation of Fc and the release of Fe2+ and hydroxyl radical in the presence of elevated H2O2 in the tumor microenvironment. The Fc‐conjugated amphiphilic copolymers self‐assemble into nanoscale micelles wherein a model sonosensitizer, protoporphyrin IX is physically encapsulated. Upon triggering, the mechano‐responsive micelles produce both singlet oxygen and hydroxyl radical for apoptotic cell death in a model murine breast cancer cell line (4T1). The ROS also depletes intracellular glutathione and thioredoxin, which together with the heightened Fe2+ level boosts lipid peroxidation and hence ferroptotic cell death. The interactive apoptosis and ferroptosis induction and sensitization is further demonstrated in a 4T1 tumor‐bearing mice model with negligible adverse effects. The current work provides a novel approach to simultaneously sensitize apoptosis and ferroptosis for efficient on‐demand cancer therapy.
Engineered Nanoerythrocytes Alleviate Central Nervous System Inflammation by Regulating the Polarization of Inflammatory Microglia
Authors: Yin Na , Zhao Yuzhen , Liu Changhua , Yang Yue , Wang Zhi‐Hao , Yu Wenyan , Zhang Kaixiang , Zhang Zhenzhong , Liu Junjie , Zhang Yun , Shi Jinjin
Published: April 2022

Microglial polarization is one of the most promising therapeutic strategies for multiple central nervous system (CNS) disorders. However, safe, effective, and controllable microglial regulation still faces formidable challenges. Although some anti‐inflammatory factors promote microglia polarization, their short half‐life, high cost, unpredictable in vivo behavior, and complex delivery operations, hamper their clinical application. Here, inspired by the natural microhemorrhage cleaning mechanism, an MG1 peptide and RVG29 peptide engineered nanoerythrocyte (NEMR) that can reprogram microglia are developed from classical M1 toward alternative M2 by inducing heme oxygenase‐1 (HO‐1), stimulating Notch1/Hes1/Stat3 signaling, and further inhibiting NF‐κB p65 translocation. Moreover, anti‐inflammatory carbon monoxide (CO) and bilirubin produced by endogenous metabolism of heme further reinforces the anti‐inflammatory effect. In middle cerebral artery occlusion and experimental autoimmune encephalomyelitis models, a satisfactory prognosis is achieved, with precise regulation of inflammatory microglia in lesion sites, increased expression of anti‐inflammatory factors, reduced blood–brain barrier permeability, as well as promotion of neurogenesis and functional recovery. Furthermore, NEMR can be integrated with clinical therapeutic agents, which facilitates precise drug delivery to enhance therapeutic effects. Hence, the natural nanoerythrocytes, as a feasible, efficient, safe, and practical tool, provides a new strategy for rebalancing of the immune environment in the CNS disorders.
Ultrathin, Transparent, and High Density Perovskite Scintillator Film for High Resolution X‐Ray Microscopic Imaging
Authors: Wu Xiaochen , Guo Zhao , Zhu Shuang , Zhang Bingbing , Guo Sumin , Dong Xinghua , Mei Linqiang , Liu Ruixue , Su Chunjian , Gu Zhanjun
Published: April 2022

Inorganic perovskite quantum dots CsPbX3 (X = Cl, Br, and I) has recently received extensive attention as a new promising class of X‐ray scintillators. However, relatively low light yield (LY) of CsPbX3 and strong optical scattering of the thick opaque scintillator film restrict their practical applications for high‐resolution X‐ray microscopic imaging. Here, the Ce3+ ion doped CsPbBr3 nanocrystals (NCs) with enhanced LY and stability are obtained and then the ultrathin (30 µm) and transparent scintillator films with high density are prepared by a suction filtration method. The small amount Ce3+ dopant greatly enhances the LY of CsPbBr3 NCs (about 33 000 photons per MeV), which is much higher than that of bare CsPbBr3 NCs. Moreover, the scintillator films made by these NCs with high density realize a high spatial resolution of 862 nm thanks to its thin and transparent feature, which is so far a record resolution for perovskite scintillator‐based X‐ray microscopic imaging. This strategy not only provides a simple way to increase the resolution down to nanoscale but also extends the application of as‐prepared CsPbBr3 scintillator for high resolution X‐ray microscopic imaging.
Self‐Supporting 3D Lithiophilic and Flexible Carbon Nanofiber Film as a High‐Loading Li Host
Authors: Liu Ting , Zhang Ye-Qiang , Huang Ying , Wang Run-Tong , Zhou Sheng-Qi , Sun Peng-Fei , Chen Jia-Jia
Published: April 2022

Herein, a Zn and N co‐doped carbon nanofiber film (Zn–N–CNF) is successfully fabricated via a convenient electrospinning technique, which can be used as hybrid lithiophilic current collector to accommodate high‐loading lithium. Contributing to the lithiophilic active sites and 3D network structure of Zn–N–CNF, metallic Li can be reversibly electrochemical plated and stripped. Consequently, the Zn–N–CNF@Li electrode exhibits a high exchange current density of 4.731 mA cm−2, providing fast charge‐transfer kinetics for Li plating and stripping. Then, an average Coulombic efficiency of 97.3 % can be achieved at 1.0 mA cm−2 with 1.0 mAh cm−2 in 150 cycles. The corresponding symmetrical battery can stably cycle for nearly 800 h with a voltage hysteresis less than 20 mV at 0.5 mA cm−2 and 0.5 mAh cm−2. In addition, this flexible skeleton of 3D Zn–N–CNF can accommodate a high Li deposition capacity of 10 mAh cm−2 with a reversible electrochemical plating and stripping. Moreover, full cells based on the developed anode and a LiFePO4 cathode also demonstrate superior rate capability and stable cycle life. Herein, a promising strategy to construct dendrite‐free lithium metal anodes toward high‐performance lithium metal batteries is provided.