bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution patterns of over-represented k-mers
in non-coding yeast DNA
Authors: Hampson Steven , Kibler Dennis , Baldi Pierre 
Published: July 2002

Abstract
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.
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

Abstract
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

Abstract
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 &lt; 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.
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

AbstractThe 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

AbstractYersinia 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.
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

AbstractObjectivesTo improve patient education delivered over telemedicine by using a “flipped classroom”‐inspired approach.MethodsA “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.ResultsOverall, 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.ConclusionsPatient 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

AbstractCell‐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

AbstractThe 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

AbstractMicroglial 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

AbstractInorganic 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.
RETRACTED: The research on application of agricultural big data agricultural economic management
Authors: Zhao Yuxuan 
Published: April 2022

AbstractThis paper applies agricultural big data into agricultural economics management in order to improve agricultural economics management effects and comprehensively analyzes criterion and trending, maturity and advancement, practice and advancement, usability and extension of the platform according to the structure of agricultural economics management system by using big data. Meanwhile the paper describes the actual application condition of agricultural economics management, designs tests to analyze the agricultural economics data and digs the effects according to the agricultural economics management data through the crawler technology, and explains the application effects in the agricultural economics management. Tests and studies prove the reliability of the method put in the paper.