bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compensator models for fluence field modulated computed tomography
Authors: Bartolac Steven , Jaffray David 
Published: November 2013

Purpose:Fluence field modulated computed tomography (FFMCT) presents a novel approach for acquiring CT images, whereby a patient model guides dynamically changing fluence patterns in an attempt to achieve task‐based, user‐prescribed, regional variations in image quality, while also controlling dose to the patient. This work aims to compare the relative effectiveness of FFMCT applied to different thoracic imaging tasks (routine diagnostic CT, lung cancer screening, and cardiac CT) when the modulator is subject to limiting constraints, such as might be present in realistic implementations.Methods:An image quality plan was defined for a simulated anthropomorphic chest slice, including regions of high and low image quality, for each of the thoracic imaging tasks. Modulated fluence patterns were generated using a simulated annealing optimization script, which attempts to achieve the image quality plan under a global dosimetric constraint. Optimization was repeated under different types of modulation constraints (e.g., fixed or gantry angle dependent patterns, continuous or comprised of discrete apertures) with the most limiting case being a fixed conventional bowtie filter. For each thoracic imaging task, an image quality map (IQMsd) representing the regionally varying standard deviation is predicted for each modulation method and compared to the prescribed image quality plan as well as against results from uniform fluence fields. Relative integral dose measures were also compared.Results:Each IQMsd resulting from FFMCT showed improved agreement with planned objectives compared to those from uniform fluence fields for all cases. Dynamically changing modulation patterns yielded better uniformity, improved image quality, and lower dose compared to fixed filter patterns with optimized tube current. For the latter fixed filter cases, the optimal choice of tube current modulation was found to depend heavily on the task. Average integral dose reduction compared to a uniform fluence field ranged from 10% using a bowtie filter to 40% or greater using an idealized modulator.Conclusions:The results support that FFMCT may achieve regionally varying image quality distributions in good agreement with user‐prescribed values, while limiting dose. The imposition of constraints inhibits dose reduction capacity and agreement with image quality plans but still yields significant improvement over what is afforded by conventional dose minimization techniques. These results suggest that FFMCT can be implemented effectively even when the modulator has limited modulation capabilities.
In Vitro
Responses of Acinetobacter baumannii to Two- and Three-Drug Combinations following Exposure to Colistin and Doripenem
Authors: Oleksiuk Louise M. , Nguyen M. Hong , Press Ellen G. , Updike Cassaundra L. , O'Hara Jessica A. , Doi Yohei , Clancy Cornelius J. , Shields Ryan K. 
Published: November 2013

ABSTRACT

We compared
in vitro
killing of colistin, doripenem, and sulbactam by time-kill methods against
Acinetobacter baumannii
isolates collected from patients before and after colistin-doripenem treatment (initial and recurrent isolates, respectively). Colistin-doripenem bactericidal activity against recurrent isolates was attenuated (mean log
10
kill, −5.74 versus −2.88;
P
= 0.01) but was restored by adding sulbactam. Doripenem MICs rather than colistin MICs correlated with the activity of colistin-doripenem. Among colistin-resistant isolates, colistin-doripenem-sulbactam combinations achieved greater killing than colistin-doripenem alone (−5.65 versus −2.43;
P
= 0.04).
Histatin 5-Spermidine Conjugates Have Enhanced Fungicidal Activity and Efficacy as a Topical Therapeutic for Oral Candidiasis
Authors: Tati Swetha , Li Rui , Puri Sumant , Kumar Rohitashw , Davidow Peter , Edgerton Mira 
Published: November 2013

ABSTRACT

Oropharyngeal candidiasis (OPC) is caused by the opportunistic fungi
Candida albicans
and is prevalent in immunocompromised patients, individuals with dry mouth, or patients with prolonged antibiotic therapies that reduce oral commensal bacteria. Human salivary histatins, including histatin 5 (Hst 5), are small cationic proteins that are the major source of fungicidal activity of saliva. However, Hsts are rapidly degraded
in vivo
, limiting their usefulness as therapeutic agents despite their lack of toxicity. We constructed a conjugate peptide using spermidine (Spd) linked to the active fragment of Hst 5 (Hst 5
4–15
), based upon our findings that
C. albicans
spermidine transporters are required for Hst 5 uptake and fungicidal activity. We found that Hst 5
4–15
-Spd was significantly more effective in killing
C. albicans
and
Candida glabrata
than Hst 5 alone in both planktonic and biofilm growth and that Hst 5
4–15
-Spd retained high activity in both serum and saliva. Hst 5
4–15
-Spd was not bactericidal against streptococcal oral commensal bacteria and had no hemolytic activity. We tested the effectiveness of Hst 5
4–15
-Spd
in vivo
by topical application to tongue surfaces of immunocompromised mice with OPC. Mice treated with Hst 5
4–15
-Spd had significant clearance of candidal tongue lesions macroscopically, which was confirmed by a 3- to 5-log fold reduction of
C. albicans
colonies recovered from tongue tissues. Hst 5
4–15
-Spd conjugates are a new class of peptide-based drugs with high selectivity for fungi and potential as topical therapeutic agents for oral candidiasis.
Contemporary Diversity of β-Lactamases among Enterobacteriaceae in the Nine U.S. Census Regions and Ceftazidime-Avibactam Activity Tested against Isolates Producing the Most Prevalent β-Lactamase Groups
Authors: Castanheira Mariana , Farrell Sarah E. , Krause Kevin M. , Jones Ronald N. , Sader Helio S. 
Published: November 2013

ABSTRACT

Escherichia coli
(328 isolates),
Klebsiella pneumoniae
(296),
Klebsiella oxytoca
(44), and
Proteus mirabilis
(33) isolates collected during 2012 from the nine U.S. census regions and displaying extended-spectrum-β-lactamase (ESBL) phenotypes were evaluated for the presence of β-lactamase genes, and antimicrobial susceptibility profiles were analyzed. The highest ESBL rates were noted for
K. pneumoniae
(16.0%, versus 4.8 to 11.9% for the other species) and in the Mid-Atlantic and West South Central census regions. CTX-M group 1 (including CTX-M-15) was detected in 303 strains and was widespread throughout the United States but was more prevalent in the West South Central, Mid-Atlantic, and East North Central regions. KPC producers (118 strains [112
K. pneumoniae
strains]) were detected in all regions and were most frequent in the Mid-Atlantic region (58 strains). Thirteen KPC producers also carried
bla
CTX-M
. SHV genes encoding ESBL activity were detected among 176 isolates. Other β-lactamase genes observed were CTX-M group 9 (72 isolates), FOX (10), TEM ESBL (9), DHA (7), CTX-M group 2 (3), NDM-1 (2 [Colorado]), and CTX-M groups 8 and 25 (1). Additionally, 62.9% of isolates carried ≥2 β-lactamase genes. KPC producers were highly resistant to multiple agents, but ceftazidime-avibactam (MIC
50/90
, 0.5/2 μg/ml) and tigecycline (MIC
50/90
, 0.5/1 μg/ml) were the most active agents tested. Overall, meropenem (MIC
50
, ≤0.06 μg/ml), ceftazidime-avibactam (MIC
50
, 0.12 to 0.5 μg/ml), and tigecycline (MIC
50
, 0.12 to 2 μg/ml) were the most active antimicrobials when tested against this collection. NDM-1 producers were resistant to all β-lactams tested. The diversity and increasing prevalence of β-lactamase-producing
Enterobacteriaceae
have been documented, and ceftazidime-avibactam was very active against the vast majority of β-lactamase-producing strains isolated from U.S. hospitals.
Antimicrobial-Related Severe Adverse Events during Treatment of Bone and Joint Infection Due to Methicillin-Susceptible Staphylococcus aureus
Authors: Valour Florent , Karsenty Judith , Bouaziz Anissa , Ader Florence , Tod Michel , Lustig Sébastien , Laurent Frédéric , Ecochard René , Chidiac Christian , Ferry Tristan 
Published: November 2013

ABSTRACT

Prolonged antimicrobial therapy is recommended for methicillin-susceptible
Staphylococcus aureus
(MSSA) bone and joint infections (BJI), but its safety profile and risk factors for severe adverse events (SAE) in clinical practice are unknown. We addressed these issues in a retrospective cohort study (2001 to 2011) analyzing antimicrobial-related SAE (defined according to the Common Terminology Criteria for Adverse Events) in 200 patients (male, 62%; median age, 60.8 years [interquartile range {IQR}, 45.5 to 74.2 years]) with MSSA BJI admitted to a reference regional center with acute (66%) or chronic arthritis (7.5%), osteomyelitis (9.5%), spondylodiscitis (16%), or orthopedic device-related infections (67%). These patients received antistaphylococcal therapy for a median of 26.6 weeks (IQR, 16.8 to 37.8 weeks). Thirty-eight SAE occurred in 30 patients (15%), with a median time delay of 34 days (IQR, 14.75 to 60.5 days), including 10 patients with hematologic reactions, 9 with cutaneomucosal reactions, 6 with acute renal injuries, 4 with hypokalemia, and 4 with cholestatic hepatitis. The most frequently implicated antimicrobials were antistaphylococcal penicillins (ASP) (13 SAE/145 patients), fluoroquinolones (12 SAE/187 patients), glycopeptides (9 SAE/101 patients), and rifampin (7 SAE/107 patients). Kaplan-Meier curves and stepwise binary logistic regression analyses were used to determine the risk factors for the occurrence of antimicrobial-related SAE. Age (odds ratio [OR], 1.479 for 10-year increase; 95% confidence interval [CI], 1.116 to 1.960;
P
= 0.006) appeared to be the only independent risk factor for SAE. In patients receiving ASP or rifampin, daily dose (OR, 1.028; 95% CI, 1.006 to 1.051;
P
= 0.014) and obesity (OR, 8.991; 95% CI, 1.453 to 55.627;
P
= 0.018) were associated with the occurrence of SAE. The high rate of SAE and their determinants highlighted the importance of the management and follow-up of BJI, with particular attention to be paid to older persons, especially for ASP dosage, and to rifampin dose adjustment in obese patients.
Loss of Sigma Factor RpoN Increases Intestinal Colonization of Vibrio parahaemolyticus in an Adult Mouse Model
Authors: Whitaker W. Brian , Richards Gary P. , Boyd E. Fidelma 
Published: November 2013

ABSTRACT

Vibrio parahaemolyticus
is the leading cause of bacterial seafood-borne gastroenteritis worldwide, yet little is known about how this pathogen colonizes the human intestine. The alternative sigma factor RpoN/sigma-54 is a global regulator that controls flagellar synthesis, as well as a wide range of nonflagellar genes. We constructed an in-frame deletion mutation in
rpoN
(VP2670) in
V. parahaemolyticus
RIMD2210633, a clinical serogroup O3:K6 isolate, and examined the effects
in vivo
using a streptomycin-treated mouse model of colonization. We confirmed that deletion of
rpoN
rendered
V. parahaemolyticus
nonmotile, and it caused reduced biofilm formation and an apparent defect in glutamine synthetase production. In
in vivo
competition assays between the
rpoN
mutant and a wild-type RIMD2210633 strain marked with the β-galactosidase gene
lacZ
(WBWlacZ), the mutant colonized significantly more proficiently. Intestinal persistence competition assays also demonstrated that the
rpoN
mutant had enhanced fitness and outcompeted WBWlacZ. Mutants defective in the polar flagellum biosynthesis FliAP sigma factor also outcompeted WBWlacZ but not to the same level as the
rpoN
mutant, which suggested that lack of motility is not the sole cause of the fitness effect. In an
in vitro
growth competition assay in mouse intestinal mucus, the
rpoN
mutant also outcompeted the wild type and exhibited faster doubling times when grown in mucus and on individual components of mucus. Genes in the pathways for the catabolism of mucus sugars also had significantly higher expression levels in a Δ
rpoN
mutant than in the wild type. These data suggest that in
V. parahaemolyticus
, RpoN plays an important role in carbon utilization regulation, which may significantly affect host colonization.
AN INVARIANCE PRINCIPLE FOR THE TAGGED PARTICLE PROCESS IN CONTINUUM WITH SINGULAR INTERACTION POTENTIAL
Authors: CONRAD FLORIAN , FATTLER TORBEN , GROTHAUS MARTIN 
Published: November 2013

We consider the dynamics of a tagged particle in an infinite particle environment moving according to a stochastic gradient dynamics. For singular interaction potentials this tagged particle dynamics was constructed first in Ref. 7, using closures of pre-Dirichlet forms which were already proposed in Refs. 13 and 24. The environment dynamics and the coupled dynamics of the tagged particle and the environment were constructed separately. Here we continue the analysis of these processes: Proving an essential m-dissipativity result for the generator of the coupled dynamics from Ref. 7, we show that this dynamics does not only contain the environment dynamics (as one component), but is, given the latter, the only possible choice for being the coupled process. Moreover, we identify the uniform motion of the environment as the reversed motion of the tagged particle. (Since the dynamics are constructed as martingale solutions on configuration space, this is not immediate.) Furthermore, we prove ergodicity of the environment dynamics, whenever the underlying reference measure is a pure phase of the system. Finally, we show that these considerations are sufficient to apply Ref. 4 for proving an invariance principle for the tagged particle process. We remark that such an invariance principle was studied before in Ref. 13 for smooth potentials, and shown by abstract Dirichlet form methods in Ref. 24 for singular potentials. Our results apply for a general class of Ruelle measures corresponding to potentials possibly having infinite range, a non-integrable singularity at 0 and a nontrivial negative part, and fulfill merely a weak differentiability condition on ℝd\{0}.
Proteogenomic Analysis Reveals Unanticipated Adaptations of Colorectal Tumor Cells to Deficiencies in DNA Mismatch Repair
Authors: Halvey Patrick J. , Wang Xiaojing , Wang Jing , Bhat Ajaz A. , Dhawan Punita , Li Ming , Zhang Bing , Liebler Daniel C. , Slebos Robbert J.C. 
Published: November 2013

Abstract
A growing body of genomic data on human cancers poses the critical question of how genomic variations translate to cancer phenotypes. We used standardized shotgun proteomics and targeted protein quantitation platforms to analyze a panel of 10 colon cancer cell lines differing by mutations in DNA mismatch repair (MMR) genes. In addition, we performed transcriptome sequencing (RNA-seq) to enable detection of protein sequence variants from the proteomic data. Biologic replicate cultures yielded highly consistent proteomic inventories with a cumulative total of 6,513 protein groups with a protein false discovery rate of 3.17% across all cell lines. Networks of coexpressed proteins with differential expression based on MMR status revealed impact on protein folding, turnover and transport, on cellular metabolism and on DNA and RNA synthesis and repair. Analysis of variant amino acid sequences suggested higher stability of proteins affected by naturally occurring germline polymorphisms than of proteins affected by somatic protein sequence changes. The data provide evidence for multisystem adaptation to MMR deficiency with a stress response that targets misfolded proteins for degradation through the ubiquitin-dependent proteasome pathway. Enrichment analysis suggested epithelial-to-mesenchymal transition in RKO cells, as evidenced by increased mobility and invasion properties compared with SW480. The observed proteomic profiles demonstrate previously unknown consequences of altered DNA repair and provide an expanded basis for mechanistic interpretation of MMR phenotypes. Cancer Res; 74(1); 387–97. ©2013 AACR.
DNA Damage-Binding Complex Recruits HDAC1 to Repress Bcl-2 Transcription in Human Ovarian Cancer Cells
Authors: Zhao Ran , Han Chunhua , Eisenhauer Eric , Kroger John , Zhao Weiqiang , Yu Jianhua , Selvendiran Karuppaiyah , Liu Xingluo , Wani Altaf A. , Wang Qi-En 
Published: November 2013

AbstractElevated expression of the antiapoptotic factor Bcl-2 is believed to be one of the contributing factors to an increased relapse rate associated with multiple cisplatin-resistant cancers. DNA damage-binding protein complex subunit 2 (DDB2) has recently been revealed to play an important role in sensitizing human ovarian cancer cells to cisplatin-induced apoptosis through the downregulation of Bcl-2, but the underlying molecular mechanism remains poorly defined. Here, it is report that DDB2 functions as a transcriptional repressor for Bcl-2 in combination with DDB1. Quantitative ChIP and EMSA analysis revealed that DDB2 binds to a specific cis-acting element at the 5′-end of Bcl-2 P1 promoter. Overexpression of DDB2 resulted in marked losses of histone H3K9,14 acetylation along the Bcl-2 promoter and enhancer regions, concomitant with a local enrichment of HDAC1 to the Bcl-2 P1 core promoter in ovarian cancer cells. Coimmunoprecipitation and in vitro binding analyses identified a physical interaction between DDB1 and HDAC1, whereas downregulation of HDAC1 significantly enhanced Bcl-2 promoter activity. Finally, in comparison with wild-type DDB2, mutated DDB2, which is unable to repress Bcl-2 transcription, mediates a compromised apoptosis upon cisplatin treatment. Taken together, these data support a model wherein DDB1 and DDB2 cooperate to repress Bcl-2 transcription. DDB2 recognizes and binds to the Bcl-2 P1 promoter, and HDAC1 is recruited through the DDB1 subunit associated with DDB2 to deacetylate histone H3K9,14 across Bcl-2 regulatory regions, resulting in suppressed Bcl-2 transcription.Implications: Increasing the expression of DDB complex may provide a molecular strategy for cancer therapy. Mol Cancer Res; 12(3); 370–80. ©2013 AACR.
Synergistic Role of Protein Phosphatase Inhibitor 1 and Sarco/Endoplasmic Reticulum Ca
2+
-ATPase in the Acquisition of the Contractile Phenotype of Arterial Smooth Muscle Cells
Authors: Lipskaia Larissa , Bobe Regis , Chen Jiqiu , Turnbull Irene C. , Lopez Jose J. , Merlet Elise , Jeong Dongtaq , Karakikes Ioannis , Ross Alexandra S. , Liang Lifan , Mougenot Nathalie , Atassi Fabrice , Lompré Anne-Marie , Tarzami Sima T. , Kovacic Jason C. , Kranias Evangelia , Hajjar Roger J. , Hadri Lahouaria 
Published: November 2013

Background—
Phenotypic modulation or switching of vascular smooth muscle cells from a contractile/quiescent to a proliferative/synthetic phenotype plays a key role in vascular proliferative disorders such as atherosclerosis and restenosis. Although several calcium handling proteins that control differentiation of smooth muscle cells have been identified, the role of protein phosphatase inhibitor 1 (I-1) in the acquisition or maintenance of the contractile phenotype modulation remains unknown.

Methods and Results—

In human coronary arteries, I-1 and sarco/endoplasmic reticulum Ca
2+
-ATPase expression is specific to contractile vascular smooth muscle cells. In synthetic cultured human coronary artery smooth muscle cells, protein phosphatase inhibitor 1 (I-1 target) is highly expressed, leading to a decrease in phospholamban phosphorylation, sarco/endoplasmic reticulum Ca
2+
-ATPase, and cAMP-responsive element binding activity. I-1 knockout mice lack phospholamban phosphorylation and exhibit vascular smooth muscle cell arrest in the synthetic state with excessive neointimal proliferation after carotid injury, as well as significant modifications of contractile properties and relaxant response to acetylcholine of femoral artery in vivo. Constitutively active I-1 gene transfer decreased neointimal formation in an angioplasty rat model by preventing vascular smooth muscle cell contractile to synthetic phenotype change.

Conclusions—

I-1 and sarco/endoplasmic reticulum Ca
2+
-ATPase synergistically induce the vascular smooth muscle cell contractile phenotype. Gene transfer of constitutively active I-1 is a promising therapeutic strategy for preventing vascular proliferative disorders.
‘Struck (with Blood)’. The Meaning and Etymology of παλάσσω and Its Middle Perfect πεπάλακτο
Authors: van Beek Lucien 
Published: November 2013

Abstract
Among Homer’s bloody descriptions of battle scenes, we find the thrice-repeated phrase ἐγκέφαλος δὲ / ἔνδον ἅπας πεπάλακτο (Il. 11.97 f., 12.185 f., 20.399 f.). The middle pluperfect of παλάσσω is interpreted by commentators and dictionaries either as ‘the brain was spattered (against the inside of the helmet)’, or as ‘the brain was sprinkled (with blood)’. Both interpretations of πεπάλακτο yield syntactic and/or semantic problems. In this paper, I discuss these problems and, after reconsidering the attestations of παλάσσω during the history of Greek, propose a new solution. It is argued that παλάσσω does not primarily mean ‘sprinkle, bespatter’, but (i) ‘strike’, out of which (ii) ‘soil, defile’ developed. In the problematic Homeric phrase, I suggest to translate πεπάλακτο with ‘was struck’. Moreover, I propose an etymology for παλάσσω, deriving the middle perfect πεπάλακτο (which I consider to be the oldest formation) from the same root as πλήσσω ‘strike’, viz., PIE *pleh2g-. This etymology is corroborated by the comparison between ἐµπαλάσσοµαι and ἐνιπλήσσω, both ‘be stuck (in)’.
Cassius Dio on Julia Domna: A Study of the Political and Ethical Functions of Biographical Representation in Dio’s Roman History
Authors: Mallan C.T. 
Published: November 2013

AbstractOf the individuals who appear in the closing books of Cassius Dio’sRoman History, there is perhaps none more beguiling than Julia Domna. Dio’s account of the life of Domna is the fullest surviving from antiquity. Yet, Dio’s portrayal of Domna is not a miscellany of facts about the empress, and thus should not be treated as such. Rather, it is a contrived literary portrayal that fulfilled important moralizing functions within the Severan narrative of theRoman History. This article provides an analysis of Dio’s portrayal of Domna. It suggests that Dio shaped his portrayal of Domna to serve two purposes within the text: firstly, to act as a foil to his portrayals of C. Fulvius Plautianus and Caracalla; and, secondly, to explore through the figure of Domna political and ethical themes relevant to Dio’s appraisal of the Severan period.