bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disaster, Time, and Dialogue: A Couple Lessons from Hurricane Katrina
Authors: Kroll‐Smith Steve , Madsen Rachel S. 
Published: May 2014

There is much to learn about ourselves and the worlds we fashion “when all hell breaks loose” (W. Lloyd Warner 1947:1).
This brief paper is about The Katrina Bookshelf, specifically about a couple of the contributions several of the forthcoming books on The Shelf will make to the social study of disaster. It is both a collective and an individual achievement. Imagine The Katrina Bookshelf as a composition and each book on The Shelf a movement, a part of the composition that is more or less complete in and of itself. Any one of the books could be taken from The Shelf and read alone, independent of the others. Each has its own voice and reaches its own resolution. But examined together, The Shelf reveals the phenomenal human complexity that is Hurricane Katrina.
ASpace‐Time RasterGISData Model for Spatiotemporal Analysis of Vegetation Responses to a Freeze Event
Authors: Zhao Ziliang , Shaw Shih‐Lung , Wang Dali 
Published: May 2014

AbstractMany past space‐timeGISdata models viewed the world mainly from a spatial perspective. They attached a time stamp to each state of an entity or the entire area of study. This approach is less efficient for certain spatio‐temporal analyses that focus on how locations change over time, which require researchers to view each location from a temporal perspective. In this article, we present a data model to organize multi‐temporal remote sensing datasets and track their changes at the individual pixel level. This data model can also integrate raster datasets from heterogeneous sources under a unified framework. The proposed data model consists of several object classes under a hierarchical structure. Each object class is associated with specific properties and behaviors to facilitate efficient spatio‐temporal analyses. We apply this data model to a case study of analyzing the impact of the 2007 freeze in Knoxville, Tennessee. The characteristics of different vegetation clusters before, during, and after the 2007 freeze event are compared. Our findings indicate that the majority of the study area is impacted by this freeze event, and different vegetation types show different response patterns to this freeze.
Heme‐related molecules induce rapid production of neutrophil extracellular traps
Authors: Kono Mari , Saigo Katsuyasu , Takagi Yuri , Takahashi Takayuki , Kawauchi Sawako , Wada Atsushi , Hashimoto Makoto , Minami Yosuke , Imoto Shion , Takenokuchi Mariko , Morikawa Takashi , Funakoshi Kunihiro 
Published: May 2014

BackgroundPulmonary endothelial cell damages caused by neutrophil overactivation could result in acute lung injuries including transfusion‐related acute lung injury (TRALI). We previously reported that heme‐related molecules derived from hemolysis induced the production of reactive oxygen species from neutrophils. Recently, neutrophil extracellular traps (NETs) have been demonstrated to associate with the onset of TRALI.Study Design and MethodsIn this study, neutrophils' morphologic changes induced by the heme‐related molecule hemin were confirmed to be NETs via confocal laser scanning microscopy and electron microscopy (EM). Additionally, concentrations of hemin in red blood cell (RBC) components were measured via enzyme‐linked immunosorbent assay and possible contribution of these molecules to the onset of TRALI was discussed.ResultsSYTOX green staining observation via confocal laser scanning microscopy revealed that neutrophil morphology changed rapidly upon addition of hemin. The nuclei began to be enlarged and become segmented after 5 minutes, and NET‐like structures were released from neutrophils after 15 minutes. In EM observation, NET‐like structures appeared after 10 minutes and the nucleoplasm was partially separated from the nuclear membrane, which were consistent with the features of NET formation. These structures stained positively for both myeloperoxidase and histone H3 antibodies.ConclusionThus, our results suggest that hemin induced NETs in 15 minutes, a quicker reaction than NET induction by phorbol myristate acetate requiring 3 hours. Moreover, since RBC components, especially those with long‐term storage, contained sufficient hemin concentration to induce NETs, special attention to hemolysis of stored RBC components is important.
Long‐term impacts from damming and water level manipulation on flow and salinity regimes in Lake Urmia, Iran
Authors: Zeinoddini Mostafa , Bakhtiari Arash , Ehteshami Majid 
Published: May 2014

AbstractLake Urmia in the north‐west of Iran is very large, very shallow and several times more saline than ocean water. The salinity of this terminal lake is of great ecological consequence for the existence and growth of Artemia Urmiana, a unique zooplankton endemic to the lake. It is a main food source for large bird populations. During the past decades, Lake Urmia has been strained by a number of anthropogenic and natural causes. They include extensive damming on the contributory rivers, building a dike‐type causeway and climate change. This paper deals with the long‐term impacts of damming, fresh water overexploitation and water level manipulation on flow and salinity conditions in Lake Urmia. For this purpose, the flow and salinity regimes were numerically simulated for the next four decades. The validity of the pseudo‐three‐dimensional hydrodynamic and advection‐dispersion models was assessed through sensitivity analysis of the models and comparing the simulated results against field measurements. The model predicted that because of damming on the rivers, the mean water level in the lake will possibly experience a drop of 2.2–2.8 m over next 40 years. The results indicated that, over decadal time periods, the lake most probably will be split into two interconnected smaller lakes. The northern lake was foreseen to become extremely saline, which will seriously threaten the Artemia's survival in this area. Over the long‐term periods, the southern lake seemed not to deviate much from its existing conditions. It however appeared to become more responsive to seasonal climatic changes and to the rivers inflow, as compared with its current conditions. Effects from climate changes were not considered in the current study.
Deletion of the Uracil Permease Gene Confers Cross-Resistance to 5-Fluorouracil and Azoles in Candida lusitaniae and Highlights Antagonistic Interaction between Fluorinated Nucleotides and Fluconazole
Authors: Gabriel Frédéric , Sabra Ayman , El-Kirat-Chatel Sofiane , Pujol Sophie , Fitton-Ouhabi Valérie , Brèthes Daniel , Dementhon Karine , Accoceberry Isabelle , Noël Thierry 
Published: May 2014

ABSTRACT

We characterized two additional membrane transporters (Fur4p and Dal4p) of the nucleobase cation symporter 1 (NCS1) family involved in the uptake transport of pyrimidines and related molecules in the opportunistic pathogenic yeast
Candida lusitaniae
. Simple and multiple null mutants were constructed by gene deletion and genetic crosses. The function of each transporter was characterized by supplementation experiments, and the kinetic parameters of the uptake transport of uracil were measured using radiolabeled substrate. Fur4p specifically transports uracil and 5-fluorouracil. Dal4p is very close to Fur4p and transports allantoin (glyoxyldiureide). Deletion of the
FUR4
gene confers resistance to 5-fluorouracil as well as cross-resistance to triazoles and imidazole antifungals when they are used simultaneously with 5-fluorouracil. However, the nucleobase transporters are not involved in azole uptake. Only fluorinated pyrimidines, not pyrimidines themselves, are able to promote cross-resistance to azoles by both the salvage and the
de novo
pathway of pyrimidine synthesis. A reinterpretation of the data previously obtained led us to show that subinhibitory doses of 5-fluorocytosine, 5-fluorouracil, and 5-fluorouridine also were able to trigger resistance to fluconazole in susceptible wild-type strains of
C. lusitaniae
and of different
Candida
species. Our results suggest that intracellular fluorinated nucleotides play a key role in azole resistance, either by preventing azoles from targeting the lanosterol 14-alpha-demethylase or its catalytic site or by acting as a molecular switch for the triggering of efflux transport.
Selective Pharmacologic Inhibition of a PASTA Kinase Increases Listeria monocytogenes Susceptibility to β-Lactam Antibiotics
Authors: Pensinger Daniel A. , Aliota Matthew T. , Schaenzer Adam J. , Boldon Kyle M. , Ansari Israr-ul H. , Vincent William J. B. , Knight Benjamin , Reniere Michelle L. , Striker Rob , Sauer John-Demian 
Published: May 2014

ABSTRACT

While β-lactam antibiotics are a critical part of the antimicrobial arsenal, they are frequently compromised by various resistance mechanisms, including changes in penicillin binding proteins of the bacterial cell wall. Genetic deletion of the
p
enicillin binding protein
a
nd
s
erine/
t
hreonine kinase-
a
ssociated protein (PASTA) kinase in methicillin-resistant
Staphylococcus aureus
(MRSA) has been shown to restore β-lactam susceptibility. However, the mechanism remains unclear, and whether pharmacologic inhibition would have the same effect is unknown. In this study, we found that deletion or pharmacologic inhibition of the PASTA kinase in
Listeria monocytogenes
by the nonselective kinase inhibitor staurosporine results in enhanced susceptibility to both aminopenicillin and cephalosporin antibiotics. Resistance to vancomycin, another class of cell wall synthesis inhibitors, or antibiotics that inhibit protein synthesis was unaffected by staurosporine treatment. Phosphorylation assays with purified kinases revealed that staurosporine selectively inhibited the PASTA kinase of
L. monocytogenes
(PrkA). Importantly, staurosporine did not inhibit a
L. monocytogenes
kinase without a PASTA domain (Lmo0618) or the PASTA kinase from MRSA (Stk1). Finally, inhibition of PrkA with a more selective kinase inhibitor, AZD5438, similarly led to sensitization of
L. monocytogenes
to β-lactam antibiotics. Overall, these results suggest that pharmacologic targeting of PASTA kinases can increase the efficacy of β-lactam antibiotics.
In Vitro
and
In Vivo
Evidence for Amphotericin B as a P-Glycoprotein Substrate on the Blood-Brain Barrier
Authors: Wu Ji-Qin , Shao Kun , Wang Xuan , Wang Rui-Ying , Cao Ya-Hui , Yu Yun-Qiu , Lou Jin-Ning , Chen Yan-Qiong , Zhao Hua-Zhen , Zhang Qiang-Qiang , Weng Xin-Hua , Jiang Chen , Zhu Li-Ping 
Published: May 2014

ABSTRACT

Amphotericin B (AMB) has been a mainstay therapy for fungal infections of the central nervous system, but its use has been limited by its poor penetration into the brain, the mechanism of which remains unclear. In this study, we aimed to investigate the role of P-glycoprotein (P-gp) in AMB crossing the blood-brain barrier (BBB). The uptake of AMB by primary brain capillary endothelial cells
in vitro
was significantly enhanced after inhibition of P-gp by verapamil. The impact of two model P-gp inhibitors, verapamil and itraconazole, on brain/plasma ratios of AMB was examined in both uninfected CD-1 mice and those intracerebrally infected with
Cryptococcus neoformans
. In uninfected mice, the brain/plasma ratios of AMB were increased 15 min (3.5 versus 2.0;
P
< 0.05) and 30 min (5.2 versus 2.8;
P
< 0.05) after administration of verapamil or 45 min (6.0 versus 3.9;
P
< 0.05) and 60 min (5.4 versus 3.8;
P
< 0.05) after itraconazole administration. The increases in brain/plasma ratios were also observed in infected mice treated with AMB and P-gp inhibitors. The brain tissue fungal CFU in infected mice were significantly lower in AMB-plus-itraconazole or verapamil groups than in the untreated group (
P
< 0.005), but none of the treatments protected the mice from succumbing to the infection. In conclusion, we demonstrated that P-gp inhibitors can enhance the uptake of AMB through the BBB, suggesting that AMB is a P-gp substrate.
New Amphiphilic Neamine Derivatives Active against Resistant Pseudomonas aeruginosa and Their Interactions with Lipopolysaccharides
Authors: Sautrey Guillaume , Zimmermann Louis , Deleu Magali , Delbar Alicia , Souza Machado Luiza , Jeannot Katy , Van Bambeke Françoise , Buyck Julien M. , Decout Jean-Luc , Mingeot-Leclercq Marie-Paule 
Published: May 2014

ABSTRACT

The development of novel antimicrobial agents is urgently required to curb the widespread emergence of multidrug-resistant bacteria like colistin-resistant
Pseudomonas aeruginosa
. We previously synthesized a series of amphiphilic neamine derivatives active against bacterial membranes, among which 3′,6-di-
O
-[(2″-naphthyl)propyl]neamine (3′,6-di2NP), 3′,6-di-
O
-[(2″-naphthyl)butyl]neamine (3′,6-di2NB), and 3′,6-di-
O
-nonylneamine (3′,6-diNn) showed high levels of activity and low levels of cytotoxicity (L. Zimmermann et al., J. Med. Chem. 56:7691–7705, 2013). We have now further characterized the activity of these derivatives against colistin-resistant
P. aeruginosa
and studied their mode of action; specifically, we characterized their ability to interact with lipopolysaccharide (LPS) and to alter the bacterial outer membrane (OM). The three amphiphilic neamine derivatives were active against clinical colistin-resistant strains (MICs, about 2 to 8 μg/ml), The most active one (3′,6-diNn) was bactericidal at its MIC and inhibited biofilm formation at 2-fold its MIC. They cooperatively bound to LPSs, increasing the outer membrane permeability. Grafting long and linear alkyl chains (nonyl) optimized binding to LPS and outer membrane permeabilization. The effects of amphiphilic neamine derivatives on LPS micelles suggest changes in the cross-bridging of lipopolysaccharides and disordering in the hydrophobic core of the micelles. The molecular shape of the 3′,6-dialkyl neamine derivatives induced by the nature of the grafted hydrophobic moieties (naphthylalkyl instead of alkyl) and the flexibility of the hydrophobic moiety are critical for their fluidifying effect and their ability to displace cations bridging LPS. Results from this work could be exploited for the development of new amphiphilic neamine derivatives active against colistin-resistant
P. aeruginosa
.
Emergence of Resistance to Atovaquone-Proguanil in Malaria Parasites: Insights from Computational Modeling and Clinical Case Reports
Authors: Cottrell Gilles , Musset Lise , Hubert Véronique , Le Bras Jacques , Clain Jérôme 
Published: May 2014

ABSTRACT

The usefulness of atovaquone-proguanil (AP) as an antimalarial treatment is compromised by the emergence of atovaquone resistance during therapy. However, the origin of the parasite mitochondrial DNA (mtDNA) mutation conferring atovaquone resistance remains elusive. Here, we report a patient-based stochastic model that tracks the intrahost emergence of mutations in the multicopy mtDNA during the first erythrocytic parasite cycles leading to the malaria febrile episode. The effect of mtDNA copy number, mutation rate, mutation cost, and total parasite load on the mutant parasite load per patient was evaluated. Computer simulations showed that almost any infected patient carried, after four to seven erythrocytic cycles,
de novo
mutant parasites at low frequency, with varied frequencies of parasites carrying varied numbers of mutant mtDNA copies. A large interpatient variability in the size of this mutant reservoir was found; this variability was due to the different parameters tested but also to the relaxed replication and partitioning of mtDNA copies during mitosis. We also report seven clinical cases in which AP-resistant infections were treated by AP. These provided evidence that parasiticidal drug concentrations against AP-resistant parasites were transiently obtained within days after treatment initiation. Altogether, these results suggest that each patient carries new mtDNA mutant parasites that emerge before treatment but are killed by high starting drug concentrations. However, because the size of this mutant reservoir is highly variable from patient to patient, we propose that some patients fail to eliminate all of the mutant parasites, repeatedly producing
de novo
AP treatment failures.
Population Pharmacokinetics and Clinical Response for Artemether-Lumefantrine in Pregnant and Nonpregnant Women with Uncomplicated Plasmodium falciparum Malaria in Tanzania
Authors: Mosha Dominic , Guidi Monia , Mwingira Felista , Abdulla Salim , Mercier Thomas , Decosterd Laurent Arthur , Csajka Chantal , Genton Blaise 
Published: May 2014

ABSTRACT

Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated malaria in the second and third trimesters of pregnancy. Its efficacy during pregnancy has recently been challenged due to altered pharmacokinetic (PK) properties in this vulnerable group. The aim of this study was to determine the PK profile of AL in pregnant and nonpregnant women and assess their therapeutic outcome. Thirty-three pregnant women and 22 nonpregnant women with malaria were treated with AL (80/480 mg) twice daily for 3 days. All patients provided five venous plasma samples for drug quantification at random times over 7 days. Inter- and intraindividual variability was assessed, and the effects of covariates were quantified using a nonlinear mixed-effects modeling approach (NONMEM). A one-compartment model with first-order absorption and elimination with linear metabolism from drug to metabolite fitted the data best for both arthemether (AM) and lumefantrine (LF) and their metabolites. Pregnancy status and diarrhea showed a significant influence on LF PK. The relative bioavailability of lumefantrine and its metabolism rate into desmethyl-lumefantrine were, respectively, 34% lower and 78% higher in pregnant women than in nonpregnant patients. The overall PCR-uncorrected treatment failure rates were 18% in pregnant women and 5% in nonpregnant women (odds ratio [OR] = 4.04;
P
value of 0.22). A high median day 7 lumefantrine concentration was significantly associated with adequate clinical and parasitological response (
P
= 0.03). The observed reduction in the relative bioavailability of lumefantrine in pregnant women may explain the higher treatment failure in this group, mostly due to lower posttreatment prophylaxis. Hence, a modified treatment regimen of malaria in pregnancy should be considered.
In Vivo
and
In Vitro
Acquisition of Resistance to Voriconazole by Candida krusei
Authors: Ricardo Elisabete , Miranda Isabel M. , Faria-Ramos Isabel , Silva Raquel M. , Rodrigues Acácio Gonçalves , Pina-Vaz Cidália 
Published: May 2014

ABSTRACT

Candida krusei
is an important agent of opportunistic infections that often displays resistance to several antifungals. We describe here the
in vivo
acquisition of resistance to voriconazole (VRC) by
C. krusei
isolates recovered from a leukemia patient during a long period of VRC therapy. In order to mimic the
in vivo
development of VRC resistance, a susceptible
C. krusei
isolate was exposed daily to 1 μg/ml of VRC
in vitro
. Interestingly, after 5 days of exposure to VRC, a MIC of 4 μg/ml was achieved; this value remained constant after 25 additional days of treatment with VRC and also after 30 consecutive days of incubation in VRC-free medium. Our objective was to determine the associated molecular resistance mechanisms, such as expression of efflux pump genes and
ERG11
gene mutations, among the resistant strains. Synergistic effects between the efflux blocker tacrolimus (FK506) and VRC were found in all of the resistant strains. Moreover,
ABC1
gene expression increased over time in both the
in vivo
- and
in vitro
-induced resistant strains, in contrast to the
ABC2
and
ERG11
genes, whose expression was invariably lower and constant.
ERG11
gene sequencing showed two different types of mutations, i.e., heterozygosity at T1389T/C, corresponding to synonymous mutations, in
C. krusei
strains and a missense mutation at position T418C, resulting in a change from Tyr to His, among resistant
C. krusei
clinical isolates. This study highlights the relevance of ATP-dependent efflux pump (namely, Abc1p) activity in VRC resistance and describes new mutations in the
ERG11
gene among resistant
C. krusei
clinical isolates.
Eight More Ways To Deal with Antibiotic Resistance
Authors: Metz Matthew , Shlaes David M. 
Published: May 2014

ABSTRACT
The fight against antibiotic resistance must be strengthened. We propose actions that U.S. government agencies and private sector entities can take to build a more comprehensive effort. These actions can increase the viability of investing in new antibiotics, ensure the quality and stewardship of all antibiotics, and make responses to emerging resistance more informed. Success requires the thoughtful exercise of federal authority and a firm commitment to share data and reward developers for the value generated with new, life-saving antibiotics.
Extended-Infusion versus Standard-Infusion Piperacillin-Tazobactam for Sepsis Syndromes at a Tertiary Medical Center
Authors: Cutro Scott R. , Holzman Robert , Dubrovskaya Yanina , Chen Xian Jie Cindy , Ahuja Tania , Scipione Marco R. , Chen Donald , Papadopoulos John , Phillips Michael S. , Mehta Sapna A. 
Published: May 2014

ABSTRACT

Piperacillin-tazobactam (PTZ) is frequently used as empirical and targeted therapy for Gram-negative sepsis. Time-dependent killing properties of PTZ support the use of extended-infusion (EI) dosing; however, studies have shown inconsistent benefits of EI PTZ treatment on clinical outcomes. We performed a retrospective cohort study of adult patients who received EI PTZ treatment and historical controls who received standard-infusion (SI) PTZ treatment for presumed sepsis syndromes. Data on mortality rates, clinical outcomes, length of stay (LOS), and disease severity were obtained. A total of 843 patients (662 with EI treatment and 181 with SI treatment) were available for analysis. Baseline characteristics of the two groups were similar, except for fewer female patients receiving EI treatment. No significant differences between the EI and SI groups in inpatient mortality rates (10.9% versus 13.8%;
P
= 0.282), overall LOS (10 versus 12 days;
P
= 0.171), intensive care unit (ICU) LOS (7 versus 6 days;
P
= 0.061), or clinical failure rates (18.4% versus 19.9%;
P
= 0.756) were observed. However, the duration of PTZ therapy was shorter in the EI group (5 versus 6 days;
P
< 0.001). Among ICU patients, no significant differences in outcomes between the EI and SI groups were observed. Patients with urinary or intra-abdominal infections had lower mortality and clinical failure rates when receiving EI PTZ treatment. We did not observe significant differences in inpatient mortality rates, overall LOS, ICU LOS, or clinical failure rates between patients receiving EI PTZ treatment and patients receiving SI PTZ treatment. Patients receiving EI PTZ treatment had a shorter duration of PTZ therapy than did patients receiving SI treatment, and EI dosing may provide cost savings to hospitals.