bluuebunny/crossref_metadata_2025_split huggingface dataset:
The (mis)fortunes of exceeding a small local air market: Comparing Amsterdam and Brussels
Authors: Burghouwt Guillaume , Dobruszkes Frédéric 
Published: April 2014

AbstractComparing air service growth in Amsterdam and Brussels, this paper aims to understand how the strategies of airlines and public authorities allow certain medium‐sized cities to succeed in exceeding their local market by connecting passengers, while others do not. In contrast to Brussels, Amsterdam has become one of the most air serviced European cities, reaching a highly disproportionate level of service given both its size and its airport catchment area. Amsterdam has reached its rank thanks to a successful, global hub‐and‐spokes strategy led by KLM and its partners. Such a success story would have been impossible without support from the State pursuing the expansion of numerous, liberal bilateral air service agreements and a regional development strategy which facilitated the expansion of Amsterdam Schiphol airport in the 1990s. Finally, this paper shows how public and corporate governances might be able to convert themselves to the rules of the market economy.
An Exploration of Memory‐making in the Digital Era: Remembering the FEPOW Story Online
Authors: Muzaini Hamzah , Yeoh Brenda S.A. 
Published: April 2014

AbstractSymptomatic of the digital era, web‐memorials and web‐communities have become highly prevalent as a means of commemorating the past. Drawing on the analysis of fepow‐community.org.uk, an online network devoted to honouring the stories of Allied soldiers interned by the Japanese during the Second World War (also known as FEPOWs), and an online survey of its members, this paper examines the extent that such platforms facilitate more inclusionary allowances for doing so vis‐à‐vis physical sites of memory. Specifically, while web‐memorials do remedy some of the shortcomings linked to the latter, they too are plagued by criticisms limiting them as a more democratic way of remembering. It also highlights how physical sites of memory provide certain affective resonances virtual memorials do not. Consequently, both genres of memory are often capitalised upon complementarily (rather than in a mutually exclusive way) as each feeds into the other, both salient to memory work.
Integrating Spatial Data Linkage and Analysis Services in a Geoportal for China Urban Research
Authors: Zhu Xinyan , She Bing , Guo Wei , Bao Shuming , Chen Di 
Published: April 2014

AbstractMany geoportals are now evolving into online analytical environments, where large amounts of data and various analysis methods are integrated. These spatiotemporal data are often distributed in different databases and exist in heterogeneous forms, even when they refer to the same geospatial entities. Besides, existing open standards lack sufficient expression of the attribute semantics. Client applications or other services thus have to deal with unrelated preprocessing tasks, such as data transformation and attribute annotation, leading to potential inconsistencies. Furthermore, to build informative interfaces that guide users to quickly understand the analysis methods, an analysis service needs to explicitly model the method parameters, which are often interrelated and have rich auxiliary information. This work presents the design of the spatial data linkage and analysis services in a geoportal for China urban research. The spatial data linkage service aggregates multisource heterogeneous data into linked layers with flexible attribute mapping, providing client applications and services with a unified access as if querying a big table. The spatial analysis service incorporates parameter hierarchy and grouping by extending the standard WPS service, and data‐dependent validation in computation components. This platform can help researchers efficiently explore and analyze spatiotemporal data online.
Adenosine receptor inhibition attenuates the suppression of postexercise cutaneous blood flow
Authors: McGinn Ryan , Fujii Naoto , Swift Brendan , Lamarche Dallon T. , Kenny Glen P. 
Published: April 2014

Key points
Skin blood flow (SkBF) is an important avenue for heat loss; however, it is rapidly suppressed after exercise despite persistently high core and muscle temperatures.
This has been ascribed to altered active vasodilation; however, recent work has identified a role for adenosine receptors in the decrease in SkBF following passive heating.
In this study, we examined whether adenosine receptors are involved in the postexercise regulation of SkBF by infusion of 4 mm theophylline (a non‐selective adenosine receptor antagonist) via microdialysis.
We show that adenosine receptors have a major role in modulating postexercise SkBF, as evidenced by a marked elevation during theophylline infusion compared to a control site.
These results help us to better understand the mechanisms underlying the postexercise reduction in SkBF and subsequently heat loss which is associated with heat‐related illness and/or injury.
AbstractThe time‐dependent contributions of active vasodilation (e.g. nitric oxide) and noradrenergic vasoconstriction to the postexercise suppression of cutaneous perfusion despite persistent hyperthermia remain unknown. Moreover, adenosine receptors have been shown to mediate the decrease in cutaneous perfusion following passive heating. We examined the time‐dependent modulation of nitric oxide synthase, noradrenergic vasoconstriction and adenosine receptors on postexercise cutaneous perfusion. Eight males performed 15 min of high‐intensity (85% ) cycling followed by 60 min of recovery in temperate ambient conditions (25°C). Four microdialysis probes were inserted into the forearm skin and continuously infused with: (1) lactated Ringer solution (Control); (2) 10 mm NG‐nitro‐l‐arginine methyl ester (l‐NAME; nitric oxide synthase inhibitor); (3) 10 mm bretylium tosylate (BT; inhibitor of noradrenergic vasoconstriction); or (4) 4 mm theophylline (THEO; adenosine receptor inhibitor). Cutaneous vascular conductance (CVC) was expressed as a percentage of maximum and was calculated as perfusion units (laser Doppler) divided by mean arterial pressure. End‐exercise CVC was similar in Control, THEO and BT (P > 0.1), but CVC with l‐NAME (39 ± 4%) was lower than Control (59 ± 4%, P < 0.01). At 20 min of recovery, Control CVC (22 ± 3%) returned to baseline levels (19 ± 2%, P = 0.11). Relative to Control, CVC was reduced by l‐NAME for the first 10 min of recovery whereas CVC was increased with BT for the first 30 min of recovery (P < 0.03). In contrast, CVC with THEO was elevated throughout the 60 min recovery period (P ≤ 0.01) compared to Control. We show that adenosine receptors appear to have a major role in postexercise cutaneous perfusion whereas nitric oxide synthase and noradrenergic vasoconstriction are involved only earlier during recovery.
The Combination of Alisporivir plus an NS5A Inhibitor Provides Additive to Synergistic Anti-Hepatitis C Virus Activity without Detectable Cross-Resistance
Authors: Chatterji Udayan , Garcia-Rivera Jose A. , Baugh James , Gawlik Katarzyna , Wong Kelly A. , Zhong Weidong , Brass Clifford A. , Naoumov Nikolai V. , Gallay Philippe A. 
Published: April 2014

ABSTRACT

Alisporivir (ALV), a cyclophilin inhibitor, is a host-targeting antiviral (HTA) with multigenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. Recent advances have supported the concept of interferon (IFN)-free regimens to treat chronic hepatitis C. As the most advanced oral HTA, ALV with direct-acting antivirals (DAAs) represents an attractive drug combination for IFN-free therapy. In this study, we investigated whether particular DAAs exhibit additive, synergistic, or antagonistic effects when combined with ALV. Drug combinations of ALV with NS3 protease, NS5B polymerase, and NS5A inhibitors were investigated in HCV replicons from genotypes 1a, 1b, 2a, 3, and 4a (GT1a to -4a). Combinations of ALV with DAAs exerted an additive effect on GT1 and -4. A significant and specific synergistic effect was observed with ALV-NS5A inhibitor combination on GT2 and -3. Furthermore, ALV was fully active against DAA-resistant variants, and ALV-resistant variants were fully susceptible to DAAs. ALV blocks the contact between cyclophilin A and domain II of NS5A, and NS5A inhibitors target domain I of NS5A; our data suggest a molecular basis for the use of these two classes of inhibitors acting on two distinct domains of NS5A. These results provide
in vitro
evidence that ALV with NS5A inhibitor combination represents an attractive strategy and a potentially effective IFN-free regimen for treatment of patients with chronic hepatitis C. Due to its high barrier and lack of cross-resistance, ALV could be a cornerstone drug partner for DAAs.
Activities of Ceftazidime and Avibactam against β-Lactamase-Producing Enterobacteriaceae in a Hollow-Fiber Pharmacodynamic Model
Authors: Coleman Ken , Levasseur Premavathy , Girard Anne-Marie , Borgonovi Monica , Miossec Christine , Merdjan Henri , Drusano George , Shlaes David , Nichols Wright W. 
Published: April 2014

ABSTRACT
Avibactam is a novel non-β-lactam β-lactamase inhibitor that is currently undergoing phase 3 clinical trials in combination with ceftazidime. Ceftazidime is hydrolyzed by a broad range of β-lactamases, but avibactam is able to inhibit the majority of these enzymes. The studies described here attempt to provide insight into the amount of avibactam required to suppress bacterial growth in an environment where the concentrations of both agents are varying as they would when administered to humans. Following the simulation of a single intravenous dose of the drug, ceftazidime alone had no effect on any test organism, but a ceftazidime-avibactam combination resulted in rapid killing of all of the strains, with growth suppressed for the 8 h of the study. For seven of eight strains, this was achieved with a 1-g–250-mg profile, but a 2-g–500-mg profile was necessary to completely suppress a high-level-AmpC-producing isolate. When ceftazidime was infused continuously for 24 h with a single bolus dose of avibactam, rapid killing of all of the strains was again observed, with growth suppressed for 10 to >24 h. Regrowth appeared to commence once the avibactam concentration dropped below a critical concentration of approximately 0.3 μg/ml. In a third series of studies, ceftazidime was administered every 8 h for 24 h with avibactam administered at fixed concentrations for short periods during each ceftazidime dose profile. Simulating a 1-g dose of ceftazidime, an avibactam pulse of >0.25 and <0.5 μg/ml was required to suppress growth for 24 h.
Discovery of Novel Cell Wall-Active Compounds Using P

ywaC

, a Sensitive Reporter of Cell Wall Stress, in the Model Gram-Positive Bacterium Bacillus subtilis
Authors: Czarny T. L. , Perri A. L. , French S. , Brown E. D. 
Published: April 2014

ABSTRACT

The emergence of antibiotic resistance in recent years has radically reduced the clinical efficacy of many antibacterial treatments and now poses a significant threat to public health. One of the earliest studied well-validated targets for antimicrobial discovery is the bacterial cell wall. The essential nature of this pathway, its conservation among bacterial pathogens, and its absence in human biology have made cell wall synthesis an attractive pathway for new antibiotic drug discovery. Herein, we describe a highly sensitive screening methodology for identifying chemical agents that perturb cell wall synthesis, using the model of the Gram-positive bacterium
Bacillus subtilis
. We report on a cell-based pilot screen of 26,000 small molecules to look for cell wall-active chemicals in real time using an autonomous luminescence gene cluster driven by the promoter of
ywaC
, which encodes a guanosine tetra(penta)phosphate synthetase that is expressed under cell wall stress. The promoter-reporter system was generally much more sensitive than growth inhibition testing and responded almost exclusively to cell wall-active antibiotics. Follow-up testing of the compounds from the pilot screen with secondary assays to verify the mechanism of action led to the discovery of 9 novel cell wall-active compounds.
Echinocandin Failure Case Due to a Previously Unreported
FKS1
Mutation in Candida krusei
Authors: Jensen Rasmus Hare , Justesen Ulrik Stenz , Rewes Annika , Perlin David S. , Arendrup Maiken Cavling 
Published: April 2014

ABSTRACT

Echinocandins are the preferred therapy for invasive infections due to
Candida krusei
. We present here a case of clinical failure involving
C. krusei
with a characteristic
FKS1
hot spot mutation not previously reported in
C. krusei
that was isolated after 14 days of treatment. Anidulafungin MICs were elevated by ≥5 dilution steps above the clinical breakpoint but by only 1 step for a
Candida albicans
isolate harboring the corresponding mutation, suggesting a notable species-specific difference in the MIC increase conferred by this mutation.
Evaluation of the Pharmacokinetics and Pharmacodynamics of Liposomal Amikacin for Inhalation in Cystic Fibrosis Patients with Chronic Pseudomonal Infections Using Data from Two Phase 2 Clinical Studies
Authors: Okusanya Olanrewaju O. , Bhavnani Sujata M. , Hammel Jeffrey P. , Forrest Alan , Bulik Catharine C. , Ambrose Paul G. , Gupta Renu 
Published: April 2014

ABSTRACT

The pharmacokinetic-pharmacodynamic (PK-PD) relationships between serum exposure measures of liposomal amikacin for inhalation (LAI) and the change in pulmonary function test (PFT) measures and number of CFU from baseline were evaluated in cystic fibrosis (CF) patients chronically infected with
Pseudomonas aeruginosa
. A dose of 70, 140, 280, or 560 mg of LAI or placebo was administered to CF patients once daily for 28 days. PFTs and sputum samples for microbiology were assessed on days 7, 14, 21, 28, 35 (for log
10
CFU), and 56 (for PFTs). Serum, urine, and sputum samples were collected for PK evaluation. The relationships between efficacy endpoints (relative change in forced expiratory volume in 1 s [FEV
1
{expressed in liters}] and FEV
1
% predicted and the absolute change in log
10
CFU of
P. aeruginosa
from baseline) and exposure measures (dose, day 1 area under the curve [AUC], dose/MIC ratio, and day 1 AUC/MIC ratio) and baseline MIC value were assessed. The serum and urine PK data were best fit by a 3-compartment model (lung, serum, and urine) with linear clearance and interoccasional variation on total and renal clearance. Significant univariable relationships between dose or day 1 AUC and the relative change in PFT measures (
P
≤ 0.017) or the absolute change in log
10
CFU from baseline (
P
≤ 0.037) on the study days were identified. Repeated-measures mixed-effects models, which showed dose- and AUC-related improvements for each efficacy endpoint (
P
≤ 0.041), predicted the observed data well. The increases in the relative change in FEV
1
and FEV
1
% predicted of 11% and 9.9%, respectively, and a 1.23-log
10
CFU reduction per 560 mg of LAI estimated on day 7 were comparable to the observed increases of 10.7% and 10.3%, respectively, and a 1.24-log
10
CFU reduction on the same day. The model-estimated PFT effects were predicted to be sustained to day 28. An additional 0.451-log
10
CFU reduction (
P
= 0.022) was estimated on day 14 relative to day 7, with a persistence of effect predicted to day 35.
Host Biomarkers of Invasive Pulmonary Aspergillosis To Monitor Therapeutic Response
Authors: Krel Mila , Petraitis Vidmantas , Petraitiene Ruta , Jain Mohit Raja , Zhao Yanan , Li Hong , Walsh Thomas J. , Perlin David S. 
Published: April 2014

ABSTRACT

Invasive pulmonary aspergillosis (IPA) is a life-threatening disease of immunocompromised patients that requires aggressive therapy. Detection of the disease and monitoring of the therapeutic response during IPA are complex, and current molecular diagnostics are not suitably robust. Here, we explored proteomic profiles of bronchoalveolar lavage fluid (BALF) specimens from a persistently neutropenic rabbit model of IPA. Three experimental arms, uninfected control animals, infected untreated animals, and animals infected and treated with ravuconazole/amphotericin B, were studied. Total proteins were evaluated by two-dimensional (2D) gel electrophoresis, followed by matrix-assisted laser desorption ionization–time of flight/time of flight (MALDI-TOF/TOF) mass spectrometry (MS) and quantified by enzyme-linked immunosorbent assay (ELISA). Host-derived proteins haptoglobin (Hp), C-reactive protein (CRP), and annexin A1 (Anx A1) were prominently found in BALF during the IPA infection and showed significant changes in response to antifungal therapy (
P
< 0.0001). In serum, differences in Hp (
P
= 0.0001) between infected and treated rabbits were observed. Preliminary
in vitro
studies revealed that
Aspergillus fumigatus
-secreted proteases may contribute to the cleavage of Anx A1 during IPA. In summary, host protein biomarkers Hp, CRP, and Anx A1 may have value in monitoring therapeutic response to antifungal agents in IPA patients with confirmed disease.
Deoxysugars as Antituberculars and Alpha-Mannosidase Inhibitors
Authors: Kashyap Vivek , Sharma Smriti , Singh Vinayak , Sharma Sandeep K. , Saquib Mohammad , Srivastava Ranjana , Shaw Arun K. 
Published: April 2014

ABSTRACT

A promising modified sugar molecule was identified which was active against multidrug-resistant (MDR) strains of
Mycobacterium tuberculosis
, suggesting involvement of a new target. The compound was demonstrated to be bactericidal, inhibited the growth of
M. tuberculosis
in mice, and targeted alpha-mannosidase as a competitive inhibitor with a

K
i

value of 353.9 μM.
Biochemical Analysis of Metallo-β-Lactamase NDM-3 from a Multidrug-Resistant Escherichia coli Strain Isolated in Japan
Authors: Tada Tatsuya , Miyoshi-Akiyama Tohru , Shimada Kayo , Kirikae Teruo 
Published: April 2014

ABSTRACT

New Delhi metallo-β-lactamase-3 (NDM-3) was identified in a multidrug-resistant
Escherichia coli
isolate, NCGM77, obtained from the feces of a patient in Japan. The enzymatic activities of NDM-3 against β-lactams were similar to those of NDM-1, although NDM-3 showed slightly lower
k
cat
/

K
m

ratios for all the β-lactams tested except for doripenem. The genetic context for
bla
NDM-3
was
tnpA-bla
NDM-3
-
ble
MBL
-
trpF-dsbC-tnpA-sulI-qacEdeltaI-aadA2-dfrA1
, which was present on an approximately 250-kb plasmid.
Citrullination and Proteolytic Processing of Chemokines by Porphyromonas gingivalis
Authors: Moelants Eva A. V. , Loozen Gitte , Mortier Anneleen , Martens Erik , Opdenakker Ghislain , Mizgalska Danuta , Szmigielski Borys , Potempa Jan , Van Damme Jo , Teughels Wim , Proost Paul 
Published: April 2014

ABSTRACTThe outgrowth ofPorphyromonas gingivaliswithin the inflammatory subgingival plaque is associated with periodontitis characterized by periodontal tissue destruction, loss of alveolar bone, periodontal pocket formation, and eventually, tooth loss. Potential virulence factors ofP. gingivalisare peptidylarginine deiminase (PPAD), an enzyme modifying free or peptide-bound arginine to citrulline, and the bacterial proteases referred to as gingipains (Rgp and Kgp). Chemokines attract leukocytes during inflammation. However, posttranslational modification (PTM) of chemokines by proteases or human peptidylarginine deiminases may alter their biological activities. Since chemokine processing may be important in microbial defense mechanisms, we investigated whether PTM of chemokines byP. gingivalisenzymes occurs. Upon incubation of interleukin-8 (IL-8; CXCL8) with PPAD, only minor enzymatic citrullination was detected. In contrast, Rgp rapidly cleaved CXCL8in vitro. Subsequently, differentP. gingivalisstrains were incubated with the chemokine CXCL8 or CXCL10 and their PTMs were investigated. No significant CXCL8 citrullination was detected for the tested strains. Interestingly, although considerable differences in the efficiency of CXCL8 degradation were observed with full cultures of various strains, similar rates of chemokine proteolysis were exerted by cell-free culture supernatants. Sequencing of CXCL8 incubated with supernatant or bacteria showed that CXCL8 is processed into its more potent forms consisting of amino acids 6 to 77 and amino acids 9 to 77 (the 6-77 and 9-77 forms, respectively). In contrast, CXCL10 was entirely and rapidly degraded byP. gingivalis, with no transient chemokine forms being observed. In conclusion, this study demonstrates PTM of CXCL8 and CXCL10 by gingipains ofP. gingivalisand that strain differences may particularly affect the activity of these bacterial membrane-associated proteases.
High knee abduction moments are common risk factors for patellofemoral pain (PFP) and anterior cruciate ligament (ACL) injury in girls: Is PFP itself a predictor for subsequent ACL injury?
Authors: Myer Gregory D , Ford Kevin R , Di Stasi Stephanie L , Foss Kim D Barber , Micheli Lyle J , Hewett Timothy E 
Published: April 2014

BackgroundIdentifying risk factors for knee pain and anterior cruciate ligament (ACL) injury can be an important step in the injury prevention cycle.ObjectiveWe evaluated two unique prospective cohorts with similar populations and methodologies to compare the incidence rates and risk factors associated with patellofemoral pain (PFP) and ACL injury.MethodsThe ‘PFP cohort’ consisted of 240 middle and high school female athletes. They were evaluated by a physician and underwent anthropometric assessment, strength testing and three-dimensional landing biomechanical analyses prior to their basketball season. 145 of these athletes met inclusion for surveillance of incident (new) PFP by certified athletic trainers during their competitive season. The ‘ACL cohort’ included 205 high school female volleyball, soccer and basketball athletes who underwent the same anthropometric, strength and biomechanical assessment prior to their competitive season and were subsequently followed up for incidence of ACL injury. A one-way analysis of variance was used to evaluate potential group (incident PFP vs ACL injured) differences in anthropometrics, strength and landing biomechanics. Knee abduction moment (KAM) cut-scores that provided the maximal sensitivity and specificity for prediction of PFP or ACL injury risk were also compared between the cohorts.ResultsKAM during landing above 15.4 Nm was associated with a 6.8% risk to develop PFP compared to a 2.9% risk if below the PFP risk threshold in our sample. Likewise, a KAM above 25.3 Nm was associated with a 6.8% risk for subsequent ACL injury compared to a 0.4% risk if below the established ACL risk threshold. The ACL-injured athletes initiated landing with a greater knee abduction angle and a reduced hamstrings-to-quadriceps strength ratio relative to the incident PFP group. Also, when comparing across cohorts, the athletes who suffered ACL injury also had lower hamstring/quadriceps ratio than the players in the PFP sample (p<0.05).ConclusionsIn adolescent girls aged 13.3 years, >15 Nm of knee abduction load during landing is associated with greater likelihood of developing PFP. Also, in girls aged 16.1 years who land with >25 Nm of knee abduction load during landing are at increased risk for both PFP and ACL injury.