bluuebunny/crossref_metadata_2025_split huggingface dataset:
Road vectorisation from high‐resolution imagery based on dynamic clustering using particle swarm optimisation
Authors: Ameri Fateme , Valadan Zoej Mohammad J. 
Published: December 2015

AbstractThis paper introduces an innovative automatic road‐vectorisation algorithm based on dynamic pixel clustering using particle swarm optimisation. A new cost function is designed to optimise the number and position of road keypoints and is capable of deriving road centrelines without considering geometric, spectral or topological characteristics in the road model. The algorithm is applied to different high‐resolution images (IKONOS, QuickBird and aerial photographs) and is evaluated with respect to RMSE, correctness and completeness. Moreover, a new quality parameter is defined to evaluate a “kinking” effect in roads. Extraction of different road shapes with an acceptable precision in both urban and rural environments proves the efficiency of the algorithm in yielding complete road networks.
Mycobacterium bovis hip bursitis in a lung transplant recipient
Authors: Dan J.M. , Crespo M. , Silveira F.P. , Kaplan R. , Aslam S. 
Published: December 2015

AbstractWe present a report of extrapulmonary Mycobacterium bovis infection in a lung transplant recipient. M. bovis is acquired predominantly by zoonotic transmission, particularly from consumption of unpasteurized foods. We discuss epidemiologic exposure, especially as relates to the Mexico–US border, clinical characteristics, resistance profile, and treatment.
Determinants of the Status of an International Financial Centre
Authors: Moosa Imad , Li Larry , Jiang Riley 
Published: December 2015

AbstractIn March 2014, New York overtook London as the number one financial centre in the world as ranked by the global financial centre index (GFCI). This move has raised questions as to what has actually happened to justify such a change in ranking. Some questions are also raised such as why Mauritius is ranked higher than Helsinki. Notwithstanding the problems associated with the GFCI as a measure of the status of an international financial centre, an attempt is made to identify the determinants of the status of 53 financial centres using 24 potential explanatory variables and the technique of extreme bounds analysis (EBA). The results show that the important determinants include, among others, the corporate tax rate, global competitiveness, global credit rating, occupancy cost and property rights. A policy implication of the results is that attention should be paid to these determinants if a financial centre is to consolidate its position.
Gold Nanoparticle Conjugation Enhances the Antiacanthamoebic Effects of Chlorhexidine
Authors: Aqeel Yousuf , Siddiqui Ruqaiyyah , Anwar Ayaz , Shah Muhammad Raza , Khan Naveed Ahmed 
Published: December 2015

ABSTRACT

Acanthamoeba
keratitis is a serious infection with blinding consequences and often associated with contact lens wear. Early diagnosis, followed by aggressive topical application of drugs, is a prerequisite in successful treatment, but even then prognosis remains poor. Several drugs have shown promise, including chlorhexidine gluconate; however, host cell toxicity at physiologically relevant concentrations remains a challenge. Nanoparticles, subcolloidal structures ranging in size from 10 to 100 nm, are effective drug carriers for enhancing drug potency. The overall aim of the present study was to determine whether conjugation with gold nanoparticles enhances the antiacanthamoebic potential of chlorhexidine. Gold-conjugated chlorhexidine nanoparticles were synthesized. Briefly, gold solution was mixed with chlorhexidine and reduced by adding sodium borohydride, resulting in an intense deep red color, indicative of colloidal gold-conjugated chlorhexidine nanoparticles. The synthesis was confirmed using UV-visible spectrophotometry that shows a plasmon resonance peak of 500 to 550 nm, indicative of gold nanoparticles. Further characterization using matrix-assisted laser desorption ionization-mass spectrometry showed a gold-conjugated chlorhexidine complex at
m/z
699 ranging in size from 20 to 100 nm, as determined using atomic force microscopy. To determine the amoebicidal and amoebistatic effects, amoebae were incubated with gold-conjugated chlorhexidine nanoparticles. For controls, amoebae also were incubated with gold and silver nanoparticles alone, chlorhexidine alone, neomycin-conjugated nanoparticles, and neomycin alone. The findings showed that gold-conjugated chlorhexidine nanoparticles exhibited significant amoebicidal and amoebistatic effects at 5 μM. Amoebicidal effects were observed by parasite viability testing using a Trypan blue exclusion assay and flow-cytometric analysis using propidium iodide, while amoebistatic effects were observed using growth assays. In contrast, chlorhexidine alone, at a similar concentration, showed limited effects. Notably, neomycin alone or conjugated with nanoparticles did not show amoebicidal or amoebistatic effects. Pretreatment of
A. castellanii
with gold-conjugated chlorhexidine nanoparticles reduced amoeba-mediated host cell cytotoxicity from 90% to 40% at 5 μM. In contrast, chlorhexidine alone, at similar concentrations, had no protective effects for the host cells. Similarly, amoebae treated with neomycin alone or neomycin-conjugated nanoparticles showed no protective effects. Overall, these findings suggest that gold-conjugated chlorhexidine nanoparticles hold promise in the improved treatment of
A. castellanii
keratitis.
GS-5806 Inhibits a Broad Range of Respiratory Syncytial Virus Clinical Isolates by Blocking the Virus-Cell Fusion Process
Authors: Perron Michel , Stray Kirsten , Kinkade April , Theodore Dorothy , Lee Gary , Eisenberg Eugene , Sangi Michael , Gilbert Brian E. , Jordan Robert , Piedra Pedro A. , Toms Geoffery L. , Mackman Richard , Cihlar Tomas 
Published: December 2015

ABSTRACT

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and young children. In addition, RSV causes significant morbidity and mortality in hospitalized elderly and immunocompromised patients. Currently, only palivizumab, a monoclonal antibody against the RSV fusion (F) protein, and inhaled ribavirin are approved for the prophylactic and therapeutic treatment of RSV, respectively. Therefore, there is a clinical need for safe and effective therapeutic agents for RSV infections. GS-5806, discovered via chemical optimization of a hit from a high-throughput antiviral-screening campaign, selectively inhibits a diverse set of 75 RSV subtype A and B clinical isolates (mean 50% effective concentration [EC
50
] = 0.43 nM). The compound maintained potency in primary human airway epithelial cells and exhibited low cytotoxicity in human cell lines and primary cell cultures (selectivity > 23,000-fold). Time-of-addition and temperature shift studies demonstrated that GS-5806 does not block RSV attachment to cells but interferes with virus entry. Follow-up experiments showed potent inhibition of RSV F-mediated cell-to-cell fusion. RSV A and B variants resistant to GS-5806, due to mutations in F protein (RSV A, L138F or F140L/N517I, and RSV B, F488L or F488S), were isolated and showed cross-resistance to other RSV fusion inhibitors, such as VP-14637, but remained fully sensitive to palivizumab and ribavirin. In summary, GS-5806 is a potent and selective RSV fusion inhibitor with antiviral activity against a diverse set of RSV clinical isolates. The compound is currently under clinical investigation for the treatment of RSV infection in pediatric, immunocompromised, and elderly patients.
Comparison of Verona Integron-Borne Metallo-β-Lactamase (VIM) Variants Reveals Differences in Stability and Inhibition Profiles
Authors: Makena Anne , Düzgün Azer Ö. , Brem Jürgen , McDonough Michael A. , Rydzik Anna M. , Abboud Martine I. , Saral Ayşegül , Çiçek Ayşegül Ç. , Sandalli Cemal , Schofield Christopher J. 
Published: December 2015

ABSTRACT
Metallo-β-lactamases (MBLs) are of increasing clinical significance; the development of clinically useful MBL inhibitors is challenged by the rapid evolution of variant MBLs. The Verona integron-borne metallo-β-lactamase (VIM) enzymes are among the most widely distributed MBLs, with >40 VIM variants having been reported. We report on the crystallographic analysis of VIM-5 and comparison of biochemical and biophysical properties of VIM-1, VIM-2, VIM-4, VIM-5, and VIM-38. Recombinant VIM variants were produced and purified, and their secondary structure and thermal stabilities were investigated by circular dichroism analyses. Steady-state kinetic analyses with a representative panel of β-lactam substrates were carried out to compare the catalytic efficiencies of the VIM variants. Furthermore, a set of metalloenzyme inhibitors were screened to compare their effects on the different VIM variants. The results reveal only small variations in the kinetic parameters of the VIM variants but substantial differences in their thermal stabilities and inhibition profiles. Overall, these results support the proposal that protein stability may be a factor in MBL evolution and highlight the importance of screening MBL variants during inhibitor development programs.
Biochemical Characterization of CPS-1, a Subclass B3 Metallo-β-Lactamase from a Chryseobacterium piscium Soil Isolate
Authors: Gudeta Dereje Dadi , Pollini Simona , Docquier Jean-Denis , Bortolaia Valeria , Rossolini Gian Maria , Guardabassi Luca 
Published: December 2015

ABSTRACT

CPS-1 is a subclass B3 metallo-β-lactamase from a
Chryseobacterium
piscium
isolate collected from soil, showing 68% amino acid identity to the GOB-1 enzyme. CPS-1 was overproduced in
Escherichia coli
Rosetta (DE3), purified by chromatography, and biochemically characterized. This enzyme exhibits a broad-spectrum substrate profile, including penicillins, cephalosporins, and carbapenems, which overall resembles those of L1, GOB-1, and acquired subclass B3 enzymes AIM-1 and SMB-1.
Population Pharmacokinetics of Pyronaridine in Pediatric Malaria Patients
Authors: Ayyoub Amal , Methaneethorn Janthima , Ramharter Michael , Djimde Abdoulaye A. , Tekete Mamadou , Duparc Stephan , Borghini-Fuhrer Isabelle , Shin Jang-Sik , Fleckenstein Lawrence 
Published: December 2015

ABSTRACT

Pyramax is a pyronaridine (PYR)-artesunate (PA) combination for the treatment of uncomplicated malaria in adult and pediatric patients. A granule formulation of this combination is being developed for treatment of uncomplicated
P. falciparum
and
P. vivax
malaria in pediatric patients. The aims of this study were to describe the pharmacokinetics of PYR using a total of 1,085 blood PYR concentrations available from 349 malaria patients younger than 16 years of age with mild to moderate uncomplicated malaria and to confirm the dosing regimen for the pediatric granule formulation. Nonlinear mixed-effects modeling using NONMEM software was used to obtain the pharmacokinetic and inter- and intraindividual variability parameter estimates. The population pharmacokinetics of PYR were described by a two-compartment model with first-order absorption and elimination. Allometric scaling was implemented to address the effect of body weight on clearance and volume parameters. The final parameter estimates of PYR apparent clearance (CL/
F
), central volume of distribution (
V
2
/
F
), peripheral volume of distribution (
V
3
/
F
), intercompartmental clearance (
Q
/
F
), and absorption rate constant (

K
a

) were 377 liters/day, 2,230 liters, 3,230 liters, 804 liters/day and 17.9 day
−1
, respectively. Covariate model building conducted using forward addition (
P
< 0.05) followed by backward elimination (
P
< 0.001) yielded two significant covariate-parameter relationships, i.e., age on
V
2
/
F
and formulation on

K
a

. Evaluation of bootstrapping, visual predictive check, and condition number indicated that the final model displayed satisfactory robustness, predictive power, and stability. Simulations of PYR concentration-time profiles generated from the final model show similar exposures across pediatric weight ranges, supporting the proposed labeling for weight-based dosing of Pyramax granules. (These studies have been registered at ClinicalTrials.gov under registration no. NCT00331136 [phase II study] and NCT00541385, NCT00403260, NCT00422084, and NCT00440999 [phase III studies]. The most recent phase III study was registered at pactr.org under registration no. PACTR201105000286876.)
Discovery of Dual-Stage Malaria Inhibitors with New Targets
Authors: Raphemot Rene , Lafuente-Monasterio Maria J. , Gamo-Benito Francisco Javier , Clardy Jon , Derbyshire Emily R. 
Published: December 2015

ABSTRACT

Malaria remains a major global health problem, with more than half of the world population at risk of contracting the disease and nearly a million deaths each year. Here, we report the discovery of inhibitors that target multiple stages of malaria parasite growth. To identify these inhibitors, we took advantage of the Tres Cantos Antimalarial Compound Set (TCAMS) small-molecule library, which is comprised of diverse and potent chemical scaffolds with activities against the blood stage of the malaria parasite, and investigated their effects against the elusive liver stage of the malaria parasite using a forward chemical screen. From a screen of nearly 14,000 compounds, we identified and confirmed 103 compounds as dual-stage malaria inhibitors. Interestingly, these compounds show preferential inhibition of parasite growth in liver- versus blood-stage malaria parasite assays, highlighting the drug susceptibility of this parasite form. Mode-of-action studies were completed using genetically modified and drug-resistant
Plasmodium
parasite strains. While we identified some compound targets as classical antimalarial pathways, such as the mitochondrial electron transport chain through cytochrome

bc
1

complex inhibition or the folate biosynthesis pathway, most compounds induced parasite death through as yet unknown mechanisms of action. Importantly, the identification of new chemotypes with different modes of action in killing
Plasmodium
parasites represents a promising opportunity for probing essential and novel molecular processes that remain to be discovered. The chemical scaffolds identified with activity against drug-resistant
Plasmodium
parasites represent starting points for dual-stage antimalarial development to surmount the threat of malaria parasite drug resistance.
Identification and Characterization of FTY720 for the Treatment of Human African Trypanosomiasis
Authors: Jones Amy J. , Kaiser Marcel , Avery Vicky M. 
Published: December 2015

ABSTRACT

The screening of a focused library identified FTY720 (Fingolimod; Gilenya) as a potent selective antitrypanosomal compound active against
Trypanosoma brucei gambiense
and
T. brucei rhodesiense
, the causative agents of human African trypanosomiasis (HAT). This is the first report of trypanocidal activity for FTY720, an oral drug registered for the treatment of relapsing multiple sclerosis, and the characterization of sphingolipids as a potential new class of compounds for HAT.
Pharmacokinetic and Pharmacodynamic Evaluation following Vaginal Application of IQB3002, a Dual-Chamber Microbicide Gel Containing the Nonnucleoside Reverse Transcriptase Inhibitor IQP-0528 in Rhesus Macaques
Authors: Pereira Lara E. , Mesquita Pedro M. M. , Ham Anthony , Singletary Tyana , Deyounks Frank , Martin Amy , McNicholl Janet , Buckheit Karen W. , Buckheit Robert W. , Smith James M. 
Published: December 2015

ABSTRACT

We evaluated the
in vivo
pharmacokinetics and used a complementary
ex vivo
coculture assay to determine the pharmacodynamics of IQB3002 gel containing 1% IQP-0528, a nonnucleoside reverse transcriptase inhibitor (NNRTI), in rhesus macaques (RM). The gel (1.5 ml) was applied vaginally to 6 simian-human immunodeficiency (SHIV)-positive female RM. Blood, vaginal fluids, and rectal fluids were collected at 0, 1, 2, and 4 h. RM were euthanized at 4 h, and vaginal, cervical, rectal, and regional lymph node tissues were harvested. Anti-human immunodeficiency virus (HIV) activity was evaluated
ex vivo
by coculturing fresh or frozen vaginal tissues with activated human peripheral blood mononuclear cells (PBMCs) and measuring the p24 levels for 10 days after an HIV-1
Ba-L
challenge. The median levels of IQP-0528, determined using liquid chromatography-tandem mass spectroscopy (LC-MS/MS) methods, were between 10
4
and 10
5
ng/g in vaginal and cervical tissue, between 10
3
and 10
4
ng/g in rectal tissues, and between 10
5
and 10
7
ng/ml in vaginal fluids over the 4-h period. The vaginal tissues protected the cocultured PBMCs from HIV-1 infection
ex vivo
, with a viral inhibition range of 81 to 100% in fresh and frozen tissues that were proximal, medial, and distal relative to the cervix. No viral inhibition was detected in untreated baseline tissues. Collectively, the median drug levels observed were 5 to 7 logs higher than the
in vitro
50% effective concentration (EC
50
) range (0.21 ng/ml to 1.29 ng/ml), suggesting that 1.5 ml of the gel delivers IQP-0528 throughout the RM vaginal compartment at levels that are highly inhibitory to HIV-1. Importantly, antiviral activity was observed in both fresh and frozen vaginal tissues, broadening the scope of the
ex vivo
coculture model for future NNRTI efficacy studies.
Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia
Authors: Lei Guang-Sheng , Zhang Chen , Zimmerman Michelle K. , Lee Chao-Hung 
Published: December 2015

ABSTRACT

The combination of all-
trans
retinoic acid (ATRA) and primaquine (PMQ) has been shown to be effective for therapy of
Pneumocystis
pneumonia (PCP). Since a high concentration of ATRA has significant adverse effects, the possibility that vitamin D can be used to replace ATRA for PCP therapy was investigated. C57BL/6 mice were immunosuppressed by depleting CD4
+
cells and infected with
Pneumocystis
murina
1 week after initiation of immunosuppression. Three weeks after infection, the mice were treated orally for 3 weeks with vitamin D
3
(VitD3) alone, PMQ alone, a combination of VitD3 and PMQ (VitD3-PMQ), or a combination of trimethoprim and sulfamethoxazole (TMP-SMX). Results showed that VitD3 (300 IU/kg/day) had a synergistic effect with PMQ (5 mg/kg/day) for therapy of PCP. Flow cytometric studies showed that this VitD3-PMQ combination recovered the CD11b
low
CD11c
high
alveolar macrophage population in mice with PCP as effectively as TMP-SMX. The VitD3-PMQ combination also reduced the massive infiltration of inflammatory cells into the lungs and the severity of lung damage. VitD3 was also shown to reduce the dose of TMP-SMX required for effective treatment of PCP. Taken together, results of this study suggest that a VitD3-PMQ combination can be used as an alternative therapy for PCP.
Long-Term Fosfomycin-Tromethamine Oral Therapy for Difficult-To-Treat Chronic Bacterial Prostatitis
Authors: Los-Arcos Ibai , Pigrau Carles , Rodríguez-Pardo Dolors , Fernández-Hidalgo Nuria , Andreu Antonia , Larrosa Nieves , Almirante Benito 
Published: December 2015

ABSTRACT

This is a retrospective study of 15 difficult-to-treat (i.e., exhibiting previous failure, patient side effects, or resistance to ciprofloxacin and co-trimoxazole) chronic bacterial prostatitis infections (5 patients with multidrug-resistant
Enterobacteriaceae
[MDRE]) receiving fosfomycin-tromethamine at a dose of 3 g per 48 to 72 h for 6 weeks. After a median follow-up of 20 months, 7 patients (47%) had a clinical response, and 8 patients (53%) had persistent microbiological eradication; 4/5 patients with MDRE isolates achieved eradication. There were no side effects. Fosfomycin-tromethamine is a possible alternative therapy for chronic bacterial prostatitis.
Maresin 1 Biosynthesis and Proresolving Anti-infective Functions with Human-Localized Aggressive Periodontitis Leukocytes
Authors: Wang Chin-Wei , Colas Romain A. , Dalli Jesmond , Arnardottir Hildur H. , Nguyen Daniel , Hasturk Hatice , Chiang Nan , Van Dyke Thomas E. , Serhan Charles N. 
Published: December 2015

ABSTRACT

Localized aggressive periodontitis (LAP) is a distinct form of early-onset periodontitis linked to periodontal infection with uncontrolled inflammation and leukocyte-mediated tissue destruction. The resolution of inflammation is an active process orchestrated by specialized proresolving lipid mediators (SPMs). Since the level of the Maresin pathway marker 14-hydroxy-docosahexaenoic acid (14-HDHA) was lower in activated peripheral blood from LAP patients, we investigated the Maresin 1 (MaR1) biosynthetic pathway in these subjects and its role in regulating phagocyte functions. Macrophages from LAP patients had a lower level of expression of 12-lipoxygenase (∼30%) and reduced MaR1 (LAP versus healthy controls [HC], 87.8 ± 50 pg/10
6
cells versus 239.1 ± 32 pg/10
6
cells). Phagocytosis by LAP macrophages was reduced ∼40% compared to that of HC, and killing of periodontal pathogens, including
Porphyromonas gingivalis
and
Aggregatibacter actinomycetemcomitans
, were similarly reduced. LAP neutrophils also displayed slower kinetics (∼30%) and decreased maximal phagocytosis (∼20% lower) with these pathogens than those of HC. The administration of MaR1 at 1 nM enhanced phagocytosis (31 to 65% increase), intracellular antimicrobial reactive oxygen species production (26 to 71% increase), bacterial killing of these periodontal pathogens (22 to 38% reduction of bacterial titers), and restored impairment of LAP phagocytes. Together, these results suggest that therapeutics targeting the Maresin pathway have clinical utility in treating LAP and other oral diseases associated with infection, inflammation, and altered phagocyte functions.