bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in the hydrological functioning of a playa‐lake complex under increasing agricultural pressures (Andalusia, Southern Spain)
Authors: Beltran M. , Moral F. , Rodríguez‐Rodríguez M. 
Published: August 2011

AbstractThe La‐Lantejuela playa‐lakes endorheic complex is a groundwater‐dependent ecosystem located within the Guadalquivir River Basin (Southern Spain) in an area mainly devoted to agriculture production with increasing groundwater extractions for irrigation from the Osuna‐La Lantejuela (O‐LL) aquifer. The O‐LL aquifer was hydrogeologically characterised in previous works made by the authors. New data and the combination of more field observations, together with the use of morphologic indexes of the playa lakes, has permitted to analyse the relationships between the aquifer and each one of the playa lakes in the complex, assessing whether their hydrological functioning would have been affected by the expansion of irrigated agriculture. Furthermore, the analysis of the results obtained has allowed establishing a hypothesis of the hydrological functioning of the whole system under natural conditions. This case study represents a useful example to understand how agriculture in semi‐arid environments can induce alterations on the wetlands hydrological functioning.
Efficacy of Human-Simulated Exposures of Tomopenem (Formerly CS-023) in a Murine Model of Pseudomonas aeruginosa and Methicillin-Resistant Staphylococcus aureus Infection
Authors: Sugihara Kiyoshi , Tateda Kazuhiro , Yamamura Naotoshi , Koga Tetsufumi , Sugihara Chika , Yamaguchi Keizo 
Published: August 2011

ABSTRACT

Tomopenem (formerly CS-023) is a novel carbapenem with improved activity against diverse hospital pathogens, including
Pseudomonas aeruginosa
and methicillin-resistant
Staphylococcus aureus
(MRSA), and has a half-life about twice longer than the half-lives of other carbapenems such as imipenem and meropenem. Our objective in this study was to estimate the efficacy of tomopenem in humans by human-simulated exposures in a neutropenic murine thigh infection model against 9 clinical isolates of
P. aeruginosa
with MICs of 4 to 32 μg/ml and 9 clinical isolates of MRSA with MICs of 4 to 16 μg/ml. Human-simulated dosing regimens in neutropenic mice were designed to approximate the cumulative percentage of a 24-h period that the free drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (
f
%
T
MIC
) observed with tomopenem at 750 and 1,500 mg given as a 0.5-h infusion three times a day (TID) in humans. As reported previously, there was no difference between the target values of
P. aeruginosa
and MRSA required for efficacy (K. Sugihara et al., Antimicrob. Agents Chemother.
54:
5298-5302, 2010). Tomopenem at 750 mg showed bactericidal or bacteriostatic effects against 10 of 11 strains of
P. aeruginosa
and MRSA with MICs of ≤8 μg/ml (
f
%
T
MIC
≥ 41), and tomopenem at 1,500 mg showed bactericidal effects against 16 of 17 strains of
P. aeruginosa
and MRSA with MICs of ≤16 μg/ml (
f
%
T
MIC
≥ 43). Meropenem at 1,000 mg TID was tested for comparison purposes and showed bactericidal or bacteriostatic effects against 3 of 4 strains of
P. aeruginosa
with MICs of ≤4 μg/ml (
f
%
T
MIC
≥ 33). From these results, tomopenem is expected to be effective with an
f
%
T
MIC
of over 40 against
P. aeruginosa
and MRSA strains with MICs of ≤8 μg/ml at doses of 750 mg TID and strains with MICs of ≤16 μg/ml at doses of 1,500 mg TID.
Antibacterial Mechanism of Action of Arylamide Foldamers
Authors: Mensa Bruk , Kim Yong Ho , Choi Sungwook , Scott Richard , Caputo Gregory A. , DeGrado William F. 
Published: August 2011

ABSTRACT

Small arylamide foldamers designed to mimic the amphiphilic nature of antimicrobial peptides (AMPs) have shown potent bactericidal activity against both Gram-negative and Gram-positive strains without many of the drawbacks of natural AMPs. These foldamers were shown to cause large changes in the permeability of the outer membrane of
Escherichia coli
. They cause more limited permeabilization of the inner membrane which reaches critical levels corresponding with the time required to bring about bacterial cell death. Transcriptional profiling of
E. coli
treated with sublethal concentrations of the arylamides showed induction of genes related to membrane and oxidative stresses, with some overlap with the effects observed for polymyxin B. Protein secretion into the periplasm and the outer membrane is also compromised, possibly contributing to the lethality of the arylamide compounds. The induction of membrane stress response regulons such as
rcs
coupled with morphological changes at the membrane observed by electron microscopy suggests that the activity of the arylamides at the membrane represents a significant contribution to their mechanism of action.
Interleukin-1 Receptor-Associated Kinase 4 Is Essential for Initial Host Control of Brucella abortus Infection
Authors: Oliveira Fernanda S. , Carvalho Natália B. , Brandão Ana Paula M. S. , Gomes Marco Túlio R. , de Almeida Leonardo A. , Oliveira Sérgio C. 
Published: August 2011

ABSTRACT

Brucella abortus
is a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans. Recent studies have revealed that Toll-like receptor (TLR)-initiated immune response to
Brucella
spp. depends on myeloid differentiation factor 88 (MyD88) signaling. Therefore, we decided to study the role of the interleukin-1 receptor-associated kinase 4 (IRAK-4) in host innate immune response against
B. abortus
. After
Brucella
infection, it was shown that the number of CFU in IRAK-4
−/−
mice was high compared to that in IRAK-4
+/−
animals only at 1 week postinfection. At 3 and 6 weeks postinfection, IRAK-4
−/−
mice were able to control the infection similarly to heterozygous animals. Furthermore, the type 1 cytokine profile was evaluated. IRAK-4
−/−
mice showed lower production of systemic interleukin-12 (IL-12) and gamma interferon (IFN-γ). Additionally, a reduced percentage of CD4
+
and CD8
+
T cells expressing IFN-γ was observed compared to IRAK-4
+/−
. Further, the production of IL-12 and tumor necrosis factor alpha (TNF-α) by macrophages and dendritic cells from IRAK-4
−/−
mice was abolished at 24 h after stimulation with
B. abortus
. To investigate the role of IRAK-4 in mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways, macrophages were stimulated with
B. abortus
, and the signaling components were analyzed by protein phosphorylation. Extracellular signal-regulated kinase 1 (ERK1) and ERK2 and p38 as well as p65 NF-κB phosphorylation was profoundly impaired in IRAK-4
−/−
and MyD88
−/−
macrophages activated by
Brucella
. In summary, the results shown in this study demonstrated that IRAK-4 is critical to trigger the initial immune response against
B. abortus
but not at later phases of infection.
The Phosphoinositide-3-Kinase–Akt Signaling Pathway Is Important for Staphylococcus aureus Internalization by Endothelial Cells
Authors: Oviedo-Boyso Javier , Cortés-Vieyra Ricarda , Huante-Mendoza Alejandro , Yu Hong B. , Valdez-Alarcón Juan J. , Bravo-Patiño Alejandro , Cajero-Juárez Marcos , Finlay B. Brett , Baizabal-Aguirre Víctor M. 
Published: August 2011

ABSTRACT

Internalization of
Staphylococcus aureus
in bovine endothelial cells (BEC) is increased by tumor necrosis factor alpha stimulation and NF-κB activation. Because the phosphoinositide-3-kinase (PI3K)–Akt signaling pathway also modulates NF-κB activity, we considered whether the internalization of
S. aureus
by BEC is associated with the activity of PI3K and Akt. We found a time- and multiplicity of infection-dependent phosphorylation of Akt on Ser473 in BEC infected with
S. aureus
. This phosphorylation was inhibited by LY294002 (LY), indicating the participation of PI3K. Inhibition of either PI3K with LY or wortmannin, or Akt with SH-5, strongly reduced the internalization of
S. aureus
. Transfection of BEC with a dominant-negative form of the Akt gene significantly decreased
S. aureus
internalization, whereas transfection with the constitutively active mutant increased the number of internalized bacterium. Inhibition of PDK1 activity with OSU-03012 did not affect the level of
S. aureus
internalization, demonstrating that phosphorylation of Akt on Thr308 is not important for this process. Compared to the untreated control, the adherence of
S. aureus
to the surface of BEC was unaltered when cells were transfected or incubated with the pharmacological inhibitors. Furthermore, Akt activation by internalized
S. aureus
triggered a time-dependent phosphorylation of glycogen synthase kinase-3α (GSK-3α) on Ser21 and GSK-3β on Ser9 that was partially inhibited with SH-5. Finally, treatment of BEC with LY prior to
S. aureus
infection inhibited the NF-κB p65 subunit phosphorylation on Ser536, indicating the involvement of PI3K. These results suggest that PI3K-Akt activity is important for the internalization of
S. aureus
and phosphorylation of GSK-3α, GSK-3β, and NF-κB.
Proteomic Analysis of Anaplasma phagocytophilum during Infection of Human Myeloid Cells Identifies a Protein That Is Pronouncedly Upregulated on the Infectious Dense-Cored Cell
Authors: Troese Matthew J. , Kahlon Amandeep , Ragland Stephanie A. , Ottens Andrew K. , Ojogun Nore , Nelson Kristina T. , Walker Naomi J. , Borjesson Dori L. , Carlyon Jason A. 
Published: August 2011

ABSTRACT

Anaplasma phagocytophilum
is an obligate intracellular bacterium that invades neutrophils to cause the emerging infectious disease human granulocytic anaplasmosis.
A. phagocytophilum
undergoes a biphasic developmental cycle, transitioning between an infectious dense-cored cell (DC) and a noninfectious reticulate cell (RC). To gain insights into the organism's biology and pathogenesis during human myeloid cell infection, we conducted proteomic analyses on
A. phagocytophilum
organisms purified from HL-60 cells. A total of 324 proteins were unambiguously identified, thereby verifying 23.7% of the predicted
A. phagocytophilum
proteome. Fifty-three identified proteins had been previously annotated as hypothetical or conserved hypothetical. The second most abundant gene product, after the well-studied major surface protein 2 (P44), was the hitherto hypothetical protein APH_1235. APH_1235 homologs are found in other
Anaplasma
and
Ehrlichia
species but not in other bacteria. The
aph
_
1235
RNA level is increased 70-fold in the DC form relative to that in the RC form. Transcriptional upregulation of and our ability to detect APH_1235 correlate with RC to DC transition, DC exit from host cells, and subsequent DC binding and entry during the next round of infection. Immunoelectron microscopy pronouncedly detects APH_1235 on DC organisms, while detection on RC bacteria minimally, at best, exceeds background. This work represents an extensive study of the
A. phagocytophilum
proteome, discerns the complement of proteins that is generated during survival within human myeloid cells, and identifies APH_1235 as the first known protein that is pronouncedly upregulated on the infectious DC form.
Metabolic Imaging: A Link between Lactate Dehydrogenase A, Lactate, and Tumor Phenotype
Authors: Serganova Inna , Rizwan Asif , Ni Xiaohui , Thakur Sunitha B. , Vider Jelena , Russell James , Blasberg Ronald , Koutcher Jason A. 
Published: August 2011

AbstractPurpose: We compared the metabolic profiles and the association between LDH-A expression and lactate production in two isogenic murine breast cancer cell lines and tumors (67NR and 4T1). These cell lines were derived from a single mammary tumor and have different growth and metabolic phenotypes.Experimental Design: LDH-A expression, lactate concentration, glucose utilization, and oxygen consumption were measured in cells, and the potential relationship between tumor lactate levels [measured by magnetic resonance spectroscopic imaging (MRSI)] and tumor glucose utilization [measured by [18F]2-deoxy-2-fluoro-d-glucose positron emission tomography ([18F]FDG-PET)] was assessed in orthotopic breast tumors derived from these cell lines.Results: We show a substantial difference in LDH-A expression between 67NR and 4T1 cells under normoxia and hypoxia. We also show that small orthotopic 4T1 tumors generate 10-fold more lactate than corresponding 67NR tumors. The high lactate levels in small primary 4T1 tumors are associated with intense pimonidazole staining (a hypoxia indicator). Less-intense hypoxia staining was observed in the larger 67NR tumors and is consistent with the gradual increase and plateau of lactate concentration in enlarging 67NR tumors.Conclusions: Lactate-MRSI has a greater dynamic range than [18F]FDG-PET and may be a more sensitive measure with which to evaluate the aggressive and metastatic potential of primary breast tumors. Clin Cancer Res; 17(19); 6250–61. ©2011 AACR.
Adoptive Transfer of Autologous Natural Killer Cells Leads to High Levels of Circulating Natural Killer Cells but Does Not Mediate Tumor Regression
Authors: Parkhurst Maria R. , Riley John P. , Dudley Mark E. , Rosenberg Steven A. 
Published: August 2011

Abstract
Purpose: Adoptive transfer of tumor-infiltrating lymphocytes (TIL) can mediate regression of metastatic melanoma. However, many patients with cancer are ineligible for such treatment because their TIL do not expand sufficiently or because their tumors have lost expression of antigens and/or MHC molecules. Natural killer (NK) cells are large granular lymphocytes that lyse tumor cells in a non–MHC-restricted manner. Therefore, we initiated in a clinical trial to evaluate the efficacy of adoptively transferred autologous NK cells to treat patients with cancers who were ineligible for treatment with TIL.
Experimental Design: Patients with metastatic melanoma or renal cell carcinoma were treated with adoptively transferred in vitro activated autologous NK cells after the patients received a lymphodepleting but nonmyeloablative chemotherapy regimen. Clinical responses and persistence of the adoptively transferred cells were evaluated.
Results: Eight patients were treated with an average of 4.7 × 1010 (± 2.1 × 1010) NK cells. The infused cells exhibited high levels of lytic activity in vitro. Although no clinical responses were observed, the adoptively transferred NK cells seemed to persist in the peripheral circulation of patients for at least one week posttransfer and, in some patients, for several months. However, the persistent NK cells in the circulation expressed significantly lower levels of the key activating receptor NKG2D and could not lyse tumor cell targets in vitro unless reactivated with IL-2.
Conclusions: The persistent NK cells could mediate antibody-dependent cell-mediated cytotoxicity without cytokine reactivation in vitro, which suggests that coupling adoptive NK cell transfer with monoclonal antibody administration deserves evaluation. Clin Cancer Res; 17(19); 6287–97. ©2011 AACR.
Clinical and Economic Outcomes of Liberal Versus Selective Drug-Eluting Stent Use
Authors: Venkitachalam Lakshmi , Lei Yang , Stolker Joshua M. , Mahoney Elizabeth M. , Amin Amit P. , Lindsey Jason B. , Kennedy Kevin F. , Pencina Michael J. , Lopez John J. , Kleiman Neal S. , Cohen David J. ,   for the EVENT Registry Investigators
Published: August 2011

Background—
Although the benefits of drug-eluting stents (DES) for reducing restenosis after percutaneous coronary intervention are well established, the impact of alternative rates of DES use on population-level outcomes is unknown.

Methods and Results—

We used data from the Evaluation of Drug Eluting Stents and Ischemic Events (EVENT) registry to examine the clinical impact and cost-effectiveness of varying DES use rates in routine care. Between 2004 and 2007, 10 144 patients undergoing percutaneous coronary intervention were enrolled in the EVENT registry at 55 US centers. Clinical outcomes and cardiovascular-specific costs were assessed prospectively over 1 year of follow-up. Use of DES decreased from 92 in 2004 to 2006 (liberal use era; n=7587) to 68 in 2007 (selective use era; n=2557;
P
<0.001). One-year rates of death or myocardial infarction were similar in both eras. Over this time period, the incidence of target lesion revascularization increased from 4.1 to 5.1, an absolute increase of 1.0 (95 confidence interval, 0.1 to 1.9;
P
=0.03), whereas total cardiovascular costs per patient decreased by $401 (95 confidence interval, 131 to 671;
P
=0.004). The risk-adjusted incremental cost-effectiveness ratio for the liberal versus selective DES era was $16 000 per target lesion revascularization event avoided, $27 000 per repeat revascularization avoided, and $433 000 per quality-adjusted life-year gained.

Conclusions—
In this prospective registry, a temporal reduction in DES use was associated with a small increase in target lesion revascularization and a modest reduction in total cardiovascular costs. These findings suggest that although clinical outcomes are marginally better with unrestricted DES use, this approach represents a relatively inefficient use of healthcare resources relative to several common benchmarks for cost-effective care.
Risk of Constrictive Pericarditis After Acute Pericarditis
Authors: Imazio Massimo , Brucato Antonio , Maestroni Silvia , Cumetti Davide , Belli Riccardo , Trinchero Rita , Adler Yehuda 
Published: August 2011

Background—
Constrictive pericarditis (CP) is considered a rare, dreaded possible complication of acute pericarditis. Nevertheless, there is a lack of prospective studies that have evaluated the specific risk according to different etiologies. The aim of this study is to evaluate the risk of CP after acute pericarditis in a prospective cohort study with long-term follow-up.

Methods and Results—
From January 2000 to December 2008, 500 consecutive cases with a first episode of acute pericarditis (age, 51±16 years; 270 men) were prospectively studied to evaluate the evolution toward CP. Etiologies were viral/idiopathic in 416 cases (83.2%), connective tissue disease/pericardial injury syndromes in 36 cases (7.2%), neoplastic pericarditis in 25 cases (5.0%), tuberculosis in 20 cases (4.0%), and purulent in 3 cases (0.6%). During a median follow-up of 72 months (range, 24 to 120 months), CP developed in 9 of 500 patients (1.8%): 2 of 416 patients with idiopathic/viral pericarditis (0.48%) versus 7 of 84 patients with a nonviral/nonidiopathic etiology (8.3%). The incidence rate of CP was 0.76 cases per 1000 person-years for idiopathic/viral pericarditis, 4.40 cases per 1000 person-years for connective tissue disease/pericardial injury syndrome, 6.33 cases per 1000 person-years for neoplastic pericarditis, 31.65 cases for 1000 person-years for tuberculous pericarditis, and 52.74 cases per 1000 person-years for purulent pericarditis.

Conclusions—
CP is a relatively rare complication of viral or idiopathic acute pericarditis (<0.5%) but, in contrast, is relatively frequent for specific etiologies, especially bacterial.
A High-Resolution Topographic Correction Method for Clear-Sky Solar Irradiance Derived with a Numerical Weather Prediction Model
Authors: Ruiz-Arias José A. , Pozo-Vázquez David , Lara-Fanego Vicente , Santos-Alamillos Francisco J. , Tovar-Pescador J. 
Published: August 2011

AbstractRugged terrain is a source of variability in the incoming solar radiation field, but the influence of terrain is still not properly included by most current numerical weather prediction (NWP) models. In this work, a downscaling postprocessing method for NWP-model solar irradiance through terrain effects is presented. It allows one to decrease the estimation bias caused by terrain shading and sky-view reduction, and to account for elevation variability, surface orientation, and surface albedo. The method has been applied to a case study in southern Spain using the Weather Research and Forecasting (WRF) mesoscale model with a spatial resolution of 30 arc s, resulting in disaggregated maps of 3 arc s. The validation was based on a radiometric network made of eight stations located in the Natural Park of Sierra Mágina over an area of roughly 30 × 35 km2and 12 carefully selected cloudless days during a year. Three of the stations were equipped with tilted pyranometers. Their inclination and aspect were visually adjusted to the inclination and aspect of the local terrain and then carefully measured. For horizontal surface, the downscaled irradiance has proven to reduce the root-mean-square error of the WRF model by 20% to about 25 W m−2in winter and autumn and 60 W m−2in spring and summer. For tilted surface, downscaling to different spatial resolutions resulted in the best performance for 9 arc s, with root-mean-square error of 45% (57 W m−2) and a mean bias error close to zero.
Near-infrared spectroscopy as a possible device for continuous monitoring of arterial carbon dioxide tension during cardiac surgery
Authors: Park CS , Kwak JG , Lee C , Lee C-H , Lee SK , Kim YL 
Published: August 2011

Background: Insufflation of carbon dioxide (CO2) to the operative field has been used to prevent major organ injury attributed to air embolisms in cardiac surgery. However, it may be preferable to avoid hypercapnia induced by CO2 insufflation, owing to its potentially harmful effect. To investigate the effectiveness of near-infrared spectroscopy (NIRS) as a possible method for continuous monitoring of arterial CO2 tension during cardiac surgery, we evaluated the correlation between the change in arterial CO2 tension and the change in regional cerebral oxygen saturation (rScO2) obtained from NIRS in as controlled a condition as possible. Methods: Thirty patients who underwent surgical correction for atrial or ventricular septal defects were enrolled in this study. Patients who had pulmonary hypertension or other intracardiac anomalies were excluded. Anesthetic and cardiopulmonary bypass (CPB) management were conducted according to our standard institutional practice. Data obtained from arterial blood gas analyses and corresponding regional cerebral oxygen saturation (rScO2) recorded from NIRS before and after the insufflations of CO2 during CPB were used for analysis. Results: The change in arterial CO2 tension correlated with the change in rScO2 in the left hemisphere (r = 0.681, p <0.001, y = −1.393 + 0.547x) and right hemisphere (r = 0.690, p <0.001, y = −1.999 + 0.486x). To control the effects of other variables, including hematocrit and temperature, these relationship were not reduced (left hemisphere: r=0.678, p<0.001; right hemisphere: r=0.634, p<0.001). Conclusions: Since the change in regional cerebral oxygen saturation was correlated with the change in arterial CO2 tension during mild hypothermic CPB, NIRS might be a possible non-invasive method for monitoring of arterial CO2 tension without incurring additional cost in this setting.