bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response of Rotary Blood Pumps to Changes in Preload and Afterload at a Fixed Speed Setting Are Unphysiological When Compared With the Natural Heart
Authors: Salamonsen Robert F. , Mason David G. , Ayre Peter J. 
Published: March 2011

AbstractResponses of four rotary blood pumps (Incor, Heartmate II, Heartware, and Duraheart) at a single speed setting to changes in preload and afterload were assessed using the human left ventricle as a benchmark for comparison. Data for the rotary pumps were derived from pressure flow relations reported in the literature while the natural heart was characterized by the Frank–Starling curve adjusted to fit outputs at different afterloads reported in the literature. Preload sensitivity (mean ± SD) for all pumps at all afterloads tested was 0.105 ± 0.092 L/min/mm Hg, while afterload sensitivity was 0.09 ± 0.034 L/min/mm Hg—values that were not significantly different (t‐test, P = 0.56). By contrast, preload sensitivity of the natural heart was over twice as high (0.213 ± 0.03 L/min/mm Hg) and afterload sensitivity about one‐third (0.03 ± 0.01 L/min/mm Hg) the values recorded for rotary pumps (t‐test, P < 0.001). Maximum preload sensitivity and minimum afterload sensitivity allow the right and left ventricles to synchronize outputs without neural or humoral intervention. This theoretical study reinforces the need to provide preload sensitive control mechanisms of sufficient power to enable the pump and left ventricle in combination to adapt to changes in right ventricular output automatically.
The effect of agriculture on repayment efficiency: a look at MFI borrowing groups
Authors: Raghunathan Uthra K. , Escalante Cesar L. , Dorfman Jeffrey H. , Ames Glenn C. W. , Houston Jack E. 
Published: March 2011

AbstractThere is a widely held industry assumption from microfinance institutions that agricultural loans have poorer repayment rates, which has resulted in many loans being provided for small businesses as opposed to agricultural purposes. Using data from a sample of 100 borrowing groups from a south Indian Microfinance Institutions (MFI), this study challenges this belief by analyzing the repayment efficiency of borrowing groups and reflects on the implications for agricultural microfinance loans. The analysis is run using Bayesian stochastic frontier estimation with an exponential hierarchical prior on the efficiency term. Our results indicate that the average efficiency of the borrowing groups analyzed was approximately 75% and that having a higher percentage of agricultural loans increased borrowing group efficiency while gains in efficiency also rose as the size of the borrowing group increases.
Migration of bone marrow‐derived cells and improved perfusion after treatment with erythropoietin in a murine model of myocardial infarction
Authors: Brunner Stefan , Huber Bruno C. , Weinberger Tobias , Vallaster Marcus , Wollenweber Tim , Gerbitz Armin , Hacker Marcus , Franz Wolfgang‐Michael 
Published: March 2011

AbstractErythropoietin (EPO) was shown to have protective effects after myocardial infarction (MI) by neovascularization and antiapoptotic mechanisms. Beside direct receptor‐dependent mechanisms, mobilization and homing of bone marrow‐derived cells (BMCs) may play a pivotal role in this regard. In this study, we intended to track different subpopulations of BMCs and to assess serially myocardial perfusion changes in EPO‐treated mice after MI. To allow tracking of BMCs, we used a chimeric mouse model. Therefore, mice (C57BL/6J) were sublethally irradiated, and bone marrow (BM) from green fluorescent protein transgenic mice was transplanted. Ten weeks later coronary artery ligation was performed to induce MI. EPO was injected for 3 days with a total dose of 5000 IU/kg. Subpopulations (CD31, c‐kit, CXCR‐4 and Sca‐1) of EGFP+ cells were studied in peripheral blood, bone marrow and hearts by flow cytometry. Myocardial perfusion was serially investigated in vivo by pinhole single‐photon emission computed tomography (SPECT) at days 6 and 30 after MI. EPO‐treated animals revealed an enhanced mobilization of BMCs into peripheral blood. The numbers of these cells in BM remained unchanged. Homing of all BMCs subpopulations to the ischaemic myocardium was significantly increased in EPO‐treated mice. Among the investigated subpopulations, EPO predominantly affected migration of CXCR‐4+ (4.3‐fold increase). Repetitively SPECT analyses revealed a reduction of perfusion defects after EPO treatment over time. Our study shows that EPO treatment after MI enhances the migration capacity of BMCs into ischaemic tissue, which may attribute to an improved perfusion and reduced size of infarction, respectively.
α‐Lipoic acid attenuates vascular calcification via reversal of mitochondrial function and restoration of Gas6/Axl/Akt survival pathway
Authors: Kim Hyunsoo , Kim Han‐Jong , Lee Kyunghee , Kim Jin‐Man , Kim Hee Sun , Kim Jae‐Ryong , Ha Chae‐Myeong , Choi Young‐Keun , Lee Sun Joo , Kim Joon‐Young , Harris Robert A. , Jeong Daewon , Lee In‐Kyu 
Published: March 2011

AbstractVascular calcification is prevalent in patients with chronic kidney disease and leads to increased cardiovascular morbidity and mortality. Although several reports have implicated mitochondrial dysfunction in cardiovascular disease and chronic kidney disease, little is known about the potential role of mitochondrial dysfunction in the process of vascular calcification. This study investigated the effect of α‐lipoic acid (ALA), a naturally occurring antioxidant that improves mitochondrial function, on vascular calcification in vitro and in vivo. Calcifying vascular smooth muscle cells (VSMCs) treated with inorganic phosphate (Pi) exhibited mitochondrial dysfunction, as demonstrated by decreased mitochondrial membrane potential and ATP production, the disruption of mitochondrial structural integrity and concurrently increased production of reactive oxygen species. These Pi‐induced functional and structural mitochondrial defects were accompanied by mitochondria‐dependent apoptotic events, including release of cytochrome c from the mitochondria into the cytosol, subsequent activation of caspase‐9 and ‐3, and chromosomal DNA fragmentation. Intriguingly, ALA blocked the Pi‐induced VSMC apoptosis and calcification by recovery of mitochondrial function and intracellular redox status. Moreover, ALA inhibited Pi‐induced down‐regulation of cell survival signals through the binding of growth arrest‐specific gene 6 (Gas6) to its cognate receptor Axl and subsequent Akt activation, resulting in increased survival and decreased apoptosis. Finally, ALA significantly ameliorated vitamin D3‐induced aortic calcification and mitochondrial damage in mice. Collectively, the findings suggest ALA attenuates vascular calcification by inhibiting VSMC apoptosis through two distinct mechanisms; preservation of mitochondrial function via its antioxidant potential and restoration of the Gas6/Axl/Akt survival pathway.
Allometric patterns of fetal head growth in mysticetes and odontocetes: Comparison of Balaena mysticetus and Stenella attenuata
Authors: Armfield Brooke A. , George J. Craig , Vinyard Christopher J. , Thewissen J. G. M. 
Published: March 2011

AbstractUnlike other mammals, odontocetes and mysticetes have highly derived craniofacial bones. A growth process referred to as “telescoping” is partly responsible for this morphology. Here, we explore how changes in facial morphology during fetal growth relate to differences in telescoping between the adult odontocete Stenella attenuata and the mysticete Balaena mysticetus. We conclude that in both Stenella and Balaena head size increases allometrically. Similarly, odontocete nasal length and mysticete mouth size have strong positive allometry compared to total body length. However, the differences between odontocetes and mysticetes in telescoping are not directly associated with their fetal growth patterns. Our results suggest that cranial changes related to echolocation and feeding between odontocetes and mysticetes, respectively, begin during ontogeny before telescoping is initiated.
Reduction in the environmental impact of waste discharged by fish farms through feed and feeding
Authors: Amirkolaie Abdolsamad K. 
Published: March 2011

AbstractThe discharge of waste from aquaculture operations can lead to eutrophication and destruction of natural ecosystem in receiving water body. A controlled waste production strategy is necessary to maintain sustainable aquaculture growth into the future. As feed is the major source of waste in aquaculture, the management of aquaculture waste should be approached through diet formulation or feeding strategies. Highly digestible diets have been introduced as a solution to reduce solid waste excretion. Further reductions in solid waste can be achieved through careful selection of feed ingredients and feed processing to improve nutrient availability. An increase in faeces consistency by diet manipulation can improve solid removal efficiency. This condition can reduce the proportion of solids in discharged water in the effluent and also improve farm water quality. A reduction in dissolved nitrogen waste can be achieved by ensuring a balance between protein and energy causing fish to use non‐protein sources as energy. Phosphorous waste can be decreased through careful ingredient selection and proper processing to improve digestibility. A proper feed ration and feeding method for each species should be adopted because feed waste constitutes a large part of waste production.
Development and characterisation of 20 microsatellite loci isolated from the large bent‐wing bat, Miniopterus schreibersii (Chiroptera: Miniopteridae) and their cross‐taxa utility in the family Miniopteridae
Authors: WOOD REBECCA , WEYENETH NICOLE , APPLETON BELINDA 
Published: March 2011

AbstractThe large bent‐wing bat, Miniopterus schreibersii (Kuhl 1819), has a long history of taxonomic uncertainty and many populations are known to be in a state of decline. Microsatellite loci were developed for the taxonomic and population genetic assessment of the Australian complex of this species. Of the 33 primer sets designed for this research, seven (21%) were deemed suitably polymorphic for population‐level analyses of the Australian taxa, with five (71%) of these loci revealing moderate to high levels of polymorphism (PIC = 0.56 to 0.91). The cross‐taxa utility of the M. schreibersii microsatellite markers was assessed in the microbat (Chiroptera) family Miniopteridae. Sub‐species and species covering the Miniopteridae’s global distribution (with the exception of the Middle East) were selected, numbering 25 taxa in total. Amplification was successful for 26 loci, of which 20 (77%) were polymorphic. High cross‐taxa utility of markers was observed with amplification achieved for all taxa for between four (20%) and 20 (100%) loci, and polymorphism was considered moderate to high (PIC = 0.47–0.91) for 12 (60%) of these loci. The high cross‐taxa utility of the microsatellites reported herein reveal versatile and cost‐effective molecular markers, contributing an important genetic resource for the research and conservation of Miniopteridae species worldwide.
Regulation of NR4A nuclear receptor expression by oncogenic BRAF in melanoma cells
Authors: Smith Aaron G. , Lim Wen , Pearen Michael , Muscat George E. O. , Sturm Richard A. 
Published: March 2011

SummaryActivating mutations in the MAPK pathway effectors, NRAS or BRAF, are detected in over 70% of melanomas. Accordingly, the identification of downstream targets of constitutive MAPK signalling in melanoma represents a major goal in understanding the genesis of this disease. We report here the regulation of members of the NR4A family of nuclear receptors by the BRAF‐MEK‐ERK cascade in melanoma cells. Expression profiling of melanoma cells in which both the NR4A1 and NR4A2 family members have been down‐regulated by siRNA revealed alterations in genes associated with proliferation, survival and invasiveness of tumour cells. Notably, the up‐regulation of Wnt/β‐catenin pathway antagonists, DACT1 and CITED1, following NR4A1/2 ablation suggests a possible link between NR4A and β‐catenin activity in melanoma cells. Taken together, these data suggest that dysregulation of NR4A nuclear receptors expression and function by the MAPK pathway may contribute to melanoma tumourigenicity.
Enhanced dissolution and stability of adefovir dipivoxil by cocrystal formation
Authors: Gao Yuan , Zu Hui , Zhang Jianjun 
Published: March 2011

Abstract

Objectives
The objectives of this study were to prepare and characterize the novel adefovir dipivoxil–saccharin cocrystal and to demonstrate the enhanced dissolution and stability of adefovir dipivoxil by cocrystal formation.

Methods
Adefovir dipivoxil–saccharin cocrystal was prepared using a novel solution crystallization approach and scaled up to 30 g for subsequent studies. DSC, IR and XRPD were used to characterize the novel solid form. The stoichiometry of the cocrystal was analysed by HPLC. Dissolution and chemical stability were assessed and compared with marketed adefovir dipivoxil (form 1) used in marketed Hepsera Tablets.

Key findings
A new solid adefovir dipivoxil–saccharin cocrystal with unique melting point, DSC, FTIR and XRPD data was obtained. The molar ratio of adefovir dipivoxil and saccharin in the cocrystal was determined to be 1 : 1. The cocrystal had a pH-independent dissolution profile and showed a two-fold increase in the dissolution efficiency in water and phosphate buffer (pH 6.8) compared with adefovir dipivoxil. The cocrystal was kinetically much more stable than form 1. Form 1 degraded almost completely at 60°C in 18 days, while adefovir dipivoxil–saccharin cocrystal remained unchanged for 47 days at 60°C.

Conclusions
This study demonstrated that the dissolution and stability of adefovir dipivoxil could be significantly enhanced by its cocrystal formation with saccharin. The use of cocrystals could be a feasible and valuable approach for improving the physicochemical properties of adefovir dipivoxil.
Assessment of biological activity of novel peptide analogues of angiotensin IV
Authors: Gard Paul R , Olivier George , Golding Bruno , Bourner Claire , Dang Tony , Haliru Haliru , Higgins Eleanor , Kimberley Helen , Loginova Olga , Madhavi Shahnaz , Ryan Denis 
Published: March 2011

Abstract

Objectives
Angiotensin IV (Ang IV) is a metabolite of angiotensin II which acts on specific AT4 receptors identified as the enzyme insulin regulated aminopeptidase (IRAP). The transduction process of these receptors is unresolved, but Ang IV inhibits the aminopeptidase activity. Ang IV improves cognition in animal models thus there is a desire to develop metabolically stable analogues for further development.

Methods
Peptide analogues of Ang IV were obtained commercially or synthesised. Each peptide was tested in vitro for its ability to inhibit the aminopeptidase activity (IRAP) of mouse brain homogenates and for its effects on isolated rat uterine smooth muscle.

Key findings
[Des-Val1]-Ang IV, acetylated-Ang IV-amide, Ang IV-amide and [des-His4]-Ang IV all inhibited IRAP. [Sar1, Ile8]-Angiotensin II (10 µm) had an effect greater than that of Ang IV or any of the other analogues studied. In isolated uterine smooth muscle, angiotensins II and IV induced contractions, which could be antagonised by an AT1-receptor antagonist. None of the novel peptides induced uterine smooth muscle contractions, but [Sar1, des Arg2-Gly8]-angiotensin II showed significant antagonism of the contractile effects of angiotensin II and carboxyamide-terminated Ang IV-NH2 showed antagonism of Ang IV-induced contractions.

Conclusions
This study provides five novel inhibitors of IRAP worthy of assessment in behavioural models of learning and memory. The analogues are devoid of AT1 receptor agonist properties, and the carboxyamide analogue presents an opportunity to elucidate the mechanism of action of Ang IV as, like Ang IV, it inhibits IRAP, but antagonises the effects of Ang IV on isolated smooth muscle.
Entrapment of 5-fluorouracil into PLGA matrices using supercritical antisolvent processes
Authors: Kalantarian Pardis , Haririan Ismaeil , Najafabadi Abdolhossein Rouholamini , Shokrgozar Mohammad Ali , Vatanara Alireza 
Published: March 2011

Abstract

Objectives
Two different supercritical antisolvent processes were performed to co-precipitate 5-fluorouracil (5-FU) and poly(lactide-co-glycolide) simultaneously. 5-FU is a hydrophilic antitumor agent, and is more effective when administered at a lower dose for a longer period of time.

Methods
Controlled-release polymeric systems of 5-FU were produced, and morphology, thermal behavior, in-vitro release and cytotoxicity of microparticles were analysed.

Key findings
Dissolution studies showed that 33% of drug was released in 21 days, which represents a long-lasting profile. To evaluate the efficacy of the released drug on cancer cells, the MTT assay cytotoxicity test was performed using human lung carcinoma A549 cell lines. There was no significant difference between the cell inhibition rates of the released drug and unprocessed 5-FU at the same drug concentration level. IC50 values were 69.12 mg/ml for unprocessed 5-FU and 68.71 mg/ml for the released drug.

Conclusions
Application of supercritical processing for co-precipitation of 5-FU and PLGA provided mild and non-aqueous conditions, so the hydrophilic drug incorporated in the polymer had good stability during the process.
Population Pharmacokinetic and Pharmacodynamic Analysis of Linezolid and a Hematologic Side Effect, Thrombocytopenia, in Japanese Patients
Authors: Sasaki Tomohiro , Takane Hiroshi , Ogawa Katsuhiro , Isagawa Sayaka , Hirota Takeshi , Higuchi Shun , Horii Toshinobu , Otsubo Kenji , Ieiri Ichiro 
Published: March 2011

ABSTRACT

Linezolid is an antimicrobial agent to treat infections by Gram-positive pathogens, including methicillin-resistant
Staphylococcus aureus
(MRSA). While effective, linezolid treatment frequently is associated with hematological side effects, especially thrombocytopenia. However, little is known about the mechanism of this side effect and the exposure-response relationship. The present population pharmacokinetic/pharmacodynamic (PPK/PD) study was undertaken to elucidate the factors that determine linezolid levels, the relationship between exposure to linezolid and a decrease in platelet counts, and appropriate dosage adjustments based on exposure levels. In total, 50 patients (135 plasma samples) were used for the PPK analysis. The PPK analysis revealed that renal function and severe liver cirrhosis (Child Pugh grade C) significantly affect the pharmacokinetics of linezolid according to the equation clearance (liter/h) = 2.85 × (creatinine clearance/60.9)
0.618
× 0.472
CIR
(CIR indicates cirrhosis status; 0 for noncirrhosis, 1 for cirrhosis patients). Using 603 platelet counts from 45 patients, a PPK/PD analysis with a semimechanistic pharmacodynamic model described the relationship between linezolid exposure and platelet counts quantitatively, and the newly constructed model was validated using external data (776 platelet counts from 60 patients). Simulation indicated considerable risks in patients with insufficient renal function (creatinine clearance, ≤30 ml/min) or severe liver cirrhosis. For these patients, a reduced dosage (600 mg/day) would be recommended for sufficient efficacy (area under the concentration-time curve over 24 h in the steady state divided by the MIC, >100) and safety.
Identification of Pyruvate Kinase in Methicillin-Resistant Staphylococcus aureus as a Novel Antimicrobial Drug Target
Authors: Zoraghi Roya , See Raymond H. , Axerio-Cilies Peter , Kumar Nag S. , Gong Huansheng , Moreau Anne , Hsing Michael , Kaur Sukhbir , Swayze Richard D. , Worrall Liam , Amandoron Emily , Lian Tian , Jackson Linda , Jiang Jihong , Thorson Lisa , Labriere Christophe , Foster Leonard , Brunham Robert C. , McMaster William R. , Finlay B. Brett , Strynadka Natalie C. , Cherkasov Artem , Young Robert N. , Reiner Neil E. 
Published: March 2011

ABSTRACTNovel classes of antimicrobials are needed to address the challenge of multidrug-resistant bacteria such as methicillin-resistantStaphylococcus aureus(MRSA). Using the architecture of the MRSA interactome, we identified pyruvate kinase (PK) as a potential novel drug target based upon it being a highly connected, essential hub in the MRSA interactome. Structural modeling, including X-ray crystallography, revealed discrete features of PK in MRSA, which appeared suitable for the selective targeting of the bacterial enzyme.In silicolibrary screening combined with functional enzymatic assays identified an acyl hydrazone-based compound (IS-130) as a potent MRSA PK inhibitor (50% inhibitory concentration [IC50] of 0.1 μM) with >1,000-fold selectivity over human PK isoforms. Medicinal chemistry around the IS-130 scaffold identified analogs that more potently and selectively inhibited MRSA PK enzymatic activity andS. aureusgrowthin vitro(MIC of 1 to 5 μg/ml). These novel anti-PK compounds were found to possess antistaphylococcal activity, including both MRSA and multidrug-resistantS. aureus(MDRSA) strains. These compounds also exhibited exceptional antibacterial activities against other Gram-positive genera, including enterococci and streptococci. PK lead compounds were found to be noncompetitive inhibitors and were bactericidal. In addition, mutants with significant increases in MICs were not isolated after 25 bacterial passages in culture, indicating that resistance may be slow to emerge. These findings validate the principles of network science as a powerful approach to identify novel antibacterial drug targets. They also provide a proof of principle, based upon PK in MRSA, for a research platform aimed at discovering and optimizing selective inhibitors of novel bacterial targets where human orthologs exist, as leads for anti-infective drug development.