bluuebunny/crossref_metadata_2025 huggingface dataset:
General Douglas MacArthur: Supreme Public Administrator of Post–World War II Japan
Authors: Leavitt William M.
Published: January 2015

This article examines General Douglas MacArthur’s six years as Supreme Commander for the Allied Powers in post–World War II Japan. MacArthur was appointed by President Harry S. Truman in 1945 to preside over and administer the reconstruction of postwar Japan. No American serving in the role of a public administrator has ever had a more difficult task than the one MacArthur took on in Japan. At the end of World War II, Japan was devastated, and the entire population faced starvation. MacArthur’s administrative style and his successes and failures in Japan are examined in this Administrative Profile. Fifty years after his death, the influence of MacArthur’s policies during his tenure as Supreme Commander are still felt in Japan.
When doctors shape policy: The impact of self‐regulation on governing human biotechnology
Authors: Engeli Isabelle , Rothmayr Allison Christine
Published: January 2015

This paper investigates the development and adoption of governance modes in the field of human biotechnology. As the field of human biotechnology is relatively new, voluntary professional self‐regulation constituted the initial governing mode. In the meantime, with the exception of Ireland, all Western European countries have moved toward greater state intervention. Nevertheless, they have done so in contrasting ways and the resulting governance modes for assisted reproductive technology and embryonic stem‐cell research vary greatly. Instead of imposing their steering capacity in a “top‐down” fashion, governments have taken pre‐existing self‐regulatory arrangements in the field into account and built up governance mechanisms in conjunction with private actors and pre‐existing modes of private governance. Our analysis demonstrates that the form and content of the initial self‐regulation explain why the self‐steering capacity of the medical profession was largely or at least partially preserved through hybrid governance systems in Britain and Germany, while in France the self‐regulation was entirely replaced by governmental intervention.
Influence of step length and landing pattern on patellofemoral joint kinetics during running
Authors: Willson J. D. , Ratcliff O. M. , Meardon S. A. , Willy R. W.
Published: January 2015

Elevated patellofemoral joint kinetics during running may contribute to patellofemoral joint symptoms. The purpose of this study was to test for independent effects of foot strike pattern and step length on patellofemoral joint kinetics while running. Effects were tested relative to individual steps and also taking into account the number of steps required to run a kilometer with each step length. Patellofemoral joint reaction force and stress were estimated in 20 participants running at their preferred speed. Participants ran using a forefoot strike and rearfoot strike pattern during three different step length conditions: preferred step length, long (+10%) step length, and short (−10%) step length. Patellofemoral kinetics was estimated using a biomechanical model of the patellofemoral joint that accounted for cocontraction of the knee flexors and extensors. We observed independent effects of foot strike pattern and step length. Patellofemoral joint kinetics per step was 10–13% less during forefoot strike conditions and 15–20% less with a shortened step length. Patellofemoral joint kinetics per kilometer decreased 12–13% using a forefoot strike pattern and 9–12% with a shortened step length. To the extent that patellofemoral joint kinetics contribute to symptoms among runners, these running modifications may be advisable for runners with patellofemoral pain.
A Novel In Vivo Approach to Assess Radial and Axial Distensibility of Large and Intermediate Pulmonary Artery Branches
Authors: Bellofiore A. , Henningsen J. , Lepak C. G. , Tian L. , Roldan-Alzate A. , Kellihan H. B. , Consigny D. W. , Francois C. J. , Chesler N. C.
Published: January 2015

Pulmonary arteries (PAs) distend to accommodate increases in cardiac output. PA distensibility protects the right ventricle (RV) from excessive increases in pressure. Loss of PA distensibility plays a critical role in the fatal progression of pulmonary arterial hypertension (PAH) toward RV failure. However, it is unclear how PA distensibility is distributed across the generations of PA branches, mainly because of the lack of appropriate in vivo methods to measure distensibility of vessels other than the large, conduit PAs. In this study, we propose a novel approach to assess the distensibility of individual PA branches. The metric of PA distensibility we used is the slope of the stretch ratio–pressure relationship. To measure distensibility, we combined invasive measurements of mean PA pressure with angiographic imaging of the PA network of six healthy female dogs. Stacks of 2D images of the PAs, obtained from either contrast enhanced magnetic resonance angiography (CE-MRA) or computed tomography digital subtraction angiography (CT-DSA), were used to reconstruct 3D surface models of the PA network, from the first bifurcation down to the sixth generation of branches. For each branch of the PA, we calculated radial and longitudinal stretch between baseline and a pressurized state obtained via acute embolization of the pulmonary vasculature. Our results indicated that large and intermediate PA branches have a radial distensibility consistently close to 2%/mmHg. Our axial distensibility data, albeit affected by larger variability, suggested that the PAs distal to the first generation may not significantly elongate in vivo, presumably due to spatial constraints. Results from both angiographic techniques were comparable to data from established phase-contrast (PC) magnetic resonance imaging (MRI) and ex vivo mechanical tests, which can only be used in the first branch generation. Our novel method can be used to characterize PA distensibility in PAH patients undergoing clinical right heart catheterization (RHC) in combination with MRI.
Design of a Pulsatile Flow Facility to Evaluate Thrombogenic Potential of Implantable Cardiac Devices
Authors: Arjunon Sivakkumar , Ardana Pablo Hidalgo , Saikrishnan Neelakantan , Madhani Shalv , Foster Brent , Glezer Ari , Yoganathan Ajit P.
Published: January 2015

Due to expensive nature of clinical trials, implantable cardiac devices should first be extensively characterized in vitro. Prosthetic heart valves (PHVs), an important class of these devices, have been shown to be associated with thromboembolic complications. Although various in vitro systems have been designed to quantify blood-cell damage and platelet activation caused by nonphysiological hemodynamic shear stresses in these PHVs, very few systems attempt to characterize both blood damage and fluid dynamics aspects of PHVs in the same test system. Various numerical modeling methodologies are also evolving to simulate the structural mechanics, fluid mechanics, and blood damage aspects of these devices. This article presents a completely hemocompatible small-volume test-platform that can be used for thrombogenicity studies and experimental fluid mechanics characterization. Using a programmable piston pump to drive freshly drawn human blood inside a cylindrical column, the presented system can simulate various physiological and pathophysiological conditions in testing PHVs. The system includes a modular device-mounting chamber, and in this presented case, a 23 mm St. Jude Medical (SJM) Regents® mechanical heart valve (MHV) in aortic position was used as the test device. The system was validated for its capability to quantify blood damage by measuring blood damage induced by the tester itself (using freshly drawn whole human blood). Blood damage levels were ascertained through clinically relevant assays on human blood while fluid dynamics were characterized using time-resolved particle image velocimetry (PIV) using a blood-mimicking fluid. Blood damage induced by the tester itself, assessed through Thrombin-anti-Thrombin (TAT), Prothrombin factor 1.2 (PF1.2), and hemolysis (Drabkins assay), was within clinically accepted levels. The hydrodynamic performance of the tester showed consistent, repeatable physiological pressure and flow conditions. In addition, the system contains proximity sensors to accurately capture leaflet motion during the entire cardiac cycle. The PIV results showed skewing of the leakage jet, caused by the asymmetric closing of the two leaflets. All these results are critical to characterizing the blood damage and fluid dynamics characteristics of the SJM Regents® MHV, proving the utility of this tester as a precise system for assessing the hemodynamics and thrombogenicity for various PHVs.
On the Effectiveness of Two Isolation Systems for the Seismic Protection of Elevated Tanks
Authors: Paolacci Fabrizio
Published: January 2015

This paper deals with the effectiveness of two isolation systems for the seismic protection of elevated steel storage tanks. In particular, the performance of high damping rubber bearings (HDRB) and friction pendulum isolators (FPS) has been analyzed. As case study, an emblematic example of elevated tanks collapsed during the Koaceli Earthquake in 1999 at Habas pharmaceutics plant in Turkey is considered. A time-history analysis conducted using lumped mass models demonstrates the high demand in terms of base shear required to the support columns and their inevitable collapse due to the insufficient shear strength. A proper design of HDRB and FPS isolator according to the EN1998 and a complete nonlinear analysis of the isolated tanks proved the high effectiveness of both isolation systems in reducing the response of the case tank. Actually, the stability conditions imposed by the code and a reduced level of convective base shear obtained with the second isolation typology suggests the use of FPS isolators rather than HDRB devices.
Improved image quality in pinhole SPECT by accurate modeling of the point spread function in low magnification systems
Authors: Pino Francisco , Roé Nuria , Aguiar Pablo , Falcon Carles , Ros Domènec , Pavía Javier
Published: January 2015

Purpose:

Single photon emission computed tomography (SPECT) has become an important noninvasive imaging technique in small‐animal research. Due to the high resolution required in small‐animal SPECT systems, the spatially variant system response needs to be included in the reconstruction algorithm. Accurate modeling of the system response should result in a major improvement in the quality of reconstructed images. The aim of this study was to quantitatively assess the impact that an accurate modeling of spatially variant collimator/detector response has on image‐quality parameters, using a low magnification SPECT system equipped with a pinhole collimator and a small gamma camera.

Methods:

Three methods were used to model the point spread function (PSF). For the first, only the geometrical pinhole aperture was included in the PSF. For the second, the septal penetration through the pinhole collimator was added. In the third method, the measured intrinsic detector response was incorporated. Tomographic spatial resolution was evaluated and contrast, recovery coefficients, contrast‐to‐noise ratio, and noise were quantified using a custom‐built NEMA NU 4–2008 image‐quality phantom.

Results:

A high correlation was found between the experimental data corresponding to intrinsic detector response and the fitted values obtained by means of an asymmetric Gaussian distribution. For all PSF models, resolution improved as the distance from the point source to the center of the field of view increased and when the acquisition radius diminished. An improvement of resolution was observed after a minimum of five iterations when the PSF modeling included more corrections. Contrast, recovery coefficients, and contrast‐to‐noise ratio were better for the same level of noise in the image when more accurate models were included. Ring‐type artifacts were observed when the number of iterations exceeded 12.

Conclusions:

Accurate modeling of the PSF improves resolution, contrast, and recovery coefficients in the reconstructed images. To avoid the appearance of ring‐type artifacts, the number of iterations should be limited. In low magnification systems, the intrinsic detector PSF plays a major role in improvement of the image‐quality parameters.
RSV Bronchiolitis: Tale of an Overzealous Helper?
Authors: Lemaire Mathieu
Published: January 2015

TLR4 genotypes and nasal bacterial carriage trigger an exaggerated type 2 helper T cell response during severe RSV bronchiolitis.
Lymph Nodes “On Demand”
Authors: Stephan Matthias
Published: January 2015

Injected microparticles spontaneously form three-dimensional structures that can mobilize anticancer immune responses.
Fear as a Cardiovascular Risk Factor
Authors: Tsalik Ephraim L.
Published: January 2015

Fear is one of the factors associated with a paradoxical rise in heart rate during aging.
Genomic Avenue to Avian Colisepticemia
Authors: Huja Sagi , Oren Yaara , Trost Eva , Brzuszkiewicz Elzbieta , Biran Dvora , Blom Jochen , Goesmann Alexander , Gottschalk Gerhard , Hacker Jörg , Ron Eliora Z. , Dobrindt Ulrich
Published: January 2015

Here we present an extensive genomic and genetic analysis of Escherichia coli strains of serotype O78 that represent the major cause of avian colisepticemia, an invasive infection caused by avian pathogenic
Escherichia coli
(APEC) strains. It is associated with high mortality and morbidity, resulting in significant economic consequences for the poultry industry. To understand the genetic basis of the virulence of avian septicemic E. coli, we sequenced the entire genome of a clinical isolate of serotype O78—O78:H19 ST88 isolate 789 (O78-9)—and compared it with three publicly available APEC O78 sequences and one complete genome of APEC serotype O1 strain. Although there was a large variability in genome content between the APEC strains, several genes were conserved, which are potentially critical for colisepticemia. Some of these genes are present in multiple copies per genome or code for gene products with overlapping function, signifying their importance. A systematic deletion of each of these virulence-related genes identified three systems that are conserved in all septicemic strains examined and are critical for serum survival, a prerequisite for septicemia. These are the plasmid-encoded protein, the defective ETT2 (
E. coli
type 3 secretion system 2) type 3 secretion system ETT2
sepsis
, and iron uptake systems. Strain O78-9 is the only APEC O78 strain that also carried the regulon coding for yersiniabactin, the iron binding system of the
Yersinia
high-pathogenicity island. Interestingly, this system is the only one that cannot be complemented by other iron uptake systems under iron limitation and in serum.

IMPORTANCE
Avian colisepticemia is a severe systemic disease of birds causing high morbidity and mortality and resulting in severe economic losses. The bacteria associated with avian colisepticemia are highly antibiotic resistant, making antibiotic treatment ineffective, and there is no effective vaccine due to the multitude of serotypes involved. To understand the disease and work out strategies to combat it, we performed an extensive genomic and genetic analysis of Escherichia coli strains of serotype O78, the major cause of the disease. We identified several potential virulence factors, conserved in all the colisepticemic strains examined, and determined their contribution to growth in serum, an absolute requirement for septicemia. These findings raise the possibility that specific vaccines or drugs can be developed against these critical virulence factors to help combat this economically important disease.
Comparative Genomics Suggests Primary Homothallism of
Pneumocystis
Species
Authors: Almeida João M. G. C. F. , Cissé Ousmane H. , Fonseca Álvaro , Pagni Marco , Hauser Philippe M.
Published: January 2015

Pneumocystis
species are fungal parasites of mammal lungs showing host specificity.
Pneumocystis jirovecii
colonizes humans and causes severe pneumonia in immunosuppressed individuals. In the absence of
in vitro
cultures, the life cycle of these fungi remains poorly known. Sexual reproduction probably occurs, but the system of this process and the mating type (
MAT
) genes involved are not characterized. In the present study, we used comparative genomics to investigate the issue in P. jirovecii and
Pneumocystis carinii
, the species infecting rats, as well as in their relative Taphrina deformans. We searched sex-related genes using 103 sequences from the relative
Schizosaccharomyces pombe
as queries. Genes homologous to several sex-related role categories were identified in all species investigated, further supporting sexuality in these organisms. Extensive
in silico
searches identified only three putative
MAT
genes in each species investigated (
matMc
,
matMi
, and
matPi
). In P. jirovecii, these genes clustered on the same contig, proving their contiguity in the genome. This organization seems compatible neither with heterothallism, because two different
MAT
loci on separate DNA molecules would have been detected, nor with secondary homothallism, because the latter involves generally more
MAT
genes. Consistently, we did not detect
cis
-acting sequences for mating type switching in secondary homothallism, and PCR revealed identical
MAT
genes in P. jirovecii isolates from six patients. A strong synteny of the genomic region surrounding the putative
MAT
genes exists between the two Pneumocystis species. Our results suggest the hypothesis that primary homothallism is the system of reproduction of Pneumocystis species and T. deformans.

IMPORTANCE
   Sexual reproduction among fungi can involve a single partner (homothallism) or two compatible partners (heterothallism). We investigated the issue in three pathogenic fungal relatives:
Pneumocystis jirovecii
, which causes severe pneumonia in immunocompromised humans;
Pneumocystis carinii
, which infects rats; and the plant pathogen Taphrina deformans. The nature, the number, and the organization within the genome of the genes involved in sexual reproduction were determined. The three species appeared to harbor a single genomic region gathering only three genes involved in sexual differentiation, an organization which is compatible with sexual reproduction involving a single partner. These findings illuminate the strategy adopted by fungal pathogens to infect their hosts.
Oral squamous cell carcinoma in a patient treated with long-term pegylated liposomal doxorubicin for recurrent ovarian cancer
Authors: Pezzoli Matteo , Bona Galvagno Maurizio , Bongioannini Guido
Published: January 2015

We present a case of a woman who developed an oral squamous cell carcinoma (SCC) after being treated for a recurrent ovarian carcinoma with subtotal gastric resection and adjuvant pegylated liposomal doxorubicin (PLD). She received six cycles of PLD induction and maintenance therapy, which was continued for 5 years. She was free from disease at the following visits but 3 years later she developed SCC of her left inferior edentulous gums. The patient was negative for human papillomavirus and had never smoked in her life or had a history of alcohol use or any other environmental risk factors. PLD is known to accumulate in eccrine glands of the hands and the feet and in the oral mucosa, therefore causing skin toxicity and mucositis. It is conceivable that this specific biodistribution to the oral mucosa may be responsible for the onset of SCC.
Rabies encephalitis in a child: a failure of rabies post exposure prophylaxis?
Authors: Tinsa Faten , Borgi Aida , Jahouat Imen , Boussetta Khadija
Published: January 2015

Rabies remains a serious public health problem in many developing countries. The diagnosis is easy when a non-immunised patient presents with hydrophobia and hypersalivation after a bite by a known rabid animal but more difficult when a patient presents atypical symptoms after having received rabies postexposure prophylaxis. Rabies postexposure prophylaxis failure is rare. We report a case of a 6-year-old boy who presented febrile seizure with agitation and cerebellar signs, without hydrophobia or hypersalivation, 17 days after a dog bite. Despite four doses of rabies vaccine and immunoglobulin, he died. Diagnostic confirmation of rabies encephalitis was made in post mortem on brain biopsies by fluorescent antibody technique.
Concussion in youth rugby union and rugby league: a systematic review
Authors: Kirkwood Graham , Parekh Nikesh , Ofori-Asenso Richard , Pollock Allyson M
Published: January 2015

Background

Children and adolescents who play rugby are at increased risk of concussion and its effects. Competitive rugby union and rugby league feature as major sports in the school sport curriculum in the UK. There is a need for a thorough understanding of the epidemiology of concussion in youth rugby, the mechanisms involved in injuries and predisposing risk factors.

Data Sources

The publication databases Pubmed, Embase and SportDISCUS were searched in April 2014 for primary research studies of child and adolescent rugby union and rugby league (under 20 years) in English language with data on concussion injuries. The review was conducted within a larger all injury systematic review on rugby union and rugby league where key words used in the search included rugby, injury and concussion with child, adolescent, paediatric and youth.

Results

There were 25 studies retrieved with data on child or adolescent rugby and concussion, 20 were on rugby union, three on rugby league and in two the code of rugby was unspecified. There was significant heterogeneity in the definitions of injuries and of concussion. The incidence of child and adolescent match concussion ranged from 0.2 to 6.9 concussions per 1000 player-hours for rugby union and was 4.6 and 14.7 concussions per 1000 player-hours for rugby league, equivalent to a probability of between 0.3% and 11.4% for rugby union and of 7.7% and 22.7% for rugby league.

Conclusions

There is a significant risk of concussion in children and adolescents playing rugby union and rugby league evident from the studies included in this systematic review. There is a need for reliable data through routine monitoring and reporting in schools and clubs and in hospital emergency departments in order to inform prevention. Concussion protocols should be implemented and tested.
Older people's perspectives on participation in physical activity: a systematic review and thematic synthesis of qualitative literature
Authors: Franco Marcia R , Tong Allison , Howard Kirsten , Sherrington Catherine , Ferreira Paulo H , Pinto Rafael Z , Ferreira Manuela L
Published: January 2015

Background

Physical inactivity accounts for 9% of all deaths worldwide and is among the top 10 risk factors for global disease burden. Nearly half of people aged over 60 years are inactive. Efforts to identify which factors influence physical activity behaviour are needed.

Objective

To identify and synthesise the range of barriers and facilitators to physical activity participation.

Methods

Systematic review of qualitative studies on the perspectives of physical activity among people aged 60 years and over. MEDLINE, EMBASE, CINAHL, PsychINFO and AMED were searched. Independent raters assessed comprehensiveness of reporting of included studies. Thematic synthesis was used to analyse the data.

Results

From 132 studies involving 5987 participants, we identified six major themes: social influences (valuing interaction with peers, social awkwardness, encouragement from others, dependence on professional instruction); physical limitations (pain or discomfort, concerns about falling, comorbidities); competing priorities; access difficulties (environmental barriers, affordability); personal benefits of physical activity (strength, balance and flexibility, self-confidence, independence, improved health and mental well-being); and motivation and beliefs (apathy, irrelevance and inefficacy, maintaining habits).

Conclusions

Some older people still believe that physical activity is unnecessary or even potentially harmful. Others recognise the benefits of physical activity, but report a range of barriers to physical activity participation. Strategies to enhance physical activity participation among older people should include (1) raising awareness of the benefits and minimise the perceived risks of physical activity and (2) improving the environmental and financial access to physical activity opportunities.
Use and evaluation of a semi-permeable mesh implant in vertebral augmentation for the treatment of painful osteoporotic vertebral compression fractures
Authors: Ortiz A Orlando
Published: January 2015

Objective

To assess the efficacy of a semi-permeable mesh implant in the treatment of painful thoracic and lumbar osteoporotic vertebral compression fractures.

Methods

Patients with painful thoracic and lumbar osteoporotic vertebral compression fractures which were refractory to conventional medical management and less than 3 months of age were considered possible candidates for this vertebral augmentation technique. Data recorded for the procedure included patient age, gender, fracture level and morphology, mesh implant size, amount of cement injected, cement extravasation, complications, and pre- and post-procedure numeric pain scores and Oswestry Disability Index (ODI) scores.

Results

17 patients were included in this retrospective study; 12 women and 5 men, with an average age of 78.6 years. Each patient had one level treated with the mesh implant; 4 thoracic levels and 13 lumbar levels. The 10×15 mm implant was used in 13 treated vertebrae, including the two thoracic vertebrae; the 10×20 mm implant was used to treat 3 lumbar vertebrae, and one 10×25 mm implant was used to treat an L1 vertebra. An average of 2.4 mL of acrylic bone cement was injected, and there was fluoroscopic evidence of a small amount of cement leakage in one case. No patient related complications were seen and there were no device failures. All patients, followed-up to at least 3 weeks, showed significant pain relief. The average pretreatment numeric pain score of 9 and ODI of 50 decreased to an average post-treatment score of 0.6 and 12, respectively (p<0.001).

Conclusions

Vertebral augmentation with a semi-permeable mesh stent implant can be used to effectively and safely treat osteoporotic vertebral compression fractures within the lower thoracic and lumbar spine.
Windthrow and growth response following a spruce budworm inspired, variable retention harvest in New Brunswick, Canada
Authors: Wilson Edward A. , MacLean David A.
Published: January 2015

Forest management regimes increasingly focus on the emulation of natural disturbance events, e.g., fire or insect outbreaks, to help increase ecosystem sustainability. We determined the residual stand response to a variable retention harvest inspired by spruce budworm (Choristoneura fumiferana (Clemens)) outbreaks in New Brunswick, Canada. Our objectives were to analyze the differences between surviving residual trees and those that succumbed to windthrow and to quantify growth release. The treatment was based on harvesting the estimated spruce budworm outbreak mortality, i.e., 90% of mature balsam fir (Abies balsamea (L.) Mill., 60% of mature spruce (Picea spp.), and no hardwoods. Windthrow increased with the proportion of trees harvested and averaged 52% over 7–9 years in these stands with high balsam fir – spruce content. One-third of 42 harvested plots sustained >30% windthrow, whereas 73% of 11 similar unharvested plots had <10% windthrow. Balsam fir had higher windthrow than spruce at 53% and 41%, respectively. Windthrown balsam fir trees had significantly larger diameters at breast height (DBH, 1.3 m), larger heights, and smaller crown ratios than surviving residual trees. Substantial growth release occurred, with DBH increment of residual trees 48%–64% greater than trees in unharvested plots. Balsam fir and intolerant hardwoods exhibited the largest growth response. We suggest that future spruce budworm inspired harvests in stands with high balsam fir – spruce content use two or three entries about 5 years apart to reduce windthrow.
Characterization of the dystrophin–glycoprotein complex in airway smooth muscle: role of δ-sarcoglycan in airway responsiveness
Authors: Sharma Pawan , Jha Aruni , Stelmack Gerald L. , Detillieux Karen , Basu Sujata , Klonisch Thomas , Unruh Helmut , Halayko Andrew J.
Published: January 2015

The dystrophin–glycoprotein complex (DGC) is an integral part of caveolae microdomains, and its interaction with caveolin-1 is essential for the phenotype and functional properties of airway smooth muscle (ASM). The sarcoglycan complex provides stability to the dystroglycan complex, but its role in ASM contraction and lung physiology in not understood. We tested whether δ-sarcoglycan (δ-SG), through its interaction with the DGC, is a determinant of ASM contraction ex vivo and airway mechanics in vivo. We measured methacholine (MCh)-induced isometric contraction and airway mechanics in δ-SG KO and wild-type mice. Last, we performed immunoblotting and transmission electron microscopy to assess DGC protein expression and the ultrastructural features of tracheal smooth muscle. Our results reveal an age-dependent reduction in the MCh-induced tracheal isometric force and significant reduction in airway resistance at high concentrations of MCh (50.0 mg/mL) in δ-SG KO mice. The changes in contraction and lung function correlated with decreased caveolin-1 and β-dystroglycan abundance, as well as an age-dependent loss of caveolae in the cell membrane of tracheal smooth muscle in δ-SG KO mice. Collectively, these results confirm and extend understanding of a functional role for the DGC in the contractile properties of ASM and demonstrate that this results in altered lung function in vivo.
Mitigation of malicious attacks on network observation
Authors: Xiao Yan-Dong , Lao Song-Yang , Hou Lv-lin , Bai Liang
Published: January 2015

In the modeling, controlling, and monitoring of complex networks, a fundamental problem concerns the determination and observation of the system's states by using measurements or sensors as few as possible, defined as network observation. This work aims to investigate the robustness of network observation when an approach of minimum dominating set is considered in observing a network. We first investigate the structural properties of the minimum dominating sets, e.g. how the size depends on the degree–degree correlations and how to assess the nodes' importance in the malicious attacks. Then, we introduce a new measurement of robustness for network observation, and implement a hill-climbing algorithm to improve its robustness by edge rewiring. Furthermore, we propose a novel rewiring strategy, called smart rewiring, which could speed up the increment of robustness index. In comparison with previous strategy of edge rewiring, the smart rewiring has been found to be successfully useful on real-world and synthetic networks.
The Schwarzschild solution to the Nexus graviton field
Authors: Marongwe Stuart
Published: January 2015

The Schwarzschild approach is applied to solve the field equations describing a Nexus graviton field. The resulting solutions are free from singularities which have been a problem in general relativity since its inception. Findings from this work also demonstrate that at the Hubble radius, the metric signature of space-time changes generating short-lived but intense bursts of energy during the transition process. The solutions in this paper also provide an explanation to the enigma of late time cosmic acceleration, the galaxy rotation curve problem and the coincidence problem.
Changing Practice of Anticoagulation: Will Target-Specific Anticoagulants Replace Warfarin?
Authors: Arepally Gowthami M. , Ortel Thomas L.
Published: January 2015

The target-specific oral anticoagulants are a class of agents that inhibit factor Xa or thrombin. They are effective and safe compared to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation and for the treatment of venous thromboembolism, and they are comparable to low-molecular-weight heparin for thromboprophylaxis after hip or knee arthroplasty. For other indications, however, such as the prevention of stroke in patients with mechanical heart valves, initial studies have been unfavorable for the newer agents, leaving warfarin the anticoagulant of choice. Further studies are needed before the target-specific anticoagulants can be recommended for patients with cancer-associated thrombosis or heparin-induced thrombocytopenia. Concerns also persist about difficulties with the laboratory assessment of anticoagulant effect and the lack of a specific reversal agent. For these reasons, we anticipate that the vitamin K antagonists will continue to be important anticoagulants for years to come.
A cholinergic contribution to the circulatory responses evoked at the onset of handgrip exercise in humans
Authors: Vianna Lauro C. , Fadel Paul J. , Secher Niels H. , Fisher James P.
Published: January 2015

A cholinergic (muscarinic) contribution to the initial circulatory response to exercise in humans remains controversial. Herein, we posit that this may be due to exercise mode with a cholinergic contribution being important during isometric handgrip exercise, where the hyperemic response of the muscle is relatively small compared with the onset of leg cycling, where a marked increase in muscle blood flow rapidly occurs as a consequence of multiple redundant mechanisms. We recorded blood pressure (BP; brachial artery), stroke volume (pulse contour analysis), cardiac output, and systemic vascular resistance (SVR) in young healthy males, while performing either 20 s of isometric handgrip contraction at 40% maximum voluntary contraction ( protocol 1; n = 9) or 20 s of low-intensity leg cycling exercise ( protocol 2; n = 8, 42 ± 8 W). Exercise trials were conducted under control (no drug) conditions and following cholinergic blockade (glycopyrrolate). Under control conditions, isometric handgrip elicited an initial increase in BP (+5 ± 2 mmHg at 3 s and +3 ± 1 mmHg at 10 s, P < 0.05), while SVR dropped after 3 s (−27 ± 6% at 20 s; P < 0.05). Cholinergic blockade abolished the isometric handgrip-induced fall in SVR and, thereby, augmented the pressor response (+13 ± 3 mmHg at 10 s; P < 0.05 vs. control). In contrast, cholinergic blockade had a nonsignificant effect on changes in BP and SVR at the onset of leg cycling exercise. These findings suggest that a cholinergic mechanism is important for the BP and SVR responses at the onset of isometric handgrip exercise in humans.
Laser speckle contrast imaging reveals large-scale synchronization of cortical autoregulation dynamics influenced by nitric oxide
Authors: Mitrou Nicholas , Scully Christopher G. , Braam Branko , Chon Ki H. , Cupples William A.
Published: January 2015

Synchronization of tubuloglomerular feedback (TGF) dynamics in nephrons that share a cortical radial artery is well known. It is less clear whether synchronization extends beyond a single cortical radial artery or whether it extends to the myogenic response (MR). We used LSCI to examine cortical perfusion dynamics in isoflurane-anesthetized, male Long-Evans rats. Inhibition of nitric oxide synthases by Nω-nitro-l-arginine methyl ester (l-NAME) was used to alter perfusion dynamics. Phase coherence (PC) was determined between all possible pixel pairs in either the MR or TGF band (0.09–0.3 and 0.015–0.06 Hz, respectively). The field of view (≈4 × 5 mm) was segmented into synchronized clusters based on mutual PC. During the control period, the field of view was often contained within one cluster for both MR and TGF. PC was moderate for TGF and modest for MR, although significant in both. In both MR and TGF, PC exhibited little spatial variation. After l-NAME, the number of clusters increased in both MR and TGF. MR clusters became more strongly synchronized while TGF clusters showed small highly coupled, high-PC regions that were coupled with low PC to the remainder of the cluster. Graph theory analysis probed modularity of synchronization. It confirmed weak synchronization of MR during control that probably was not physiologically relevant. It confirmed extensive and long-distance synchronization of TGF during control and showed increased modularity, albeit with larger modules seen in MR than in TGF after l-NAME. The results show widespread synchronization of MR and TGF that is differentially affected by nitric oxide.
Expression of a dominant negative PKA mutation in the kidney elicits a diabetes insipidus phenotype
Authors: Gilbert Merle L. , Yang Linghai , Su Thomas , McKnight G. Stanley
Published: January 2015

PKA plays a critical role in water excretion through regulation of the production and action of the antidiuretic hormone arginine vasopressin (AVP). The AVP prohormone is produced in the hypothalamus, where its transcription is regulated by cAMP. Once released into the circulation, AVP stimulates antidiuresis through activation of vasopressin 2 receptors in renal principal cells. Vasopressin 2 receptor activation increases cAMP and activates PKA, which, in turn, phosphorylates aquaporin (AQP)2, triggering apical membrane accumulation, increased collecting duct permeability, and water reabsorption. We used single-minded homolog 1 ( Sim1)-Cre recombinase-mediated expression of a dominant negative PKA regulatory subunit (RIαB) to disrupt kinase activity in vivo and assess the role of PKA in fluid homeostasis. RIαB expression gave rise to marked polydipsia and polyuria; however, neither hypothalamic Avp mRNA expression nor urinary AVP levels were attenuated, indicating a primary physiological effect on the kidney. RIαB mice displayed a marked deficit in urinary concentrating ability and greatly reduced levels of AQP2 and phospho-AQP2. Dehydration induced Aqp2 mRNA in the kidney of both control and RIαB-expressing mice, but AQP2 protein levels were still reduced in RIαB-expressing mutants, and mice were unable to fully concentrate their urine and conserve water. We conclude that partial PKA inhibition in the kidney leads to posttranslational effects that reduce AQP2 protein levels and interfere with apical membrane localization. These findings demonstrate a distinct physiological role for PKA signaling in both short- and long-term regulation of AQP2 and characterize a novel mouse model of diabetes insipidus.
Shear stress is normalized in glomerular capillaries following ⅚ nephrectomy
Authors: Ferrell Nicholas , Sandoval Ruben M. , Bian Aihua , Campos-Bilderback Silvia B. , Molitoris Bruce A. , Fissell William H.
Published: January 2015

Loss of significant functional renal mass results in compensatory structural and hemodynamic adaptations in the nephron. While these changes have been characterized in several injury models, how they affect hemodynamic forces at the glomerular capillary wall has not been adequately characterized, despite their potential physiological significance. Therefore, we used intravital multiphoton microscopy to measure the velocity of red blood cells in individual glomerular capillaries of normal rats and rats subjected to ⅚ nephrectomy. Glomerular capillary blood flow rate and wall shear stress were then estimated using previously established experimental and mathematical models to account for changes in hematocrit and blood rheology in small vessels. We found little change in the hemodynamic parameters in glomerular capillaries immediately following injury. At 2 wk postnephrectomy, significant changes in individual capillary blood flow velocity and volume flow rate were present. Despite these changes, estimated capillary wall shear stress was unchanged. This was a result of an increase in capillary diameter and changes in capillary blood rheology in nephrectomized rats.
Ovarian hormones and prolactin increase renal NaCl cotransporter phosphorylation
Authors: Rojas-Vega Lorena , Reyes-Castro Luis A. , Ramírez Victoria , Bautista-Pérez Rocío , Rafael Chloe , Castañeda-Bueno María , Meade Patricia , de los Heros Paola , Arroyo-Garza Isidora , Bernard Valérie , Binart Nadine , Bobadilla Norma A. , Hadchouel Juliette , Zambrano Elena , Gamba Gerardo
Published: January 2015

Unique situations in female physiology require volume retention. Accordingly, a dimorphic regulation of the thiazide-sensitive Na+-Cl−cotransporter (NCC) has been reported, with a higher activity in females than in males. However, little is known about the hormones and mechanisms involved. Here, we present evidence that estrogens, progesterone, and prolactin stimulate NCC expression and phosphorylation. The sex difference in NCC abundance, however, is species dependent. In rats, NCC phosphorylation is higher in females than in males, while in mice both NCC expression and phosphorylation is higher in females, and this is associated with increased expression and phosphorylation of full-length STE-20 proline-alanine-rich kinase (SPAK). Higher expression/phosphorylation of NCC was corroborated in humans by urinary exosome analysis. Ovariectomy in rats resulted in decreased expression and phosphorylation of the cotransporter and promoted the shift of SPAK isoforms toward the short inhibitory variant SPAK2. Conversely, estradiol or progesterone administration to ovariectomized rats restored NCC phosphorylation levels and shifted SPAK expression and phosphorylation towards the full-length isoform. Estradiol administration to male rats induced a significant increase in NCC phosphorylation. NCC is also modulated by prolactin. Administration of this peptide hormone to male rats induced increased phosphorylation of NCC, an effect that was observed even using the ex vivo kidney perfusion strategy. Our results indicate that estradiol, progesterone, and prolactin, the hormones that are involved in sexual cycle, pregnancy and lactation, upregulate the activity of NCC.
Transdermal contraception and the renin-angiotensin-aldosterone system in premenopausal women
Authors: Odutayo Ayodele , Cherney David , Miller Judith , Ahmed Sofia B. , Lai Vesta , Dunn Sheila , Pun Nicole , Moineddin Rahim , Hladunewich Michelle A.
Published: January 2015

The oral contraceptive pill (OCP) activates the renin-angiotensin-aldosterone system (RAAS) through first-pass hepatic metabolism. Although usually benign, RAAS activation may have detrimental effects on renal and hemodynamic function in some women. Since combined hormonal contraception with the transdermal patch (EVRA) does not undergo first-pass hepatic metabolism, we hypothesized that the RAAS response would be different from that of OCP subjects. Thirty-five nonsmoking, premenopausal women (15 control subjects, 10 OCP subjects, and 10 contraceptive patch subjects) without evidence of cardiovascular disease, renal disease, or diabetes were studied. Baseline angiotensinogen, renin, angiotensin II, aldosterone, and plasma renin activity were assessed along with hormonal and hemodynamic responses to simulated orthostatic stress using incremental lower body negative pressure (LBNP; −15, −25, and −40 mmHg). Baseline levels of angiotensinogen, angiotensin II, and plasma renin activity were significantly higher in OCP subjects compared with normotensive control and contraceptive patch subjects ( P < 0.05), whereas aldosterone was significantly higher in OCP versus control subjects only ( P < 0.05). Plasma renin levels were significantly lower at baseline in contraceptive patch subjects compared with normotensive control and OCP subjects ( P < 0.05). In response to LBNP, increases in renin, angiotensin II, and aldosterone were attenuated in contraceptive patch subjects in conjunction with an exaggerated decline in mean arterial pressure ( P < 0.05 vs. control and OCP subjects). The contraceptive patch in healthy premenopausal women is associated with an impaired ability to maintain blood pressure in response to LBNP, possibly due to insensitivity of the endogenous RAAS. Further evaluation may be beneficial in women with kidney disease.
Podocyte injury-driven intracapillary plasminogen activator inhibitor type 1 accelerates podocyte loss via uPAR-mediated β1-integrin endocytosis
Authors: Kobayashi Namiko , Ueno Toshiharu , Ohashi Kumi , Yamashita Hanako , Takahashi Yukina , Sakamoto Kazuo , Manabe Shun , Hara Satoshi , Takashima Yasutoshi , Dan Takashi , Pastan Ira , Miyata Toshio , Kurihara Hidetake , Matsusaka Taiji , Reiser Jochen , Nagata Michio
Published: January 2015

Podocyte-endothelial cell cross-talk is paramount for maintaining the filtration barrier. The present study investigated the endothelial response to podocyte injury and its subsequent role in glomerulosclerosis using the podocyte-specific injury model of NEP25/LMB2 mice. NEP25/LMB2 mice showed proteinuria and local podocyte loss accompanied by thrombotic microangiopathy on day 8. Mice showed an increase of glomerular plasminogen activator inhibitor type 1 (PAI-1) mRNA and aberrant endothelial PAI-1 protein already on day 1, before thrombosis and proteinuria. A PAI-1-specific inhibitor reduced proteinuria and thrombosis and preserved podocyte numbers in NEP25/LMB2 mice by stabilization of β1-integrin translocation. Heparin loading significantly reduced thrombotic formation, whereas proteinuria and podocyte numbers were unchanged. Immortalized podocytes treated with PAI-1 and the urokinase plasminogen activator (uPA) complex caused significant cell detachment, whereas podocytes treated with PAI-1 or uPA alone or with the PAI-1/uPA complex pretreated with an anti-uPA receptor (uPAR) antibody failed to cause detachment. Confocal microscopy and cell surface biotinylation experiments showed that internalized β1-integrin was found together with uPAR in endocytotic vesicles. The administration of PAI-1 inhibitor or uPAR-blocking antibody protected cultured podocytes from cell detachment. In conclusion, PAI-1/uPA complex-mediated uPAR-dependent podocyte β1-integrin endocytosis represents a novel mechanism of glomerular injury leading to progressive podocytopenia. This aberrant cross-talk between podocytes and endothelial cells represents a feedforward injury response driving podocyte loss and progressive glomerulosclerosis.
Nasotemporal ERP differences: evidence for increased inhibition of temporal distractors
Authors: Huber-Huber Christoph , Grubert Anna , Ansorge Ulrich , Eimer Martin
Published: January 2015

Previous research has demonstrated behavioral advantages for stimuli in the temporal relative to the nasal visual hemifield. To investigate whether this nasotemporal asymmetry reflects a genuinely attentional bias, we recorded event-related potentials in a task where participants identified a color-defined target digit in one visual hemifield that was accompanied by an irrelevant distractor in the opposite hemifield ( experiment 1). To dissociate the processing of stimuli in nasal and temporal visual hemifields, an eye-patching procedure was used. Targets triggered N2pc components that marked their attentional selection. Unexpectedly, these N2pc components were larger and emerged earlier for nasal relative to temporal targets. Experiment 2 provided evidence that this nasotemporal asymmetry for the N2pc is linked to an increased attentional inhibition of temporal distractors. Relative to nasal distractors, temporal distractors elicited an increased inhibition-related contralateral positivity, resulting in more pronounced differences between contralateral and ipsilateral event-related potentials on trials with temporal distractors and nasal targets. These results provide novel evidence for a genuinely attentional contribution to nasotemporal asymmetries and suggest that such asymmetries are associated with top-down controlled distractor inhibition.