bluuebunny/crossref_metadata_2025_split huggingface dataset:
FMS-Like Tyrosine Kinase 3 Ligand Treatment of Mice Aggravates Acute Lung Injury in Response to Streptococcus pneumoniae: Role of Pneumolysin
Authors: Brumshagen Christina , Maus Regina , Bischof Andrea , Ueberberg Bianca , Bohling Jennifer , Osterholzer John J. , Ogunniyi Abiodun D. , Paton James C. , Welte Tobias , Maus Ulrich A. 
Published: September 2012

ABSTRACT

FMS-like tyrosine kinase-3 ligand (Flt3L) is a dendritic cell (DC) growth and differentiation factor with potential in antitumor therapies and antibacterial immunization strategies. However, the effect of systemic Flt3L treatment on lung-protective immunity against bacterial infection is incompletely defined. Here, we examined the impact of deficient (in Flt3L knockout [KO] mice), normal (in wild-type [WT] mice), or increased Flt3L availability (in WT mice pretreated with Flt3L for 3, 5, or 7 days) on lung DC subset profiles and lung-protective immunity against the major lung-tropic pathogen,
Streptococcus pneumoniae
. Although in Flt3L-deficient mice the numbers of DCs positive for CD11b (CD11b
pos
DCs) and for CD103 (CD103
pos
DCs) were diminished, lung permeability, a marker of injury, was unaltered in response to
S. pneumoniae
. In contrast, WT mice pretreated with Flt3L particularly responded with increased numbers of CD11b
pos
DCs and with less pronounced numbers of CD103
pos
DCs and impaired bacterial clearance and with increased lung permeability following
S. pneumonia
e challenge. Notably, infection of Flt3L-pretreated mice with
S. pneumoniae
lacking the pore-forming toxin, pneumolysin (PLY), resulted in substantially less lung CD11b
pos
DCs activation and reduced lung permeability. Collectively, this study establishes that Flt3L treatment enhances the accumulation of proinflammatory activated lung CD11b
pos
DCs which contribute to acute lung injury in response to PLY released by
S. pneumoniae
.
Network-aware service placement in a distributed cloud environment
Authors: Steiner Moritz , Gaglianello Bob Gaglianello , Gurbani Vijay , Hilt Volker , Roome W.D. , Scharf Michael , Voith Thomas 
Published: September 2012

We consider a system of compute and storage resources geographically distributed over a large number of locations connected via a wide-area network. By distributing the resources, latency to users can be decreased, bandwidth costs reduced and availablility increased. The challenge is to distribute services with varying characteristics among the data centers optimally. Some services are very latency sensitive, others need vast amounts of storage, and yet others are computationally complex but do not require hard deadlines on execution. We propose efficient algorithms for the placement of services to get the maximum benefit from a distributed cloud systems. The algorithms need input on the status of the network, compute resources and data resources, which are matched to application requirements.
This demonstration shows how a network-aware cloud can combine all three resource types - computation, storage, and network connectivity - in distributed cloud environments. Our dynamic service placement algorithm monitors the network and data center resources in real-time. Our prototype uses the information gathered to place or migrate services to provide the best user experience for a service.
AutoNetkit
Authors: Knight Simon , Jaboldinov Askar , Maennel Olaf , Phillips Iain , Roughan Matthew 
Published: September 2012

We present a methodology that brings simplicity to large and complex test labs by using abstraction. The networking community has appreciated the value of large scale test labs to explore complex network interactions, as seen in projects such as PlanetLab, GENI, DETER, Emulab, and SecSI. Virtualization has enabled the creation of many more such labs. However, one problem remains: it is time consuming, tedious and error prone to setup and configure large scale test networks. Separate devices need to be configured in a coordinated way, even in a virtual lab.
AutoNetkit, an open source tool, uses abstractions and defaults to achieve both configuration and deployment and create such large-scale virtual labs. This allows researchers and operators to explore new protocols, create complex models of networks and predict consequences of configuration changes. However, our abstractions could also allow the discussion of the broader configuration management problem. Abstractions that currently configure networks in a test lab can, in the future, be employed in configuration management tools for real networks.
Towards detecting BGP route hijacking using the RPKI
Authors: Wählisch Matthias , Maennel Olaf , Schmidt Thomas C. 
Published: September 2012

Prefix hijacking has always been a big concern in the Internet. Some events made it into the international world-news, but most of them remain unreported or even unnoticed. The scale of the problem can only be estimated.
The Resource Publication Infrastructure (RPKI) is an effort by the IETF to secure the inter-domain routing system. It includes a formally verifiable way of identifying who owns legitimately which portion of the IP address space. The RPKI has been standardized and prototype implementations are tested by Internet Service Providers (ISPs). Currently the system holds already about 2% of the Internet routing table.
Therefore, in theory, it should be easy to detect hijacking of prefixes within that address space. We take an early look at BGP update data and check those updates against the RPKI---in the same way a router would do, once the system goes operational. We find many interesting dynamics, not all can be easily explained as hijacking, but a significant number are likely operational testing or misconfigurations.
Joint hop-by-hop and receiver-driven interest control protocol for content-centric networks
Authors: Carofiglio Giovanna , Gallo Massimo , Muscariello Luca 
Published: September 2012

Content-centric networking (CCN) advocates a new transport model tailored to named-data communication. Three features distinguish CCN transport from the TCP/IP model: unique endpoint at the receiver, pull-based data retrieval in a point to multi-point fashion and in-path caching.
The definition of transport control mechanisms is of fundamental importance within the CCN architectural design and beyond, in the broader scope of information-centric networks. In this work, we propose a joint Hop-by-hop and Receiver-driven Interest Control Protocol (HR-ICP) to regulate user requests (Interests) either at the receiver and at intermediate nodes via Interest shaping. We prove that HR-ICP is stable and converges to an efficient and max-min fair equilibrium. Compared to controlling traffic only at the receiver, HR-ICP accelerates congestion reaction and reduces the loss rate, as we show by means of CCN packet-level simulations. In different network scenarios, we highlight the advantages of our solution in terms of faster convergence to the optimal throughput, robustness against misbehaving receivers and flow protection of delay-sensitive applications.
Clinical and Angiographic Risk Stratification and Differential Impact on Treatment Outcomes in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial
Authors: Brooks Maria Mori , Chaitman Bernard R. , Nesto Richard W. , Hardison Regina M. , Feit Frederick , Gersh Bernard J. , Krone Ronald J. , Sako Edward Y. , Rogers William J. , Garber Alan J. , King Spencer B. , Davidson Charles J. , Ikeno Fumiaki , Frye Robert L. 
Published: September 2012

Background—
The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial assigned patients with type 2 diabetes mellitus to prompt coronary revascularization plus intensive medical therapy versus intensive medical therapy alone and reported no significant difference in mortality. Among patients selected for coronary artery bypass graft surgery, prompt coronary revascularization was associated with a significant reduction in death/myocardial infarction/stroke compared with intensive medical therapy. We hypothesized that clinical and angiographic risk stratification would affect the effectiveness of the treatments overall and within revascularization strata.

Methods and Results—

An angiographic risk score was developed from variables assessed at randomization; independent prognostic factors were myocardial jeopardy index, total number of coronary lesions, prior coronary revascularization, and left ventricular ejection fraction. The Framingham Risk Score for patients with coronary disease was used to summarize clinical risk. Cardiovascular event rates were compared by assigned treatment within high-risk and low-risk subgroups. Overall, no outcome differences between the intensive medical therapy and prompt coronary revascularization groups were seen in any risk stratum. The 5-year risk of death/myocardial infarction/stroke was 36.8% for intensive medical therapy compared with 24.8% for prompt coronary revascularization among the 381 coronary artery bypass graft surgery–selected patients in the highest angiographic risk tertile (
P
=0.005); this treatment effect was amplified in patients with both high angiographic and high Framingham risk (47.3% intensive medical therapy versus 27.1% prompt coronary revascularization;
P
=0.010; hazard ratio=2.10;
P
=0.009). Treatment group differences were not significant in other clinical-angiographic risk groups within the coronary artery bypass graft surgery stratum, or in any subgroups within the percutaneous coronary intervention stratum.

Conclusion—
Among patients with diabetes mellitus and stable ischemic heart disease, a strategy of prompt coronary artery bypass graft surgery significantly reduces the rate of death/myocardial infarction MI/stroke in those with extensive coronary artery disease or impaired left ventricular function.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00006305.
Sex-Related Trends in Mortality in Hospitalized Men and Women After Myocardial Infarction Between 1985 and 2008
Authors: Nauta Sjoerd T. , Deckers Jaap W. , van Domburg Ron T. , Akkerhuis K. Martijn 
Published: September 2012

Background—
We aimed to study sex-related differences in temporal trends in short- and long-term mortality from 1985 to 2008 in patients hospitalized for acute myocardial infarction.

Methods and Results—
We included a total of 14 434 consecutive patients admitted to our intensive coronary care unit between 1985 and 2008 for myocardial infarction. A total of 4028 patients (28%) were women. Women were more likely to present with a higher risk profile and were equally likely to receive pharmacological and invasive reperfusion therapy compared with men. Women had a higher unadjusted mortality rate at 30 days (odds ratio, 1.3; 95% confidence interval, 1.1–1.5) and during 20 years (hazard ratio, 1.1; 95% confidence interval, 1.0–1.2) of follow-up. After adjustment for baseline characteristics, 30-day mortality was equal (adjusted odds ratio, 1.0; 95% confidence interval, 0.85–1.2) but the hazard for 20-year mortality was lower (adjusted hazard ratio, 0.77; 95% confidence interval, 0.66–0.90) in women compared to men. For 30-day mortality, there was no significant interaction between sex and age, diagnosis, or diabetes mellitus. Survival improved between 1985 and 2008. Temporal mortality reductions between 1985 and 2008 were at least as high in women as in men with myocardial infarction for both 30-day mortality and long-term mortality hazard.

Conclusions—
The fact that adjusted mortality rates for men and women treated for myocardial infarction in an intensive coronary care unit were similar and declined markedly over a 24-year period suggests that both sexes benefit from the evidence-based therapies that have been developed and implemented during this time period.
Phosphoinositide 3-Kinase γ Protects Against Catecholamine-Induced Ventricular Arrhythmia Through Protein Kinase A–Mediated Regulation of Distinct Phosphodiesterases
Authors: Ghigo Alessandra , Perino Alessia , Mehel Hind , Zahradníková Alexandra , Morello Fulvio , Leroy Jérôme , Nikolaev Viacheslav O. , Damilano Federico , Cimino James , De Luca Elisa , Richter Wito , Westenbroek Ruth , Catterall William A. , Zhang Jin , Yan Chen , Conti Marco , Gomez Ana Maria , Vandecasteele Grégoire , Hirsch Emilio , Fischmeister Rodolphe 
Published: September 2012

Background—
Phosphoinositide 3-kinase γ (PI3Kγ) signaling engaged by β-adrenergic receptors is pivotal in the regulation of myocardial contractility and remodeling. However, the role of PI3Kγ in catecholamine-induced arrhythmia is currently unknown.

Methods and Results—

Mice lacking PI3Kγ (PI3Kγ
−/−
) showed runs of premature ventricular contractions on adrenergic stimulation that could be rescued by a selective β
2
-adrenergic receptor blocker and developed sustained ventricular tachycardia after transverse aortic constriction. Consistently, fluorescence resonance energy transfer probes revealed abnormal cAMP accumulation after β
2
-adrenergic receptor activation in PI3Kγ
−/−
cardiomyocytes that depended on the loss of the scaffold but not of the catalytic activity of PI3Kγ. Downstream from β-adrenergic receptors, PI3Kγ was found to participate in multiprotein complexes linking protein kinase A to the activation of phosphodiesterase (PDE) 3A, PDE4A, and PDE4B but not of PDE4D. These PI3Kγ-regulated PDEs lowered cAMP and limited protein kinase A–mediated phosphorylation of L-type calcium channel (Ca
v
1.2) and phospholamban. In PI3Kγ
−/−
cardiomyocytes, Ca
v
1.2 and phospholamban were hyperphosphorylated, leading to increased Ca
2+
spark occurrence and amplitude on adrenergic stimulation. Furthermore, PI3Kγ
−/−
cardiomyocytes showed spontaneous Ca
2+
release events and developed arrhythmic calcium transients.

Conclusions—
PI3Kγ coordinates the coincident signaling of the major cardiac PDE3 and PDE4 isoforms, thus orchestrating a feedback loop that prevents calcium-dependent ventricular arrhythmia.
Public management reform and citizen perceptions of the UK health system
Authors: Grosso Ashley L. , Van Ryzin Gregg G. 
Published: September 2012

The United Kingdom (UK) instituted a performance framework for the National Health Service (NHS) in the late 1990s that, inspired by the New Public Management (NPM), employed performance measurement and management in an effort to improve the quality of health services to citizens, in addition to realizing efficiency goals. Using data from the 1996 and 2002 Eurobarometer and a difference in differences analytical approach, we evaluate the impacts of these performance reforms by comparing the UK to other European Union countries in terms of overall citizen satisfaction with the health care system and perceptions of how well the health care system performs. In general, our results suggest that citizen satisfaction and performance perceptions in the UK were more favorable after the reforms than what would have occurred, absent the implementation of the reforms. The estimated improvement in satisfaction and perceived performance is both statistically and substantively significant, and thus provides evidence that the UK’s NPM-inspired performance framework did accomplish at least some of its goals. Points for practitioners The New Public Management and performance measurement movements in public administration have called for a focus on customer service and citizen satisfaction. We evaluate the effects of performance-focused reforms in the health care system in the UK over time in comparison to other EU countries. Our results suggest that the quality and customer-focused aspects of New Public Management that were applied through the UK’s health system reforms seem to have improved citizen satisfaction with health care and perceived performance of the health system. Practitioners’ efforts to measure, report, and improve quality may have noticeable effects on citizens’ attitudes.
Of alternating waves and shifting shores: the configuration of reform values in the US federal bureaucracy
Authors: Park Sung Min , Joaquin M. Ernita 
Published: September 2012

Scholars have noted that United States federal government reforms come in waves ( Barley and Kunda, 1992 ; Kettl, 2002 ; Light, 1998 ), often accompanied by values that alternate between rational and normative conceptions of public administration and service. The idea of alternation also suggests the importance of time in gauging the effect of new reforms when previous reforms have accumulated from the past (see Pollitt, 2008 ). Time is a necessary variable in implementing reforms; time is crucial to know if reform values have taken hold. Extending Paul Light’s (1998) reform waves metaphor, we investigate here whether two predominant management philosophies have influenced and reconfigured the shoreline of values found among federal agencies over a particular period of time. Using empirical methods, we examine how the values of New Public Management and its humanist (post-NPM) counterpart have settled and taken hold among US federal agencies. We followed three lines of inquiry: determining the existence of reform values in the bureaucracy, examining the prevalence of different sets of values, and investigating whether ‘crowding out’ of values occurred, that is, whether there was a detectable shift in the distribution of values as a new wave came on top of others. Our analysis yields evidence for the predominance of certain NPM and post-NPM values and indicates that bureaucracy concurrently holds what may be regarded as competing values side-by-side. Implications for research and future reforms are suggested in the final section of the article. Points for practitioners Practicing public administration requires constantly navigating reform pressures that espouse different, sometimes opposing, value sets. NPM and post-NPM reforms differed in their emphasis on applying rationalistic and humanistic values to the work of government. Based on federal workforce surveys, NPM values appeared ascendant from the reinvention period till the end of the Bush administration, when a more humanist outlook began to emerge. Bureaucratic values are dynamic and change could go faster with network structures. Following previous research, this study suggests that a ‘layering’ of reform occurs; the strongest values are held intact even as newer philosophies of organization and management are introduced. Results suggest that government professionals can adhere to differing values, but further study is required to see how those values actually influence their work.
The New Public Management reform of state-funded social service nonprofit organizations and the changing politics of welfare in Hong Kong
Authors: Lee Eliza W.Y. 
Published: September 2012

What are the political impact and significance of New Public Management (NPM) reform on social service nonprofit organizations (NPOs) in Hong Kong? Social service NPOs have a long history as a significant part of Hong Kong’s ‘welfare mix’, not only in their role as state agents in the provision of service, but also because of their political and societal roles in affecting social policy making during the colonial era. The exercise of such agencies under an authoritarian setting was made possible through a governance regime historically formed under the peculiar situation of the old politics of welfare. The NPM reform and the associated governance regime change is a significant part of the new politics of welfare that has arisen with the dissolution of the old social pact. It facilitates the transition of the governance regime from strategic partnership to executive dominance, which maximizes the flexibility of the state in containing social spending and maneuvering the new distributive politics arising from the increasing societal demand for social care. Points for practitioners The NPM reform of social service NPOs is closely tied to the change in the welfare system and has significant impact on the environment within which these NPOs operate. The impact and significance of reform is also affected by the characteristics of the political system and the preexisting relationship between the state and the nonprofit sector. Social service NPOs assume multiple roles as state agents, political agents, and societal agents. In Hong Kong, NPM reform unfavorably affects the space for NPOs to exercise their societal agency. The fierce competition for resources also stifles the development of newer organizations.
Integrity management and the public service ethos in the UK: patchwork quilt or threadbare blanket?
Authors: Heywood Paul M. 
Published: September 2012

This article focuses on integrity management in contemporary UK public life. Despite traditionally high standards of integrity in the public service, it has recently been argued that the UK’s approach resembles a patchwork quilt of poorly defined institutional roles, questionable independence, and contested notions of how best to disseminate and uphold ethical practice. The article traces how the British public service ethos (PSE), which places emphasis on informal codes of conduct and moral integrity, has evolved within broader systemic changes to the style of public service delivery. It is argued that pressures to decentralize public service delivery sit in tension with, and feed into, piecemeal attempts to centralize and codify integrity management. This dynamic is presented in terms of the tension between compliance-based and values-based approaches to integrity management. The article is structured in three parts. The first traces the evolution of the British public service ethos in order to situate integrity management in both its institutional and structural context. The second addresses recent academic debates and recommendations from key bodies such as the Committee on Standards in Public Life (CSPL) and the House of Commons Public Administration Select Committee (PASC). It is shown how recommendations to create independent statutory bodies of ethical oversight have not been fully implemented. The third part seeks to place the UK experience within a broader context. In doing so, the article reflects on ways in which we can understand the concept and application of integrity management within and beyond the UK experience. Point for practitioners The article discusses the tensions between values-based and compliance-based approaches to integrity management in the United Kingdom. It seeks to explore how the former is closely linked to the existence and reproduction of what has been termed a ‘public service ethos'. As that ethos has been challenged by reforms associated with New Public Management, a series of scandals in the public sector has given rise to the adoption of more compliance-based responses. The key challenge for those designing approaches to integrity management is to reconcile the core values which underpin the public service ethos with accountability mechanisms that can be assessed on the basis of measurable performance indicators.