Inhalationally administered semifluorinated alkanes (SFAs) as drug carriers in an experimental model of acute respiratory distress syndrome

Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients’ outcomes. This might be because dependent lung areas cannot be reached by conventional aerosols. Due to their physicochemical properties, semifluorinated alkanes (SFAs) could address this problem. After induction of ARDS, 26 pigs were randomized into three groups: (1) control (Sham), (2) perfluorohexyloctane (F6H8), and (3) F6H8-ibuprofen. Using a nebulization catheter, (2) received 1 mL/kg F6H8 while (3) received 1 mL/kg F6H8 with 6 mg/mL ibuprofen. Ibuprofen plasma and lung tissue concentration, bronchoalveolar lavage (BAL) fluid concentration of TNF-α, IL-8, and IL-6, and lung mechanics were measured. The ibuprofen concentration was equally distributed to the dependent parts of the right lungs. Pharmacokinetic data demonstrated systemic absorption of ibuprofen proofing a transport across the alveolo-capillary membrane. A significantly lower TNF-α concentration was observed in (2) and (3) when compared to the control group (1). There were no significant differences in IL-8 and IL-6 concentrations and lung mechanics. F6H8 aerosol seemed to be a suitable carrier for pulmonary drug delivery to dependent ARDS lung regions without having negative effects on lung mechanics

Degrees of tenant isolation for cloud-hosted software services : a cross-case analysis

A challenge, when implementing multi-tenancy in a cloud-hosted software service, is how to ensure that the performance and resource consumption of one tenant does not adversely affect other tenants. Software designers and architects must achieve an optimal degree of tenant isolation for their chosen application requirements. The objective of this research is to reveal the trade-offs, commonalities, and differences to be considered when implementing the required degree of tenant isolation. This research uses a cross-case analysis of selected open source cloud-hosted software engineering tools to empirically evaluate varying degrees of isolation between tenants. Our research reveals five commonalities across the case studies: disk space reduction, use of locking, low cloud resource consumption, customization and use of plug-in architecture, and choice of multi-tenancy pattern. Two of these common factors compromise tenant isolation. The degree of isolation is reduced when there is no strategy to reduce disk space and customization and plug-in architecture is not adopted. In contrast, the degree of isolation improves when careful consideration is given to how to handle a high workload, locking of data and processes is used to prevent clashes between multiple tenants and selection of appropriate multi-tenancy pattern. The research also revealed five case study differences: size of generated data, cloud resource consumption, sensitivity to workload changes, the effect of the software process, client latency and bandwidth, and type of software process. The degree of isolation is impaired, in our results, by the large size of generated data, high resource consumption by certain software processes, high or fluctuating workload, low client latency, and bandwidth when transferring multiple files between repositories. Additionally, this research provides a novel explanatory framework for (i) mapping tenant isolation to different software development processes, cloud resources and layers of the cloud stack; and (ii) explaining the different trade-offs to consider affecting tenant isolation (i.e. resource sharing, the number of users/requests, customizability, the size of generated data, the scope of control of the cloud application stack and business constraints) when implementing multi-tenant cloud-hosted software services. This research suggests that software architects have to pay attention to the trade-offs, commonalities, and differences we identify to achieve their degree of tenant isolation requirements

The power of names: radical identities in the Reformation Era

Book synopsis: This volume of essays explores the themes of radicalism and dissent within Protestantism. The comparisons highlight the contingent nature of particular settlements and narratives, and reveal the extent to which the definition of religious radicalism was dependent upon immediate context and show that radicalism and dissent were truly transnational phenomena. The historiography of the so-called radical reformation has been unduly shaped by the hostile categories imposed by mainstream or magisterial reformers during the sixteenth and seventeenth centuries. This volume argues that scholars should adopt an open-ended understanding of evangelical reform, and recognize that the boundaries between radicalism and its opposite were not always firmly drawn. The distinction between the two is an inheritance of the Lutheran Reformation of the 1520s, which shaped not only the later course of the Reformation in the Holy Roman Empire but also attitudes towards and writings on religious dissent in the Netherlands and England. Radical critique is immanent within mainstream Protestantism, in a faith that emphasizes the power of the gospel with its unrelenting demands

High density lipoprotein mediates anti-inflammatory transcriptional reprogramming of macrophages via the transcriptional repressor ATF3

High Density Lipoprotein (HDL) mediates reverse cholesterol transport and it is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. Here we identify the transcriptional repressor ATF3, as an HDL-inducible target gene in macrophages that down-regulates the expression of Toll-like receptor (TLR)-induced pro-inflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo. Our findings may explain the broad anti-inflammatory and metabolic actions of HDL and provide the basis for predicting the success of novel HDL-based therapies

Optimal deployment of components of cloud-hosted application for guaranteeing multitenancy isolation

One of the challenges of deploying multitenant cloud-hosted services that are designed to use (or be integrated with) several components is how to implement the required degree of isolation between the components when there is a change in the workload. Achieving the highest degree of isolation implies deploying a component exclusively for one tenant; which leads to high resource consumption and running cost per component. A low degree of isolation allows sharing of resources which could possibly reduce cost, but with known limitations of performance and security interference. This paper presents a model-based algorithm together with four variants of a metaheuristic that can be used with it, to provide near-optimal solutions for deploying components of a cloud-hosted application in a way that guarantees multitenancy isolation. When the workload changes, the model based algorithm solves an open multiclass QN model to determine the average number of requests that can access the components and then uses a metaheuristic to provide near-optimal solutions for deploying the components. Performance evaluation showed that the obtained solutions had low variability and percent deviation when compared to the reference/optimal solution. We also provide recommendations and best practice guidelines for deploying components in a way that guarantees the required degree of isolation

HIV and incarceration: prisons and detention

The high prevalence of HIV infection among prisoners and pre-trial detainees, combined with overcrowding and sub-standard living conditions sometimes amounting to inhuman or degrading treatment in violation of international law, make prisons and other detention centres a high risk environment for the transmission of HIV. Ultimately, this contributes to HIV epidemics in the communities to which prisoners return upon their release

Anabaptist Spirituality and the Heidelberg Catechism

Although the Anabaptists are not explicitly mentioned in the Heidelberg Catechism, it is generally acknowledged that the catechism influenced by the debates with the so-called radical reformation. This paper assesses Zacharias Ursinus’ Commentary on the Heidelberg Catechism and the report of the 1571 Frankenthal disputation in order to get a clearer picture of this influence. It concludes that the implicit polemics against the Anabaptists regard the relationship between the Old and the New Testaments and Christology. The spirituality of the Heidelberg Catechism stresses the continuity between creation and recreation, between ‘Paradise Lost’ and ‘Paradise Regained’. Over against the restitution of the church it advocates its reformation and instead of a new creation it expects the redemption of the fallen world from the power of sin and death

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Positionsregelung eines elektronisch kommutierten Motors

Zusammenfassung: Im Rahmen des Projektes flexible Mehrfingergreifer werden elektronisch kommutierte Motoren als Aktoren eingesetzt. Der Aufbau eines Positionsregelungssystems mit dem Faulhabermotor SBL1 2444 war Aufgabe der Studienarbeit. Zur Ansteuerung des Motors wurde ein drehzahlgeregelter Servoverstärker aufgebaut. Zur Erfassung der Meßwerte Rotorposition, Drehzahl Drehrichtung wurde ein Interface für einen IBM-kompatiblen PC entwickelt. Als Sensoren zur Erfassung der Meßwerte werden dabei wahlweise ein optischer Inkrementalgeber oder die im Motor integrierten Hallsensoren verwendet. Der Positionsregler ist in der Programmiersprache C auf dem Rechner implementiert worden. Am Abtrieb eines Getriebes mit einer Untersetzung von 1:100 läßt sich bei Verwendung der Hallsensoren eine Winkelauflösung von 0,6 Grad erzielen. Mit dem optischen Inkrementalgeber (ohne Getriebe) erreicht man eine Winkelauflösung von 0,9 Grad