The Virtual Machine (VM) Scaler: An Infrastructure Manager Supporting Environmental Modeling on IaaS Clouds

Infrastructure-as-a-service (IaaS) clouds provide a new medium for deployment of environmental modeling applications. Harnessing advancements in virtualization, IaaS clouds can provide dynamic scalable infrastructure to better support scientific modeling computational demands. Providing scientific modeling as-a-service requires dynamic scaling of server infrastructure to adapt to changing user workloads. This paper presents the Virtual Machine (VM) Scaler, an autonomic resource manager for IaaS Clouds. We have developed VM-Scaler, a REST/JSON-based web services application which supports infrastructure provisioning and management to support scientific modeling for the Cloud Services Innovation Platform (CSIP) [Lloyd et al. 2012]. VM-Scaler harnesses the Amazon Elastic Compute Cloud (EC2) application programming interface to support model- service scalability, cloud management, and infrastructure configuration for supporting modeling workloads. VM-Scaler provides cloud control while abstracting the underlying IaaS cloud from the end user. VM-Scaler is extensible to support any EC2 compatible cloud and currently supports the Amazon public cloud and Eucalyptus private clouds versions 3.1 and 3.3. VM-Scaler provides a platform to improve scientific model deployment by supporting experimentation with: hot spot detection schemes, VM management and placement approaches, and model job scheduling/proxy services

The Virtual Machine (VM) Scaler: An Infrastructure Manager Supporting Environmental Modeling on IaaS Clouds

Infrastructure-as-a-service (IaaS) clouds provide a new medium for deployment of environmental modeling applications. Harnessing advancements in virtualization, IaaS clouds can provide dynamic scalable infrastructure to better support scientific modeling computational demands. Providing scientific modeling as-a-service requires dynamic scaling of server infrastructure to adapt to changing user workloads. This paper presents the Virtual Machine (VM) Scaler, an autonomic resource manager for IaaS Clouds. We have developed VM-Scaler, a REST/JSON-based web services application which supports infrastructure provisioning and management to support scientific modeling for the Cloud Services Innovation Platform (CSIP) [Lloyd et al. 2012]. VM-Scaler harnesses the Amazon Elastic Compute Cloud (EC2) application programming interface to support model- service scalability, cloud management, and infrastructure configuration for supporting modeling workloads. VM-Scaler provides cloud control while abstracting the underlying IaaS cloud from the end user. VM-Scaler is extensible to support any EC2 compatible cloud and currently supports the Amazon public cloud and Eucalyptus private clouds versions 3.1 and 3.3. VM-Scaler provides a platform to improve scientific model deployment by supporting experimentation with: hot spot detection schemes, VM management and placement approaches, and model job scheduling/proxy services

Moving Toward, Moving Against, and Moving Away: An Interpersonal Approach to Construct Validation of the Horney–Coolidge Type Inventory

Karen Horney’s interpersonal theory of adjustment defined three different neurotic trends involving characteristic social behavior and motives: compliant (moving toward people), aggressive (moving against people), and detached (moving away from people). The Horney–Coolidge Type Inventory (HCTI) was developed to assess these trends, but has not been validated using standard methods in the interpersonal perspective. The studies reported here refined the structure of the HCTI, and utilized the structural summary method (SSM) to identify relationships of the three shortened HCTI trend scales with the interpersonal circumplex (IPC) in single university (n = 514) and multisite university (n = 3,283) samples. Results across both studies confirmed predicted interpersonal characteristics of each trend: Compliance was associated with warm submissiveness, aggression was associated with hostile dominance, and detachment was associated with hostile or cold submissiveness. However, analyses of facets within the three HCTI trend domains revealed significant differences. Results are discussed as a potential guide to further refinement of assessments of the Horney maladaptive trends, and support inclusion of Horney’s model in current interpersonal theory

Data Provisioning for the Object Modeling System (OMS)

The Object Modelling System (OMS) platform supports initiatives to build or re - factor agro - environmental models and deploy them in different business contexts as model services on cloud computing platforms. Whether traditional desktop, client - server, or emerging cloud deployments, success especially at the enterprise level relies on stable and efficient data provisioning to the models. In this paper we describe recent experience and trends with tools and services to supply data for model inputs. Solutions range from simple pre - processing tools to data services deployed to cloud platforms. Also, systematic, sustained data stewardship and alignment with standards organizations impart stability to data provisioning efforts

An Exploratory Investigation on the Invasiveness of Environmental Modeling Frameworks

Environmental modeling frameworks provide an array of useful features that model developers can harness when implementing models. Each framework differs in how it provides features to a model developer via its Application Programming Interface (API). Environmental modelers harness framework features by calling and interfacing with the framework API. As modelers write model code, they make framework-specific function calls and use framework specific data types for achieving the functionality of the model. As a result of this development approach, model code becomes coupled with and dependent on a specific modeling framework. Coupling to a specific framework makes migration to other frameworks and reuse of the code outside the original framework more difficult. This complicates collaboration between model developers wishing to share model code that ma y have been developed in a variety of languages and frameworks. This paper provides initial results of an exploratory investigation on the invasiveness of environmental modeling frameworks. Invasiveness is defined as th e coupling between application (i.e., model) and framework code used to implement the model. By comparing the implementation of an environmental model across several modeling frameworks, we aim to better understand the consequences of framework design. How frameworks present functionality to modelers through APIs can lead to consequences with respect to model development, model maintenance, reuse of model code, and ultimately collaboration among model developers. By measuring framework invasiveness, we hope to provide environmental modeling framework developers and environmental modelers with valuable in formation to assist in future development efforts. Eight implementations (six framework-based) of Thornthwaite, a simple water balance model, were made in a variety of environmental modeling frameworks and languages. A set of software metrics were proposed and applied to measure invasiveness between model implementation code and framework code. The metrics produced a rank ordering of invasiveness for the framework-based implementations of Thornthwaite. We compared model invasiveness results with several popular software metrics including size in lines of code (LOC), cyclomatic complexity, and object oriented coupling. To investigate software quality implications of framework invasiveness we checked for relationships between the Chidamber and Kemerer (1994) object oriented software metrics and our framework invasiveness measures. For the six framework-based implementations of Thornthwaite we found a five-fold variation in code size (LOC). We observed up to a seven-fold variation in total cyclomatic complexity, and a two to three-fold variation in object oriented coupling. For the model implementations we found that total size, total complexity, and total coupling all had a significant positive correlation. The raw count version of our invasiveness measures correlated with application size (LOC), total cyclomatic complexity, total efferent coupling (fan out) and total afferent coupling (fan in). Large size, complexity, and high levels of coupling between units (classes, modules) in a software system are often cited in software engineering as causes of high maintenance costs due to poor understandability and flexibility of the code. This study provides initial results but further investigation is desired to evaluate the utility of our invasiveness measurement approach as well as the software quality implications of framework invasiveness

Environmental Modeling Framework Invasiveness: Analysis and Implications

Environmental modeling frameworks support scientific model development by providing an Application Programming Interface (API) which model developers use to implement models. This paper presents results of an investigation on the framework invasiveness of environmental modeling frameworks. Invasiveness is defined as the quantity of dependencies between model code and the modeling framework. This research investigates relationships between invasiveness and the quality of modeling code. Additionally, we investigate the relationship between invasiveness and two common framework designs (lightweight vs. heavyweight). Five metrics to measure framework invasiveness were proposed and applied to measure invasiveness between model and framework code of several implementations of Thornthwaite and the Precipitation-Runoff Modeling System (PRMS), two hydrological models. Framework invasiveness measurements were compared with existing software metrics including size (lines of code), cyclomatic complexity, and object-oriented coupling with generally positive correlations being found. We found that models with lower framework invasiveness tended to be smaller, less complex, and have lower coupling. In addition, the lightweight framework implementations of the Thornthwaite and PRMS models were less invasive than the heavyweight framework model implementations. Our initial results suggest that framework invasiveness is undesirable for model code quality and that lightweight frameworks may help reduce invasiveness

Examination of a blood-brain barrier targeting β-galactosidase-monoclonal antibody fusion protein in a murine model of GM1-gangliosidosis

GM1-gangliosidosis is a lysosomal disease resulting from a deficiency in the hydrolase β-galactosidase (β-gal) and subsequent accumulation of gangliosides, primarily in neuronal tissue, leading to progressive neurological deterioration and eventually early death. Lysosomal diseases with neurological involvement have limited non-invasive therapies due to the inability of lysosomal enzymes to cross the blood-brain barrier (BBB). A novel fusion enzyme, labeled mTfR-GLB1, was designed to act as a ferry across the BBB by fusing β-gal to the mouse monoclonal antibody against the mouse transferrin receptor and tested in a murine model of GM1-gangliosidosis (β-ga

Pharmacological Targeting of Native CatSper Channels Reveals a Required Role in Maintenance of Sperm Hyperactivation

The four sperm-specific CatSper ion channel proteins are required for hyperactivated motility and male fertility, and for Ca2+ entry evoked by alkaline depolarization. In the absence of external Ca2+, Na+ carries current through CatSper channels in voltage-clamped sperm. Here we show that CatSper channel activity can be monitored optically with the [Na+]i-reporting probe SBFI in populations of intact sperm. Removal of external Ca2+ increases SBFI signals in wild-type but not CatSper2-null sperm. The rate of the indicated rise of [Na+]i is greater for sperm alkalinized with NH4Cl than for sperm acidified with propionic acid, reflecting the alkaline-promoted signature property of CatSper currents. In contrast, the [Na+]i rise is slowed by candidate CatSper blocker HC-056456 (IC50 ∼3 µM). HC-056456 similarly slows the rise of [Ca2+]i that is evoked by alkaline depolarization and reported by fura-2. HC-056456 also selectively and reversibly decreased CatSper currents recorded from patch-clamped sperm. HC-056456 does not prevent activation of motility by HCO3− but does prevent the development of hyperactivated motility by capacitating incubations, thus producing a phenocopy of the CatSper-null sperm. When applied to hyperactivated sperm, HC-056456 causes a rapid, reversible loss of flagellar waveform asymmetry, similar to the loss that occurs when Ca2+ entry through the CatSper channel is terminated by removal of external Ca2+. Thus, open CatSper channels and entry of external Ca2+ through them sustains hyperactivated motility. These results indicate that pharmacological targeting of the CatSper channel may impose a selective late-stage block to fertility, and that high-throughput screening with an optical reporter of CatSper channel activity may identify additional selective blockers with potential for male-directed contraception

The effect of lengthening contractions on neuromuscular junction structure in adult and old mice

Skeletal muscles of old mice demonstrate a profound inability to regenerate fully following damage. Such a failure could be catastrophic to older individuals where muscle loss is already evident. Degeneration and regeneration of muscle fibres following contraction-induced injury in adult and old mice are well characterised, but little is known about the accompanying changes in motor neurons and neuromuscular junctions (NMJs) following this form of injury although defective re-innervation of muscle following contraction-induced damage has been proposed to play a role in sarcopenia. This study visualised and quantified structural changes to motor neurons and NMJs in Extensor digitorum longus (EDL) muscles of adult and old Thy1-YFP transgenic mice during regeneration following contraction-induced muscle damage. Data demonstrated that the damaging contraction protocol resulted in substantial initial disruption to NMJs in muscles of adult mice, which was reversed entirely within 28 days following damage. In contrast, in quiescent muscles of old mice, ∼15 % of muscle fibres were denervated and ∼80 % of NMJs showed disruption. This proportion of denervated and partially denervated fibres remained unchanged following recovery from contraction-induced damage in muscles of old mice although ∼25 % of muscle fibres were completely lost by 28 days post-contractions. Thus, in old mice, the failure to restore full muscle force generation that occurs following damage does not appear to be due to any further deficit in the percentage of disrupted NMJs, but appears to be due, at least in part, to the complete loss of muscle fibres following damag