Framework Programmable Platform for the Advanced Software Development Workstation: Preliminary system design document

The Framework Programmable Software Development Platform (FPP) is a project aimed at combining effective tool and data integration mechanisms with a model of the software development process in an intelligent integrated software environment. Guided by the model, this system development framework will take advantage of an integrated operating environment to automate effectively the management of the software development process so that costly mistakes during the development phase can be eliminated. The focus here is on the design of components that make up the FPP. These components serve as supporting systems for the Integration Mechanism and the Framework Processor and provide the 'glue' that ties the FPP together. Also discussed are the components that allow the platform to operate in a distributed, heterogeneous environment and to manage the development and evolution of software system artifacts

Editorial

Which Birds? Searching the Scripture

Insecticides Based on Differences in Metabolic Pathways

Insects have been major pests of humankind at least since the beginning of recorded history. To this day insects continue to cause problems in domestic, agricultural, and health situations. It is no wonder that people have continually sought new solutions to controlling insect pests. Even when new control methods are discovered and established, insects evolve into resistant species so that the method is only of real value for a few brief years. Modern science and technology are now enabling scientists to tear away the fabric that has so long masked physiological and biochemical events critical to insects. Armed with this new knowledge, researchers should be able to develop novel control strategies that focus on key physiological, biological, and biochemical events such that they can be altered, influenced, disrupted, and/or inhibited. Three promising areas that may lead or are currently leading to new insect control methods are the cuticle, prostaglandins, and steroids. We discuss each of these areas in regard to their biological significance, current research, metabolic inhibitors and their modes of action

Psychoactive substances and the political ecology of mental distress

The goal of this paper is to both understand and depathologize clinically significant mental distress related to criminalized contact with psychoactive biotic substances by employing a framework known as critical political ecology of health and disease from the subdiscipline of medical geography. The political ecology of disease framework joins disease ecology with the power-calculus of political economy and calls for situating health-related phenomena in their broad social and economic context, demonstrating how large-scale global processes are at work at the local level, and giving due attention to historical analysis in understanding the relevant human-environment relations. Critical approaches to the political ecology of health and disease have the potential to incorporate ever-broadening social, political, economic, and cultural factors to challenge traditional causes, definitions, and sociomedical understandings of disease. Inspired by the patient-centered medical diagnosis critiques in medical geography, this paper will use a critical political ecology of disease approach to challenge certain prevailing sociomedical interpretations of disease, or more specifically, mental disorder, found in the field of substance abuse diagnostics and the related American punitive public policy regimes of substance abuse prevention and control, with regards to the use of biotic substances. It will do this by first critically interrogating the concept of "substances" and grounding them in an ecological context, reviewing the history of both the development of modern substance control laws and modern substance abuse diagnostics, and understanding the biogeographic dimensions of such approaches. It closes with proposing a non-criminalizing public health approach for regulating human close contact with psychoactive substances using the example of cannabis use

Reproductive development and performance of inbred and crossbred boars

This report includes much of the material presented by the senior author as a doctoral dissertation--P. [3].Digitized 2007 AES.Includes bibliographical references (page 56)

Partnership, ownership and control: the impact of corporate governance on employment relations

Prevailing patterns of dispersed share ownership and rules of corporate governance for UK listed companies appear to constrain the ability of managers to make credible, long-term commitments to employees of the kind needed to foster effective labour-management partnerships. We present case study evidence which suggests that such partnerships can nevertheless emerge where product market conditions and the regulatory environment favour a stakeholder orientation. Proactive and mature partnerships may also be sustained where the board takes a strategic approach to mediating between the claims of different stakeholder groups, institutional investors are prepared to take a long-term view of their holdings, and strong and independent trade unions are in a position to facilitate organisational change

Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): Exome sequencing of trios, monozygotic twins and tumours

BACKGROUND: Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is thought to be a genetic disease caused by de novo mutations, though causative mutations have yet to be identified. We searched for de novo coding mutations among a carefully-diagnosed and clinically homogeneous cohort of 35 ROHHAD patients. METHODS: We sequenced the exomes of seven ROHHAD trios, plus tumours from four of these patients and the unaffected monozygotic (MZ) twin of one (discovery cohort), to identify constitutional and somatic de novo sequence variants. We further analyzed this exome data to search for candidate genes under autosomal dominant and recessive models, and to identify structural variations. Candidate genes were tested by exome or Sanger sequencing in a replication cohort of 28 ROHHAD singletons. RESULTS: The analysis of the trio-based exomes found 13 de novo variants. However, no two patients had de novo variants in the same gene, and additional patient exomes and mutation analysis in the replication cohort did not provide strong genetic evidence to implicate any of these sequence variants in ROHHAD. Somatic comparisons revealed no coding differences between any blood and tumour samples, or between the two discordant MZ twins. Neither autosomal dominant nor recessive analysis yielded candidate genes for ROHHAD, and we did not identify any potentially causative structural variations. CONCLUSIONS: Clinical exome sequencing is highly unlikely to be a useful diagnostic test in patients with true ROHHAD. As ROHHAD has a high risk for fatality if not properly managed, it remains imperative to expand the search for non-exomic genetic risk factors, as well as to investigate other possible mechanisms of disease. In so doing, we will be able to confirm objectively the ROHHAD diagnosis and to contribute to our understanding of obesity, respiratory control, hypothalamic function, and autonomic regulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13023-015-0314-x) contains supplementary material, which is available to authorized users

Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model

BACKGROUND: Both cell-associated and cell-free HIV virions are present in semen and cervical secretions of HIV-infected individuals. Thus, topical microbicides may need to inactivate both cell-associated and cell-free HIV to prevent sexual transmission of HIV/AIDS. To determine if the mild acidity of the healthy vagina and acid buffering microbicides would prevent transmission by HIV-infected leukocytes, we measured the effect of pH on leukocyte motility, viability and intracellular pH and tested the ability of an acidic buffering microbicide (BufferGel(®)) to prevent the transmission of cell-associated HIV in a HuPBL-SCID mouse model. METHODS: Human lymphocyte, monocyte, and macrophage motilities were measured as a function of time and pH using various acidifying agents. Lymphocyte and macrophage motilities were measured using video microscopy. Monocyte motility was measured using video microscopy and chemotactic chambers. Peripheral blood mononuclear cell (PBMC) viability and intracellular pH were determined as a function of time and pH using fluorescent dyes. HuPBL-SCID mice were pretreated with BufferGel, saline, or a control gel and challenged with HIV-1-infected human PBMCs. RESULTS: Progressive motility was completely abolished in all cell types between pH 5.5 and 6.0. Concomitantly, at and below pH 5.5, the intracellular pH of PBMCs dropped precipitously to match the extracellular medium and did not recover. After acidification with hydrochloric acid to pH 4.5 for 60 min, although completely immotile, 58% of PBMCs excluded ethidium homodimer-1 (dead-cell dye). In contrast, when acidified to this pH with BufferGel, a microbicide designed to maintain vaginal acidity in the presence of semen, only 4% excluded dye at 10 min and none excluded dye after 30 min. BufferGel significantly reduced transmission of HIV-1 in HuPBL-SCID mice (1 of 12 infected) compared to saline (12 of 12 infected) and a control gel (5 of 7 infected). CONCLUSION: These results suggest that physiologic or microbicide-induced acid immobilization and killing of infected white blood cells may be effective in preventing sexual transmission of cell-associated HIV

An EGF-like Protein Forms a Complex with PfRh5 and Is Required for Invasion of Human Erythrocytes by Plasmodium falciparum

Invasion of erythrocytes by Plasmodium falciparum involves a complex cascade of protein-protein interactions between parasite ligands and host receptors. The reticulocyte binding-like homologue (PfRh) protein family is involved in binding to and initiating entry of the invasive merozoite into erythrocytes. An important member of this family is PfRh5. Using ion-exchange chromatography, immunoprecipitation and mass spectroscopy, we have identified a novel cysteine-rich protein we have called P. falciparum Rh5 interacting protein (PfRipr) (PFC1045c), which forms a complex with PfRh5 in merozoites. Mature PfRipr has a molecular weight of 123 kDa with 10 epidermal growth factor-like domains and 87 cysteine residues distributed along the protein. In mature schizont stages this protein is processed into two polypeptides that associate and form a complex with PfRh5. The PfRipr protein localises to the apical end of the merozoites in micronemes whilst PfRh5 is contained within rhoptries and both are released during invasion when they form a complex that is shed into the culture supernatant. Antibodies to PfRipr1 potently inhibit merozoite attachment and invasion into human red blood cells consistent with this complex playing an essential role in this process