CCN2/CTGF is required for matrix organization and to protect growth plate chondrocytes from cellular stress

CCN2 (connective tissue growth factor (CTGF/CCN2)) is a matricellular protein that utilizes integrins to regulate cell proliferation, migration and survival. The loss of CCN2 leads to perinatal lethality resulting from a severe chondrodysplasia. Upon closer inspection of Ccn2 mutant mice, we observed defects in extracellular matrix (ECM) organization and hypothesized that the severe chondrodysplasia caused by loss of CCN2 might be associated with defective chondrocyte survival. Ccn2 mutant growth plate chondrocytes exhibited enlarged endoplasmic reticula (ER), suggesting cellular stress. Immunofluorescence analysis confirmed elevated stress in Ccn2 mutants, with reduced stress observed in Ccn2 overexpressing transgenic mice. In vitro studies revealed that Ccn2 is a stress responsive gene in chondrocytes. The elevated stress observed in Ccn2-/- chondrocytes is direct and mediated in part through integrin α5. The expression of the survival marker NFκB and components of the autophagy pathway were decreased in Ccn2 mutant growth plates, suggesting that CCN2 may be involved in mediating chondrocyte survival. These data demonstrate that absence of a matricellular protein can result in increased cellular stress and highlight a novel protective role for CCN2 in chondrocyte survival. The severe chondrodysplasia caused by the loss of CCN2 may be due to increased chondrocyte stress and defective activation of autophagy pathways, leading to decreased cellular survival. These effects may be mediated through nuclear factor κB (NFκB) as part of a CCN2/integrin/NFκB signaling cascade.

Occupational beryllium exposure: Reconciling federal policies, regulations and contractor implementation guides to protect worker health

Beryllium is a widely distributed, highly toxic metal. When beryllium particulates enter the body, the body's defense mechanisms are engaged. When the body's defenses cannot easily remove the particulates, then a damage and repair cycle is initiated. This cycle produces chronic beryllium disease (CBD), a progressive, fibrotic respiratory involvement which eventually suffocates exposed individuals. ^ Beryllium disease is an occupational disease, and as such it can be prevented by limiting exposures. In the 1940s journalists reported beryllium deaths at Atomic Energy Commission (AEC) facilities, the Department of Energy's (DOE) predecessor organization. These reports energized public pressure for exposure limits, and in 1949 AEC implemented a 2 μg/m3 permissible exposure limit (PEL). ^ The limits appeared to stop acute disease. In contrast, CBD has a long latency period between exposure and diagnosable disease, between one and thirty years. The lack of immediate adverse health consequences masked the seriousness of chronic disease and pragmatically removed CBD from AEC/DOE's political concern. ^ Presently the PEL for beryllium at DOE sites remains at 2 μg/m 3. This limit does not prevent CBD. This conclusion has long been known, although denied until recently. In 1999 DOE acknowledged the limit's ineffectiveness in its federal regulation governing beryllium exposure, 10 CFR 850. ^ Despite this admission, the PEL has not been reduced. The beryllium manufacturer and AEC/DOE have a history of exerting efforts to maintain and protect the status quo. Primary amongst these efforts has been creation and promotion of disinformation within peer reviewed health literature which discusses beryllium, exposures, health effects and treatment, and targeting graduate school students so that their perspective is shaped early. ^ Once indoctrinated with incorrect information, professionals tend to overlook aerosol and respiratory mechanics, immunologic and carcinogenic factors. They then apply tools and perspectives derived from the beryllium manufacturer and DOE's propaganda. Conclusions drawn are incorrect. The result is: health research and associated policy is conducted with incorrect premises. Effective disease management practices are not implemented. ^ Public health protection requires recognition of the disinformation and its implications. When disinformation is identified, then effective health policies and practices can be developed and implemented. ^

Implementing the Global Plan of Action on workers' health: Components to protect health care workers

Health care workers are at risk for percutaneous injuries and infection with blood born pathogens due to needle stick injuries with contaminated needles. The most common pathogens transmitted are hepatitis B, and C and HIV/AIDS. According to the WHO Global Plan of Action (GPA) a large gap exist between and within countries with regards to the health status of workers and their exposure to occupational risk. Less than 15% of the world's work forces have access to occupational health services despite the availability of effective interventions that can prevent occupational hazards, or protect and promote health in the workplace. The 2006 World Health Report declared that there is a global crisis in the health care work force. 1 in 400 of the world's health care workers work in Sub-Saharan Africa. 1 in 3 work in the U.S or Canada. The shortage of health care workers is worst in Southeast Asia and Sub-Saharan Africa. These countries have the highest burden of exposure to contaminated sharps. They rarely, if ever monitor the exposure or health impact of occupational ailments and injuries on workers. Many injuries are unreported. Occupational health services in the developing world are virtually non existent. Many health care workers leave their home countries and go to work in other countries where the working conditions, occupational services included, are better. The inability of countries to provide the necessary numbers of health care workers to provide a high level of health coverage is a threat to national and international public health security. Immunizing health care workers against hepatitis B and providing them PEP, PPE, education and safety training is an essential part of increasing and maintaining the numbers of health care workers in the critical shortage areas. ^

Targeted immunization to protect infants against pertussis in the United States

Pertussis is an infectious disease caused by the bacteria Bordetella pertussis, and is associated with a serious respiratory infection, a prolonged cough, and can require hospitalization. A vaccine for adolescents and adults has been available since 2005. This paper examines one recommended immunization strategy to prevent pertussis among infants, called “cocooning.” The strategy focuses on creating immunity among adult caregivers so they serve as a protective cocoon to the newborns, who are too young to be vaccinated. This paper looks at relevant studies summarizing implementation of cocooning strategies and addresses the question – Does the research literature support the view of using cocooning as an effective strategy to prevent pertussis in infants? After exclusions, 8 studies remained for synthesis. The evidence shows that cocooning is complex strategy and the evidence is mixed when it comes to ensuring an increase in immunization of caregivers. ^

Is it appropriate protective figure "Plant Micro-Reserves" to protect tree species? The example of Betula pendula subsp. fontqueri in "La Garganta de los Caballeros" (Ávila)

The figure of protection "micro-reserves" was created in the Region of Valencia (ANONYMOUS, 1994) with the aim of protecting endangered plant species. This is one of the areas of greatest floristic richness and uniqueness of the western Mediterranean. In this area rare, endemic or threatened vascular flora has a peculiar distribution: they appear to form small fragments spread over the entire region (LAGUNA, 1994; LAGUNA, 2001) The protection of every these small populations of great scientific value has significant challenges. It doesn´t try to protect every species that set out in Annex IV of the by then existing Law 4 / 1989 (repealed in 2007), or to protect to the most ecological level with the creation of Natural Protected Area but an intermediate level: the plant community of small size. According to the decree: “as Micro-Reserve will be declared the natural parcels of land under 20 hectares that contain a high concentration of rare plants, endemic, threatened or of high scientific interest” (ANONYMOUS, 1994) . Of course, the statement of an area as micro-reserve carries certain prohibitions that are harmful to the vegetal community

Cooperative Multi-robot Patrolling: A study of distributed approaches based on mathematical models of game theory to protect infrastructures

El principio de Teoría de Juegos permite desarrollar modelos estocásticos de patrullaje multi-robot para proteger infraestructuras criticas. La protección de infraestructuras criticas representa un gran reto para los países al rededor del mundo, principalmente después de los ataques terroristas llevados a cabo la década pasada. En este documento el termino infraestructura hace referencia a aeropuertos, plantas nucleares u otros instalaciones. El problema de patrullaje se define como la actividad de patrullar un entorno determinado para monitorear cualquier actividad o sensar algunas variables ambientales. En esta actividad, un grupo de robots debe visitar un conjunto de puntos de interés definidos en un entorno en intervalos de tiempo irregulares con propósitos de seguridad. Los modelos de partullaje multi-robot son utilizados para resolver este problema. Hasta el momento existen trabajos que resuelven este problema utilizando diversos principios matemáticos. Los modelos de patrullaje multi-robot desarrollados en esos trabajos representan un gran avance en este campo de investigación. Sin embargo, los modelos con los mejores resultados no son viables para aplicaciones de seguridad debido a su naturaleza centralizada y determinista. Esta tesis presenta cinco modelos de patrullaje multi-robot distribuidos e impredecibles basados en modelos matemáticos de aprendizaje de Teoría de Juegos. El objetivo del desarrollo de estos modelos está en resolver los inconvenientes presentes en trabajos preliminares. Con esta finalidad, el problema de patrullaje multi-robot se formuló utilizando conceptos de Teoría de Grafos, en la cual se definieron varios juegos en cada vértice de un grafo. Los modelos de patrullaje multi-robot desarrollados en este trabajo de investigación se han validado y comparado con los mejores modelos disponibles en la literatura. Para llevar a cabo tanto la validación como la comparación se ha utilizado un simulador de patrullaje y un grupo de robots reales. Los resultados experimentales muestran que los modelos de patrullaje desarrollados en este trabajo de investigación trabajan mejor que modelos de trabajos previos en el 80% de 150 casos de estudio. Además de esto, estos modelos cuentan con varias características importantes tales como distribución, robustez, escalabilidad y dinamismo. Los avances logrados con este trabajo de investigación dan evidencia del potencial de Teoría de Juegos para desarrollar modelos de patrullaje útiles para proteger infraestructuras. ABSTRACT Game theory principle allows to developing stochastic multi-robot patrolling models to protect critical infrastructures. Critical infrastructures protection is a great concern for countries around the world, mainly due to terrorist attacks in the last decade. In this document, the term infrastructures includes airports, nuclear power plants, and many other facilities. The patrolling problem is defined as the activity of traversing a given environment to monitoring any activity or sensing some environmental variables If this activity were performed by a fleet of robots, they would have to visit some places of interest of an environment at irregular intervals of time for security purposes. This problem is solved using multi-robot patrolling models. To date, literature works have been solved this problem applying various mathematical principles.The multi-robot patrolling models developed in those works represent great advances in this field. However, the models that obtain the best results are unfeasible for security applications due to their centralized and predictable nature. This thesis presents five distributed and unpredictable multi-robot patrolling models based on mathematical learning models derived from Game Theory. These multi-robot patrolling models aim at overcoming the disadvantages of previous work. To this end, the multi-robot patrolling problem was formulated using concepts of Graph Theory to represent the environment. Several normal-form games were defined at each vertex of a graph in this formulation. The multi-robot patrolling models developed in this research work have been validated and compared with best ranked multi-robot patrolling models in the literature. Both validation and comparison were preformed by using both a patrolling simulator and real robots. Experimental results show that the multirobot patrolling models developed in this research work improve previous ones in as many as 80% of 150 cases of study. Moreover, these multi-robot patrolling models rely on several features to highlight in security applications such as distribution, robustness, scalability, and dynamism. The achievements obtained in this research work validate the potential of Game Theory to develop patrolling models to protect infrastructures.

A p53-dependent S-phase checkpoint helps to protect cells from DNA damage in response to starvation for pyrimidine nucleotides

Normal mammalian cells arrest primarily in G1 in response to N-(phosphonacetyl)-l-aspartate (PALA), which starves them for pyrimidine nucleotides, and do not generate or tolerate amplification of the CAD gene, which confers resistance to PALA. Loss of p53, accompanied by loss of G1 arrest, permits CAD gene amplification and the consequent formation of PALA-resistant colonies. We have found rat and human cell lines that retain wild-type p53 but have lost the ability to arrest in G1 in response to PALA. However, these cells still fail to give PALA-resistant colonies and are protected from DNA damage through the operation of a second checkpoint that arrests them reversibly within S-phase. This S-phase arrest, unmasked in the absence of the G1 checkpoint, is dependent on p53 and independent of p21/waf1.

Erythropoietin crosses the blood–brain barrier to protect against experimental brain injury

Erythropoietin (EPO), recognized for its central role in erythropoiesis, also mediates neuroprotection when the recombinant form (r-Hu-EPO) is directly injected into ischemic rodent brain. We observed abundant expression of the EPO receptor at brain capillaries, which could provide a route for circulating EPO to enter the brain. In confirmation of this hypothesis, systemic administration of r-Hu-EPO before or up to 6 h after focal brain ischemia reduced injury by ≈50–75%. R-Hu-EPO also ameliorates the extent of concussive brain injury, the immune damage in experimental autoimmune encephalomyelitis, and the toxicity of kainate. Given r-Hu-EPO's excellent safety profile, clinical trials evaluating systemically administered r-Hu-EPO as a general neuroprotective treatment are warranted.

Balancing Wetland Management with the Military: Using Special Area Management Plans (SAMPs) to protect wetlands on U.S. Air Force Installations

U.S. Air Force installations by virtue of their isolation and often remote locations provide protection to critical habitats that would otherwise be susceptible to development and other stressors. While Air Force activities may not always compliment environmental protection, a balance between environmental protection and Air Force requirements must be achieved to minimize conflict. Special Area Management Plans (SAMPs) are a possible solution in the quest to balance conservation with mission requirements. Beale Air Force Base, California is the first military installation to pursue implementation of a SAMP. This project found that SAMP implementation could be a tool to successfully balance conservation efforts with military requirements on other Air Force installations; however, further education on the SAMP process would be required.

Steel Pedestrian Bridge to Protect a Unique Tree

This paper describes the “Variation Guggenheim 3: Mirador de la palmera” project, situated in Daya Vieja (Alicante-Spain). This structure is inspired by the Guggenheim museum of New York and is designed to protect a land-mark palm-tree from wind loads. This six – trunk palm tree was declared monument by the Valencian government in 2012. The structure that now protect it appears to fly around de palm tree creating a helicoidally skywalk made of steel, while retrofitting the lateral trunks of the tree to protect them from collapse. An 18 m. long straight beam starts on the top of this helix, and stretches towards a lookout point that offers a view of the whole village and its surroundings. The reduction of the visual impact of the structure on the tree was a major aim for the project design. The structural elements are as slender as possible to avoid the visual obstruction of tree. They are painted white, while the walkway steel corrugated plate is painted green in order to highlight its neat shape among the blur created by the apparent mess of bars of the supporting structure. The two main piles of this pedestrian bridge were designed in steel and geometrically resemble trees. A Ground Penetrating Radar analysis was performed to detect the palm root location and to decide the best foundation system. Slender cast in-situ steel-concrete micropiles along with a concrete pile-cap, raised some centimeters above the ground level, were used to reduce the damage to the roots. The projected pile-cap is a slender, continuous, circular ring; which geometry resembles a concrete bench. This structure has been a finalist in the Architecture Awards for the 2010-2014 best construction projects, held by the Diputación de Alicante.