Antithrombotic potency of hirudin is increased in nonhuman primates by fibrin targeting

BACKGROUND: Inhibition of thrombin by either the indirect thrombin inhibitor heparin or by more potent direct thrombin inhibitors such as hirudin reduces thrombus formation after arterial injury. The present study was designed to determine if a fibrin-specific thrombin inhibitor could, by local thrombin inhibition, prevent thrombosis more effectively. METHODS AND RESULTS: We first studied antithrombotic potency in vitro, comparing fibrin-targeted hirudin (recombinant hirudin covalently linked to the Fab' fragment of the anti-fibrin monoclonal antibody 59D8) to recombinant hirudin in baboon plasma. Fibrin-targeted hirudin was nine times more effective than recombinant hirudin in inhibiting fibrin deposition on experimental clot surfaces in baboon plasma (P < .01). The potency of fibrin-targeted hirudin was then compared with that of recombinant hirudin in a baboon model of thrombus formation. 111In-labeled platelet deposition was measured in a synthetic graft segment of an extracorporeal arteriovenous shunt in control animals and in animals receiving either fibrin-targeted hirudin or hirudin. In these experiments, fibrin-targeted hirudin was 10-fold more potent than hirudin in inhibiting platelet deposition and thrombus formation (P < .05). CONCLUSIONS: These data indicate that targeting a thrombin inhibitors such as hirudin to an epitope present in thrombi results in increased antithrombotic potency.     

Non-financial barriers to combined heat and power in the United States - A qualitative study

The economic viability of new energy technologies is held as a central tenet to their future deployment; conventional wisdom posits economically rational decision-makers will readily invest in proven low-risk and affordable technologies. But what happens when this is not true. This paper examines the non-financial barriers facing economically viable Combined Heat and Power (CHP) projects. CHP is a mature and lower carbon technology that efficiently uses waste heat from thermal electricity generation; CHP can also provide flexibility services to help integrate variable renewable resources. CHP is low risk and many industrialized countries, particularly those in colder climates in Northern Europe and Russia, generate as much as 50% of their electricity and heat needs from CHP, but United States deployment remains low and investment hurdle rates high. While lower U.S. energy costs make some projects un-economic, many economically-viable CHP projects are stalled or killed by non-financial barriers. To better understand why financially viable CHP projects are not getting built, developers, owners and operators, regulators, and other stakeholders of this technology were interviewed and three major barriers emerged a) the business model of the electrical utility b) negative subjective impressions and c) challenges in allocating the risks and benefits.     

Visualizing green oil in live algal cells

We report here that BODIPY 505/515, a green lipophilic fluorescent dye, serves as an excellent vital stain for the oil-containing lipid bodies of live algal cells. BODIPY 505/515 vital staining can be used in combination with fluorescent activated cell sorting to detect and isolate algal cells possessing high lipid content.     

Challenges in securing the domain name system

Two main security threats exist for DNS in the context of query/response transactions. Attackers can spoof authoritative name servers responding to DNS queries and alter DNS responses in transit through man-in-the-middle attacks, and alter the DNS responses stored in caching name servers. The IETF has defined the digital signature-based DNSSEC for protecting DNS query/response transactions through a series of requests for comments.     

Associative symmetry versus independent associations in the memory for object-location associations.

The formation of associations between objects and locations is a vital aspect of episodic memory. More specifically, remembering the location where one experienced an object and, vice versa, the object one encountered at a specific location are both important elements for the memory of an event. Whether episodic associations are holistic representations of individual components or whether there are unidirectional, separately modifiable connections between them has been investigated nearly exclusively using verbal stimuli. A preliminary conclusion concerning this controversy is that verbal associations are, at least, highly correlated (M. J. Kahana, 2002). This theoretical debate, which in the past has undergone a major empirical effort, is still of relevance for the concurrent global matching models of associative memory (S. E. Clark & S. D. Gronlund, 1996). The authors used variations of a novel object-location learning paradigm to complement the accumulated evidence regarding the nature of episodic associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Access to Pediatric Neurologists - Will Telemedicine Close the Gap?

Many times both physicians and patients take for granted that they are qualified to treat certain ages and certain conditions. Neurological conditions are diagnosed and treated by neurologists, pediatric neurologists, and neurosurgeons. What is the difference and why does it matter? It is a balancing act of risk and benefit and the physician’s obligation to know her/his limitations. Telemedicine may play a key role in enabling a greater access to pediatric neurologists. If telemedicine becomes more available, then access even in more remote areas without child neurologists may be possible. As this article discusses, there may be certain limitations to using telemedicine, which is distinguishable from telehealth, in relation to pediatric neurology. This article examines the type of neurological physician that is the most appropriate; the availability of and access to pediatric neurologists; and the applicability of telemedicine to the diagnosis and treatment of pediatric neurological conditions.     

Cognitive and learning difficulties and how they affect access to IT systems

In October 2005, the IBM Human Ability and Accessibility Center and T.J. Watson Research Center hosted a symposium on “cognitive and learning difficulties and how they affect access to IT systems”. The central premise of the symposium was the recognition that cognitive and learning difficulties have a profound impact on a person’s ability to interact with information technology (IT) systems, but that little support is currently being offered by those systems. By bringing together internationally renowned experts from a variety of different, but complementary, research fields, the symposium aimed to provide a complete overview of the issues related to this topic. This paper summarises the discussions and findings of the symposium.     

Constrained clustering as an optimization method

A deterministic annealing approach to clustering is derived on the basis of the principle of maximum entropy. This approach is independent of the initial state and produces natural hierarchical clustering solutions by going through a sequence of phase transitions. It is modified for a larger class of optimization problems by adding constraints to the free energy. The concept of constrained clustering is explained, and three examples are are given in which it is used to introduce deterministic annealing. The previous clustering method is improved by adding cluster mass variables and a total mass constraint. The traveling salesman problem is reformulated as constrained clustering, yielding the elastic net (EN) approach to the problem. More insight is gained by identifying a second Lagrange multiplier that is related to the tour length and can also be used to control the annealing process. The open path constraint formulation is shown to relate to dimensionality reduction by self-organization in unsupervised learning. A similar annealing procedure is applicable in this case as well     

Reconceptualizing classroom-based research in computers and composition

In this article, Webb maps out three dominant forms of research that have been undertaken in the field of computers and composition—theoretical, case studies, and limited quantitative. She then identifies a fourth mode that has begun to appear—a multimodal approach. Arguing for ways in which this method could help us answer research questions that have been previously unanswerable by other research methods, she calls for the field to reconsider incorporating this multimodal approach more within our research studies.