Marcos S. Ferreira

Discovery of LASSBio-772, a 1,3-benzodioxole N-phenylpiperazine derivative with potent alpha 1A/D-Adrenergic receptor blocking properties

We described herein the discovery of 1-(2-(benzo[d] [1,3]dioxol-6-yl)ethyl)-4-(2-methoxyphenyl) piperazine (LASSBio-772), as a novel potent and selective alpha 1A/1D adrenoceptor (AR) antagonist selected after screening of functionalized N-phenylpiperazine derivatives in phenylephrine-induced vasoconstriction of rabbit aorta rings. The affinity of LASSBio-772 for alpha 1A and alpha 1B AR subtypes was determined through displacement of [(3)H]prazosin binding. We obtained Ki values of 0.14 nM for the alpha 1A-AR, similar to that displayed by tamsulosin (K(i) = 0.13 nM) and 5.55 nM for the alpha 1B-AR, representing a 40-fold higher affinity for alpha 1A-AR. LASSBio-772 also presented high affinity (K(B) = 0.025 nM) for the alpha 1D-AR subtype in the functional rat aorta assay, showing to be equipotent to tamsulosin (K(B) = 0.017 nM).

Counteracting effect of glycyrrhizin on the hemostatic abnormalities induced by Bothrops jararaca snake venom

1 Envenomation by the snake Bothrops jararaca is typically associated with hemostatic abnormalities including pro‐ and anticoagulant disturbances. Glycyrrhizin (GL) is a plant‐derived thrombin inhibitor that also exhibits in vivo antithrombotic properties. Here, we evaluated the ability of GL to counteract the hemostatic abnormalities promoted by B. jararaca venom. 2 GL inhibited the human fibrinogen clotting (IC50=∼1.0 mg ml−1; 1.2 mM), H‐D‐phenylalanyl‐L‐pipecolyl‐L‐arginine‐p‐nitroanilide dihydrochloride hydrolysis (IC50=∼0.4 mg ml−1; 0.47 mM) and platelet aggregation (IC50=∼0.28 mg ml−1; 0.33 mM) induced by B. jararaca venom, in vitro. 3 The in vivo effect of GL was tested in rats using a model of venous thrombosis in which intravenous (i.v.) administration of B. jararaca venom (100 μg kg−1) produced in all animals a thrombus with a mean weight of 10.6±1.7 mg. 4 Prior administration of GL (180 mg kg−1) or antibothropic serum (27 μl kg−1) inhibited thrombus formation by 86 and 67%, respectively. Remarkably, co‐administration of ineffective doses of GL and antibothropic serum markedly decreased thrombus weight, suggesting a synergistic effect. 5 Co‐administration of GL with antibothropic serum abolished venom‐induced bleeding. Ex vivo clotting times showed that rat plasma was non‐clotting after i.v. administration of B. jararaca venom. Treatment with GL, antibothropic serum or both before venom administration efficiently prevented this abnormality. 6 Altogether, we demonstrate here that GL prevents both in vitro and in vivo venom‐induced changes in hemostasis, suggesting a potential antiophidic activity.

Bothrojaracin, a Bothrops jararaca Snake Venom-Derived (Pro)Thrombin Inhibitor, as an Anti-Thrombotic Molecule

Bothrojaracin (BJC) is a selective and potent thrombin inhibitor (KD = 0.6 nM) which also binds to prothrombin on proexosite I (KD = 175 nM). Incubation of BJC with human or rat plasma produced a band that co-migrates with purified prothrombin-BJC complex. We further analyzed the in vivo anti-thrombotic effect of BJC on a venous thrombosis model in rats that combines stasis and hypercoagulability. The administration of 1 mg/kg (i.v.) doses of BJC decreased thrombus weight by ∼95%. Evaluation of the in vivo effect of BJC in mice using a pulmonary thromboembolism model induced by thrombin showed that BJC protects 100% of mice from death. Altogether, our data show that BJC is a potent anti-thrombotic agent that could further help the development of new prothrombin-directed drugs.

Information Needs for Meeting Facilitation

In many group work settings, meetings take up a reasonable amount of time and often do not achieve satisfactory outcomes. One of the techniques that has been introduced to ensure meetings run smoothly and reach their goals places an individual in the role of meeting facilitator. Facilitation involves putting together the meeting agenda, designing meeting dynamics and overseeing the meeting at run time, to ensure goals are met. This may involve intervening or adjusting meeting structure to produce desired results. Thus, a facilitator should be able to act according to perceived group dynamics or problems. In this paper, we investigate information needs during facilitation activities. Our goal is to be able to construct systems that provide information to the facilitator so he or she can decide when to act and what to do.

AgendaBuilder: A system to support meeting design

Meetings take a large amount of time, and frequently, meeting facilitators are called in to help steer the meeting in the right direction. Unfortunately, facilitation is still something of an art. To assist facilitators, the thinkLet technique has been proposed. Through the use of thinkLets, facilitators may plan the meeting beforehand, deciding which activities to perform at each point. However, designing a meeting is not an easy task, especially for novice facilitators. In this paper we present AgendBuilder, a system to assist the design of meetings, electronic or otherwise, using thinkLets and compatibility rules. The system helps facilitators select and link thinkLets together in and orderly fashion, designing the meeting in the process.

Time Based Activity Profiles to Recommend Partnership in a P2P Network

In large communities, finding experts or partners can sometimes be hard. Normally, to find new partners one asks for recommendations from known acquaintances. This is a form of social navigation, whereby one searches for others in the network, who might fit required profiles. Time is an important factor in this type of situation, as needs, interests and expertise levels change rapidly. This paper presents a peer-to-peer system to assist social network navigation and search. It builds user profiles through an analysis of ongoing activities that takes time into account, and matches these to find opportunities for collaboration.

Tools to Assist Meeting Planning

Meetings take up a large amount of time, especially at the upper managerial levels. To help meetings progress smoothly and reach desired goals, meeting facilitators are frequently called in. Facilitators have at their disposal a number of techniques, including thinkLets. Through the use of thinkLets, facilitators can plan the meeting beforehand, deciding which activities to perform at each point. However, even with the use of thinkLets, designing a meeting is not an easy task, in particular for novice facilitators. A number of considerations must be made when selecting activities and designing the meeting dynamics. In this paper, the authors discuss this problem and present a framework and a system to assist the design of meetings, electronic or otherwise, using thinkLets and compatibility rules. The framework implements rules to help facilitators select and link thinkLets together in and orderly fashion, designing the meeting in the process.

Algebraic solutions of Jacobi equations

We propose an algorithm to compute exactly the algebraic solutions of Jacobi equations over the projective plane.

Temporal Profiling for Opportunistic Partnership Recommendation

Locating experts or work partners in large communities can sometimes be hard. The most common way of accomplishing this task is through recommendations from known acquaintances. This networked search for others who fit required profiles is a form of social navigation. However, needs, interests and expertise change rapidly, so time is an important factor in this type of situation, and recommendations need to be time-sensitive. This paper presents a peer-to-peer system for social network navigation, which builds user profiles through a temporal analysis of ongoing activities and matches these to find opportunities for collaboration.