Synthesis and pharmacological analysis of high affinity melatonin receptor ligands

We report the synthesis and radioligand binding analysis of a series of naphthalenic melatonin receptor ligands, N-[2-(7-alkoxy-2-methoxy-1-naphthyl)ethyl]propionamide. This series of ligands exhibits subpicomolar binding affinity to both MT1 and MT2 melatonin receptors expressed in chinese hamster ovary (CHO) cells.     

Measuring the charges of QCD jets

We investigate the effects of perturbative branching upon the accuracy with which one can determine the charge of the underlying QCD quantum from the charge structure of a given hadronic jet. We show explicitly how at asymptoticQ ² we lose all such charge information. We investigate these effects at current PETRA energies using the Monte Carlo program of Fox and Wolfram; and find that a reasonably accurate charge determination is still possible at these energies. We suggest the variation of the jet charge structure with multiplicity, at a given energy, as a sensitive probe of the onset of perturbative branching inside jets.     

Impact of the Casimir-Polder potential and Johnson noise on Bose-Einstein condensate stability near surfaces

We investigate the stability of magnetically trapped atomic Bose-Einstein condensates and thermal clouds near the transition temperature at small distances 0.5 microm< or =d< or =10 microm from a microfabricated silicon chip. For a 2 microm thick copper film, the trap lifetime is limited by Johnson noise induced currents and falls below 1 s at a distance of 4 microm. A dielectric surface does not adversely affect the sample until the attractive Casimir-Polder potential significantly reduces the trap depth.     

Llama-derived single-domain antibodies for the detection of botulinum A neurotoxin

Single-domain antibodies (sdAb) specific for botulinum neurotoxin serotype A (BoNT A) were selected from an immune llama phage display library derived from a llama that was immunized with BoNT A toxoid. The constructed phage library was panned using two methods: panning on plates coated with BoNT A toxoid (BoNT A Td) and BoNT A complex toxoid (BoNT Ac Td) and panning on microspheres coupled to BoNT A Td and BoNT A toxin (BoNT A Tx). Both panning methods selected for binders that had identical sequences, suggesting that panning on toxoided material may be as effective as panning on bead-immobilized toxin for isolating specific binders. All of the isolated binders tested were observed to recognize bead-immobilized BoNT A Tx in direct binding assays, and showed very little cross-reactivity towards other BoNT serotypes and unrelated protein. Sandwich assays that incorporated selected sdAb as capture and tracer elements demonstrated that all of the sdAb were able to recognize soluble (“live”) BoNT A Tx and BoNT Ac Tx with virtually no cross-reactivity with other BoNT serotypes. The isolated sdAb did not exhibit the high degree of thermal stability often associated with these reagents; after the first heating cycle most of the binding activity was lost, but the portion of the protein that did refold and recover antigen-binding activity showed only minimal loss on subsequent heating and cooling cycles. The binding kinetics of selected binders, assessed by both an equilibrium fluid array assay as well as surface plasmon resonance (SPR) using toxoided material, gave dissociation constants (K _D ) in the range 2.2 × 10⁻¹¹ to 1.6 × 10⁻¹⁰ M. These high-affinity binders may prove beneficial to the development of recombinant reagents for the rapid detection of BoNT A, particularly in field screening and monitoring applications.     

On the mechanism of the aza-Morita-Baylis-Hillman reaction: ESI-MS interception of a unique new intermediate

Solutions of aza-Morita-Baylis-Hillman (aza-MBH) reactions were directly monitored by ESI(+)-MS(/MS) spectrometry to obtain information on their mechanism. A unique bis-sulfonamide intermediate was intercepted and characterized and, based on this novel species, a mechanism that rationalizes the uniqueness of aza-MBH reactions is proposed.     

A model for πp,Kp and ψp total cross section ratios

We calculate the ratios of πp, Kp and ψp total cross sections utilizing coupled homogeneous linear integral equations supplemented with SU(4) symmetry for the couplings. Kinematic effects arising from mass splitting and t_min effects are crucial. We obtain $\text{σ}{}_{\mathrm{<mtext>\pi </mtext><mtext>p</mtext>}}\text{σ}{}_{\mathrm{<mtext>Kp</mtext>}}\text{≈ 1.7}\text{and}\text{σ}{}_{\mathrm{<mtext>\psi </mtext><mtext>p</mtext>}}\text{σ}{}_{\mathrm{<mtext>\pi </mtext><mtext>p</mtext>}}\text{≈}\text{1}\text{50}$.     

T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei

A series of fourteen 2-aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones was prepared at room temperature by T3P-mediated cyclization of N-phenyl-C-aryl imines with thionicotinic acid, two difficult substrates. The reactions were operationally simple, did not require specialized equipment or anhydrous solvents, could be performed as either two or three component reactions, and gave moderate–good yields as high as 63%. This provides ready access to N-phenyl compounds in this family, which have been generally difficult to prepare. As part of the study, the first crystal structure of neutral thionicotinic acid is also reported, and showed the molecule to be in the form of the thione tautomer. Additionally, the synthesized compounds were tested against T. brucei, the causative agent of Human African Sleeping Sickness. Screening at 50 µM concentration showed that five of the compounds strongly inhibited growth and killed parasites.     

Beliefs and Attitudes Toward Mathematics Among Third- and Fifth-Grade Students: A Descriptive Study

A survey on attitudes toward mathematics of third- and fifth-grade students enrolled in a large urban school district was conducted in the spring of 1994 as part of a review of the mathematics program. Student responses to survey items were analyzed with respect to gender and grade level. Although girls and boys were equally likely to indicate that they like mathematics, in both Grades 3 and 5, boys were more likely than girls to report being good at mathematics. This result has often been reported for older students but has rarely been explored in younger children. Some gender and grade differences were observed in students' attitudes towards the specific strands of mathematics. Both girls and boys in Grade 5 were more likely than students in Grade 3 to believe that mathematics was relevant to their lives. Virtually all children thought that both girls and boys needed to study mathematics. No gender or grade differences in students' beliefs regarding the process of learning mathematics were observed. The results support the need for further research to identify variables that influence the development of student perceptions and attitudes toward mathematics during elementary school.