Stable DHLA-PEG capped PbS quantum dots: from synthesis to near-infrared biomedical imaging.

The short shelf-life of water-soluble quantum dots (QDs) due to colloidal instability represents a major drawback to their exploitation. This work examines the colloidal stability of PbS nanoparticles capped with dihydrolipoic acid-polyethylene glycol (DHLA-PEG) ligands terminated with functional groups such as -NH2, -COOH, OMe and -N3. and their application for in vivo imaging. We prove a mechanism of colloidal instability and develop a strategy to produce for the first time stable PEG-capped PbS quantum dots with high quantum yield and optical emission in the first and the second near-infrared (NIR) windows of low absorption of biological tissues. The NIR imaging of in vivo biodistribution is demonstrated at wavelengths >1000 nm, with benefits of reduced tissue absorption and light scattering. The stability, biocompatibility and potential for further QD functionalization open up realistic prospects for non-invasive bioimaging applications.

Injection locking of violet laser diodes with a 3.2 GHz offset frequency for driving Raman transitions in 43Ca+.

Two cw single-mode violet (397 nm) diode lasers are locked to a single external-cavity master diode laser by optical injection locking. A double-pass 1.6 GHz acousto-optic modulator is used to provide a 3.2 GHz offset frequency between the two slave lasers. We achieve up to 20 mW usable output in each slave beam, with as little as 25 µW of injection power at room temperature. An optical heterodyne measurement of the beat note between the two slave beams gives a linewidth of ≤10 Hz at 3.2 GHz. We also estimate the free-running linewidth of the master laser to be approximately 3 MHz by optical heterodyning with a similar device.

Tailoring the physical properties of thiol-capped PbS quantum dots by thermal annealing.

We show that the thermal annealing of thiol-capped PbS colloidal quantum dots provides a means of narrowing the nanoparticle size distribution, increasing the size of the quantum dots and facilitating their coalescence preferentially along the 100 crystallographic axes. We exploit these phenomena to tune the photoluminescence emission of an ensemble of dots and to narrow the optical linewidth to values that compare with those reported at room temperature for single PbS quantum dots. We probe the influence of annealing on the electronic properties of the quantum dots by temperature dependent studies of the photoluminescence and magneto-photoluminescence.

Acyl derivatives of coenzyme A inhibit platelet function via antagonism at P2Y1 and P2Y12 receptors: a new finding that may influence the design of anti-thrombotic agents.

We have performed a detailed investigation of the effects on platelet function of coenzyme A (CoA) and several acyl-CoAs. Platelet aggregation was measured by turbidimetry and by platelet counting; platelet shape change was measured using light scattering; P-selectin, Ca2+ mobilization and vasodilator-stimulated phosphoprotein (VASP) phosphorylation were measured by flow cytometry. The compounds investigated inhibited ADP-induced platelet aggregation; those with saturated acyl groups containing 16-18 carbons were most effective. The effects of palmitoyl-CoA (16:0) were studied in depth. It inhibited platelet shape change and Ca2+ mobilization brought about by ADP (but not other agonists) indicating antagonism at P2Y(1) receptors, and also inhibited ADP-induced P-selectin expression. Effects of palmitoyl-CoA on the platelet aggregation and Ca2+ mobilization induced by several different agonists and agonist combinations were compared with those of MRS 2179 (a P2Y(1) antagonist) and AR-C69931 (a P2Y(12) antagonist), and were consistent with palmitoyl-CoA acting mainly at P2Y(1) but also with partial antagonism at P2Y(12) receptors. Antagonism at P2Y(12) receptors was confirmed in studies of VASP-phosphorylation. Palmitoyl-CoA did not act as an antagonist at P2X(1) receptors. The results are discussed in relation to the possibility that acyl-CoAs may contribute as endogenous modulators of platelet function and might serve as lead compounds for the design of novel antithrombotics.

Long-lived mesoscopic entanglement outside the Lamb-Dicke regime.

We create entangled states of the spin and motion of a single 40Ca+ ion in a linear ion trap. We theoretically study and experimentally observe the behavior outside the Lamb-Dicke regime, where the trajectory in phase space is modified and the motional coherent states become squeezed. We directly observe the modification of the return time of the trajectory, and infer the squeezing. The mesoscopic entanglement is observed up to Deltaalpha=5.1 with coherence time 170 micros and mean phonon excitation n = 16.

Atypical antipsychotics in bipolar and schizoaffective disorders.

No data are available comparing the relative efficacy of different atypical agents in patients with bipolar disorder. A chart review of bipolar and schizoaffective disorder patients who had received courses of at least two atypical agents (n = 33) in a community psychiatry system was conducted. No differences in rates of hospitalizations were found between individual atypical agents or between atypical agents as a class and conventional neuroleptics. However, a significant reduction in rates of emergency room visits was found with atypical agents compared to conventional neuroleptics, with a trend toward greater reduction with clozapine compared to other atypical antipsychotics. Larger prospective studies are needed to confirm these preliminary observations.

Hapten design for the generation of catalytic antibodies.

This article brings together all of the kinetic data on catalytic antibodies available in the published literature at the time of writing (September, 1993). The data have been presented so that they can be analyzed for any significant trends that arise from relating the structure of the transition-state analog/hapten to the type and efficiency of the catalytic antibody activity elicited.

Site-directed mutagenesis of a catalytic antibody: an arginine and a histidine residue play key roles.

Individual residues important for ligand binding and catalytic activity were identified by computer modeling and investigated by site-directed mutagenesis for catalytic antibody 43C9, which accelerates amide hydrolysis by a factor of 10(6). On the basis of a computer model, Tyr L32, His L91, Arg L96, His H35, and Tyr H95 were chosen for replacement by site-directed mutagenesis. To facilitate these studies, an expression system was developed in which properly folded 43C9 single-chain antibody was secreted from an engineered Escherichia coli host. Substitution of His L91 by Gln produced a mutant with no catalytic activity, but whose affinities for ligands were nearly the same as those of the wild-type, identifying His L91 as the nucleophile that forms the acyl intermediate implicated by previous kinetic studies. Arg L96 is also critical for catalytic activity and appears to function as a oxyanion hole for the tetrahedral transition states. Two substitutions for His H35 resulted in mutant proteins with no catalytic activity as well as altered affinities for ligands, indicating an important structural role for this residue. Substitutions for Tyr L32 and Tyr H95 were made in an attempt to improve the catalytic efficiency of 43C9. The results of these mutations allow us to propose a mechanism for 43C9-catalyzed hydrolysis: Substrate binding to 43C9 orients the scissile carbonyl group adjacent to both the His L91 and Arg L96 side chains. The imidazole of His L91 acts as a nucleophile, forming an acyl-antibody intermediate that breaks down by hydroxide attack to afford the products and regenerate the catalyst.

A comparison of pyridoxal 5'-phosphate dependent decarboxylase and transaminase enzymes at a molecular level.

Pyridoxal 5'-phosphate is a coenzyme for a number of enzymes which catalyse reactions at C alpha of amino acid substrates including transaminases, decarboxylases and serine hydroxymethyltransferase. Using the X-ray coordinates for a transaminase, aspartate aminotransferase, and the results of stereochemical and mechanistic studies for decarboxylases and serine hydroxymethyltransferase, an active-site structure for the decarboxylase group is constructed. The structure of the active-site is further refined through active-site pyridoxyllysine peptide sequence comparison and a 3-D catalytic mechanism for the L-alpha-amino acid decarboxylases is proposed. The chemistry of serine hydroxymethyltransferase is re-examined in the light of the proposed decarboxylase mechanism.

Masseter and temporalis electromyographic activity in asymptomatic, subclinical, and temporomandibular joint dysfunction patients.

The research and clinical literature on biofeedback treatment of temporomandibular joint (TMJ) dysfunction is devoid of normative or comparative electromyographic (EMG) studies examining muscle activity in either patient or normal samples. For the present study, resting EMG levels for each masseter and temporalis were obtained from three groups of subjects: asymptomatic (female, N = 24, mean age = 26.4); subclinical (female, N = 31, mean age = 28.6); and patient (N = 61, female 70%, mean age = 31.9). A Biocomp 2001 biofeedback system was used to gather the EMG data from each of the four sites during a six- to eight-minute resting baseline period. The patient group demonstrated significantly higher EMG activity than the asymptomatic or subclinical groups for all variables except the right masseter (F (8,220) = 6.65, p less than 0.001). The temporalis was found to be the site of greatest EMG activity more frequently than the masseter. These findings strengthen diagnostic and assessment procedures and criteria, as well as suggest alternate treatment and research protocols.

Freeway space measurement using mandibular kinesiograph and EMG before and after TENS.

This investigation expands on a previous pilot study of the effects of TENS on the resting position of the mandible. The tendency is for an increase in freeway space, but the variability of results makes individual evaluation essential.

A precaution when preparing very large plasmids by alkaline lysis procedure.

The extractabilities of plasmids of different sizes by the sodium lauryl sulfate (SDS)-alkali procedure were compared using either sodium acetate or potassium acetate buffer as the neutralizing agent. There was a selective loss of large plasmids (above 100 kb) when the potassium salt was used. When N-lauryl sarcosine instead of SDS was used as the detergent, no loss of large plasmids occurred in the presence of potassium salt. A comparison of the kinetics of precipitate formation with sodium acetate and potassium acetate indicated that the rate and the amount of lauryl sulfate precipitated were lower with the sodium salt. It is suggested that faster precipitation of lauryl sulfate with potassium acetate leads to trapping of large denatured plasmids that cannot renature as fast as the small ones.

Vertical dimension and freeway space. A kinesiographic study.

A statistical correlation is found between the S-N/mandibular plane angle and clinical freeway space, but there was no correlation after TENS stimulation. The S-N/MP angle did not prove to be a reliable predictor of freeway space.

An electromyographic study of mastication in the freely-moving rat.

The EMG patterns of temporalis, masseter and digastric muscles of twenty Wistar white rats were studied as they ate large and small standard food pellets, bread and pudding. Bipolar EMG electrodes were placed in the muscles and led subcutaneously to a connector pedestal on the rat's head. Integrated records of the EMG patterns were used for analysis. The open-close chewing cycle was initiated by digastric activity to open the mouth; temporalis began the closing phase, followed soon thereafter by activity in masseter. A second burst of activity from digastric occurred during this closing phase analogous to the human lateral pterygoid muscle in stabilizing the structures of the mandibular joint.

Relationship of masseter electromyographic activity to mandible position in the freely-moving rat.

Simultaneous records of masseter-EMG activity and position of the mandible were made on 4 Wistar rats eating four food types: standard food pellets (large pellets), 45 mg precision food pellets (small pellets), bread and pudding. Masseter activity was recorded with chronic bipolar silver EMG electrodes placed within the muscle and led subcutaneously to a pedestal on the head. The transducer indicating jaw position consisted of two tiny inductance coils, placed on the head and under the mandibular symphysis. The lower coil acted as a receiving aerial for the carrier signal supplied via the upper coil, so that distance between the coils, and thus relative jaw position, was traced on the oscilloscope screen. A silent period was found in the masseter-EMG bursts similar to that found in man, where the silent period represents tooth contact and the occlusal phase of chewing (time during which teeth are in the intercuspal position) is defined as the interval between the silent period and the termination of the EMG activity in the muscle. Applying this to the rat data, opening represented 70-75 per cent of the total cycle while the combined closing and occlusion phases comprized 25-30 per cent when either type of pellet was eaten. With bread, closing and occlusal phases represented 56 per cent of the total cycle. For all three food types, muscular force, as indicated by the jaw-closing movement registered by the transducer, continued beyond the masseter EMG. Irregular jaw movements seen when the animals lapped pudding were not correlated directly with masseter activity.

The role of calcitonin in the calcification of ental matrix.

Chronic calcitonin (CT) deficiency was shown to have several effects on the incisors of young growing rats. The incisors had a significantly wider predentin layer, interglobular dentin, and frequent pulpal exposures at the incisal edge. It was concluded that CT plays a role in the normal calcification of dentin matrix.