Bidirectional light-induced conductance switching in molecular wires containing a dimethyldihydropyrene unit.

Photochromic coordination polymers, based on zinc(ii) bis-terpyridine-appended dimethyldihydropyrene building blocks, have been synthesized following stepwise synthesis on a surface yielding photo-switchable molecular junctions. Under irradiation, reversible structural changes occur by the isomerization of the photosensitive units, thus inducing conductance switching of the molecular junctions with a good reproducibility.

Self-assembled dimethyldihydropyrene-pyridyl substituted ligands with zinc(ii) meso-tetraphenylporphyrin via axial coordination.

A series of dimethyldihydropyrene (DHP)-pyridyl photochromic derivatives has been synthesized and its photochemical behaviour characterized by spectroscopic and electrochemical methods. The corresponding noncovalently-linked electron donor-acceptor complexes have been isolated. They combine the DHP-pyridyl ligand as a donor and the zinc(ii) tetraphenylporphyrin as acceptor. Such association allowed to explore the efficiency of dative bonds to monitor the interactions between the two units.

Broadband modeling of downslope propagation in a penetrable wedge.

Sound propagation in a wedge-shaped environment with a penetrable bottom is simulated with broadband adiabatic mode, coupled mode, and parabolic equation model computations. Simulated results are compared to measured data taken in a tank experiment by Tindle et al. The coupled mode formalism is shown to predict, in agreement with that experiment, that modal wave fronts in penetrable wedges are approximately circular arcs centered at the apex of the wedge for a source near the apex. It is also shown that for wedge angles up to 6 degrees, the received waveforms are well approximated by the adiabatic waveforms time-shifted by a depth-dependent interval to account for the curvature of the modal wave fronts. A small deviation from circularity in the modal wave fronts is possibly observed in the 6 degrees case.

Syntheses, structural determination, and electrochemistry of Ru(2)(Fap)(4)Cl and Ru(2)(Fap)(4)(NO)Cl.

Ru(2)(Fap)(4)Cl and Ru(2)(Fap)(4)(NO)Cl, where Fap is the 2-(2-fluoroanilino)pyridinate anion, were synthesized, and their structural, electrochemical, and spectroscopic properties were characterized. Ru(2)(Fap)(4)Cl, which was obtained by reaction between Ru(2)(O(2)CCH(3))(4)Cl and molten HFap, crystallizes in the monoclinic space group P2(1)/c, with a = 11.2365(4) A, b = 19.9298(8) A, c = 19.0368(7) A, beta = 90.905(1) degrees, and Z = 4. The presence of three unpaired electrons on the Ru(2)(5+) core and the 2.2862(3) A Ru-Ru bond length for Ru(2)(Fap)(4)Cl are consistent with the electronic configuration (sigma)(2)(pi)(4)(delta)(2)(pi*)(2)(delta*)(1). The reaction between Ru(2)(Fap)(4)Cl and NO gas yields Ru(2)(Fap)(4)(NO)Cl, which crystallizes in the orthorhombic space group Pbca, with a = 10.0468(6) A, b = 18.8091(10) A, c = 41.7615(23) A, and Z = 8. The Ru-Ru bond length of Ru(2)(Fap)(4)(NO)Cl is 2.4203(8) A, while its N-O bond length and Ru-N-O bond angle are 1.164(8) A and 155.8(6) degrees, respectively. Ru(2)(Fap)(4)(NO)Cl can be formulated as a formal Ru(2)(II,II)(NO(+)) complex with a linear Ru-N-O group, and the proposed electronic configuration for this compound is (sigma)(2)(pi)(4)(delta)(2)(pi*)(3)(delta*)(1). The binding of NO to Ru(2)(Fap)(4)Cl leads to some structural changes of the Ru(2)(Fap)(4) framework and a stabilization of the lower oxidation states of the diruthenium unit. Also, IR spectroelectrochemical studies of Ru(2)(Fap)(4)(NO)Cl show that NO remains bound to the complex upon reduction and that the first reduction involves the addition of an electron on the diruthenium core and not on the NO axial ligand.

Behavioral intervention to reduce child distress during self-injection.

We investigated the effects of a cognitive-behavioral treatment package on reduction of anticipatory fear of pain during self-administered insulin injections. Two patients diagnosed with insulin-dependent diabetes mellitus participated. An ABAB design was employed; the intervention conditions consisted of cue-controlled breathing, filmed modeling, pacing, and reinforcement. A substantial reduction in the mean time for injection and a reduction in behaviors indicative of anticipatory distress were achieved under intervention conditions. The clinical importance of the study is discussed and areas for future research are identified.

Immunochemical identification of ubiquitin and heat-shock proteins in corpora amylacea from normal aged and Alzheimer's disease brains.

Corpora amylacea (CA) accumulation in the central nervous system (CNS) is associated with both normal aging and neurodegenerative conditions such as Alzheimer's disease (AD). CA is reported to be primarily composed of glucose polymers, but approximately 4% of the total weight of CA is consistently composed of protein. CA protein resolved on sodium dodecylsulfate-polyacrylamide gel electrophoresis showed a broad range of polypeptides ranging from 24 to 133 kDa, with four abundant bands. Immunoblots of the profile of polypeptides solubilized from purified CA, showed positive ubiquitin (Ub) immunoreactivity for all the bands. Antisera to heat-shock proteins (hsp) 28 and 70 reacted selectively with bands of 30 and 67 kDa. These results show that Ub is associated with the primary protein components of CA and that the polypeptides are likely to be Ub conjugates. Immunostaining experiments were performed to specifically characterize the protein components of CA in brain tissue sections as well as those of CA purified from both AD and normal aged brains. In all cases CA showed positive reactions with antibodies to Ub, with antibodies raised against either paired helical filaments or hsp 28 or 70, the most prominent staining being with antibodies to Ub, hsp 28 or hsp 70. The presence of Ub and hsp 28 and 70, which are actively induced after stress, suggests that accumulation of altered proteins, possibly attributed to an increased frequency of unusual post-translational modifications or to a sustained physiological stress (related to both normal aging and neurodegenerative process), may be involved in the pathogenesis of CA.

Toothbrushing and transient bacteremia in patients undergoing orthodontic treatment.

This study was made to determine whether and to what extent bacteremia occurred after toothbrushing in patients undergoing orthodontic treatment with fixed appliances. Twenty patients were selected, all with negative history of heart or hematologic disorders. These patients had not taken antibiotics or had a history of a cold in the previous 30 days. Blood samples of 20 ml were drawn before and 5 minutes after brushing. The immune status of the patients was tested by measurement of isohemagglutins and immunoglobulin levels. Blood samples were incubated in paired culture bottles containing trypticase soy broth (TSB) with an agar paddle and Columbia broth. All samples taken before brushing were negative for bacteria. Five of the 20 patients (25% of the sample) had positive blood tests after brushing. Both anaerobic and aerobic bacteria were identified from the blood samples. Those patients who were found to have a bacteremia did not display poor oral hygiene.

Ubiquitin is a component of polypeptides purified from corpora amylacea of aged human brain.

Corpora amylacea (CA) are one of the conspicuous features of brain tissue in normal aging and neurodegenerative diseases. Quantitative protein determination of purified CA revealed a protein content of about 4% of total weight. Qualitative protein analysis revealed a broad range of polypeptides, with four being more abundant. High performance liquid chromatography (HPLC) fractionation of this protein material showed four peaks which are related to the four major polypeptides with molecular weights of 24 KD, 42 KD, 94 KD, and 133 KD. Amino acid content analysis of the 24 KD, 42 KD and 94 KD polypeptides indicated that distinct protein species are involved. N-terminal amino acid sequence analysis of the 24 KD and 42 KD polypeptides revealed in both cases homology with the N-terminal sequence of human ubiquitin.

Lack of association between two restriction fragment length polymorphisms in the genes for the light and heavy neurofilament proteins and Alzheimer's disease.

The etiology of Alzheimer disease (AD) remains unknown. The hypothesis of genetic factors playing a role in the causation of the disease, at least in its familial form, has been borne out by results showing linkage in several early-onset AD families to a locus on the proximal part of the long arm of chromosome 21. Linkage was not detected in several other families using the same markers. The metabolism of neurofilaments is perturbed in AD, as indicated by the presence of neurofilament epitopes in neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit in AD brain. To detect a possible anomaly that might relate to the disease, we have searched for an association between the genes for the light subunit and the heavy subunit of the neurofilament triplet, and AD. Genotypes for restriction fragment length polymorphisms (RFLP) at each of the two loci were determined for an AD group and a control group. Allelic frequencies at a TaqI-defined RFLP for the gene for the light neurofilament subunit were 0.70 for the 3.7 kb allele and 0.30 for the 2.9 kb allele. HincII detected an RFLP for the heavy neurofilament subunit gene with frequencies of 0.31 for the 18.0 kb allele and 0.69 for the 6.8 kb allele. Frequencies were found to be similar in the two groups for both light and heavy neurofilament subunit loci. Although it cannot be excluded that mutations at other sites of the neurofilament genes are relevant to AD, the data reported here do not support an association between these genes and the disease.

Purification and polypeptide composition of corpora amylacea from aged human brain.

Corpora amylacea (CA) accumulation in the brain is a normal correlate of ageing. The presence of a small amount of protein in these polyglucosan bodies is a consistent finding, although the nature of this protein material remains unknown. Using sucrose gradient fractionation and density centrifugation on Percoll, a method was developed to obtain highly pure preparations of CA from human brain. The protein content of isolated CA was estimated to be approx. 4% of the total fraction by weight. SDS-PAGE analysis of CA fractions showed several polypeptide bands with molecular weights ranging from 24 to 133 kDa. Four of these bands with molecular weights of 133, 94, 42 and 24 kDa are more abundant. Thus, pure preparations of CA can be obtained that are suitable for protein analysis.

Ascertainment of informative Alzheimer disease families from the IMAGE Project registry for genetic linkage analysis studies.

Genetic linkage analysis requires the identification and documentation of large families with many affected members present, preferably in more than one generation. The IMAGE Project has been establishing a population-based Alzheimer disease (AD) registry in the Saguenay - Lac-Saint-Jean region of the Province of Quebec. The population of this region has a well-documented ancestry, with reliable genealogical records (since 1842) computerized by SOREP. We have recently begun to investigate the pedigrees of selected probands (definite, probable and possible) from the IMAGE registry in order to identify informative pedigrees for genetic linkage analysis. Interviews were carried out with close relatives of the probands (at least one informant per sibship) to identify secondary AD cases. The questionnaires used pertain to the accuracy of genealogical records, to family medical history and to a retrospective diagnosis of AD for people with cognitive deficits. By these means, we have documented a large extended pedigree in which a total of 15 individuals with cognitive deficits were ascertained over three generations. Of these cases, 7 are still living and there is autopsy confirmation in another one. Computer simulations using the program SIMLINK revealed that this is a potentially informative family for linkage analysis. Horizontal extension of the pedigree to second cousins of the proband is now being carried out. This will render the family IMAGE/1 even more informative in genetic linkage analysis studies.

Localization of transferrin within the developing vertebrate nervous system.

Transferrin is one of several serum proteins localized within neurons during development of the nervous system. The expression of transferrin receptors appears to precede the active accumulation of transferrin by neurons. The first cells immunoreactive for transferrin appear adjacent to the ventricles or to the central canal of the spinal cord. These cells then appear to migrate from this site. These neurons become progressively more immunoreactive for transferrin, attain a peak of reactivity and then lose their reaction to antitransferrin antibodies. Thus, a "window" of transferrin immunoreactivity is found. As neurons lose their reactivity to antitransferrin antibodies, glia and the walls of capillaries become positive. In the rat nervous system, the gradual decrease in intraneuronal transferrin is accompanied by an increase in mitochondrial malate dehydrogenase, an enzyme of the tricarboxylic acid cycle. Thus, the accumulation of transferrin appears to closely precede the ontogeny of oxidative metabolism in the brain. As transferrin appears transiently in all neurons, this protein may be involved in a number of other important developmental events such as the expression of dopamine D2 receptors and the period of "programmed" cell death in the spinal cord.

Immunocytochemical Localization of Ribulose-1,5-Bisphosphate Carboxylase in the Pyrenoid and Thylakoid Region of the Chloroplast of Chlamydomonas reinhardtii.

The distribution of the large and small subunits of ribulose-1,5-bisphosphate carboxylase in the chloroplast of Chlamydomonas reinhardtii was studied by immunoelectron microscopy by labeling Lowicryl-embedded sections with antibody to each subunit followed by protein A-gold. In light-harvested synchronously dividing cells, antibodies to each subunit heavily labeled the pyrenoid, whereas the thylakoid region of the plastid was lightly labeled. By estimating the volume of each chloroplast compartment, it was determined that approximately 40% of the total small subunit in the plastid and 30% of the large subunit are localized in the thylakoid region, presumably in the stroma. In synchronously dividing cells exposed to an extended dark period, the amount of labeling of the pyrenoid region by antibody to the small subunit stayed constant, but the labeling of the thylakoid region decreased. In stationary phase cells, the proportion of the label over the pyrenoid is higher than in synchronously dividing cells suggesting that the pyrenoid may be a storage organelle.

Immunocytochemical distribution of transferrin and its receptor in the developing chicken nervous system.

Transferrin is the plasma protein responsible for iron transport in all vertebrates. While transferrin is known to have growth-promoting activity on a variety of cells in culture, the role of transferrin and its membrane receptor in neuronal development is unknown. Using antibodies to transferrin and transferrin receptors, we studied the immunocytochemical localization of transferrin and its receptor in developing chicken neural tissues by the peroxidase-antiperoxidase method. In 5-day-old embryonic brain, germinal cells of the ventricular zone showed a positive reaction for transferrin receptors but were negative for transferrin. By 6-7 days, transferrin-positive cells were seen in the inner layer of the ventricular zone and a few 'patches' of transferrin-positive cells were also seen in the adjacent area. By 10 days, large neurons throughout the brain were strongly positive for transferrin. By 11-16 days, all neurons in the brain showed a strong positive reaction for the protein. Thereafter, the transferrin-positive reaction became gradually weaker in neurons whereas the walls of blood capillaries showed a positive reaction for transferrin. In the adult brain, neurons showed very weak or negative staining. A similar staining pattern for transferrin was observed in the developing spinal cord and dorsal root ganglia (DRG). By 10-12 days, both spinal cord neurons and DRG neurons showed strong reactions for transferrin. Thereafter, the transferrin-positive reaction gradually diminished in older spinal cord neurons and completely disappeared from DRG neurons. Cultured cerebral hemisphere, spinal cord, and DRG neurons showed positive staining reactions for both transferrin and its receptor. Our results suggest that: transferrin is initially taken up by developing neurons from cerebrospinal fluid via receptor-mediated endocytosis; the accumulation of transferrin ultimately reaches a maximum level within immunoreactive neurons and then declines just prior to hatching; in contrast to other CNS neurons, DRG neurons accumulate transferrin only briefly and then become negative for transferrin by immunocytochemistry; and after closure of the blood-brain barrier, transferrin may reach neurons by transport across capillaries into the 'paravascular' spaces. In view of these results, transferrin may play some important but unrecognized role in early neuronal development in vivo as well as in vitro.

Evaluation of albumin-globulin ratio to confirm the clinical stages of sarcoidosis.

The serum albumin-globulin ratio (A/G) has been evaluated and correlated to confirm the clinical stages of sarcoidosis in clinically diagnosed cases. In comparing each clinical stage of sarcoidosis, using Student's t test (P = .05), a significant difference was observed. Overall, men maintained a higher A/G ratio than women in all of the clinical stages. The authors conclude that the serum A/G ratio, which can be computed from serum analyses of albumin and globulins by a suitable method, can be an additional and reliable index requiring no extra serum sample or cost per test to confirm clinical stages of sarcoidosis. This measurement can easily be used in monitoring the progression of disease or efficacy of the therapy.

Toothbrushing and transient bacteremia in patients undergoing orthodontic treatment.

A study was made to determine the extent of bacteremia experienced by patients undergoing orthodontic treatment with fixed appliances during periods of routine oral hygiene--namely, brushing the teeth. Sixteen orthodontic patients made up the population--11 who practiced good oral hygiene and five who demonstrated poor oral hygiene. Blood was drawn aseptically from the median cubital vein of the subjects before and 15 minutes after brushing the teeth. An aliquot of each blood specimen was added to separate blood culture bottles and incubated at 37 degrees C for a period of up to 5 days. Blood was also used to determine the immune status of the subjects. Anaerobic bacteria were recovered from the blood of nine of the 16 patients studied; aerobic bacteria were not recovered. A negative blood culture before brushing and positive blood culture after brushing were expected but did not occur. Some subjects showed bacteremia before brushing and a negative blood culture after brushing. Others showed bacteremia before and after brushing. The unexpected results could be attributed to the patients eating and/or brushing before starting the test. The study showed the capacity of specific anaerobic bacteria to remain in the bloodstream for a 15-minute period. It also demonstrated a presence of bacteria in the bloodstream before the test began.