Enhanced emission from hBN in sputtered microcavities.

In this observational study, we embed few-layer hexagonal boron nitride (hBN) inside a planar Fabry-Perot cavity fabricated using a pulsed DC magnetron sputtering system and show that the hBN retains its inherent visible range, defect-based luminescent properties following relatively energetic deposition processing. The observed surface-normal emission enhancement factor of ∼40 is in good agreement with theoretical predictions. We also found that embedded hBN subjected to a rapid thermal annealing treatment exhibits a cracking effect where the edges of the material glow distinctly brighter than adjacent regions. Our results might inform future efforts involving monolithic integration of hBN active layers.

Limited efficacy of ketoconazole in treatment-refractory major depression.

The authors examined the efficacy of ketoconazole in 16 adults with treatment-refractory major depressive disorder. Subjects participated in a 6-week, double-blind, placebo-controlled trial. Assessments of mood were made using the Hamilton Rating Scale for Depression (HAM-D), the Beck Depression Inventory (BDI), and the Clinical Global Impression Scale (CGI). Results showed that none of eight patients randomly assigned to receive placebo and two of eight patients randomly assigned to receive ketoconazole met criteria for response. As a group, patients assigned to receive ketoconazole showed no significant reductions in HAM-D, BDI, or CGI scores during the 6-week trial compared with those receiving placebo. These findings suggest a limited efficacy for ketoconazole in patients with treatment-refractory major depression.

Tryptophan depletion during continuous CSF sampling in healthy human subjects.

The tryptophan (TRP) depletion paradigm has been employed to investigate mood and behavioral effects of acutely lowering plasma TRP, and presumably brain serotonin (5-hydroxytryptamine [5-HT]) levels through administration of a special diet and/or amino acid drink. Our goal was to test the assumption that a corresponding fall in central levels of TRP and 5-HT (measured by its major metabolite, 5-hydroxyindoleacetic acid [5-HIAA]) occurs during the standard execution of this method in healthy adult subjects. Three males and two females completed the protocol, which included a one-day low-TRP diet and a TRP-free amino acid drink. Lumbar puncture was performed, with placement of an indwelling catheter connected to a peristaltic pump and fraction collector. Cerebrospinal fluid (CSF) was sampled continuously for a 13.5-hour period (before, during, and after the drink), with fractions removed every 15 minutes. Plasma samples were simultaneously obtained. CSF TRP levels and plasma TRP levels were highly correlated, falling a mean of 92% and 85% from baseline, respectively. CSF nadirs were reached several hours after plasma nadirs. CSF 5-HIAA decreased modestly (24% to 40%, mean 31% change from baseline), with lowest concentrations observed 8-12 hours after the amino acid drink. These data suggest that TRP depletion results in substantial declines in central 5-HT turnover.

Assessment of diurnal variation of cerebrospinal fluid tryptophan and 5-hydroxyindoleacetic acid in healthy human females.

The role of serotonin (5-HT) in the pathogenesis and treatment of major neuropsychiatric disorders, including mood and anxiety disorders, continues to be the subject of extensive research. Previous studies examining central 5-HT functioning measured cerebrospinal fluid (CSF) levels of 5-hydroxyindoleacetic acid (5-HIAA) by using single or multiple lumbar punctures. A number of investigators have demonstrated the feasibility of continuous CSF sampling via an indwelling lumbar catheter to study CSF neurochemistry in healthy subjects and patients with neuropsychiatric illness. Four healthy female volunteers, aged 21-34 years, underwent continuous CSF sampling. CSF was collected at a constant rate of 1 ml every 10 minutes over a 30-hour period, with levels of tryptophan (TRP) and 5-HIAA measured every hour. Plasma was also obtained hourly for TRP determination. The results of this study indicate that CSF 5-HIAA, CSF TRP, and plasma TRP levels showed variation over time, but failed to show diurnal fluctuation. Intra-individual coefficients of variation determined for CSF 5-HIAA, CSF TRP, and plasma TRP ranged from 9.2 to 14.9%, 8.8 to 14.6%, and 14.7 to 19.0%, respectively. Continuous CSF sampling is safe and feasible in humans, and may prove useful for studies of central 5-HT neurotransmission in neuropsychiatric illness.

A comparative cost analysis of alternative models of adult day care.

An analysis of the component costs of adult day care (ADC) programs in the Commonwealth of Pennsylvania indicates widely varying experiences in terms of fiscal and contractual administrative arrangements. Medical model ADC, program-funded services, and those agencies performing their own client assessments reported higher client per diems than the social model, slot-funded, and non-ADC assessed programs. For-profits displayed cost characteristics similar to their not-for-profit counterparts. Medical and slot-funded programs more frequently turned to multiple sources for budget supplementation. All program types tended to depend on voluntary client contribution methods as compared to means-tested approaches when determining fee-for-service.

Characterization of the structure and conformation of platelet-derived growth factor-BB (PDGF-BB) and proteinase-resistant mutants of PDGF-BB expressed in Saccharomyces cerevisiae.

A detailed biophysical study of the secondary and tertiary structures of recombinant platelet-derived growth factor (PDGF)-BB produced in yeast has been carried out. The secondary structure of the molecule is composed of 54% beta-sheet with less than 5% ordered helix. The single tryptophan residue has been shown to be solvent-accessible; however, the ability of the side chain to rotate is severely restricted. The fluorescence emission is quenched at pH 7.0 and in the presence of high salt, but dequenched by titration to lower pH with a pK of 5.8. Two proteinase-resistant mutants of PDGF [( Ser28]- and [Pro32]-PDGF-BB) have also been characterized and shown to have secondary and tertiary structures indistinguishable from wild-type PDGF-BB. These are, therefore, suitable stable background molecules in which to carry out structure-activity-relationship studies on PDGF-BB.

Purification and analysis of proteinase-resistant mutants of recombinant platelet-derived growth factor-BB exhibiting improved biological activity.

Recombinant platelet-derived growth factor (PDGF)-BB was expressed and secreted from yeast in order to study the structure-function relationships of this mitogen. A simple purification scheme has been developed which yields greater than 95% pure PDGF-BB. Analysis of this recombinant PDGF-BB shows partial proteolysis after arginine-32. Substitution of this arginine residue, or arginine-28 [a potential KEX2 (lysine-arginine endopeptidase) cleavage site], prevents or reduces cleavage of PDGF-BB respectively. These mutations result in a 5-fold increase in expression levels of PDGF-BB, and the resulting mutant proteins show higher activity in a number of biological assays than the cleaved wildtype PDGF-BB. These data are in accord with previous work by Giese, LaRochelle, May-Siroff, Robbins & Aaronson [(1990) Mol. Cell Biol. 10, 5496-5501] suggesting that the region isoleucine-25-phenylalanine-37 is involved in PDGF-receptor binding.

Intergenerational continuity and reciprocity through the use of community-based services: theory and practice.

This paper aims to expand the current debate on intergenerational issues by examining the interactions of the generations and their sentiments as represented in recent community program studies, participant-observation reports, and autobiographical work. The error in intergenerational inequity thinking is asserted to be in its belief that a generation that otherwise would have had to support its parents would be in favor of cutting social security benefits. Two, if researchers and policy makers take into account only economic exchange, they will never be able to predict usage or plan appropriate programs. Three, the state has a stake in supporting informal caregivers. Finally, real equity lies in normative social exchange.

Service consumption patterns over time among adult day care program participants.

A study of 59 adult day care (ADC) programs funded by area agencies on aging in Pennsylvania provides data which profiles the classic package of ADC services utilized by elder participants and traces the relationship between formal service consumption and the helping behaviors of family caregivers. Elder clients rejected 1 or more services offered by ADC staff 59% of the time. Consumption of homemaking, transportation, and counseling services escalated over time although total formal services used remained minimal. Family helpers performed both a greater range and intensity of support functions as compared to ADC programs (p less than .001). Program strategies and future research directions are suggested.

Transport of proteins into chloroplasts. Import and maturation of precursors to the 33-, 23-, and 16-kDa proteins of the photosynthetic oxygen-evolving complex.

The 33-, 23-, and 16-kDa proteins of the photosynthetic oxygen-evolving complex are synthesized as precursors in the cytoplasm and transported into the thylakoid lumen of higher plant chloroplasts. In this report we have analyzed the import and maturation of these precursors, using reconstituted protein import assays and partially purified preparations of the processing peptidases involved. Precursors of the 33- and 23-kDa proteins from Spinacia and Triticum aestivum are processed by a stromal peptidase to intermediate forms; polypeptides of similar size are observed during the transport of these precursors and possibly that of the 16-kDa protein, into isolated chloroplasts. Complete maturation of the 33- and 23-kDa proteins is carried out by a thylakoidal peptidase shown previously to be involved in plastocyanin biogenesis. The data support an import mechanism involving successive cleavages by the stromal and thylakoidal processing peptidases.

ATP-dependent import of a lumenal protein by isolated thylakoid vesicles.

The 33 kd protein of the photosynthetic oxygen-evolving complex is synthesized in the cytoplasm as a larger precursor and transported into the thylakoid lumen via a stromal intermediate form. In this report we describe a reconstituted system in which the later stages of this import pathway can be studied in isolation. We demonstrate import of the 33 kd protein, probably as the intermediate form, into isolated pea thylakoids by a mechanism which is stimulated by the addition of ATP. The imported protein is processed to the mature size and is resistant to digestion by proteases. The thylakoidal protein transport system is specific in that non-chloroplast proteins and precursors of stromal proteins are not imported.

Transport of proteins into chloroplasts. Organization, orientation, and lateral distribution of the plastocyanin processing peptidase in the thylakoid network.

Plastocyanin is synthesized in the cytoplasm as a larger precursor and transported into the thylakoid lumen of the chloroplast. Maturation of preplastocyanin involves successive cleavages by a stromal peptidase and a distinct thylakoidal peptidase. In this report we have analyzed the precise location and orientation of the thylakoidal peptidase with respect to the thylakoid membrane. Experiments involving differential centrifugation of thylakoid extracts and sonication of isolated vesicles indicate that the peptidase is tightly bound to the thylakoid membrane but not intimately associated with any of the major thylakoid protein complexes. Analysis of the lateral distribution of the peptidase has shown that the enzyme is exclusively located in the non-appressed lamellae of the thylakoid network. The active site of the peptidase is on the lumenal face of the thylakoid membrane.

Early parental loss and development of adult psychopathology.

We assessed the effect of parental loss during childhood on the development of psychopathology in 90 adults. The subjects with a history of adult psychopathology (PATH group), in comparison with subjects with no history of a psychiatric disorder (NO PATH group), had poorer quality of childhood home life and personal adaptation subsequent to parental loss as assessed by the Home Life and Personal Adaptation (HAPA) scale developed by us. Total HAPA scale scores were the single most powerful predictor of adult psychopathology, accounting for correct prediction of adult psychopathology in 80% (72/90) of the subjects. The PATH subjects had significantly increased plasma levels of cortisol and beta-endorphin immunoreactivity. Moreover, cortisol and adrenocorticotropic hormone levels significantly correlated with total HAPA scores. First-degree family history of psychiatric disorders, age at loss, and parental vs maternal loss were not significantly different between PATH and NO PATH subjects. We conclude that the quality of home life subsequent to early parental loss is critically related to the development of adult psychopathology. The hypothesis that early trauma results in enduring neuroendocrine alterations in hypothalamic-pituitary-adrenal axis function is examined.

Performance of schizophrenic patients on putative neuropsychological tests of frontal lobe function.

Though individual tests thought to assess frontal lobe function have been administered to patients with schizophrenia for many years, approaches in which a number of tests thought to tap a single function or brain region have rarely been used. Such an approach might define a critical test or a common dysfunctional cognitive process. In the present study four putative neuropsychological tests of frontal lobe integrity, namely, the Wisconsin Card Sorting Test, the Category Test, Trail Making B, and verbal fluency, were administered to 28 patients with schizophrenia. Seventy-five percent performed abnormally on at least one test. However, relationships among the test results were difficult to characterize, either by correlation or factor analysis. A hierarchical arrangement in which "higher order" tests proscribe performance on "lower order" tests did not appear to be present. Regarding sensitivity, Trails B, the only timed test, was most frequently impaired and verbal fluency was least frequently impaired. The results suggest that the tests assess somewhat different aspects of frontal lobe function, and that no single frontal lobe test is uniquely sensitive to cognitive impairment in schizophrenia.

Correlates of service utilization among adult day care clients.

This study of adult day care clients (N = 48) in three suburban programs reports on the relationship between client impairments, the age of primary caregivers and the services used by these clients. The results support the low use of services among the multi-impaired aged that has been previously reported. This is true even for the multi-impaired who have been attending adult day care programs for over seventeen months. Providers of formal aging services may benefit from these data when coordinating service plans for the multi-impaired elder who has an intact informal social support system and has not had a life history of mental illness.

Transport of proteins into chloroplasts. Partial purification of a thylakoidal processing peptidase involved in plastocyanin biogenesis.

Plastocyanin is synthesized in the cytoplasm as a larger precursor and transported across three membranes into the chloroplast thylakoid lumen. Processing to the mature size involves successive cleavages by a stromal and a thylakoidal peptidase. In this report we describe the partial purification and characterization of the thylakoidal peptidase involved. The enzyme has been purified 36-fold from Pisum sativum thylakoids after solubilization using Triton X-100. The peptidase processes the plastocyanin import intermediate to the mature size, but no further, and is capable of processing pre-plastocyanin to the mature size but at a lower rate. No detectable activity is displayed against non-chloroplast proteins or precursors of stromal proteins. The enzyme has a pH optimum of 6.5-7 and is activated by chelating agents such as EDTA and EGTA. No inhibitors of the peptidase have been found to date.

Secretion-coupled protein degradation: studies on mammary casein.

Mammary explants from midpregnant rabbits were cultured for 18 h at 37 degrees C with insulin, prolactin and cortisol. Subsequently, explants were labelled for 2 h with inorganic [32P]phosphate, L-[5-3H]proline or L-[4,5-3H]leucine, washed and chased for up to 3 h. The radiolabelling profile of [32P]casein or [3H]casein during the chase period, obtained by isoelectric focussing or immunoprecipitation indicates extensive destruction of neosynthesized casein. The extent of casein destruction in mammary explants in culture (measured after radiolabelling with L-[5-3H]proline), is inversely related to casein secretion. Least casein degradation is observed in explants after 48 h in culture when casein secretion is maximal (observed histochemically). Subsequently, when the extracellular alveolar lumen is filled with secretion products (72 h), rapid intracellular casein destruction is again observed. When the chase was carried out in the presence of drugs which inhibit degradation and/or secretion, the results indicate that secretion-coupled casein degradation is dependent on an intact functional microfilamentous-microtubular network, casein is not degraded by an autophagosome requiring process, degradation is inhibited by leupeptin, amino-acid analogue containing casein does not undergo secretion-coupled degradation and inhibition of N-glycosylation of intracellular vesicular membrane proteins prevents secretion-coupled degradation. Secretion-coupled protein destruction is discussed in relation to the post-translational regulation of the net production of secretory proteins in eukaryotic cells.

The effect of descriptive anger expression, insult, and no feedback on interpersonal aggression, hostility, and empathy motivation.

In a test of the hypothesis that descriptive anger expression elicits less subsequent aggression and greater empathy than does aggressive insult, 60 male undergraduates were instructed to set varying levels of shock for an opponent during a series of competitive trials before and after hearing one of four types of taped comment. Results indicated that descriptive anger expression led to a significant decrease in aggression, while no feedback (opponent said nothing) led to an increase in aggression. Insult and no anger feedback resulted in little change in aggressive behavior. In contrast, descriptive anger expression, insult, and no anger feedback produced more residual hostility than did no feedback. Descriptive anger expression Ss appeared to be more motivated by empathy in setting shocks, as compared to the other three groups. Empathy was found to be generally associated with lower shock settings initially and with reductions in shock settings following the opponent's comments. Empathy, however, was not related to Ss' hostility ratings. The results tend to support the clinical utility of descriptive anger expression in improving interpersonal relations.