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Calmodulin-dependent protein kinase III (CaM kinase III) phosphorylates and thereby inactivates eukaryotic elongation factor-2 (EF-2). This enzyme, purified to homogeneity from either rabbit reticulocytes or rat pancreas, had similar properties: it migrated with an apparent M(r) of 140,000 by gel filtration, was comprised of a major polypeptide of M(r) 95,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and had a high affinity for CaM (half-maximal activation

Measurements have been made of the low-temperature magnetic response of single, isolated, micron-size Au loops. The magnetic response is found to contain a component which oscillates with the applied magnetic flux with a fundamental period of ${\mathrm{\ensuremath{\Phi}}}_{0}$=h/e. The amplitude of the oscillatory component corresponds to a persistent current of \ensuremath{\simeq}(0.3--2.0)${\mathit{ev}}_{\mathit{F}}$/L, 1 to 2 orders of magnitude larger than predicted by current theories.

We report a systematic experimental study of the superconducting resistive transition in one-dimensional Al wires of length 0.6 to 110 \ensuremath{\mu}m. Shorter wires show a peak in resistance as a function of temperature near ${\mathit{T}}_{\mathit{c}}$, with a value above the normal-state resistance. Near the peak, the resistance decreases sharply in a magnetic field of only a few Oe. In the same regime, the current-voltage characteristic resembles that of a superconductor-insulator-normal tunnel junction. These new results may be a manifestation of coherent effects in small superconducting samples.

An exceptionally broadband method for pulse magnetic resonance detection is described which enables measurements over a broad range of applied magnetic fields and affords excellent coupling to microscopic specimens. Employing a picosecond magneto‐optic sampling technique with high temporal and spatial resolution, the precessing magnetization of a spin system is directly observed as a function of time following a photoconductively triggered spin tipping pulse. Free induction decays from 200 MHz to 200 GHz have been measured using a single device, for which the frequency limit in principle is of order 1 THz. Examples are presented for ferromagnetic resonance in yttrium iron garnet films at room temperature.

A protocol was developed in 3T3-L1 adipocytes that resulted in the specific desensitization of glycogen synthase activation by insulin. Cells were pretreated for 15 min with 100 nm insulin, and then recovered for 1.5 h in the absence of hormone. Subsequent basal and insulin-induced phosphorylation of the insulin receptor, IRS-1, MAPK, Akt kinase, and GSK-3 were similar in control and pretreated cells. Additionally, enhanced glucose transport and incorporation into lipid in response to insulin were unaffected. However, pretreatment reduced insulin-stimulated glycogen synthesis by over 50%, due to a nearly complete inhibition of glycogen synthase activation. Removal of extracellular glucose during the recovery period blocked the increase in glycogen levels, and restored insulin-induced glycogen synthase activation. Furthermore, incubation of pretreated 3T3-L1 adipocytes with glycogenolytic agents reversed the desensitization event. Separation of cellular lysates on sucrose gradients revealed that glycogen synthase was primarily located in the dense pellet fraction, with lesser amounts in the lighter fractions. Insulin induced glycogen synthase translocation from the lighter to the denser glycogen-containing fractions. Interestingly, insulin preferentially activated translocated enzyme while having little effect on the majority of glycogen synthase activity in the pellet fraction. In insulin-pretreated cells, glycogen synthase did not return to the lighter fractions during recovery, and thus did not move in response to the second insulin exposure. These results suggest that, in 3T3-L1 adipocytes, the translocation of glycogen synthase may be an important step in the regulation of glycogen synthesis by insulin. Furthermore, intracellular glycogen levels can regulate glycogen synthase activation, potentially through modulation of enzymatic localization.

Most of the commonly used quality of life (QOL) instruments in oncology do not include spirituality as a core domain. However, previous research suggests that spirituality might be an important aspect of QOL for cancer patients and that it may, in fact, be especially salient in the context of life-threatening illness. This study used a large (n=1610) and ethnically diverse sample to address three questions relevant to including spirituality in QOL measurement: (1) Does spirituality demonstrate a positive association with QOL?; (2) Is this association unique?; and (3) Is there clinical utility in including spirituality in QOL measurement? Spirituality, as measured by the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp), was found to be associated with QOL to the same degree as physical well-being, a domain unquestioned in its importance to QOL. The significant association between spirituality and QOL was unique, remaining after controlling for core QOL domains as well as other possible confounding variables. Furthermore, spiritual well-being was found to be related to the ability to enjoy life even in the midst of symptoms, making this domain a potentially important clinical target. It is concluded that these results support the move to the biopsychosocialspiritual model for QOL measurement in oncology.

The objective of this study was to compare the quality of life (QOL) of younger (or =50 years) versus older (50 years) women on recent completion of treatment of breast carcinoma.Data reported herein were obtained from a baseline assessment of 304 breast carcinoma patients. These patients were enrolled in a multiinstitutional, randomized trial testing a psychosocial telephone counseling intervention for breast carcinoma patients immediately after treatment. The assessment was made using a self-administered (mail) questionnaire, with an overall response rate of 86%. Included in this questionnaire were standardized measures of QOL using the Functional Assessment of Cancer Therapy-Breast instrument, the Center for Epidemiologic Studies Depression Scale, and the Impact of Event Scale.Comparisons of baseline data analyzed according to age approximating menopausal status (or =50 years and50 years) indicated that younger women reported significantly greater QOL disturbance. QOL was significantly worse for younger women globally (P = 0.021), and with regard to domains of emotional well-being (P = 0.0002) and breast carcinoma specific concerns (P = 0.022). Furthermore, symptoms of depression (P = 0.041) and disease specific intrusive thoughts (P = 0.013) were significantly worse for younger women. No significant sexual dysfunction or body image differences were noted.Results from this analysis suggest that younger women with breast carcinoma should be considered to be at high risk for QOL disruption and significant clinical distress. Targeted interventions for this cohort are recommended.

The Telephone Counseling Trial for Breast Cancer Survivors is a randomized, controlled study designed to test the impact of a telephone-based counseling intervention on quality of life of early-stage breast cancer patients who have completed adjuvant treatment. A psychoeducational counseling model is utilized to promote adaptive coping to re-entry stressors and survivorship issues. Adaptation is fostered through the exploration of thematic materials, application of active coping strategies, encouragement of a personal expression of the breast cancer experience and the provision of psychological support. Patients are being recruited in collaboration with two NCI-designated clinical cooperative oncology groups: the Eastern Cooperative Oncology Group (ECOG) and the Southwest Cooperative Oncology Group (SWOG). The recruitment goal is 400 breast cancer survivors with Stage 1, Stage 2 and Stage 3 disease (with no greater than 10 positive lymph nodes involved). Patients are being enrolled by data managers on-site during their last treatment visit. The intervention is being delivered by the Cancer Information and Counseling Line (CICL) of the AMC Cancer Research Center. It includes 16 telephone outcalls which are delivered over a 12-month period. Primary outcome measures are quality of life, mood, social support, self-efficacy, and sexual functioning, assessed at baseline, 3, 6, 12 and 18 months follow-up. This article provides a description of the intervention protocol and study design. It is argued that this study could provide a model for developing and testing other psychosocial interventions within clinical cooperative groups nationwide.

Insulin is a potent stimulator of intermediary metabolism, however the basis for the remarkable specificity of insulin's stimulation of these pathways remains largely unknown. This review focuses on the role compartmentalization plays in insulin action, both in signal initiation and in signal reception. Two examples are discussed: (1) a novel signalling pathway leading to the phosphorylation of the caveolar coat protein caveolin, and (2) a recently identified scaffolding protein, PTG, involved directly in the regulation of enzymes controlling glycogen metabolism.

The stimulation of glycogen-targeted protein phosphatase 1 (PP1), glycogen synthase, and glycogen synthesis by insulin was examined during the differentiation of 3T3-L1 fibroblasts into adipocytes. Insulin treatment barely changed the low levels of glycogen synthesis measured in fibroblasts. Following differentiation into adipocytes, insulin increased glycogen synthesis up to 40-fold. After further culturing of the adipocytes for a week, insulin stimulated glycogen accumulation 700-fold. Differentiation of 3T3-L1 cells also resulted in the increased expression of glycogen synthase and in increases in both total glycogen synthase activity and -fold stimulation by insulin. While the levels of PP1 protein were unchanged by differentiation, PP1 specific activity decreased over 60%, although sensitivity to insulin treatment was augmented. Concurrently, levels of the PP1 inhibitor protein DARPP-32 were dramatically induced upon 3T3-L1 adipogenesis. DARPP-32 in both 3T3-L1 and primary rat adipocytes was exclusively localized to the particulate fractions, including the glycogen-enriched pellet. PP1 activity from 3T3-L1 adipocytes exhibited a kinetic lag in vitro, which was not present in fibroblast extracts. Insulin pretreatment of the adipocyte cells overcame the in vitro lag in PP1 activity, resulting in up to 5-fold stimulation of PP1 activity being measured at early assay time points. These results suggest that in 3T3-L1 adipocytes, DARPP-32 may maintain glycogen-targeted PP1 activity in a low basal state, priming the phosphatase for stimulation by insulin.

Assessment of the impact of bone marrow transplantation (BMT) on long-term physical and psychosocial functioning has been hampered by a paucity of prospective research. While evidence suggests that many adult BMT recipients experience deficits in physical and psychosocial functioningor = 1 year following BMT, whether these deficits existed prior to BMT is not known. Observed post-BMT deficits could be attributable to conventional treatments received prior to BMT and thus could have antedated BMT. The physical and psychosocial status of 28 adult BMT recipients was assessed prior to BMT and 12-16 months after BMT. Analysis of group means indicated few significant differences between pre- and post-BMT assessments. However, inspection of residual change scores suggested that physical and psychosocial status improved following BMT for some individuals, while that of others declined. Analysis of residual change scores indicated that males and older patients at time of BMT reported the largest declines in physical and psychosocial status. Longer follow-up is necessary to determine whether decrements observed 12-16 months after BMT reflect a slower process of post-BMT recovery or whether they constitute fairly permanent deficits.

The psychosocial impact of bone marrow transplantation (BMT) was investigated in 172 disease-free adult BMT survivors drawn from five different BMT treatment centers. Respondents were a mean of 43.5 months after BMT. Both questionnaire and interview assessments were utilized. Survivors' perceptions of whether they had 'returned to normal' following BMT, recollections of pre-BMT expectations for returning to normal and current psychological distress were assessed. The results indicated that only a minority of respondents considered themselves to have 'returned to normal' following BMT. Reports of less than normal physical, cognitive, occupational, sexual and/or interpersonal functioning were common. In contrast, few patients reported pre-BMT expectations for such. Discordance between pre-BMT expectations for returning to normal and current functional status was associated with greater current psychological distress. Finally, despite the presence of any functional deficits and despite any discordance between pre-BMT expectations and current functional status, survivors' evaluations of their decision to pursue BMT were generally quite positive. Results are discussed in terms of their implications for: (1) the process of obtaining informed consent for BMT, and (2) clinical strategies for enhancing post-BMT psychological adjustment.

Nerve growth factor (NGF) treatment of PC12 cells led to the rapid phosphorylation of a calmodulin-binding protein of 100 kDa (CaM-BP100) identified on blot overlays with 125I-labeled CaM. The effect was detected as a retardation in the mobility of the protein by an apparent 10 kDa on SDS gels. The mobility shift was complete within 5 min and was maintained for 24 h in the continued presence of NGF. The protein was present in both the soluble and crude particulate fractions, and the gel mobility shift occurred in both fractions. Epidermal growth factor elicited a similar response, but the mobility shift was reversed within 12 h. The gel retardation was due to phosphorylation of CaM-BP100, as it could be reversed if cytoplasmic extracts were held under dephosphorylating conditions at 37 degrees C for 10 min prior to electrophoresis; dephosphorylation was inhibited by okadaic acid but not vanadate, suggesting the participation of a Ser/Thr phosphatase. Treatment with either acid or alkaline phosphatase also reversed the mobility shift. CaM-BP100 phosphorylation was stimulated by 12-O-tetradecanoylphorbol-13-acetate in intact cells, but the effect of NGF did not involve a protein kinase C-dependent process, because it occurred in PC12 cells depleted of protein kinase C. The phosphorylation event appeared to be due to an NGF-stimulated protein kinase, as mixing extracts from NGF-treated cells with extracts from control cells in the presence of ATP and Mg2+ reconstituted the mobility shift in vitro. CaM-BP100 appears to be a minor cellular phosphoprotein, as 32P labeling of the protein could not be detected in crude cell extracts. These results suggest that receptor tyrosine kinases communicate with at least one component of the Ca2+/calmodulin-signaling pathway early in signal transduction.

Long-term cognitive impairment has been reported in adult bone marrow transplant (BMT) recipients. However, the degree to which such impairment is attributable to the procedure or is a condition existing before BMT is not known.The presence, nature, and correlates of neuropsychologic impairment were investigated in 55 adult BMT candidates, all of whom had a malignant condition. Impairment was assessed using a screening battery of standardized neuropsychologic tests.Results indicated that: (1) neuropsychologic performance was associated with specific disease and treatment risk factors, in particular a history of cranial radiation or central nervous system disease treated with intrathecal chemotherapy; (2) performance on tests reflecting memory or higher cognitive processing was more likely to be impaired; and (3) the risk of impairment increased as the number of disease and treatment risk factors for cognitive impairment in the patient increased.It was concluded that neuropsychologic impairment occurs in a significant minority of adult patients before BMT. Research is necessary to determine the extent to which such impairment significantly compromises patients' abilities to: (1) make decisions regarding undergoing BMT or participating in research protocols and (2) understand and execute self-care behaviors after BMT. More broadly, greater attention should be devoted to investigating the presence of long-term neuropsychologic impairment in adult patients with cancer.

We have measured the ultraviolet dispersion of several microscope objectives and we find that all of them are limited by axial chromatic aberration when used for polychromatic exposure of photoresist. We show how to measure and correct for the ultraviolet focus shift, and estimate the corrected resolution. Certain lenses are able to produce micron features over millimeter fields.

We have used a new technique to simultaneously measure the surface topography and surface potential of current-carrying polycrystalline Au 60 Pd 40 thin films using a scanning tunneling microscope. We find abrupt steps in the surface potential due to scattering from grain boundaries in these films.

An ancient beach-ridge plain along the eastern Yucatan Peninsula is underlain by a body of carbonate grainstones 150 km long, 0.5 to 4 km wide, and 3 to 10 m thick. Primary structures and textures suggest that these calcarenites are a regressive sequence deposited in the nearshore and beach zones of a high-energy coast environment. Their accumulation built a strand plain along the prograding Yucatan coast during the late Pleistocene high stand of sea level. In typical vertical sequence (from bottom to top) the upper Pleistocene calcarenite deposits consist of: (a) lower shoreface--low-angle cross-bedded, burrowed bioclastic, fine-coarse calcarenite with calcirudite lenses; (b) upper shoreface--multidirectional trough cross-bedded, bioclastic, pelletoid, and oolitic, fine to coarse calcarenite with calcirudite layers containing shells, corals, caliche lithoclasts, and intraclasts of beachrock; and (c) foreshore-backshore--parallel-laminated oolitic, bioclastic, and pelletoid, fine to medium calcarenite with rhizocretions in the upper part and caliche crusts at the top. In the southern part of the study area the strand-plain grainstones overlie nonbedded bioclastic calcarenite and micrite that were deposited in the offshore between the mainland and a coral barrier reef which fringed the shelf edge. This section overlies thin, discontinuous caliche clast-shell-coral calcirudites (transgressive lag), which lie on a pholad- and sponge-bored subaerial crust (caliche) developed on older limestones. Farther north the strand-plain calcarenites lie directly on the subaerial crust. The shoreface section is largely storm deposits composed of material derived both from offshore and from the shoreline. Storm waves also probably deposited much of the foreshore calcarenite. Thinly coated ooids that are concentrated in the beach and inner-shoreface deposits probably were coated in the high-energy nearshore. These coastal-zone limestones show that significant volumes of porous and permeable carbonate grainstone can be accumulated by seaward advance of the shoreline during high stands of sea level. Ancient strandline grainstones are potential hydrocarbon reservoirs in updip carbonate sequences.

The Upper Cambrian Johns Wash Limestone Member of the Orr Formation constitutes part of the miogeoclinal "carbonate belt" of the Great Basin. In the House Range of western Utah the member may be subdivided into five facies: (1) a bioclastic facies of thin-bedded fossiliferous or mottled wackestones, (2) an oolitic facies of cross-bedded oolitic intraclastic grainstones, (3) a stromatolitic facies consisting of diverse types of algal stromatolites in an oolitic matrix, (4) a pelletoidal facies of burrowed, light gray, oolitic grainstones and pelletoidal packstones, and (5) a fenestral facies of extensively burrowed and bored, light gray mudstones and packstones which possess fenestral fabric. The facies are interpreted as reflecting deposition on a broad platform on which an oolite shoal separated a shallow-water lagoon from a more open marine environment to the west. Landward of the lagoon, the fenestral facies accumulated on an extensive tidal flat. Westward progradation of these environments resulted in superposition of the facies which compose the regressive carbonate sequence of the Johns Wash Limstone in the House Range.

We have used a new technique to measure simultaneously the surface topography and surface potential of current-carrying polycrystalline Au/sub 60/Pd/sub 40/ thin films using a scanning tunneling microscope. The variations of the gradients of the surface potential from a macroscopically constant value which are associated with scattering from grain boundaries in these films are observed. We find that the local potential changes abruptly at the boundaries between the grains.

We report a simple technique for making flip‐chip contacts. The equipment required, in addition to a small‐scale photoresist clean room, is a beaker of molten solder.

The use of cod liver oil as a prophylactic and therapeutic agent in the treatment of patients with rickets, while widespread and generally satisfactory, is being somewhat supplanted by irradiated ergosterol. It was felt desirable to study a controlled group of infants, some of whom were given cod liver oil, some irradiated ergosterol and others cod liver oil and irradiated ergosterol, keeping a number to whom no antirachitic agent was given. A great many of the present observations on the therapeutic and prophylactic value of irradiated ergosterol are based on experiments on laboratory animals, and these reports are made still less accurate in that the dosage of irradiated ergosterol is stated in milligrams, though it is well known that different batches of irradiated ergosterol vary tremendously in the amount of vitamin D contained. The only satisfactory way to make comparative evaluations of cod liver oil and irradiated ergosterol as antirachitic