cssi/SciSciGPT-SciSciNet huggingface dataset:
mRNA at the synapse: analysis of a synaptosomal preparation enriched in hippocampal dendritic spines

Previous studies have demonstrated that the branched spines of the mossy fiber-CA3 hippocampal synapse contain a particularly large number of polyribosomes (Chicurel and Harris, 1989, 1992). We analyzed a preparation of synaptosomes isolated from this region and have found it to contain a restricted RNA population: certain mRNAs, presumably derived from the dendritic spines and the fine astrocytic processes surrounding the pre- and postsynaptic elements of the synapse, are enriched in the synaptosome preparation as compared to the total hippocampus; other mRNAs are less prevalent or altogether absent. In addition, neural BC1, a small noncoding RNA thought to be involved in pre- or posttranslational regulatory processes in dendrites, is a major RNA component of the dendritic spine. These results support the hypothesis that local translational regulation of gene expression may be important in establishing and modulating synaptic function.
Abstract 13878: Smooth Muscle-specific IGF-1 Receptor Deficiency Increases Atherosclerosis and Promotes Features of Unstable Plaque

Insulin-like growth factor I (IGF-1) has pleiotropic effects, stimulating growth, differentiation, survival and anabolism, in multiple tissues and cell types including smooth muscle cells (SMC). Although IGF-1 is a SMC mitogen, we have previously shown that systemic IGF-1 infusion reduces atherosclerosis in Apoe-null mice. To determine the role of SMC IGF-1 receptor (IGF-1R) signaling in atherogenesis, we generated SMC-specific IGF-1R/Apoe-double knockout mice (22KO) by crossing floxed IGF-1R mice (FIR) with mice expressing Cre recombinase under control of the SM22α promoter. 22KO mice had >80% reduction in aortic IGF-1R expression vs. FIR mice, no change in serum IGF-1 levels (22KO: 325.99±24.24 ng/ml vs FIR: 348.11±18.79 ng/ml, P=NS), reduced body weight (15±3% decrease, p<0.05) and weight of SMC-rich organs (urinary bladder, 37±4% decrease; aorta, 18±2% decrease, p<0.05), thinner aortic wall media (40±5% decrease, p<0.05), reduced size of individual aortic SMC (23±3% decrease, P<0.05) without a change ...
Middle and late adolescents' conflict resolution skills with siblings : Associations with interparental and parent-adolescent conflict resolution

The present study examined whether conflict resolution skills utilized in the interparental and parent–adolescent relationships were related to adolescents' conflict resolution skills with siblings. The associations between interparental, parent–adolescent, and sibling conflict resolution skills were compared for middle and late adolescents. Middle adolescents (N = 89) and late adolescents (N = 90) reported their perceptions of attack and compromise conflict resolution styles for both family members within a dyadic relationship. Differences were found between middle and late adolescents regarding their perceptions of attack and compromise resolution styles utilized in family dyadic relationships. Path analysis results indicated that the influence of interparental conflict resolution on sibling conflict resolution was mediated by mom–adolescent and dad–adolescent resolution for both middle and late adolescents. Theoretical and empirical implications of these findings are discussed here.
Stress and Mental Illness

Social scientific research has highlighted that stressful experiences, social statuses, and environments contribute to the development of mental illness. Sociologists have contributed to our knowledge with social stress theory, which acknowledges levels of exposure to stress and access to coping resources. Numerous studies have used the social stress process model to explain the link between social inequality and mental health disparities. This model is the basis for social stress theory. According to social stress theory, people with disadvantaged social status are more likely to be exposed to stressors and to be more vulnerable to stress because they have limited psychosocial coping resources; these in turn lead to a higher risk of mental illness. Sociological studies have further revealed that chronic stressors have a more harmful influence on mental health than acute stressors, such as life events. Therefore, chronic stressors should be taken into account, as well as the number of stressful life events, in assessing exposure and mental health risk. This entry will discuss key advances in the social scientific literature on stress and mental illness. Keywords: coping; social causation; sociology of mental health; stress
Human Subjects Research, Ethics, Research on Vulnerable Populations

Introduction Vulnerable Populations in Biomedical Research Genetic Research with Vulnerable Populations Subject Selection Predicament—Exclusion or Inclusion? Perils of the Therapeutic Misconception: Making the Distinction Between Clinical Treatment and Biomedical Research Impact and Influence of International Codes, U.S. Regulatory Policies, and Bioethics Commissions on Research with Vulnerable Subjects International Codes Evolution of U.S. Policies for Protection of Vulnerable Human Research Subjects Recent Efforts to Establish Appropriate Safeguards for Vulnerable Subjects Ethically Controversial Research Design Research Anticipatory Planning Genealogy of Research Advance Directives Unanticipated Circumstances and the Appointment of a Surrogate Decision Maker Capacity to Engage in Anticipatory Planning Research Risk Assessment Ambiguities That Reinforce Need for Anticipatory Planning Keywords: human subjects research; ethics
Metallothionein III is expressed in neurons that sequester zinc in synaptic vesicles

MT-III, a brain-specific member of the metallothionein gene family, binds zinc and may facilitate the storage of zinc in neurons. The distribution of MT-III mRNA within the adult brain was determined by solution and in situ hybridization and compared to that of MT-I mRNA. MT-III mRNA is particularly abundant within the cerebral cortex, hippocampus, amygdala, and nuclei at base of the cerebellum. Transgenic mice generated using 11.5 kb of the mouse MT-III 5' flanking region fused to the E. coli lacZ gene express beta-galactosidase in many of the same regions identified by in situ hybridization. MT-III mRNA was present in readily identifiable neurons within the olfactory bulb, hippocampus, and cerebellum, and beta-galactosidase activity was localized to neurons throughout the brain, but not to glia, as determined by costaining with X-Gal and neural- and glia-specific antibodies. There is marked correspondence between the neurons that are rich in MT-III mRNA and those neurons that store zinc in their terminal vesicles. MT-III is found complexed with zinc in vivo and its expression in cultured cells leads to the intracellular accumulation of zinc and enhanced histochemical detection of zinc. These results are discussed in light of the possibility that MT-III may participate in the utilization of zinc as a neuromodulator.
Digestion and metabolism of sugars

Many factors potentially influence the digestion, absorption, and metabolism of the various species of sugars occurring in the human diet. Experimental evidence indicates that the source of sugars in foods does not in itself affect the rate of absorption or the metabolism of the sugars. However, the form in which the sugars are ingested and the physical and chemical properties of the food matrices do have significant effects on the rates of absorption. Food matrices influence gastric emptying and through their physical properties affect the rate of transport across the small intestinal mucosa. Disaccharides form the major proportion of ingested carbohydrates in the small intestine and the digestion and transport systems for these sugars, except for lactose, are the most efficient. After absorption, the pathways of the different dietary sugars converge and the original dietary source has only minimal effects on metabolism.
Chronic Pain: Biological Understanding and Treatment Suggestions for Mental Health Counselors

Biopsychosocial factors related to chronic pain are discussed as a necessary foundation for understanding and helping clients who are in pain. Familiar evidence-based counseling approaches that have proven useful for working with clients who are in pain are reviewed to identify how practitioners can use their counseling skills to help these clients. Approaches reviewed are assessment considerations, use of psychotropic medications, cognitive-behavioral strategies, hypnosis and imagery techniques, family considerations, and positive psychology.
COUNTERFEITING THE NATION? Skopje 2014 and the Politics of Nation Branding in Macedonia

This article analyzes the political dynamics centered on Skopje 2014, an urban renovation project sponsored by the government of the Republic of Macedonia, which is linked to efforts to define a distinctive nation brand for the country. Examining the project and the controversies it has generated, I argue that the form of nation branding represented by Skopje 2014 indicates a new modality of neoliberal governance in which the state functions as an entrepreneurial subject within a competitive global marketplace oriented to the attraction of deterritorialized finance capital. I show how promoting a national brand image defined a field of state management where the development project was imagined to mediate Macedonia's relationship to foreign investment and tourism. However, as illustrated by the Macedonian case, nation branding not only rationalizes a new state project but also grounded an idiom of popular claim-making on the state. Through portrayals of the Skopje 2014 project as an inauthentic and counterfeit copy of other European cities, critics have constructed counterproductive national promotion as both an economic and existential threat to citizen-subjects. The article therefore explores how nation branding can open a new space of politics when nation-brand images emerge as sites of popular contestation. [nation branding, national identity, representation, citizenship, neoliberalism, Macedonia]
The effects of overt intralist retrieval on subsequent free recall

Twenty Ss learned five 12-word lists. Following the immediate free recall of the fifth list, the Ss were asked to recall and recognize all the 60 words in the previous lists. The Ss in the experimental group were instructed to study each presented word carefully and, after the presentation of every 3 words, to overtly recall the preceding 3 words. Although this intralist retrieval procedure provides a basis for grouping, it has a detrimental effect not only on item accessibility, but also on item availability. A “removal property” of short-term memory was proposed as the locus of this effect. In addition, examination of the response pattern of the final free recall shows that the differential rehearsal interpretation proposed by Cohen (1970) is inappropriate.
Students With and At Risk for Emotional and Behavioral Disorders: Meeting Their Social and Academic Needs

Given the negative outcomes experienced by students with emotional and behavioral disorders (EBD), it is imperative that these students receive empirically validated interventions to meet their educational needs. This issue is dedicated to providing educators with both the research base and the practical tools for meeting these challenges. Specifically, this issue will offer feasible, effective procedures for conducting social skills interventions that address some of the core limitations in the social skills literature. Furthermore, this issue will address the academic needs of students with EBD by (a) documenting teachers' self-reported professional needs development and use of instructional modifications and (b) providing guidelines for supporting secondary students with EBD as they meet the call for high-stakes testing and transition from school to life.
Statistical Modeling of Agatston Score in Multi-Ethnic Study of Atherosclerosis (MESA)

The MESA (Multi-Ethnic Study of Atherosclerosis) is an ongoing study of the prevalence, risk factors, and progression of subclinical cardiovascular disease in a multi-ethnic cohort. It provides a valuable opportunity to examine the development and progression of CAC (coronary artery calcium), which is an important risk factor for the development of coronary heart disease. In MESA, about half of the CAC scores are zero and the rest are continuously distributed. Such data has been referred to as “zero-inflated data” and may be described using two-part models. Existing two-part model studies have limitations in that they usually consider parametric models only, make the assumption of known forms of the covariate effects, and focus only on the estimation property of the models. In this article, we investigate statistical modeling of CAC in MESA. Building on existing studies, we focus on two-part models. We investigate both parametric and semiparametric, and both proportional and nonproportional models. For various models, we study their estimation as well as prediction properties. We show that, to fully describe the relationship between covariates and CAC development, the semiparametric model with nonproportional covariate effects is needed. In contrast, for the purpose of prediction, the parametric model with proportional covariate effects is sufficient. This study provides a statistical basis for describing the behaviors of CAC and insights into its biological mechanisms.
Magnification of rRNA gene number in a Neurospora crassa strain with a partial deletion of the nucleolus organizer

Some progeny from crosses between the Neurospora crassa translocation strain T(IL→ VL)OY321 and normal sequence N. crassa strains are duplication strains with a partial deletion of the nucleolus organizer. Despite the deletion, these progeny are viable and produce a functional nucleolus. Quantification of rRNA gene number in these deletion progeny demonstrated a significant loss of rRNA genes, down to 60% of the parental wild-type level. Initially, all of these reduced nucleolus organizer (RNO) strains demonstrated a reduction in the rate of mycelial elongation in growth tubes. After several vegetative growth cycles some progeny reverted to the normal growth phenotype, and also showed an increase in the number of rRNA genes to approximately that of the wild type.
Latent semantic indexing is an optimal special case of multidimensional scaling

Latent Semantic Indexing (LSI) is a technique for representing documents, queries, and terms as vectors in a multidimensional real-valued space. The representtions are approximations to the original term space encoding, and are found using the matrix technique of Singular Value Decomposition. In comparison Multidimensional Scaling (MDS) is a class of data analysis techniques for representing data points as points in a multidimensional real-valued space. The objects are represented so that inter-point similarities in the space match inter-object similarity information provided by the researcher. We illustrate how the document representations given by LSI are equivalent to the optimal representations found when solving a particular MDS problem in which the given inter-object similarity information is provided by the inner product similarities between the documents themselves. We further analyze a more general MDS problem in which the interdocument similarity information, although still in inner product form is arbitrary with respect to the vector space encoding of the documents.
Urban Residents' Perceptions of Environmental Impacts

This article examines urban residents' perceptions of environmental impacts in the city of Pigeon Forge, Tennessee. The study vies to contribute to knowledge concerning how citizens in Tennessee view tourism and its impact on the environment. A mail survey was administered to 400 registered voters. Factor analysis, Cramer's V statistical measures of association, chi-square tests, and Spearman correlation coefficients were employed for the analysis and interpretation of the data. Tests and associations support three hypotheses; residents' perceptions of the impact of tourism are influenced by employment status and short-term residency. Greater lengths of residency, age, and annual income do not influence residents' perceptions.
Inorganic and Organometallic Polymers — An Overview

In the years since we organized our first symposium on inorganic and organometallic polymers in 19711 and five subsequent symposia in 1977,2 1979,3 1985,4 1989,5 and 1994,6 we have seen this field produce a wide variety of materials with diverse applications such as polymeric conductors and semiconductors, preceramic materials, polymer bound catalysts, shields for UV and other high energy radiation, biosensors, polymers with high thermal stability, flame retardency, and a wide variety of applications. Indeed, what can be expected when you incorporate the entire periodic table into a field that formerly had concentrated primarily on C, H, N, O, S, Si and the halogens?
Performance characteristics of the anaerobic baffled reactor

Abstract An anaerobic sludge blanket process, termed the anaerobic baffled reactor (ABR), has been developed and shows promise for industrial wastewater treatment. It combines the advantages of high stability and reliability with a high void volume. The risk of clogging and sludge bed expansion with resulting high microbial losses is reduced and there is no need for special gas collection or biological solids separation systems. Organic loadings as high as 36 g COD l−1day−1 have been achieved with COD removal rates of more than 24 g COD l−1 day−1 and methane production rates exceeding 6 volumes per day per unit volume of reactor. The hypothesis, that the ABR may be adequately modeled as a fixed-film reactor, has been supported. Therefore, a unified approach, based on fundamentals of bacterial kinetics and mass transport, appears useful for modeling this and similar systems. Pilot plant studies are necessary to determine the scaling factors of the system as well as the overall efficiency and costs.
Uniqueness Results for Extremal Holomorphic Functions in Product Domains

In this note, we prove a generalized version of the classical Schwarz Lemma in product domains. This generalization of the Schwarz Lemma to product domains follows from a more general uniqueness result for extremal holomorphic functions in product domains.
Modulation of hexose transport in cultured skeletal muscle

The modulation of hexose transport due to insulin and glucose starvation was investigated in cultures derived from the breast musculature of embryonic quail. Fused myotubes at 37 degrees C exhibited a saturable, stereospecific basal uptake of both D-glucose and 3-O-methylglucose which was markedly inhibited by cytochalasin B, a potent inhibitor of hexose transport in other cell systems. In the presence of insulin, 3-O-methylglucose uptake was stimulated relative to untreated controls. Kinetic analysis indicated that insulin increased the Vmax of transport with no significant increase in the apparent Km. Incubation of myotubes in glucose-free medium for 24 h resulted in an increase in D-glucose and 3-O-methylglucose transport activity. Cycloheximide abolished this stimulation effect when it was included during the starvation period, but had no effect on transport in glucose-fed cells. Insulin binding studies on these myotubes indicate that high-affinity insulin receptors are present and continue to increase throughout the life of the culture. This high-affinity binding as well as the capacity to degrade insulin in these cells is characteristically similar to effects observed in other insulin-sensitive cell systems.
An exact solution for surface temperature in down grinding

A model has previously been developed for heat transfer in down grinding. A numerical solution algorithm was used to solve the system of equations. In this paper, an exact solution is found for this set of equations. The effect of the location of heat generation (i.e., at wear flats or shear planes) is explored for three typical grinding conditions: conventional grinding with aluminum oxide abrasives, creep feed grinding with aluminum oxide abrasives, and conventional grinding with cubic boron nitride (CBN) abrasives. It is found that during grinding with CBN, there is a strong effect of the assumed location of heat generation.
Practical Issues in Physician-Assisted Suicide

Support for the participation of physicians in the suicides of terminally ill patients is increasing, and the concrete effects on physician practice of a policy change with regard to physician-assisted suicide must be carefully considered. If physician-assisted suicide is legalized, physicians will need to gain expertise in understanding patients' motivations for requesting physician-assisted suicide, assessing mental status, diagnosing and treating depression, maximizing palliative interventions, and evaluating the external pressures on the patient. They will be asked to prognosticate not only about life expectancy but also about the onset of functional and cognitive decline. They will need access to reliable information about effective medications and dosages. The physician's position on physician-assisted suicide must be open to discussion between practitioner and patient. Protection of the patient's right to confidentiality must be balanced against the need of health care professionals and institutions to know about the patient's choice. Insurance coverage and managed care options may be affected. All of these issues need to be further explored through research, education, decision making by individual practitioners, and ongoing societal debate.
Purification of anti-fibrinogen antibodies.

Abstract Anti-fibrinogen antibodies can be harvested in pure and fully active form by simply precipitating them in combination with fibrinogen and subsequently retrieving them free of fibrinogen by redissolving and selectively salting out the fibrinogen at pH 2.4.
Probe diffusion in concentrated polyelectrolyte solutions : Effect of background interactions on competition between electrostatic and viscous forces

We have used fluorescence recovery after photobleaching (FRAP) to measure the diffusion coefficient D of a small probe protein, green fluorescent protein (GFP), in solutions of the polyelectrolyte sodium polystyrenesulfonate (NaPSS) over a wide range of conditions. We covered a range of polyelectrolyte concentrations that resulted in solution viscosities η from 1 to 50−100 cP, contrasted the behavior of high molecular weight (1 × 106 Da) and low molecular weight (7 × 104 Da) NaPSS, and explored the effects of low and high salt concentrations. We worked at a solution pH of 5.5, slightly higher than the isoelectric point of the GFP, which therefore had a small net negative charge. We observed positive deviations as large as 10-fold from Stokes−Einstein (S−E) behavior in high molecular weight NaPSS at low ionic strength. However, in low molecular weight NaPSS, approximately the same molecular weight as the DNA from our previous studies, deviations from S−E behavior were more modest, less than 2-fold. For hig...
Cerebrospinal fluid abnormalities in acute posterior multifocal placoid pigment epithelialopathy.

Two patients with acute posterior multifocal placoid pigment epithelialopathy also had cerebrospinal fluid pleocytosis and elevated protein levels. A 24-year-old white women had visual acuity of counting fingers in each eye. The cerebrospinal fluid contained 56 lymphocytes per cubic millimeter and a protein level of 48 mg/100 ml. When the retinopathy resolved, visual acuity returned to R.E.: 6/60 (20/200), AND L.E.: 6/9 (20/30). A 22-year-old white man had visual acuity of counting fingers bilaterally. The initial lumbar puncture showed 70 lymphocytes and a protein level of 76 mg/100 ml. A second cerebrospinal tab showed 64 lymphocytes and a protein level of 86 mg/100 ml. Final visual acuity was R.E.: 6/15 (20/50), and L.E.: 6/6 (20/20). Neither patient received treatment for this disorder. The findings of cerebrospinal fluid cells and elevated protein levels in acute posterior multifocal placoid pigment epithelialopathy probably represent a mild viral meningitis as part of a systemic viral infection that also involves the retinal pigment epithelium or choriocapillaris.
An 18 000-dalton protein metabolically labeled by polyamines in various mammalian cell lines

The possible role of polyamines in the covalent modification of cellular protein(s) was investigated by studying the metabolic labeling of NB-15 mouse neuroblastoma cells by [14C]putrescine in fresh Dulbecco's medium followed by separation of cellular proteins through sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Under such incubation conditions, a single protein band with an apparent molecular weight of 18000 was radioactively labeled. [14C]Spermidine also specifically labeled this protein. The majority of the radioactivity covalently linked to the 18-kDa protein was recovered as hypusine. The radioactive labeling of this protein was stimulated 1.3-fold by 1 mM dibutyryl cAMP and 2.8-fold by 4% fetal calf serum. Fetal calf serum also stimulated the labeling of many other cellular proteins. This may be due to the conversion of putrescine to amino acids via the formation of gamma-aminobutyric acid. Aminoguanidine, a potent inhibitor of diamine oxidase, completely inhibited the fetal calf serum-stimulated labeling of these cellular proteins but had no effect on the labeling of the 18-kDa protein. The specific labeling of the 18-kDa protein by [14C]putrescine occurred in various mammalian cells examined including the N-18 mouse neuroblastoma cells, 3T3-L1 murine preadipocytes, and H-35 rat hepatoma cells. The specificity of labeling of the apparently ubiquitous 18-kDa protein and the stimulation of this labeling by fetal calf serum suggest that this protein may be important in mediating some of the actions of polyamines in cell growth regulation.
Simultaneous 68Ga-DOTA-TOC PET/MRI with gadoxetate disodium in patients with neuroendocrine tumor

To evaluate a simultaneous PET/MRI approach to imaging patients with neuroendocrine tumor using a combination of 68Ga-DOTA-TOC as a PET contrast agent and gadoxetate disodium as a hepatobiliary MRI contrast agent. Ten patients with neuroendocrine tumor with known or suspected hepatic disease were imaged using a 68Ga-DOTA-TOC PET/CT immediately followed by a 3.0T time-of-flight PET/MRI, using a combined whole body and liver specific imaging. The presence of lesions and DOTA-TOC avidity were assessed on CT, PET from PET/CT, diffusion weighted imaging, hepatobiliary phase imaging (HBP), and PET from PET/MRI. Maximum standardized uptake values (SUVmax) in hepatic lesions and nodal metastases were compared between PET/CT and PET/MRI, as were detection rates using each imaging approach. A total of 101 hepatic lesions were identified, 47 of which were DOTA-TOC avid and able to be individually measured on both PET/CT and PET/MRI. HBP imaging had a higher sensitivity for detection of hepatic lesions compared to CT or PET (99% vs. 46% and 64%, respectively; p values <0.001). There was a strong correlation between SUVmax of liver lesions obtained with PET/CT compared to PET/MR imaging (Pearson’s correlation = 0.91). For nodal disease, CT had a higher sensitivity compared to whole body MRI (p = 0.015), although PET acquired from PET/MRI detected slightly more lesions compared to PET from PET/CT. A simultaneous PET/MRI using both 68Ga-DOTA-TOC and gadoxetate disodium was successful in whole body staging of patients with neuroendocrine tumor. HBP imaging had an increased detection rate for hepatic metastases.
Anorectic agents lower a body weight set point

Abstract A new theory of the action of “appetite suppressant” agents proposes that they act primarily by lowering a body weight set point and only secondarily by suppressing appetite (1, 2). Evidence is reviewed that body weight is regulated in animals rendered overwieght or underweight by hypothalmic lesions as well as in those of normal weight. A very recent study can be interpreted as indicating that both amphetamine and fenfluramine lower a body weight set point in experimental animals (3). Clinical evidence also supports this theory, notably the rapid regaining of body weight following withdrawal of “appetite-suppressant” medication, in contrast to the relative stability of weight losses achieved without medication (4). This set point explanation of the rebound in body weight following withdrawal of medication has not been proposed before. One reason may be the long-standing belief that tolerance to this medication develops very rapidly. For, if an agent quickly lost its effectiveness, it could not lower a set point over long periods of time and withdrawing it would not result in an elevation of that set point. At least three clinical findings argue against the development of tolerance. In addition to the rebound in body weight, they include little slowing in the rate of weight loss and no increase in hunger during several months of treatment with fenfluramine (2, 4). If tolerance had developed, slowing of the rate of weight loss and increase in hunger would have been expected. This theory and these findings suggest a radical revision in prescribing practices for “appetite-suppressant” medication: use it on a chronic basis or not at all. The reason for discontinuing the current practice of restricting it to short-term use is the opposite of that currently invoked: not because of the development of tolerance, but precisely because tolerance does not develop. If medication lowers a body weight set point, discontinuing the medication, with elevation of the set point to its previous level, subjects patients to powerful pressures to regain the weight they had lost. The chronic use of “appetite-suppressant” medication should be seriously considered. The benefits may well outweight the risks, particularly for some obese people.
Gliomas in patients with acquired immune deficiency syndrome.

Background. Ten percent of patients with acquired immune deficiency syndrome (AIDS) have intracerebral mass lesions of which the majority are due either to toxoplasmosis or primary central nervous system lymphomas. Methods. Three patients with AIDS presented with solitary intracerebral mass lesions and were found by pathologic examination to have gliomas. Results. After surgery, all patients were treated with radiotherapy and procarbazine, comustine, and vincristine multiagent chemotherapy. Median follow-up is 12 months. Conclusions. Occasionally, patients with AIDS and intracerebral mass lesions have primary nonlymphomatous brain tumors, an occurrence not related clearly to underlying immunoincompetence.
Semiparametric Models for Longitudinal Data with Application to CD4 Cell Numbers in HIV Seroconverters

The paper describes a semiparametric model for longitudinal data which is illustrated by its application to data on the time evolution of CD4 cell numbers in HIV seroconverters. The essential ingredients of the model are a parametric linear model for covariate adjustment, a nonparametric estimation of a smooth time trend, serial correlation between measurements on an individual subject, and random measurement error. A back-fitting algorithm is used in conjunction with a cross-validation prescription to fit the model. A notable feature in the application is that the onset of HIV infection is associated with a sudden drop in CD4 cells followed by a longer-term slower decay. The model is also used to estimate an individual's curve by combining his data with the population curve. Shrinkage toward the population mean trajectory is controlled in a natural way by the estimated covariance structure of the data.
Rural Electric Demand Research

In cooperative research with rural power suppliers in Nebraska, 35 recording demand meters were installed. The demand study was started in December of 1980 and concluded in March of 1983. Data collection in Nebraska was concentrated in a five-county area in eastcentral Nebraska. Customers were sampled based on a stratified randomized design. Electrical demands were recorded for 5-min intervals. Coincidental peak demands for 60-min intervals were determined for selected peak power use days in 1981 and 1982. In addition, 15-min coincidental demands showing maximum average and minimum demands for each month for the two-year study are presented. Demands predicted by the Rural Electrification Administration demand tables were generally lower than the measured demands while demands predicted by linear regression analysis were higher than the measured demands. Measured coincidental peak demands per customer for the total of all stratified groups ranged from 5.7 to 8.6 kW.
Oligonucleotide antiviral therapeutics: Antisense and RNA interference for highly pathogenic RNA viruses

RNA viruses are a significant source of morbidity and mortality in humans every year. Additionally, the potential use of these viruses in acts of bioterrorism poses a threat to national security. Given the paucity of vaccines or postexposure therapeutics for many highly pathogenic RNA viruses, novel treatments are badly needed. Sequence-based drug design, under development for almost 20 years, is proving effective in animal models and has moved into clinical trials. Important advances in the field include the characterization of RNA interference in mammalian cells and chemical modifications that can dramatically increase the in vivo stability of therapeutic oligonucleotides. Antisense strategies utilize single-stranded DNA oligonucleotides that inhibit protein production by mediating the catalytic degradation of target mRNA, or by binding to sites on mRNA essential for translation. Double-stranded RNA oligonucleotides, known as short-interfering RNAs (siRNAs), also mediate the catalytic degradation of complementary mRNAs. As RNA virus infection is predicated on the delivery, replication, and translation of viral RNA, these pathogens present an obvious target for the rapidly advancing field of sequence-specific therapeutics. Antisense oligonucleotides or siRNAs can be designed to target the viral RNA genome or viral transcripts. This article reviews current knowledge on therapeutic applications of antisense and RNA interference for highly pathogenic RNA viral infections.
Isotopic evidence for the origin of the Manihiki and Ontong Java oceanic plateaus

Abstract Pb, Nd, and Sr isotopic results for lavas of the Cretaceous Ontong Java and Manihiki oceanic plateaus fall well within the modern-day oceanic island or hotspot field. The data provide no evidence of old continental basements but indicate a major involvement of “Kerguelen-type” or “EM-I”-like mantle in the sources of both plateaus, which appear to have probably been formed, at least in part, by hotspots. However, the presently active hotspots that Pacific plate reconstructions suggest might have been possible plateau sources lack Kerguelen-type isotopic compositions. Either these hotspots did not participate in the formation of the two plateaus, or if they did, Kerguelen-type material must have been volumetrically much more important early in their existence. Two hypotheses for the origins of these plateaus which involve hotspot sources are consistent with the sparse available geochemical, geochronological and geophysical data. The first holds that the plateaus formed cataclysmically in association with surfacing plume heads; the second posits a relatively steady but robust hotspot at or near a ridge crest and requires a much longer period of formation. A near-ridge origin appears to be indicated by evidence that most of the Pacific plateaus were built largely on relatively young ocean crust. However, we suggest that a near-ridge origin is also compatible with the plume head concept in that plume heads appear very likely to become associated with spreading axes through their influence on rift propagation, which should be substantially greater than for ordinary hotspots. In either case, the lack of hotspot tracks (seamount chains) attached to the two plateaus would be a consequence of ridge migration or rift propagation in a near-ridge setting.
Synergistic Activation of Glucose-6-Phosphate Dehydrogenase and NAD(P)H oxidase by Src kinase Elevates Superoxide in Type 2 Diabetic, Zucker fa/fa, Rat Liver

Type 2 diabetes affects approximately 170 million people around the world and these numbers are rapidly rising every year [1]. This metabolic syndrome is now widely recognized as a risk factor for liver disorders, obesity and cardiovascular diseases. Several studies have suggested that oxidative stress is elevated by chronic hyperglycemia in diabetic animal models as well as in diabetic patients [2–7]. Overproduction of superoxide anion (O2−) by the mitochondria, polyol pathway, NAD(P)H oxidase, uncoupled nitric oxide synthase, and reduced endogenous antioxidant enzymes have been proposed to increase oxidative stress in hyperglycemia. Yet, the underlying mechanism that activates reactive oxygen species generation in hyper-glycemia or -insulinemia is far from clear. Brownlee and colleagues [8], have proposed that an increase in advanced glycation end products, activation of protein kinase C (β isoform), and activation of aldosereductase in diabetes, elevate O2− generation from mitochondrial respiratory chain. Furthermore, other studies have shown that in streptozotocin-treated (type 1 diabetes) rat model there is over-expression of NAD(P)H oxidase (Nox-2 and Nox-4) in the vascular system and kidneys with a concomitant elevation in O2− production [2, 9]. In most tissue types, constitutively active NAD(P)H oxidase produces low levels of O2− [10]. Additionally, in pathophysiological conditions, activation of NADPH oxidase following stimulation by factors such as, angiotensin II, thrombin, and TNFα [10, 11], leads to subsequent elevation in O2− generation. Other investigators and we have shown that NADPH derived from glucose-6-phosphate dehydrogenase (G6PD), a rate limiting enzyme in the pentose phosphate pathway (PPP) that produces a major portion of NADPH in the cell, fuels NADPH oxidase and O2− production in the failing heart [12, 13], angiotensin-II and PKC agonist treated vasculature [14, 15], and neutrophiles in basal state [16] and during respiratory burst [17]. Since NADPH levels have been shown to be elevated in the endothelial cells of diabetic (type 1) BB rats [18], we postulated that an increase in G6PD-derived NADPH in type 2 diabetes could elevate NADPH oxidase-derived oxidative stress. This study was, therefore, designed to investigate the implications of imbalance in glucose metabolism observed in type 2 diabetes, on oxidoreductases enzymes such as G6PD and NADPH oxidase in the liver of young Zucker fa/fa rats, an animal model of type 2 diabetes, resembling human diabetes. In particular we investigated whether; [i] the G6PD expression and activity is up-regulated, [ii] protein expression and activity of NAD(P)H oxidase is altered, and [iii] PI3Kinase and Src kinases-dependent signaling pathways and G6PD-derived NADPH evoke Nox-derived O2− in liver from young (9–11 weeks old animals) Zucker fa/fa rats as compared to the lean rats.
Axenfeld-Rieger syndrome in the age of molecular genetics.

Abstract %PURPOSE: To review the molecular genetics of Axenfeld-Rieger syndrome and related phenotypes and to discuss how this information might affect the way that we classify these disorders. METHODS: A review of historical and recent literature on Axenfeld-Rieger syndrome and related disorders. The review includes clinical and molecular genetic literature relevant to these phenotypes. RESULTS: Three chromosomal loci have recently been demonstrated to link to Axenfeld-Rieger syndrome and related phenotypes. These loci are on chromosomes 4q25, 6p25, and 13q14. The genes at chromosomes 4q25 and 6p25 have been identified as PITX2 and FKHL7, respectively. Mutations in these genes can cause a wide variety of phenotypes that share features with Axenfeld-Rieger syndrome. Axenfeld anomaly, Rieger anomaly, Rieger syndrome, iridogoniodysgenesis anomaly, iridogoniodysgenesis syndrome, iris hypoplasia, and familial glaucoma iridogoniodysplasia all have sufficient genotypic and phenotypic overlap that they should be considered one condition. CONCLUSIONS: Axenfeld-Rieger syndrome is a term that can be used to describe a variety of overlapping phenotypes. To date, at least three known genetic loci can cause these disorders. The single most important feature of these phenotypes is that they confer a 50% or greater risk of developing glaucoma. Currently there is a fairly arbitrary grouping of disorders into small categories. Considering all of these phenotypes under the heading of Axenfeld-Rieger syndrome will allow easier communication between clinicians and scientists and eliminate arbitrary and confusing subclassification.
Career path and skill set for PharmDs as successful clinical pharmacology scientists: A case study and perspective of a former industry scientist

Abstract Objective Most pharmacy graduates are not fully informed of the highly specialized opportunities in the pharmaceutical industry. The purpose of this report is to outline a career path and define the skill set for PharmDs who want to pursue a career as clinical pharmacology (CP) scientists. Methods Three case studies are presented of PharmDs who enrolled in postgraduate fellowship programs and gained employment in the industry as clinical pharmacologists. They were followed up after being on the job for at least two years with a questionnaire on training, mentorship and career path. Results Data showed areas needing additional training included, how to efficiently design and run clinical studies, effective communication with team members, advanced pharmacokinetics/pharmacodynamics (PK/PD) analysis and interpretation, dosage forms and bioavailability issues, and metabolism and transporter issues. Conclusions Initiatives by academia and industry are needed to coordinate the training of PharmD scientists preparing to pursue careers in CP. Efforts should include academic institutions offering electives and redesigning fellowships to address today's complex drug-development needs.
Dissociation of endogenous components of auditory evoked potentials following carbachol microinjection into the cholinoceptive pontine inhibitory area.

Abstract Microinjections of the cholinergic agonist, carbachol, into an area ventromedial to the principal nucleus of the locus coeruleus produce pronounced suppression of postural somatomotor and sympathetic visceromotor functions, and profound unresponsiveness to external stimuli. In order to clarify whether this unresponsiveness is due exclusively to disruption of motor components of various behavioral responses, we examined changes in the endogenous components of auditory evoked potentials recorded in conjunction with a tone discrimination task. Concomitant with carbachol-induced behavioral unresponsiveness, the late positive component (LPC) at 250–350 ms disappeared, while the early positive component at 80–150 ms was enhanced. This result suggests that, after the onset of carbachol-induced behavioral unresponsiveness, external stimuli enter the brain but are not integrated in neural processes reflected in LPC which has previously been implicated in processes mediating orienting responses, selective attention, and/or cognitive evaluation.
ON THE DIFFUSION OF LOAD FROM A TRANSVERSE TENSION-BAR INTO A SEMI-INFINITE ELASTIC SHEET.

Abstract : The paper deals with the load-diffusion from a tension-bar of finite length and uniform cross-section into a semi-infinite sheet, the axis of the bar being perpendicular to the edge of the sheet. The bar is regarded as a one-dimensional elastic continuum, whereas the elastic sheet is treated within the two-dimensional theory of generalized plane stress. Three alternative models for the stringer-attachment are considered: (a) line-contact; (b) area-contact based on matching the axial stringer-strain and the corresponding average sheet-strain across the width of the strip of adhesion; (c) area-contact based on matching the stringer-strain and the corresponding sheet-strain along the centerline of the strip of adhesion. It is shown that the line-contact model, in contrast to both area-contact models, does not admit the transmission of portions of the applied load through forces concentrated at the ends of the adhering bar-segment. Further, asymptotic estimates are deduced for the end-slopes of the load-diffusion curves appropriate to the three models under consideration. The integro-differential equation for the stringer-force in Case (b) and Case (c) is reduced to a standard Fredholm integral equation, which is solved numerically. The results thus obtained are compared with available experimental findings. (Author)
International school psychology: psychology's worldwide portal to children and youth.

International school psychology is discussed in reference to scholarly and professional development within psychology, the emergence of an international association of school psychology, its efforts to promote school psychology, prevailing characteristics of school psychologists, and additional efforts needed to further enhance its development. Nine issues that will help shape the future of international school psychology are also identified. The importance of psychology, including school psychology, in promoting children's needs and rights is underscored.
Observation of coherent sheared turbulence flows in the DIII-D Tokamak.

Time-resolved measurements of the turbulent density flow field in a tokamak plasma reveal low-frequency ($\ensuremath{\sim}15\text{ }\text{ }\mathrm{K}\mathrm{H}\mathrm{z}$), coherent oscillations in the poloidal flow, ${\stackrel{\texttildelow{}}{v}}_{\ensuremath{\theta}}$. These flow oscillations have a long poloidal wavelength ($ml3$) and narrow radial extent (${k}_{r}{\ensuremath{\rho}}_{i}\ensuremath{\sim}0.2$). The estimated flow-shearing rate is of the same order of magnitude as the turbulence decorrelation rate and may thus regulate the turbulence amplitude. These features are consistent with theoretically predicted axisymmetric, self-regulating, sheared flows recognized as geodesic acoustic modes.
Considering the next generation of nuclear power plants

Abstract Nuclear power will be needed for future energy demands, which are expected to grow at different rates around the world. The opportunities for building new nuclear power plants around the world will be depend on need, energy demand growth, and issues related to global warming and climate change. However, four major barriers exist for the expansion of nuclear power: economics, proliferation, safety, and wate. These issues must be addressed in the ongoing research and development of nuclear energy technology and applications. The evolution of nuclear power plant technology is presented as four distinct design generations: (1) prototypes, (2) current operating plants, (3) advanced light water reactor technology, and (4) revolutionary design concepts (i.e., Generation IV) that are now under development. The U.S. DOE Nuclear Energy Research Initiative (NERI) program is focused on the research and development of Generation IV designs that are safe, economic, proliferation-resistant, and will address current waste issues. NERI provides grants for independently peer-reviewed proposals from universities, national laboratories and industry for advanced nuclear research and development. Several NERI projects awarded in 1999 are described in terms of how they remove barriers to nuclear power plant expansion. Another DOE effort, the Accelerator Transmutation of Waste program, will seek to reduce and ameliorate civilian reactor waste. The Accelerator Transmutation of Waste program will involve a six-year science-based research plan to define key technical issues. Finally, the need for international collaboration is stressed for fourth-generation nuclear power technology development.