cssi/SciSciGPT-SciSciNet huggingface dataset:
Live imaging defines the dynamics and molecular basis of in vivo mitophagy

Mitophagy defects are linked to aging, sarcopenia, and neurodegenerative diseases. To target this process for clinical intervention, the in vivo mitophagy dynamics and molecular mechanisms under physiologically relevant stresses must be better understood. Here, we characterized newly generated mitophagy reporter zebrafish and discovered high basal mitophagy rates in many organs during embryonic development and organogenesis. Rapid time-lapse imaging revealed in vivo dynamics of fasting-induced mitophagy, which occur via a piecemeal process. Baseline and stress-induced mitophagy were precisely assessed through ratiometric and volumetric image quantification algorithms. Activation of Hypoxia-inducible factor through physiological stress or chemical or genetic modulation provoked bnip3-dependent mitophagy in muscle independent of pink1. Surprisingly, disruption of bnip3la (nix) or fundc1, putative hypoxia-associated mitophagy receptors, had no effect on mitophagy. Our results discover fundamental mitophagy dynamics and molecular mechanisms with important implications for mitochondrial quality control and highlight the importance of live imaging in vivo studies.
Seliš ontological perspectives of environmental sustainability from oral traditions

Selis [Salish] oral stories engage with deep time and hold potential to stimulate hierophanies that establish connection between humanness and nature. Creation stories are integral to the establishment of values and sacredness and how the ‘sacred’ should be treated. Oral traditions are fallen out of use threatening ontological teachings of the Selis people, a Native American tribal group. Five Selis creations stories are examined to establish the ontology that animals offer as reflection of a reality that the environment and Selis people are intertwined in all aspect of life. This analysis also dispels Eurocentric stereotyping of Native American oral stories, establishing that the animals in these stories are much like humans of today, exhibiting failings, vices and defects.
Diversity Across the Pancreatic Ductal Adenocarcinoma Disease Spectrum Revealed by Network-Anchored Functional Genomics

Cancers are highly complex ecosystems composed of molecularly distinct sub-populations of tumor cells, each exhibiting a unique spectrum of genetic features and phenotypes, and embedded within a complex organ context. To substantially improve clinical outcomes, there is a need to comprehensively define inter- and intra-tumor phenotypic diversity, as well as to understand the genetic dependencies that underlie discrete molecular subpopulations. To this end, we integrated CRISPR-based co-dependency annotations with a tissue-specific co-expression network developed from patient-derived models to establish CoDEX, a framework to quantitatively associate gene-cluster patterns with genetic vulnerabilities in pancreatic ductal adenocarcinoma (PDAC). Using CoDEX, we defined multiple prominent anticorrelated gene-cluster signatures and specific pathway dependencies, both across genetically distinct PDAC models and intratumorally at the single-cell level. Of these, one differential signature recapitulated the characteristics of classical and basal-like PDAC molecular subtypes on a continuous scale. Anchoring genetic dependencies identified through functional genomics within the gene-cluster signature defined fundamental vulnerabilities associated with transcriptomic signatures of PDAC subtypes. Subtype-associated dependencies were validated by feature-barcoded CRISPR knockout of prioritized basal-like-associated genetic vulnerabilities (SMAD4, ILK, and ZEB1) followed by scRNAseq in multiple PDAC models. Silencing of these genes resulted in a significant and directional clonal shift toward the classical-like signature of more indolent tumors. These results validate CoDEX as a novel, quantitative approach to identify specific genetic dependencies within defined molecular contexts that may guide clinical positioning of targeted therapeutics.
Blood–Brain Barrier Modulation to Improve Glioma Drug Delivery

The blood-brain barrier (BBB) is formed by brain microvascular endothelial cells that are sealed by tight junctions, making it a significant obstacle for most brain therapeutics. The poor BBB penetration of newly developed therapeutics has therefore played a major role in limiting their clinical success. A particularly challenging therapeutic target is glioma, which is the most frequently occurring malignant brain tumor. Thus, to enhance therapeutic uptake in tumors, researchers have been developing strategies to modulate BBB permeability. However, most conventional BBB opening strategies are difficult to apply in the clinical setting due to their broad, non-specific modulation of the BBB, which can result in damage to normal brain tissue. In this review, we have summarized strategies that could potentially be used to selectively and efficiently modulate the tumor BBB for more effective glioma treatment.
Emotional Facial Expression Perception and Processing in AUD Subgroups: A Behavioral and Electroencephalographic Investigation of Polysubstance Use

Deficits in emotion processing among individuals with AUD are well accepted, however the potential impact of polysubstance use in this population remains uninvestigated. The current work begins to fill this gap by analyzing affective perception and processing in community controls (CCs) and two AUD subgroups differentiated by presence (Alc-Drug) or absence (Alc-Only) of polysubstance use. Behavioral task performance and electroencephalographic (EEG) indices (N170, P3) were measured for an emotion judgement task where participants classified emotional facial expressions (EFEs) morphed to 65 or 95 percent intensity. Mixed model analyses detected deficits in emotion classification accuracy among Alc-Drug relative to other groups. Although there was a main effect of emotion (greater accuracy for positive vs. negative emotions), there was no group by emotion interaction. N170 amplitude analyses found only a main effect for emotion (greater amplitude for negative vs. positive emotions). P3 amplitude analyses detected differences between control and AUD individuals, but no difference between AUD subgroups. No correlation was found between accuracy and ERP amplitudes. These findings contribute to the developing literature on emotional processing deficits in AUD, including highlighting the importance of considering polysubstance use in characterizing these deficits.
Integrative analysis reveals unique features of the Smc5/6 complex

Structural maintenance of chromosomes (SMC) complexes are critical chromatin modulators. In eukaryotes, the cohesin and condensin SMC complexes organize chromatin, while the Smc5/6 complex directly regulates DNA replication and repair. The molecular basis for Smc5/6s distinct functions is currently poorly understood. Here, we report an integrative structural study of the budding yeast Smc5/6 complex using electron microscopy, cross-linking mass spectrometry, and computational modeling. We show that while the complex shares a similar overall organization with other SMC complexes, it possesses several unique features. In contrast to the reported folded-arm structures of cohesin and condensin, our data suggest that Smc5 and Smc6 arm regions do not fold back on themselves. Instead, these long filamentous regions interact with subunits uniquely acquired by the Smc5/6 complex, namely the Nse2 SUMO ligase and the Nse5-Nse6 subcomplex. Further, we show that Nse5-Nse6 subcomplex adopts a novel structure with an extensive dimerization interface and multiple domains contacting other subunits of the Smc5/6 complex. We also provide evidence that the Nse5-Nse6 module uses its SUMO-binding motifs to contribute to Nse2-mediated sumoylation. Collectively, our integrative multi-scale study identifies distinct structural features of the Smc5/6 complex and functional cooperation amongst its co-evolved unique subunits.
Understanding Donor Motivation

Research about philanthropy and charitable giving has expanded considerably in recent decades, and an area that has particularly benefitted is the study of donor motivations. Gifts often follow solicitations, but the solicitation itself is simply a culminating experience bringing donor interests and institutional needs together. This is especially true as the gift size increases. By recognizing the exchange of values that is at the heart of major giving and empathically focusing donors’ specific motivations and purposes, faculty and academic leaders can structure effective and authentic engagement strategies and gift discussions. Making a commitment to learn about a donor—including organizational foundation or company donor—before asking them to give also helps reduce the tendency to rely on popular beliefs or unfounded assumptions in predicting donor behaviors.
Identification of Translocated Substrates of the Legionella pneumophila Dot/Icm System without the use of Eukaryotic Host Cells

This chapter describes alternate approaches that take advantage of special properties of Legionella pneumophila strains that allowed the formulation of simple screens using toothpicks and petri dishes containing bacteriological medium. Developing readouts in the microorganism that allow screens on solid medium has allowed a number of translocated substrates to be identified. Interestingly, it was found that dotL mutants producing low levels of DotA were able to grow on agar plates. This important finding allowed considerable manipulation of phenotypes, because the behavior of mutants that would otherwise be inviable could now be evaluated during intracellular growth. The great majority of mutations, in fact, appeared to directly affect the assembly of the Dot/Icm system or disrupt function of DotL, and many of the impaired proteins are involved in either membrane biogenesis or membrane protein folding. In several T4SSs,Mob protein can be transferred into recipient cells in the absence of DNA mobilization, indicating that protein translocation into bacteria can occur in the same fashion that is observed when the pathogen contacts a mammalian cell. Furthermore, elimination of multiple paralogs of a single gene family does not solve the redundancy issue, suggesting that a similar amino acid sequence does not necessarily mean the proteins have similar functions. Development of functional and biochemical assays for these proteins will be necessary to sort out their roles in intracellular growth.
Ergonomic Interventions for Computer Users with Cumulative Trauma Disorders

This chapter examines ergonomic interventions for computer users who experience cumulative trauma disorders (CTDs) in the workplace. CTDs are defined. The complex nature of these disorders and the need for holistic and comprehensive evaluation is discussed. Statistics of prevalence and incidence are reviewed. The role of occupational therapy in the management of these disorders is examined. Examples of interventions for these disorders are cited, and a systematic review of the effectiveness of the ergonomic interventions is provided. Finally, recommendations for occupational therapy practice and further research are provided.
A Closer Look at Gender in NAEP Mathematics Achievement and Affect Data: Intersections with Achievement, Race/Ethnicity, and Socioeconomic Status.

In this article we describe gender gaps in mathematics achievement and attitude as measured by the U.S. National Assessment of Educational Progress (NAEP) from 1990 to 2003. Analyzing relationships among achievement and mathematical content, student proficiency and percentile levels, race, and socioeconomic status (SES), we found that gender gaps favoring males (1) were generally small but had not diminished across reporting years, (2) were largest in the areas of measurement, number and operations (in Grades 8 and 12) and geometry (in Grade 12), (3) tended to be concentrated at the upper end of the score distributions, and (4) were most consistent for White, high-SES students and non-existent for Black students. In addition, we found that female students' attitudes and self-concepts related to mathematics continued to be more negative than those of male students.
Sadness Revealed: Insights on Women's Depression

A Secret Sadness: The Hidden Relationship Patterns That Make Women Depressed. VALERIE E. WHIFFEN. Oakland, CA: New Harbinger Publications, 2006. 196 pp., $24.95 (hardcover), ISBN: 1–57224–469–0.
Congressional Oversight of the Clinton Administration and Congressional Procedure

This article demonstrates the significant role congressional practices and procedures play in shaping congressional oversight and administrative law. Using the "positive political theory" and its objective approach to government institutions, the author examines how congressional procedures interact with Congress' influence on agency action.Analyzing the roles of committees, the appropriations process, and the differences between Senate and House procedures, the author explains how congressional procedures have shaped U.S. military action, environmental efforts, and Medicare budgets. Through these and other examples, the author demonstrates the importance of the oversight system in a functioning democracy. Congressional oversight, through its dealings with expenditures, national security, and health care issues, creates an orderly system of lawmaking that affects every aspect of public life. Therefore, the rules governing its practice and procedures cannot be ignored.
Monaural speech segregation and oscillatory correlation

Summary form only given. Speech segregation from a monaural recording is a primary task of auditory grouping, and has proven to be very challenging. Theoretical and empirical investigations of brain functions point to the mechanism of oscillatory correlation as a plausible framework for perceptual grouping. In this framework, an assembly of synchronized oscillators represents a stream, and oscillator assemblies that desynchronize from one another represent different groups. We describe a multi-stage model for the monaural speech segregation task. The model starts with simulated auditory periphery. A subsequent stage computes mid-level auditory representations, including correlograms and cross-channel correlations. Underlying auditory segmentation and grouping is a neural oscillator network that implements oscillatory correlation. The network encodes proximity in frequency and time, periodicity, and amplitude modulation (AM). Motivated by psychoacoustic observations, our system employs different mechanism to handle resolved and unresolved harmonics. The model has been systematically evaluated, and it yields substantially better performance than previous systems.
Selection in reference to biological groups. VI. Use of extreme forms of nonrandom groups to increase selection efficiency.

The strategy of using non-random groups to increase the efficiency of truncation selection is discussed. The present study, which considers extreme forms of non-random groups, complements a previous study involving full-sib groups. It is shown that of the two kinds of non-randomness, i.e. that due to homozygosity or that due to homogeneity (as represented by cloning), the latter is the most effective. This suggests that with those plant crops in which intense competition among plants exists, use of clonal propagation to produce non-random groups should be investigated.
Performance evaluation using data flow graphs for concurrent processing

The authors present a systematic procedure to find the exact iteration bound for an arbitrary nonterminating data flow graph (DFG). The complexity of the procedure to identify the critical loop and the iteration bound is O(n/sup 3/ log n), where n is the number of nodes in the DFG. Lookahead is another technique to enhance concurrency. It inserts delays in the critical loop of the DFG, resulting in better performance than the iteration bound. To achieve the maximum degree of improvement it is further necessary to identify the next-critical loop. A method to identify the next-critical loop of a nonterminating DFG is also presented. >
Lymphocytes induce monocyte chemoattractant protein-1 production by renal cells after Fcγ receptor cross-linking: role of IL-1β

Leukocyte recruitment to the kidney in immune complex disease like systemic lupus erythematosus (SLE) is mediated in part by local expression of chemokines such as monocyte chemoattractant protein-1 (MCP-1). Recent studies from this laboratory demonstrated that cross-linking Fc gammaR on lymphocytes causes release of a soluble factor that induces monocyte chemokine production. To explain the induction of renal chemokine expression in immune complex disease, we postulated that this lymphocyte factor stimulates renal parenchymal cell MCP-1 expression. To test this hypothesis, human peripheral blood lymphocytes were incubated on immobilized IgG, a model for immune complex Fc gammaR cross-linking. Supernatants from these lymphocyte cultures significantly increased MCP-1 production by human mesangial, glomerular capillary endothelial, and proximal tubular epithelial cells. Mesangial cells incubated on immobilized IgG or with soluble, preformed immune complexes did not secrete MCP-1 above control levels. Lymphocyte supernatant-induced MCP-1 production appeared to be dependent on the presence of interleukin (IL)-1beta in the supernatant. Removing IL-1beta from the supernatants, antagonizing its activity, or preventing conversion to mature IL-1beta abrogated renal cell MCP-1 expression by the lymphocyte supernatants. These data demonstrate that in response to cross-linking Fc gammaR, lymphocytes induce renal cell MCP-1 expression by secreting IL-1beta. Renal chemokine expression in immune complex disease may thus be triggered as lymphocytes traffic through the kidney and encounter deposited immune complexes.
Interpreting Hierarchical Linear and Hierarchical Generalized Linear Models With Slopes as Outcomes

Current descriptions of results from hierarchical linear models (HLM) and hierarchical generalized linear models (HGLM), usually based only on interpretations of individual model parameters, are incomplete in the presence of statistically significant and practically important "slopes as outcomes" terms in the models. For complete description of the resulting interactive models, detailed simple effect descriptions analogous to those long used in factorial ANOVA-based research are needed. The required procedure is described and illustrated for 2- and 3-level HLM and HGLM relationships.
Study on stress evolution in the cooling process of micro hot embossing

Cooling of an embossed part has been recognized as one of the critical steps in the hot embossing of polymer microdevices. Numerical analysis was performed to study the stress developed in an embossed microstructure during the cooling process of hot embossing. A hemisphere-tipped post was selected as an example structure to demonstrate the stress evolution. The posts are located at 5, 10, 15, and 20 mm from the center of the embossed part. The results of the analysis showed that stresses of the posts increased as the radial locations of the post increased. In addition, the stress rapidly increased until the cooling time reached about 100.0 s. The maximum stresses of 28.9, 30.2, 32.3, and 34.5 MPa were estimated at the post locations of 5, 10, 15, and 20 mm from the center of the part, respectively. Experiments were performed to verify the numerical models. Undercut at the bottom of a post was observed as it was predicted in the numerical analysis.
Electrostatic binding of anions and cations to graphite electrodes coated with a polyelectrolyte containing both positive and negative fixed charges

Abstract Graphite electrodes were coated with a polyelectrolyte based on poly(4-vinylpyridine). Three types of charged groups were introduced in the polymer to vary its net ionic charge: Protonated pyridinium cations, quaternized pyridinium cations and pentacyanoferrate anions. The charge carried by the Fe(CN)5 groups (2− or 3−) was controlled electrochemically so that the net charge of the coatings could be varied continuously between polycationic and polyanionic states. The equilibrium incorporation of multiplycharged electroactive ions by the resulting coatings was measured as a function of the net charges of the polyelectrolyte. Preferential intra-polymer charge compensation by interaction between fixed anionic and cationic sites was demonstrated in this way.
Measuring the Cost of Time in Recreation Demand Analysis: Comment

In the February 1981 issue of the Journal, McConnell and Strand present a model of recreation demand in which the opportunity cost of an hour of travel to a recreation site is assumed not to equal the average hourly income of the recreating family. They test the model with data from a 1978 survey of sportfishermen in the Chesapeake Bay region. Simply stated, the model hypothesizes that the sportfishermen will behave as if the "price" of a recreational trip is the sum of cash costs and the opportunity cost of travel time. This opportunity cost is hypothesized to be some ratio, k, of average family income per hour times the travel time. McConnell and Strand estimate the value of k by regressing recreation days against cash costs and opportunity cost of time as separate variables. The ratio of regression coefficients then is an estimate of k. They go on to estimate the ratio, k, of the opportunity cost of travel to the average income for sportfishermen in the Chesapeake Bay region. The authors hypothesize that the ratio (k) falls between 0 and 1, implying that sportfishermen value the time in transit lower than their average income when working. Sufficient conditions for k to equal one include (a) the tax rate is zero, (b) marginal earnings are constant, and (c) nonwork income equals zero. This comment is written to point out certain aspects of the study which may have led to an underestimation of the value of k. It is argued that McConnell and Strand have misspecified their demand equation in such a way that their estimate for k (.612) is biased downward. McConnell and Strand hypothesize the demand relation
Discrimination within Religious Schools

Places of contact between religion and the state has increased considerably over time; as this overlap has increased, liberals have increasingly seen fit to call for state intervention in religions that are internally discriminatory in the name of equal citizenship. By looking at the issue of direct and indirect state support for discriminatory schools, I argue for a more pluralistic and tolerant view of religion than that of many liberals. Preserving diversity is an important liberal good that should not lost sight of, though there are limits to the kinds of discrimination the liberal state should support. Much of my argument rests on the distinction between direct and indirect support. The liberal state should impose strict standards on funds it grants directly to organizations, but it should be more relaxed for indirect support it gives, except in exceptional circumstances.
Characterization of transforming growth factor-β1 gene expression in porcine immune cells

Abstract We have investigated the regulation of transforming growth factor β1 gene expression in a variety of porcine immune cell populations, including peripheral blood mononuclear cells (PBMC), peripheral blood monocytes, alveolar macrophages and lymphoid cells from various swine lymphoid tissues. Using porcine transforming growth factor β1 cDNA probes in Northern blot assays, messages of 2.5 and 3.5kb TGFβ1 mRNA were detected in the cells investigated. A variety of mitogenic and immunomodulatory substances were examined for their ability to induce TGFβ1 mRNA expression. These include phorbol 12-myristate 13-acetate (PMA), phytohemagglutinin (PHA), concanavalin A (Con A), lipopolysaccharide (LPS), dexamethasone (Dex), tumor necrosis factor (TNF) and interleukin (IL)-1α. While low level constitutive expression of TGFβ1 mRNA was detected from all cells investigated, PMA treatment of PBMC and alveolar macrophages resulted in a more than 10-fold increase in the steady-state level of TGFβ1 mRNA within 2 hr of PMA addition. Also, the effect of opiate drugs, methadone (Md) and morphine (Mor), on TGFβ1 gene expression was determined. Cells treated with opiates expressed the same levels of TGFβ1 mRNA as untreated cells. Since TGFβ l biological activity can be induced by opiates, the regulation of TGFβ1 gene expression likely involves mechanisms that do not cause changes in mRNA levels.
Knowing what it takes: the effect of perceived learner advantages on dance teachers’ use of critical‐thinking activities

The Critical Thinking Belief Appraisal was administered to practicing dance teachers (n = 52) in the USA to investigate their beliefs (and use of) critical‐thinking activities with high‐advantage and low‐advantage learners. Results point to an ‘advantage effect’ in dance teachers’ beliefs about critical thinking: the higher the perceived learner advantages, the more likely teachers are to favor high ­critical‐thinking activities. This effect also appears to be a more absolute belief in the efficacy of teaching high‐advantage learners than previously thought. These results extend to teachers’ classroom behavior as well as their espoused beliefs and are not an artifact of teachers’ critical‐thinking ability and disposition, or their need for social approval. Implications and the need for further research are discussed.
Streamlining administrative procedures at the Defense Language Institute: The strategic impact model in action

Performance at the Defense Language Institute was examined through the prism of human performance technology and the strategic impact model. This examination revealed performance deficiencies in the administrative realm that required mainly a noninstructional intervention. A systematic analysis showed that digitizing administrative procedures could substantially decrease operational costs, enhance procedural transparency, and increase employees' satisfaction.
Studies on the fine structure of the protozoan Cyclidium, with special reference to the mitochondria, pellicle and surface-associated bacteria.

The ultrastructure of Cyclidium, including the cilia, kinetosomes, pellicle, microtubules and kinetodesmal fibers is similar to that recorded for other ciliates. Of special interest is the attachment of rod-shaped bacteria within the longitudinally directed shallow surface folds of the protozoan. Both the bacteria and the surface of Cyclidium seem to possess an outer coating of a sticky substance which upon contact holds the bacteria to the protozoan. The bacteria appear to be attached by only a relatively small area of their surfaces. A dense substance appears within the alveolus of the pellicle at the regions of the attachment of the bacteria. The association of the organisms is probably a temporary one, and it is unknown whether either organism is benefited or harmed by the association. The position of the mitochondria in Cyclidium is unusual in that they all lie flattened against the inner membrane of the pellicle, usually in a position directly opposite to that of the attachment of the bacteria to the surface, thus being separated from the bacteria by only the outer cell membrane and the pellicle. Whether or not this close topographical relationship is of significance is unknown.
Niemann-Pick Type C2 Deficiency in Human Fibroblasts Confers Robust and Selective Activation of Prostaglandin E2 Biosynthesis

Activated fibroblasts, also known as myofibroblasts, are mediators of several major human pathologies including proliferative fibrotic disorders, invasive tumor growth, rheumatoid arthritis, and atherosclerosis. We previously identified Niemann-Pick type C2 (NPC2) protein as a negative regulator of fibroblast activation (Csepeggi, C., Jiang, M., Kojima, F., Crofford, L. J., and Frolov, A. (2011) J. Biol. Chem. 286, 2078–2087). Here we report that NPC2-deficiency leads to a dramatic up-regulation of the arachidonic acid (AA) metabolic pathway in human fibroblasts. The major enzymes in this pathway, cPLA2 type IVA, COX-2, and mPGES-1, were dramatically up-regulated at both the transcriptional and translational levels. The specific phenotypic changes resulted in a >10-fold increase in the production and secretion of a key modulator of inflammation and immunity, prostaglandin E2. More importantly, AA metabolome profiling by liquid chromatography/tandem mass-spectrometry revealed the very specific nature of prostaglandin E2 up-regulation as the other analyzed AA metabolites derived from the COX-2, cytochrome P450, 5/15-lipoxygenase, and non-enzymatic oxidative pathways were mostly down-regulated. Blocking activity of cPLA2 efficiently suppressed expression of inflammatory cytokines, IL-1β and IL-6, thereby identifying cPLA2 as an important regulator of the inflammatory program in NPC2-null cells. Altogether, these studies highlight NPC2 as a specific regulator of AA metabolism and inflammation that suggests potential for NPC2 protein or its related signaling in the treatment of inflammatory diseases characterized by the presence of activated fibroblasts. Background: NPC2 is a protein that negatively regulates fibroblast activation. Results: NPC2-null human fibroblasts display induction of cPLA2, COX-2, and mPGES-1 expression that may contribute to the observed robust and selective activation of PGE2 biosynthesis. Conclusion: NPC2 may regulate the activated fibroblast inflammatory program through modulation of a cPLA2-dependent biosynthetic pathway. Significance: NPC2 may represent a novel therapeutic tool for the treatment of inflammatory diseases.
Theoretical studies of disilabenzenes

Abstract Ab initio calculations have been carried out on the three isomers of disilabenzene. All three structures display significant delocalization, with the most delocalized and most stable being predicted to be the meta (1,3) isomer. The relative stabilities are rationalized with the aid of contour plots of the occupied π molecular orbitals and the contributions of various Kekule structures to each isomer.
Directionality Between Tolerance of Deviance and Deviant Behavior is Age-Moderated in Chronically Stressed Youth

Problem behavior theory posits that tolerance of deviance is an antecedent to antisocial behavior and substance use. In contrast, cognitive dissonance theory implies that acceptability of a behavior may increase after experiencing the behavior. Using structural equation modeling, this investigation tested whether changes in tolerance of deviance precede changes in conduct disorder criteria or substance use or vice versa, or if they change concomitantly. Two-year longitudinal data from 246 8- to 16-year-olds suggested that tolerance of deviance increases after conduct disorder criteria or substance use in 8-to-10- and 11-to-12-year-olds. These results were consistent with cognitive dissonance theory. In 13-to-16- year-olds, no directionality was suggested, consistent with neither theory. These results were replicated in boys and girls and for different types of conduct disorder criteria aggression (covert behavior), deceitfulness and vandalism (overt behavior), and serious rule-breaking (authority conflict). The age-specific directionality between tolerance of deviance and conduct disorder criteria or substance use is consistent with unique etiologies between early onset versus adolescent-onset subtypes of behavior problems.
Nucleation Kinetics and Microstructure Evolution of Traveling ASTM F75 Droplets

A method is devised for the prediction and control of the nucleation kinetics and solidification microstructure of traveling droplets of a cobalt-base biocompatible alloy ASTM F75. Mono-size droplets produced by the uniform-droplet spray (UDS) process (a capillary jet breakup process) are quenched on substrates at different flight distances to determine nucleation distance from the splat morphology. Using the nucleation temperatures estimated from the splat morphology as references, the nucleation kinetics of F75 droplets is predicted and presented in the form of a continuous-cooling transformation diagram. Cooling 300 µm F75 UDS droplets in argon gas resulted in an estimated supercooling of 132 K and formation of a well-defined dendritic microstructure, whereas cooling the same droplets in helium gas produced a larger supercooling of 377 K and a microcrystalline structure indicative of dendrite fragmentation. This process, with stringent control of nucleation kinetics, can produce F75 balls with a rapid solidification microstructure suitable for bio-implant applications.
Conceptual and Moral Development of Substance Abuse Counselors: Implications for Training

The relationship among substance abuse counselors' education, experience, recovery status, and cognitive development (conceptual complexity and moral reasoning levels) was examined in a simultaneous multiple regression. Significant relationships were found between counselors' level of conceptual complexity and moral reasoning and their education. Implications for counselor training are presented.
Improved Protection of the Hypertrophied Left Ventricle by Histidine-Containing Cardioplegia

Background Myocardial hypertrophy has been shown to lead to increased susceptibility to ischemia with accelerated loss of high-energy nucleotides, greater accumulation of H+ and lactate, and earlier onset of contracture. Methods and Results To determine whether promoting anaerobic glycolysis during ischemia by buffering H+ results in improved preservation of the hypertrophied heart, we studied the effect of a histidine-containing solution (HBS) on recovery of contractile function and energetic state. Hypertrophied rabbit hearts (aortic banding at 10 days) were subjected to 40 minutes of 37°C ischemia and reperfusion in an isolated Langendorff model. This group was compared with groups receiving St Thomas solution and high-potassium Krebs buffer solution (KCl). Although both phosphocreatine (PCr) and ATP were lower in hypertrophied hearts by end-ischemia compared with nonhypertrophied age-matched controls, there was significantly higher PCr, ATP, and intracellular pH in the HBS group compared with the St T...
Introduction to complex fault protection software testing

This paper describes how fault protection (FP) software verification testing has been addressed for the attitude and articulation control subsystem on the Saturn-bound Cassini spacecraft. The verification included definition of failure injection capabilities to the test beds. The Cassini fault protection test program evolved using several test phases to complete separate goals which taken together encompassed all of the flight software complexities. This phased testing approach developed high confidence in the robustness and correctness of the FP flight software. Over 500 prelaunch tests of the flight software in a realistically modeled environment were used to ensure the design is robust to single faults. In the process we found that many double fault scenarios are handled by the Cassini attitude and articulation control subsystem FP software design.
Vitamin D in organ transplantation.

Vitamin D deficiency is prevalent among patients with end-stage organ failure awaiting transplant. Low serum 25-hydroxyvitamin D (25-OHD) levels in these patients may be related to many disease-specific factors, as well as decreased sunlight exposure and limited intake of foods containing vitamin D. Low serum 25-OHD levels are also extremely common following solid organ transplantation, both during the immediate postoperative period and in long-term graft recipients. Demographic and lifestyle factors are important in determining D status in transplant recipients. Worse vitamin D status is associated with poorer general health, lower albumin, and even decreased survival among these patients. Although several studies have demonstrated that active forms of vitamin D and its analogues prevent bone loss following transplantation, the data do not show consistent benefit. These therapies may have particular utility after renal transplantation. However, given the narrow therapeutic window with respect to hypercalcemia and hypercalciuria, and the demonstrated efficacy of bisphosphonates to prevent post-transplantation bone loss, we regard these agents as adjunctive rather than primary therapy for transplantation osteoporosis. The effects of 1,25(OH)2D on the immune system, which are still being elucidated, may have potential for reducing infections and preventing allograft rejection after transplantation.
Joint Attention and Imitative Learning in Children, Chimpanzees, and Enculturated Chimpanzees*

In this study we compared the nature of the joint attentional interactions that occurred as chimpanzees and human children engaged with a human experimenter (E). Subjects were three chimpanzees raised mostly with conspecifics (mother-reared), three chimpanzees raised in a human-like cultural environment (encultur-ated), and six 18-month-old human children. Of particular interest were possible differences between the two groups of chimpanzees that might have resulted from their different ontogenetic histories. Observations were made as subjects participated in an imitative learning task involving a number of novel objects. Variables coded were such things as subjects' looks to the object, looks to E, the coordination of such looks in periods of joint engagement with E, and gestural attempts to direct E's attention or behavior (declaratives and imperatives). Results showed that encultur-ated chimpanzees were most similar to human children in social interactions involv-ing objects, for example, in their attention to the object in compliance with E's request, their joint attentional interactions during less structured periods, and their use of declarative gestures to direct E's attention to objects. They were not similar to children, but rather resembled their mother-reared conspecifics, in the duration of their looks to E's face. A positive relation between subjects' joint attentional skills and their imitative learning skills was found for both chimpanzee and human sub-jects. It is concluded that a human-like sociocultural environment is an essential component in the development of human-like social-cognitive and joint attentional skills for chimpanzees, and perhaps for human beings as well
Commodity trading advisors' leverage and reported margin‐to‐equity ratios

We investigate the effect of leverage on Commodity Trading Advisors' (CTAs) performance measurement. We find that leverage has important effects on the cross section of CTA returns, volatility, and survival experience. On average, a 100-basis points increase in leverage is associated with a 27-basis points increase in returns. After performance is adjusted for leverage, volatility, and survival experience, CTAs' style variables have no significant effect on performance. The amount of leverage used by a CTA is found to reduce the likelihood of survival. However, the total effect of leverage on survival is much smaller than its partial effect. Contrary to common beliefs, we find that CTA diversification leads to higher levels of leverage and volatility. This apparent contradiction is related to how the diversification process affects the use of leverage. The findings in this study have implications for measuring and comparing managers' performance track records. © 2003 Wiley Periodicals, Inc. Jrl Fut Mark 23:1003–1017, 2003
The enhancement of morphine antinociception in mice by delta9-tetrahydrocannabinol.

We have previously reported that intracerebroventricular or intrathecal administration of inactive doses of delta9-tetrahydrocannabinol (THC) greatly enhance the antinociceptive potency of morphine in the mouse tail-flick test. Experiments were conducted to test the hypothesis that morphine's potency would be enhanced in mice receiving THC and morphine by conventional per os (p.o.) and subcutaneously (s.c.) routes of administration. Antinociception was measured in the tail-flick test of radiant heat after administration of different combinations of THC and morphine p.o. and s.c. Subcutaneous administration of THC (4 and 25 mg/kg) increased the potency of s.c. morphine 8.5- and 22.3-fold, respectively, while s.c. THC (25 mg/kg) increased the potency of p.o. morphine 3.1-fold. Per os administration of THC (10 and 20 mg/kg) increased the potency of s.c. and p.o. morphine 11.4-fold and 7.6-fold, respectively. Thus, morphine's potency was significantly increased regardless of the enteral and parenteral routes of THC and morphine administration. The synthetic receptor selective cannabinoid CP-55, 940 (0.1 mg/kg, s.c.) also enhanced morphine's potency. Finally, the ability of the CB1 receptor antagonist SR141716A to antagonize the enhancement of morphine by THC indicates that THC was acting through a cannabinoid receptor mechanism.
Effectiveness of language elicitation tasks with two-year-olds

One unstructured and two structured language sampling conditions were compared to determine the ways in which different types of structure would affect 2-year-olds' productions of the possessor + possession semantic relation. In the unstructured, naturalistic condition, the clinician followed the child's lead and responded in ways that would encourage the produc tion of the possessive construction. In the structured conditions, the clinician utilized wh-questions and sentence completion tasks to elicit the possessive construction. While the subjects produced a greater quantity and diversity of possessive constructions in the structured conditions, no differences were observed between the two types of linguistic elicitation techniques. Implications for sampling language with young children are discussed.
Homophobic Bullying and Same-Sex Desire in Anglo-American Schools: An Historical Perspective

SUMMARY Homophobic bullying has come into new prominence given its alleged connection to several recent acts of school violence. This article traces the historiography of homophobic bullying, both in recent years and with reference to the original era of concern over this problem, Victorian England. As can be seen through novels and autobiographies of school life, Victorians linked bullying and sexuality in several important ways. Their traditional understanding actually supported many acts of bullying as a way to teach boys accepted codes of masculine behavior. In the late- and post-Victorian era, growing scientific investigation into human sexual behavior and increasing openness about homosexuality changed this picture to some extent, leading writers to understand bullying as a product of the bully's repressed same-sex desires. Both these views persist today and provide a stimulating context for present-day investigations of homophobic bullying.
Lower Bounds for Sonic Booms in the Midfield

This paper presents new lower bounds for sonic booms based on minimizing either the overpressure or the shock strength of the positive part of the boom wave. The results are not restricted to the limit of large distance from the aircraft. They reduce to the Jones lower bound infinitely far from the aircraft in a uniform atmosphere but they give reductions from the Jones lower bound of the order of 50% for planned supersonic transport conditions. This is because the asymptotic results of Jones are approached very slowly (as r~1/4) in a uniform atmosphere and are never reached in the real atmosphere. The direct application of these results depends upon additionally keeping the tail shock intensity less than or equal to that of the front shock.
Presental Cellulitis Caused by Mycobacterium intracellulare

Abstract A case of preseptal cellulitis caused by Mycobacterium intracellulare is presented. A 56-year-old white woman developed erythema, induration, and tenderness of the lids of her right eye after chalazion removal, which did not respond to three weeks of broad spectrum antibiotics. Incision and drainage with biopsy revealed granuloma, and acid-fast bacilli were seen. Mycobacterium intracellulare was isolated on culture, resistant to all the antimicrobials that the patient was given. Antimicrobial therapy was discontinued, and the infection resolved over 15 months.
Fractals in Heterogeneous Catalysis

Abstract In a recent review on the influence of particle size on catalytic properties of supported metals [l], evidently a most important aspect of heterogeneous catalysis by any account, the authors end on a fairly discouraging note since they suggest doing even more work — with ever more sophisticated techniques and methods as well as normalized procedures — on top of an already formidable amount of literature. At such a state of the art it may be appropriate to reflect and to ask whether full pursuit of reductionism as scientific method needs fresh thinking in order to progress more effectively. Perhaps the difficulties are rooted in emphasis on mere data collection, the lack of a good empirical guiding principle, inappropriate models; in brief, the frequent simplification of a vastly complicated object — the real catalyst — into the sum of phenomena of better-understood idealized subsets. It might even be argued that a thorough knowledge of a well-characterized prototype or a particular model catalyst...
The golden years: a tribute to Erminio Costa.

Abstract In June of 1968 the NIMH established the Laboratory of Preclinical Pharmacology (LPP) under the leadership of Erminio Costa at St. Elizabeths Hospital in Washington, DC. From its inception until 1985 more than 170 scientists produced over 800 scientific publications that largely influenced the direction of neuroscience research. Under Dr. Costa's scientific guidance LPP made numerous discoveries that contributed to the understanding of neuronal function and push the fledging field of neuroscience forward. Methods were developed to measure the turnover rate of catecholamines, serotonin, acetylcholine and GABA, and to assess the dynamic state of neuronal stores of peptides; the regulation of tyrosine hydroxylase activity was revealed; the molecular mechanisms underlying neurotransmitter receptor signaling and regulation were explored; the concept that opioid peptides function as neuromodulators in structures that are not involved in pain threshold regulation was proposed; the role of GABAergic transmission for the action of benzodiazepines was pioneered; the endogenous mechanisms operative in opiate tolerance were elucidated; and approaches to measure mRNA and evaluate its regulation were introduced. As a tribute to Dr. Costa, this article presents the initial journey and the many contributions to teaching and research that he made from 1963 to 1985, a period that I worked with him and call it “the golden years”.
Laser effect on DMBA-induced dyskeratoses of the hamster cheek pouch.

Results of 21 months of experimental investigation of 120 Syrian hamsters with 9, 10 dimethylbenz (a) anthracene-induced dyskeratoses and subsequent papillomas and squamous-cell carcinomas, and the reaction to treatment of pulsed ruby laser are presented. In addition, tentative results of experiments with continuous argon-ion laser radiation are presented and histopathology of the lesions is reported. Conclusions are given involving statistical analysis of the data which strongly support the hypothesis that pulsed laser radiation has an inhibitory effect on tumor growth, reducing the rate of cell division. On the basis of this work, it is postulated that an approximately eightfold reduction in mitotic rate in hamster oral tumor growth occurs, along with a decrease of incidence of tumor formation to approximately one half of control results.