cssi/SciSciGPT-SciSciNet huggingface dataset:
APP Is Cleaved by Bace1 in Pre-Synaptic Vesicles and Establishes a Pre-Synaptic Interactome, via Its Intracellular Domain, with Molecular Complexes that Regulate Pre-Synaptic Vesicles Functions

Amyloid Precursor Protein (APP) is a type I membrane protein that undergoes extensive processing by secretases, including BACE1. Although mutations in APP and genes that regulate processing of APP, such as PSENs and BRI2/ITM2B, cause dementias, the normal function of APP in synaptic transmission, synaptic plasticity and memory formation is poorly understood. To grasp the biochemical mechanisms underlying the function of APP in the central nervous system, it is important to first define the sub-cellular localization of APP in synapses and the synaptic interactome of APP. Using biochemical and electron microscopy approaches, we have found that APP is localized in pre-synaptic vesicles, where it is processed by Bace1. By means of a proteomic approach, we have characterized the synaptic interactome of the APP intracellular domain. We focused on this region of APP because in vivo data underline the central funtional and pathological role of the intracellular domain of APP. Consistent with the expression of APP in pre-synaptic vesicles, the synaptic APP intracellular domain interactome is predominantly constituted by pre-synaptic, rather than post-synaptic, proteins. This pre-synaptic interactome of the APP intracellular domain includes proteins expressed on pre-synaptic vesicles such as the vesicular SNARE Vamp2/Vamp1 and the Ca2+ sensors Synaptotagmin-1/Synaptotagmin-2, and non-vesicular pre-synaptic proteins that regulate exocytosis, endocytosis and recycling of pre-synaptic vesicles, such as target-membrane-SNAREs (Syntaxin-1b, Syntaxin-1a, Snap25 and Snap47), Munc-18, Nsf, α/β/γ-Snaps and complexin. These data are consistent with a functional role for APP, via its carboxyl-terminal domain, in exocytosis, endocytosis and/or recycling of pre-synaptic vesicles.
Globalization and the distribution of income: The economic arguments

One of the issues currently being debated in the ongoing discussion of the pros and cons of today's globalization concerns the effects of greater world trade as well as of the changes in technology on a country's internal distribution of income, especially on skilled versus unskilled wage rates. In this article, I attempt to spell out some of the arguments concerning internal income distribution that have been put forth both by labor economists and international trade theorists. The impact of globalization on the wage premium between the skilled and unskilled may not be as obvious as is first imagined.
Separation of Product Associating E. coli Host Cell Proteins OppA and DppA from Recombinant Apolipoprotein A-Imilano in an Industrial HIC Unit Operation

We have shown how product associating E. coli host cell proteins (HCPs) OppA and DppA can be substantially separated from apolipoprotein A-I(Milano) (apo A-I(M)) using Butyl Sepharose hydrophobic interaction chromatography (HIC). This work illustrates the complex problems that frequently arise during development and scale-up of biopharmaceutical manufacturing processes. Product association of the HCPs is confirmed using co-immunoprecipitation and Western blotting techniques. Two-dimensional gel electrophoresis and mass spectrometry techniques are used to confirm the identity of OppA and DppA. In this example, clearance of these difficult to separate HCPs decreased significantly when the process was scaled to a 1.4 m diameter column. Laboratory-scale experimentation and trouble shooting identified several key parameters that could be further optimized to improve HCP clearance. The key parameters included resin loading, peak cut point on the ascending side, wash volume, and wash salt concentration. By implementing all of the process improvements that were identified, it was possible to obtain adequate HCP clearance so as to meet the final specification. Although it remains speculative, it is believed that viscosity effects may have contributed to the lower HCP clearance observed early in the manufacturing campaign.
Improving Mobility and Community Access in an Adult With Ataxia

This case report summarizes the evaluation and treatment used to provide occupational therapy services to a man living with multiple sclerosis. Primary impairments included ataxia, paraparesis, and decreased endurance. The focus of this case study was on improving the client's ability to use powered mobility to access the community despite severe ataxia. A task-oriented approach was used as a frame of reference to guide the evaluation and intervention process. The primary goals of intervention were to control the degrees of freedom required for task participation and simultaneously increase postural stability, resulting in independent control of a power wheelchair. A combination of occupational therapy interventions is illustrated, including assistive technology, positioning, orthotic prescription, and adaptation of movement patterns.
Noise as a Risk Factor in Elementary Classrooms: Applicability of Life-cycle Value Tradeoff of Noise-mitigating Measures Using Multicriteria Decision Modeling

Research shows that noise is detrimental to developing children from many perspectives, cognitive, social, behavioral, and psychological; yet noise levels in classrooms are far from recommended standards. Studies suggest that the problem of poor acoustics exists for many reasons including lack of acoustics education for architects and engineers; lack of perception of the problem and its solution on the part of the professionals involved. Furthermore, these features are often discarded during value engineering or simply removed from the project to meet a predetermined budget. The issue is how we bridge the gap between research results, acoustics standards, and real practice of classroom design and construction. The problem of classroom acoustics involves multiple criteria, multiple decision makers, multiple stakeholders, and multiple alternatives; therefore, it is a valid problem for applying the theories and principles of multi criteria decision making (MCDM). Consequently, the hypothesis of this study is that a robust structured decision making framework to facilitate choice of optimal classroom acoustics can be developed. This decision making framework is expected to facilitate decision-makers implementing new standards and policies; as well as provide professionals who are involved with school design and construction with decision rules for making informed choice about classroom acoustics within a specific decision context rather than just being guided by cost-effectiveness.
A gap-based approach for regenerating pine species and reducing surface fuels in multi-aged mixed conifer stands in the Sierra Nevada, California

Summary Multi-aged stands in a mixed conifer forest of California were treated to mitigate harvest-related increases in surface fuels and to prepare sites for natural regeneration of Pinus species. The study was designed to (1) assess effectiveness of small gap fuel treatments (piling and burning in 0.04 ha gaps) on surface fuel and modelled fire behaviour; (2) test the effect of substrate quality on germination of Pinus species; (3) measure the influence of gap creation on light availability and stand-level light heterogeneity. While the fuel treatment only covered 10 per cent of stand area, it was effective in avoiding increases in stand-level surface fuel following harvests. Fire behaviour was predicted to be moderate following the treatments. The harvest coupled with the gap surface fuel treatments did not change predicted fire behaviour compared with the pretreatment stands. There was a significant but variable increase in germination of Pinus ponderosa seed when sowed on ash substrates compared with bare soil. No substrate effect was detected for Pinus lambertiana. The 0.04-ha gaps created distinct pockets of light and greatly increased stand-level light heterogeneity. This gap-based approach to regenerating multi-aged stands coupled with small-scale fuel treatments is promising for reducing fire hazard and regenerating shade-intolerant species.
Speeding up the memory hierarchy in Flat COMA multiprocessors

Scalable Flat Cache Only Memory Architectures (Flat COMA) are designed for reduced memory access latencies while minimizing programmer and operating system involvement. Indeed, to keep memory access latencies low, neither the programmer needs to perform clever data placement nor the operating system needs to perform page migration. The hardware automatically replicates the data and migrates it to the attraction memories of the nodes that use it. Unfortunately, part of the latency of memory accesses is superfluous. In particular, reads often perform unnecessary attraction memory accesses, require too many network hops, or perform necessary attraction memory accesses inefficiently. In this paper, we propose relatively inexpensive schemes that address these three problems. To eliminate unnecessary attraction memory accesses, we propose a small direct-mapped cache called Invalidation Cache (IVC). To reduce the number of network hops, the IVC is augmented with hint pointers to processors. These hint pointers are faster and have more applicability than in older hint schemes. Finally, to speed up necessary accesses to set-associative attraction memories, we optimize the locality of windows in page-mode DRAMs. We evaluate these optimizations with 32-processor simulations of 8 Splash and Perfect Suite applications. We show that these optimizations speed up the applications by an average of 20% at a modest cost.
Sleep restores loss of generalized but not rote learning of synthetic speech

Sleep-dependent consolidation has been demonstrated for declarative and procedural memory but few theories of consolidation distinguish between rote and generalized learning, suggesting similar consolidation should occur for both. However, studies using rote and generalized learning have suggested different patterns of consolidation may occur, although different tasks have been used across studies. Here we directly compared consolidation of rote and generalized learning using a single speech identification task. Training on a large set of novel stimuli resulted in substantial generalized learning, and sleep restored performance that had degraded after 12 waking hours. Training on a small set of repeated stimuli primarily resulted in rote learning and performance also degraded after 12 waking hours but was not restored by sleep. Moreover performance was significantly worse 24-h after rote training. Our results suggest a functional dissociation between the mechanisms of consolidation for rote and generalized learning which has broad implications for memory models.
Developmental Placement Does It Prevent Future Learning Problems

This study examined if the use of developmental placement, based on the results of the Gesell School Readiness Screening Test, affects children's use of remedial services, referrals to and classification by the Committee on the Handicapped (COH), enrollment in a program for gifted children, retention after grade 2, or placement in sixth grade reading groups. Two hundred and twenty-three children, coded as buy-a-year (BAY), overplaced (OP), or traditional (TR) based on their Gesell placement status, were studied. There were no significant differences between the TR, BAY, or OP children on their referrals to or classification as handicapped by the COH or on their receipt of speech and language services, remedial reading, remedial math, or counseling. Significantly more (p >.05) BAY children were referred to the adaptive motor and resource room program than were either the TR or OP children. Information on the children's placement in a program for the gifted and sixth grade reading groups is also presented.
A Flexible Resource Management Architecture for the Blue Gene/P Supercomputer

Blue Genereg/P are a massively parallel supercomputer intended as the successor to Blue Gene/L. It leverages much of the existing architecture of its predecessor to provide scalability up to a petaflop of peak computing power. The resource management software for such a large parallel system faces several challenges, including system fragmentation due to partitioning, presenting resource usage information using a polling or event driven model, and acting as a barrier between external resource management systems and the Blue Gene/P core. This paper describes how the Blue Gene/P resource management architecture is extremely flexible by providing multiple methodologies for obtaining resource usage information to make scheduling decisions. Three distinctly separate resource management services can be described. First, the Bridge API, a full-featured API suitable for fine tuning scheduling and allocation decisions. Second, a light-weight allocator API for allocating resources without substantial development costs. And lastly, configuring the system into static partitions. Job scheduling strategies utilizing each of the methods can be discussed.
MULTIDIMENSIONAL ASSIGNMENT PROBLEMS

Each of the many two-dimensional variations of the classical assignment problem has at least one counterpart in higher dimensions. This paper is a tutorial on these higher dimensional assignment models and their applications. It is a synthesis of a vast literature scattered throughout a great variety of journal articles and other miscellaneous sources. We have attempted to make the paper a complete bibliography with the emphasis on topics important to practitioners of decision sciences. These topics include original results by the authors, most notably, a polynomial solution approach for a class of multidimensional assignment problems which often arise in scheduling applications.
Scaling of Dynamics in the Earliest Stages of Walking

Background and Purpose: Although the description of mature walking is fairly well established, less is known about what is being learned in the process. Such knowledge is critical to the physical therapist who wants to teach children with developmental delays. The purpose of this experiment was to test the notion that learning to walk efficiently involves fine-tuning the body’s controllable stiffness (by co-contraction and isometric muscle contractions against gravity) to match (at a 1:1 scaling) the gravitational (pendular) stiffness of the swing leg. Subjects: The study participants were 7 children with typical development and the newly emerged ability to walk 6 steps without falling (ages 11 months to 1 year 5 months at the onset of walking). Methods: Pendular stiffness and spring stiffness were estimated from the equations of motion for a hybrid model with kinematic data as children walked over ground. Testing occurred once per month for the first 7 months of walking. Results: After the first month of walking, children walked with greater spring stiffness than would be predicted by the model. The ratio began to approach the predicted value (1:1) as the months progressed. Discussion and Conclusion: The results of this and a previous study of the pendular dynamics of gait suggest that learning to walk is a 2-stage process. The first stage involves the child’s discovery of how to conserve energy by inputting a particular muscular force at the correct moment in the cycle. The second stage involves the fine-tuning of the soft-tissue stiffness that takes advantage of the resonance characteristics of tissues. In order to address developmental delays, investigators must discover the dynamic resources used for the activity and attempt to foster their development. A number of interventions that probe this approach are discussed.
Minor salivary gland mucoepidermoid carcinoma in children and adolescents: a case series and review of the literature

Because well-documented cases of mucoepidermoid carcinomas that are of minor salivary gland origin and occur in children and adolescents have rarely been reported, little information regarding their clinical features and biologic behavior is available. This case report represents a retrospective clinical analysis of five minor salivary gland mucoepidermoid carcinomas accessioned from a 35-year period at the Louisiana State University School of Dentistry and combines the data with 15 well-documented cases from the English language literature. The five mucoepidermoid carcinomas in patients from birth to 19 years of age accounted for 1.3% of the accessioned minor salivary gland neoplasms. There were an additional 15 well-documented cases in the literature. Combining the data for the 20 mucoepidermoid carcinomas resulted in a mean age of 13.5 years and a 2.3:1 female-to-male ratio. Collectively, the hard palate, soft palate, and hard palate/soft palate junction accounted for 85% of the cases. Thirty-five percent of the cases presented as a fluctuant submucosal swelling with surface color alterations. The average duration was five months, and bone involvement occurred in seven cases. A histologic grade of low to intermediate predominated (95%). Surgical removal was the treatment in all cases. Thirteen cases had adequate follow-up of three years or more, and recurrence was documented in only one case. There were no cases of death or metastasis in this series. In children and adolescents, mucoepidermoid carcinomas have a female predilection and occur most commonly on the hard or soft palate or both. A fluctuant submucosal lump with a bluish color is a helpful diagnostic clue. The histologic grades of most mucoepidermoid carcinomas in the first and second decades of life are low and, to a lesser degree, intermediate. Complete surgical excision is the treatment of choice and results in a recurrence rate of less than 10%.
The effect of structure and rate on the recognition and description of auditory temporal patterns

Each trial consisted of dichotomous (high and low frequency) tones started in a random sequence which changed to a patterned sequence. S pressed a switch when he recognized that the sequence was patterned and pressed it again when he could describe the pattern. Rate of presentation was varied. Descriptions were verbalized or tapped. The data showed that descriptions were begun with the longest run of identical tones at the slow rate (1 tone/sec) and ended with the longest run at the fast rate (4 tones/sec). This effect was greater with verbalized than with tapped descriptions. At the medium rate (2 tones/sec), descriptions began with the longest run for patterns of nine tones or more and ended with the longest run for patterns of eight tones or less. Pattern recognition occurred substantially sooner than pattern description. The difference in time between these two responses remained constant across rate, while the difference in number of tones increased with rate. The results are discussed in terms of mode of processing, level of processing, and short-term storage.
Sakaltutan Four Centuries Ago

Twenty-five years ago, when anthropologist Paul Stirling did the fieldwork for his book Turkish Village , he tried to find out what the villagers of Sakaltutan knew about the origin and history of their village. The villagers apparently had very little sense of their past, and the longest genealogies covered only six generations. On the basis of their information and other observations and opinions, Stirling estimated the age of the village at about two hundred years and suggested that the village ‘was probably founded by people from villages nearer Kayseri, who had made a temporary summer camp there for pasture, and later decided to settle permanently and plough’.
Rare missense variants in CHRNB4 are associated with reduced risk of nicotine dependence

Genome-wide association studies have identified common variation in the CHRNA5–CHRNA3–CHRNB4 and CHRNA6–CHRNB3 gene clusters that contribute to nicotine dependence. However, the role of rare variation in risk for nicotine dependence in these nicotinic receptor genes has not been studied. We undertook pooled sequencing of the coding regions and flanking sequence of the CHRNA5, CHRNA3, CHRNB4, CHRNA6 and CHRNB3 genes in African American and European American nicotine-dependent smokers and smokers without symptoms of dependence. Carrier status of individuals harboring rare missense variants at conserved sites in each of these genes was then compared in cases and controls to test for an association with nicotine dependence. Missense variants at conserved residues in CHRNB4 are associated with lower risk for nicotine dependence in African Americans and European Americans (AA P 5 0.0025, odds-ratio (OR) 5 0.31, 95% confidence-interval (CI) 5 0.31‐0.72; EA P 5 0.023, OR 5 0.69, 95% CI 5 0.50‐0.95). Furthermore, these individuals were found to smoke fewer cigarettes per day than non-carriers (AA P 5 6.6 3 10 25 ,E AP 5 0.021). Given the possibility of stochastic differences in rare allele frequencies between groups replication of this association is necessary to confirm these findings. The functional effects of the two CHRNB4 variants contributing most to this association (T375I and T91I) and a missense variant in CHRNA3 (R37H) in strong linkage disequilibrium with T91I were examined in vitro. The minor allele of each polymorphism increased cellular response to nicotine (T375I P 5 0.01, T91I P 5 0.02, R37H P 5 0.003), but the largest effect on in vitro receptor activity was seen in the presence of both CHRNB4 T91I and CHRNA3 R37H (P 5 2 3 10 26 ).
Epidemiology of Gambling and Depression in an Adult Sample

As a relationship has been reported between pathological gambling and depression, the objective of this study was to explore whether there was a relationship between gambling and depression in a sample of 400 adults. No relationship was found.
Myopericarditis associated with Fusobacterium nucleatum-caused liver abscess

A wide clinical spectrum of bacteremic disease caused by Fusobacterium has been presented in this journal. We wish to extend this spectrum by presenting a case of myopericarditis resulting from a liver abscess caused by F. nucleatum. While F. nucleatum plays an important role in periodontal disease, and has been isolated from skin ulcers, liver abscesses, urinary tract infections, and endocarditis, a single case of F. nucleatum-induced pericarditis is documented in the literature.
The Interpersonal Aspects of Coercive Threats and Offers

Je defends ici une conception interpersonnelle des menaces et des offres coercitives, centree sur les intentions de ceux qui font de telles menaces ou de telles offres. Je critique, ce faisant, un groupe de conceptions fort influentes, appelees «baseline accounts». Robert Nozick, qui adopte une approche de ce genre, incorpore a son analyse des menaces coercitives des elements non moraux aussi bien que des elements moraux. Les approches de Daniel Lyons et de David Zimmerman peuvent etre vues, a certains egards, comme des ameliorations par rapport a celle de Nozick. On essaiera de montrer, cependant, qu'aucune de ces approches ne fournit une analyse adequate des menaces et des offres coercitives.
The End of Eurasia: Russia on the Border Between Geopolitics and Globalization

Dmitri Trenin. Washington, DC: Carnegie Endowment for International Peace, 2000. 329 pp., maps, notes, and index. $24.95 paper (ISBN 0-87003-190-2). The collapse of the USSR was the impetus for wha...
Clinical Challenges on Adhesive Dentistry on its 60th Anniversary

Adhesive dentistry allowed restoring lost tooth structures using Minimally Invasive direct or indirect bonded restorations. Adhesive systems and bonding techniques have been constantly evolving since the introduction of Sevriton Cavity Seal, in 1940 by Oskar Hagger. As we celebrate the 60th anniversary of adhesive dentistry in 2015 the future of the Minimally Invasive Adhesive Dentistry is more promising than ever. A better understanding of long-term resin-dentin bonds interaction is guiding the development of materials and techniques that overcome the limitation of current bonding agents and restorative procedures. A brief statement would be stated.
A Comparison of Damage Detection Methodologies Using Analytic Models and Identified Models

Sensitivity enhancing control (SEC) uses the intrinsic relationship between feedback control gains and structure dynamics to enhance the sensitivity of vibration-based damage metrics to structural damage. Previous research has shown that the SEC concept can enhance the sensitivity of the lowest few structural modal frequencies to local stiffness damage significantly, making such metrics more attractive in damage detection. In this paper, SEC is explored in the context of damage localization using inverse approaches. Using full state feedback control laws designed from an analytic model, inverse or model updating approaches to damage localization can be developed such that only the lowest few modal frequencies and mode shapes are required to localize stiffness damage. Using modal data from both closed-loop systems and open-loop systems for updating a global stiffness matrix in a finite-element model avoids the need to measure higher order modal properties. However, recognizing that practical means of realizing SEC are necessary, the paper also considers the use of identified models in designing sensitivity enhancing control laws. Issues regarding the use of state estimate feedback in SEC are described, and an example demonstrates that a controller-observer system design from an identified model has similar properties in enhancing modal frequency shifts due to stiffness damage as a full state feedback controller designed from an analytic (finite-element) model.
Characterization of radiolabeled fluoromisonidazole as a probe for hypoxic cells

Radiolabeled fluoromisonidazole has been characterized as a probe for hypoxic cells in vitro and in vivo. The uptake and retention of [3H]fluoromisonidazole and [3H]misonidazole were compared in V-79 cell monolayers and spheroids by varying incubation time and O2 levels in contact with the medium. The two labeled drugs were retained similarly in cell populations isolated from different depths in spheroids, and the amount of each drug bound in cells at the spheroid periphery increased with decreasing O2 level. The labeling patterns in autoradiographs were similar for spheroids incubated with the two labeled drugs, with most silver grains located over a zone of viable and presumed hypoxic cells intermediate between the necrotic center and the periphery of the spheroid. Biodistribution of the two tritiated drugs was compared in C3H mice bearing KHT tumors with 15% radiobiologically hypoxic cells. Tumor:blood and tumor:muscle ratios greater than 5.0 were achieved in mice sacrificed 4 h after the last of three injections of 5 or 20 mumol/kg of [3H]fluoromisonidazole. These ratios are compatible with imaging and are higher than those obtained with 50 mumol/kg misonidazole in a similar administration protocol. TLC analysis of plasma from mice injected with [3H]fluoromisonidazole indicated that the drug was stable in vivo for up to 2 h and that the metabolites formed were too polar to be dehalogenation products. Fluoromisonidazole labeled with 18F at the end of the alkyl side chain would retain the label on metabolites that bind in hypoxic cells in vivo. Fluoromisonidazole binds stably in the same populations of hypoxic cells as does misonidazole, and we conclude that [18F]fluromisonidazole has potential use as a hypoxia imaging agent in vivo.
Role of Oxygen Vacancies on the Performance of Li[Ni0.5–xMn1.5+x]O4 (x = 0, 0.05, and 0.08) Spinel Cathodes for Lithium-Ion Batteries

Investigation of the high-voltage Li[Ni0.5–xMn1.5+x]O4 (x = 0, 0.05, 0.08) spinels prepared at temperatures of T ≤ 900 °C and given different thermal treatments has shown that the solubility limit for oxygen vacancies in the disordered spinel phase is small at 600 °C. With x = 0, long-range ordering of Ni2+ and Mn4+ and elimination of all oxygen vacancies occurs after an anneal at 700 °C. Above 700 °C, a reversible transition from spinel to rock-salt is initiated, to accommodate oxygen loss. A sample quenched from 900 °C into liquid nitrogen traps some rock-salt second phase; the volume fraction of rock-salt phase decreases with oxygen uptake to 600 °C. However, upon slow cooling (1 °C min–1) from 900 °C, the particles have time to eliminate most of the rock-salt phase by 700 °C; upon further cooling below 700 °C, the spinel phase and the oxygen gain are retained. However, the spinel phase retains oxygen vacancies and attendant Mn3+ with only short-range order of Ni and Mn. The rock-salt phase lowers shar...
Alcohol and anesthetic actions on myocardial contractility. Evidence for a lipophilic/electrophilic sarcoplasmic reticulum site.

While volatile anesthetics typically depress cardiac contractility, the actions of the presently used volatile anesthetics (halothane, enflurane, isoflurane) upon the pattern and magnitude of myocardial tension development differ significantly, suggesting different sites of action.1–3 Previous physiological and biochemical studies have suggested multiple mechanisms of action for the volatile agents, primarily implicating altered control of Ca delivery to myofibrils (depression of Ca entry and depression of sarcoplasmic reticulum uptake and release of Ca).4 To better understand the alterations in myocardial tension development, which may in part be related to the lipid solubility of the anesthetic agents, the aliphatic alcohols were employed as model anesthetic compounds with known physical characteristics which vary in a systematic fashion. With increasing chain length, the aliphatic alcohols possess increasing general anesthetic potency as well as increasing ability to inhibit nerve conduction.5 The actions of alcohols can thus be compared not only with the volatile anesthetics, but also with effects of the local anesthetics (LAs), also known to selectively alter myocardial contractility.3,6 Effects of these various anesthetic compounds were also contrasted with the effects of ryanodine, a plant alkaloid which binds with very high affinity to the Ca release channel of the sarcoplasmic reticulum (SR) and reduces the release of Ca2+ from the SR.7–10
Factors associated with residents' attitudes toward dying patients.

BACKGROUND AND OBJECTIVES Management of the dying patient often elicits anxiety in physicians. This study identified the association of physicians' personal fear of death, tolerance of uncertainty, and attachment style with physician attitudes toward dying patients. METHODS Four psychological scales were distributed to family practice residents located in Texas, Missouri, and Maine. The scales were "Death Anxiety," "Death Attitudes," "Physicians' Reactions to Uncertainty," and "Experiences in Close Relationships." The scores from the measures and demographic data were used to determine which factors were associated with physician attitudes toward caring for terminally ill patients. RESULTS Completed surveys were received from 157 residents. Younger residents (< 30 years) reported more stress from uncertainty and were more uncomfortable with the care of dying patients. Residents who reported higher death anxiety were also more uncomfortable with caring for dying patients. In a multivariate analysis, uncertainty, death anxiety, and age predicted 26% of the total outcome variance of the death attitudes score. CONCLUSIONS Physician tolerance of uncertainty plays a significant role in physician attitudes toward the dying patient. Our findings suggest that decreasing physicians' stress from uncertainty by educating them in the management of the dying patient may improve their attitude toward death and may better prepare them to provide end-of-life care.
Temporal Dynamics of Sensorimotor Networks in Effort-Based Cost-Benefit Valuation: Early Emergence and Late Net Value Integration.

UNLABELLED Although physical effort can impose significant costs on decision-making, when and how effort cost information is incorporated into choice remains contested, reflecting a larger debate over the role of sensorimotor networks in specifying behavior. Serial information processing models, in which motor circuits simply implement the output of cognitive systems, hypothesize that effort cost factors into decisions relatively late, via integration with stimulus values into net (combined) value signals in dorsomedial frontal cortex (dmFC). In contrast, ethology-inspired approaches suggest a more active role for the dorsal sensorimotor stream, with effort cost signals emerging rapidly after stimulus onset. Here we investigated the time course of effort cost integration using event-related potentials in hungry human subjects while they made decisions about expending physical effort for appetitive foods. Consistent with the ethological perspective, we found that effort cost was represented from as early as 100-250 ms after stimulus onset, localized to dorsal sensorimotor regions including middle cingulate, somatosensory, and motor/premotor cortices. However, examining the same data time-locked to motor output revealed net value signals combining stimulus value and effort cost approximately -400 ms before response, originating from sensorimotor areas including dmFC, precuneus, and posterior parietal cortex. Granger causal connectivity analysis of the motor effector signal in the time leading to response showed interactions between these sensorimotor regions and ventrolateral prefrontal cortex, a structure associated with adjusting behavior-response mappings. These results suggest that rapid activation of sensorimotor regions interacts with cognitive valuation systems, producing a net value signal reflecting both physical effort and reward contingencies. SIGNIFICANCE STATEMENT Although physical effort imposes a cost on choice, when and how effort cost influences neural correlates of decision-making remains contested. This dispute reflects a larger disagreement between cognitive neuroscience and ethology over the role of sensorimotor systems in behavior: are sensorimotor circuits merely implementing the late-stage output of cognitive systems, or engaged rapidly and interactively from early in decision-making? We find that, although early representation of effort cost is associated with sensorimotor regions, these signals are also integrated with cognitive stimulus value representations in the time leading up to motor response. These data suggest that sensorimotor networks interact dynamically with cognitive systems to guide decision-making, providing a first step toward reconciling differing perspectives on sensorimotor roles in valuation and choice.
The impact of cancer and quality of life among long-term survivors of breast cancer in Austria

This study explores the relationship between the perceived impact of cancer among long-term breast cancer survivors, sociodemographic and clinical variables, and mental and physical health-related quality of life outcomes in Austria. One hundred and fifty-two long-term survivors of breast cancer (on average 13 years after initial diagnosis) completed three mailed surveys, including the Short Form-36 (SF-36), the Impact of Cancer (version 2) to assess the perceived positive and negative aspects of cancer survivorship, and a general sociodemographic and clinical questionnaire. Linear regression models were constructed to determine the effects of the perceived positive and negative impact of cancer on mental and physical health-related quality of life. Respondents reported a physical health status that centered on population norms for Austria, but scored lower on mental health status. After controlling for age, chemotherapy, exercise, and BMI, the positive impact of cancer was associated with improved physical functioning (p = 0.0014) and the negative impact of cancer was associated with poorer physical functioning (p < 0.0001). After controlling for age, marital status, the belief in emotional distress as a cause of cancer, and high stress levels, the negative impact of cancer was associated with poorer mental functioning (p < 0.0001). Higher perceived positive impact of cancer was not associated with improved mental functioning. Long-term survivors of breast cancer in Austria perceive both positive and negative impacts of breast cancer. These perceptions, in particular the negative impact of cancer, appear to influence, or are potentially influenced by, physical and mental health-related quality of life.
The Value of Midterm Student Feedback in Cross-Disciplinary Graduate Programs

End-of-course student evaluations are frequently used to evaluate university faculty teaching. However, employing midterm student feedback has been found to be instrumental in informing faculty abo...
Ethical issues in microbiome research and medicine

The human microbiome is the collection of bacteria, viruses, and fungi that live on and in the human organism’s skin, mucosa, and intestinal tract. Re-examining commonly accepted ethical standards from the perspective of this new area of research provides an opportunity to reassess our current thinking about research regulations as well as the importance of some principles and distinctions. In this commentary, I explain ethical issues illuminated by research on the human microbiome related to personal identity, privacy, property, research ethics, public health, and biobanks.
The Association Between Lipoproteins, Disability, and Physical Function Among Older Costa Rican Adults.

Objective: To examine the relationship between total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) with disability and physical performance. Method: Wave 1 ...
The Advent of Environmental Disclosure: Utilities’ Responses to Public and Private Politics

Recent scholarship highlights that corporations attempt to manage the impressions of social movement actors through using environmental disclosures. As a whole, these studies create a relatively ambiguous understanding of the relationship between movement activities and variation in environmental disclosure. In this paper, I argue this ambiguity arises because of a failure to consider both public and private political activities. To remedy this oversight, I explore the question of how public and private political activities shape environmental disclosure. I pursue this question within a specific historical and industry context. Namely, I explore the advent of utilities’ environmental disclosures in response to movement activities between 1960 and 1975. My findings demonstrate that public political activities, and not private political activities, are determinants of utilities’ first environmental disclosure. These findings highlight that utilities used disclosure to contest and shape emerging environmenta...
The capacity value of optimal wind and solar portfolios

Abstract Using large data sets of simulated wind and solar energy production, we create optimal wind, solar and blended (combined wind and solar) portfolios over various spatial and temporal scales, and use portfolio theory to quantify the capacity benefits in various portions of the electric grid in the Eastern United States. We add to the existing literature on portfolio analysis of renewable energy resources by (i) studying the benefits of optimal aggregation over various spatial and temporal scales, (ii) quantifying the capacity benefits of renewable portfolios over space and time, and (iii) analyzing spatial distributions of renewable installations in optimal renewable portfolios. The results indicate that full time availability of wind and blended portfolios are respectively 14 and 17 times larger than full time availability of an individual wind farm and adding solar to wind portfolios increases the availability factor of renewable portfolios by more than 40% in most regions. Further, optimal hourly portfolios provide higher capacity value relative to daily and weekly portfolios.
UTILITY OF ALKALINE PHOSPHATASE AS A SCREENING TEST FOR RICKETS IN YOUNG CHILDREN

Objective To determine if alkaline phosphatase (AP) levels are a useful screening test for vitamin D-deficient rickets in children who have been breastfed. Methods The study was conducted in Seattle, Washington, USA. Blood for AP determination was obtained from eligible patients who were healthy children 6–15 months old who were exclusively breastfed for >6 months and did not receive supplemental vitamin D. Radiographs were obtained on children with values classified as elevated by the reference laboratory (females 281 U/l, males 324 U/l). Radiographs were classified as rickets or no rickets by the study radiologist. Children with normal AP levels and those with normal radiographs were categorised as not having rickets. Separate analyses were conducted using a cut-off value for AP of 500 U/l. Results AP levels were obtained on 221 children; levels were elevated in 30 (13.6%); levels were >500 in nine patients (5.0%). Radiographs were obtained in 17 patients with elevated AP levels. No rickets was seen in all eight children with elevated levels 500. If 500 is used as the cut-off value, the specificity of AP as a screen for rickets was 97.5% (97.5% CI 94.4% to 99.2%); the prevalence of rickets in this population was 1.9% (95% CI 0.5% to 4.9%). Conclusion AP determination, an inexpensive test requiring a small amount of blood, could be a useful screen for rickets in healthy young children who have been breastfed.
Enhanced postsynaptic inhibitory strength in hippocampal principal cells in high-performing aged rats

Hyperactivity within the hippocampal formation, frequently observed in aged individuals, is thought to be a potential contributing mechanism to the memory decline often associated with aging. Consequently, we evaluated the postsynaptic strength of excitatory and inhibitory synapses in the granule cells of the dentate gyrus and CA1 pyramidal cells of a rat model of aging, in which each individual was behaviorally characterized as aged impaired (AI) or aged unimpaired (AU, with performance comparable to young (Y) individuals). In hippocampal slices of these 3 aged groups (Y, AI, AU), we found that compared to the young, the miniature excitatory and inhibitory currents (mEPSCs and mIPSCs) were larger in amplitude in the granule cells of the AU group and smaller in the AI group. In contrast, in CA1 cells, neither the mEPSCs nor the mIPSCs were affected by age, whereas the extrasynaptic conductance responsible for tonic inhibition was selectively enhanced in CA1 cells of AU individuals. Tonic inhibition conductance was not affected by age in the granule cells. These results support the notion that upregulation of synaptic inhibition could be a necessary condition for the maintenance of performance during aging. These findings also underscore the notions that successful aging requires adaptive upregulation, not merely the preservation of youthful functionality, and that age effects are not homogeneous across hippocampal subfields.
Adaptive sensitivity analysis with nonlinear power load modeling

Voltage fluctuation in power networks is a critical issue for VLSI designs. The analysis and optimization of the voltage drops rely on accurate sensitivity calculation. Due to the high complexity of large-scale circuits, in practice active devices are simplified with power load models. In order to grasp the details of voltage fluctuation, we propose a nonlinear power load model as a function of the supply voltage. We adopt an adaptive analysis algorithm to accelerate the calculation. The power load model provides efficient and accurate noise prediction at system-level.
Patient Safety in Outpatient Care

The outpatient setting, where most medical care is delivered, has unique features with respect to patient safety. Through the cases below we demonstrate the importance of information availability and care transitions, patient self-management skills, and patient–provider communication in addressing patient safety problems in the outpatient setting. Using Wagner’s chronic care model, we describe the health system conditions and patient and provider characteristics that promote safety in ambulatory care.
Truss Topology Design for Elastic/Softening Materials

A general formulation is established for the design of trusses having members made of elastic/softening materials. Implementation of a variational statement for the analysis of such nonlinear structures provides a convenient form for carrying out parametric studies in the design problem. This analysis is represented via an extremum principle stated in terms of mixed stress and deformation variables; constitutively unstable as well as stable material simulations are covered. The design problem formulation is exploited to demonstrate via simple example solutions how for the nonlinear system the optimal topology depends on load state. A formulation is presented for a second design problem, one which provides for the prediction of the optimal strengthening of a given set of softening materials. The optimality condition for this problem states a requirement that at the solution plastic strain of the individual material constituents has constant value over the structural system.
Neuroendocrine Effects of Lifelong Dietary Restriction by Intermittent Feeding in Mice

Lifelong dietary restriction has been shown to increase mean and maximum life span and to delay the onset of pathophysiologic changes associated with aging in rodents (Barrows and Kokkonen, 1978). The mechanisms underlying the modulation of aging by dietary restriction remain unknown. Based on studies using several levels of dietary restriction in mice, Weindruch et al. (1986) suggested that increased metabolic efficiency may be related to longevity, since the longest-lived mice at each level of dietary restriction studies also were the heaviest. Although a number of studies support the hypothesis that increased body weight is associated with increased longevity in dietarily restricted rodents, (reviewed by Ingram and Reynolds, 1987), the relationship between body weight and life span is complex, and it is difficult to make generalized statements relating longevity to body weight.
Heritability of the aged glutathione phenotype is dependent on tissue of origin

Glutathione is a ubiquitous antioxidant that protects cells against reactive oxygen species and other chemical stressors. Despite its functional importance, the impact of genetics on the glutathione system has yet to be fully appreciated. Here, we investigated the heritability of glutathione levels and redox status in a disease-relevant condition: advanced age. We assembled a panel of 18-21-month-old mice representing 19 inbred strains and quantified the levels of reduced and oxidized glutathione, and their sums and ratios, in liver, kidney, heart, pancreas, cerebral cortex, and striatum. Heritability values were calculated for each phenotype and the results varied by tissue of origin. Cardiac glutathione phenotypes exhibited the highest heritabilities (G2 = 0.44-0.67), while striatal glutathione was least heritable (G2 = 0.11-0.29). Statistical relationships between tissues were evaluated, and the emergence of significant correlations suggested that despite tissue-specific heritabilities, at least some shared regulatory mechanisms may exist. Overall, these data highlight another mechanism by which genetic background determines antioxidant protection and stress resistance.