cssi/SciSciGPT-SciSciNet huggingface dataset:
Bioluminescence imaging of G protein-coupled receptor activation in living mice

G protein-coupled receptors (GPCRs), a superfamily of cell-surface receptors involved in virtually all physiological processes, are the major target class for approved drugs. Imaging GPCR activation in real time in living animals would provide a powerful way to study their role in biology and disease. Here, we describe a mouse model that enables the bioluminescent detection of GPCR activation in real time by utilizing the clinically important GPCR, sphingosine-1-phosphate receptor 1 (S1P1). A synthetic S1P1 signaling pathway, designed to report the interaction between S1P1 and β-arrestin2 via the firefly split luciferase fragment complementation system, is genetically encoded in these mice. Upon receptor activation and subsequent β-arrestin2 recruitment, an active luciferase enzyme complex is produced, which can be detected by in vivo bioluminescence imaging. This imaging strategy reveals the dynamics and spatial specificity of S1P1 activation in normal and pathophysiologic contexts in vivo and can be applied to other GPCRs.
The potential value of probabilistic tractography-based for MR-guided focused ultrasound thalamotomy for essential tremor.

Abstract Magnetic Resonance-guided Focused UltraSound (MRgFUS) offers an incisionless approach to treat essential tremor (ET). Due to lack of evident internal anatomy on traditional structural imaging, indirect targeting must still be used to localize the lesion. Here, we investigate the potential predictive value of probabilistic tractography guided thalamic targeting by defining how tractography-defined targets, lesion size and location, and clinical outcomes interrelate. MR imaging and clinical outcomes from 12 ET patients that underwent MRgFUS thalamotomy in a pilot study at the University of Virginia were evaluated in this analysis. FSL was used to evaluate each patient's voxel-wise thalamic connectivity with FreeSurfer generated pre- and post-central gyrus targets, to generate thalamic target maps. Using Receiver Operating Characteristic curves, the overlap between these thalamic target maps and the MRgFUS lesion was systematically evaluated relative to clinical outcome. To further define the connectivity characteristics of effective MRgFUS thalamotomy lesions, we evaluated whole brain probabilistic tractography of lesions (using post-treatment imaging to define the lesion pre-treatment diffusion tensor MRI). The structural connectivity difference was explored between subjects with the best clinical outcome relative to all others. Ten of twelve patients presented high percentage of overlapping between connectivity-based thalamic segmentation maps and lesion area. The improvement of clinical score was predicted (AUC: 0.80) using the volume of intersection between the thalamic target (precentral gyrus) map and MRgFUS induced lesion as feature. The main structural differences between those with different magnitudes of response were observed in connectivity to the pre- and post-central gyri and brainstem/cerebellum. MRgFUS thalamotomy lesions characterized by strong structural connectivity to precentral gyrus demonstrated better responses in a cohort of patients treated with MRgFUS for ET. The intersection between lesion and thalamic-connectivity maps to motor - sensory targets proved to be effective in predicting the response to the therapy. These imaging techniques can be used to increase the efficacy and consistency of outcomes with MRgFUS and potentially shorten treatment times by identifying optimal targets in advance of treatment.
Single Cell Lysis on Microfluidic Devices

Methods to rapidly lyse cells are needed for studying biochemical reaction systems in cells with short half-lives such as protein phosphorylation. Chemical and electrical methods, therefore, were examined to rapidly lyse cells on microfabricated fluidic devices. The most effective cell membrane disruption involved a combination of both chemical and electrical lysing techniques.
Ecophysiological drivers of hardwood plantation diameter growth under non-limiting light conditions

Abstract While light is a primary driver of tree growth and development, other environmental variables are also essential, including water, nutrients, and temperature. Ecophysiological studies have helped to uncover mechanisms underlying these interactive processes, but such trials have been mainly conducted on seedlings, with relatively few dealing with trees past the sapling stage. We used environmental and ecophysiological data collected on 28 trees (age 14–20 years) across three study sites in Indiana, USA for several growing seasons to identify variables that drive diameter growth of plantation-grown hardwoods past the sapling stage under non-limiting light conditions. Results showed that water stress (as reflected in leaf water potential) had the greatest influence on growth; relative diameter growth of black walnut (Juglans nigra L.), northern red oak (Quercus rubra L.), and white oak (Quercus alba L.) was reduced with increasing water stress. Compared to previous studies carried out with seedlings, results provide some evidence to suggest that ecophysiological responses to water stress may differ between seedlings, juveniles, and mature trees of the same species. Relative diameter growth of black walnut and northern red oak increased with increasing soil or leaf nitrogen. We did not find relationships between relative diameter growth of white oak and nutrient variables. Overall, these results have important implications for reforestation and forest management efforts in light of climate change.
"Culture, Psychological Contract Breach and Co-Worker Exclusion"

Social exclusion has negative implications in the workplace, yet we know little about its causes. We argue that psychological contract breach from the organization (towards a focal employee) will s...
Longitudinal trends in sentiment polarity and readability of an online masters of computer science course

In four years, the Georgia Tech Online MS in CS (OMSCS) program has grown from 200 students to over 6000. Despite early evidence of success, there is a need to evaluate the program's effectiveness. In this paper, we focus on trends from Fall 2014 to Fall 2017 in the on-campus and online sections of one OMSCS course, Knowledge-Based Artificial-Intelligence (KBAI). We leverage sentiment analysis and readability assessments to quantify the evolving quality of discourse on the online forum discussions of the various sections. The research was conducted as a longitudinal study, and aims to evaluate the success of the KBAI course by comparing trends between residential and online sections. Despite slight downward trends in online discourse quality and sentiment polarity, our results suggest that the growing OMSCS program has been successful in replicating the quality of learning experienced by on-campus students in the KBAI course.
Indikation der Laserlithotripsie bei Gallengangsteinen

Die Steinextraktion nach endoskopischer Papillotomie (EPT) hat eine hohe Erfolgsrate von 85 bis 95% und ist als Standardmethode bei Choledocholithiasis anzusehen Die Fragmentierung von Gallengangssteinen kann bei schwierigen Steinen die Extraktion erleichtern und die Erfolgsrate erhohen. Sie ist aber auch bei unkomplizierten Gangsteinen erforderlich, wenn eine Extraktion ohne EPT durchgefuhrt warden soll, da lediglich Steine bis zu 6 mm Durchmesser in toto ohne EPT aus dem Ductus choledochus komplikationslos entfernt werden konnen. In Zukunft ist zu erwarten, das die Laserlithotripsie unter Durchleuchtung als Ein-Mann-Methode breiteren Einsatz findet und hierdurch das Risiko einer Blutung und Perforation significant reduziert werden kann.
Regrading as a conversational practice

Abstract The purpose of this paper is to initiate the topicalization of upgrading and downgrading (regrading) in conversational interaction; that is, to offer some fundamental considerations for viewing regrading as an object of study rather than as a taken-for-granted conversational practice. I begin by describing the conversation analytic conception and use of regrading and distinguishing three subtypes. I note further that regrading is a manifestation of scaling, the relationship between the two being reflexive. Regrading, from an interactional perspective, involves a positioning followed by a repositioning on a scale, and so is inherently sequential. I discuss the relationship of contrast and scaling, secondary scales, and certain sequential aspects of regrading. Through the examination of transcribed segments of talk, I comment on the prevalence of regrading as a conversational practice, and on scales as constituting, to a large extent, the underlying structure of talk. I want to claim that (1) Interaction consists, to some considerable extent, of movements, i.e. regrading, on various scales. (2) Understanding of those scales guides interpretation, especially implicature and implication. And (3) understanding word choices as scaling choices is a key to the analysis of how utterances function.
Breaking the rules? A corpus-based comparison of informal features in L1 and L2 undergraduate student writing

Abstract This study reports findings of a comparative corpus-based analysis of informality in L1 and L2 undergraduate student argumentative essays. Data consist of two corpora of student essays: 101 high-rated essays written by L1-English students and 254 high-rated essays written by ESL students in US universities. Based on a taxonomy of the 10 most common informal features cited in style manuals, we compared informal language use in L1-English and ESL undergraduate student essays. Results reveal that overall frequency of informal features is significantly greater in L2 student texts. Findings also indicate that both groups rely on similar informal elements, yet they differ in distinct ways. While ESL student writers tend to employ significantly more anaphoric pronoun it and second-person pronouns, they use most other types less frequently than L1 writers, and generally appear to observe prescriptive rules more strictly. In contrast, L1-English writers tend to adopt a more liberal attitude toward these rules, employing a broader range of informal types, particularly those that have become relatively legitimized in academic writing. The paper concludes with implications for ESL composition pedagogy.
The routledge handbook of consumer behaviour in hospitality and tourism

The Routledge Handbook of Consumer Behaviour in Hospitality and Tourism, edited by Saurabh Kumar Dixit is a very comprehensive collection of chapters focused on consumer behavior and all its facets...
BRCA1/BARD1-dependent ubiquitination of NF2 regulates Hippo-YAP1 signaling

Coordination of growth and genomic stability is critical for normal cell physiology. Although the E3 ubiquitin ligase BRCA1 is a key player in maintenance of genomic stability, its role in growth signaling remains elusive. Here, we show that BRCA1 facilitates stabilization of YAP1 protein and turning "off" the Hippo pathway through ubiquitination of NF2. In BRCA1-deficient cells Hippo pathway is "turned On." Phosphorylation of YAP1 is crucial for this signaling process because a YAP1 mutant harboring alanine substitutions (Mt-YAP5SA) in LATS1 kinase recognition sites not only resists degradation but also rescues YAP1 transcriptional activity in BRCA1-deficient cells. Furthermore, an ectopic expression of the active Mt-YAP5SA, but not inactive Mt-YAP6SA, promotes EGF-independent proliferation and tumorigenesis in BRCA1-/- mammary epithelial cells. These findings establish an important role of BRCA1 in regulating stability of YAP1 protein that correlates positively with cell proliferation.
Innovations in Classroom Technology for Students with Disabilities

Students with high-incidence disabilities (e.g., learning disabilities, emotional behavior disorders, and autism spectrum disorders) often receive most of their education in general education class...
Topological chaos in active nematics

Active nematics are out-of-equilibrium fluids composed of rod-like subunits, which can generate large-scale, self-driven flows. We examine a microtubule-kinesin-based active nematic confined to two dimensions, exhibiting chaotic flows with moving topological defects. Applying tools from chaos theory, we investigate self-driven advection and mixing on different length scales. Local fluid stretching is quantified by the Lyapunov exponent. Global mixing is quantified by the topological entropy, calculated from both defect braiding and curve extension rates. We find excellent agreement between these independent measures of chaos, demonstrating that the extensile stretching between microtubules directly translates into macroscopic braiding of positive defects. Remarkably, increasing extensile activity (through ATP concentration) does not increase the dimensionless topological entropy. This study represents an application of chaotic advection to the emerging field of active nematics and quantification of the collective motion of an ensemble of defects (through topological entropy) in a liquid crystal. Braiding by topological defects in an active nematic fluid produces macroscopic chaotic advection, such that the defects themselves act as effective stirring rods. The resultant mixing is revealed to be a result of sliding on a molecular scale.
Abstract 915: Dysregulation of the Myosin and Myosin Binding Protein-C interaction in Hypertrophic Cardiomyopathy

Rationale: Affecting 1 in 300 individuals, hypertrophic cardiomyopathy (HCM) is a genetic heart disease characterized by left ventricular hypertrophy, myocardial disarray, and sudden cardiac death....
Ocean sound levels in the northeast Pacific recorded from an autonomous underwater glider

Ocean gliders are a quiet and efficient mobile autonomous platform for passive acoustic monitoring and oceanographic measurements in remote marine environments. During July 20-August 6 2012, we used a Teledyne Webb Research Slocum G2 glider equipped with a hydrophone logging system to record ocean sound along a 458 km north to south traverse of the outer continental shelf break along the U.S. Pacific Northwest coast. Glider derived recordings yielded a unique perspective on the variation of ambient sound with depth, where natural wind generated surface processes were identified as a dominant acoustic contributor to spectral levels in the region. Near and far-field vessel radiated noise were also found to add significant energy to ambient conditions. Spatially distributed measurements of ambient sound levels recorded from the glider were consistent with long-term spectral estimates from fixed station, deep ocean hydrophone array measurements during the 1990-2000's in the region. Ocean sound level measurements captured by a mobile glider are shown to be an effective and valuable asset for describing ocean surface wind conditions and characterizing spatial and temporal changes in the underwater acoustic environment over a broad regional scale.
Prestructuring ANNs via a priori knowledge

The work to be described has as its objective development of a constructive method that uses certain a priori information about a problem domain to design the starting structure of an artificial neural network (ANN). For the prestructuring process, there is motivation to move away from homogeneous structures to ones that comprise modules of smaller ANNs. Issues of concern include physical realizability, scalability of training time with large numbers of connections, and successful generalization. The method explored is based on a general systems theory methodology (here called GSM) that calculates a kinds of structural information of the problem domain via analyzing I/O pairs from that domain. This GSM-based information is used for developing a modularized ANN starting structure. Extensive experiments on 3-input, 1-output Boolean mappings verify our predictions. In addition, the experiments indicate that the GSM-based modularized-ANN design is `conservative' in the sense that the PS of the modularized ANN contains at least all the mappings included in the GSM category used to design the ANN. Experiments with 5-input, 1-output Boolean functions provide further support of the conclusions.
Disassembling cattle and enskilling subjectivities: Butchering techniques and the emergence of new colonial subjects in Santiago de Guatemala:

When they introduced cattle into Guatemala in the 16th century, Europeans also brought a whole new industry involving ranches, slaughterhouses, and new forms of labor. On the one hand, cattle produ...
Communicative institutionalization of CSR: a content analysis of firms’ motivations in social reports from three market economies

Drawing on institutional theory, this content analysis explored firms' social reports for a ten-year period in three market economies. Specifically, this study analyzed firms' motivations for corpo...
Doing Family Differently in School-to-Home Contexts: Gay Fathers at the Schoolhouse Door.

Purpose: This qualitative, phenomenological study explores gay fatherhood visibility in schools. The study was guided by prior research on families headed by lesbian, gay, bisexual, trans, and quee...
Moving prevention of functional impairment upstream: is middle age an ideal time for intervention?

To live independently, individuals must be able to perform basic activities of daily living (ADLs), including bathing, dressing, and transferring out of a bed or chair. When older adults develop difficulty or the need for help performing ADLs, they experience decreased quality of life and an increased risk of acute care utilization, nursing home admission, and death. For these reasons, slowing or preventing the progression to functional problems is a key focus of the care of older adults. While preventive efforts currently focus mainly on older people, difficulty performing basic ADLs (“functional impairment”) affects nearly 15% of middle-aged adults, and this prevalence is increasing. People who develop functional impairment in middle age are at increased risk for adverse outcomes similar to those experienced by older adults. Developing ADL impairment in middle age also impacts work force participation and health expenditures, not just in middle age but also older age. Middle-aged adults have a high capacity for recovery from functional impairment, and many risk factors for developing functional impairment in middle and older age have their roots in mid-life. Taken together, these findings suggest that middle age may be an ideal period to intervene to prevent or delay functional impairment. To address the rising prevalence of functional impairment in middle age, we will need to work on several fronts. These include developing improved prognostic tools to identify middle-aged people at highest risk for functional impairment and developing interventions to prevent or delay impairment among middle-aged people. More broadly, we need to recognize functional impairment in middle age as a problem that is as prevalent and central to health outcomes as many chronic medical conditions.
How Federalism Built the FBI, Sustained Local Police, and Left Out the States

This Article examines the endurance of police localism amid the improbable growth of the FBI in the early twentieth century when the prospect of a centralized law enforcement agency was anathema to the ideals of American democracy. It argues that doctrinal accounts of federalism do not explain these paradoxical developments. By analyzing how the Bureau made itself indispensable to local police departments rather than encroaching on their turf, the Article elucidates an operational, or collaborative, federalism that not only enlarged the Bureau’s capacity and authority but also strengthened local autonomy at the expense of the states. Collaborative federalism is crucial for understanding why the police have gone for so long without meaningful state or federal oversight, with consequences still confronting the country today. This history highlights how structural impediments to institutional accountability have been set over time and also identifies a path not taken, but one that can still be pursued, to expand the states’ supervisory role over local police.
Long-term implications of oil discoveries for international saving in a DSGE model

Abstract Possession and production of oil reserves affects the host country’s current account. Throughout the history of the North Sea oil, Norway ran persistent current account surpluses and accumulated public “oil funds.” The other major producer, the United Kingdom did not establish an oil fund. This work models how oil discoveries impact the current account. A small open economy DSGE model with an oil sector expresses the current account as a function of oil discoveries. In this model, an oil discovery creates a long-term borrowing-repayment-saving cycle. Some of the characteristics of the economy that affect oil-related decisions include: the presence of an oil fund, the equity home bias, and the technology of the oil industry. These characteristics are estimated structurally using the North Sea data for Norway and the United Kingdom. The estimation suggests that, upon discovering oil in the North Sea, the populations of Norway and the United Kingdom made similar economic choices but under different circumstances: Norway’s export revenues were amplified by a period of high oil prices in the 2000s, whereas the UK largely balanced its oil trade and did not benefit from the oil price. Similar decisions made under different circumstances led to remarkably different effects of oil discoveries on the current accounts.
Prior COVID-19 Infection and Antibody Response to Single Versus Double Dose mRNA SARS-CoV-2 Vaccination

The double dose regimen for mRNA vaccines against SARS-CoV-2 presents both a hope and a challenge for global efforts to curb the COVID-19 pandemic. With supply chain logistics impacting the rollout of population-scale vaccination programs, increasing attention has turned to the potential efficacy of single versus double dose vaccine administration for select individuals. To this end, we examined response to Pfizer-BioNTech mRNA vaccine in a large cohort of healthcare workers including those with versus without prior COVID-19 infection. For all participants, we quantified circulating levels of SARS-CoV-2 anti-spike (S) protein IgG at baseline prior to vaccine, after vaccine dose 1, and after vaccine dose 2. We observed that the anti-S IgG antibody response following a single vaccine dose in persons who had recovered from confirmed prior COVID-19 infection was similar to the antibody response following two doses of vaccine in persons without prior infection (P≥0.58). Patterns were similar for the post-vaccine symptoms experienced by infection recovered persons following their first dose compared to the symptoms experienced by infection naive persons following their second dose (P=0.66). These results support the premise that a single dose of mRNA vaccine could provoke in COVID-19 recovered individuals a level of immunity that is comparable to that seen in infection naive persons following a double dose regimen. Additional studies are needed to validate our findings, which could allow for public health programs to expand the reach of population wide vaccination efforts.
Double Devil’s Advocacy: Were They or Weren’t They? Only Nil Sorskii Knew

This scholar’s work on Nil Sorskii and Iosif Volotskii progressed unevenly from adhering to Ia.S. Lur’e’s modification of the traditional Nil vs. Iosif paradigm to a strident assertion of their collaborative alliance promoting monasticism and resolutely opposing dissidence, with a mixture of intersection and compatible differences of emphasis in their original writings. But one must concede the possibility that Nil’s collaboration did not include support of Iosif’s enthusiastic endorsement of monasterial riches, the commemoration culture that bolstered it, and the harshest measures against convicted heretics. And while in in no way provable, one cannot know for certain that Nil did not speak up in some way against monasterial riches at a Moscow synod in 1503.
The Potential Utility of Prebiotics to Modulate Alzheimer’s Disease: A Review of the Evidence

The gut microbiome has recently emerged as a critical modulator of brain function, with the so-called gut-brain axis having multiple links with a variety of neurodegenerative and mental health conditions, including Alzheimer’s Disease (AD). Various approaches for modulating the gut microbiome toward compositional and functional states that are consistent with improved cognitive health outcomes have been documented, including probiotics and prebiotics. While probiotics are live microorganisms that directly confer beneficial health effects, prebiotics are oligosaccharide and polysaccharide structures that can beneficially modulate the gut microbiome by enhancing the growth, survival, and/or function of gut microbes that in turn have beneficial effects on the human host. In this review, we discuss evidence showing the potential link between gut microbiome composition and AD onset or development, provide an overview of prebiotic types and their roles in altering gut microbial composition, discuss the effectiveness of prebiotics in regulating gut microbiome composition and microbially derived metabolites, and discuss the current evidence linking prebiotics with health outcomes related to AD in both animal models and human trials. Though there is a paucity of human clinical trials demonstrating the effectiveness of prebiotics in altering gut microbiome-mediated health outcomes in AD, current evidence highlights the potential of various prebiotic approaches for beneficially altering the gut microbiota or gut physiology by promoting the production of butyrate, indoles, and secondary bile acid profiles that further regulate gut immunity and mucosal homeostasis, which are associated with beneficial effects on the central immune system and brain functionality.
Self-Organization and Semiosis in Jazz Improvisation

The complex systems principle of self-organization provides a new way of understanding the behavioral dynamics behind the emergent, spontaneous exchanges of musical performance. In biological self-organization, energy is expended in the form of work which operates to maintain order in a system, collectively constraining the possible behaviors the components of the system can exhibit. When two self-organized systems become closely coupled they form a synergistic, teleodynamic system, such that in a circularly causal manner each system's work helps to maintain and self-sustain one another's behavioral dynamics. The semiotic exchange between two improvising jazz musicians can also be understood as forming a synergistic, teleodynamic system, with musicians expending energy in the form of musical 'work' that operates to mutually constrain the semiotic form of their own and their co-musicians playing behavior. In more specific terms, the two musicians form a higher-order autopoietic system that both creates and maintains the collective order of the co-playing musicians via the nonlinear, self-organizing dynamics that characterize non-equilibrium dissipative systems. Here the authors introduce this self-organization framework and describe its implications for developing new theories of musical semiotics that adequately address the spontaneous and emergent nature of improvised musical performances. The authors also describe how corresponding methods of non-linear time series analyses can provide the tools necessary for explicating the dynamical processes that shape such complex social exchanges.
Moderate Exercise Mitigates the Detrimental Effects of Aging on Tendon Stem Cells

Aging is known to cause tendon degeneration whereas moderate exercise imparts beneficial effects on tendons. Since stem cells play a vital role in maintaining tissue integrity, in this study we aimed to define the effects of aging and moderate exercise on tendon stem/progenitor cells (TSCs) using in vitro and in vivo models. TSCs derived from aging mice (9 and 24 months) proliferated significantly slower than TSCs obtained from young mice (2.5 and 5 months). In addition, expression of the stem cell markers Oct-4, nucleostemin (NS), Sca-1 and SSEA-1 in TSCs decreased in an age-dependent manner. Interestingly, moderate mechanical stretching (4%) of aging TSCs in vitro significantly increased the expression of the stem cell marker, NS, but 8% stretching decreased NS expression. Similarly, 4% mechanical stretching increased the expression of Nanog, another stem cell marker, and the tenocyte-related genes, collagen I and tenomodulin. However, 8% stretching increased expression of the non-tenocyte-related genes, LPL, Sox-9 and Runx-2, while 4% stretching had minimal effects on the expression of these genes. In the in vivo study, moderate treadmill running (MTR) of aging mice (9 months) resulted in the increased proliferation rate of aging TSCs in culture, decreased lipid deposition, proteoglycan accumulation and calcification, and increased the expression of NS in the patellar tendons. These findings indicate that while aging impairs the proliferative ability of TSCs and reduces their stemness, moderate exercise can mitigate the deleterious effects of aging on TSCs and therefore may be responsible for decreased aging-induced tendon degeneration.
Effective Vehicle Driving Simulation: Lessons from Aviation

Recent advances in computer and display systems technology have made vehicle driving simulators a viable training and evaluation resource for both civilian and military operations. Such computer-aided simulation has unlimited human factors applications for improving the safety, efficiency, and cost of a wide variety of mechanical vehicle systems. However, technological capabilities do not, by themselves, improve the design or training process. For simulators to be effective, users must understand the complexities of the simulation system, exercise control over the simulator’s technological capabilities, and determine relevant criteria for simulation fidelity. Drawing on the experiences of the aviation community, this paper focuses on four important issues/applications for vehicle driving simulation: 1) modeling the simulation environment, 2) simulator fidelity and design, 3) automotive design evaluation (displays and controls), and 4) driver education and training.
A New Approach to Porphyria

The traditional division of porphyrias into erythropoietic and hepatic (10), based on occurrence of the intermediates in tissues, blood, feces, and urine, has been very helpful for their diagnosis (8). Consecutive biochemical and clinical findings subdivided each group: erythropoietic porphyrias on the basis of different porphyrins occurring in the blood, hepatic porphyrias on the basis of porphyrins and precursors in urine, feces, and liver (8) (Table 1). Further investigations confirmed the existence of intermediate types (6), named erythrohepatic (6). Chemical porphyrias are caused by chemicals, e.g., hexachlorobenzene, allylisopropylacetamide, lead (2). Additional classification contrasts acquired vs. hereditary porphyrias (8) (Table 1); however, there are some controversial cases, e.g., porphyria cutanea tarda (8). The genetic porphyrias, the character of which is presently agreed upon, are listed in Table 1. Any classification based on fragmentary analysis of excreted intermediate porphyrins had to be complex since the excretion of the intermediates (8) does not only depend on the type of porphyria (5, 7). Uroporphyrin is excreted in urine, and frequently, in spite of typical hepatic classification, occurs also in the blood; protoporphyrin is excreted in feces, although protoporphyrin might be found in the blood and originate in bone marrow (6, 7).
Serological Dissection of Human Breast Cancer with Mouse and Human Monoclonal Antibodies

Over the past two years our group has taken two distinct approaches in the study of breast cancer: The first is the definition of the antigenic phenotype of breast cancer using mouse monoclonal antibodies as serological probes. The second approach has been the dissection of the humoral immune response to breast cancer and other tumors using antibodies in sera and human monoclonal antibodies generated by the hybridoma technology.
Latch-up characterization and checking of a 55 nm CMOS mixed voltage design

Mixed Voltage Design has become predominant in the semiconductor industry due to the integration of high voltage and low voltage circuits in the pad ring. Latch-up characterization and analysis of a 55 nm CMOS technology has been done to determine the effects of various protection strategies on the trigger and holding parameters of SCRs to develop a design rule checker.
‘The Changelessness of God’ as Kierkegaard's Final Theodicy: God and the Gift of Suffering

In the midst of his final ‘attack on Christendom’, Kierkegaard published a short discourse devoted to James 1:17–21 entitled ‘The Changelessness of God’. Aside from providing a pleasant rhetorical anomaly at this juncture in his corpus, Kierkegaard's final discourse also introduces another surprise: a defense of the God who sits silently by and watches true Christianity disappear from Denmark. Kierkegaard's defense of God also accounts for Christian suffering – Christ's, the apostles' and perhaps his own – and it does so by creating a sharp division of reality between temporality and eternity, a division that echoes through from the earliest discourses on the same biblical passage. This article contextualizes ‘The Changelessness of God’ by tracing these developments and then continues to press the logic of Kierkegaard's construal of the relationship between temporality and eternity which ultimately leads to a rather problematic description of suffering as a necessary good and perfect gift from God.
Paracrystalline inclusions of a novel ferritin containing nonheme iron, produced by the human gastric pathogen Helicobacter pylori: evidence for a third class of ferritins.

Abstract An abundant 19.3-kDa Helicobacter pylori protein has been cloned, and the sequence is homologous with a ferritin-like protein produced by Escherichia coli K-12. Homologies are also present with a number of eucaryotic ferritins, as well as with the heme group-containing bacterioferritins. All amino acids involved in chelation of inorganic iron by ferritins from humans and other higher species are conserved in the H. pylori protein. Consistent with the structural data indicating an iron-binding function, E. coli overexpressing the H. pylori ferritin-like protein accumulates almost 10 times more nonheme iron than vector controls, and the iron-binding activity copurifies with the 19.3-kDa protein. Immunoelectron microscopy of H. pylori, as well as of E. coli overexpressing the H. pylori gene, demonstrates that the gene product has a cytoplasmic location where it forms paracrystalline inclusions. On the basis of these structural and functional data, we propose that the H. pylori gene product (termed Pfr) forms the basis for a second class of bacterial ferritins designed to store nonheme iron.
CONTINUOUS DAMAGE MECHANICS MODEL OF FRACTURE IN LAMINATED COMPOSITES

ABSTRACT A modified version of the Kachanov damage accumulation law is employed to study the damage kinetics in laminated composite materials, such as epoxy/ graphite laminates embrittled by low (76K) temperatures. KEYWORDS: Composites; expoxy/graphite; mechanical properties; damage accumulation; fracture.
A Commentary on “A New Initiative on Precision Medicine”

U.S. President Barack Obama recently announced a new Precision Medicine Initiative, and Drs. Francis Collins and Harold Varmus have begun to provide a vision for how some of this initiative might be implemented by the U.S. National Institutes of Health (NIH) (1). Precision medicine may be defined as “an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person” (2). A vision of the NIH portion of the Precision Medicine Initiative is to launch a large-scale national cohort study of a Million or more Americans to advance understanding of how to optimize treatments customized to individual variability in genomic and environmental health-determinants (2). A precision-medicine approach, using shared-decision making with patients and their providers as partners in patient-centered care, offers an important opportunity to improve substance-use disorders (SUDs) prevention and treatment outcomes (3, 4). Pertinent to precision medicine, the Collaborative Research on Addictions at NIH, comprising the National Institute on Drug Abuse, National Institute on Alcohol Abuse and Alcoholism, and the National Cancer Institute, in partnership with other NIH Institutes, Centers and Offices, is currently planning to launch a longitudinal cohort study of Adolescent Brain and Cognitive Development (ABCD). This study will follow 10,000 youth over up to a 10-year period, approximately ages 9–10 at baseline when largely naive to use of alcohol, marijuana, nicotine, and other drugs. This national cohort study presents a key opportunity to answer fundamentally important questions to informing a precisionmedicine approach regarding prevention of SUDs in youth (5). Several relevant questions are: (1) how does repeated exposure to abused substances, such as nicotine, alcohol, and cannabis, impact normative brain development essential for memory and cognitive functioning? (2) How do drug-altered brain-maturation pathways inform precision-medicine-tailored SUDs prevention approaches targeting high-risk youth? (3) Which brain-development events altered following adolescent drug use heighten likelihood of transformation of unhealthy drug use into full-blown SUDs in subpopulations with, or without, co-occurring mental health disorders? (4) How do druginduced alterations in brain-development and memory impairments interact with genomic and epigenetic risk factors in these different subpopulations to increase vulnerability to SUDs? (5) In what manner does use of specific substances impact use of other substances? Thus, the objective of the ABCD study is timely to precision medicine: to better understand how exposure to abused substances modifies brain-development trajectories and how this relates to emotional and mental health, social development, memory and other cognitive function, as well as academic and other outcomes (5).
A bivariate frequency analysis of extreme rainfall with implications for design

[1] Analysis of extreme rainfall events has conventionally been performed by prespecifying rainfall duration as a filter to abstract annual maximum rainfall depths as the only variable for analysis. However, this univariate approach does not account for dependence between rainfall properties. To characterize extreme rainfall events, a bivariate analysis is conducted in this study using hourly precipitation data from Indiana, USA. Samples of extreme rainfall events are chosen on the basis of three different criteria: annual maximum volume (AMV), annual maximum peak intensity (AMI), and annual maximum cumulative probability (AMP) based on empirical copulas. Rainfall characteristics, such as total depth, duration, and peak intensity are analyzed using copulas to describe the dependence structures between rainfall variables and to construct their joint distribution for extreme rainfall events. Results from the derived bivariate models are compared to those from conventional univariate analysis by computing the corresponding conditional distributions. Traditional univariate analysis seems to provide reasonable estimates of rainfall depths for durations greater than 10 hours. For shorter durations, a bivariate analysis with extreme events defined on the basis of AMP is recommended. The univariate analysis combined with Huff curves grossly underestimates peak intensities, and again AMP estimates are recommended. Results of this study have implications for current hydrologic design in that they provide better estimates of design rainfall.
Sequential Synthesis of Histidine-degrading Enzymes in Bacillus subtilis

Abstract l-Histidine induces the formation of the four enzymes constituting the histidine-degrading pathway in Bacillus subtilis. Studies of the kinetics of induction of histidase and of FGA hydrolase demonstrated that the two enzymes appear after induction in sequence, separated by a 2-min interval. The results of experiments in which chloramphenicol was used to arrest peptide bond formation indicate that both enzymes are first formed as enzymatically inactive precursors. The basis for the sequential appearance of these enzymes and of their precursors was shown to be the sequential appearance of their respective enzyme-forming capacities. Experiments using rifampicin, an inhibitor of the initiation of transcription, provide good evidence that the synthesis of messenger RNA specifying both enzymes is initiated upon addition of the inducer. These findings support the hypothesis that the structural genes of the two enzymes are transcribed into a single polycistronic messenger.
“O my Luve’s like a red, red rose”: does Burns’s melody really matter?

An exploration of Burns's original choice of tune 'Major Graham's Strathspey' for his most famous love song. The essay provides a detailed publication history of the song and compares the melodies various editors have chosen over the past 200 years.
Suicide and Social Processes

Suicide evokes the image of a lonely, hopeless, deeply distressed person—nearly 80% are men—often influenced by alcohol or drugs, taking their lives following losses or disruptive life experiences. Younger persons’ suicides may be less contemplated but typically just as lonely and disconnected. Older persons, for whom planning is more common, are more lethal in their attempts, with older white men having the highest rates in the United States—occurring in the context of social isolation, pain, and medical problems that prune the scope of their lives. The greatest overall burdens in the United States occur among men and women in the middle years of life, which has fueled the recent stark increase in suicide rates in our country.... Language: en
Search for Superconductivity in Lithium

We report on the results of a search for superconductivity in Li. We find no evidence for the predicted transition to superconducti vity at any temperature down to 5 mK in magnetic fields down to 0.4 uT. However, an unexpected Curie- Weiss temperature dependence in the magnetic susceptibility is observed. We discuss the possibility that this signal arises from the Li itself, the possibility that it arises from Kondo behavior, and the implications of the effect for the predicted Tc of Li.
Programmable shunts and headphones: Are they safe together?

OBJECT Programmable shunts have a valuable role in the treatment of patients with hydrocephalus, but because a magnet is used to change valve settings, interactions with external magnets may reprogram these shunts. Previous studies have demonstrated the ability of magnetic toys and iPads to erroneously reprogram shunts. Headphones are even more ubiquitous, and they contain an electromagnet for sound projection that sits on the head very close to the shunt valve. This study is the first to look at the magnetic field emissions of headphones and their effect on reprogrammable shunt valves to ascertain whether headphones are safe for patients with these shunts to wear. METHODS In this in vitro study of the magnetic properties of headphones and their interactions with 3 different programmable shunts, the authors evaluated Apple earbuds, Beats by Dr. Dre, and Bose QuietComfort Acoustic Noise Cancelling headphones. Each headphone was tested for electromagnetic field emissions using a direct current gaussmeter. T...
Activity of long-lead burst neurons in pontine reticular formation during head-unrestrained gaze shifts.

Primates explore a visual scene through a succession of saccades. Much of what is known about the neural circuitry that generates these movements has come from neurophysiological studies using subjects with their heads restrained. Horizontal saccades and the horizontal components of oblique saccades are associated with high-frequency bursts of spikes in medium-lead burst neurons (MLBs) and long-lead burst neurons (LLBNs) in the paramedian pontine reticular formation. For LLBNs, the high-frequency burst is preceded by a low-frequency prelude that begins 12–150 ms before saccade onset. In terms of the lead time between the onset of prelude activity and saccade onset, the anatomical projections, and the movement field characteristics, LLBNs are a heterogeneous group of neurons. Whether this heterogeneity is endemic of multiple functional subclasses is an open question. One possibility is that some may carry signals related to head movement. We recorded from LLBNs while monkeys performed head-unrestrained gaze shifts, during which the kinematics of the eye and head components were dissociable. Many cells had peak firing rates that never exceeded 200 spikes/s for gaze shifts of any vector. The activity of these low-frequency cells often persisted beyond the end of the gaze shift and was usually related to head-movement kinematics. A subset was tested during head-unrestrained pursuit and showed clear modulation in the absence of saccades. These “low-frequency” cells were intermingled with MLBs and traditional LLBNs and may represent a separate functional class carrying signals related to head movement.
Patterns of mother and father involvement in day care

Twenty-eight dual-earner couples were interviewed 10 times each to determine their involvement in their young child’s day care center. Mothers picked up the child significantly more often than did fathers. Mothers and fathers spent about equal amounts of time in the center during their visits. In comparison to fathers, mothers were significantly more communicative with caregivers and the director. There were many similarities between mothers and fathers in the topics they discussed with staff.
814 EXPRESSION OF A BACTERIAL GENE IN TRANSGENIC MICE

We studied the tissue specificity and the developmental stage of expression of a bacterial gene, Ecogpt, following its introduction into the pronuclei of fertilized mouse oocytes by microinjection. Ecogpt, a gene not present in mammalian cells, codes for XGPRT (xanthine guanine pyrophosphoribosyl transferase), a purine salvage enzyme. We looked for both the presence of the gene and activity of the enzyme in tissues of embryos, fetuses and adults. The vectors used to introduce Ecogpt included the 69% fragment of bovine papilloma virus, pSV2-gpt, RD-114, and polyomavirus. Liveborn mice were assayed for the presence of the genes injected by Southern blot analysis of DNA extracted from tail tips. Where possible, we have assayed for enzyme activity by utilizing 14C-xanthine as a substrate for XGPRT in cell homogenates, and at all stages of development we have used an immunocytochemical procedure to detect XGPRT in tissue sections. To date, our results indicate that the BPV vector is embryotoxic since in those few animals born with BPV sequences, they are highly rearranged and there is no XGPRT activity detectable.
The Nucleotide Sequence of the Translated and Untranslated Regions of a cDNA for Myotoxinafrom the Venom of Prairie Rattlesnake (Crotalus viridis viridis)

Abstract Myotoxin a , isolated from C. viridis viridis venom, is a myonecrotizing agent present in many snake venoms. A cDNA library was prepared from mRNA obtained from the venom glands of a C. viridis viridis. The complete base sequence of a cDNA corresponding to an mRNA encoding myotoxin a was determined. The 5′ untranslated region has 15 nucleotides, while the 3′ untranslated region has 109 nucleotides. The translated portion of the myotoxin a cDNA encodes a start methionine, a signal peptide, the myotoxin a peptide sequence, and an additional lysine residue. It is likely that myotoxin a is secreted as the cDNA encodes a signal peptide immediately 5′ to the myotoxin a peptide code.
High Speed Spectral Domain Phase Microscopy for Quantitative Cell Surface and Cytoplasmic Flow Measurements

We demonstrate cellular applications for high-speed SDPM using a system with 19kHz maximum line-rate. Two-dimensional phase B-scan images taken at 13Hz show flow sensitivity in a single-celled organism.