cssi/SciSciGPT-SciSciNet huggingface dataset:
RAS and RAF-1 form a signalling complex with MEK-1 but not MEK-2.

Abstract Recent studies have demonstrated the existence of a physical complex containing p21ras (RAS), p74raf-1 (RAF-1), and MEK-1. Although it is clear that formation of this complex depends on the activation state of RAS, it is not known whether this complex is regulated by the activation state of the cell and whether MEK-2 is also present in the complex. To analyze the regulation and specificity of this complex, we utilized immobilized RAS to probe lysates of cultured NIH 3T3 fibroblasts and analyzed the proteins complexing with RAS following serum starvation or stimulation. Complex formation among RAS, RAF-1, and MEK-1 was dependent only on RAS:GMP-PNP and not on cell stimulation. Incubations of lysates with immobilized RAS depleted all RAF-1 from the lysate but bound only a small fraction of cytosolic MEK-1, and further MEK-1 could bind immobilized RAS only if exogenous RAF-1 was added to the lysate. This indicates that binding of MEK-1 to RAS depends on the presence of RAF-1 or an equivalent protein. In contrast to MEK-1, MEK-2 was not detected in the RAS signalling complex. A proline-rich region of MEK-1 containing a phosphorylation site appears to be essential for signalling complex formation. Consistent with the preferential binding of MEK-1 to RAS:RAF-1, the basal activity of MEK-1 in v-ras-transformed cells was found to be elevated sixfold, whereas MEK-2 was elevated only twofold, suggesting that the RAS signalling pathway favors MEK-1 activation.
A New Species of Hippolytid Shrimp from Rocas Alijos

While sorting decapod crustaceans from among sponges taken at Rocas Alijos during the 1990 Cordell Expedition, I found a specimen of an unidentified shrimp. It proved to be an undescribed species of Thor (Caridea: Hippolytidae). Additional specimens of this species were found among the collections of the United States Museum of Natural History (USNM), and among unidentified specimens sent to me by Gabriel Ramos of Cali, Colombia. The holotype was donated to the collections of the Allan Hancock Foundation, University of Southern California (USC).
Character displacement in the fighting colours of Hetaerina damselflies

Aggression between species is a seldom-considered but potentially widespread mechanism of character displacement in secondary sexual characters. Based on previous research showing that similarity in wing coloration directly influences interspecific territorial aggression in Hetaerina damselflies, we predicted that wing coloration would show a pattern of character displacement (divergence in sympatry). A geographical survey of four Hetaerina damselfly species in Mexico and Texas showed evidence for character displacement in both species pairs that regularly occurs sympatrically. Hetaerina titia, a species that typically has large black wing spots and small red wing spots, shifted to having even larger black spots and smaller red wing spots at sites where a congener with large red wing spots is numerically dominant (Hetaerina americana or Hetaerina occisa). Hetaerina americana showed the reverse pattern, shifting towards larger red wing spots where H. titia is numerically dominant. This pattern is consistent with the process of agonistic character displacement, but the ontogenetic basis of the shift remains to be demonstrated.
Mutual Enhancement of Differentiation of Osteoblasts and Osteocytes Occurs Through Direct Cell–Cell Contact

There is increasing evidence that osteocytes regulate multiple aspects of bone remodeling through bi-directional communication with osteoblasts. This is potentially mediated through cell-cell contact via osteocytic dendritic processes, through the activity of secreted factors, or both. To test whether cell-cell contact affects gene expression patterns in osteoblasts and osteocytes, we used a co-culture system where calvarial osteoblasts and IDG-SW3 osteocytes were allowed to touch through a porous membrane, while still being physically separated to allow for phenotypic characterization. Osteoblast/osteocyte cell-contact resulted in up-regulation of osteoblast differentiation genes in the osteoblasts, when compared to wells where no cell contact was allowed. Examination of osteocyte gene expression when in direct contact with osteoblasts also revealed increased expression of osteocyte-specific genes. These data suggest that physical contact mutually enhances both the osteoblastic and osteocytic character of each respective cell type. Interestingly, Gja1 (a gap junction protein) was increased in the osteoblasts only when in direct contact with the osteocytes, suggesting that Gja1 may mediate some of the effects of direct cell contact. To test this hypothesis, we treated the direct contact system with the gap junction inhibitor 18-alpha-glycyrrhetinic acid and found that Bglap expression was significantly inhibited. This suggests that osteocytes may regulate late osteoblast differentiation at least in part through Gja1. Identification of the specific factors involved in the enhancement of differentiation of both osteoblasts and osteocytes when in direct contact will uncover new biology concerning how these bone cells communicate.
Taxation and Corporate Governance: An Economic Approach

How do the tax system and corporate governance arrangements interact? This chapter begins by reviewing an emerging literature that explores how agency problems create such interactions and provides evidence on their importance. This literature has neglected how taxation can interact with the various mechanisms that have arisen to ameliorate the corporate governance problem, such as concentrated ownership, accounting and information systems, high-powered incentives, financing choices, payout policy, and the market for corporate control. The remainder of the chapter outlines potentially fruitful areas for future research into how these mechanisms may respond to the tax system.
Endogenous versus exogenous fatty acid availability affects lysosomal acidity and MHC class II expression

Although the immune system, inflammation, and cellular metabolism are linked to diseases associated with dyslipidemias, the mechanism(s) remain unclear. To determine whether there is a mechanistic link between lipid availability and inflammation/immune activation, we evaluated macrophage cell lines incubated under conditions of altered exogenous and endogenous lipid availability. Limiting exogenous lipids results in decreased lysosomal acidity and decreased lysosomal enzymatic activity. Both lysosomal parameters are restored with the addition of oleoyl-CoA, suggesting that fatty acids play a role in the regulation of lysosomal function. Cell surface expression of major histocompatibility complex (MHC)-encoded molecules is also decreased in the absence of exogenous lipids. Additionally, we observe decreased γ-interferon stimulation of cell surface MHC class II. Using cerulenin to limit the endogenous synthesis of fatty acids results in decreased cell surface expression of MHC class II but does not appear to alter lysosomal acidity, suggesting that lysosomal acidity is dependent on exogenous, but not endogenous, fatty acid availability. Testing these conclusions in an in vivo mouse model, we observed statistically significant, diet-dependent differences in lysosomal acidity and MHC class II cell surface expression. Collectively, these data demonstrate a mechanistic link between lipid availability and early events in the immune response.
Reproductive decisions under threat of predation: squirrel treefrog (Hyla squirella) responses to banded sunfish (Enneacanthus obesus)

We tested whether the presence of a predator (non-lethal effect) could produce patterns of prey distribution and abundance attributed historically to direct mortality. Sixteen experimental ponds (1,000 l cattle watering tanks) were established; eight containing seven enclosed banded sunfish, Enneacanthus obesus, and eight predator-free controls. Ponds were colonized by ovipositing squirrel treefrogs, Hyla squirella, and a total of 33,128 eggs and tadpoles were recovered from the experimental ponds. Significantly more eggs and tadpoles (94.8%) were recorded from the predator-free treatments. These data support an alternative mechanism, based primarily on maternal behavior, explaining classic patterns of anuran species composition across a landscape of breeding sites.
Nuclear matrix bound fibroblast growth factor receptor is associated with splicing factor rich and transcriptionally active nuclear speckles.

We have used confocal microscopy combined with computer image analysis to evaluate the functional significance of a constitutively expressed form of the receptor tyrosine kinase FGFR1 (fibroblast growth factor receptor 1) in the nucleus of rapidly proliferating serum stimulated TE 671 cells, a medullobastoma human cell line. Our results demonstrate a limited number of large sites and numerous smaller sites of FGFR1 in the nuclear interior. The larger sites showed virtually complete colocalization (>90%) with splicing factor rich nuclear speckles while the smaller sites showed very limited overlap (<20%). Similar results were found for several other proliferating cell lines grown in culture. An in situ transcription assay was used to determine colocalization with transcription sites by incorporating 5-bromouridine triphosphate (BrUTP) followed by dual staining for BrUTP and FGFR1. These results combined with those from using an antibody against the large subunit of RNA polymerase II suggest a significant degree of colocalization (26-38%) over both the large and small sites. No colocalization was detected with sites of DNA replication. The spatial arrangements of FGFR1 sites and colocalization with nuclear speckles were maintained following extraction for nuclear matrix. Moreover, immunoblots indicated a significant enrichment of FGFR1 in the nuclear matrix fraction. Our findings suggest an involvement of a nuclear matrix bound FGFR1 in transcriptional and RNA processing events in the cell nucleus. We further propose that nuclear speckles, aside from a role in transcriptional/RNA processing events, may serve as fundamental regulatory factories for the integration of diverse signaling and regulatory factors that impact transcription and cellular regulation.
On the immortality of television sets: "function" in the human genome according to the evolution-free gospel of ENCODE.

A recent slew of ENCyclopedia Of DNA Elements (ENCODE) Consortium publications, specifically the article signed by all Consortium members, put forward the idea that more than 80% of the human genome is functional. This claim flies in the face of current estimates according to which the fraction of the genome that is evolutionarily conserved through purifying selection is less than 10%. Thus, according to the ENCODE Consortium, a biological function can be maintained indefinitely without selection, which implies that at least 80 − 10 = 70% of the genome is perfectly invulnerable to deleterious mutations, either because no mutation can ever occur in these “functional” regions or because no mutation in these regions can ever be deleterious. This absurd conclusion was reached through various means, chiefly by employing the seldom used “causal role” definition of biological function and then applying it inconsistently to different biochemical properties, by committing a logical fallacy known as “affirming the consequent,” by failing to appreciate the crucial difference between “junk DNA” and “garbage DNA,” by using analytical methods that yield biased errors and inflate estimates of functionality, by favoring statistical sensitivity over specificity, and by emphasizing statistical significance rather than the magnitude of the effect. Here, we detail the many logical and methodological transgressions involved in assigning functionality to almost every nucleotide in the human genome. The ENCODE results were predicted by one of its authors to necessitate the rewriting of textbooks. We agree, many textbooks dealing with marketing, mass-media hype, and public relations may well have to be rewritten.
THE NEUROLEPTIC MALIGNANT AND SEROTONIN SYNDROMES

The neuroleptic malignant syndrome and the serotonin syndrome share many clinical features and may exist on a spectrum of the same disorder. The neuroleptic malignant syndrome, however, is an idiosyncratic drug reaction, whereas the serotonin syndrome is an effect of drug toxicity. Both syndromes present with varying degrees of mental status changes and autonomic instability. In general, patients with the neuroleptic malignant syndrome have higher fevers and pronounced extrapyramidal signs with muscle rigidity, whereas patients with the serotonin syndrome have lower fevers, more gastrointestinal dysfunction, and myoclonus. Treatment for both syndromes consists of removing the offending agent and providing intensive supportive care. Syndrome-specific therapies are controversial.
Instability and freezing in a solidifying melt conduit

Abstract Previous works have shown that when liquid flows in a pipe whose boundary temperature is below freezing, a tubular drainage conduit forms surrounded by solidified material that freezes shut under the appropriate combination of forcing conditions. We conduct laboratory experiments with wax in which the tube freezes shut below a certain value of flux from a pump. As the flux is gradually decreased to this value, the total pressure drop across the length of the tube first decreases to a minimum value and then rises before freezing. Previous theoretical models of a tube driven by a constant pressure drop suggest that once the pressure minimum is reached, the states for a lower flux should be unstable and the tube should therefore freeze-up. In our experiments, flux and pressure drop were coupled, and this motivates us to extend the theory for low Reynolds number flow through a tube with solidification to incorporate a simple pressure-drop–flux relationship. Our model predicts a steady-state relationship between flux and pressure drop that has a minimum pressure as the flux is varied. The stability properties of these steady states depend on the boundary conditions: for a fixed flux, they are all stable, whereas for fixed pressure drop, only those with a flux larger than that at the pressure drop minimum are stable. For a mixed pressure–flux condition, the stability threshold of the steady states lies between these two end members. This provides a possible mechanism for the experimental observations.
Mechanical resonance of quartz microfibers and boundary condition effects

We have measured the mechanical resonance of microscale quartz fibers to qualify the method of obtaining the Young’s modulus of nanowires from their resonance frequency and geometry. An equation for a circular beam with a linearly varying cross-section is derived and used to calculate the resonance frequency shift. We have established a model to discuss the boundary condition effect on the resonance frequency. The Young’s modulus of the quartz fibers has been determined by measuring the resonance frequency, and the geometry, and by applying the model that treats the influence of the type of clamp. The mean value from measurements of the fundamental resonance on 14 different microfibers is 70±6 GPa. This mean value is close to 72 GPa, the Young’s modulus of bulk fused quartz. Four resonance modes were observed in high vacuum and air. The mechanical resonance in high vacuum is linear at the fundamental vibration mode, and nonlinear for higher modes.
Genetic diversity of Alternaria alternata isolated from tomato in California assessed using RAPDs

Black mould lesions were caused by Alternaria alternata in 76% of 228 tomato fruit with characteristic sunken black lesions collected from fields of processing tomatoes in California. Analysis of 29 RAPD primers revealed a high level of genetic diversity among the 69 isolates tested. Two major phenetic groups (Group 1 with 55 isolates and Group 2 with 14) were identified independently by PCA and by UPGMA of Jaccard similarity coefficients. Only 34 of 137 RAPD markers were monomorphic for all isolates and the genetic similarity between the two groups was 50%. Co-infection of black mould lesions by genetically distinct strains of A. alternata occurred in two of 10 isolates tested. There was no evidence for geographic clustering of isolates with high levels of genetic similarity, suggesting that isolates are widely dispersed across California. Only one isolate was identified which also caused stem canker disease on a susceptible tomato cv., suggesting that these strains play a minor role in causing black mould on processing tomatoes in California. This isolate and two other known stem canker isolates were clustered together with 11 other isolates in Group 2. Group 2-specific bands were also identified in a survey of seven additional isolates known to produce host-specific toxins.
Thoreau's Alternative Economics: Work, Liberty, and Democratic Cultivation

Henry Thoreau's Walden is frequently read as the tale of a disaffected Romantic individualist escaping the rigors of community and modern society to seek refuge in a pondside idyll. I argue that this is a fundamental misreading which misses the political import of the book. Walden reveals itself to be a democratic advice-book focusing on the tensions between the political ideal of free self-direction and the unfavorable work conditions that laborers often face. Thoreau's goal is to set out a strategy by which economically vulnerable citizens may enact their liberty and autonomy in threatening employment conditions. To that end, Thoreau reformats themes and practices from various ancient philosophical traditions. Walden is one of the few texts in our tradition in which strategies are thought through for the individual laborer attempting to maintain freedom while at the same time making a living. It therefore merits our closest attention.
A Love Affair with Pidgin

IN RECENT years, a married couple in the United States developed a pidgin-like patois (for their own use) out of three languages that one or the other knew well but both did not share. The following account, while telling something of their story, looks at how such a private ‘language’ can impact negatively on second-language acquisition. The study seeks also to gauge the effect of this personal ‘pidgin’ on Pierre, a native speaker of Wolof, and on his acquisition of English, a language he needs to know. In one sense their private language is a success, but in another it is a problem, because Pierre needs to become fluent in the language of his new home. He and Mary have created a language style that suits their daily needs, but their very success and originality may be preventing Pierre from moving on into conventional English.
Lessons from the past: Evolutionary impacts of mass extinctions

Mass extinctions have played many evolutionary roles, involving differential survivorship or selectivity of taxa and traits, the disruption or preservation of evolutionary trends and ecosystem organization, and the promotion of taxonomic and morphological diversifications— often along unexpected trajectories—after the destruction or marginalization of once-dominant clades. The fossil record suggests that survivorship during mass extinctions is not strictly random, but it often fails to coincide with factors promoting survival during times of low extinction intensity. Although of very serious concern, present-day extinctions have not yet achieved the intensities seen in the Big Five mass extinctions of the geologic past, which each removed >50% of the subset of relatively abundant marine invertebrate genera. The best comparisons for predictive purposes therefore will involve factors such as differential extinction intensities among regions, clades, and functional groups, rules governing postextinction biotic interchanges and evolutionary dynamics, and analyses of the factors that cause taxa and evolutionary trends to continue unabated, to suffer setbacks but resume along the same trajectory, to survive only to fall into a marginal role or disappear (‘‘dead clade walking’’), or to undergo a burst of diversification. These issues need to be addressed in a spatially explicit framework, because the fossil record suggests regional differences in postextinction diversification dynamics and biotic interchanges. Postextinction diversifications lag far behind the initial taxonomic and morphological impoverishment and homogenization; they do not simply reoccupy vacated adaptive peaks, but explore opportunities as opened and constrained by intrinsic biotic factors and the ecological and evolutionary context of the radiation.
Liberation Theology: The Radicalization of Social Catholic Movements

This article argues that pre-existing networks and organizations were crucial to the development of liberation theology in Latin America. Drawing on concepts from social movement theory, I demonstrate that in the early and mid-twentieth century, the Catholic Churches in Brazil and Chile had favorable political opportunities, organizational resources, and insurgent consciousness which facilitated the rise of liberationist movements and organizations in both countries. For the case of Chile, data is drawn from forty interviews with Chilean activists and representatives of the Church with ties to social Catholic movements of the 1950s and 1960s. The article makes two contributions to the literature on liberation theology: (1) by placing lay activists at the center of analysis it offers a corrective to research which emphasizes the role of Church elites in the emergence of liberation theology; and (2) it demonstrates the importance of pre-existing networks and organizations for movement emergence. The article...
How children know the relevant properties for generalizing object names

Young children’s novel word extensions indicate that their animal categories, like those of adults, are characterized by multiple similarities among instances; whereas their artifact categories, again like those of adults, are characterized more simply by commonalities among instances in shape. Three experiments shed light on the nature and development of a mechanism that enables children to organize novel lexical categories differently for different kinds of objects. Experiment 1 shows that, by adult judgments, animals and artifacts present different category organizations. Experiment 2 shows relations between both age and the number of nouns young children have acquired, and children’s kind-specific generalizations of newly learned nouns. Experiment 3 is a training study in which even younger children show an ability to learn and then generalize highly abstract relations between different contextual cues and different category structures; and importantly, to learn more than one set of such relations at a time. Together, these three findings indicate one way in which children are able to rapidly and accurately form lexical categories that parallel those of adults in their language community.
Radiation dosimetry in CT: the role of the manufacturer

This article provides an overview of CT dose indices (CTDIs) currently used to quantify the amount of radiation used to perform clinical CT examinations. The manner in which CTDI metrics can be used to estimate the amount of radiation received by any given patient undergoing a CT examination is explained. The role of the manufacturer in providing information on the amount of radiation used to perform CT scans, as well as the corresponding patient doses, is addressed. Manufacturers have specific obligations to provide data on the quantity and quality of the x-ray radiation that is incident on patients, and should also be required to indicate whether this amount is reasonable, taking into account patient characteristics (i.e., size) and the imaging task. Manufacturers could also develop software that would provide conversion factors to enable operators to translate CT output into patient doses. Technological advances in CT scanners, and specifically cone beam CT which use wide x-ray beams, will require modification or replacement of current CTDI metrics. Alternatives to current CTDI metrics are described, and manufacturers need to assess their suitability for specifying the amount of radiation emitted by CT scanners in clinical examinations.
Probing the Long Range Distance Dependence of Noble Metal Nanoparticles

The localized surface plasmon resonance (LSPR) of noble metal nanoparticles has recently been the subject of extensive studies. Previously, it has been demonstrated that Ag nanotriangles that have been synthesized using nanosphere lithography (NSL) behave as extremely sensitive and selective chemical and biological sensors. The present work reveals information regarding the long range distance dependence of the localized surface plasmon resonance (LSPR) of silver and gold nanoparticles. Multilayer adsorbates based on the interaction of HOOC(CH2)10SH and Cu 2+ were assembled onto surface-confined nanoparticles. Measurement of the LSPR extinction peak shift versus number of layers and adsorbate thickness is non-linear and has a sensing range that is dependent on the composition, shape, in-plane width, and out-of-plane height of the nanoparticles. Theoretical modeling confirms and offers a mathematical interpretation of these results. These experiments indicate that the LSPR sensing capabilities of noble metal nanoparticles can be tuned to match the size of biological and chemical analytes by adjusting the aforementioned properties. The optimization of the LSPR nanosensor for a specific analyte will improve an already sensitive nanoparticle-based sensor.
Maternal Influences on the Developing Fetus

Observations of a link between pregnant woman and fetus, and speculation on its nature abound throughout history, literature, and across cultures. Despite the ubiquity of the phenomenon, relatively little is known about the manner in which the development of the fetus is influenced by the maternal psychological context. Scientific inquiry into the nature of this relationship has been historically hampered not by lack of interest, but by lack of access to the fetus. Although this changed considerably in the 1980s with the development of real time obstetric ultrasound, the prenatal period is the only time in development when interaction between mother and offspring cannot be directly observed and evaluated.
VENTILATION AND PULMONARY GAS EXCHANGE DURING EXERCISE IN THE SAVANNAH MONITOR LIZARD (VARANUS EXANTHEMATICUS)

During exercise, pulmonary gas exchange in reptiles was predicted to differ from that in mammals because of their less complex lung structure, which might reduce ventilation-perfusion heterogeneity (V/QL) at the expense of pulmonary diffusion limitation. To investigate this, the multiple inert gas elimination technique was used in six Varanus exanthematicus at rest and during maximal exercise. Trace amounts of six inert gases were infused into the external jugular vein and blood samples were collected from the pulmonary artery and the left atrium. Mixed expired gas samples and ventilatory and metabolic data were acquired. Indices of V/QL heterogeneity, calculated using a 50-compartment model, were low at rest (log standard deviation of perfusion distribution, logSDQ = 0.39) and increased significantly with exercise (logSDQ = 0.78). Oxygen diffusion limitation was apparent during exercise and was comparable to reported mammalian values. A molecular-mass-dependent limitation, suggesting limited intrapulmonary gas mixing, was evident only at rest. An increase in left atrial PO2 from 82mmHg at rest to 96 mmHg during exercise was associated with a corresponding decrease in PCO2. These data indicate adequacy of pulmonary ventilation and gas exchange for metabolic demands in exercising varanid lizards and suggest that less complex lung structures are not necessarily linked to increased pulmonary diffusion limitation.
Clinical Trials and Their Principles

Clinical trials are needed for the development and evaluation of any type of treatment used to detect, prevent, or treat genitourinary cancer. This chapter introduces clinical trials in this context. The discussion largely focuses on the design and implementation of a clinical trial in its various stages. Possible sources of bias in clinical trials and methods of minimizing or eliminating this bias are also discussed.
Presence+Experience: A Framework for the Purposeful Design of Presence in Online Courses

In this article, we share a framework for the purposeful design of presence in online courses. Instead of developing something new, we looked at two models that have helped us with previous instructional design projects, providing us with some assurance that the design decisions we were making were fundamentally sound. As we began to work with the two models we noted that they could be overlaid to create a useful design framework for our efforts. The framework—what we refer to as the Presence+Experience (P+E) framework—merges the Community of Inquiry (CoI) model with Kolb’s experiential learning cycle. We used this framework to guide the redesign of Science, Technology, Engineering, and Mathematics (STEM) method courses for eLearning delivery.
ASSESSMENT OF PULMONARY ARTERIAL STIFFNESS BY CARDIAC MAGNETIC RESONANCE IMAGING

Cardiac magnetic resonance imaging (CMR) in pulmonary arterial hypertension (PAH) is an evolving tool to aid in right ventricular morphology and pulmonary artery (PA) hemodynamics. As right heart catheterization (RHC) and echo are the reference standard, we hypothesize that CMR may provide value
Translating and scaling the HHS Action Plan to Prevent Healthcare-associated Infections to the local level: experience of a Los Angeles Health System.

Background The US Department of Health and Human Services National Action Plan to Prevent Healthcare-associated Infections (HAIs) set 5-year national-level goals beginning in 2009 for reducing the most common and serious HAIs. Meeting these goals on the local level depended on generalizing and sustaining evidence-based infection prevention practices at the >5000 US community and federal acute care hospitals. Objectives To describe the impact of the Federal and California State HAI Action Plans on UCLA Heath, an academic health system in Los Angeles, in planning and implementing HAI prevention activities and reducing HAI rates. Methods The Context-Input-Process-Product model and the systems functions and properties framework were applied to the evaluation of infection prevention and control activities at UCLA Health. Results Resource constraints, competing priorities, variation in care practices, provider engagement, and the expanding administrative burden of public reporting were some of the challenges to implementing and sustaining HAI prevention practices at the local level. Progress toward reducing targeted HAI rates in UCLA Health has paralleled the results observed on the state and national level, including declining infections associated with medical devices, surgical procedures, and multidrug-resistant organisms. Conclusions In California, federal funding supporting the state HAI Action Plans and mandatory public reporting requirements spurred adoption, implementation, and evaluation of HAI prevention efforts and helped to drive collaborative performance improvement and research at the facility level.
Current Epidemiology of Tuberculosis

After years of decline, tuberculosis has become an increasing cause of morbidity and mortality in the United States. Chronic problems of poverty, homelessness, substandard housing, and poor access to health care have combined to help maintain a reservoir of infected persons. The addition of HIV-associated immunodeficiency has allowed many of these infected individuals, whose infections ordinarily would have remained dormant, to develop tuberculosis at younger ages. In addition, increasing numbers of cases of tuberculosis are being identified among young foreign-born adults from countries of high tuberculosis prevalence. Transmission from these young adults has occurred in increasing numbers to children. These children form an enlarging pool of infected persons that will continue the cycle of tuberculous infection and disease for future generations. Renewed emphasis and resources need to be placed on tuberculosis, particularly in the public health sector. Only in this manner will early detection and treatment of those with infection and disease occur and the cycle of tuberculosis be broken.
The Geographic Distribution of Genetic Risk as Compared to Social Risk for Chronic Diseases in the United States.

There is an association between chronic disease and geography, and there is evidence that the environment plays a critical role in this relationship. Yet at the same time, there is known to be substantial geographic variation by ancestry across the United States. Resulting geographic genetic variation—that is, the extent to which single nucleotide polymorphisms (SNPs) related to chronic disease vary spatially—could thus drive some part of the association between geography and disease. We describe the variation in chronic disease genetic risk by state of birth by taking risk SNPs from genome-wide association study meta-analyses for coronary artery disease, diabetes, and ischemic stroke and creating polygenic risk scores. We compare the amount of variability across state of birth in these polygenic scores to the variability in parental education, own education, earnings, and wealth. Our primary finding is that the polygenic risk scores are only weakly differentially distributed across U.S. states. The magni...
Validation of Strongly Coupled Models: A Framework for Resource Allocation

In partitioned analysis, individual constituent models developed in an isolated manner are coupled to predict the behavior of a system more complex than the individual constituents themselves. Such coupled models, be they multi-scale and/or multi-physics in nature, are regularly implemented to improve engineering systems at design and off-design conditions, establish safety procedures, develop public policies, or determine legal liabilities. The only rigorous means of establishing and improving confidence in predictions of these models involves calibrating and validating them against physical experiments. In this paper, the authors propose a model calibration framework tailored specifically for strongly coupled numerical models to assist in resource allocation strictly from the perspective of predictive maturity. The focus herein is not only on the allocation of resources between code development efforts and physical experiments conducted for validation, but also on determining the most efficient means of allocating resources in accomplishing code development and data collection tasks. Thus, an approach for prioritization of code development efforts as well as an approach for design of optimal experiments is provided. Furthermore, the framework defines a domain within which the model is executed to make predictions and takes a sufficient coverage of this domain through physical experiments into account. This paper thoroughly explains this framework and demonstrates its application and feasibility through a series of complex case study applications.
An Outline of Vector Graphs and Conditional Banach Spaces

We show that in several analytic problems our concern is with a non-linear manifold m of a vector space x, which is homogeneous and nearly additive in that for x,y ∈ m, we have x+y in m provided that x and y are in a relation c. We are thus led to the study of the graph (x, c). We outline the fundamentals of the theory of such graphs.
Welfare and Capitalism in Postwar Japan: Historical Patterns of Structural Logic in Postwar Japan

Chapter 2 has demonstrated that it is possible to construct a structural logic of social protection by identifying the configuration of veto players and the specific institutional constraints on their preferences (that is, district magnitude and the relative importance of the personal vote). This chapter applies my structural logic approach to explain welfare state development in Japan. In contrast to the more comparative orientation of the previous chapter, this chapter claims that my structural logic approach can explain two sets of variations in policy outcomes within the same country: (i) cross-policy variations during the same period; and (ii) historical variations. To put it simply, cross-policy variations can be understood as a reflection of the relative power of different actors and their preferences. In other words, programs sought by influential actors have a better chance of being adopted, whereas programs they oppose have a worse chance. My structural logic explains cross-policy variations by predicting which actors have the most power in a specific institutional context. Granted this approach, it follows that policy shifts in social protection happen when (i) the veto player configuration changes; and/or (ii) veto players' preferences change. Historical shifts in welfare politics can be understood in terms of the shifts in the power distribution within a polity and the changes in the preferences of the veto players. This chapter proceeds in four sections. Section 1 chronicles historical shifts in the government type, district magnitude, and the relative importance of the personal vote that occurred in postwar Japan.
Brief Announcement: Using Read-k Inequalities to Analyze a Distributed MIS Algorithm

Until recently, the fastest distributed MIS algorithm, even for simple graphs, e.g., unoriented trees, has been the simple randomized algorithm discovered in the 80s. This algorithm (commonly called Luby's algorithm) computes an MIS in O(log n) rounds (with high probability). This situation changed when Lenzen and Wattenhofer (PODC 2011) presented a randomized O(√log n} ⋅ log\log n)-round MIS algorithm for unoriented trees. This algorithm was improved by Barenboim et al. (FOCS 2012), resulting in an MIS algorithm running in O(√log n ⋅ log\log n) rounds.The analyses of these tree MIS algorithms depends on "near independence" of probabilistic events, a feature of the tree structure of the network. In their paper, Lenzen and Wattenhofer hope that their algorithm and analysis could be extended to graphs with bounded arboricity. We show how to do this in this note. By using a new tail inequality for read-k families of random variables due to Gavinsky et al. Random Struct Algorithms, 2015), we show how to deal with dependencies induced by the recent tree MIS algorithms when they are executed on bounded arboricity graphs. Specifically, we analyze a version of the tree MIS algorithm of Barenboim et al. and show that it runs in O(poly(α) ⋅ √log n ⋅ log log n) rounds in the CONGEST model for arboricity-α graphs.
A Very Brief History of Health Care Ethics: Four Decades from the Golden Age of Bioethics to the Dawn of Interprofessional Ethics

An eighteen-month-old girl’s death from dehydration in 2010 at Johns Hopkins Hospital in Baltimore provides a sobering example of the need for interprofessional ethics training. In a New York Times interview, Dr. Peter Pronovost, medical director of the Quality and Safety Research Group at the hospital, admitted, “We had dysfunctional teamwork because of an exceedingly hierarchal culture. When confrontations occurred, the problem was rarely framed in terms of what was best for the patient” (March 9, 2010). Lives are lost sometimes, in other words, on account of poor teamwork. Hence, promoting effective teamwork is an ethical imperative. Teaching a coherent and consistent clinical and research ethics framework that is shared by all professions, in an interprofessional setting, will allow bioethics to be more successfully integrated into the work of all health care professionals. This chapter proposes a brief history of bioethics broken into three periods: a “golden age” when foundational texts and institutions first appeared, a “silver age” in which the ideas spread to all medical specialties and to all other health professions, and a new epoch of interprofessional healthcare ethics that began in the 21st century. This book is one of the first to explicitly address the outlines of interprofessional ethics, and propose cases to help develop understanding of the field.
Urinary Angiotensinogen: A Promising Biomarker of AKI Progression in Acute Decompensated Heart Failure: What Does It Mean?

Several biomarkers that may precede increases in serum creatinine, the clinical marker of GFR, have been proposed for early detection of AKI. A kinetic GFR formula ([1][1]) is, in our opinion, a sensitive tool to recognize AKI early and more precisely estimate the decline and recovery of kidney
A Rab5 endosomal pathway mediates Parkin-dependent mitochondrial clearance.

Damaged mitochondria pose a lethal threat to cells that necessitates their prompt removal. The currently recognized mechanism for disposal of mitochondria is autophagy, where damaged organelles are marked for disposal via ubiquitylation by Parkin. Here we report a novel pathway for mitochondrial elimination, in which these organelles undergo Parkin-dependent sequestration into Rab5-positive early endosomes via the ESCRT machinery. Following maturation, these endosomes deliver mitochondria to lysosomes for degradation. Although this endosomal pathway is activated by stressors that also activate mitochondrial autophagy, endosomal-mediated mitochondrial clearance is initiated before autophagy. The autophagy protein Beclin1 regulates activation of Rab5 and endosomal-mediated degradation of mitochondria, suggesting cross-talk between these two pathways. Abrogation of Rab5 function and the endosomal pathway results in the accumulation of stressed mitochondria and increases susceptibility to cell death in embryonic fibroblasts and cardiac myocytes. These data reveal a new mechanism for mitochondrial quality control mediated by Rab5 and early endosomes. Damaged mitochondria are normally cleared through canonical and alternative autophagy pathways. Here, the authors report that mitochondria can be cleared through an autophagy-independent endosomal-lysosomal pathway that depends on Parkin-dependent sequestration of mitochondria in Rab5-positive early endosomes.
PAX3–FOXO1 is essential for tumour initiation and maintenance but not recurrence in a human myoblast model of rhabdomyosarcoma

The PAX3-FOXO1 fusion gene is generated by a 2;13 chromosomal translocation and is a characteristic feature of an aggressive subset of rhabdomyosarcoma (RMS). To dissect the mechanism of oncogene action during RMS tumourigenesis and progression, doxycycline-inducible PAX3-FOXO1 and constitutive MYCN expression constructs were introduced into immortalized human myoblasts. Although myoblasts expressing PAX3-FOXO1 or MYCN alone were not transformed in focus formation assays, combined PAX3-FOXO1 and MYCN expression resulted in transformation. Following intramuscular injection into immunodeficient mice, myoblasts expressing PAX3-FOXO1 and MYCN formed rapidly growing RMS tumours, whereas myoblasts expressing only PAX3-FOXO1 formed tumours after a longer latency period. Doxycycline withdrawal in myoblasts expressing inducible PAX3-FOXO1 and constitutive MYCN following tumour formation in vivo or focus formation in vitro resulted in tumour regression or smaller foci associated with myogenic differentiation and cell death. Following regression, most tumours recurred in the absence of doxycycline. Analysis of recurrent tumours revealed a subset without PAX3-FOXO1 expression, and cell lines derived from these recurrent tumours showed transformation in the absence of doxycycline. The doxycycline-independent oncogenicity in these recurrent tumour-derived lines persisted even after PAX3-FOXO1 was inactivated with a CRISPR/Cas9 editing strategy. Whereas cell lines derived from primary tumours were dependent on PAX3-FOXO1 and differentiated following doxycycline withdrawal, recurrent tumour-derived cells without PAX3-FOXO1 expression did not differentiate under these conditions. These findings indicate that PAX3-FOXO1 collaborates with MYCN during early RMS tumourigenesis to dysregulate proliferation and inhibit myogenic differentiation and cell death. Although most cells in the primary tumours are dependent on PAX3-FOXO1, recurrent tumours can develop by a PAX3-FOXO1-independent mechanism, in which rare cells are postulated to acquire secondary transforming events that were activated or selected by initial PAX3-FOXO1 expression. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Role of Autophagy in Atherogenesis

Atherosclerosis, the primary cause of cardiovascular disease, is characterized by the progressive build-up of cholesterol-rich plaques in the arteries. Accumulating evidence suggests an involvement of autophagy in the initiation and progression of atherosclerosis. In this review we discuss how oxidized lipids, advanced glycation products, and inflammation, three hallmarks of atherosclerotic disease, activate autophagy in the different cell types found within plaques. The involvement of autophagy at different steps of lipid metabolism is reviewed, including apoB-containing lipoprotein secretion and cellular cholesterol homeostasis at the level of synthesis, uptake, and efflux. We provide a summary of the latest insights from mouse models of atherosclerosis showing the progressive dysfunction of autophagy leading to plaque progression. Thus, autophagy-stimulating therapies are an attractive area for further research and may be of use for human therapeutics to prevent atherosclerosis and/or treat existing atherosclerotic plaques.
The Ferns of Brazilian Amazonia

Abstract An annotated list of the pteridophytes of Brazilian Amazonia is presented, with the geographic occurrence of the species by States and Territories. The flora includes 12 families, 58 genera and 279 species, with only four species possibly endemic. Two new combinations are Arachnoides macrostegia (Hook.) Tryon & Conant and Thelypteris juruensis (C. Chr.) Tryon & Conant. Some general comments on the geography of Amazonian ferns are included as well as ecological studies presenting data on the local environmental preferences of six species.
Risk of Knee Sepsis After Treatment of Open Tibia Fractures: A Multicenter Comparison of Suprapatellar and Infrapatellar Approaches.

Objectives The suprapatellar approach for medullary nailing of the tibia is increasing. This requires intra-articular passage of instruments, which theoretically places the knee at risk of postoperative sepsis in the setting of open fracture. We hypothesized that the risk of knee sepsis is similar after suprapatellar or infrapatellar nailing of open tibia fractures. Design Retrospective, multicenter. Setting Three urban level 1 trauma centers. Patients All patients treated with medullary nailing for open diaphyseal tibia fractures (OTA 42) from 2009 to 2015. Patients younger than 18 years of age and with less than 12 weeks of follow-up were excluded. We identified 289 fractures in 282 patients. Intervention Suprapatellar (SP) or infrapatellar (IP) medullary nailing of open tibia fractures. Main outcome measurement Occurrence of ipsilateral knee sepsis, defined as presence of a positive culture from knee aspiration or arthrotomy. Deep infection requiring operative debridement, superficial infection requiring antibiotic therapy alone, and all-cause reoperation were also recorded. Results IP nailing was used for 142 fractures. There were 20 infections (14.1%), of which 14 (9.8%) were deep. Fourteen tibias (9.8%) required reoperation for noninfectious reasons for 28 total reoperations (19.7%). SP nailing was used in 147 fractures. There were 24 infections (16.2%), of which 16 (10.8%) were deep. Fourteen additional tibias (9.5%) required reoperation for noninfectious reasons for a total of 30 reoperations (20.4%). There were no differences in the rates of infection, deep infection, or reoperation between groups. There were 2 cases of knee sepsis after SP nailing (1.4%) but zero cases after IP nailing (P = 0.5). Conclusions There was no significant difference in the rate of knee sepsis with SP or IP approaches. The risk of knee sepsis after SP nailing of open fractures is low, but present. Level of evidence Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.