cssi/SciSciGPT-SciSciNet huggingface dataset:
Roles of RNA polymerase IV in gene silencing

Eukaryotes typically have three multi-subunit enzymes that decode the nuclear genome into RNA: DNA-dependent RNA polymerases I, II and III (Pol I, II and III). Remarkably, higher plants have five multi-subunit nuclear RNA polymerases: the ubiquitous Pol I, II and III, which are essential for viability; plus two non-essential polymerases, Pol IVa and Pol IVb, which specialize in small RNA-mediated gene silencing pathways. There are numerous examples of phenomena that require Pol IVa and/or Pol IVb, including RNA-directed DNA methylation of endogenous repetitive elements, silencing of transgenes, regulation of flowering-time genes, inducible regulation of adjacent gene pairs, and spreading of mobile silencing signals. Although biochemical details concerning Pol IV enzymatic activities are lacking, genetic evidence suggests several alternative models for how Pol IV might function.
Child Psychiatry: What Are We Teaching Medical Students?

Objective The author describes child and adolescent psychiatry (CAP) undergraduate teaching in American and Canadian medical schools.
Magnetospectroscopy of CaF2:Dy2+ in the submillimeter∗☆

Abstract The FIR (E2 → T2)-like transitions in CaF2:Dy2+ have been observed with both a Fourier transform spectrometer and Submillimeter lasers at magnetic fields of up to 50 kG. Both the 1 → 6 and 2 → 6 transitions exhibit minima of transition energy vs magnetic field. The possibility of utilizing the 2 → 6 transition energy minimum in conjunction with an optically-pumped D2O laser to produce tunable FIR laser radiation is discussed.
Circulating mitotic figures in CMV-associated hydrops fetalis

![Figure][1] A male neonate was born at 28 weeks of gestational age by C-section because of intrauterine growth restriction and fetal anomalies. Radiographic scans showed cardiomegaly, pleural effusion, and ascites, consistent with hydrops fetalis. He developed a disseminated rash,
Laparoscopic iliac and iliofemoral lymph node resection for melanoma

Regional lymphadenectomy in the iliac and groin, originally devised by Basset in 1912, is performed for the treatment of melanoma metastatic to this lymphatic basin [1]. Laparoscopic iliac node dissection may be a valuable management option because it allows performance of the same procedure as in open surgery [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13] but with significant benefits such as decreased operative morbidity due to decreased surgical trauma, less violation of the abdominal muscles or the inguinal ligament, reduced postoperative pain, and increased patient satisfaction with the cosmetic appearance. The authors’ approach makes use of a laparoscopic technique [14] to offer an alternative to traditionally described lymph node dissection for melanoma. A review of the literature showed few laparoscopic approaches in this context. Jones et al. [15] do not perform the resection en bloc and do not address the iliofemoral lymph node dissection with a combined retroperitoneal technique such as the current authors use. Two authors in the literature use laparoscopy through a transperitoneal approach, with a piecemeal removal of nodes [16, 17]. Delman et al. [18] limit their technique to the inguinal and high femoral basin alone. The video demonstrates the novel use of a laparoscopic method to harvest iliac lymph nodes in combination with a minimally invasive approach to groin dissection for metastatic melanoma. After a laparoscopic resection of these nodes, the authors deliver the iliac nodal contents through the groin using a minimally invasive approach. This approach is highly beneficial to the patient. He is able to leave the hospital significantly earlier than he would have after a traditional open procedure. He can return to his job as a car mechanic within 1 week and is metastasis free at the 9-month follow-up assessment without evidence of lymphocele formation. The authors do not believe that this technique has any significant implication for lymphocele formation compared with an open procedure because in essence, the same resection is being performed. A larger prospective series is necessary to determine lymphocele outcomes.
The limits of science and the scientific method

Abstract The claim is made that as science moves increasingly closer to the human limits of perceptibility, not only the financial, manpower, and epistemological factors present problems (as discussed in an earlier article), but that the scientific method itself also deteriorates. In particular, the interaction between theory and experiment weakens and becomes very slow, because experiments take a long time and are indecisive, and because theories become overly mathematically motivated and tend also to be the “slippery” kind that can evade verification or falsification. The sociological environment of scientists working in these Big Science fields is also detrimental to the workings of the usual scientific method, in that the influence of personalities can become stronger than the influence of more objective factors, and because the need for the acquisition of large public resources for research stifles critique and controversy. While no science is entirely free of these effects, science at the limits of perceptibility becomes dominated by them. It is urged that substantive assessments be made of the progress (or lack thereof) occuring in such fields of science. The teams performing such assessments should include scientists from neighbouring fields. Such assessments would try to call attention to and then try to correct the various aspects of the deterioration of the scientific methodology in these fields of science, thus improving the prospects for substantive progress in such fields.
Removal of TiO2 nanoparticles by porous media: Effect of filtration media and water chemistry

Abstract The use of nanoparticles in manufacturing as well as in commercial products continues to rise despite concerns over the environmental release and potentially negative ecological and health effects. Some aqueous waste streams carry a large fraction of released nanoparticles and thus should be targeted for treatment. Conventional porous media filtration has focused on sand as the bed material with discouraging results. This study investigated the effectiveness of three different bed materials, namely, sand, activated carbon, and diatomaceous earth, on the removal of nano-TiO2 from aqueous streams. Additionally, the impact of solution chemistry (a commercial dispersant and the two organic compounds lysozyme and glycine) on nanoparticle retention by the various bed materials was evaluated. Diatomaceous earth displayed great promise in nanoparticle capture, providing full retention of a 50 mg TiO2 L−1 stream for the 30 bed volumes tested as compared to zero and only 20% TiO2 capture for sand and activated carbon, respectively. Batch isotherms showed that diatomaceous earth, with specific loading capacities exceeding 25 mg TiO2 g medium - 1 , has a high affinity for nano-TiO2. This loading capacity is 20- and 1000-fold higher compared to activated carbon and sand, respectively. The solution contaminants investigated had varying effects on nano-TiO2 retention depending on the bed material, indicating the need for investigation of co-contaminants and their role on nanoparticle filtration. This study demonstrates the superiority of diatomaceous earth as a filtration material compared to conventional sand and indicates its suitability as a new material for the removal of nanoparticles in porous media filtration.
An empirical analysis of US state court citation practices of international human social rights treaties

This study analyses US state court behaviours in citing international human rights treaties to advance human social rights. Employing case analysis and logistic regression, we find that US state court citation practices to human rights treaties provide support for human social rights depending upon the type of human rights treaty cited; whether the case opinion is a published decision; and, whether the judicial opinion is a criminal or civil case. These judicial citation practices provide US state judges with the institutional capacity to advance universal human social rights. Theoretical and empirical implications are presented in the concluding section.
Using environmental bonds to regulate the risks of GM crops: problems and prospects

We examine the characteristics and limitations of the existing system of tort liability for addressing potential environmental damages from GM crops and consider whether environmental bonding could be used to address these risks. We find that in the case of GM crops, a bonding mechanism would complement some of the strengths of tort liability. Specifically, the bonding mechanism provides some protection against bankruptcy, and also shifts the burden of risk toward life science companies that develop the technology. These factors could encourage additional early research by life science firms. However, a bonding mechanism adds to the regulatory apparatus, and would likely increase administrative costs, over tort liability, for public and private parties. Nevertheless, an attractive possibility is that the cumulative outcomes of bonding, e.g., shifting the risk burden, providing a measure of bankruptcy protection, and introducing an additional regulatory component, would mitigate some of the political and social objections to the environmental release of GM crops.
Hierarchial shape representation and shape-preserving approximations

We present planar curve descriptors that allow a hierarchical representation of curves. The descriptors are based on wavelet and multiwavelet transforms and they decompose a curve into components of different scales.
Multiple listing for pediatric heart transplantation in the USA: Analysis of OPTN registry data from 1995 through 2009

Multiple listing is associated with shorter waitlist durations and increased likelihood of transplantation for renal candidates. Little is known about multiple listing in pediatric heart transplantation. We examined the prevalence and outcomes of multiple listing using OPTN data from 1995 through 2009. Characteristics and waitlist outcomes of propensity-score-matched single- and multiple-listed patients were compared. Multiple listing occurred in 23 of 6290 listings (0.4%). Median days between listings was 35 (0–1015) and median duration of multiple listings was 32 days (3–363). Among multiple-listed patients, there were trends toward less ECMO use (0% vs. 11%, p = 0.1) and more frequent requirement for a prospective cross-match (17% vs. 8%, p = 0.08). Multiple-listed patients more commonly had private insurance (78% vs. 56%; p = 0.03). Urgency status at listing was similar between groups (1/1A: 61% vs. 64%, 1B/2: 39 vs. 36%; p = 0.45) as were weight, age, diagnosis, ventilator/inotrope use, and median income (each p ≥ 0.17). There was a trend toward increased incidence of heart transplantation for multiple-listed patients at three, six, and 24 months (50%, 65%, 80%) vs. single-listed patients (40%, 54%, 64%; p = 0.11). Multiple listing for pediatric heart transplantation in the USA occurs infrequently and is more common in patients with private insurance.
Photon echo studies of photosynthetic light harvesting

The broad linewidths in absorption spectra of photosynthetic complexes obscure information related to their structure and function. Photon echo techniques represent a powerful class of time-resolved electronic spectroscopy that allow researchers to probe the interactions normally hidden under broad linewidths with sufficient time resolution to follow the fastest energy transfer events in light harvesting. Here, we outline the technical approach and applications of two types of photon echo experiments: the photon echo peak shift and two-dimensional (2D) Fourier transform photon echo spectroscopy. We review several extensions of these techniques to photosynthetic complexes. Photon echo peak shift spectroscopy can be used to determine the strength of coupling between a pigment and its surrounding environment including neighboring pigments and to quantify timescales of energy transfer. Two-dimensional spectroscopy yields a frequency-resolved map of absorption and emission processes, allowing coupling interactions and energy transfer pathways to be viewed directly. Furthermore, 2D spectroscopy reveals structural information such as the relative orientations of coupled transitions. Both classes of experiments can be used to probe the quantum mechanical nature of photosynthetic light-harvesting: peak shift experiments allow quantification of correlated energetic fluctuations between pigments, while 2D techniques measure quantum beating directly, both of which indicate the extent of quantum coherence over multiple pigment sites in the protein complex. The mechanistic and structural information obtained by these techniques reveals valuable insights into the design principles of photosynthetic light-harvesting complexes, and a multitude of variations on the methods outlined here.
Evidence against specificity of electrical stimulation of the nucleus locus coeruleus in activating the sympathetic nervous system in the rat

Summary Electrical stimulation of the central nucleus locus coeruleus (LC) was previously shown to increase activity of the peripheral sympathetic nervous system (SNS) as measured by increases in plasma levels of the norepinephrine (NE) metabolite 3-methoxy-4-hydroxyphenthyleneglycol (MHPG) in the rat 5 . Four experimental approaches were designed to test the specificity of the LC cell group in activating the SNS in the stimulation paradigm. Varying the stimulation current amplitude, varying the site of stimulating electrode placement, and electrolytic lesions of the LC yielded results consistent with the hypothesis that the site of SNS activation was within the anatomical region of the LC cell group. Neurochemical lesioning with intraventricular 6-hydroxydopamine, however, did not effectively block the plasma MHPG increase observed after stimulation of the LC region. The possibility that non-noradrenergic cells, fibers of passage, or terminals in the LC region of the midbrain may be responsible for SNS activation when the LC is electrically stimulated is discussed. These studies are pertinent to all studies of LC function which employ electrical stimulation of the LC nucleus, including investigations of the role of the LC in social behavior, intracranial self-stimulation, and blood pressure regulation.
Cognitive deficits in interleukin-10-deficient mice after peripheral injection of lipopolysaccharide.

Abstract Interleukin (IL)-10 is important for regulating inflammation but whether it protects against infection-related deficits in cognitive function is unknown. Therefore, the current study evaluated sickness behavior, hippocampal-dependent matching-to-place performance and several inflammatory cytokines and neurotrophins in wild-type (IL-10+/+) and IL-10-deficient (IL-10−/−) mice after i.p. injection of lipopolysaccharide (LPS). Additionally, morphology of dendrites of pyramidal neurons in the dorsal CA1 hippocampus was assessed. Treatment with LPS increased IL-1β, IL-6, and tumor necrosis factor α (TNFα) mRNA in all brain areas examined including the hippocampus, in both IL-10+/+ and IL-10−/− mice but the increase was largest in IL-10−/− mice. Plasma IL-1β, IL-6 and TNFα were also higher in IL-10−/− mice compared to IL-10+/+ mice after LPS. Consistent with increased inflammatory cytokines in IL-10−/− mice after LPS treatment, were a more lengthy sickness behavior syndrome and a more prominent reduction in hippocampal levels of nerve growth factor mRNA; brain-derived neurotrophic factor mRNA was reduced similarly in both genotypes after LPS. In a test of hippocampal-dependent learning and memory that required mice to integrate new information with previously learned information and switch strategies to master a task, IL-10−/− mice were found to be less efficient after LPS than were similarly treated wild-type mice. LPS did not affect morphology of dendrites of pyramidal neurons in the dorsal CA1 hippocampus in either genotype. Taken together the results are interpreted to suggest that during peripheral infection IL-10 inhibits sickness behavior and tribulations in hippocampal-dependent working memory via its propensity to mitigate inflammation. We conclude that IL-10 is critical for maintaining normal neuro-immune communication during infection.
Low-risk percutaneous coronary interventions without on-site cardiac surgery: Two years' observational experience and follow-up

Abstract Background We studied the safety and efficacy of performing low-risk elective and acute infarct percutaneous coronary interventions at a community hospital without cardiac surgical capability. Methods Immanuel St Joseph's Hospital is located 85 miles from St Mary's Hospital, which is the nearest center with on-site cardiac surgery. All components of the Mayo Clinic percutaneous coronary intervention program were replicated at Immanuel St Joseph's Hospital, including a telemedicine system to enable real-time consultation with interventional and cardiac surgical colleagues during procedures. Results From March 1999 to June 2001, 196 patients underwent elective percutaneous coronary intervention at Immanuel St Joseph's Hospital. Procedural success was achieved in 195 (99.5%) patients, with 1 (0.5%) inhospital death. At mean follow-up of 8.2 months, 2 (1.0%) additional patients died of noncardiac causes and 15 (7.7%) patients required target vessel revascularization. From March 2000 to June 2001, 89 patients underwent primary percutaneous coronary intervention for acute myocardial infarction. Procedural success was achieved in 83 (93.3%) patients, with 3 (3.4%) inhospital deaths. At 30-day follow up, no additional patients died, had recurrent myocardial infarction, or required target vessel revascularization. No patients required transfer to another facility for emergent cardiac surgery for a procedure-related complication. Conclusions Low-risk elective and acute infarct percutaneous coronary interventions can be performed with safety and efficacy at a community hospital without cardiac surgical capability by following rigorous standards. (Am Heart J 2003;145:278-84.)
Safety and Efficacy of Febuxostat Treatment in Subjects with Gout and Severe Allopurinol Adverse Reactions

Objective. Allopurinol, a purine base analog inhibitor of xanthine oxidase (XO) activity, remains the standard for pharmacologic urate-lowering management of gout. Allopurinol is efficacious and safe in most patients, but intolerance is estimated to occur in up to 10% of treated patients. Severe or life-threatening allopurinol adverse reactions (AE) occur much less frequently, and include severe cutaneous allopurinol reactions, vasculitis, and/or a multisystem allopurinol hypersensitivity syndrome. During clinical development of febuxostat (FEB), a recently approved non-purine analog inhibitor of XO, subjects with severe allopurinol intolerance were excluded from randomized double-blind FEB/allopurinol comparative trials. Methods. In this retrospective study, safety and urate-lowering efficacy of FEB was assessed in 13 successively encountered gout patients with prior documented severe allopurinol reactions. Results. FEB was well tolerated in 12 of 13 patients, each of whom remains on treatment. One patient previously hospitalized with documented exfoliative erythroderma during allopurinol treatment, developed biopsy-confirmed cutaneous leukocytoclastic vasculitis. None of the other 12 patients treated with FEB showed rash, worsening hepatic function, blood cytopenia or eosinophilia. Conclusion. In 12 of our 13 gout patients with previously documented severe allopurinol AE, FEB treatment was safe. However, the development of a hypersensitivity type cutaneous vasculitis (likely but not definitively FEB-related) early in treatment mandates caution, careful dose escalation, and close monitoring when FEB urate-lowering therapy of allopurinol-intolerant patients is considered.
Secondary orgasmic dysfunction. I. Analysis and strategies for treatment.

Following treatment of six cases of primary orgasmic dysfunction and six cases of secondary orgasmic dysfunction, an analysis of assessment and outcome data indicated that (1) clients with secondary orgasmic dysfunction and those with primary orgasmic dysfunction did not differ significantly in most aspects of sexual behavior before treatment; (2) before treatment, secondary orgasmic dysfunction tended to be associated with a disturbed marital relationship, while primary orgasmic dysfunction did not; (3) following a behavioral treatment program focused on anxiety reduction and sexual skill training, orgasm in coitus was attained by clients with primary orgasmic dysfunction but not by clients with secondary orgasmic dysfunction. Based on these findings, suggestions for effective treatment of secondary orgasmic dysfunction are made.
Equal time: Origins of section 18 of the radio act of 1927

(1980). Equal time: Origins of section 18 of the radio act of 1927. Journal of Broadcasting: Vol. 24, No. 3, pp. 367-380.
Resource Dependence, Economic Performance, and Political Stability:

In many resource-dependent states, elites may face an important trade-off between the economic benefits of diversification and the possibility for future political competition that diversification ...
Iron, copper, and iron regulatory protein 2 in Alzheimer’s disease and related dementias

Accumulating evidence implicates a role for altered iron and copper metabolism in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, imbalances in the levels of the various forms of iron at different stages of AD have not been examined. In this pilot study we extracted and measured the levels of loosely bound, non-heme and total iron and copper in the frontal cortex and hippocampus of patients with mild-moderate AD (n=3), severe AD (n=8) and dementia with Lewy bodies (DLB, n=6), using graphite furnace atomic absorption spectrometry (GFAAS). Additionally, the expression of iron regulatory protein 2 (IRP2) was examined in relation to the pathological hallmarks of AD and DLB, amyloid plaques, neurofibrillary tangles (NFT), and Lewy bodies, by immunohistochemistry. We found significantly decreased loosely bound iron in the hippocampal white matter of mild-moderate and severe AD patients and a trend towards increased non-heme iron in the hippocampal gray matter of severe AD patients. Furthermore, decreased levels of total copper were seen in severe AD and DLB frontal cortex compared to controls, suggesting an imbalance in brain metal levels in both AD and DLB. The decrease in loosely bound iron in mild-moderate AD patients may be associated with myelin breakdown seen in the beginning stages of AD and implicates that iron dysregulation is an early event in AD pathogenesis.
Why does Venus lack a magnetic field

Venus and Earth have similar radii and estimated bulk compositions, and both have an iron core that is at least partially liquid. However, despite these similarities, Venus lacks an appreciable dipolar magnetic field. Here I examine the hypothesis that this absence is due to Venus9s also lacking plate tectonics for the past 0.5 b.y. The generation of a global magnetic field requires core convection, which in turn requires extraction of heat from the core into the overlying mantle. Plate tectonics cools Earth9s mantle; on the basis of elastic thickness estimates and convection models, it is argued here that the mantle temperature on Venus is currently increasing. This heating will reduce the heat flux out of the core to zero over ∼1 b.y., halting core convection and magnetic field generation. If plate tectonics was operating on Venus prior to ca. 0.5 Ga, a magnetic field may also have existed. On Earth, the geodynamo may be a consequence of plate tectonics; this connection between near-surface processes and core magnetism may also be relevant to the generation of magnetic fields on Mars, Mercury, and Ganymede.
The Civil Service Reform Act of 1978: A 30-Year Retrospective and a Look Ahead: Symposium Introduction

President Jimmy Carter initiated the most sweeping reforms of the U.S. federal civil service in 95 years when he signed the Civil Service Reform Act (CSRA) on October 13, 1978. This introduction reviews the substantive reforms whose implementation began with creation of the U.S. Office of Personnel Management (OPM), on January 1, 1979. CSRA's provisions were wide-ranging. They included reorganization of the agencies tasked with civil service management and regulation, establishment of a Senior Executive Service, creation of performance appraisal and merit pay programs, and clarification and simplification of appeal procedures for personnel actions. The introduction concludes with summaries of the five articles that appear in the symposium and their significance in the context of CSRA and developments of the past 30 years.
Performability of an algorithm for connection admission control

Connection admission control (CAC) in broadband, ATM-based telecommunication networks is a problem of recognized importance. Its solution calls for real-time algorithms that can accurately decide whether a connection request may be granted without compromising specified quality of service (QoS) requirements. We consider an algorithm for this purpose that accommodates variable bit rate (VBR) connections and is based on effective bandwidth computations. Arriving VBR traffic streams are assumed to be leaky-bucket regulated and are represented by worst-case, periodic, on-off, fluid sources that are randomly phased. Moreover, certain traffic classes may benefit from statistical multiplexing (S-VBR), while others may not (NS-VBR). We then evaluate the ability of such a CAC algorithm to perform in the presence of fluctuating channel capacity, where the performability variable Y/sub T/ is the fraction of some specified busy period T during which the quality of service requirement is violated. A general base model that supports Y/sub T/ is then formulated and instances of the resulting performability model are constructed and solved using UltraSAN. In particular, the evaluation experiments reveal some interesting differences in how QoS degrades with respect to the control of S-VBR vs. NS-VBR traffic.
Small firms embracing technology and tourism development: evidence from two nations in Central America

Abstract This research note reports the findings of a study that explored the types of technology used within hospitality-related small-to-medium enterprises (SMEs) in Costa Rica and Nicaragua. The study investigated the perceptions of value and the levels of awareness of entrepreneurs and managers regarding various technologies commonly used in similar organizations in the United States. The results suggest that there are minimal technology applications in back-office and front-office processing activities in SMEs in Costa Rica and Nicaragua. The evidence further suggests that the levels of awareness of entrepreneurs and managers concerning these applications are practically non-existent.
Campaign Management of the Fourth Generation

Campaign management enables companies to address customers in the best possible way with suitable campaigns according to given marketing objectives. Currently three approaches of campaign management have evolved in practice, differing in the way of selecting customers for competing campaigns. These three generations of campaign management still show clear improvement potential, so a new beginning is introduced in this contribution. This paper shows a new approach for campaign management based on improvement potential of the preceding generations. The major aspect of our approach is a simultaneous selection of customers and campaigns. The expected utility for all customers and campaigns is maximized taking into account the whole planning horizon and all resource limitations. For the implementation of this new approach optimisation models and specific heuristics are introduced. They can be used separately or in combination depending on the complexity of the problem. It is shown that this simultaneous planning of the fourth generation is superior to present approaches.
Potentiometric Studies of the Interaction of Bovine Serum Albumin and Poly(dimethyldiallylammonium chloride)

Potentiometric and turbidimetric titrations were used to study the interaction between bovine serum albumin (BSA) and poly(diallyldimethylammonium chloride) (PDADMAC). Binding between BSA and PDADMAC, which takes place only above some critical initial pH (pHc), leads to a decrease in the pH of solution, indicating that the interactions enhance the dissociation constant Ka of the ionizable groups on BSA and result in an increase of the number of net negative charge on the protein. The pH difference caused by the interaction, ΔpH, decreases with added salt, which indicates that the effect of the interaction on the pKa of BSA increases with a decrease of ionic strength. Protein binding to PDADMAC imposes a stronger influence on the Ka of the carboxylic groups than on the Ka of the imidazolium and ammonium groups. The fraction of BSA bound (fb = [BSA]b/Cpr) increases with polymer concentration Cp until all BSA are bound. The rate at which fb increases with added polymer at low Cp depends on the initial pH (pH...
A Tool for Range Sensing and Environment Discovery for the Blind

This paper describes the development of a hand-held environment discovery tool for the blind. The final device will be composed of a laser-based range sensor and of an onboard processor. As the user swings the hand-held system around, he/she will receive local range information by means of a tactile interface. In addition, the time profile of the range will be analyzed by the onboard processor to detect environmental features that are critical for mobility, such as curbs, steps and drop-offs. In our current implementation, range is collected by a short-baseline triangulation system formed by a point laser and a miniaturized camera, producing readings at frame rate. An Extended Kalman filter is used to track the range data and detect environmental features of interest.
Transcriptional control of cardiac fibroblast plasticity

Cardiac fibroblasts help maintain the normal architecture of the healthy heart and are responsible for scar formation and the healing response to pathological insults. Various genetic, biomechanical, or humoral factors stimulate fibroblasts to become contractile smooth muscle-like cells called myofibroblasts that secrete large amounts of extracellular matrix. Unfortunately, unchecked myofibroblast activation in heart disease leads to pathological fibrosis, which is a major risk factor for the development of cardiac arrhythmias and heart failure. A better understanding of the molecular mechanisms that control fibroblast plasticity and myofibroblast activation is essential to develop novel strategies to specifically target pathological cardiac fibrosis without disrupting the adaptive healing response. This review highlights the major transcriptional mediators of fibroblast origin and function in development and disease. The contribution of the fetal epicardial gene program will be discussed in the context of fibroblast origin in development and following injury, primarily focusing on Tcf21 and C/EBP. We will also highlight the major transcriptional regulatory axes that control fibroblast plasticity in the adult heart, including transforming growth factor β (TGFβ)/Smad signaling, the Rho/myocardin-related transcription factor (MRTF)/serum response factor (SRF) axis, and Calcineurin/transient receptor potential channel (TRP)/nuclear factor of activated T-Cell (NFAT) signaling. Finally, we will discuss recent strategies to divert the fibroblast transcriptional program in an effort to promote cardiomyocyte regeneration. This article is a part of a Special Issue entitled "Fibrosis and Myocardial Remodeling".
Markets and Dignity: The Essential Link (With an Application to Health Care)

As most economists will tell you, markets, under ideal conditions of perfect competition, maximize the allocative and productive efficiency of the economy. Those ideal conditions are familiar to introductory economics students, and include large numbers of buyers and sellers, perfect information about the prices and terms sellers offer, homogeneous products, and no barriers to entry (or exit). If any of these conditions do not hold, then efficiency is compromised, and government intervention (such as price regulation and antitrust measures) is often recommended in order to bring the outcomes of the imperfect competition closer to the ideal of perfect competition.
The Invention of the Passport: Toward the “Crustacean Type of Nation”: The Proliferation of Identification Documents From the Late Nineteenth Century to the First World War

Despite the generally liberal attitude toward freedom of movement that carried the day in Europe during the late nineteenth century, governments became increasingly oriented to making distinctions between their own citizens/subjects and others, a distinction that could be made only on the basis of documents. At first this concern was typically directed at specific groups of undesirable outsiders, but it gradually spread and became a general trait of ever more socially integrated “national” societies. Thus despite the fact that the period from the late nineteenth century until the First World War has been frequently viewed as an unexampled era of free movement in the modern age, the period also saw the spread of various kinds of identification documents that sharpened the line between national and alien and thereby contributed to what has aptly been called the “naturalization of nativism.” In the United States, for example, which had been more or less open to free movement for the white population, the development of passports and identification documents grew dramatically toward the end of the nineteenth century. As elsewhere, the ultimate result would be to promote the institutionalization of documentary controls designed to regulate movement and to distinguish clearly between nationals and others. As the preferred destination of enormous numbers of migrants from around the world during this period, the posture of the United States played a crucial role in the shift toward more rigorous and bureaucratic mechanisms for regulating movement.
Process and Outcome Measures of Medical Care Quality: Causal Implications

In the era of scientific medicine, the importance of the causal relationship between the process of medical intervention and the outcome of medical care can never be overemphasized. Ideally speaking, the diagnostic procedures should guide the treatment intervention and the outcome of care should be the product of the antecedent treatment intervention. Donabedian emphasizes causal validity which refers to the capacity of specified process to produce specified outcomes under specified conditions (Donabedian 1980). This implies that the causal validity requires a causal direction and relationship between diagnosis, treatment and outcome.
Focal mechanism analyses for eastern Tennessee earthquakes (1981-1983)

To investigate the neotectonic processes in the Southern Appalachians, 10 single-event focal mechanisms and 6 composite focal mechanisms were determined from 37 events that occurred in eastern Tennessee between September 1981 and July 1983. Both P -wave polarities and ( SV/P ) z amplitude ratios are input to a computer program that systematically searches the focal sphere for solutions acceptable within preset error limits. Hypocenter locations, azimuth, and departure angles are taken from locations obtained by the Tennessee Earthquake Information Center with a four-layer velocity model. A gradient velocity model, developed to improve focal depth estimates and to provide continuously varying (rather than discrete) departure angles, is used to relocate the seismic events for which single-event focal mechanisms and composite focal mechanisms solutions are obtained. The two different velocity models each produced focal mechanisms with similar nodal plane and P -axis orientations, indicating stable and reliable mechanism solutions; the differences between average strike, dip, and rake angles of the two data sets range from 2° to 11°. Both single-event focal mechanisms and composite focal mechanisms solutions exhibit predominantly strike-slip motion along nearly vertical northerly (right-lateral) or easterly (left-lateral) oriented nodal planes. Standard deviations about the average strike, dip, and rake angles are generally less than 20°. P -axis trends average about N50°E, with a nearly horizontal average plunge, and both trend and plunge estimates have standard deviations of 25° or less.
Prognostic impact of clinical tumor size on overall survival for subclassifying stages I and II vaginal cancer: A SEER analysis.

Abstract Purpose This study accessed the Surveillance, Epidemiology and End Results (SEER) database to determine if tumor size is an independent predictor of overall survival (OS) for patients with stages I and II vaginal cancer (VC). Materials and methods We identified in the SEER database, patients with available tumor size having stage I or II squamous cell histology from January 2004 through December 2012 with minimum follow-up of six months. Univariate analyses (UA) and multivariable analyses (MVA) evaluated the effect of several prognostic factors, including tumor size, regarding OS. Results 529 SEER patients were found with recorded tumor sizes, of which 293 (55.4%) were stage I and 236 (44.6%) stage II. UA found the following significant prognostic factors of worse OS: tumor size >2cm (HR=1.80, p=0.02) and older age at diagnosis (p 2cm (HR=2.13, p=0.04) and older age at diagnosis (p 2cm were 79.2% vs. 66.1% in stage I (p=0.0187) and 80.9% vs. 51.2% in stage II (p=0.0369). MVA confirmed about double risk of death for patients with tumor size >2cm (HRs: 1.88 in stage I and 2.06 in stage II). Conclusions Tumor size seems to predict OS outcome in patients with stages I/II VC. Further confirmatory investigations are recommended to firmly establish its incorporation into currently accepted staging criteria for these patients.
Development of haptic CAM system for 5-axis machining

This paper deals with the method of tool path generation on CAM system for 5-axis machining using a concept of haptic virtual reality. 5-axis machining has been used for complicated shapes such as turbine blades, molds and dies due to the efficient and accurate machining. However, present CAM systems for 5-axis machining lacks in generality and functions for the tool path generation. Especially, the interference between a tool and surrounding objects in computing the tool path is still a big problem. The method of tool path generation devised in this study uses operator's assistance. In this CAM system, first of all, the operator inputs information of suitable tool posture for all polygons constructing object shape. After that, the CAM system can compute a tool path without repetitive algorithms because tool posture avoids interference have been already input the system. Using a haptic device and a newly developed rapid interference detection algorithm, it is possible to touch the surface of the object, and easily input information of suitable tool posture into the CAM system. From the experimental results, the validity of the method is confirmed.
Enhancing Superconducting Parameters by Array of External Magnetic Dots

Enhancing the pinning force in high-Tc superconductors can be achieved by externally introduced periodic magnetic dots. We use a novel nano-technique to deposit periodic sub-micon Ni dots on YBa2Cu3O7 thin films. The current versus voltage characteristics of an YBa2Cu3O7 thin film strip with uniform Ni dots are measured at various temperatures and magnetic fields. They are compared with the current versus voltage characteristics of a bare YBa2Cu3O7 thin film strip without magnetic dots. It is found the critical current value of the strip with Ni dots reduces with a much slower pace as the magnetic field strength increases in comparison with the value of the bare sample.
EglN2 positively regulates mitochondrial function in breast cancer

ABSTRACTOxygen sensing is associated with mitochondrial function. EglN2, which contributes to breast tumorigenesis as a prolyl hydroxylase, has recently been identified as a transcription co-activator through interaction with NRF1 and PGC1α to regulate mitochondrial function under conditions of normoxia and hypoxia. FDXR is the important downstream target gene that mediates this regulation.
Resolution of a Mobile Right Atrial Thrombus Complicating Acute Pulmonary Embolism With Low-Dose Tissue Plasminogen Activator in a Patient With Recent Craniotomy

Right heart thrombus in transit (RHTT) is a rare, severe form of venous thromboembolism that carries a high mortality rate. The optimal treatment for RHTT has not been well established. Thrombolysis is a therapeutic modality for RHTT but carries the risk of bleeding complications including intracranial hemorrhage. Low-dose thrombolysis has been shown to be effective in treating submassive pulmonary emboli without an increased risk in bleeding complications, but it has not been studied in patients with RHTT. Here, we discuss the case of a 74-year-old male with lung cancer and recent craniotomy with metastasectomy 30 days prior to admission presenting with RHTT and bilateral pulmonary emboli (PE). He was treated successfully with low-dose thrombolysis, despite his relative contraindication to thrombolytics. To our knowledge, this is the first reported case of low-dose alteplase (tissue plasminogen activator [tPA]) used to treat an in-transit PE in the setting of recent craniotomy with metastasectomy.
Managing smoke inhalation injuries.

PreviewTelevised public service announcements warn us that smoke kills more people than fire. Immediate intervention and ongoing evaluation are necessary to prevent serious illness or death in patients with smoke inhalation injuries. Drs Desai and Herndon and Ms Rutan provide guidelines for diagnosis and management of these patients.
QOL and outcomes research in prostate cancer patients with low socioeconomic status.

The VA Cancer of the Prostate Outcomes Study (VA CaPOS) is collecting quality-of-life (QOL) information from prostate cancer patients, spouses, and physicians at six VA medical centers. Currently, 601 men with prostate
N-nitrosodibenzylamine in boneless hams processed in elastic rubber nettings

Boneless hams processed in elastic rubber nettings contain high levels of nitrosamines in the outermost layer. The precursors of the nitrosamines are zinc dibutyl- or dibenzyldithlocarbamate used as a vulcanizing agent in the formulation of the rubber. The outermost layer from 59 commercial hams was analyzed for 11 volatile nitrosamines including N-nitrosodibutylamine (NDBA) and N-nitrosodibenzylamine (NDBzA). The principal nitrosamine, NDBzA, was detected in 32 (54%) ham samples at the 10-100 ppb range; it exceeded 100 ppb in 18 (30%) samples, with the highest at 512.2 ppb. No nitrosamine was detected in 7 of 59 ham samples. To determine the cause of the high NDBzA values, various types of unused nettings (from different manufacturers) accompanying the samples were analyzed for nitrosamines. No correlation was found between the NDBzA content of the hams and the nettings. The results suggest that the problem of nitrosamine formation in these products has not yet been resolved.
Multislice CEST MRI improves the spatial assessment of tumor pH.

Purpose Multislice maps of extracellular pH (pHe) are needed to interrogate the heterogeneities of tumors and normal organs. To address this need, we have developed a multislice chemical exchange saturation transfer (CEST) MRI acquisition method with a CEST spectrum-fitting method that measures in vivo pHe over a range of 6.3 to 7.4. Methods The phase offset multiplanar (POMP) method was adapted for CEST fast imaging with steady-state free precession (FISP) MRI to acquire multiple image slices with a single CEST saturation pulse. The Bloch-McConnell equations were modified to include pH based on a calibration of pH and chemical exchange rate for the contrast agent iopamidol. These equations were used to estimate the pixel-wise pHe values throughout the multislice acidoCEST MR images of the tumor, kidney, bladder, and other tissues of a MDA-MB-231 tumor model. Results Multislice acidoCEST MRI successfully mapped a gradient of pHe from 6.73 to 6.81 units from the tumor core to rim, and also mapped a gradient of pHe 6.56 to 6.97 across the mouse kidney. The bladder was found to be pHe 6.3. Conclusion AcidoCEST MRI with POMP acquisition and Bloch-McConnel analysis can map pHe in multiple imaging slices through the tumor, kidney, and bladder. This multislice evaluation facilitates assessments of spatial heterogeneity of tissue pHe. Magn Reson Med 78:97–106, 2017. © 2016 International Society for Magnetic Resonance in Medicine
What Philosophers Know: The rise and fall of counterexamples: Gettier, Goldman, and Lewis

For all their analytic acuity, Quine and Kripke were dealing with a sweeping range of issues that, we might think, make it hard to stay on the narrow path of rigorous argument and call for flights of philosophical imagination or depths of intuitive penetration. Perhaps we should look at a narrower issue that has allowed analytic philosophers to focus their argumentative resources on specific, well-defined points. Here an obvious choice is the search for a definition of knowledge that has occupied epistemologists since the early 1960s. The choice seems particularly appropriate, since epistemology has been driven by what may seem to be the purely argumentative power of counterexamples, which, we have seen, constituted Kripke's most effective use of argument in Naming and Necessity . We begin with Gettier's two famous counterexamples and the debate they spawned over the definition of knowledge, then move to Alvin Goldman's use of counterexamples in his seminal paper, “What Is Justified Belief?,” and conclude with the more complex forms of argumentation deployed in David Lewis' recent but already classic “Elusive Knowledge.” TWO COUNTEREXAMPLES THAT SHOOK THE EPISTEMOLOGICAL WORLD Plato, in the Theatetus and the Meno , suggested defining knowledge as justified true belief . Although he himself does not unequivocally endorse the idea and although for centuries the topic was little discussed outside commentaries on Plato, the definition seems intuitively right and earlier analytic philosophers such as Ayer and Chisholm had put forward definitions along its lines.
Comparison of Composite Measure Methodologies for Rewarding Quality of Care: An Analysis From the American Heart Association's Get With The Guidelines Program

Background Composite indices of health care performance are an aggregation of underlying individual performance measures and are increasingly being used to rank hospitals. We sought to conduct an observational analysis to determine the influence of the opportunity-based and all-or-none composite performance measures on hospital rankings. Methods and Results We examined 194 245 patients hospitalized with acute myocardial infarction between July 2006 and June 2009 from 334 hospitals participating in the Get With The Guidelines–Coronary Artery Disease (GWTG–CAD) quality improvement program. We analyzed hospital opportunity-based and all-or-none composite scores and 30-day risk-standardized all-cause mortality and readmission rates. We found that the median calculated opportunity-based score for these hospitals was 95.5 (interquartile range, 90.4, 98.0). The median all-or-none score was 88.9 (interquartile range, 79.7, 94.4). The 2 scoring methods were significantly correlated with one another ( r =0.98, P r =0.93, P r =−0.25, P r =−0.24, P Conclusions The opportunity-based and all-or-none coronary artery disease composite indices are highly correlated and yield similar ranking of the top and bottom quintiles of hospitals. The two methods provide similarly modest correlations with 30-day mortality, but not readmission.