cssi/SciSciGPT-SciSciNet huggingface dataset:
Distinct Influences of Carboxyl Terminal Segment Structure on Function in the Two Isoforms of Prostaglandin H Synthase

The cyclooxygenase activity of the two prostaglandin H synthase (PGHS) isoforms, PGHS-1 and -2, is a major control element in prostanoid biosynthesis. The two PGHS isoforms have 60% amino acid identity, with prominent differences near the C-terminus, where PGHS-2 has an additional 18-residue insert. Some mutations of the C-terminal residue in PGHS-1 and -2 have been found to disrupt catalytic activity and/or intracellular targeting of the proteins, but the relationship between C-terminal structure and function in the two isoforms has been poorly defined. Crystallographic data indicate the PGHS-1 and -2 C-termini are positioned to interact with the endoplasmic reticulum (ER) membrane, although the C-terminal segment structure was not resolved for either isoform. We constructed a series of C-terminal substitution, deletion, and insertion mutants of human PGHS-1 and -2 and evaluated the effects on cyclooxygenase activity and intracellular targeting in transfected COS-1 cells expressing the recombinant proteins. PGHS-1 cyclooxygenase activity was strongly disrupted by C-terminal substitutions and deletions, but not by elongation of the C-terminal segment, even when the ultimate residue was altered. Similar alterations to PGHS-2 had markedly less effect on cyclooxygenase activity. The results indicate that the functioning of the longer C-terminal segment in PGHS-2 is distinctly more tolerant of structural change than the shorter PGHS-1 C-terminal segment. C-Terminal substitutions or deletions did not change the subcellular localization of either isoform, even at short times after transfection, indicating that neither C-terminal segment contains indispensable intracellular targeting signals.
Abstract LB-106: A novel TCL1-Tg:p53−/− mouse model of human CLL

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the United States and Europe. CLL patients with loss of p53 due to chromosome 17p deletion often exhibit more malignant disease phenotype, are refractory to standard treatment, and have poor clinical outcomes. Although there are several mouse models that resemble the chronic disease processes of CLL, no animal model has been reported that mimic the aggressive disease phenotype of CLL with loss of p53. To facilitate the investigation of the biology of aggressive CLL with loss of p53 and the underlying mechanisms, we generated a mouse model with Eu-TCL1-Tg:p53−/− genotype by crossing the Eu-TCL1-Tg mice with p53 knockout mice. The Eu-TCL1-Tg:p53−/- mice developed CLL disease at 3-4 months, significantly earlier than the parental Eu-TCL1-Tg mice that developed CLL disease at 8-12 months. Flow cytometry analysis showed that the IgM+/CD5+ cell population appeared in the peritoneal cavity, bone marrow, and the spleens of Eu-TCL1-Tg:p53−/- mice significantly earlier than that of the parental Eu-TCL1-Tg mice. Massive infiltration and accumulation of leukemia cells were found in the spleen, liver, and peritoneal cavity. In vitro study showed that the leukemia cells isolated from the Eu-TCL1-Tg:p53−/- mice were more resistant to fludarabine treatment than the leukemia cells isolated from spleens of TCL1-Tg mice. Interestingly, TUNEL assay revealed that there was higher apoptotic cell death found in the TCL1-Tg spleen tissue compared to the spleens of the Eu-TCL1-Tg:p53−/- mice, suggesting that the loss of p53 compromises the apoptotic process in vivo, and this might in part explain the drug resistant phenotype of CLL cells with 17p deletion. Further molecular analysis showed that the expression of MCL-1, a key survival molecule for CLL, was significantly increased at the mRNA and protein levels in the leukemia cells isolated from Eu-TCL1-Tg:p53−/- mice, which seemed to be associated with the abnormal expression of certain microRNAs including miR15a and miR-16. Overall, the Eu-TCL1-Tg:p53−/- mice display a disease phenotypes that resemble human CLL with 17p deletion, and represent a useful animal model for mechanistic study as well as evaluation of in vivo therapeutic efficacy of anti-CLL agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-106. doi:1538-7445.AM2012-LB-106
Molecular Structure Information From X-Ray Photoelectron Spectroscopy

A discussion is given of the types of molecular structure information available from X-ray photoelectron spectroscopy. A complete set of atomic charges in a molecule can be deduced from core-level binding energy shifts. Atomic-orbital composition of molecular orbitals is derived from relative intensities. Correlation peaks yield information about electron correlation. Relaxation energies are related to basicity for certain functional groups.
Negative Symptoms in Schizophrenia: Depressive or Deficit Syndrome

The development of a comprehensive understanding of the etiology, treatment, and prevention of psychiatric disorders has been slow and hampered by uncertainties about the existence of etiologically distinct illnesses within the larger domain of psychiatric illness. Early attempts at subtyping psychiatric disorders relied heavily on clinical observation and the abilities of clinicians to recognize patterns of recurring symptoms and outcome within their clinics and practices. From this approach emerged the seminal descriptions of Kraepelin and Bleuler, and the foundation of current clinical nosology. Key to the early systems (and to our current DSM III-R system) (1) was the distinction between affective illnesses conceptualized as disorders of mood disturbance (such as manic-depressive psychosis), and schizophrenic illnesses conceptualized as being associated with a fundamental defect in the emotions or volition [according to Kraepelin (2)] or capacity for appropriate affective response or goal-directed activity [(according to Bleuler (3)]. Schizophrenic illnesses were seen as more permanent in nature, with a progressively deteriorating course, and often characterized by disordered thinking, delusional beliefs, or impairments in perceptual processes (hallucinations).
Idempotente (automorphe) Zahlen in q-Stellenwertsystemen

Idempotente Zahlen bezeichnen hier Zahlen, die mit den letzten Ziffern all ihrer Potenzen ubereinstimmen, was offenbar vom zugrunde liegenden Stellenwertsystem abhangt. Der Artikel untersucht den mathematischen Mikrokosmos dieser Zahlen: ihre Eigenschaften und Beziehungen untereinander sowie zu verschiedenen Stellenwerten. All dies geschieht auf elementarem Niveau, um zu belegen, dass die Beschaftigung mit diesen speziellen Zahlen auch fur interessierte Schuler lohnend sein kann.
SILCA: Fast-Yet-Accurate Time-Domain Simulation of VLSI Circuits with Strong Parasitic Coupling Effects

We propose a new circuit analysis method, namely Semi-Implicit Linear-Centric Analysis (SILCA), for efficient SPICE-accurate transient simulation of deep-submicron VLSI circuits with strong parasitic coupling effects introduced by interconnect lines, common substrate, power/ground networks, etc. SILCA is based on two linear-centric techniques. First, a new semi-implicit iterative numerical integration scheme is developed, which applies dynamic time step control accounting for stiff systems and meanwhile keeps constant equivalent conductance for capacitor/inductor companion models. Its convergence and stability properties are characterized. Second, to achieve constant linearized conductance for nonlinear devices during nonlinear iteration process, a successive variable chord method is introduced as an alternative of the Newton-Raphson method and the rank-one update technique is implemented for fast LU factorization. With these techniques, SILCA reduces the number and cost of required LU factorizations dramatically. Experimental results on substrate and power/ground networks have demonstrated that SILCA yields SPICE-like accuracy with an over 80X reduction in LU factorization cost, and an about 20X overall CPU time speedup over SPICE3 for circuits with tens of thousands elements, and the efficiency increases further with the size of a circuit.
Effect of Porosity on Ductility Variation in Investment Cast 17-4PH

The stainless steel alloy 17-4PH contains a martensitic microstructure and second phase delta ({delta}) ferrite. Strengthening of 17-4PH is attributed to Cu-rich precipitates produced during age hardening treatments at 900-1150 F (H900-H1150). For wrought 17-4PH, the effects of heat treatment and microstructure on mechanical properties are well-documented [for example, Ref. 1]. Fewer studies are available on cast 17-4PH, although it has been a popular casting alloy for high strength applications where moderate corrosion resistance is needed. Microstructural features and defects particular to castings may have adverse effects on properties, especially when the alloy is heat treated to high strength. The objective of this work was to outline the effects of microstructural features specific to castings, such as shrinkage/solidification porosity, on the mechanical behavior of investment cast 17-4PH. Besides heat treatment effects, the results of metallography and SEM studies showed that the largest effect on mechanical properties is from shrinkage/solidification porosity. Figure 1a shows stress-strain curves obtained from samples machined from castings in the H925 condition. The strength levels were fairly similar but the ductility varied significantly. Figure 1b shows an example of porosity on a fracture surface from a room-temperature, quasi-static tensile test. The rounded features represent the surfaces ofmore » dendrites which did not fuse or only partially fused together during solidification. Some evidence of local areas of fracture is found on some dendrite surfaces. The shrinkage pores are due to inadequate backfilling of liquid metal and simultaneous solidification shrinkage during casting. A summary of percent elongation results is displayed in Figure 2a. It was found that higher amounts of porosity generally result in lower ductility. Note that the porosity content was measured on the fracture surfaces. The results are qualitatively similar to those found by Gokhale et al. and Surappa et al. in cast A356 Al and by Gokhale et al. for a cast Mg alloys. The quantitative fractography and metallography work by Gokhale et al. illustrated the strong preference for fracture in regions of porosity in cast material. That is, the fracture process is not correlated to the average microstructure in the material but is related to the extremes in microstructure (local regions of high void content). In the present study, image analysis on random cross-sections of several heats indicated an overall porosity content of 0.03%. In contrast, the area % porosity was as high as 16% when measured on fracture surfaces of tensile specimens using stereology techniques. The results confirm that the fracture properties of cast 17-4PH cannot be predicted based on the overall 'average' porosity content in the castings.« less
Response of a Molecule to Adding or Removing an Electron

Abstract The ab initio calculation of molecular electron affinities (EA) and ionization potentials (IP) is a difficult task because the energy of interest is a very small fraction of the total electronic energy of the parent species. For example, EAs typically lie in the 0.01–10 eV range, but the total electronic energy of even a small molecule, radical, or ion is usually several orders of magnitude larger. Moreover, the EA or IP is an intensive quantity but the total energy is an extensive quantity, so the difficulty in evaluating EAs and IPs to within a fixed specified ( e.g. , ± 0.1 eV ) accuracy becomes more and more difficult as the system's size and number of electrons grows. The situation becomes especially problematic when studying extended systems such as solids, polymers, or surfaces for which the EA or IP is an infinitesimal fraction of the total energy. Equations of motion (EOM) methods such as the author developed in the 1970s in collaboration with P. Jorgensen and others offer a route to calculating the intensive EAs and IPs directly as eigenvalues of a set of working equations. A history of the development of EOM theories as applied to EAs and IPs, their numerous practical implementations, and their relations to Greens function or propagator theories are given in this contribution. EOM methods based upon Moller–Plesset, multiconfiguration self-consistent field, and coupled-cluster reference wave functions are included in the discussion as is the application of EOM methods to metastable states of anions.
Time reversal with MISO for ultra-wideband communications: experimental results

Time reversal (TR) communications marks a paradigm shift in UWB communications. The system complexity can be shifted from the receiver to the transmitter, which is ideal to UWB sensors. UWB multiple input single output (MISO) is enabled by the use of the TR scheme. Two basic problems are investigated experimentally using short UWB radio pulses (nanosecond duration). Temporal focusing and SNR increase with the number of antennas are verified. Also, reciprocity of realistic channels, the foundation of TR, is demonstrated for the first time in electromagnetics.
Two-dimensional electron gas charged-coupled devices (2DEG-CCD's)

The two-dimensional electron gas charged-coupled device (2DEG-CCD) structure for III-V and other heterojunction materials is reviewed. Device design considerations for gate, insulator, and channel material parameters are presented. Optimization of 2DEG-CCD performance parameters such as well capacity, dark current, and transfer efficiency is discussed. Experimental results on AlGaAs-GaAs uniform-doped and planar-doped devices are reviewed. AlGaAs-GaAs 2DEG-CCDs have been shown to operate with 0.9997 charge transfer efficiency, at frequencies ranging from 130 kHz to 1 GHz. A review of fundamental principles of operation and a discussion of structural and material configurations are presented. >
Role of the Clinical Mycobacteriology Laboratory in Diagnosis and Management of Tuberculosis in Low-Prevalence Settings

Tuberculosis (TB) remains a global epidemic, despite a significant decline in reported cases in the United States between 2008 and 2009. While the exact nature of this decline is unclear, one thing remains certain: TB, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB, is no longer restricted to developing regions of the globe. It is of vital importance that both public and private mycobacteriology laboratories maintain the ability to detect and identify Mycobacterium tuberculosis from patient specimens, as well as correctly determine the presence of antibiotic resistance. To do this effectively requires careful attention to preanalytical, analytical, and postanalytical aspects of testing. Respiratory specimens require digestion and concentration followed by fluorescence microscopy. The Centers for Disease Control and Prevention (CDC) recommends the performance of a direct nucleic acid amplification method, regardless of smear results, on specimens from patients in whom the suspicion of tuberculosis is high. Liquid-based technologies are more rapid and sensitive for the detection of M. tuberculosis in culture and nucleic acid probes, but biochemicals are preferred for identification once growth is detected. Susceptibility testing is most often done using either the agar proportion method or a commercial broth system. New genotypic and phenotypic methods of susceptibility testing include first- and second-line agents and are promising, though not yet widely available. Finally, gamma interferon release assays are preferred to the tuberculin skin test for screening certain at-risk populations, and new CDC guidelines are available that assist clinicians in their use.
Use of loan loss provisions for capital, earnings management and signalling by Australian banks

This study examines whether and to what extent Australian banks use loan loss provisions (LLPs) for capital, earnings management and signalling. We examine if there were changes in the use of LLPs as a result of the implementation of banking regulations consistent with the Basel Accord of 1988, which made loan loss reserves no longer part of Tier I capital in the numerator of the capital adequacy ratio. We find some evidence to indicate that Australian banks use LLPs for capital management, but we find no evidence of a change in this behaviour after the implementation of the Basel Accord. Our results indicate that banks in Australia use LLPs to manage earnings. Furthermore, listed commercial banks engage more aggressively in earnings management using LLPs than unlisted commercial banks. We also find that earnings management behaviour is more pronounced in the post-Basel period. Overall, we find a significant understating of LLPs in the post-Basel period relative to the pre-Basel period. This indicates that reported earnings might not reflect the true economic reality underlying those numbers. Finally, Australian banks do not appear to use LLPs for signalling future intentions of higher earnings to investors.
Fluoride in Dog Parotid Saliva After Intravenous Administration of Sodium Fluoride, Sodium Monofluorophosphate, and Calcium Fluoride

Sodium fluoride, sodium monofluorophosphate, or calcium fluoride, in amounts equivalent to 0.5 mg/kg, were given intravenously to dogs and the effect on parotid saliva F was determined. Significant (P < 0.01) differences in saliva F levels were related to the ionization of NaF, the hydrolysis of the PO3F ion, and the insolubility of CaF2.
The protective and therapeutic function of small heat shock proteins in neurological diseases

Historically, small heat shock proteins (sHSPs) have been extensively studied in the context of being intracellular molecular chaperones. However, recent studies looking at the role of sHSPs in neurological diseases have demonstrated a near universal upregulation of certain sHSPs in damaged and diseased brains. Initially, it was thought that sHSPs are pathological in these disease states because they are found in the areas of damage. However, transgenic overexpression and exogenous administration of sHSPs in various experimental disease paradigms have shown just the contrary – that sHSPs are protective, not pathological. This review examines small heat shock proteins in neurological diseases and highlight the potential of using these neuroprotective sHSPs as novel therapeutics. It will first address the endogenous expression of sHSPs in a variety of neurological disorders. Secondly, it will focus on recent studies that have investigated the therapeutic potential of small heat shock proteins. Finally, it will provide a model of what we think is the function of small heat shock proteins in neurological diseases.
The Initial Mass Function

As we have already heard, estimates of the fraction of a star-forming cloud that is converted into stars and of the overall star formation rate in galaxies depend crucially on the assumed stellar initial mass function, which must be known before any quantitative conclusions can be drawn about galactic evolution. Instead of attempting to summarize current knowledge on the subject, it may be more useful at this point to emphasize the large uncertainties that still remain. The importance of these uncertainties was made clear in the excellent talk by Walterbos on star formation in M31: in order to derive the total star formation rate from various data indicating the number of massive stars present, Walterbos adopted a “middle-of-the-road” IMF previously used by Kennicutt, but pointed out that if the steeper IMF proposed by Miller and Scalo in 1979 were used instead, the inferred SFR would have to be multiplied by 3.4, whereas if a flatter IMF with x = 1 (cf. Van Buren, Astrophys. J. 294, 567, 1985) were adopted, the SFR would be multiplied by 0.25. Thus the compromise IMF adopted by Walterbos could yield an SFR that is incorrect by a factor of four, and we are not even sure whether it is more likely to be too high or too low. It should nevertheless be noted that Van Buren’s more recent work used a larger sample of stars than previous studies and applied more careful corrections for extinction, and the result was a flatter IMF, i.e. a larger proportion of massive stars. This suggests that the widely used Miller-Scalo IMF may be too steep for the most massive stars, and that many estimated SFRs based on it should be revised downward.
Analytic Treatments of Matter Enhanced Solar Neutrino Oscillations

Mikheyev and Smirnov have pointed out that flavor oscillations of solar neutrinos could be greatly enhanced. The Mikheyev-Smirnov-Wolfenstein mechanism depends on the effective electron neutrino mass that arises from charged-current scattering off solar electrons, a phenomenon first discussed by Wolfenstein. Two analytic treatments, the adiabatic approximation and Landau-Zener (LZ) approximation, have been used in studies of this mechanism. I discuss a simple extension of the LZ approximation that merges naturally with the adiabatic approximation and is free of certain troublesome pathologies that arise in the conventional treatment. In this extension the solar density is approximated as in the conventional treatment, except that the starting and ending densities are the physical ones. Results of this finite LZ approximation are compared to those from the standard LZ approximation, the adiabatic approximation, and ``exact'' numerical integrations. The new approximation is virtually exact regardless of the point of origin of the neutrino in the solar core. This approximation is used to efficiently calculate the solar-neutrino capture rates for $^{37}\mathrm{Cl}$, $^{71}\mathrm{Ga}$, and $^{98}\mathrm{Mo}$. The spatial extent of the solar core, the contributions of minor neutrino species, and the effects of $^{8}\mathrm{B}$ neutrino capture to excited nuclear states are treated with care. Limits imposed on \ensuremath{\delta}${m}^{2}$ and ${\mathrm{sin}}^{2}$2${\mathrm{theta}}_{\mathrm{v}}$ by the nonzero $^{37}\mathrm{Cl}$ capture rate are derived by considering the expected uncertainties in standard-solar-model flux estimates. Those oscillation parameters are determined that could account for the $^{37}\mathrm{Cl}$ puzzle and yet lead to a $^{71}\mathrm{Ga}$ counting rate above the minimum astronomical value. I determine, in the event that such an ambiguous result arises, the extended region of the \ensuremath{\delta}${m}^{2}$-${\mathrm{sin}}^{2}$2${\mathrm{theta}}_{\mathrm{v}}$ plane that would be ruled out. The possibility that the $^{8}\mathrm{B}$ neutrino capture cross section for $^{37}\mathrm{Cl}$ may be slightly larger than the conventional value is briefly discussed.
Speaking of the I-Word

The paper aims to demonstrate the influence of word choice in historical discourse, especially across languages. The critical word here is the ill-defined “improvise.” The modern discourses discussed here concern European musical practices of the Middle Ages and the eighteenth century. “Improvisation” occurs in modern discourses about medieval texts only as a result of misreading of medieval sources. Its presence in modern discourses about eighteenth-century texts and practices is owing to the unauthorized translation of Fantasie and fantasieren in German sources. The consequence of this thematization of the “improvise” group for the characterization of medieval and eighteenth-century practices is at the expense of attention to the ex tempore mechanisms of the former and to the preoccupation with fantasy, creativity, affect, and autonomy in the latter.
Towards Finding Relevant Information Graphics: Identifying the Independent and Dependent Axis from User-Written Queries

Information graphics (non-pictorial graphics such as bar charts and line graphs) contain a great deal of knowledge. Information retrieval research has focused on retrieving textual documents and on extracting images based on words appearing in the accompanying article or based on low-level features such as color or texture. Our goal is to build a system for retrieving information graphics that reasons about the content of the graphic itself in deciding its relevance to the user query. As a first step, we aim to identify, from a full sentence user query, what should be depicted on the independent and dependent axes of potentially relevant graphs. Natural language processing techniques are used to extract features from the query and machine learning is employed to build a model for hypothesizing the content of the axes. Results have shown that our models can achieve accuracy higher than 80% on a corpus of collected user queries.
Leadership and management skills for psychiatry trainees: An integral part of curriculum?

•Management and leadership skills are often ignored in curriculum for psychiatric trainees.•Incorporation of these elements in training is likely to benefit all trainees.•The benefits of including these elements far outweigh the cons.
Large-Scale Diversity Minimization via Parallel Genetic Algorithms

Diversity minimization is a class of large-scale combinatorial optimization problems arising from the assignment of processors to database fragments in a parallel database environment. These problems may be formulated as nonconvex assignment problems, but they are very difficult to solve via standard optimization techniques because of their large size and because they have many alternative optima. The method described here utilizes theoretical results regarding the form of optimal solutions as the basis for the development of a high-level parallel genetic algorithm. In effect, the genetic operators serve to produce good starting points and neighborhoods for exploration by a heuristic that uses knowledge of the small number of alternatives for desirable processor assignment patterns. Computational results from a parallel implementation of the algorithm on a Connection Machine CM-5 are reported, including the computation of optimal solutions to a million-variable diversity minimization problem.
‘Dissolving Boundaries’ – An Analysis of Threshold Concepts Within Disability Theology

This article focuses on an analysis of threshold concepts (TCs) within disability theology. It explores a range of ideas linked to TCs and the experience of people living with a disability (people LWD). The world in which Christian parishioners encounter people LWD (the focus of this article), could be described as a ‘liquid world’ which is fuzzy, uncertain, unstable and marked by ‘dissolving boundaries’ (Barnett, R. 2012. “The Coming of the Ecological Learner.” In Transitions and Transformations in Learning and Education, edited by P. Tynjala, M.-L. Stenstrom and M. Saarnivaara, 9–20. Dordrecht, NL: Springer) The authors argue that, despite such boundaries, or perhaps because of them, certain thresholds need to be crossed by members of faith communities in order for a person LWD to feel as if he/she genuinely belongs to a community. Nevertheless it is acknowledged that some people involved might be both people LWD and parishioners. The three interrelated thresholds examined within this article are — empo...
The Molecular Epidemiology of Tuberculosis

The ability to track specific strains of Mycobacterium tuberculosis as they spread through a population is critical for our understanding of the transmission and pathogenesis of tuberculosis. However, until recently, the only phenotypic markers that distinguished different strains of M. tuberculosis were drug resistance patterns and mycobacterial phage typing (Gruft et al. 1984). Molecular genotyping techniques that allow us to differentiate isolates of M. tuberculosis for the purpose of tracking strains in the Community and designing prevention and control strategies to block further transmission of M. tuberculosis are now available.
Using digital rocks and simulations of pore-scale multiphysics to characterize a sandstone reservoir

AbstractThe modeling and prediction of transport and elastic properties for sandstones are critical steps in the exploration and appraisal of hydrocarbon reservoirs, particularly in deepwater settings where seismic data are abundant and well costs are high. Reliable multiphysics modeling of reservoir rocks requires robust models that respect the underlying geologic character and microstructure of the geomaterial and honor the measured properties. We have developed a case study that integrates traditional laboratory measurements with computational methods to quantify and relate physical properties of reservoir sandstones. We evaluate the complementary use of digital rock simulations as a practical technology that adds physical insight into the development and calibration of rock-property relationships. We also determine the challenges faced while applying digital rock physics to interpret laboratory data, and the steps taken to overcome those limitations. Combining physical and computational methods, we ac...
Esophageal Cancer: Background and Clinical Evidence

Although esophageal cancer represents only 6 % of all gastrointestinal malignancies diagnosed in the United States, it remains a highly lethal disease and the seventh most common cause of cancer death in males. Rates of squamous cell carcinoma have been declining, while the incidence of esophageal adenocarcinoma is increasing with rising rates of gastroesophageal reflux disease (GERD) and associated risk factors. Although the overall prognosis of esophageal cancer patients is poor, particularly with more advanced disease, trimodality therapy with radiation, chemotherapy, and surgery has improved outcomes. This chapter reviews the clinical data underlying the current management of esophageal cancer.
Absorption effects on plane waves in layered media

Abstract We present equations which can be used in conjunction with estimates of material properties to determine whether exact linear viscoelastic modeling will give significantly different results from elastic ray calculations. We apply the viscoelastic version of Snell9s law to assess the effects of anelasticity on phase velocities, attenuation coefficients, transmission angles, and travel times for a plane wave propagating through a stack of plane viscoelastic layers described by the velocity and Q for a homogeneous wave in each layer. We include a survey of the viscoelastic theory of plane waves to provide a context for the results. Our analysis shows that the most general version of Snell9s law leads to a complex two-dimensional vector ray parameter in which case plane P -wave motion does not decouple from horizontal transverse S -wave motion. We show that in a layered medium the fields generated by a symmetric point source, a vector point force, a double-couple point force, or a plane of tractions corresponding to a complex vector parameter, as well as other “reasonable” sources, can be calculated by integrating over real ray parameters, but in all of these cases, one must consider the coupling in laterally heterogeneous media. Differences from elastic ray behavior are found to be well correlated with the behavior of the parameter χ ≡ 1 + Q - 2 cos 2 γ where γ is the angle of inhomogeneity of the wave. We present equations for χ in terms of layer parameters and both the vector ray parameter and incident wave parameters. Examples presented to illustrate the method show significant (5 to 10 per cent) deviations from elastic travel times, and offsets in a given layer may be possible in very lossy layered materials.
An Argument for the Use of High Fear Appeals as an Effective Type II Diabetes Health Messaging Strategy: A Structured Abstract

Recent estimates are that half of all deaths in the USA are due to mostly preventable diseases. Thus disease prevention is necessarily an increasingly important focus of modern public policy. Diabetes rates are rising globally, but in the USA over the last 30 years type II diabetes has risen 132 %. The Centers for Disease Control reports that type II diabetes costs the US economy $245 billion per year in direct medical costs and that of 29 million diagnosed diabetics in the USA, 95 % are type II diabetics. An additional 8.1 million Americans remain undiagnosed type II diabetics. Of particular concern is that diabetes does much of its damage before the patient experiences symptoms. By 2050, if left unchecked fully 1/3 of all Americans will be diabetic (CDC 2012). Clearly, current efforts in health messaging toward potential type II diabetics are not working.
Tourism and transitions toward sustainability: Developing tourists’ pro-sustainability agency

Leveraging human agency for sustainability transitions may benefit from interventions at the subjective level. This paper explores nature-based tourism as an example of a social process through which pro-sustainability agency could be promoted in tourists. We examine the potential of nature-based tourism to advance sustainability through a model linking tourism experience, personal change and pro-sustainability agency. Our conceptual model is explored through an empirical study of tourists surveyed before and after one-day whitewater rafting tours on Costa Rica’s Pacuare River. Results suggest that tourists’ past experiences, motivation, predispositions to change and fit with personal development processes are leveraging factors for the design of nature-based experiences that promote pro-sustainability agency. These findings have significant implications for the design of tourism, including ways to extend tourists’ experiences, increase collaboration among tourism operations and enhance the guides’ role in tour impact. This research highlights tourism sustainability as a necessary complement to sustainable tourism, and the opportunity of tourism actors to design activities that encourage pro-sustainability agency.
Greater future global warming inferred from Earth’s recent energy budget

Climate models provide the principal means of projecting global warming over the remainder of the twenty-first century but modelled estimates of warming vary by a factor of approximately two even under the same radiative forcing scenarios. Across-model relationships between currently observable attributes of the climate system and the simulated magnitude of future warming have the potential to inform projections. Here we show that robust across-model relationships exist between the global spatial patterns of several fundamental attributes of Earth's top-of-atmosphere energy budget and the magnitude of projected global warming. When we constrain the model projections with observations, we obtain greater means and narrower ranges of future global warming across the major radiative forcing scenarios, in general. In particular, we find that the observationally informed warming projection for the end of the twenty-first century for the steepest radiative forcing scenario is about 15 per cent warmer (+0.5 degrees Celsius) with a reduction of about a third in the two-standard-deviation spread (-1.2 degrees Celsius) relative to the raw model projections reported by the Intergovernmental Panel on Climate Change. Our results suggest that achieving any given global temperature stabilization target will require steeper greenhouse gas emissions reductions than previously calculated.
Effects of medication assisted treatment (MAT) for opioid use disorder on functional outcomes: A systematic review

This systematic review synthesizes evidence on the effects of Medication-Assisted Treatment (MAT) for opioid use disorder (OUD) on functional outcomes, including cognitive (e.g., memory), physical (e.g., fatigue), occupational (e.g., return to work), social/behavioral (e.g., criminal activity), and neurological (e.g., balance) function. Five databases were searched from inception to July 2017 to identify English-language controlled trials, case control studies, and cohort comparisons of one or more groups; cross-sectional studies were excluded. Two independent reviewers screened identified literature, abstracted study-level information, and assessed the quality of included studies. Meta-analyses used the Hartung-Knapp method for random-effects models. The quality of evidence was assessed using the GRADE approach. A comprehensive search followed by 1411 full text publication screenings yielded 30 randomized controlled trials (RCTs) and 10 observational studies meeting inclusion criteria. The studies reported highly diverse functional outcome measures. Only one RCT was rated as high quality, but several methodologically sound observational studies were identified. The statistical power to detect differences in functional outcomes was unclear in most studies. When compared with matched "healthy" controls with no history of substance use disorder (SUD), in two studies MAT patients had significantly poorer working memory and cognitive speed. One study found MAT patients scored worse in aggressive responding than did "healthy" controls. A large observational study found that MAT users had twice the odds of involvement in an injurious traffic accident as non-users. When compared with persons with OUD not on MAT, one cohort study found lower fatigue rates among buprenorphine-treated OUD patients. No differences were reported for occupational outcomes and results for criminal activity and other social/behavioral areas were mixed. There were few differences among MAT drug types. A pooled analysis of three RCTs found a significantly lower prevalence of fatigue with buprenorphine compared to methadone, while a meta-analysis of the same RCTs found no statistical difference in insomnia prevalence. Three RCTs that focused on cognitive function compared the effects of buprenorphine to methadone; no statistically significant differences in memory, cognitive speed and flexibility, attention, or vision were reported. The quality of evidence for most functional outcomes was rated low or very low. In sum, weaknesses in the body of evidence prevent strong conclusions about the effects of MAT for opioid use disorder on functional outcomes. Rigorous studies of functional effects would strengthen the body of literature.
Impact wave attenuation using Maxwell-type oscillators in dissipative elastic metamaterials

This work studies the development of a dissipative elastic metamaterial with single and dual-Maxwell type resonator for stress wave mitigation. Mass-spring-damper elements are used to model and analyze the mechanism of wave dissipation effect on the vibration characteristics. It is found that broadband wave attenuation region can be obtained and expanded to a wider range by properly utilizing interactions from resonant motions and viscoelastic effects of the Maxwell-type oscillators. In addition, numerical verifications are conducted for various cases, and excellent agreement between theoretical and numerical frequency response functions are obtained. The design of this dissipative metamaterial system is further applied for blast wave mitigation. By means of the bandgap merging effect that is induced by the Maxwell-type oscillator, the passing blast wave can be almost completely suppressed in the low-frequency range. A significantly improved performance of the proposed dissipative metamaterials for stress wave mitigation is verified in both time and frequency domains.
Molecular recognition of RAS/RAF complex at the membrane: Role of RAF cysteine-rich domain

Activation of RAF kinase involves the association of its RAS-binding domain (RBD) and cysteine-rich domain (CRD) with membrane-anchored RAS. However, the overall architecture of the RAS/RBD/CRD ternary complex and the orientations of its constituent domains at the membrane remain unclear. Here, we have combined all-atom and coarse-grained molecular dynamics (MD) simulations with experimental data to construct and validate a model of membrane-anchored CRD, and used this as a basis to explore models of membrane-anchored RAS/RBD/CRD complex. First, simulations of the CRD revealed that it anchors to the membrane via insertion of its two hydrophobic loops, which is consistent with our NMR measurements of CRD bound to nanodiscs. Simulations of the CRD in the context of membrane-anchored RAS/RBD then show how CRD association with either RAS or RBD could play an unexpected role in guiding the membrane orientations of RAS/RBD. This finding has implications for the formation of RAS-RAS dimers, as different membrane orientations of RAS expose distinct putative dimerization interfaces.
A Southwest Oncology Group: Chemotherapy Versus Chemotherapy Plus Radiotherapy in Treatment of Stage III Hodgkin’s Disease

The Southwest Oncology Group (SWOG) performed a randomized study (SWOG 7518, CAR 2) of chemotherapy using ten courses of nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) plus low-dose bleomycin (LDB), versus three courses of combined therapy, MOPP + LDB plus radiotherapy (XRT) from October, 1974, to April 1980, in pathologic stage III Hodgkin’s disease. The present report includes data on 136 registered patients, of whom 112 are fully or partially evaluable. At this preliminary analysis, complete remission rates are 82% for chemotherapy alone and 82% for combined treatment. There are no statistically significant differences in survival or relapse-free survival between the two treatment programs, and no specific trends for stage IIIA versus IIIB. The estimated 3-year survival rate for all patients was 82%. Toxicities are comparable when considering the highest grades. There was one case of acute myeloblasts leukemia on combined treatment. Preliminary evidence suggests that patients with nodular sclerosis histologic type are more likely to relapse on chemotherapy alone than on combined treatment.
Emergency Department Presentation

Patients with acute coronary syndrome (ACS) may present to the emergency department (ED) via emergency medical services or self-transport. When they present via emergency medical services, a diagnostic-quality prehospital 12-lead EKG may enhance the sensitivity and specificity of ACS diagnosis and shorten time to treatment. The ED evaluation of the patient at risk for ACS includes a thorough history and physical assessment of major risk factors for coronary artery disease (diabetes mellitus, hyperlipidemia, hypertension, family history, smoking history), timely and repeated 12-lead EKG, and cardiac biomarkers (preferably point-of-care testing). When evaluating a patient for ACS, the emergency physician must be conscientious of the prevalence of atypical ACS symptoms such as dyspnea, nausea, diaphoresis syncope or pain in the arms, epigastrium, shoulder, or neck. These atypical presentations are most notably studied in the patients of older age, with diabetes mellitus, of female gender, and of nonwhite race. In addition to assessing for the presence of ACS, other life-threatening conditions must also be considered, the most important being aortic dissection, pulmonary embolism, pericarditis with pericardial tamponade, esophageal perforation (Boerhaave’s syndrome), and spontaneous pneumothorax.
Phosphorylation-dependent prolyl isomerization: a novel cell cycle regulatory mechanism.

Protein phosphorylation by proline-directed protein kinases plays an essential role in triggering a programmed set of cell cycle events. We have recently isolated an essential and conserved mitotic regulator, Pint. Pint is a phosphorylation-dependent prolyl isomerase that specifically isomerizes the phosphorylated serine/threonine-proline bond. Pin1 also binds and regulates the function of a conserved set of mitosisspecific phosphoproteins. These results suggest phosphorylation-dependent prolyl isomerization to be a novel cell cycle regulatory mechanism. This new post-translational regulation may allow the general increase in protein phosphorylation to be converted into the organised and programmed set of structural modifications that occur during mitosis. In addition, since inhibition of Pint induces mitotic arrest and apoptosis, Pini may be a potential new drug target.
Feedback-related neurophysiology in children and their parents: Developmental differences, familial transmission, and relationship to error-monitoring.

Abstract The feedback negativity (FN) and reward positivity (RewP) are event-related brain potentials (ERPs) that follow the presentation of negative and positive feedback information, respectively, and have become the focus of recent research on psychopathology because of their associations with symptom severity of and risk for depression. We advanced our understanding of these feedback-related ERPs by examining developmental differences, familial transmission, and associations with error-monitoring ERPs. Parents and their children completed parallel, developmentally-tailored guessing and go/no-go tasks while feedback- and error-related ERPs were measured. We found that the Δ FN and RewP amplitudes increased with age and were larger in males than females among the child participants. The RewP also demonstrated familial transmission between fathers and their children. Finally, the FN and RewP were associated with error-related ERPs in children and adults, albeit in different ways. The current findings demonstrate that the FN and RewP have promise as developmentally-sensitive neural markers of reward and action monitoring processes associated with risk for psychopathology.
Stella: geotagging images via crowdsourcing

Geotagged data (e.g. images or news items) have empowered various important applications, e.g., search engines and news agencies. However, the lack of available geotagged data significantly reduces the impact of such applications. Meanwhile, existing geotagging approaches rely on the existence of prior knowledge, e.g., accurate training dataset for machine learning techniques. This paper presents Stella; a crowdsourcing framework for image geotagging. The high accuracy of Stella is resulted by being able to recruit workers near the image location even without knowing its location. In addition, Stella also return its confidence about the reported location to help users in understanding the result quality. Experimental evaluation shows that Stella consistently geotags an image with an average of 95% accuracy and 90% of confidence.
Expansive microbial metabolic versatility and biodiversity in dynamic Guaymas Basin hydrothermal sediments

Microbes in Guaymas Basin (Gulf of California) hydrothermal sediments thrive on hydrocarbons and sulfur and experience steep, fluctuating temperature and chemical gradients. The functional capacities of communities inhabiting this dynamic habitat are largely unknown. Here, we reconstructed 551 genomes from hydrothermally influenced, and nearby cold sediments belonging to 56 phyla (40 uncultured). These genomes comprise 22 unique lineages, including five new candidate phyla. In contrast to findings from cold hydrocarbon seeps, hydrothermal-associated communities are more diverse and archaea dominate over bacteria. Genome-based metabolic inferences provide first insights into the ecological niches of these uncultured microbes, including methane cycling in new Crenarchaeota and alkane utilization in ANME-1. These communities are shaped by a high biodiversity, partitioning among nitrogen and sulfur pathways and redundancy in core carbon-processing pathways. The dynamic sediments select for distinctive microbial communities that stand out by expansive biodiversity, and open up new physiological perspectives into hydrothermal ecosystem function.