cssi/SciSciGPT-SciSciNet huggingface dataset:
p19(ARF) is dispensable for oncogenic stress-induced p53-mediated apoptosis and tumor suppression in vivo.

Recent studies have shown the p19ARF tumor suppressor to be involved in the response to oncogenic stress by regulating the activity of p53. This response is mediated by antagonizing the function of Mdm2, a negative regulator of p53, indicating a pathway for tumor suppression that involves numerous genes altered in human tumors. We previously described a transgenic mouse brain tumor model in which oncogenic stress, provided by cell-specific inactivation of the pRb pathway, triggers a p53-dependent apoptotic response. This response suppresses the growth of developing tumors and thus represents a bona fide in vivo tumor suppressor activity. We further showed that E2F1, a transcription factor known to induce p19ARF expression, was required for the response. Here, we use a genetic approach to test whether p19ARF functions to transduce the signal from E2F1 to p53 in this tumor suppression pathway. Contrary to the currently accepted hypothesis, we show that a deficiency in p19ARF has no impact on p53-mediated apoptosis or tumor suppression in this system. All measures of p53 function, including the level of apoptosis induced by pRb inactivation, the expression of p21 (a p53-responsive gene), and the rate of tumor growth, were comparable in mice with and without a functional p19ARF gene. Thus, although p19ARF is required in some cell types to transmit an oncogenic response signal to p53, it is dispensable for this function in an in vivo epithelial system. These results underscore the complexity of p53 tumor suppression and further indicate the existence of distinct cell-specific pathways that respond to similar stimuli.
On the effects of grid ill-conditioning in three dimensional finite element vector potential magnetostatic field computations

The effects of finite-element grid geometries and associated ill conditioning were studied in single-medium and multimedia (air-iron) three-dimensional magnetostatic-field computation problems. The sensitivities of these 3-D field computations to finite-element grid geometries were investigated. It was found that in single-medium applications the unconstrained magnetic vector potential curl-curl formulation in conjunction with first-order finite elements produces global results which are almost totally insensitive to grid geometries. However, it was found that in multimedia (air-iron) applications first-order finite-element results are sensitive to grid geometries and consequent elemental shape ill conditioning. These sensitivities were almost totally eliminated by the use of second-order finite elements in the field-computation algorithms. Practical examples are given to demonstrate these findings. >
Validating MCNP for LEU Fuel Design via Power Distribution Comparisons

The mission of the Reduced Enrichment for Research and Test Reactors (RERTR) Program is to minimize and, to the extent possible, eliminate the use of highly enriched uranium (HEU) in civilian nuclear applications by working to convert research and test reactors, as well as radioisotope production processes, to low enriched uranium (LEU) fuel and targets. Oak Ridge National Lab (ORNL) is reviewing the design bases and key operating criteria including fuel operating parameters, enrichment-related safety analyses, fuel performance, and fuel fabrication in regard to converting the fuel of the High Flux Isotope Reactor (HFIR) from HEU to LEU. The purpose of this study is to validate Monte Carlo methods currently in use for conversion analyses. The methods have been validated for the prediction of flux values in the reactor target, reflector, and beam tubes, but this study focuses on the prediction of the power density profile in the core. A current 3-D Monte Carlo N-Particle (MCNP) model was modified to replicate the HFIR Critical Experiment 3 (HFIRCE-3) core of 1965. In this experiment, the power profile was determined by counting the gamma activity at selected locations in the core. Foils (chunks of fuel meat and clad) were punched out of the fuel elements in HFIRCE-3 following irradiation and experimental relative power densities were obtained by measuring the activity of these foils and comparing each foil s activity to the activity of a normalizing foil. The current work consisted of calculating corresponding activities by inserting volume tallies into the modified MCNP model to represent the punchings. The average fission density was calculated for each foil location and then normalized to the normalizing foil. Power distributions were obtained for the clean core (no poison in moderator and symmetrical rod position at 17.5 inches) and fully poisoned-moderator (1.35 g B/liter in moderator and rods fully withdrawn) conditions. The observed deviations between the experimental and calculated values for both conditions were within the reported experimental uncertainties except for some of the foils located on the top and bottom edges of the fuel plates.
RNA Interference Demonstrates a Novel Role for Integrin-Linked Kinase as a Determinant of Pancreatic Adenocarcinoma Cell Gemcitabine Chemoresistance

Integrin-linked kinase (ILK) facilitates signal transduction between extracellular events and important intracellular survival pathways involving protein kinase B/Akt. We examined the role of ILK in determining pancreatic adenocarcinoma cellular chemoresistance to the nucleoside analogue gemcitabine. Cellular ILK expression was quantified by Western blot analysis. We examined the effects of overexpression of active ILK and of ILK knockdown induced by RNA interference on gemcitabine chemoresistance. We also examined the effects of modulating ILK expression on gemcitabine-induced caspase 3–mediated apoptosis, phosphorylation status of Akt (Ser 473 ) and glycogen synthase kinase. Overexpression of ILK increased cellular gemcitabine chemoresistance, whereas ILK knockdown induced chemosensitization via increased caspase 3–mediated apoptosis. ILK knockdown attenuated Akt Ser 473 and glycogen synthase kinase phosphorylation, whereas overexpression of constitutively active myristoylated Akt was sufficient to induce significant recovery in gemcitabine chemoresistance in the presence of ILK knockdown. Levels of ILK expression affect gemcitabine chemoresistance in pancreatic adenocarcinoma cells. This novel finding suggests that therapies directed against ILK and its downstream signaling targets may have the potential to enhance the efficacy of gemcitabine-based chemotherapy.
A Note on Gluing Dirac Type Operators on a Mirror Quantum Two-Sphere

The goal of this paper is to introduce a class of operators, which we call quantum Dirac type operators on a noncommutative sphere, by a gluing construction from copies of noncommutative disks, subject to an appropriate local boundary condition. We show that the resulting operators have compact resolvents, and so they are elliptic operators.
Transient virulence of emerging pathogens

Should emerging pathogens be unusually virulent? If so, why? Existing theories of virulence evolution based on a tradeoff between high transmission rates and long infectious periods imply that epidemic growth conditions will select for higher virulence, possibly leading to a transient peak in virulence near the beginning of an epidemic. This transient selection could lead to high virulence in emerging pathogens. Using a simple model of the epidemiological and evolutionary dynamics of emerging pathogens, along with rough estimates of parameters for pathogens such as severe acute respiratory syndrome, West Nile virus and myxomatosis, we estimated the potential magnitude and timing of such transient virulence peaks. Pathogens that are moderately evolvable, highly transmissible, and highly virulent at equilibrium could briefly double their virulence during an epidemic; thus, epidemic-phase selection could contribute significantly to the virulence of emerging pathogens. In order to further assess the potential significance of this mechanism, we bring together data from the literature for the shapes of tradeoff curves for several pathogens (myxomatosis, HIV, and a parasite of Daphnia) and the level of genetic variation for virulence for one (myxomatosis). We discuss the need for better data on tradeoff curves and genetic variance in order to evaluate the plausibility of various scenarios of virulence evolution.
Modeling and design optimization of planar power transformer for aerospace application

A new low profile, light weight, high power density and high efficiency planar transformer for aerospace application is presented. In this paper, a systematic optimizing procedure is illustrated with a detailed design of a flyback transformer. We use Double 2D Finite Element Method (FEM) [1] modeling strategies to calculate the power loss and to optimize the design. The strategies, interleaving and horizontal and vertical parallel windings for reducing the winding loss are discussed. A 6-layer PCB layout is shown to validate the design.
Estimation of ability from homework items when there are missing and/or multiple attempts

Scoring of student item response data from online courses and especially massively open online courses (MOOCs) is complicated by two challenges, potentially large amounts of missing data and allowances for multiple attempts to answer. Approaches to ability estimation with respect to both of these issues are considered using data from a large-enrollment electrical engineering MOOC. The allowance of unlimited multiple attempts sets up a range of observed score and latent-variable approaches to scoring the constructed response homework. With respect to missing data, two classical approaches are discussed, treating omitted items as incorrect or missing at random (MAR). These treatments turn out to have slightly different interpretations depending on the scoring model. In all, twelve different homework scores are proposed based on combinations of scoring model and missing data handling. The scores are computed and correlations between each score and the final exam score are compared, with attention to different populations of course participants.
The Measurement of Suburban Sprawl: An Evaluation:

We review and analyze how suburban sprawl has been conceptualized and measured in recent urban research. We find that indexes created to measure sprawl in metropolitan areas do so in three differen...
Ovulatory follicle dysfunction in lactating dairy cows after treatment with Folltropin-V at the onset of luteolysis.

The objective was to examine growth of the ovulatory follicle after FSH (Folltropin-V; Bioniche Animal Health, Belleville, Ontario, Canada) was given at the onset of induced luteolysis during a synchronization of ovulation protocol. Using GnRH or hCG for inducing ovulation enabled assessing ovulatory follicle responsiveness to an endogenous versus exogenous surge of LH activity. At 8 to 10 days after estrus (synchronized estrus = Day 0), lactating dairy cows received an Eazi-Breed CIDR (Pfizer Animal Health) plus 100 μg GnRH. After 7 days, controlled internal drug release devices (CIDRs) were removed, cows were given 500 μg cloprostenol, and then randomly allocated to receive 80 mg Folltropin-V (FSH; N = 19) or 4 mL sterile saline (SAL; N = 16). After 49 hours, FSH and SAL cows were randomly allocated to receive 100 μg GnRH or 3000 IU hCG. Five cows ovulated 30 to 42 hours (38.4 ± 1.2 hours) after FSH treatment. In the remaining FSH (N = 14) or SAL (N = 16) cows, ovulatory follicle size was similar at CIDR removal (14.5 ± 0.6 and 14.7 ± 0.6 mm, respectively; P = 0.85) and when GnRH/hCG was given (16.6 ± 0.6 and 17.7 ± 0.6 mm, respectively; P = 0.23). Estradiol-17β concentrations were lower in FSH cows at 36 and 49 hours after CIDR removal (FSH by time interaction, P < 0.005). After GnRH or hCG treatment, four FSH cows failed to ovulate. In cows exhibiting ovulation, the last recorded size of the ovulatory follicle was not influenced by FSH (18.1 ± 0.9 and 17.5 ± 0.6 mm for FSH and SAL, respectively; P = 0.59) or hormonal induction approach (18.4 ± 0.9 and 17.2 ± 0.7 mm for GnRH and hCG, respectively; P = 0.29). The interval from onset of luteolysis to ovulation and pharmaceutical induction to ovulation was shorter in FSH cows given GnRH (FSH by pharmaceutical inducer [GnRH vs. hCG] interaction; P = 0.01). Cows receiving GnRH had an LH surge; hCG-treated cows did not. Maximum LH concentrations were greater (P < 0.04) in SAL versus FSH cows after GnRH treatment (10.9 ± 1.2 vs. 6.7 ± 1.4 ng/mL, respectively). In three FSH cows failing to ovulate after GnRH treatment, the maximum LH concentration was <4 ng/mL. When analyzed from GnRH treatment, average time to LH maximum concentration was similar (P = 0.50) to values obtained in cows receiving FSH and GnRH and SAL and GnRH (1.7 ± 0.2 vs. 1.9 ± 0.1 hours, respectively). Interval to maximum hCG concentrations was shorter (P = 0.02) for cows receiving SAL versus FSH (8.0 ± 0.8 and 10.0 ± 0.8 hours for SAL and FSH, respectively). Ovulatory dysfunction of this magnitude highlighted the lack of suitability of Folltropin-V at a dose of 80 mg at the time of induction of luteolysis in fixed timed AI protocols.
Microenvironmental effects limit efficacy of thymoquinone treatment in a mouse model of ovarian cancer

Ovarian cancer is the most lethal gynecologic malignancy, with limited treatment options for chemoresistant disease. An important link between inflammation and peritoneal spread of ovarian cancer is NF-κB signaling. Thymoquinone (TQ) exerts multiple anti-tumorigenic cellular effects, including NF-κB inhibition. We aimed to investigate the therapeutic potential of TQ in an established murine syngeneic model of ovarian cancer. ID8-NGL mouse ovarian cancer cells stably expressing an NF-κB reporter transgene were injected intra-peritoneally into C57BL/6 mice, and mice were treated with TQ or vehicle for 10 or 30 days. TQ was combined with the macrophage depleting drug, liposomal clodronate, in selected experiments. Effects on peritoneal tumor burden were measured by volume of ascites, number of peritoneal implants and mesenteric tumor mass. NF-κB reporter activity and markers of proliferation and apoptosis were measured in tumors and in confirmatory in vitro experiments. Protein or mRNA expression of M1 (anti-tumor) and M2 (pro-tumor) macrophage markers, and soluble cytokine profiles, were examined from harvested ascites fluid, peritoneal lavages and/or tumor sections. 2-tailed Mann–Whitney tests were used for measuring differences between groups in in vivo experiments. Consistent with its effects in vitro, TQ reduced proliferation and increased apoptosis in ID8-NGL tumors after 10 and 30 day treatment. Prolonged TQ treatment did not significantly alter tumor number or mass compared to vehicle, but rather exerted an overall deleterious effect by stimulating ascites formation. Increased ascites was accompanied by elevated NF-κB activity in tumors and macrophages, increased pro-tumor M2 macrophages and expression of pro-tumorigenic soluble factors such as VEGF in ascites fluid, and increased tumor infiltration of M2 macrophages. In contrast, a 10 day exposure to TQ produced no ascites, and reduced tumor NF-κB activity, M2 macrophages and soluble VEGF levels. Peritoneal macrophage depletion by clodronate significantly reduced tumor burden. However, TQ-stimulated ascites was further enhanced by co-treatment with clodronate, with macrophages present overwhelmingly of the M2 phenotype. Our findings show that pro-tumorigenic microenvironmental effects limited the efficacy of TQ in a syngeneic mouse model of ovarian cancer, and provide caution regarding its potential use in clinical trials in ovarian cancer patients.
Effect of the red imported fire ant (Hymenoptera: Formicidae) and carcass type on the daily occurrence of postfeeding carrion-fly larvae (Diptera: Calliphoridae, Sarcophagidae)

Red imported fire ants, Solenopsis invicta Buren, caused an increased in the proportion of gaps in the daily occurrence of postfeeding larvae of Cochliomyia macellaria (F.) in carrion-baited traps. Chrysomya rufifacies appeared later in the decomposition process and over a wider period of days in goat than in rabbit carcasses. The dependence of presence or absence of a carrion arthropod taxon at a given point in succession on interactions between other arthropods or carcass type must be considered when using successional data to estimate postmortem intervals.
Total anomalous pulmonary venous drainage into the portal vein

Abstract 1. 1. The fifth case of total anomalous pulmonary venous drainage into the portal vein to be reported in the literature is presented. 2. 2. Clinical and pathologic data are discussed. 3. 3. The hemodynamics of the lesion are considered. 4. 4. The importance of cardiac catheterization in early diagnosis is stressed. 5. 5. The promise of eventual surgical correction is entertained.
Recent progress toward development of vaccines against conception

Although there are several methods of contraception available, the population explosion and unintended pregnancies continue to cause major health issues and constrain resources worldwide. A better method of contraception that is acceptable in developed as well as developing countries is urgently needed. Contraceptive vaccines (CVs) can fulfil most of the properties of an ideal contraceptive. The development of CVs is an exciting proposition and has drawn significant attention lately. The purpose of this article is to review the present status and future perspectives of CVs for human use, and for control of farm, feral, stray and domestic animal populations.
RELATIVE TRANSFER OF ESTRIOL AND ITS CONJUGATES ACROSS THE FETAL MEMBRANES IN VITRO.

The transport and metabolism of estriol, estriol-3-sulfate and estriol-16- glucosiduronate by human chorion and amnion have been studied in simple in vitro systems. Estriol is transferred more rapidly than its conjugates through both membranes. Transfer of all compounds is more rapid through amnion than chorion. Incubation of estriol sulfate with intact chorion or the homogenate results in significant hydrolysis. This is not true of amnion. Neither membrane sulfurylates estriol nor hydrolyzes the glucosiduronate. These observations are compared with those obtained previously with placenta and an explanation is offered for their similarity, based on common origin and function. (Endocrinology 76: 722,1965)
Myosin-II Tails Confer Unique Functions in Schizosaccharomyces pombe: Characterization of a Novel Myosin-II Tail

show that the tails rather than the structurally similar heads determine the gene-specific functions of myp2 1 and myo2 1 . The Myo2p tail is a rod-shaped coiled-coil dimer that aggregates in low salt like other myosin-II tails. The Myp2p tail is monomeric in high salt and is insoluble in low salt. Biophysical properties of the full-length Myp2p tail and smaller subdomains indicate that two predicted coiled-coil regions fold back on themselves to form a rod-shaped antiparallel coiled coil. This suggests that Myp2p is the first type II myosin with only one head. The C-terminal two-thirds of Myp2p tail are essential for function in vivo and may interact with components of the salt response pathway.
Equilibration in an Eddy Resolving Model with Simplified Physics

The role of waves in maintaining the midlatitude tropospheric climate is investigated in a dry high-resolution quasigeostrophic b-plane channel model coupled to both a simplified model of the atmospheric boundary layer and an interactive static stability. The climate of the model’s equilibrated state is found to be separated into two dynamical regimes, one within the boundary layer and the other within the free troposphere. Thermal diffusion in the atmospheric boundary layer prevents the eddies from modifying the mean temperature structure there by damping temperature fluctuations. The potential vorticity gradients are essentially eliminated in the lower troposphere above the boundary layer, in agreement with observations. The homogenization of potential vorticity occurs in the region where the baroclinic waves have a critical layer, and is accomplished mainly by an increase in the static stability in the lower troposphere due to the vertical eddy heat fluxes. Even though the model has kinetic energy and enstrophy spectra characteristic of a fully turbulent flow, the equilibrated state of the model is essentially maintained by wave‐mean flow interaction, primarily by the interaction between wave 5 and the zonal mean state. The zonal mean of the equilibrated state is found to be linearly stable to all waves. The largest-scale wave in the fully nonlinear state, wave 4, is found to be maintained by an energy cascade from the higher wavenumbers. However when wave 4 is large, stability analysis indicates that it is unstable, with the growing mode dominated by wave 6. This instability appears to saturate quickly and hand its energy over to wave 5. The result is that the amplitude of waves 4 and 5 in the equilibrated state are strongly anticorrelated, but the fluctuations in total eddy kinetic energy are strongly correlated with the fluctuations in the sum of the energy in waves 4 and 5.
International Climate Change Policies

Climate change has led to broad consensus need for low carbon and climate resilient development pathways, as evidenced by a broad global consensus to limit temperature increase to 2 C. Moving towards such a pathway at the speed demanded by science needs clear policy direction from the international community, in the form of a new international agreement where emissions are cut by all nations. Developed countries must think of investing in developing countries to mitigate climate change. Climate change is a global phenomena that has impacts on all nations. The most vulnerable continent to climate change is Africa. Reaching consensus to invest in Africa for adaptation and mitigation would significantly benefit all. Investing into policy barrier removals in developing countries are prime factors for global debate.
Microarray analysis of PBMC after Plasmodium falciparum infection: Molecular insights into disease pathogenesis.

Abstract Objective To find out host gene expression profiles after malarial infection. Methods Further time-course microarray analysis of peripheral blood mononuclear cells focusing on malaria pathogenesis was performed. Results Up-regulation of coagulation-related genes, heat shock proteins, glycolytic enzymes, glucose transporters, and vacuolar H + -ATPases was found in acute febrile malaria. In early malaria, prior to detectable parasitemia, CD36 and ICAM1 were up-regulated. During acute malaria, there is correlation between IL-1β and heat shock proteins. CD163, a hemoglobin scavenger receptor, was up-regulated in acute malaria to potentially facilitate free hemoglobin up-take by leukocytes. In acute malaria, high MafB gene expression was negatively correlated with hemoglobin and platelet counts. Consistent with hemoglobin down-regulation, peripheral red blood cell counts tended to increase during acute malaria. Up-regulations of red blood cell and leukocyte binding mediators like CD36, ICAM1, thrombospondin, and thrombomodulin may contribute to the pathogenesis of cerebral malaria. Similarly, up-regulation of correlated glycolytic enzymes, glucose transporter and H + -ATPases may contribute to the hypoglycemia and metabolic acidosis frequently observed in serious malaria patients. Overall gender effects on gene expression profiles between male and female were not apparent, except for some hemoglobins were significantly down-regulated in male versus female, which suggesting males are prone to malaria-related anemia. Conclusions Leukocyte gene expression profiles can explain the pathogenesis of malarial complication such as fever, metabolic acidosis, hypoglycemia, anemia, and coagulopathy.
The source of gypsum in Mammoth Cave, Kentucky

Mammoth Cave (Kentucky, USA) is the world9s longest human-navigable cave system. Gypsum (CaSO 4 ∙2H 2 O) crystals line many dry passages of the limestone cave and the source of sulfur for the gypsum remains uncertain. Previous workers have suggested sulfate from pyrite oxidation, Mississippian-aged sulfate evaporites, and Pleistocene soil sulfate as possible sulfur sources. We use sulfur isotopes (δ 34 S) to constrain the gypsum sulfur source by comparing the δ 34 S values of different possible sources to that of gypsum throughout the cave. δ 34 S gypsum values (n = 106) from 12 different locations within the Mammoth Cave system are along a continuum of δ 34 S values from –12.0‰ to +12.8‰, with little variability along the crystal growth axis or between samples within the same cave chamber. Neither sulfur from coeval sedimentary evaporites (i.e., gypsum, anhydrite) nor from formations overlying the cave is required to explain the δ 34 S gypsum data. Rather, the range of pyrite δ 34 S in strata immediately surrounding the cave is sufficient to generate the spectrum of observed δ 34 S gypsum . Modern water δ 34 S SO 4 values are similar to the host formation δ 34 S pyrite , suggesting that oxidized pyrite from the host formation continues to be a major sulfur source to this day. Together, these observations strongly suggest a significant local source of sulfur for Mammoth Cave gypsum, the majority (66%–100%) of which is derived from the oxidation of pyrite in strata adjacent to the cave.
Wahrheitsinduzierende Mechanismen, Fehlallokationen und kollusives Verhalten bei der Investitionsbudgetierung

Zur Bestimmung optimaler Investitionsbudgets in einer divisionalisierten Unternehmung ist die Zentrale auf die wahrheitsgemase Meldung der Gewinnpotentiale durch die einzelnen Divisionen angewiesen. Einen Losungsvorschlag fur dieses Problem stellt der sogenannte Groves-Mechanimus dar, unter dem die wahrheitsgemasen Meldungen immer dominante Strategien im Spiel der Divisionsmanager sind. Es wird gezeigt, das die Anreizkompatibilitat dieses Verfahrens nicht nur bei der Annahme expliziten kooperativen Verhaltens der Divisionsmanager verlorengeht, sondern das sogar stets Gleichgewichtspunkte, bestehend aus wahrheitswidrigen Meldungen, existieren, welche alle Manager besser stellen als wahrheitsgetreues Verhalten aller Beteiligten. Abschliesend wird an einem Beispiel diskutiert, inwieweit auser uberhohten Entlohnungen auch falsche Budgetierungsergebnisse resultieren konnen.
Organization and Functional Dynamics of the Avian Ovary

Publisher Summary The avian ovary evolved from that of an ancestral sauropsid (reptilian) lineage, and its derived features reflect characteristics adaptive for seasonal breeding and flight. This chapter provides an updated integration of endocrine, paracrine, and autocrine factors (including associated cell-signaling mechanisms) regulating the organization and adaptive functions of the avian ovary. The development of avian ovarian follicles at the beginning of the reproductive season is followed by atresia and reabsorption of all growing follicles at the termination of breeding. This seasonal cyclicity is postulated to be an adaptation to minimize the metabolic cost of flight and reduce the risk of predation. A distinct hierarchy of growing and, in particular, preovulatory follicles enables multiple yolk-filled ova to be sequentially ovulated and fertilized over a series of days prior to the initiation of egg incubation. The species-specific number of eggs laid (the clutch size) ideally represents an attribute that enables the female and male parents to adequately nurture each offspring with an optimal investment of energy.
YouTube Nature Preferences: A Content Analysis Study

Considering that increased urbanization will continue well into this century, humanistic counselors must reevaluate methods for integrating nature into counseling settings. The use and preferences of nature media accessed through YouTube were studied as a way to begin exploring the indirect ways in which counselors might infuse nature into counseling.
Locked Up and Shut Out: The Suffering of Incarcerated Psychopaths

In their article “Neurosurgery for Psychopaths? An Ethical Analysis,” Dietmar Hubner and Lucie White (2016) consider the ethical merits of deep brain stimulation (DBS) therapy for incarcerated psyc...
On fixed-accuracy and bounded accuracy confidence interval estimation problems in Fisher’s “Nile” example

ABSTRACTFisher’s “Nile” example is a classic that involves a bivariate random variable (X,Y) having a joint probability density function given by f(x,y;&#x1d703;) = exp(−&#x1d703;x−&#x1d703;−1y), 0 0 is a single unknown parameter. We develop (i) fixed-width and (ii) fixed-accuracy confidence intervals for &#x1d703; with a preassigned confidence coeﬃcient. In problem (i), we develop a purely sequential estimation strategy along with its asymptotic properties. In problem (ii), we determine that a fixed-sample-size estimation strategy will suﬃce and yet the requisite sample size would have to be found. We have done that both exactly as well as approximately and we report that for all practical purposes the approximations nearly provide the exact sample size whether it is small, moderate, or large. The last problem we address is bounded-accuracy fixed-sample-size estimation of P&#x1d703;{X>Y}. All theoretical properties are adequately validated by large-scale simulations.
The Automatic Trust Management of Self-Adaptive Multi-Display Environments

This paper presents an approach to automatically manage user trust in self-adaptive ubiquitous computing systems which grounds on a context interpreter and a Bayesian Network as well as a feedback control loop that also provides solutions for a system adaptation. Providing knowledge to the automatic trust management of self-adaptive ubiquitous systems is of special interest due to the fact that during the use of these systems situations appear which can impair user trust and thus user acceptance. Some of these situations and adaptation approaches are presented in this paper.
Collaborative care and the modern craniofacial treatment team

Cleft lip and palate is a complex craniofacial anomaly typically requiring treatment from a range of specialists to produce excellent outcomes. Due to the challenges of coordinating this extensive range of specialists, treatment is best provided by a centralized cleft lip and palate treatment team. This article outlines the members of a modern treatment team, their contributions and responsibilities in patient care, and the benefits to both patient and practitioner when treatment is provided by an experienced multi-disciplinary team.
Visiting scholarships in cardio-thoracic surgery: a valuable experience for fostering collaboration

Visiting scholarships to other institutions have a rich history in medicine and are an exciting opportunity to exchange ideas, learn new clinical techniques and form collaborative relationships for research advancements. Such experiences are also important in fostering a well-rounded surgical education. In this article we reflect on the valuable nature of international collaboration and provide a few guidelines to optimize the experience.
SIMPLICITY: IMPOSSIBILITY THEOREMS

If a collective choice rule satisfies (1) the standard domain restriction; (2) the weak pairwise Pareto condition; (3) independence of irrelevant alternatives; and (4) base quasitransitivity, then, if a set S is weakly, locally pairwise decisive for some alternative against another, it is weakly, globally pairwise decisive between any two alternatives. The chapter presents impossibility theorems including Arrow's first impossibility theorem. Immediately after Arrow presented his first theorem, there arose critiques of the conditions used. In response to those critiques, several series of impossibility theorems have developed, each seeking to remove the use of a condition not found compelling. The chapter discusses one of these series, dealing with the condition of transitive rationality.
Defining the Transcriptional Targets of Leptin Reveals a Role For Atf3 in Leptin Action

Leptin acts via its receptor (LepRb) to modulate gene expression in hypothalamic LepRb-expressing neurons, thereby controlling energy balance and glucose homeostasis. Despite the importance of the control of gene expression in hypothalamic LepRb neurons for leptin action, the transcriptional targets of LepRb signaling have remained undefined because LepRb cells contribute a small fraction to the aggregate transcriptome of the brain regions in which they reside. We thus employed translating ribosome affinity purification followed by RNA sequencing to isolate and analyze mRNA from the hypothalamic LepRb neurons of wild-type or leptin-deficient (Lepob/ob) mice treated with vehicle or exogenous leptin. Although the expression of most of the genes encoding the neuropeptides commonly considered to represent the main targets of leptin action were altered only following chronic leptin deprivation, our analysis revealed other transcripts that were coordinately regulated by leptin under multiple treatment conditions. Among these, acute leptin treatment increased expression of the transcription factor Atf3 in LepRb neurons. Furthermore, ablation of Atf3 from LepRb neurons (Atf3LepRbKO mice) decreased leptin efficacy and promoted positive energy balance in mice. Thus, this analysis revealed the gene targets of leptin action, including Atf3, which represents a cellular mediator of leptin action.
Machine/Computer Approaches

The speaker recognition scene changes radically when attempts are made to apply modern technology to the problem. Indeed, with the seeming limitless power of electronic hardware and computers, it appears that solutions are but a step away. Yet such may not be the case. For example, many years have passed since the earliest efforts were made to develop machines that would (1) type letters dictated by voice, (2) automatically translate the speech of one language into another, (3) understand spoken speech and (4) identify a person from voice analysis alone. Authors such as Hecker (40) insist that there are no machines which are both as sensitive and as powerful (for these purposes) as the human ear. What Hecker means by “ear” is, of course, the entire auditory sensory system coupled to the brain, with all its sophisticated memory and cognitive functions. He may be correct in his assumptions, but I do not think so. Hence, the issue I will address in this chapter is: can machines/computers be made to operate at least as efficiently as the auditory system for speaker identification purposes? That is, can they be made to mimic these processes or, if not mimic them, at least parallel the recognition task by some other method? Probably so, but the task is not an easy one.
The Relevance of Multiculturalism for Aging

Though multiculturalists focus on race and minority status, issues of central importance to the aged, multiculturalism has not infiltrated the gerontology literature. However, since the so-called natural stages of life are cultural formations, each one a valuable creation, the topic of aging would certainly benefit from a connection to multiculturalism and its critique of the demands of assimilation.
The Turning Point Model State Public Health Act-Emergency Public Health Law versus Civil Liberties.

While the Model State Public Health Act does much to address inconsistent and outdated state legislation pertaining to infectious disease outbreaks and other public health emergencies, its current form has caused some concern about possible infringement of civil liberties. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.
Low-Carbohydrate Diets in the Treatment of the Metabolic Syndrome

In addition to physical activity, diet is a crucial component of lifestyle management. However, consensus as to which dietary approach is most efficacious remains elusive. Overall, energy restriction has been shown to consistently result in weight loss and to benefit adiposity-associated comorbidities, such as, dyslipidaemia, hypertension and insulin resistance. Lower carbohydrate intake results in relatively less insulin secretion to maintain normal glycaemia, which may be especially beneficial in someone who is resistant to insulin and/or has some insulin secretion abnormalities as is seen in the metabolic syndrome.
Revisiting “Organizational Abuses": Might Alleged Perpetrators be Victims?

Work-related attitudes and/or behaviors that harm other organizational members and/or the organization— thereby potentiating the onset or worsening of conflict or other consequences that threaten o...
The Price of Bread

A prime contemporary concern - how to maintain fair market relations - is addressed through this study of the regulation of bread prices. This was the single most important economic reality of Europe's daily life in the early modern period. Jan de Vries uses the Dutch Republic as a case study of how the market functioned and how the regulatory system evolved and acted. The ways in which consumer behaviour adapted to these structures, and the state interacted with producers and consumers in the pursuit of its own interests, had major implications for the measurement of living standards in this period. The long-term consequences of the Dutch state's interventions reveal how capitalist economies, far from being the outcome of unfettered market economics, are inextricably linked with regulatory fiscal regimes. The humble loaf serves as a prism through which to explore major developments in early modern European society and how public market regulation affected private economic life.
Fluid Transients in Flexible Piping Systems

Between 1970 and 1990 a substantial amount of research activity focused on understanding the mechanical interaction between unsteady flow in piping and the resulting vibration of the pipe elements and support structures. As a result, several analytical and numerical techniques were developed and reported. A primary motivation for this work emanated from the nuclear power industry, where a number of water hammer incidents and resulting pipe motion occurred. In the 1980’s, analytical methods were advanced to the point where dynamically coupled numerical predictions proved to be attainable without extensive complication.
Women Writers of Early Modern Spain: A Feminist Overview

Spanish women writers of the early modern period have consistently been undervalued owing to the lack of documentation available. New research, however, has uncovered many more female authors than previously known and has also dedicated time to the study of their historical context such as their education and social status. Women’s cultural production may thus be divided by religious and secular women, as well as by noble and non-noble women, although all contributed to such literary genres as poetry, novels, short stories, and plays. Women writers also took up the pen to write ego-documents such autobiographies, conventual foundational histories, and correspondence, and numerous women participated in literary academies and tournaments. Most importantly, however, women writers created and participated in their own lettered communities.
A baby with a widespread itchy rash.

A 7 month old baby presented to the dermatology clinic with a three month history of a widespread, itchy rash, predominantly on the trunk and limbs. The family’s general practitioner had prescribed topical steroids and oral antibiotics to treat the rash, to no avail. The baby was systemically well. On examination there was a widespread florid polymorphic eruption with erythematous papules, nodules, and coalescing plaques (fig 1). On the hands there were crusted papules over the metacarpophalangeal joints and web spaces. On the soles of both feet there were serpiginous tracts, and dermoscopy showed black dots. There was also facial involvement with a unilateral eruption …
Association between mortality rates and medication and residential treatment after in-patient medically managed opioid withdrawal: a cohort analysis.

Background and aim Medically managed opioid withdrawal (detox) can increase the risk of subsequent opioid overdose. We assessed the association between mortality following detox and receipt of medications for opioid use disorder (MOUD) and residential treatment after detox. Design Cohort study generated from individually linked public health data sets. Setting Massachusetts, USA. Participants A total of 30 681 opioid detox patients with 61 819 detox episodes between 2012 and 2014. Measurements Treatment categories included no post-detox treatment, MOUD, residential treatment or both MOUD and residential treatment identified at monthly intervals. We classified treatment exposures in two ways: (a) 'on-treatment' included any month where a treatment was received and (b) 'with-discontinuation' individuals were considered exposed through the month following treatment discontinuation. We conducted multivariable Cox proportional hazards analyses and extended Kaplan-Meier estimator cumulative incidence for all-cause and opioid-related mortality for the treatment categories as monthly time-varying exposure variables. Findings Twelve months after detox, 41% received MOUD for a median of 3 months, 35% received residential treatment for a median of 2 months and 13% received both for a median of 5 months. In on-treatment analyses for all-cause mortality compared with no treatment, adjusted hazard ratios (AHR) were 0.34 [95% confidence interval (CI) = 0.27-0.43] for MOUD, 0.63 (95% CI = 0.47-0.84) for residential treatment and 0.11 (95% CI = 0.03-0.43) for both. In with-discontinuation analyses for all-cause mortality, compared with no treatment, AHRs were 0.52 (95% CI = 0.42-0.63) for MOUD, 0.76 (95% CI = 0.59-0.96) for residential treatment and 0.21 (95% CI = 0.08-0.55) for both. Results were similar for opioid-related overdose mortality. Conclusions Among people who have undergone medically managed opioid withdrawal, receipt of medications for opioid use disorder, residential treatment or the combination of medications for opioid use disorder and residential treatment were associated with substantially reduced mortality compared with no treatment.
Ion Mobility and Gas-Phase Covalent Labeling Study of the Structure and Reactivity of Gaseous Ubiquitin Ions Electrosprayed from Aqueous and Denaturing Solutions.

Gas-phase ion/ion chemistry was coupled to ion mobility/mass spectrometry analysis to correlate the structure of gaseous ubiquitin to its solution structures with selective covalent structural prob...
Chapter 15 – Future Trends

Publisher Summary This chapter discusses the trends in sulfur research, industrial production, use, and. There are presently two key questions regarding energy. One concerns the balance between consumption and reserves; the other concerns the choice of the candidate material that will most likely prove to be the cheapest replacement for oil and gas. The chemistry will influence future events in many forms: the present and future research will determine the limits of the society's ability to produce, use, and recover sulfur, the theoretical limits of coal's utilization, and the society's ability to make maximum use of the beneficial properties of sulfur, or to limit the damage caused by inadvertent by-products. The chemical knowledge will determine the limit of the engineer's ability to translate currently available chemistry into practical, commercially viable processes; the judicious use of chemical facts by industry and government will determine the lowest possible energy price, and the physical quality of the environment.
Evaluation of 3-Dimensionality in Approved and Experimental Drug Space

The 3-dimensional (3D) structure of therapeutics and other bioactive molecules is an important factor in determining the strength and selectivity of their protein-ligand interactions. Previous efforts have considered the strain introduced and tolerated through conformational changes induced upon protein binding. Herein, we present an analysis of 3-dimentionality for energy-minimized structures from the DrugBank and ligands bound to proteins identified in the Protein Data Bank (PDB). This analysis reveals that the majority of molecules found in both the DrugBank and the PDB tend toward linearity and planarity, with few molecules having highly 3D conformations. Decidedly 3D geometries have been historically difficult to achieve, likely due to the synthetic challenge of making 3D organic molecules, and other considerations, such as adherence to the 'rule-of-five'. This has resulted in the dominance of planar and/or linear topologies of the molecules described here. Strategies to address the generally flat nature of these data sets are explored, including the use of 3D organic fragments and inorganic scaffolds as a means of accessing privileged 3D space. This work highlights the potential utility of libraries with greater 3D topological diversity so that the importance of molecular shape to biological behavior can be more fully understood in drug discovery campaigns.
Teaching Residents Communication Skills around Death and Dying in the Trauma Bay.

Abstract Background: Traumatic events are sudden, unexpected, and often devastating. The delivery of difficult news to patients and families in the trauma setting has unique challenges that necessi...
Revitalizing Urban America Through the EB-5 Immigrant Investor Program

The EB-5 Immigrant Investor Program was established by Congress in 1990 to spur economic development and job growth across the United States through foreign direct investment in American communities, job creation, and economic multipliers that stem from the migration of immigrant entrepreneurs and their families. To date, this program has been responsible for attracting billions of dollars of investment and creating thousands of jobs in the United States economy. This chapter analyzes the EB-5 Program as an economic development tool designed to revitalize urban America with capital raised from immigrant entrepreneurs. This chapter will provide an overview of the legislative intent of the EB-5 Program, which establishes the EB-5 Program as an important urban revitalization tool that can lead to positive social and economic outcomes. The author then examines an urban revitalization project in Brooklyn, NY, and argues that immigrant investors played a vital role in promoting sustainable economic development in and around the Brooklyn Navy Yard, a 300-acre industrial park located on the Brooklyn waterfront. This chapter closes with an examination of the future of the EB-5 Program and how policy changes could potentially impact the ability of the immigrant growth machine to continue to revitalize urban America.
Antitakeover provisions in corporate spin-offs.

We analyze the relation between antitakeover provisions (ATPs) and the performance of spin-off firms. We find that firms protected by more ATPs before spin-offs have higher abnormal announcement returns and greater improvements in post-spin-off operating performance than firms with fewer ATPs. Further, firms that reduce the number of ATPs after spin-offs have greater improvements in operating performance than firms that do not reduce the number of ATPs. Finally, CEOs of pre-spin-off firms tend to retain more ATPs in parent firms and assign fewer ATPs to the spun-off units if they remain as the CEOs of the parents but not the spun-off units. Overall, our results indicate a positive relation between ATPs and the value gains to spin-offs.
Societal Reentry of Prison Inmates With Mental Illness: Obstacles, Programs, and Best Practices.

Societal reentry from prison presents a wide array of extreme challenges to inmates attempting to reintegrate with society. This process is significantly more daunting for inmates suffering from me...