In the present thesis, the link between the genotype of the mouse and the concurrent phenotype is investigated employing sophisticated molecular and cellular techniques combined with in vivo cardiac performance measurements. In chapter 1 we focus on the characteristics of cardiac remodeling following an ischemic event in man. The characteristics of remodeling are thoroughly discussed through the results solely derived from studies in genetically modified mice. Despite the data available, intracellular signaling is still a mystery as we lack the tools to study several pathways simultaneously and maybe even more important the temporal changes in signaling cascade interactions.
In chapter 2 the molecular processes involved in cardiac hypertrophy are discussed. The concept of beneficial and maladaptive pathways is introduced and related to the detrimental transition of hypertrophy towards heart failure.
Open-chest and closed-chest protocols for in vivo left ventricular pressure-volume measurement are illustrated in chapter 3.We have chosen for closed-chest cardiac function assessment protocol in our ischemia-reperfusion studies, because of better systolic and diastolic performance, normal arterial-ventricular coupling and preservation of myocardial integrity.
To unravel the importance of specific signaling pathways (e.g. MEK1-ERK1/2 and calcineurin-NFAT) in ischemia-reperfusion-induced cell death techniques of transgenesis (e.g. MEK1 and GSK-3B transgenic mice) and gene targeting (e.g. ERK1 homozygous, ERK2 heterozygous and CnAB homozygous knockout mice) have been used. In chapter 4 we analyzed ERK1 homozygous knockout mice, ERK2 heterozygous knockout mice, and transgenic mice with activated MEK1-ERK1/2 signaling in the heart to determine a direct causal relationship between ERK1/2 signaling and cardioprotection. A direct cardioprotective role for ERK signaling in the heart following ischemia-reperfusion injury was demonstrated. In chapter 5 we investigate the role the calcium/calmodulin-activated protein phosphatase calcineurin plays in modulating cardiac apoptosis following acute ischemia-reperfusion injury in the heart. Calcineurin As (CnAB) gene targeted mice showed a greater loss of viable myocardium, more apoptosis, and a greater loss in functional performance following ischemia-reperfusion injury when compared to strain-matched wildtype control mice. Increased cell death was associated with a reduction of NFAT activity.
The study presented in chapter 6 was designed to elucidate the role of GSK-3B following ischemia-reperfusion. In GSK-3B transgenic mice, ischemia led to a larger infarct area and subsequent worsened cardiac performance, while post-ischemic hypertrophic remodeling was blunted.
In previous studies activation of both MEK1-ERK1/2 and calcineurin-NFAT signaling pathways were associated with hypertrophic cellular growth. The present thesis proves their involvement in anti-apoptotic protection against ischemia-reperfusion injury. The dualistic role of both resuscitative survival pathways in distinct pathogenic conditions as cardiomyocyte hypertrophy and apoptosis, is a fascinating observation. To further delineate the specific roles of individual survival pathways and investigate their potential use in clinical practice, future research should focus on studying multiple signaling cascades simultaneously and their interplay. A possible option is to cross-breed different genetically modified mice, thereby creating double knockout or knockout/transgenic mice. Another possibility could come from dynamic molecular imaging, through which protein function and interaction could be visualized. The treatment of cardiac ischemia will eventually be improved significantly through new developments in molecular science.


Real-time model-based deduction has recently emerged as a vital component in Al's tool box for developing highly autonomous reactive systems. Yet one of the current hurdles towards developing model-based reactive systems is the number of methods simultaneously employed, and their corresponding melange of programming and modeling languages. This paper offers an important step towards unification of reactive and model-based programming, providing the capability to monitor mixed hardware/software systems. We introduce RMPL, a rich modeling language that combines probabilistic, constraint-based modeling with reactive programming constructs, while offering a simple semantics in terms of hidden state Markov processes. We introduce probabilistic, hierarchical constraint automata, which allow Markov processes to be expressed in a compact representation that preserves the modularity of RMPL programs. Finally, a model-based executive, called RBurton is described that exploits this compact encoding to perform efficent simulation, belief state update and control sequence generation.


The evaluation of generic non-linear models for censored data needs to address the two complementary requirements in the software development life-cycle, of validation and verification. The former involves making a rigorous assessment of predictive accuracy in prognostic modelling and the latter is interpreted in this paper as comprising two different stages, namely model selection and rule-based interpretation of the composition of prognostic risk groups. With reference to prognostic performance is survival modelling the well-known ROC framework has recently been extended to a threshold independent, time-dependent performance index to quantify the predictive accuracy of censored data models, termed the C' index, which is briefly described. The rule-based framework for direct validation of risk group allocation against expert domain knowledge, uses low-order Boolean rules to approximate the response surfaces generated by analytical inference models. In the case of censored data, this approach serves to characterise the allocation of patients into risk groups generated by a risk staging index. Furthermore, the low-order rules define low-dimensional sub-spaces where individual data points can be directly visualised in relation to the decision boundaries for their risk group. Taken together, the quantitative performance index, Boolean explanatory rules and direct visualisation of the data, define a consistent and transparent validation framework based on triangulation of information. This information can be included in decision support systems.


Nanotechnology has demonstrated tremendous clinical utility, with potential applications in cancer immunotherapy. Although nanoparticles with intrinsic cytotoxicity are often considered unsuitable for clinical applications, such toxicity may be harnessed in the fight against cancer. Nanoparticle-associated toxicity can induce acute necrotic cell death, releasing tumor-associated antigens which may be captured by antigen-presenting cells to initiate or amplify tumor immunity. To test this hypothesis, cytotoxic cationic silica nanoparticles (CSiNPs) were directly administered into B16F10 melanoma implanted in C57BL/6 mice. CSiNPs caused plasma membrane rupture and oxidative stress of tumor cells, inducing local inflammation, tumor cell death and the release of tumor-associated antigens. The CSiNPs were further complexed with bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP), a molecular adjuvant which activates the stimulator of interferon genes (STING) in antigen-presenting cells. Compared with unformulated c-di-GMP, the delivery of c-di-GMP with CSiNPs markedly prolonged its local retention within the tumor microenvironment and activated tumor-infiltrating antigen-presenting cells. The combination of CSiNPs and a STING agonist showed dramatically increased expansion of antigen-specific CD8+ T cells, and potent tumor growth inhibition in murine melanoma. These results demonstrate that cationic nanoparticles can be used as an effective in situ vaccine platform which simultaneously causes tumor destruction and immune activation.


Bimetallic gold–iridium catalysts present a synergetic activity effect on the total oxidation of volatile organic compounds (e.g. toluene) with respect to their monometallic counterparts, leading to catalytic activity at lower temperatures. The enhancement of activity is facilitated by the intimate contact of the iridium and gold species, which modifies the electronic environment of the active sites, assisting in the oxygen activation at lower temperatures. In addition, the bimetallic system shows a considerably stronger metal–support interaction capable of diminishing the detrimental loss of activity associated with metal sintering at high reaction temperatures, in contrast to the monometallic cases whose activities are greatly lost. This paper contributes to the understanding of the key factors behind high activity and good stability of catalysts to achieve the low temperature activity of VOC compounds in air pollution remediation applications.


Abstract Practicing school psychologists were surveyed to determine if differences exist among practitioners in the various U.S. Census regions. The survey was completed by 1,056 practicing school psychologists representing all nine regions of the United States. Variability among the regions was noted for variables of (a) demographic characteristics, (b) current and preferred roles, (c) job satisfaction, (d) assessment practices, and (e) system reform beliefs and attitudes. The findings are discussed in the context of recent legislative changes and are compared to findings from previous national surveys of practicing school psychologists. Implications for future research and practice are also provided.


Achieving the health and well-being related Sustainable Development Goals (SDGs) and the World Health Organization's (WHO) Triple Billion Targets depends on informed decisions that are based on concerted data collection and monitoring efforts. Even though data availability has been increasing in recent years, significant gaps still remain for routine surveillance to guide policies and actions. The COVID-19 crisis has shown that more and better data and strengthened health information systems are needed to inform timely decisions that save lives. Traditional sources of data such as nationally representative surveys are not adequate for addressing this challenge alone. Additionally, the funding required to measure all health and well-being related SDG indicators and Triple Billion Targets using only traditional sources of data is a challenge to achieving efficient, timely and reliable monitoring systems. Citizen science, public participation in scientific research and knowledge production, can contribute to addressing some of these data gaps efficiently and sustainably when designed well, and ultimately, could contribute to the achievement of the health and well-being related SDGs and Triple Billion Targets. Through a systematic review of health and well-being related indicators, as well as citizen science initiatives, this paper aims to explore the potential of citizen science for monitoring health and well-being and for mobilizing action toward the achievement of health and well-being related targets as outlined in the SDG framework and Triple Billion Targets. The results demonstrate that out of 58 health and well-being related indicators of the SDGs and Triple Billion Targets covered in this study, citizen science could potentially contribute to monitoring 48 of these indicators and their targets, mostly at a local and community level, which can then be upscaled at a national level with the projection to reach global level monitoring and implementation. To integrate citizen science with official health and well-being statistics, the main recommendation is to build trusted partnerships with key stakeholders including National Statistical Offices, governments, academia and the custodian agencies, which is mostly the WHO for these health and well-being related targets and indicators.


Multi-local living and spatial interaction are expected to change the picture of regional development, as they emphasize the seasonal and interrelated use of areas. The article focusses on questions: What kind of spatial formation is the regional structure in Finland divided, and how common are these spatial formations in the regional structure? The results from the spatial cluster analysis show that the development of the regional structure is more diverse than previously known. Geographically, the dominating areas are seasonally growing areas which had remarkable increase in the seasonal use of areas. The results also showed that growth was more common in the regional structure than previously known, and the growth network extended from southern Finland to Lapland. The spatial formation of the stagnating areas was previously known to be narrower and more fragmented, as only a quarter of the surface area was classified as stagnating areas. The identifying of the diversity of the regional structure is essential for producing an exact picture of regional development for the needs of regional development and policy.


Urticaria and angioedema are characterized by pruritic hives and sometimes swelling of deeper mucocutaneous layers. Urticaria is caused by release of histamine and other mediators from mast cells. A cut-off of six weeks distinguishes acute and chronic forms, as these seem to differ regarding etiological and response patterns. Angioedema may be histaminergic or due to factors involving the bradykinin pathway. Medications such as ACE-Inhibitors or conditions affecting the C1-esterase inhibitor enzyme are potential causes. Acute urticaria may be related to triggers such as infections, medications or food allergy. When occurring with systemic symptoms and a temporal relationship to food or drug ingestion, IgE mediated allergy could be considered. Chronic Inducible Urticaria (CInd) is suspected on history and may be confirmed by provocation testing where physical and other specific trigger factors elicit the wheals. The term Chronic Spontaneous Urticaria (CSU) is used when symptoms persist for more than six weeks in the absence of inducible factors. A single cause is seldom found but a thorough history and clinical evaluation may elicit trigger factors and associated medical conditions such as auto-immune or thyroid disorders. Indiscriminate food allergy testing is unhelpful, but additive intolerance may be implicated in some cases. Modern non-sedating antihistamines are the mainstay of treatment, and omalizumab or immunosuppressives may be considered for refractory cases. Emotional support is needed as the condition is associated with psychological distress. If there are unusual features, vasculitis, auto-inflammatory or haematological conditions should be considered and skin biopsy or detailed immunological work-up may be indicated. Keywords: Angioedema, urticaria, chronic spontaneous, mast cells, pruritus, itch, histamine, hive, wheals, omalizumab


In our culture, which places such importance on technology, science, engineering, and mathematics, student success in mathematics courses continues to be a priority. However, many students are required to enroll in remedial or developmental mathematics courses during their post-secondary education. Many studies have been produced which show a wide variety of conclusions as to whether these remedial courses are effective. The fact is that, regardless of their effectiveness, the number of students who need to take these courses is unacceptable to education professionals. Built on concepts from developmental psychology, especially those of Jean Piaget, we formulated a hypothesis that the cause of these mathematical deficiencies in students is correlated to the students' cognitive development. We created an assessment consisting of a mathematical portion to test a student's proficiency and a psychological portion to determine at which stage of development a student is. It is the goal of this study to show a correlation between the levels of proficiency and cognitive development. While we did not find that correlation in our results, we did find a correlation between mathematical proficiency and college success as measured by grade point average. We also found a significant difference between one of the types of mathematical concepts assessed and the other two types of mathematical concepts. The specific concept is addition of fractions and the difference we found leads us to the iii conclusion that this portion of the assessment can be used in the future as a good discriminator of developmental level.


This paper examines to what extent art education, prices and standard socio-economic characteristics influence attendance at professional performing arts events (theatre, classical music, opera, ballet and dance). It distinguishes the influence such variables have on whether a person participates or not, from the effect that they have on the number of times a person decides to attend. The introduction of art education and price variables is likely to reduce the omitted variable bias present in previous empirical studies and improve estimations. Art education is highly correlated with participation, while it is not equally associated with frequency of attendance. Prices and geographical concentration are generally not correlated with participation, however there are large differences among art forms and economic resources appear to be relevant in the case of classical music. Policy makers can use information on what results can be expected from policies aimed at reducing prices or increase art education in the population in their attempt to improve attendance and increase access to the performing arts.


Magnesium hydroxide, Mg(OH)2, has great potential for CO2 capture and storage (CCS) as it can capture CO2 in aqueous and solid systems. However, the utilisation of Mg(OH)2 for CCS has been hindered due to its rare occurrence in mineral deposits, and Mg silicate minerals, despite their slow kinetics of carbonation, have been the prime focus of the investigations for CO2 sequestration owing to their abundance in nature.
In the present study, the extraction of Mg(OH)2 from Mg silicate minerals was investigated in NaOH aqueous and solid systems. The effective extraction of Mg(OH)2 from Mg silicate minerals is beneficial because it would offer not only a large CO2 storage capability but also a faster kinetics of carbonation. The direct alkaline-based extraction of Mg(OH)2 is also beneficial, as the acidic extraction commonly used requires the addition of an alkaline reactant to favour the precipitation of Mg(OH)2 and successive carbonation process.
81% yield of Mg(OH)2 extraction was achieved from dunite, an ultramafic rock mainly composed of Mg silicate minerals, reacted with NaOH aqueous systems. Despite the high efficiency of extraction, the large amount of NaOH consumed was identified as a potential obstacle for the implementation of the process.
Dunite was reacted with NaOH solid systems aiming the reduction of NaOH usage. The consumption of NaOH in solid systems was effectively reduced by 94.5 – 97% respect to the aqueous systems, maintaining significant rates of Mg(OH)2 extraction (65 – 73%). The H2O consumption was also reduced or avoided.
Mg(OH)2 carbonation was investigated in aqueous and solid systems. A significant fraction of Mg(OH)2 was converted into hydromagnesite Mg5(CO3)4(OH)2·4H2O when reacted with added H2O under supercritical CO2. The dissolution of Mg in the products from Mg(OH)2 extraction significantly improved respect to Mg silicate minerals previously tested without alkaline pre-treatment. CO2 was captured from a gas mixture of CO2 and N2 at ambient conditions using an aqueous slurry of Mg(OH)2. Mg(OH)2 and CO2 dissolved in H2O and reacted by forming soluble Mg(HCO3)2 which remained in solution under controlled pH.


SUMMARY: In contrast to other members of the influenza virus group, a strain of fowl plague virus produced large amounts of intracellular haemagglutinin in the chorioallantoic membranes of infected chick embryos. The titres of intracellular haemagglutinin obtained with the fowl plague virus were 400-2000-fold higher than those of the human influenza viruses tested. The fowl plague virus also differed from the human influenza viruses in being capable of growing through the chorioallantoic membrane when inoculated by the chorionic route. The only other myxovirus so far discovered that elicited a high intracellular haemagglutinin titre was Newcastle disease virus, although this type of virus is neither serologically nor morphologically related to the influenza viruses.
Electron microscopic investigations of membrane specimens from embryos infected with fowl plague virus showed the presence of a large number of structures, ranging in size from 300 A to more than 7000 A, with a surface configuration indistinguishable from that of the envelope component of typical particles. Similar structures were found very rarely in specimens of membranes infected with the human influenza viruses.


Despite continued high HIV risk among Hispanic men who have sex with men (HMSM), culturally tailored, theoretically based interventions have yet to be developed and tested. As a first step toward intervention development, we collected quantitative and qualitative data on sociocultural and psychological factors associated with drug use and risky sex among 566 HMSM recruited from community and Internet venues. Participants reported high rates of drug use (43%), unprotected anal sex (45%), and multiple sex partners (median 4) in the past 6 months. In multivariate analyses, use of drugs was associated with HIV seropositivity, less orientation to the Hispanic community, stronger attachment to the gay community, lower levels of homophobia, higher numbers of sex partners and more unprotected anal sex. The need for acceptance and desire to please partners emerged as core drivers of HIV risk in the qualitative data. Findings were used to guide development of Proyecto SOL, a theoretically grounded intervention that targets core determinants of HIV risk, builds on protective cultural influences, and strengthens positive social connections.


The UC Davis research involved a 24-month study (including a 4-month measurement program) in the Salton Sea to directly measure sediment resuspension using an array of OBS instruments and an acoustic wave height and current profiling instrument (AWAC). The data provided by these instruments, in conjunction with existing UC Davis temperature recording instruments in the Sea and the existing CIMIS meteorological network, point to the existence of a quasi-equilibrium condition for the suspension of sediments in the lake. Non-linear relations were developed between the wind intensity and turbidity near which were in relative agreement with relationships from reviewed literature. In particular, the extended Garcia and Parker formulation with DLM-WQ shows the best prediction to describe the seasonal trends as well as short-term variations. The relationship was incorporated into the existing DLM-WQ model. DLM-WQ, combined with this new sediment model, was used to more fully explore the potential for ecological restoration of the Salton Sea under possible future configurations. Two scenarios, the North Sea Combined Alternative and South Sea Combined Alternative, as suggested by PEIR were examined. The simulation of North Sea Combined Alternative indicates that the Marine Sea might have a better eutrophic status than that of the whole Sea because of fewer sediment resuspension events due to lower average wind speed acting on a smaller surface. On the other hand, the simulation of South Sea Combined Alternative suggested that the concentrations of nutrients in the water column would be the same or higher than those of the whole Sea, because of more sediment resuspension events due to higher average wind speed and due to shallower water depth. In the both alternatives, however, the anoxia in the hypolimnion would be spatially and temporally increased due to increased stratification periods, during which time toxic substances (such as hydrogen sulfide) and organic materials could be accumulated in the sediments. DLM-WQ with the new sediment algorithm successfully accounts for the dominant processes that control eutrophication in the current Salton Sea and provides an indication of variations in properties that could be expected in potential future configurations. In addition to being a tool for comparing future configurations, DLM-WQ provides a basis for designing future monitoring needs.


Procedural material graphs are a compact, parameteric, and resolution-independent representation that are a popular choice for material authoring. However, designing procedural materials requires significant expertise and publicly accessible libraries contain only a few thousand such graphs. We present MatFormer, a generative model that can produce a diverse set of high-quality procedural materials with complex spatial patterns and appearance. While procedural materials can be modeled as directed (operation) graphs, they contain arbitrary numbers of heterogeneous nodes with unstructured, often long-range node connections, and functional constraints on node parameters and connections. MatFormer addresses these challenges with a multi-stage transformer-based model that sequentially generates nodes, node parameters, and edges, while ensuring the semantic validity of the graph. In addition to generation, MatFormer can be used for the auto-completion and exploration of partial material graphs. We qualitatively and quantitatively demonstrate that our method outperforms alternative approaches, in both generated graph and material quality.


The antiviral cytokine interferon-λ cures persistent norovirus infection in mice. Norovirus causes >90% of the world's gastroenteritis. Norovirus can establish persistent infections, which may contribute to its spread. How does norovirus establish itself as a permanent resident of the gut and how can such persistent infections be cured (see the Perspective by Wilks and Golovkina)? Baldridge et al. studied mice persistently infected with norovirus and found that viral persistence required the gut microbiota (resident bacteria in the gastrointestinal tract). Antibiotics prevented persistent mouse norovirus infection in a way that depended on the secreted antiviral protein interferon-λ (IFN-λ). Nice et al. report that IFN-λ can cure mice persistently infected with norovirus, independent of the adaptive immune system. M. T. Baldridge, T. J. Nice, B. T. McCune, C. C. Yokoyama, A. Kambal, M. Wheadon, M. S. Diamond, Y. Ivanova, M. Artyomov, H. W. Virgin, Commensal microbes and interferon-λ determine persistence of enteric murine norovirus infection. Science 347, 266–269 (2015). [Abstract] [Full Text] T. J. Nice, M. T. Baldridge, B. T. McCune, J. M. Norman, H. M. Lazear, M. Artyomov, M. S. Diamond, H. W. Virgin, Interferon-λ cures persistent murine norovirus infection in the absence of adaptive immunity. Science 347, 269–273 (2015). [Abstract] [Full Text] J. Wilks, T. Golovkina, Interfering with interferons. Science 347, 233–234 (2015). [Summary] [Full Text]


Introduction: Previous studies provide relevant information about the relationship between personality and eating disorders (ED). The involvement of personality factors in the etiology and maintenance of ED indicates the need of emphasizing the study of the adolescent's personality when diagnosed of ED. Objectives: The aims of this study were to analyze the adolescent's personality profiles that differ significantly in anorexia nervosa (AN) and bulimia nervosa (BN), and to explore the most common profiles and their associations with those subtypes of eating disorders (ED). Methods: A total of 104 patients with AN and BN were studied by means of the Millon Adolescent Clinical Inventory (MACI). Results: The personality profiles that differ significantly in both AN and BN were submissive, egotistic, unruly, forceful, conforming, oppositional, self-demeaning and borderline. The most frequent profiles in AN were conforming (33.33%), egotistic (22.72%) and dramatizing (18.18%) while in the case of BN those profiles were unruly (18.42%), submissive (18.42%) and borderline (15.78%). We did not find any associations between the diagnostic subgroup (AN, BN) and the fact of having personality profiles that could become dysfunctional. Conclusions: Bearing in mind these results, it may be concluded that there are relevant differences between personality profiles associated with AN and BN during adolescence, so tailoring therapeutic interventions for this specific population would be important.


$^{a}$ Part of the research reported in this paper was performed at the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration.


A bistable micro-mechanical system based on magnetic repulsion is presented exploring its applicability as memory unit where the state of the bit is encoded in the rest position of a deflected cantilever. The non-linearity induced on the cantilever can be tuned through the magnetic interaction intensity between the cantilever magnet and the counter magnet in terms of geometrical parameters. A simple model provides a sound prediction of the behavior of the system. Finally we measured the energy required to store a bit of information on the system that, for the considered protocols, is bounded by the energy barrier separating the two stable states.


We analize a discrete type version of a common agency model with informed principals of Martimort and Moreira (2005) in the context of lobby games. We begin discussing issues related to the common values nature of the model, i.e.the agent cares directly about the principal's utility function. With this feature the equilibrium of Martimort and Moreira (2005) is not valid. We argue in favor of one solution, although we are not able to fully characterize the equilibrium in this context. We then turn to an application: a modification of the Grossman and Helpman (1994) model of lobbying for tariff protection to incoporate assimetric information (but disconsidering the problem of common values) in the lobbies objective function. We show that the main results of the original model do not hold and that lobbies may behave less agressively towards the police maker when there is private information in the lobbies valuation for the tariffs.


This study focused on knowledge and perception of farmers on information and communication technology (ICT) use in Ife Central Local Government Area of Osun State. A pretested and validated interview schedule was used to source information from 150 farmers selected through a multi-stage sampling procedure. Descriptive and inferential statistical tools were used to analyze the data collected. The result revealed among others, that the mean age of the respondents was 47.29 years, while the mean income was 505,600 Naira. Furthermore, majority (76.0%) of the farmers had a low awareness of ICT use, while majority (76.0%) of the farmers had a low knowledge of ICT. Also, majority (84.7%) of the farmers had an indifferent perception on ICT use. Number of year of formal education of farmers, knowledge on ICT and perception on ICT use explained 38.8% of the change in farmers' awareness on ICT in the study area. The study recommended that anytime programme that should improve the awareness of farmers' on ICT is being planned, the significant variables should be considered.

 Key words: Knowledge, perception, information communication technology, farmers.


Galactic outflows are believed to play an important role in regulating star formation in galaxies, but estimates of the outflowing mass and momentum have historically been based on uncertain assumptions. Here, we measure the mass, momentum, and energy outflow rates of seven nearby star-forming galaxies using ultraviolet absorption lines and observationally motivated estimates for the density, metallicity, and radius of the outflow. Low-mass galaxies generate outflows faster than their escape velocities with mass outflow rates up to twenty times larger than their star formation rates. These outflows from low-mass galaxies also have momenta larger than provided from supernovae alone, indicating that multiple momentum sources drive these outflows. Only 1-20\% of the supernovae energy is converted into kinetic energy, and this fraction decreases with increasing stellar mass such that low-mass galaxies drive more efficient outflows. We find scaling relations between the outflows and the stellar mass of their host galaxies (M$_\ast$) at the 2-3$\sigma$ significance level. The mass-loading factor, or the mass outflow rate divided by the star formation rate, scales as M$_\ast^{-0.4}$ and with the circular velocity as v$_\mathrm{circ}^{-1.6}$. The scaling of the mass-loading factor is similar to recent simulations, but the observations are a factor of five smaller, possibly indicating that there is a substantial amount of unprobed gas in a different ionization phase. The outflow momenta are consistent with a model where star formation drives the outflow while gravity counteracts this acceleration.


Tinted eyeglasses were selected for 768 poor-sighted patients aged 5-86 years with various ocular diseases. The frequency of tinted glasses utilization by poor-sighted patients was as follows: filter O2 was the optimal for 38% patients, filters G2 and K4 for 16-18%, and G1 for 11% patients. Filter G1 improved visual acuity by 19%, filters G2 and K4-K5 by 23%; the highest increment of visual acuity was observed with O2 filter: by 27%. Filters of different spectral characteristics and density may be useful in the same underlying ophthalmic disease, which is explained by the underlying disease and the presence, combinations, and severity of concomitant ocular diseases.


The paper considers Web services (WS). WS comprises a set of platform-neutral technologies designed to ease the delivery of network services over intranets and the Internet. Cross-platform capabilities are one of WS's key attractions because interoperability has been a dream of the distributed computing community for years. The paper lists some WS Web sites and discusses Java-based initiatives.


Future developments of end corona protection (ECP) systems require calculation of the electrical field strength along the insulating surface and the temperature profile with satisfactory accuracy. This report presents an approach for the exact calculation of relevant physical parameters for a typical ECP configuration based on the finite element method, this approach accounting for the large electrical nonlinearity as well as the weaker thermal nonlinearity of the ECP material. The peculiarities of the implemented calculation algorithm for modeling the electrically and thermally coupled system are presented and the function of the model is verified based on practical tests which confirm the extremely good correlation between the calculated and measured results.


The solar modulation effect of cosmic rays in the heliosphere is an energy-, time-, and particle-dependent phenomenon that arises from a combination of basic particle transport processes such as diffusion, convection, adiabatic cooling, and drift motion. Making use of a large collection of time-resolved cosmic-ray data from recent space missions, we construct a simple predictive model of solar modulation that depends on direct solar-physics inputs: the number of solar sunspots and the tilt angle of the heliospheric current sheet. Under this framework, we present calculations of cosmic-ray proton spectra, positron/electron and antiproton/proton ratios, and their time dependence in connection with the evolving solar activity. We report evidence for a time lag months, between solar-activity data and cosmic-ray flux measurements in space, which reflects the dynamics of the formation of the modulation region. This result enables us to forecast the cosmic-ray flux near Earth well in advance by monitoring solar activity.


We present valence-to-core x-ray emission spectroscopy of Ti, TiO and TiO2 by means of a double crystal von Hamos spectrometer based on full-cylinder highly-annealed pyrolytic graphite mosaic crystals. We demonstrate that, using a double crystal configuration, an energy resolution of E/ΔE ≈ 2700 can be achieved in a compact setup using cylindrically curved optics with a radius of curvature of 50 mm. The stated energy resolution proved to be high enough to identify and determine chemical shifts of the Kβ2,5 and Kβ" emission lines of both oxides. The experimental results are supported by calculations with the ab initio package OCEAN and compared to literature values.


This paper seeks to establish if top management (the board) of a firm should extend its overview of the governance process to the execution of strategy (i.e., strategic governance) and, if so, does the management accounting information system (MAIS) have a role in facilitating this strategy execution process. This study investigated the role of the board and MAIS in strategic governance by examining a company with a public record of both successful governance and integrated strategic management accounting processes in a high‐risk industry. The analysis demonstrates that boards should go beyond the minimum conformance (compliance) requirements of the governance‐regulatory legislation and assume ultimate responsibility for strategy execution and enterprise performance. However, while management accounting techniques, processes and reports were found to be used extensively in strategic governance to integrate the policy‐management interface in numerous conformance–performance domains, the traditional role of the management accountant was found to be limited in terms of their role in such governance. The study demonstrates that a more strategic governance role offers the management accountant a way back into senior management by using the routines of management accounting to socialize the board and curb any opportunism that may arise.


Endovascular brachytherapy has proven to be an effective tool in the reduction of restenosis following balloon angioplasty for coronary heart disease, while the range of optimal doses and precise target tissue are still unknown. However, over-dosing has been associated with increased thrombogenicity and permanent damage to vessel walls. Under-dosing has been found to stimulate neointima formation, causing restenosis. It has been suggested that restenosis near the edges (edge effect) of the intervention may be caused by the dose falloff towards near the source ends. Monte Carlo code EGS4 was used to calculate the dose distribution around the ends of a Guidant /sup 32/P source. At the ends of the source the 100% isodose curve was found to bend back toward the source starting at about 3 mm from the end of the active source (prescription to 2 mm radius). The 80% isodose line crossed the prescription line 1 mm from the source ends. Further calculations predicted improvement can be achieved by changing the specific activity within 1 mm of the ends of the source. A four-fold increase in specific activity in 0.5 mm segments at the ends of the source, followed by a 0.5 mm gap between the ends and the middle part of the source, kept the 100% isodose line at the prescription distance to within 0.5 mm of the active length of the source without any over-dosing. With five times the activity in the terminal segments, a "full length source" is achieved, involving a small over-dosing.


Many passive margins experience pulsed exhumation events late in their history as a result of plate boundary distal geodynamic mechanisms or climatic events. The onset of late Cenozoic glaciation, often associated with enhanced rates of erosion, is one such possible cause of passive margin rejuvenation. However, along passive margins the effectiveness of Plio-Pleistocene glaciers at eroding the landscape may be limited by low tectonic rock uplift rates or as a result of erosionally inefficient cold based continental ice-sheets. In this dissertation the evolution of post-orogenic topography and the effect of glaciations on denuding landscapes along the North Atlantic Passive Margin, in the White Mountains of New Hampshire and the western Scottish Highlands, was investigated. Background exhumation rates averaged over 10 yr timescale were determined using apatite (U-Th)/He thermochronology. To resolve whether or not a change in exhumation rate occurred coincident with glaciation these background exhumation rates were compared to magnitudes of erosion averaged over the glacially relevant 10 yr timescale using the in situ terrestrial cosmogenic nuclide Be. In chapter two, 10 yr timescale exhumation and burial histories across the western Scottish Highlands were determined. The results show that post-orogenic burial and exhumation is mostly a result of plate margin distal tectonic and magmatic factors that are variable across short distances (i.e., <100 km). In chapter three, patterns and magnitudes of erosion during glaciation and following deglaciation in the Scottish Highlands were investigated. The results indicate that polythermal glacial erosion denuded low elevation portions of the Scottish Highlands and preserved summits. This produced relief but did not significantly lower the maximum elevation of the landscape. Following deglaciation Scotland's sediment budget remains dominated by glaciogenic sediment. In the fourth chapter, magnitudes of background exhumation in the Presidential and Carter Ranges of the White Mountains, New Hampshire were compared to magnitudes of glacial erosion. The results indicate that most relief was produced prior to glaciation and that background exhumation rates in the Cenozoic are low (<0.01 mm yr). In the late-Cenozoic, coldbased glaciation prevented an acceleration of erosion in the White Mountains. The postglacial sediment budget is made up of dominantly glaciogenic sediment. Overall, the main findings of this dissertation are; (1) post-orogenic burial, exhumation, and relief production are mainly the result of spatially heterogeneous plate margin distal vertical crustal motions; (2) cold-based ice limits the magnitudes of late Cenozoic glacial erosion across passive margins covered by large continental ice sheets; and (3) post-glacial sediment budgets continue to be dominated by glaciogenic sediment, >10 ka after deglaciation. Post-Orogenic Exhumation and Glacial Erosion on the Flanks of the North Atlantic


This
paper discusses the "Hubble constant measurement—mystery". Independent
measurements of this cosmic parameter, referred to as H0 in abbreviated form, have all led to different
values, with the highest value ≈ 74 km·s-1·Mpc-1 and the
lowest ≈ 67 km·s-1·Mpc-1, where km denotes kilometer, s
second and Mpc-1 megaparsec. These measurements have mainly been
obtained with space telescopes. Apparently, up to now there was no way to
explain the differences. However, previously published studies seem to regard
the problem of the different measurement results for H0 [1, 2]. I have shown
that due to a symmetrical expansion of the Minkowski space (SMS), each
respective frame of reference for an observer, who rests in the zero point of
the frame, is converted into a state of apparent rest relative to the cosmic
microwave background (CMB) radiation. This SMS-relativistic effect also seems
to be responsible for the different measurement results of the Hubble constant,
especially through space telescopes.


The Outgoing Council Meeting of the Paleontological Society (PS) was called to order by President William I. Ausich on 1 November 2003 at 19:00 hrs in the Douglas Room of the Sheraton Seattle Hotel. Attending were Council members Patricia H. "Tricia" Kelley, David J. Bottjer, Mark E. Patzkowsky, Carl W. Stock, Steven M. Holland, Mark A. Wilson, Russell D. "Tim" White, Dale A. Springer, Ann F. "Nancy" Budd, Jonathan M. Adrain, William A. DiMichele, Alycia L. Rode, Christopher J. Crow, Scott M. Ritter, Rex A. Hanger, and Thomas Olszewski. Danita Brandt, Peter J. Harries, and Roger D. K. Thomas were also present.

Bill Ausich presented the President's report. He first thanked the many people who served the PS in the past year, who were leaving their positions, including members of Council and of various PS committees. Ausich then made a series of announcements. He has resisted participating in the Council of Scientific Society Presidents' meeting, an expensive activity. The American Geological Institute (AGI) careers brochure is complete, and a copy of it will be included with our journals. The PS is now a "Tier I" supporter of Paleontologia Electronica. He thanked the Mid-America Paleontology Society for their contributions of $2,000 for the Gould Student Grant Fund, and $100 toward the Harrell Strimple Award Fund. The paleontology initiative started by the National Park System appears dormant. Colin Sumrall will represent the PS at a workshop at the Florida State Museum on the "Decadal Vision of Taxonomy and Natural History Collections." President Ausich and Mark Patzkowsky will attend a workshop on the "Teaching of Paleontology in the 21st Century."

Mark Patzkowsky presented the Treasurer's report. Total assets at the end of 2002 were $1,594,872, a decrease of $54,944 from 2001. Income for 2002 was $470,440, and expenses were $431,586. He pointed out …


Preface. 1. CHANGING DEFINITIONS OF THE NEWS. A compact history of the news media. The English and Colonial press. The Federalists and Anti-Federalists, the Abolitionist press, the yellow press. The news in wartime. Changes in politics and the press. Current and future trends in the news. How each medium defines the news today and why. 2. BASIC STRUCTURES FOR MEDIA WRITING. Basic structures for news story for print, broadcast and public relations. The inverted pyramid. The magic formula. Pyramid problems. Glass shapes. Chronological order. Key subject blocks. Nutgraphs, anecdotes, quote blocks, sound bites and others. 3. TROUBLE-SPOTS. A close look at trouble-spots including noun/pronoun and noun/verb agreement, misplaced modifiers, tense shifts, misused words and phrases, parallel construction problems, cliches, jargon and more. 4. LEADS FOR MEDIA WRITING. The importance of importance. Types of leads for print and broadcast. Breaking out of the boxes. The six questions. 5. RESEARCH FOR MEDIA WRITING. Basic research and reporting skills. Sources for research information. Good and bad questions. Databases and their uses and limitations. 6. INTERVIEWING SKILLS FOR MEDIA WRITERS. PHUFA. Basic interviewing skills for print, broadcast, public relations and the Internet. Daily and non-daily interviewing skills. Phone interviewing skills. The non-verbal aspects of interviewing. Fairness and accuracy. How to use quotes in your copy. 7. REPORTING AND WRITING THE FEATURE STORY. Defining a feature. News features and independent features. Special reporting needs for various kinds of features. Features for newspapers. Features for magazines. Freelancing and competition. 8. RESEARCH AND WRITING SKILLS FOR OPINION WRITING. Defining the various kinds of opinion writing. Research for opinion writing. Structures for opinion writing. 9. REPORTING AND WRITING FOR BROADCAST. Getting the news. Formats. Differences from print. Keep it simple. Dealing with numbers. Blocking and counter-blocking. 10. WRITING FOR THE WEB. Good journalism is still good journalism. Special reporting and writing needs for web writer. Adapting to the new technology. Current limits and the wide-open future. 11. REPORTING AND WRITING FOR PUBLIC RELATIONS. Practicing good public relations. Internal and External writing. Feature approaches. Deadlines. Length. Locality. Find the angle. Other needs. 12. RESEARCH AND WRITING FOR ADVERTISING COPYWRITING. It"s not just creativity. Writing for audiences. Stay aware. HUBBA, HUBBA. Motivation. Advertorials and other issues. 13. EDITING AND REVISION FOR MEDIA WRITERS. Basic techniques for editing and revising your own work for print and broadcast. Advice on how to work with an editor. Get TRICI. Samples of stories from first draft to publication. 14. LEGAL AND ETHICAL CONCERNS. Freedom of speech and its limitations. Libel. Commercial speech. Broadcast regulations. Ethics. Copyright. Words of warning. Appendix A: Codes of Ethics. Ethical codes from organizations including the Society of Professional Journalists, the American Association of Advertising Agencies, the Public Relations Society of America, and others. Appendix B: Spelling, Punctuation, Capitalization for Journalists. A guided tour through some of the more troublesome areas of journalism grammar and style. Numerous examples of problems and their solutions. Includes lists of commonly misspelled words, common capitalization problems, and common punctuation problems. Appendix C: Ready for Anything. How to build a career in traditional and new media writing. Job skills. Pay scales. Start preparing now. Internships. Job possibilities. Predicting the media"s future. Glossary.


For over 300 years, Britain has influenced Scotland's national identity. Scottish Highland dress, which consists of kilts and tartans has been appropriated, manipulated, and transformed by the British in order to forward political, commercial, and social objectives. Scotland's national dress has contributed to a more cohesive identity within the United Kingdom. However, available research only examines specific instances of British influence on—and usage of—kilts and tartans. The purpose of this study was to identify and explore a sample of key figures and historical events that illustrate the use of Scottish Highland dress to forward British interests. The researchers triangulated databases and secondary literature along with extant objects and materials, with the aim of developing a more holistic understanding of appropriation, manipulation, and transformation. Findings indicate how the context and usage of Scottish Highland dress was transformed over time.


Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, robust microgliosis, neuroinflammation, and neuronal loss. Genome‐wide association studies recently highlighted a prominent role for microglia in late‐onset AD (LOAD). Specifically, inositol polyphosphate‐5‐phosphatase (INPP5D) is selectively expressed in brain microglia and one of its common intronic variants (rs35349669; OR=1.08, 95%CI=1.06‐1.11) has been reported to be associated with increased risk of LOAD. INPP5D is linked to the triggering receptor expressed on myeloid cells 2 (TREM2) signaling, but little is known about the function of INPP5D in microglia and how INPP5D regulates TREM2‐related AD pathogenesis. Therefore, we aim to understand the role of INPP5D in microglia and AD pathology.


Route guidance process is the dynamic game-based process of traffic authority and users, users' behavior is affected by the guidance information and it also affect guidance effect. On the basis of analysis of user equilibrium and system optimum, a game theory model between traffic authority and users is presented, and system optimum and user optimum guidance strategy are given. Simulation results show that: user optimum guidance strategy will bring oscillation of traffic flow, system optimum guidance strategy is optimal but difficult to achieve, and coordination of system optimum and user optimum is close to system optimum strategy.


Abstract. Lizard activity patterns are restricted by both intrinsic and extrinsic variables. The Mexican Plateau Horned Lizard (Phrynosoma orbiculare) is endemic to México and an ambush forager and viviparous species that becomes dormant during the cooler months. The objective of this study was to determine the spatiotemporal activity patterns of P. orbiculare and the environmental conditions related to its occurrence in the natural protected area Statal Park Sierra Morelos, State of Mexico, México. We conducted samplings during 2018 and 2019. We assessed temporal activity patterns with Watson's U2 test to determine differences in activity hours between age classes, sexes, and seasons, and we evaluated spatial activity patterns through a hotspot analysis. We conducted a logistic regression model by using landsat 8 bands and indices as independent variables. Differences in temporal activity patterns (activity timing) were detected between age classes and seasons (in the juvenile group) but not between sexes. Within the natural protected area, P. orbiculare aggregated in solar glades. There is an important contribution of ultrablue and blue landsat bands to P. orbiculare occurrence. Differences in activity between age classes could be related to the heat acquisition rate of smaller individuals; meanwhile, no differences between sexes suggests that the thermal optima of females are similar to male optima. Hotspot analysis and the distribution model reveal that P. orbiculare appears on the windward slope where sunrise occurs. Solar glades are important for the species occurrence and should be protected in the studied area. These data allow future monitoring studies to help prevent population declines and illegal extraction.


Dynamic optimal problems (DOPs) are often encountered in target search, emergency rescue, and object tracking. Motivated by the need to perform a search and rescue task, we clarify a DOP in a complex environment if a target unpredictably travels in an environment with general non-Gaussian distributed and time-varying noises. To solve this issue, we propose a recursive Bayesian estimation with a distributed sampling (RBEDS) model. Furthermore, two kinds of communication cooperative extensions, i.e., real-time communication and communication after finding the target, are analyzed. To balance between exploitation and exploration, an adaptive online co-search (AOCS) method, which consists of an online updating algorithm and a self-adaptive controller, is designed based on RBEDS. Simulation results demonstrates that searchers with AOCS can achieve a comparable search performance with a global sampling method, e.g., Markov Chain Monto Carlo estimation, by applying real-time communication. The local samples help searchers keep flexible and adaptive to the changes of the target. The proposed method with both communication and cooperation exhibits excellent performance when tracking a target. Another attractive result is that only a few searchers and local samples are demanded. The insensibility to the scale of samples makes the proposed method obtain a better solution with less computation cost than the existing methods.


IMPORTANCE
The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study.

OBJECTIVE
To perform chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic yield of these tests in a sample typical of a developmental pediatric clinic.

DESIGN, SETTING, AND PARTICIPANTS
The sample consisted of 258 consecutively ascertained unrelated children with ASD who underwent detailed assessments to define morphology scores based on the presence of major congenital abnormalities and minor physical anomalies. The children were recruited between 2008 and 2013 in Newfoundland and Labrador, Canada. The probands were stratified into 3 groups of increasing morphological severity: essential, equivocal, and complex (scores of 0-3, 4-5, and ≥6).

EXPOSURES
All probands underwent CMA, with WES performed for 95 proband-parent trios.

MAIN OUTCOMES AND MEASURES
The overall molecular diagnostic yield for CMA and WES in a population-based ASD sample stratified in 3 phenotypic groups.

RESULTS
Of 258 probands, 24 (9.3%, 95%CI, 6.1%-13.5%) received a molecular diagnosis from CMA and 8 of 95 (8.4%, 95%CI, 3.7%-15.9%) from WES. The yields were statistically different between the morphological groups. Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic etiology was 15.8% (95%CI, 9.1%-24.7%; 15/95 children). This included 2 children who received molecular diagnoses from both tests. The combined yield was significantly higher in the complex group when compared with the essential group (pairwise comparison, P = .002). [table: see text].

CONCLUSIONS AND RELEVANCE
Among a heterogeneous sample of children with ASD, the molecular diagnostic yields of CMA and WES were comparable, and the combined molecular diagnostic yield was higher in children with more complex morphological phenotypes in comparison with the children in the essential category. If replicated in additional populations, these findings may inform appropriate selection of molecular diagnostic testing for children affected by ASD.


A variety of mining and analysis problems --- ranging from association-rule discovery to contingency table analysis to materialization of certain approximate datacubes --- involve the extraction of knowledge from a set of categorical count data. Such data can be viewed as a collection of "transactions," where a transaction is a fixed-length vector of counts. Classical algorithms for solving count-data problems require one or more computationally intensive passes over the entire database and can be prohibitively slow. One effective method for dealing with this ever-worsening scalability problem is to run the algorithms on a small sample of the data. We present a new data-reduction algorithm, called EASE, for producing such a sample. Like the FAST algorithm introduced by Chen et al., EASE is especially designed for count data applications. Both EASE and FAST take a relatively large initial random sample and then deterministically produce a subsample whose "distance" --- appropriately defined --- from the complete database is minimal. Unlike FAST, which obtains the final subsample by quasi-greedy descent, EASE uses epsilon-approximation methods to obtain the final subsample by a process of repeated halving. Experiments both in the context of association rule mining and classical χ2 contingency-table analysis show that EASE outperforms both FAST and simple random sampling, sometimes dramatically.


Summary Genetic sources of phenotypic variation have been a focus of plant studies aimed at improving agricultural yield and understanding adaptive processes. Genome‐wide association studies identify the genetic background behind a trait by examining associations between phenotypes and single‐nucleotide polymorphisms (SNPs). Although such studies are common, biological interpretation of the results remains a challenge; especially due to the confounding nature of population structure and the systematic biases thus introduced. Here, we propose a complementary analysis (SNPeffect) that offers putative genotype‐to‐phenotype mechanistic interpretations by integrating biochemical knowledge encoded in metabolic models. SNPeffect is used to explain differential growth rate and metabolite accumulation in A. thaliana and P. trichocarpa accessions as the outcome of SNPs in enzyme‐coding genes. To this end, we also constructed a genome‐scale metabolic model for Populus trichocarpa, the first for a perennial woody tree. As expected, our results indicate that growth is a complex polygenic trait governed by carbon and energy partitioning. The predicted set of functional SNPs in both species are associated with experimentally characterized growth‐determining genes and also suggest putative ones. Functional SNPs were found in pathways such as amino acid metabolism, nucleotide biosynthesis, and cellulose and lignin biosynthesis, in line with breeding strategies that target pathways governing carbon and energy partition.


A Mesozoic to Paleogene polyphase tectonic model presented here for the southern United States (U.S.) Cordillera provides new insight into style and timing of Mesozoic–Paleogene deformation and basin formation in the region south of the Colorado Plateau and Mogollon-Datil volcanic field. The model proposes reverse reactivation of Jurassic normal faults during Late Cretaceous Laramide shortening. It also recognizes late Paleogene east-west– and northwest-southeast–trending normal faults formed during a north-south extensional event that postdated Laramide shortening and preceded Neogene Basin and Range extension. Late Jurassic to Early Cretaceous extension generated northwest-southeast normal faults that formed part of the Border rift system that extended from southern California to the northwestern Gulf of Mexico. The normal faults cut Mesoproterozoic basement rocks, and localized subsequent uplift of basement rocks during Late Cretaceous fault reactivation that formed northwest-southeast–trending Laramide uplifts of southwest New Mexico and southeastern Arizona. The Hidalgo uplift, reconstructed here from structural relations in the Little Hatchet and Big Hatchet Mountains of southwestern New Mexico, is bound by bivergent reverse faults that resulted from tectonic inversion of a Jurassic–Early Cretaceous graben. The Hidalgo uplift is flanked to the north by the Campanian to earliest Maastrichtian Ringbone basin, which accumulated synorogenic continental strata and basaltic andesite flows from ca. 75 to 70 Ma. The Ringbone basin was converted from a subsiding basin in the Little Hatchet Mountains to a volcanic center by ca. 69 Ma, the emplacement age of an assemblage of shallow, subvolcanic intrusions termed the Sylvanite plutonic complex. The basement-involved structural style and yoked intermontane basin resemble other Laramide uplifts and basins in the Rocky Mountain Cordillera and refute alternative Laramide models of strikeslip faulting or regionally extensive horizontal thrust faults in southwestern New Mexico, the latter of which fail to account for basement-cored uplifts. A significant difference with the Rocky Mountain Laramide province is the size of the uplifts and basins and the close association of southern U.S. Cordilleran structures to nearby Late Cretaceous magmatic centers, which contributed to interstratified volcanic and volcaniclastic rocks in the basin fill. Upper Eocene–Oligocene ignimbrites and volcaniclastic rocks of the Boot Heel volcanic field of southwestern New Mexico unconformably overlie Laramide syntectonic strata and bury eroded Laramide structures. The distribution of the Paleogene volcanic rocks in the Little Hatchet and Big Hatchet Mountains is in part controlled by synmagmatic east-west and northwest-southeast normal faults active from ca. 34 to 27 Ma, the age range of rhyolite dikes intruded along the faults. Two generations of intrusive rocks occupy these normal faults in the Little Hatchet Mountains: (1) older (ca. 34 Ma) phaneritic stocks and dikes in the central and southern parts of the range, and (2) younger (31–27 Ma) aphanitic latite and rhyolite dikes. East-west–trending faults and dikes are cut by north-south faults formed during Basin and Range extension. The late Eocene–early Oligocene north-south extension provides an important minimum age limit for Laramide shortening, which ended prior to ca. 34 Ma.


A pot experiment was conducted in the net house of the Department of Agricultural Chemistry, Bangladesh Agricultural University, Mymensingh to evaluate the influence of phosphorus (P) and sulphur (S) on major nutrient contents and their uptake by brinjal (cv. BARI brinjal-8) during the period from October, 2011 to May, 2012. The experiment was laid out in a completely randomized design with 12 treatments and 3 replications using four levels of P (0, 30, 60 and 90 kg P ha-1) and three levels of S (0, 15 and 30 kg S ha-1) along with the basal doses of urea, muriate of potash, boric acid, zinc oxide, cowdung and poultry manure. The study revealed that major nutrient contents and their uptake were significantly influenced by P and S interactions. They had positive significant effects on major nutrient contents and their uptake. Application of P increased N, P, K, Ca, Mg and S contents and their uptake upto 60 kg ha-1 and over the dose the values were reduced or near to control treatment. Similarly, the gradual increases of major nutrient contents and their uptake were found in S application upto 30 kg ha-1. Among the treatments the combination of P @ 60 kg ha-1 and S @ 30 kg ha-1 showed the highest N, P, K, S, Ca and Mg contents and their uptake. The lowest values were found in control treatment. Results showed that an appropriate interaction of P and S increased major nutrient contents of brinjal.


We have investigated the Josephson radiation from different types of YBa2Cu3O7 (YBCO) thin-film Josephson junctions: step-edge junctions (SEJs), biepitaxial junctions and SNS junctions with N=Au. The radiation was detected using a non-resonant radiometer system with a receiving frequency of 11-12 GHz. The current-voltage characteristics were measured simultaneously with the radiation spectra in the temperature range 4.2-90 K. All junctions exhibited a large emission peak at a voltage which was related to the frequency through the second Josephson relation. Typically, for high temperatures, and therefore small critical currents, the measured radiation linewidth agreed well with the theoretical predictions. At lower temperatures the experimental linewidths deviated from the theoretical values due to additional noise sources in the junctions. Some of the SEJs showed a non-monotonic dependence of the linewidth on temperature. It is suggested that such SEJ data may be discussed in terms of a model which treats the SEJ as an interferometer consisting of a parallel array of random Josephson junctions.


Due to the increasing usage of machine learning (ML) techniques in security- and safety-critical domains, such as autonomous systems and medical diagnosis, ensuring correct behavior of ML systems, especially for different corner cases, is of growing importance. In this paper, we propose a generic framework for evaluating security and robustness of ML systems using different real-world safety properties. We further design, implement and evaluate VeriVis, a scalable methodology that can verify a diverse set of safety properties for state-of-the-art computer vision systems with only blackbox access. VeriVis leverage different input space reduction techniques for efficient verification of different safety properties. VeriVis is able to find thousands of safety violations in fifteen state-of-the-art computer vision systems including ten Deep Neural Networks (DNNs) such as Inception-v3 and Nvidia's Dave self-driving system with thousands of neurons as well as five commercial third-party vision APIs including Google vision and Clarifai for twelve different safety properties. Furthermore, VeriVis can successfully verify local safety properties, on average, for around 31.7% of the test images. VeriVis finds up to 64.8x more violations than existing gradient-based methods that, unlike VeriVis, cannot ensure non-existence of any violations. Finally, we show that retraining using the safety violations detected by VeriVis can reduce the average number of violations up to 60.2%.


The existing literature on information disclosure commonly assumes full commitment to truthful disclosure and therefore revelations are always credible, which can be quite unrealistic in many circumstances. This thesis mainly contributes to the literature by studying information disclosure in the form of cheap-talk in auctions and monopoly pricing, which allows for mis-reporting and false disclosure. The thesis is composed mainly of three research papers. The first paper (Chapter 2), also the major chapter of this thesis, investigates cheap-talk information disclosure in auctions, where bidders' preferences are horizontally differentiated. The seller may reveal information of product attributes before the auction, and the disclosure policy is characterized by a partition of the attribute space. In a symmetric setting, I first show that informative equilibria reveal the feature that more precise information is provided for less popular product attributes. Second, I prove an equilibrium existence theorem that an informative equilibrium can be supported by an information partition of any degree, as long as the number of bidders is sufficiently large. And finally, the optimal disclosure policy reveals a complementarity relationship between the number of bidders and the optimal degree of equilibrium partitions. In this chapter, optimal information structure is endogenously determined. In the second paper (Chapter 3), I turn to study how a monopoly seller should reveal a product's horizontal attributes, when consumer preferences conform to a mixture distribution. I show that the optimal disclosure policy largely depends on the characteristics of the mixture distribution. Specifically, when consumer preferences are highly heterogenous, it is better for the seller to reveal information and serve different groups of consumers separately. And when the preference distribution becomes more asymmetric, cheap-talk disclosure is more likely to be dominated by no disclosure at all. In this chapter, information structure is taken as given. The third paper (Chapter 4) studies optimal regulation of risk-averse producers, in a setting of complementary production with independent cost realization. The production can be organized in the form of either component, or integrated production. I show in this paper that the relative virtues of these two forms of production depend on the degree of risk aversion of the producers.


. In reflecting upon the role of environmental capital as represented by old towns in smart cities, the author reveals the consequences of re-plastering the facade of ancient buildings while emphasizing the resulting risk of globalization of historic districts. This is followed by a critical consideration concerning the active protection of old towns and their cultural typicality and geographical context, prerequisites for the development of specific guide-lines for the European Union. Explanation is also provided about how the restoration dynamics of the old towns are irreversibly changing the urban landscape in European cities. Strict regulations regarding the preservation of European old towns will become increasingly essential to preserve local cultures and material authenticity.


An essential goal of program evaluation and scientific research is the investigation of causal mechanisms. Over the past several decades, causal mediation analysis has been used in medical and social sciences to decompose the treatment effect into the natural direct and indirect effects. However, all of the existing mediation analysis methods rely on parametric modeling assumptions in one way or another, typically requiring researchers to specify multiple regression models involving the treatment, mediator, outcome, and pre-treatment confounders. To overcome this limitation, we propose a novel nonparametric estimation method for causal mediation analysis that eliminates the need for applied researchers to model multiple conditional distributions. The proposed method balances a certain set of empirical moments between the treatment and control groups by weighting each observation; in particular, we establish that the proposed estimator is globally semiparametric efficient. We also show how to consistently estimate the asymptotic variance of the proposed estimator without additional efforts. Finally, we extend the proposed method to other relevant settings including the causal mediation analysis with multiple mediators.


A low-density parity-check (LDPC) code can be described by a Tanner graph composed of symbol nodes and check nodes. Short cycles in the Tanner graph should be avoided because such cycles will degrade the performance of the decoder and hence increase the error rate. In most of the circumstances, cycles of length 4 can be totally eliminated in the Tanner graph when the LDPC code has been designed properly. Locally, for each variable node in the Tanner graph, the girth may take the value of 6 or 8, or even higher. In this study, the authors attempt to increase the local girths of a Tanner graph with an aim to improving the error performance of the code. The authors propose and analyse the 'degree spectrum' of the symbol nodes connecting to each of the check nodes. Based on the analysis, the authors can determine if the local girths can be further increased. The authors also propose simple ways to construct codes with higher local girths. Finally, the authors show the characteristics and the error performance of the codes constructed with the proposed methods.


The incidence of posterior shoulder dislocation ranges between 2 and 5% of glenohumeral dislocations. The mechanisms most frequently involved are trauma, grand-mal seizures and electrocutions. This lesion remains a diagnostic trap, due to paucity or even lack of clinical signs, and to the apparent normality of the anteroposterior radiograph of the shoulder. Nevertheless, careful clinical examination and an axillary radiograph often allow for a correct diagnosis. We report a case of traumatic posterior dislocation, unnoticed for 7 weeks. A satisfactory functional adaption of the dislocated shoulder to everyday life and the general condition of the patient lead us to select the notreatment option.


Transmembrane tryptase (TMT)/tryptase γ is a membrane-bound serine protease stored in the secretory granules of human and mouse lung mast cells (MCs). We now show that TMT reaches the external face of the plasma membrane when MCs are induced to degranulate. Analysis of purified recombinant TMT revealed that it is a two-chain neutral protease. Thus, TMT is the only MC protease identified so far which retains its 18-residue propeptide when proteolytically activated. The genes that encode TMT and tryptase βI reside on human chromosome 16p13.3. However, substrate specificity studies revealed that TMT and tryptase βI are functionally distinct even though they are ∼50% identical. Although TMT is rapidly inactivated by the human plasma serpin α1-antitrypsin in vitro, administration of recombinant TMT (but not recombinant tryptase βI) into the trachea of mice leads to airway hyperresponsiveness (AHR) and increased expression of interleukin (IL) 13. T cells also increase their expression of IL-13 mRNA when exposed to TMT in vitro. TMT is therefore a novel exocytosed surface mediator that can stimulate those cell types that are in close proximity. TMT induces AHR in normal mice but not in transgenic mice that lack signal transducer and activator of transcription (STAT) 6 or the α-chain of the cytokine receptor that recognizes both IL-4 and IL-13. Based on these data, we conclude that TMT is an exocytosed MC neutral protease that induces AHR in lungs primarily by activating an IL-13/IL-4Rα/STAT6-dependent pathway.


The preferred orientation of mica in dolomitic slaty siltstone units from Lady Loretta, Queensland, Australia, and its relation to grain size and shape show that the larger, thicker grains have (001) subparallel to bedding, and the thinnest grains have (001) parallel to cleavage. The overall mica orientation depends primarily on bedding-cleavage angle; it bears little relation to bulk composition within the restricted range observed. The shapes of quartz dolomite–rich blebs in two of the specimens have been measured to determine the orientation and shape of their finite strain ellipsoid. The λ 1 λ 2 plane of this ellipsoid is at a low angle to the mica (001) preferred orientation defining the slaty cleavage. This is interpreted to be due either to a difference in strain between the blebs and their matrix, or to the operation of a mica-orienting mechanism that is not related rigorously to the finite strain. Predominantly mechanical orienting mechanisms are considered to be incompatible with the bimodal orientation and grain shape of mica. It is suggested that there was a well-defined preferred orientation in bedding, imposed during diagenesis, and that the cleavage mica grew with a strong preferred orientation during the deformation. A mechanism for this growth control similar to that proposed by Etheridge and others (1974) is favored.


Hellekant, G. and Y. Kasahara. Secretory fibres in the trigeminal pa'.rt of the lingual nerve to the mandibular salivary gland of the rat. Acta physiol. scand. 1973. 89. 198–207.

The nerve supply to and the secretion from the mandibular salivary gland of the rat have been studied. It was found that a) secretory fibres are given off from the chorda-lingual nerve on its peripheral course until it reaches the mandibular and sublingual ducts, b) secretion of saliva was observed and secretion could be evoked even when the facial portion of the chorda-lingual nerves was cut. The flow did not stop until its trigeminal portion was also cut, c) the cessation of secretion after the trigeminal portion was cut was not the result of a loss of sensory impulses to the CNS, d) impulses could also be recorded fiorn the nerve fibres given off from the chorda-lingual nerve to the gland after its facial portion was cut; e) electrical stimulation of the peripheral part of the trigeminal portion elicited secretion, which was generally larger than that in response to stimulation of the facial portion. Simultaneous stimulation of both portions gave the largest secretion, f) no difference between the sodium and potassium concentrations in saliva elicited by stimulation of the two nerve portions was observed. Atropine blocked the secretion caused by stimulation of any of the nerves.


The paper is an attempt to review twenty-first century regionalism and its impact on South Asia, which includes the rising role of China and Pakistan's pivot status as contributing factors to peace, growth, and development. This coincides with a more south-oriented world. The theory applied is NeoFunctionalism, which explains the European integration and may be used to explain the potential modern South Asian integration process with China as a pre-cursor. This will perhaps be a positive outcome of the twenty-first century regionalism. The paper dwells upon intra-regional integration, sighting Eurasian model of connectivity as an example, and how it can be a role-model for developing countries. The emphasis remains on improved relations between Pakistan and India as a pre-requisite for regionalism to take off in South Asia.


Modern industrial quality monitoring systems are based on optical fibre sensors, microelectronic sensory technology and miniaturized infrared spectroscopy systems based on low-power, low-cost, high-efficient and innovative hardware solutions. The proposed paper presents development work related to create remote control system for monitoring water pollution petrochemical products using optical fibre refractometer.


Abstract : This report develops robust signal processing architectures and algorithms specifically designed to achieve multi-aperture coherence on transmit and receive. A key feature of our approach is the use of orthogonal radar waveforms that allow the monostatic and bistatic target returns to be separated at each receiver's matched filter output. By analyzing these returns, we may determine the appropriate transmit times and phases in order to cohere the various radar apertures using both narrowband and wideband waveforms. This process increases the array gain on receive to N2 instead of N for the single transmitter case. Furthermore, when full coherence on transmit is achieved, the array gain is N3. The performance of our coherence algorithms is quantified using Monte Carlo simulations and compared to the Cramer-Rao lower bound. A computational complexity study shows that our aperture coherence algorithms are suitable for a real-time implementation on an SGI Origin 3000 multi-processor computer.


Reports of transcatheter treatment for dual drainage of an abnormal pulmonary venous connection are rare. Presently described is the case of a 27-year-old female with exertional dyspnea and a partial anomalous pulmonary venous connection of the left upper pulmonary vein with dual drainage to a vertical vein (VV) and the left atrium. The patient was evaluated with a balloon occlusion test to determine whether closing the anomalous VV connection would increase pulmonary pressure. The results of this test are an important guide to treatment decisions. A 12x9 mm Amplatzer Vascular Plug II device was successfully used to occlude the anomalous pulmonary venous connection using a transcatheter technique. This is a less invasive option than surgical repair and can be an appropriate choice in suitable cases.


Nonlinear Stochastic Processes addresses the frequently-encountered problem of incomplete information. The causes of this problem considered here include: missing measurements; sensor delays and saturation; quantization effects; and signal sampling. Divided into three parts, the text begins with a focus on H filtering and control problems associated with general classes of nonlinear stochastic discrete-time systems. Filtering problems are considered in the second part, and in the third the theory and techniques previously developed are applied to the solution of issues arising in complex networks with the design of sampled-data-based controllers and filters. Among its highlights, the text provides: a unified framework for filtering and control problems in complex communication networks with limited bandwidth; new concepts such as random sensor and signal saturations for more realistic modeling; and demonstration of the use of techniques such as the HamiltonJacobiIsaacs, difference linear matrix, and parameter-dependent matrix inequalities and sums of squares to handle the computational challenges inherent in these systems. The collection of recent research results presented in Nonlinear Stochastic Processes will be of interest to academic researchers in control and signal processing. Graduate students working with communication networks with lossy information and control of stochastic systems will also benefit from reading the book.


CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy camptothecin, is a well-known DNA topoisomerase I inhibitor. SN-38 is a metabolite of this compound. Both emit fluorescence when activated by a laser beam. With a confocal laser scanning microscope (CLSM), we determined the intracellular distribution of CPT-11 and SN-38 and the chronological changes in drug-treated PC-7, a cell line of human non-small cell lung cancer, and its CPT-11 resistant variant, PC-7/CPT cells. There were many more granules in the cytoplasm in PC-7/CPT than in the parent cell line (PC-7). The granule formation of the resistant cell could indicate a different drug metabolism in the cytoplasm from that of the parent cell. This technique would provide a new way of investigating the mechanism of resistance of cancer cells to anticancer drugs.


The method of net energy analysis has been applied to coal, fission, and fusion power plants. Energy consumption over the lifetime of the plants has been calculated for construction, operation and maintenance, fuel, public welfare, and land use and restoration. Thermal and electric energy requirements were obtained separately for each energy consuming sector. The results of the study are presented in three ways: total energy requirements, energy gain ratio, and payback periods. All three types of power plants are net producers of energy. The coal and fusion power plants are superior to fission plants from the energy efficiency point of view. Fission plants will improve considerably if the centrifuge replaces the gaseous diffusion as a method of enrichment.


A quantitative exploratory and descriptive study was carried out in the Hhohho region of Swaziland to describe the practices of managing menstrual hygiene by secondary school girls in boarding public schools. The researchers' curiosity was raised by the fact that, it was observed in a few schools that menstrual waste disposal was poorly managed. The study aimed at describing the manner at which the boarding school girls managed menstrual hygiene in order to recommend strategies to improve on the way they handled menstrual hygiene. Specifically, it investigated the methods used to contain, store, transport and dispose of menstrual waste and also ascertained the problems associated with the disposal of such wastes in the boarding schools. The data showed that, 100% of the girls use sanitary napkins for containing the menstrual blood and flush toilets were the main sanitary facilities that were provided by the schools. Menstrual wastes were mainly collect in bins placed in the toilets as 89% of the respondents indicated so. A large proportion (64%) of the respondents said the bins were collected on daily basis and the contents are burned in open spaces provided in the school premises as reported by 61.7% of the participants. It is concluded that menstrual hygiene is not properly managed by boarding secondary school girls as the current handling of such wastes exposes the girls and waste handlers to blood borne disease, the open burning pollutes the air and the blood being wet, could result in incomplete burning and thus threaten surface water sources. It is recommended that Government should integrate menstrual hygiene in WASH programmes in schools and the open burning of such wastes should be replaced by disposing them of in sanitary landfills or by incineration.


Using a sample of 48 emerging and developing countries in the 1970–2012 period, we investigated the interactions between the stock of sovereign debt and the quantity of corporate external borrowing. We found that public external debt hinders private-sector access to external loan and bond markets. By contrast, the stock of private debt in international financial markets exerts a positive influence on public external debt from all sources except other private creditors. We also found the incidence of bank crises, capital account openness and the rate of economic growth to be among the macroeconomic variables that have a significant impact on both public and private external debts.


This paper enlightens the significance of learner-centered approaches to language teaching. In an English as a Foreign Language (EFL) class, a teacher should adopt a specific teaching style to accomplish teaching goals. This study is an attempt to analyze and ascertaining the general principles and techniques of teaching EFL. The principal aim of the study is to highlight the needs of the learners and help the teachers to achieve their teaching goals with the planned learning outcome. The Eclectic Method of language teaching was introduced in the class to improve the communication skills and the academic performance of the learners. The Eclectic Method was pioneered in 1970 and gradually became very popular in English as a Second Language (ESL) and EFL classrooms. The Eclectic Method is a fusion of distinctive techniques of teaching and language learning approaches. This Method enables the language teachers to make it to all the learners despite the heterogeneity in their learning styles and intelligence. The author has used a Mixed Method Approach. The target group is female undergraduate students in the College of Science for Girls, King Khalid University, Abha, Kingdom of Saudi Arabia (KSA). After implementing an Eclectic Method in the language classroom, the author finds that it helps in blending multiple activities of language learning. It allows students to receive individual attention amid a populated class. It further makes the students feel more motivated and confident. The result of the study prompted that the learners have improved significantly in all the four skills: Listening, Speaking, Reading and Writing (LSRW) of language learning. The study signifies that the Eclectic Method works productively for every level of learners and makes learning easy and ingenious. The best part of this method is the teacher can design his/ her own teaching techniques based on the Proficiency and the competency of the learners to make learning more effective.


Background: Synadenium glaucescens and Commiphora swynnertonii are among the reported plants used traditionally for treatment of bacterial infections. This study reports antibacterial effects of single and combined extracts from leaves, stem and root barks of Commiphora swynnertonii and Synadenium glaucescens. Materials and Methods: Plants were collected from Manyara and Njombe regions in Tanzania. Extraction was done using dichloromethane and methanol. The extracts were assessed for antibacterial activity against Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa). Minimum Inhibitory Concentrations (MIC) was determined by broth microdilution, while Fractional Inhibitory Concentration (FIC) indices were calculated from MIC values of combined extracts to determine combination effects. Results: Strong antibacterial activities were demonstrated by all extracts of S. glaucescens (MIC 0.011-0.375mg/mL) against Gram-positive bacteria and methanol extracts of C. swynnertonii (MIC 0.047-0.375mg/mL). Synergistic effect was observed when combining methanol extracts of C. swynnertonii stem bark with S. glaucescens leaves against S. aureus (∑FIC 0.5), Other synergistic effects were observed against E. faecalis with dichloromethane extracts of C. swynnertonii stem bark and S. glaucescens stem bark (∑FIC 0.5), and C. swynnertonii root bark and S. glaucescens root bark (FIC index 0.3). For the remaining combinations, mainly additive effects were observed. Conclusion: Synergistic effects on bacteria were observed by combining different plant parts of S. glaucescens and C. swynnertonii suggesting that it could be beneficial to combine such extracts when used for antibacterial purposes.


ABSTRACT Culture fluids after growth of Mycobacterium bovis BCG on Sauton medium contain actively secreted proteins and proteins released by bacterial lysis. BCG culture fluids and sonicates ofMycobacterium tuberculosis and Mycobacterium paratuberculosis were tested after separation by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The localization of marker proteins was determined by enzyme-linked immunosorbent assay and Western blotting with selected monoclonal antibodies of known specificities. Soluble secreted proteins (MPB64 and proteins of the antigen 85 complex) and three heat shock proteins (DnaK, GroEL, and GroES) were recovered in a single peak after gel filtration, indicating their occurrence as a free monomer in the culture fluid and cytosol, respectively. Other constituents eluted in two distinct peaks during gel filtration. The first peak corresponded to the void volume, indicating complex formation between several proteins or attachment to lipids in the surface layer or the cytoplasmic membrane; the second peak corresponded to the expected monomer size indicated by SDS-PAGE under conditions that separate proteins from each other during sample preparation. The two-peak group contained constituents with known lipid contents, the 19- and 38-kDa lipoproteins and lipoarabinomannan. The 26-kDa form of MPB83 behaved similarly. After extraction with Triton X-114, these constituents entered into the detergent phase, confirming the lipoprotein nature of 26-kDa MPB83. The MPB83 molecule was shown to be available on the surface of BCG Tokyo bacilli for reaction with monoclonal antibody MBS43 by flow cytometry.


Daily variations in plasma (PcAMP), urine (UcAMP), nephrogenous cAMP (NcAMP) and hormones known to affect cAMP metabolism were studied. Circadian variations in PTH (1-84) and NcAMP were observed. Both increased significantly overnight and early morning. PcAMP and glucagon decreased overnight and following meals. PcAMP had greater fluctuations over 24h than glucagon indicating several hormones have transient effects on PcAMP production.
A 7h shift of the sleep-wake cycle moved sleep-associated prolactin secretion but caused minimal alteration in PTH (1-84). NcAMP secretion overnight decreased, suggesting PTH (1-84) end organ responses may be modified by other hormones and effectors when sleep is disturbed. PcAMP decreased overnight reaching a nadir corresponding to the lowest glucagon concentration. PcAMP fluctuations were greater when compared to normal 24h profiles.
Following a 96h fast serum phosphate, PTH (1-84) and NcAMP circadian rhythms were attenuated. Mean serum calcium and NcAMP production were significantly decreased. Fasting increased variability in PTH (1-84) secretion which may be an important signalling mechanism inducing bone resorption. Serum phosphate fluctuations may play an important role in the genesis of PTH (1-84) and NcAMP circadian rhythms. Mean glucagon concentration was increased with attenuation of the circadian rhythm and mean PcAMP concentration increased. Dissociation of bone and kidney effects of PTH (1-84) in fasting may be due to acute acidosis.
In 1°HPT the concerted overnight increase in PTH (1-84) and NcAMP was absent. Parathyroid adenoma resection restored phosphate, PTH (1-84) and NcAMP circadian rhythms. The phosphate increase may stimulate PTH (1-84) secretion which then influences the phosphate rhythm. Mean PcAMP was increased in 1°HPT but 24h PcAMP profiles differed little pre and post surgery.
24h studies indicate control of the circadian rhythms of PTH (1-84), NcAMP and PcAMP is complex. Several hormones act in concert to regulate cAMP generation and end organ responses.
Thyrotoxic patients had mean PTH (1-84) and NcAMP lower than normals, hypothyroid and treated hypothyroid patients. Increased serum calcium decreases PTH (1-84) and subsequently NcAMP in thyrotoxicosis. In hypothyroid patients PTH (1-84) and NcAMP are dissociated with mean PTH (1-84) increased compared to thyrotoxic patients but NcAMP remained similar to euthyroid subjects indicating resistance to PTH (1-84) . Thyroxine treated patients have mean PTH (1-84) concentrations lower than euthyroid controls with a relatively increased NcAMP. PcAMP is increased in thyrotoxic and thyroxine treated patients and decreased in hypothyroid patients.
Synacthen increased PcAMP with the pattern similar to the cortisol profile. This was either due to simultaneous release of cAMP and cortisol following adrenal stimulation or was a direct effect of cortisol. Dexamethasone decreased NcAMP and UcAMP with a variable effect on PcAMP. Variability in the PcAMP response is probably due to combined effects of dexamethasone and cortisol whereas decreased UcAMP and NcAMP production may represent altered kidney cell sensitivity to PTH (1-84) caused by decreased cortisol.
In 1°HPT patients a significant correlation between PTH (1-84) and NcAMP exists (r=0.66, p<0.001). A subgroup of 1°HPT patients have NcAMP inappropriately high for the measured PTH (1-84). Two patients had increased PTHrP but in the majority PTHrP was low and the discrepancy was unexplained. In three patients PcAMP concentration was lower than expected. Twelve 1°HPT patients, divided equally, received atenolol or placebo and were studied prospectively for 6 months. No significant effect of atenolol on any parameter was observed.
In patients with Paget's disease treated with bisphosphonate (APD) calcium decreased, PTH (1-84) and NcAMP increased significantly. Patients with HCM prior to therapy with APD had a suppressed or low PTH (1-84) . A high percentage had elevated NcAMP indicating the presence of a circulating humoral factor, probably PTHrP, causing hypercalcaemia. APD therapy in HCM patients resulted in a significant reduction in serum calcium. No patient developed significant hypocalcaemia. PTH (1-84) secretion was stimulated as serum calcium decreased and PTH (1-84) was detectable or elevated whilst some patients remained hypercalcaemic. The absolute concentration rather than rate of decrease of serum calcium was more important in regulating PTH (1-84) secretion. NcAMP correlated poorly with PTH (1-84) in treated HCM patients. An increase then decrease in NcAMP was observed associated with a decrease then increase in TmP04 indicating PTHrP may increase transiently following APD therapy.
PTHrP measurement confirmed the hormone's role in the aetiology of HCM and a strong correlation of PTHrP with NcAMP. In HCM patients with breast, lung and kidney malignancy PTHrP secretion commonly results in elevated NcAMP. Patients with HCM and haematological, gastrointestinal and ear-nose-throat malignancies have low circulating PTHrP and normal or low NcAMP. Squamous cell carcinomas commonly secrete PTHrP. 78% of normals had detectable PTHrP which may reflect sample collection into protease inhibitor tubes, age distribution of the normal,population, assay sensitivity and properties of the assay antibodies. Alternatively the assay may be subject to nonspecific binding effects or matrix effects. A subgroup of patients was detected with low PTHrP and low PTH (1-84) with inappropriate or elevated NcAMP. These patients may be producing a factor which stimulates NcAMP production. This factor (s) may be a fragment of PTHrP or PTH not recognised by the IRMAs or may be a new molecule causing hypercalcaemia mediated via cAMP.
Superfusion of rat renal tubules was used to study cAMP production in response to PTH stimulation. Optimal conditions producing a consistent, reproducible cAMP response were identified. Tubules were equilibrated on columns for 90 min, prior to stimulation with 2.5 units bovine PTH (1-84) at 10 min intervals. A significant decrease in cAMP production in response to PTH was observed when tubules were perfused with buffer acidic (pH 7.1) relative to normal physiological pH (pH 7.4). Perfusion with buffer relatively alkalotic (pH 7.65) had no significant effect on PTH stimulated cAMP production. 7mM arginine hydrochloride in the perfusate significantly decreased cAMP production. Superfusion of rat renal tubules was a reliable, reproducible method for studying the action of PTH.