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Many of the hypotheses advanced in discussions of economic development and growth of nations should also be applicable to regions within a nation. This paper is concerned with testing three such hypotheses in the case of the growth of the Pacific Northwest, a region that is heavily dependent upon the export of crude and processed primary products. The first hypothesis is that foreign trade (external trade) tends to decline as a proportion of total product or output as economic growth takes place. The second is that specialization in primary products means that growth will necessarily be slow relative to more industrialized areas. The third hypothesis is that an economy is subject to relatively great instability if its exports are large compared to total output, and if its exports are concentrated in primary products.

Among dominant neurodegenerative disorders, Huntington’s disease (HD) is perhaps the best candidate for treatment with small interfering RNAs (siRNAs) [1–9]. Invariably fatal, HD is caused by expansion of a CAG repeat in the Huntingtin gene, creating an extended polyglutamine tract that makes the Huntingtin protein toxic [10]. Silencing mutant Huntingtin mRNA should provide therapeutic benefit, but no siRNA strategy can yet distinguish among the normal and disease Huntingtin alleles and other mRNAs containing CAG repeats [11]. siRNAs targeting the disease isoform of a heterozygous single-nucleotide polymorphism (SNP) in Huntingtin provide an alternative [12–16], because such siRNAs should preserve expression of normal Huntingtin, which likely contributes to neuronal function [17–19]. We sequenced 22 predicted SNP sites in 225 human samples corresponding to HD and control subjects. We find that 48% of our patient population is heterozygous at a single SNP site; one isoform of this SNP is associated with HD. Several other SNP sites are frequently heterozygous. Consequently, five allele-specific siRNAs, corresponding to just three SNP sites, could be used to treat three-quarters of the United States and European HD patient populations. We have designed and validated selective siRNAs for the three SNP sites, laying the foundation for allele-specific RNAi therapy for HD.

Twenty patients with dissection of the thoracic aorta were studied by CT-scanning. In 9 patients the diagnosis was previously documented by aortography, while in the other 11 patients the diagnosis of aortic dissection was first established by CT-scanning. The latter demonstrated the characteristic signs of aortic dissection and particularly the following features: a) the false channel (95%) and the intimal flap (90%), b) the displacement of aortic wall calcifications (60%), especially when the false channel is partially thrombosed (80%). In 19 patients, a bolus injection of contrast medium was performed. In the majority of cases opacification of the false channel occurred only partially, with some delay and with a non-homogeneous pattern. Six out of the 20 patients underwent one or more follow-up examinations performed between 15 days and 2 years later. CT-scanning clearly demonstrated the late persistence of a patent false channel and particularly the delayed thrombosis, even after surgical treatment of aortic dissection. CT-scanning appears to be a reliable non-invasive method for - establishing the diagnosis of aortic dissection, - delineating the extent of dissection, - follow-up of evolution after surgical or medical therapy.

Thyroid cancer in childhood is a rare and slowly progressive but nevertheless malignant disease that has a high incidence of nodal metastasis. Six children aged 8 to 15 years with well-differentiated thyroid carcinomas were treated at the Children's University Hospital of Zurich between 1960 and 1979. Diagnostic, therapeutic and follow-up procedures are discussed. All 6 patients are alive and without recurrences 1 to 16 years after diagnosis. 1.Because of the frequency of intrathyroidal metastases, we prefer lobectomy on the affected side with resection of the isthmus and subtotal strumectomy on the opposite side, with preservation of the parathyroids. Grossly involved groups of nodes are resected. 2. Radiation therapy: Surgery is followed by external irradiation to the neck and mediastinum in cases of extrathyroidal extension of the tumour. 3. After I-131 ablation of remnant thyroid tissue, which permits the diagnosis of distant functioning metastases, several courses of radioiodine are applied as long as any functioning metastatic tissue is recognized. 4. Replacement therapy and suppression of endogenous stimulation by TSH are achieved by optimal hormonal treatment during the first years with triiodothyronine and later, after I-131 treatment has been concluded, with 1-thyroxine. 5. Lifelong follow-up is necessary, as late recurrences are possible.

Arealtime digital signal filtering system has been designed to investigate new methods of passive IR image processing with a combined staring and scanning IR array sensor. The image processing consists of cascaded spatial and temporal filters applied to the IR scene data to extract known features from cluttered and moving backgrounds. This approach concentrates on the detection of unresolved targets from large IR scenes. Testbed and simulation results have demonstratedthe detection of a target whose intensity was three orders of magnitude less than the background value.

These studies were designed to determine the role of the central nervous system, the sympathetic nervous system, the adrenal glands and the renal sympathetic nerves in yohimbine-induced renin release in conscious rats. Yohimbine (0.3–10 mg/kg, s.c.) caused time- and dose-related increases in plasma renin activity (PRA) and concentration (PRC) which were accompanied by time- and dose-related elevations of plasma norepinephrine (NE) and epinephrine (Epi) concentrations. Significant positive correlations were found between the increases in PRA and the increases in plasma NE and Epi concentrations caused by yohimbine, and propranolol (1.5 mg/kg, s.c.) blocked 90% of yohimbine (3 mg/kg, s.c.)-induced renin release. Over the entire spectrum of doses of yohimbine, the increases in PRA and plasma NE and Epi concentrations were positively correlated with the decreases in mean arterial pressure (MAP), but the γ-intercept was positive in every case and the 1 mg/ kg dose of yohimbine consistently increased PRA independent of any change in MAP. Complete renal denervation, as evidenced by a greater than 90% reduction in renal NE content, did not alter the increase in PRA caused by yohimbine (3 mg/kg, s.c.). An increase in circulating plasma catecholamine concentrations appeared to mediate yohimbine-induced renin release since propranolol prevented the rise in PRA caused by yohimbine in renal denervated rats. Prior adrenalectomy (Adx) also failed to prevent the rise in PRA produced by yohimbine (3 mg/kg, s.c.), but a combination of Adx and renal denervation caused a significant impairment of yohimbine-induced renin release. However, neither Adx alone nor the combination of Adx and renal denervation affected the increase in plasma NE concentration caused by yohimbine. Complete transection of the spinal cord at C8 caused a drastic reduction in plasma catecholamine concentrations but did not change basal PRC. Yohimbine (3 mg/kg, s.c.) did not increase PRC or plasma catecholamine concentrations after spinal transection. Based on these results, we conclude that 1) the stimulation of renin release by yohimbine is a secondary neurohormonal consequence of the generalized increase in sympathetic activity caused by yohimbine, 2) the sympathoadrenal activation produced by yohimbine results from an action in the brain which is amplified by the simultaneous blockade of prejunctional α2-adrenoceptors and 3) vasodepressor effects of the larger doses yohimbine cause a baroreflexly-mediated increase in sympathetic activity which interacts in a positive fashion with the central and peripheral sympathoexcitatory effects of yohimbine.

We used high performance liquid chromatography with fluorescence detection to measure the concentration of yohimbine in serum and brain of conscious Sprague-Dawley rats at various times after the i.v. injection of 1 mg/kg of yohimbine. The serum concentration-time profile of yohimbine was biphasic with a rapid distribution phase (t1/2 alpha = 0.048 h) followed by a very slow elimination phase t1/2 beta = 16.3 h). The clearance of yohimbine was 11 ml/h.kg-1, and the volume of distribution was 259 ml/kg. Increasing doses (0.3, 1 and 3 mg/kg, i.v.) of yohimbine produced non-linear increases in serum yohimbine concentration. Yohimbine entered the brain rapidly (5,000 ng/g at 5 min after 1 mg/kg, i.v.) and disappeared from brain with a t1/2 beta of 7.7 h. In contrast to serum yohimbine concentration, increasing doses of yohimbine (0.3, 1 and 3 mg/kg) produced linear increases in brain yohimbine concentration, a phenomenon which is consistent with concentration-dependent binding of yohimbine to plasma proteins. The rapid entry of yohimbine into the brain, the slow rate of elimination of yohimbine from serum and brain and the linear relationship of brain yohimbine concentration as a function of dose should be taken into consideration whenever yohimbine is to be used as a probe of alpha 2-adrenoceptor function in vivo.

Feeding a diet rich in eicosapentaenoic acid (EPA) to Watanabe heritable hyperlipidemic (WHHL) rabbits resulted in an attenuated aortic contractile response to the vasoconstrictor agent serotonin when compared to responses from WHHL rabbits fed normal rabbits chow. In contrast, only the maximak contractile response to norepinephrine was reduced in EPA-fed rabbit aortas. Additionally, methacholine-induced relaxations were potentiated in aortas obtained from the EPA-fed rabbits. When platelets ontained from EPA-fed rabbits were incubated with arachidonic acid, there was a reduced ability of the platelets to adhere to albumin-coated dics in comparison to control rabbit platelets. These data indicate a potentially beneficial effect of EPA in atherosclerotic WHHL rabbits.

WHHL rabbits develop progressive atherosclerosis. There are no visible signs of the disease at 1 month, however, by 12 months, the formation of aortic plaques is extensive. This study characterized arachidonic acid (AA) metabolism in 1 and 12 month old WHHL and NZW rabbit aortas. Vessels incubated with 14C-AA and A23187 metabolized AA to a number of oxygenated products as identified by high pressure liquid chromatography. The major AA metabolites produced by WHHL and NZW aortas were 6-keto PGF1 alpha, PGE2, 12- and 15-hydroxyeicosatetraenoic acids (HETEs). The structures of the HETEs were confirmed by gas chromatography-mass spectrometry. Indomethacin blocked the synthesis of prostaglandins (PGs) but not HETEs whereas ETYA, NDGA or removal of the endothelium attenuated the production of both PGs and HETEs. Measurement of 6-keto PGF1 alpha, 12- and 15-HETE by specific radioimmunoassays indicated that as the rabbits aged and as atherosclerosis progressed, aortas lost the ability to synthesize 6-keto PGF1 alpha and 15-HETE. Prior to the development of atherosclerosis, 1 month old WHHL aortas produced 70% less 15-HETE than did NZW aortas. Atherosclerotic aortas from 12 month old WHHLs synthesized 60% less 6-keto PGF1 alpha during stimulation with AA or A23187 than did 12 month old NZW aortas. We conclude that the development and expression of atherosclerosis in WHHL rabbits impairs the ability of aortas to metabolize AA to both PGs and HETEs.

The purpose of this paper is to provide further evaluation of the minimum requirements technique for estimating local export activity in economic base studies, and to present an application that seems to be free of most criticisms of the technique. The application is to estimate the sales of certain goods and services to tourists in metropolitan areas.1 The location quotient does not yield reliable estimates of exports to tourists. The argument of this paper is that minimum requirements yields better estimates of exports to tourists, but yields less reliable estimates of exports of goods than does the proper use of the location quotient. The bulk of the paper deals with the application of minimum requirements to estimating export sales to tourists.

Three cases of thoracic renal ectopia are described. Remarkable is the case of an "acquired" congenital right diaphragmatic hernia (Bochdalek's herniation) with previously normally positioned kidneys. Classification is as follows: 1. real thoracic ectopia with normally developed closed diaphragm, 2. eventration of the diaphragm (relaxatio diaphragmatica), 3. diaphragmatic hernia: a) congenital diaphragmatic defects, b) acquired herniation (Bochdalek's). 4. traumatic rupture of the diaphragm with renal ectopia.

Cyst-like cortical defects appearing a few weeks after a greenstick fracture in the undamaged part of the radius were observed in 9 children. Five children showed multiple lesions. These radiolucent cyst-like defects 2.4 to 48 mm proximal to the fracture line seemed to be situated within the zone of periosteal reaction. The diameter of the cyst-like defects varied from 3 to 7 mm, usually they were rounded or slightly oval. Fracture healing was unaffected. In three of the patients the lesions had disappeared on to three years later. We are convinced that these benign lesions are resorption cysts within the excessive periosteal reaction and related to the subperiosteal hematoma accompanying the greenstick fractures.

Sonographic evaluation of the brain offers a noninvasive, safe and inexpensive method in diagnosis and follow-up of hydrocephalus associated with meningomyelocele. Cranial computed tomography should be reserved for special questions such as assessment of bony structures, subdural effusions or if fontanelles and sutures are already closed. Ultrasound of the neonatal head is completely harmless, repeated examinations can easily be performed and sedation of the infant is usually not necessary. The method of ultrasound sections in different directions is demonstrated and compared to axial CT sections. Value, effectiveness and diagnostic interpretation of the method are demonstrated in four cases: 1. Small lumbar meningomyelocele with mild hydrocephalus without enlargement on follow-up. 2. Giant spinal defect with kyphoskoliosis, marked hydrocephalus and associated ventricle abnormalities. 3. Sonographic follow-up after ventriculo-atrial shunting in a patient with congenital hydrocephalus. 4. Cerebrospinal fluid abdominal pseudocyst after ventriculo-peritoneal shunting. Thus ultrasound is an excellent method for following ventricular size and shunt-function in meningomyelocele-patients.

Watanabe heritable hyperlipidemic (WHHL) rabbits have elevated concentrations of plasma cholesterol and develop progressive atherosclerosis. The present investigation was undertaken to evaluate the vascular responses to vasoactive compounds of aorta from WHHL rabbits and normal New Zealand White (NZW) rabbits at 1 and 6 months of age. Rings of distal thoracic aorta were suspended under isometric tension in oxygenated Krebs buffer. Developed tension was measured in response to graded concentrations of agonists. Maximal responses to KCl (40 mM) were the same in aortas from the 1-month-old and 6-month-old WHHL and NZW rabbits. Aortas from 1-month-old animals were more sensitive to serotonin than aortas from 6-month-old animals. Aortas from WHHL rabbits exhibited an increased maximal response to serotonin when compared with NZW controls. In contrast, the constrictor responses to norepinephrine were reduced in WHHL rabbits compared with NZW rabbits at both age groups. Methacholine decreased tension development in serotonin-contracted vessels. This relaxation was greatest in aortas from NZW rabbits. In 1-month-old NZW rabbits fed a high cholesterol diet, the constrictor responses to serotonin and the relaxation responses to methacholine did not differ from NZW rabbits ingesting a normal diet. However, the responses to norepinephrine were markedly attenuated in the hypercholesterolemic NZW rabbits. Microscopic evaluation of the aortas revealed occasional adherent leukocytes and irregularities in the vascular endothelium in 1-month-old WHHL animals. These changes were greater in aortas from 6-month-old WHHL animals, with more adherent leukocytes, adherent platelets, and severe irregularities in the endothelial surface.(ABSTRACT TRUNCATED AT 250 WORDS)

The main features of the program in regional and urban economics at Indiana University are summarized in this paper. This includes both undergraduate programs, graduate programs, as well as how the funding for these programs has been generated.

The wavelength-dependent albedo along the flight track of a NASA ER 2 high-altitude research aircraft has been estimated under clear-sky conditions in the 300-775 nm spectral range. We have developed an inversion technique to estimate ocean albedo which used nadir radiance measurements obtained during recent ER 2 campaigns. These are used in conjunction with a multiple-scattering radiative transfer model. This method is general and robust in that any type of surface can be handled as long as a functional form for the angular distribution of surface radiance can be specified. Comparisons have been made against a forward, iterative method and differences do not exceed 1% in the visible and were 1-2% in the near UV. Results are presented for clear-sky portions of flights from two ER 2 campaigns. Specular reflection of the sunlight off the ocean surface has been treated using the Cox and Munk statistical approach. Following this, the wavelength-dependent albedo has been estimated at selected points along various ER 2 flights. Furthermore, photolysis coefficients (or J values) for NO 2 and NO 3 have been calculated at these points so that the effects of accounting for both specular reflection and wavelength dependence on photochemistry can be assessed. The use of a wavelength-dependent albedo was found to impact J values by as much as 10%. It was also determined that, in most cases, accounting for specular reflection was found to have a minor impact on J values (1-3%), but under certain conditions, differences of up to 7% are possible.

Prostacyclin (PGI(2)) is a key mediator of pulmonary vasodilation during perinatal cardiopulmonary transition, at a time when fetal plasma estrogen levels are rising. We have previously shown that estradiol-17beta (E(2)) rapidly stimulates nitric oxide production by ovine fetal pulmonary artery endothelial cells (PAEC), and that this occurs through nongenomic mechanisms which are calcium- and tyrosine kinase-mitogen-activated protein (MAP) kinase-dependent. In the present study, we determined if E(2) acutely activates PGI(2) production in PAEC. E(2) (10(-8) M for 15 min) caused a 52% increase in PGI(2), the threshold concentration was 10(-10) M E(2), the effect occurred within 5 min, and it was not related to changes in cyclooxygenase type 1 (COX-1) or COX-2 abundance. Estrogen receptor (ER) alpha and ER beta proteins and mRNAs were found to be constitutively expressed in PAEC, and PGI(2) stimulation with E(2) was fully blocked by both ER antagonism with ICI 182,780, which is not selective for either ER isoform, and the ER beta-specific antagonist RR-tetrahydrochrysene. The rapid response to E(2) was also inhibited by calcium chelation, whereas genistein- or PD98059-induced inhibition of tyrosine kinase and MAP kinase kinase, respectively, had no effect. Thus, E(2) causes rapid stimulation of PGI(2) synthesis in fetal PAEC, this process is mediated by ER beta, and it is calcium-dependent and tyrosine kinase-MAP kinase-independent. These mechanisms may play a role in pulmonary vasodilation in the perinatal period.

This article develops some novel and fairly simple statistical techniques that enable an analyst to infer the geographic movement of a selected group of workers for which only its geographic distribution at two points in time is known. By making use of the known movements of some reference group expressed as a transition matrix, one can determine what the hypothetical distributions would have been if the selected group had moved in the same pattern as the reference group. The differences between the hypothetical and actual distributions for the selected group permit some interesting inferences regarding movement between regions. These techniques can be applied to a variety of problems other than those considered in the article.

Diatoms are single-celled, microscopic algae characterized by a siliceous cell wall. They live in almost all habitats containing water (e.g. lakes, streams, soils, rocks) and count among the most common algal groups in both freshwater and marine ecosystems. Their diversity and sensitivity to several environmental variables such as pH, organic pollution and acidification, have made them indispensable in water quality assessment. Because of those characteristics, recent research explored the use of terrestrial diatoms (i.e. diatoms living on soils) as tracers of water flow-paths during runoff events. Although the results were promising, further use was hampered by the lack of ecological knowledge on terrestrial diatoms and the large number of samples needed. To overcome the former, the spatial and temporal variability of diatom communities and their absolute abundances on soils were investigated and the occurrences of common soil diatoms were tested to an extensive set of environmental variables. Also, in order to reduce the number of samples, a suspended sediment sampler was explored for sampling drift diatom communities in streams during rainfall-runoff events. The results of the thesis allow to reduce the sampling effort and speed up the analysis of diatom-based hydrological tracer studies. They also indicate that many more diatoms can be used as environmental markers in hydrological tracing, that more locations can be sampled, and that the number of stream sampling sites can be increased in the future. The work thus improved the use of terrestrial diatoms as hydrological tracers. In het afgelopen decennium zijn terrestrische diatomeeën, een groep van microscopisch kleine algen die op bodems voorkomen, bestudeerd voor het opsporen van waterbronnen en -routes over een breed scala van ruimtelijke schalen. Ondanks bemoedigende resultaten heeft het innovatieve tracerconcept zijn grenzen bereikt enerzijds door het gebrek aan ecologische kennis over terrestrische diatomeeën en anderzijds door beperkingen met betrekking tot de mogelijke staalnamelocaties. Om de toepasbaarheid van diatomeeën als hydrologische tracers te verbeteren, werd de temporele en ruimtelijke dynamiek van terrestrische diatomeeën onderzocht en werd een nieuwe, alternatieve bemonsteringsmethode getest om drift-diatomeeëngemeenschappen te bemonsteren.

Understanding how different structural and functional elements of a catchment connect together to generate spatially and temporally variable fluxes of water, sediment and nutrients is fundamental for gaining a holistic comprehension of catchments’ hydrological behaviour. However, advancements in hydrological connectivity research still suffer from technical limitations inherent to the (i) investigation of connectivity at large scales (e.g. catchment scale), (ii) identification of intra-catchment heterogeneous landscape structures and connectivity pathways, and (iii) characterisation of the hydrological processes occurring at small scale around transition zones (e.g. the riparian zone). In this thesis, some of these challenging aspects are addressed by investigating hydrological connectivity at different spatio-temporal scales through two innovative, multidisciplinary approaches – namely terrestrial diatoms (unicellular, eukaryotic algae) and ground-based thermal infrared imagery (TIR).This thesis is wired around five studies that have explored the potential for these innovative avenues to overcome the prevailing status quo in hydrological connectivity research. Chapter 2 focuses on terrestrial diatoms’ ecological behaviour and sensitivity to environmental factors. Understanding the physiographic controls on terrestrial diatom communities is fundamental for advancing their employment as a tracer of hydrological connectivity at the catchment scale. Chapter 3 explores the potential for ground-based TIR imagery to provide instantaneous mapping of stream water mixing and mixing dynamics at confluence-scale. Cross-sectional variability in surface temperature observed through TIR imagery is found to reflect the in−stream variability of temperature and chemistry. Chapter 4 reports a technical study on the application of ground-based TIR imagery for mapping surface-saturation dynamics in the riparian zone. The results of a repeated mapping of surface saturation through ground-based TIR imagery are presented in Chapter 5. In this chapter, the seasonal dynamics of surface saturation in seven different riparian areas are characterised. The development of surface-saturation in the different areas is found to be influenced by heterogeneous catchment features such as riparian areas elevation, local riparian morphology (i.e. width of the riparian areas) and the presence or absence of groundwater exfiltration points. These heterogeneous catchment features also influence the shape of the surface-saturation vs. outlet baseflow relationship. In Chapter 6, the previously explored riparian surface-saturation dynamics are related to streamflow contributions from the corresponding stream reaches. The observed relationships provide information on the degree of hillslope-riparian-stream connectivity of different portions of the catchment.Overall, the studies presented in this thesis show how novel, multidisciplinary approaches and techniques can provide new information on hydrological connectivity across different spatial and temporal scales of investigation. An improved understanding of how connectivity is established within the catchment will eventually lead to a better management of our hydrological resources, increasingly put under pressure by climate change and anthropogenic activities.

The pressure on the scientific community to provide medium term flood forecasts with associated meaningful predictive uncertainty estimations has increased in recent years. A technique for assessing this uncertainty in hydro-meteorological forecasting systems is presented. In those, the uncertainties generally propagate from an atmospheric model through a rainfall-runoff model. Consequently, it appears to be difficult to isolate the errors that stem from the individual model components. In this study, the integrated flood forecasting system uses the 7-day rainfall and temperature forecast of the American atmospheric GFS model (deterministic run) as forcing data in a conceptual hydrologic model (deterministic run) coupled with a linear error model in order to predict river discharge. The linear error model is added to the hydrologic model run, in order to take advantage of the correlation in time between forecasting errors, thereby reducing errors that arise from hydrologic simulations. To assess the predictive uncertainty (total uncertainty) of the coupled models, the method makes use of a bivariate meta-gaussian probability density function. The latter allows estimating the probability distribution of the integrated model errors conditioned by the predicted river discharge values. The proposed methodology is applied to the case study of the Alzette river located in the Grand Duchy of Luxembourg. Confidence limits are computed for various lead times of prediction and compared with observations of river discharge.

This study considers the use of the maximum likelihood estimator proposed by Whittle for calibrating the parameters of hydrological models. Whittle’s likelihood provides asymptotically consistent estimates for Gaussian and non Gaussian data, even in the presence of long range dependence. This method may represent a valuable opportunity in the context of ungauged or scarcely gauged catchments. In fact, the only information required for model parameterization is the spectral density function of the actual process simulated by the model. When long series of calibration data are not available, the spectral density can be inferred by using old and sparse records, regionalization methods or information on the correlation properties of the process itself. The proposed procedure is applied to a case study referring to an Italian river basin, for which a lumped rainfall-runoff model is calibrated by emulating scarcely gauged situations. It is shown that the Whittle estimator can be applied in such a context with satisfactory results.