The Geographical Scope of Industrial Location Determinants: An Alternative Approach

This paper considers the estimation of the geographical scope of industrial location determinants. While previous studies impose strong assumptions on the weighting scheme of the spatial neighbour matrix, we propose a exible parametrisation that allows for di fferent (distance-based) de finitions of neighbourhood and di fferent weights to the neighbours. In particular, we estimate how far can reach indirect marginal e ffects and discuss how to report them. We also show that the use of smooth transition functions provides tools for policy analysis that are not available in the traditional threshold modelling. Keywords: count data models, industrial location, smooth transition functions, threshold models. JEL-Codes: C25, C52, R11, R30.

A general definition and nomenclature for alternative splicing events

Understanding the molecular mechanisms responsible for the regulation of the transcriptome present in eukaryotic cells isone of the most challenging tasks in the postgenomic era. In this regard, alternative splicing (AS) is a key phenomenoncontributing to the production of different mature transcripts from the same primary RNA sequence. As a plethora ofdifferent transcript forms is available in databases, a first step to uncover the biology that drives AS is to identify thedifferent types of reflected splicing variation. In this work, we present a general definition of the AS event along with anotation system that involves the relative positions of the splice sites. This nomenclature univocally and dynamically assignsa specific ‘‘AS code’’ to every possible pattern of splicing variation. On the basis of this definition and the correspondingcodes, we have developed a computational tool (AStalavista) that automatically characterizes the complete landscape of ASevents in a given transcript annotation of a genome, thus providing a platform to investigate the transcriptome diversityacross genes, chromosomes, and species. Our analysis reveals that a substantial part—in human more than a quarter—ofthe observed splicing variations are ignored in common classification pipelines. We have used AStalavista to investigate andto compare the AS landscape of different reference annotation sets in human and in other metazoan species and found thatproportions of AS events change substantially depending on the annotation protocol, species-specific attributes, andcoding constraints acting on the transcripts. The AStalavista system therefore provides a general framework to conductspecific studies investigating the occurrence, impact, and regulation of AS.

Alternative Solutions to Meet the Service Needs of Low Volume Bridges in lowa, June 2004

There is a nationwide need for a safe, efficient and cost effective transportation system. An essential component of this system is the bridges. Local agencies perhaps have an even greater task than federal and state agencies in maintaining the low volume road (LVR) bridge system due to lack of sufficient resources and funding. The primary focus of this study was to review the various aspects of off-system bridge design, rehabilitation, and replacement. Specifically, a reference report was developed to address common problems in LVR bridges. The source of information included both Iowa and national agencies. This report is intended to be a “user manual” or “tool box” of information, procedures and choices for county engineers to employ in the management of their bridge inventory plus identify areas and problems that need to be researched

Médecines complémentaires: vers un consensus "evidence-based" à l'hôpital universitaire. [Complementary and alternative medicines (CAM): towards an "evidence-based" consensus in the University hospital]

Après la votation fédérale demandant de prendre en compte les médecines complémentaires, un consensus a été recherché dans quatorze services et unités du Centre hospitalier universitaire vaudois (CHUV). Confrontés aux données de la littérature (Plus de 2000 publications en "Evidence-based complementary medicine" depuis 1998), les soignants étaient tous surpris par l'ampleur des résultats cliniques disponibles actuellement. Tous identifiaient un besoin en formation et en informations sur le sujet. Une prise de position officielle de l'institution était aussi souhaitée, instituant l'enseignement et la recherche sur les médecines complémentaires et assurant la production d'informations rigoureuses et pertinentes pour la clinique. [Abstract] While a popular vote supported a new article on complementary and alternative medicines (CAM) in the Swiss Constitution, this assessment in 14 wards of the University Hospital of Lausanne, Switzerland, attempted at answering the question: How can CAM use be better taken into account and patients informed with more rigor and respect for their choices? Confronted with a review of the literature (> 2000 publications in "Evidence-based cornplementary medicine" since 1998), respondents declared their ignorance of the clinical data presently available on CAM. All were in favour of more teaching and information on the subject, plus an official statement from the Hospital direction, ensuring production and diffusion of rigorous and cJinically significant information on CAM.

Deciphering 3'ss selection in the yeast genome reveals an RNA thermosensor that mediates alternative splicing

Poor understanding of the spliceosomal mechanisms to select intronic 3' ends (3'ss) is a major obstacle to deciphering eukaryotic genomes. Here, we discern the rules for global 3'ss selection in yeast. We show that, in contrast to the uniformity of yeast splicing, the spliceosome uses all available 3'ss within a distance window from the intronic branch site (BS), and that in 70% of all possible 3'ss this is likely to be mediated by pre-mRNA structures. Our results reveal that one of these RNA folds acts as an RNA thermosensor, modulating alternative splicing in response to heat shock by controlling alternate 3'ss availability. Thus, our data point to a deeper role for the pre-mRNA in the control of its own fate, and to a simple mechanism for some alternative splicing.

Differentiated evolutionary rates in alternative exons and the implications for splicing regulation

Background: Alternatively spliced exons play an important role in the diversification of gene function in most metazoans and are highly regulated by conserved motifs in exons and introns. Two contradicting properties have been associated to evolutionary conserved alternative exons: higher sequence conservation and higher rate of non-synonymous substitutions, relative to constitutive exons. In order to clarify this issue, we have performed an analysis of the evolution of alternative and constitutive exons, using a large set of protein coding exons conserved between human and mouse and taking into account the conservation of the transcript exonic structure. Further, we have also defined a measure of the variation of the arrangement of exonic splicing enhancers (ESE-conservation score) to study the evolution of splicing regulatory sequences. We have used this measure to correlate the changes in the arrangement of ESEs with the divergence of exon and intron sequences. Results: We find evidence for a relation between the lack of conservation of the exonic structure and the weakening of the sequence evolutionary constraints in alternative and constitutive exons. Exons in transcripts with non-conserved exonic structures have higher synonymous (dS) and non-synonymous (dN) substitution rates than exons in conserved structures. Moreover, alternative exons in transcripts with non-conserved exonic structure are the least constrained in sequence evolution, and at high EST-inclusion levels they are found to be very similar to constitutive exons, whereas alternative exons in transcripts with conserved exonic structure have a dS significantly lower than average at all EST-inclusion levels. We also find higher conservation in the arrangement of ESEs in constitutive exons compared to alternative ones. Additionally, the sequence conservation at flanking introns remains constant for constitutive exons at all ESE-conservation values, but increases for alternative exons at high ESE-conservation values. Conclusion: We conclude that most of the differences in dN observed between alternative and constitutive exons can be explained by the conservation of the transcript exonic structure. Low dS values are more characteristic of alternative exons with conserved exonic structure, but not of those with non-conserved exonic structure. Additionally, constitutive exons are characterized by a higher conservation in the arrangement of ESEs, and alternative exons with an ESE-conservation similar to that of constitutive exons are characterized by a conservation of the flanking intron sequences higher than average, indicating the presence of more intronic regulatory signals.

Determination and Evaluation of Alternative Methods for Managing and Controlling Highway-Related Dust Phase II—Demonstration Project, June 2005

The State of Iowa currently has approximately 69,000 miles of unpaved secondary roads. Due to the low traffic count on these unpaved o nts as ng e two dust ed d roads, paving with asphalt or Portland cement concrete is not economical. Therefore to reduce dust production, the use of dust suppressants has been utilized for decades. This study was conducted to evaluate the effectiveness of several widely used dust suppressants through quantitative field testing on two of Iowa’s most widely used secondary road surface treatments: crushed limestone rock and alluvial sand/gravel. These commercially available dust suppressants included: lignin sulfonate, calcium chloride, and soybean oil soapstock. These suppressants were applied to 1000 ft test sections on four unpaved roads in Story County, Iowa. Tduplicate field conditions, the suppressants were applied as a surface spray once in early June and again in late August or early September. The four unpaved roads included two with crushed limestone rock and two with alluvial sand/gravel surface treatmewell as high and low traffic counts. The effectiveness of the dust suppressants was evaluated by comparing the dust produced on treated and untreated test sections. Dust collection was scheduled for 1, 2, 4, 6, and 8 weeks after each application, for a total testiperiod of 16 weeks. Results of a cost analysis between annual dust suppressant application and biennial aggregate replacement indicated that the cost of the dust suppressant, its transportation, and application were relatively high when compared to that of thaggregate types. Therefore, the biennial aggregate replacement is considered more economical than annual dust suppressant application, although the application of annual dust suppressant reduced the cost of road maintenance by 75 %. Results of thecollection indicated that the lignin sulfonate suppressant outperformed calcium chloride and soybean oil soapstock on all four unpavroads, the effect of the suppressants on the alluvial sand/gravel surface treatment was less than that on the crushed limestone rock, the residual effects of all the products seem reasonably well after blading, and the combination of alluvial sand/gravel surface treatment anhigh traffic count caused dust reduction to decrease dramatically.

Modification du style de vie : une alternative au traitement pharmacologique lors d'hypertension modérée

[But de l'étude] Il s'agit d'effectuer un projet pilote afin de développer la méthodologie pour une large étude et d'en examiner les possibilités de réalisation. Cette large étude devrait permettre de tester l'hypothèse qu'une thérapeutique non médicamenteuse de l'hypertension artérielle modérée est une alternative valable au traitement chimiothérapeutique en termes de résultats cliniques et de rapport coût/efficacité. [Auteurs, p. 4]

The Conservation Reserve Program in the Presence of a Working Land Alternative: Implications for Environmental Quality, Program Participation, and Income Transfer, August 2005

The United States has invested large sums of resources in multiple conservation programs for agriculture over the past century. In this paper we focus on the impacts of program interactions. Specifically, using an integrated economic and bio-physical modeling framework, we consider the impacts of the presence of working land programs on a land retirement for an important agricultural region—the Upper Mississippi River Basin (UMRB). Compared to a land retirement only program, we find that the presence of a working land program for conservation tillage results in significantly lower predicted signups for land retirement at a given rental rate. We also find that the presence of both a large working land and land retirement program can result in more environmental benefits and income transfers than a land retirement only program can achieve.

Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule.

Cell death is achieved by two fundamentally different mechanisms: apoptosis and necrosis. Apoptosis is dependent on caspase activation, whereas the caspase-independent necrotic signaling pathway remains largely uncharacterized. We show here that Fas kills activated primary T cells efficiently in the absence of active caspases, which results in necrotic morphological changes and late mitochondrial damage but no cytochrome c release. This Fas ligand-induced caspase-independent death is absent in T cells that are deficient in either Fas-associated death domain (FADD) or receptor-interacting protein (RIP). RIP is also required for necrotic death induced by tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand (TRAIL). In contrast to its role in nuclear factor kappa B activation, RIP requires its own kinase activity for death signaling. Thus, Fas, TRAIL and TNF receptors can initiate cell death by two alternative pathways, one relying on caspase-8 and the other dependent on the kinase RIP.

The TPTE gene family: cellular expression, subcellular localization and alternative splicing.

The human TPTE (Transmembrane Phosphatase with TEnsin homology) gene family encodes a PTEN-related tyrosine phosphatase with four potential transmembrane domains. Chromosomal mapping revealed multiple copies of the TPTE gene on chromosomes 13, 15, 21, 22 and Y. Human chromosomes 13 and 21 copies encode two functional proteins, TPIP (TPTE and PTEN homologous Inositol lipid Phosphatase) and TPTE, respectively, whereas only one copy of the gene exists in the mouse genome. In the present study, we show that TPTE and TPIP proteins are expressed in secondary spermatocytes and/or prespermatids. In addition, we report the existence of several novel alternatively spliced isoforms of these two proteins with variable number of transmembrane domains. The latter has no influence on the subcellular localization of these different peptides as shown by co-immunofluorescence experiments. Finally, we identify another expressed TPTE copy, mapping to human chromosome 22, whose transcription appears to be under the control of the LTR of human endogenous retrovirus RTVL-H3.

Longer survival for patients with alternative lengthening of telomeres (ALT) glioblastoma multiforme is due to a less aggressive phenotype and not to improved response to adjuvant therapy

Introduction: The Alternative Lengthening of Telomeres (ALT) mechanism is a significant prognostic factor for longer survival in patients with GBM, irrespective of age. The reasons for this are unknown. We considered two possibilities; firstly that ALT identifies a subset of less aggressive GBMs, or alternatively, a group of tumours that respond more favourably to adjuvant therapy. Methods: ALT was determined by staining for ALT Associated PML Bodies (APBs) in archival tissue in a retrospective analysis of 573 GBM patients. IDH1 mutation was determined by immunohistochemistry in a subset of these. Results: We identified the presence of the telomerase-independent ALT in 15% of GBM patients and found that it correlated with survival (22% of ALT patients survive more than 2 years compared to 9% for non-ALT). This survival advantage was independent of surgery type (biopsy or full resection) and treatment (radiotherapy and chemotherapy). Interestingly ALT conferred a significant survival advantage for patients who only received surgery (13.3 months compared to 5.5 months) (19% vs 1% .2 year survival). This survival benefit was also observed in GBM patients who received surgery and radiotherapy (18.5% vs 2.4%. 2 year survival), but less so for chemotherapy (21% vs 17% . 2 year survival). For the ALT patients the fraction surviving more than 2 years did not improve significantly with adjuvant therapy. IDH1 mutation also associated with ALT. Conclusions: These data indicate ALT+ tumours are biologically distinct and associated with improved patient survival, probably due to less aggressive/invasive growth. However they respond poorly to current adjuvant treatment and therefore new therapies are urgently needed for this group.

Laboratory Study of Structural Behavior of Alternative Dowel Bars, April 2006

Load transfer across transverse joints has always been a factor contributing to the useful life of concrete pavements. For many years, round steel dowels have been the conventional load transfer mechanism. Many problems have been associated with the round steel dowels. The most detrimental effect of the steel dowel is corrosion. Repeated loading over time also damages joints. When a dowel is repeatedly loaded over a long period of time, the high bearing stresses found at the top and bottom edge of a bar erode the surrounding concrete. This oblonging creates multiple problems in the joint. Over the past decade, Iowa State University has performed extensive research on new dowel shapes and materials to mitigate the effects of oblonging and corrosion. This report evaluates the bearing stress performance of six different dowel bar types subjected to two different shear load laboratory test methods. The first load test is the AASHTO T253 method. The second procedure is an experimental cantilevered dowel test. The major objective was to investigate and improve the current AASHTO T253 test method for determining the modulus of dowel support, k0. The modified AASHTO test procedure was examined alongside an experimental cantilever dowel test. The modified AASHTO specimens were also subjected to a small-scale fatigue test in order to simulate long-term dowel behavior with respect to concrete joint damage. Loss on ignition tests were also performed on the GFRP dowel specimens to determine the resin content percentage. The study concluded that all of the tested dowel bar shapes and materials were adequate with respect to performance under shear loading. The modified AASHTO method yielded more desirable results than the ones obtained from the cantilever test. The investigators determined that the experimental cantilever test was not a satisfactory test method to replace or verify the AASHTO T253 method.

Developmental stage-specific expression of cyclic adenosine 3',5'-monophosphate response element-binding protein CREB during spermatogenesis involves alternative exon splicing.

Spermatogenesis is a temporally regulated developmental process by which the gonadotropin-responsive somatic Sertoli and Leydig cells act interdependently to direct the maturation of the germinal cells. The metabolism of Sertoli and Leydig cells is regulated by the pituitary gonadotropins FSH and LH, which, in turn, activate adenylate cyclase. Because the cAMP-second messenger pathway is activated by FSH and LH, we postulated that the cAMP-responsive element-binding protein (CREB) plays a physiological role in Sertoli and Leydig cells, respectively. Immunocytochemical analyses of rat testicular sections show a remarkably high expression of CREB in the haploid round spermatids and, to some extent, in pachytene spermatocytes and Sertoli cells. Although most of the CREB antigen is detected in the nuclei, some CREB antigen is also present in the cytoplasm. Remarkably, the cytoplasmic CREB results from the translation of a unique alternatively spliced transcript of the CREB gene that incorporates an exon containing multiple stop codons inserted immediately up-stream of the exons encoding the DNA-binding domain of CREB. Thus, the RNA containing the alternatively spliced exon encodes a truncated transcriptional transactivator protein lacking both the DNA-binding domain and nuclear translocation signal of CREB. Most of the CREB transcripts detected in the germinal cells contain the alternatively spliced exon, suggesting a function of the exon to modulate the synthesis of CREB. In the Sertoli cells we observed a striking cyclical (12-day periodicity) increase in the levels of CREB mRNA that coincides with the splicing out of the restrictive exon containing the stop codons. Because earlier studies established that FSH-stimulated cAMP levels in Sertoli cells are also cyclical, and the CREB gene promoter contains cAMP-responsive enhancers, we suggest that the alternative RNA splicing controls a positive autoregulation of CREB gene expression mediated by cAMP.

Guayule and Russian dandelion as alternative sources of natural rubber.

Natural rubber, obtained almost exclusively from the Para rubber tree (Hevea brasiliensis), is a unique biopolymer of strategic importance that, in many of its most significant applications, cannot be replaced by synthetic rubber alternatives. Several pressing motives lead to the search for alternative sources of natural rubber. These include increased evidence of allergenic reactions to Hevea rubber, the danger that the fungal pathogen Microcyclus ulei, causative agent of South American Leaf Blight (SALB), might spread to Southeast Asia, which would severely disrupt rubber production, potential shortages of supply due to increasing demand and changes in land use, and a general trend towards the replacement of petroleum-derived chemicals with renewables. Two plant species have received considerable attention as potential alternative sources of natural rubber: the Mexican shrub Guayule (Parthenium argentatum Gray) and the Russian dandelion (Taraxacum koksaghyz). This review will summarize the current production methods and applications of natural rubber (dry rubber and latex), the threats to the production of natural rubber from the rubber tree, and describe the current knowledge of the production of natural rubber from guayule and Russian dandelion.