Wind Tunnel Analysis of the Effects of Planting at Highway Grade Separation Structures, HR-202, 1979

Blowing and drifting snow has been a problem for the highway maintenance engineer virtually since the inception of the automobile. In the early days, highway engineers were limited in their capability to design and construct drift free roadway cross sections, and the driving public tolerated the delays associated with snow storms. Modern technology, however, has long since provided the design expertise, financial resources, and construction capability for creating relatively snowdrift free highways, and the driver today has come to expect a highway facility that is free of snowdrifts, and if drifts develop they expect highway maintenance crews to open the highway within a short time. Highway administrators have responded to this charge for better control of snowdrifting. Modern highway designs in general provide an aerodynamic cross section that inhibits the deposition of snow on the roadway insofar as it is economically feasible to do so.

Analyse critique des résultats de biopsies musculaires et de la méthodologie utilisée dans 889 cas d'affections neuromusculaires [Critical analysis of the results of muscle biopsies and of the methods used in 889 cases of neuromuscular disorders]

The contribution of muscle biopsies to the diagnosis of neuromuscular disorders and the indications of various methods of examination are investigated by analysis of 889 biopsies from patients suffering from myopathic and/or neurogenic disorders. Histo-enzymatic studies performed on frozen material as well as immunohistochemistry and electron microscopy allowed to provide specific diagnoses in all the neurogenic disorders (polyneuropathies and motor neuron diseases), whereas one third of myopathies remained uncertain. Confrontation of neuropathological data with the clinical indications for histological investigations shows that muscle biopsies reveal the diagnosis in 25% of the cases (mainly in congenital and metabolic myopathies) and confirm and/or complete the clinical diagnosis in 50%. In the remaining cases with non specific abnormalities neuropathological investigations may help the clinician by excluding well defined neuromuscular disorders. Analysis of performed studies and results of investigations show the contribution and specificity of each method for the diagnosis. Statistical evaluation of this series indicates that cryostat sectioning for histo- and immunochemical and electron microscopy increases the rate of diagnoses of neuromuscular diseases: full investigation was necessary for the diagnosis in 30% of the cases. The interpretation of the wide range of pathological reactions in muscles requires a close cooperation with the clinician.

The social disembedding of business theory and practice. A (neo-)institutional analysis of the homo economicus and corporate social responsibility, and the inherent responsibility of business scholars

Aim Structure of the Thesis In the first article, I focus on the context in which the Homo Economicus was constructed - i.e., the conception of economic actors as fully rational, informed, egocentric, and profit-maximizing. I argue that the Homo Economicus theory was developed in a specific societal context with specific (partly tacit) values and norms. These norms have implicitly influenced the behavior of economic actors and have framed the interpretation of the Homo Economicus. Different factors however have weakened this implicit influence of the broader societal values and norms on economic actors. The result is an unbridled interpretation and application of the values and norms of the Homo Economicus in the business environment, and perhaps also in the broader society. In the second article, I show that the morality of many economic actors relies on isomorphism, i.e., the attempt to fit into the group by adopting the moral norms surrounding them. In consequence, if the norms prevailing in a specific group or context (such as a specific region or a specific industry) change, it can be expected that actors with an 'isomorphism morality' will also adapt their ethical thinking and their behavior -for the 'better' or for the 'worse'. The article further describes the process through which corporations could emancipate from the ethical norms prevailing in the broader society, and therefore develop an institution with specific norms and values. These norms mainly rely on mainstream business theories praising the economic actor's self-interest and neglecting moral reasoning. Moreover, because of isomorphism morality, many economic actors have changed their perception of ethics, and have abandoned the values prevailing in the broader society in order to adopt those of the economic theory. Finally, isomorphism morality also implies that these economic actors will change their morality again if the institutional context changes. The third article highlights the role and responsibility of business scholars in promoting a systematic reflection and self-critique of the business system and develops alternative models to fill the moral void of the business institution and its inherent legitimacy crisis. Indeed, the current business institution relies on assumptions such as scientific neutrality and specialization, which seem at least partly challenged by two factors. First, self-fulfilling prophecy provides scholars with an important (even if sometimes undesired) normative influence over practical life. Second, the increasing complexity of today's (socio-political) world and interactions between the different elements constituting our society question the strong specialization of science. For instance, economic theories are not unrelated to psychology or sociology, and economic actors influence socio-political structures and processes, e.g., through lobbying (Dobbs, 2006; Rondinelli, 2002), or through marketing which changes not only the way we consume, but more generally tries to instill a specific lifestyle (Cova, 2004; M. K. Hogg & Michell, 1996; McCracken, 1988; Muniz & O'Guinn, 2001). In consequence, business scholars are key actors in shaping both tomorrow's economic world and its broader context. A greater awareness of this influence might be a first step toward an increased feeling of civic responsibility and accountability for the models and theories developed or taught in business schools.

Characterization of the effect of mammary gland irridiation on experimental brest cancer progression and analysis of the implicated mechanisms

SUMMARY Radiotherapy is commonly and efficiently used to treat solid cancer in the clinic. Experimental evidence however suggests that radiation can promote tumor progression by inducing chronic modifications of the tumor microenvironment. Clinically, these observations are highly relevant to aggressive tumoral lesions relapsing after radiation therapy, a leading cause of patients' death. The investigation and understanding of the biological mechanisms implicated in the malignant progression of post-radiation relapses are therefore of major importance. Here we used a syngeneic (immunocompetent) breast cancer orthotopic xenograft model, to show that local irradiation of the mammary gland promotes the appearance of an invasive and metastatic tumor phenotype. Previous studies in our laboratory revealed that inhibition of tumor-induced angiogenesis and consequent increase in tumor hypoxia promotes metastasis formation through the activation of pro-invasive programs in the tumor cells. Our results extend these observations suggesting that mammary gland irradiation induces the recruitment of CD11b+ cells to both the primary tumor and the lungs at pre-metastatic stages through the hypoxia-dependent induction of Kit-ligand (KITL) expression in primary tumors. Abrogation of KITL expression in tumor cells prevented CD11 b+ cells accumulation in both the primary tumor and lungs and significantly reduced metastases of tumors growing in irradiated mammary gland. Importantly, irradiated mammary gland enhanced tumor-induced mobilization of circulating CD11b+cKit+ myelomonocytic cells through a HIF1- and KITL-dependent process. By cell transfer experiments, mobilized circulating CD11b+cKit+ cells were shown to supply both tumor- and lungs infiltrating CD11b+ cells. Using a blocking antibody against cKit (the KITL receptor), the mobilization of CD11b+cKit+ ceils was prevented as well as lung metastases derived from tumors growing in irradiated mammary gland. Taken together, these results indicate that tumors growing in a pre-irradiated mammary gland partially promote their malignant progression through the distant mobilization of circulating myelomonocytic precursor cells. They identify KITL inhibition and/or cKit receptor neutralization as potentially promising therapeutic approaches for post-radiation relapses. RESUME La radiothérapie est largement utilisée comme traitement de choix de nombreux types de cancers. L'agressivité des récidives tumorales observée en clinique après radiothérapie suggère cependant que le recours à l'irradiation pourrait dans certains cas accélérer la progression tumorale. De récents travaux expérimentaux ont en effet permis d'appuyer cette hypothèse, en montrant notamment l'effet néfaste des modifications chroniques de l'environnement induites par l'irradiation sur la progression tumorale. A l'aide d'un modèle murin syngénique orthotopique de cancer de sein, nous avons pu montrer que l'irradiation locale de la glande mammaire facilite l'invasion et la dissémination métastatique des cellules tumorales en favorisant le recrutement de cellules myéloïdes CD11 b+ vers la tumeur primaire et les poumons à un stade pré-métastatique. Comme mécanisme impliqué dans le recrutement des cellules CD11b+, nous avons pu observer après irradiation locale de la glande mammaire une expression augmentée de Kit-ligand (KITL) dans la tumeur (induite par l'hypoxie) ainsi que la mobilisation de cellules myéloïdes circulantes exprimant le récepteur cKit et précurseurs des cellules CD11b+ infiltrant la tumeur et les poumons. En empêchant la mobilisation par la tumeur de cellules circulantes cKit+ par des approches à la fois génétique et pharmacologique nous avons pu prévenir l'accumulation de cellules myéloïdes CD11 b+ dans la tumeur primaire et les poumons ainsi que la dissémination métastatique induites par' l'irradiation de la glande mammaire. De façon générale, ces résultats montrent que la progression agressive des tumeurs qui se développent dans un environnement irradié repose à la fois sur l'expression tumorale de KITL et la mobilisation de cellules myéloïdes précurseurs cKit*. Ils auront permis d'identifier KITL et/ou cKit comme des cibles thérapeutiques potentielles intéressantes pour le traitement des récidives tumorales après radiothérapie.

An Analysis of the Benefit of Using HEV Genotype 3 Antigens in Detecting Anti-HEV IgG in a European Population

Introduction Quatre génotypes pathogènes de l'hépatite E (HEV) sont actuellement connus. Ils présentent des caractéristiques épidémiologiques différentes. Les génotypes 1 et 2 infectent uniquement l'homme et sont à l'origine d'épidémies dans des pays en voie de développement. Les génotypes 3 et 4 se présentent sous forme de zoonose, endémiques chez des cochons et autres mammifères dans des pays industrialisés. Ces derniers génotypes sont à l'origine de cas sporadiques d'hépatite E autochtones. La majorité des tests de sérologie actuellement commercialisés se basent sur des virus de génotype 1 et 2. Le bénéfice de l'utilisation d'un test sérologique basé sur le génotype 3 dans des pays industrialisés n'a pas été étudié jusqu'à présent. Dans cette étude, les performances de tests sérologiques basés sur des antigènes de plusieurs génotypes de l'HEV ont été comparées. Méthode Les tests ont été appliqués à deux populations distinctes: une population de 20 patients, chez qui une infection aiguë d'hépatite E, génotype 3, a été documentée par PCR sanguine, et une population de 550 donneurs de sang de la région de Lausanne. Le dépistage des IgGs anti-HEV a été effectué dans le sérum des deux populations par trois «Enzyme Immuno Assays» (EIA) à savoir MP Diagnostics, Dia.Pro et Fortress. Les échantillons positifs avec au moins un des EIA ont été testés par un «Immunodot Assay», le recomLine HEV IgG/IgM. Tous les EIA sont basés sur des antigènes des génotypes 1 et 2, alors que l'immunodot se base sur des antigènes des génotypes 1 et 3. Résultats Tous les échantillons des cas d'hépatite E documentés et 124 sur 550 échantillons des donneurs de sang étaient positifs avec au moins un des tests sérologique. Parmi les cas confirmés par PCR, 45 %, 65 %, 95 % et 55 % étaient respectivement positifs avec le test de MP Diagnostics, Dia.Pro, Fortress et recomLine. Parmi les échantillons positifs des donneurs de sang avec au moins un des tests, 120/124 (97 %) étaient positifs avec le test Fortress, 19/124 (15 %) étaient positifs avec tous les EIA et 51/124 (41 %) étaient positifs avec le recomLine. Parmi les cas d'hépatite E confirmés, 11/20 (55 %) étaient positifs avec le recomLine et parmi ceux-ci, une réactivité plus forte pour le génotype 3 était observée dans 1/11 (9 %) et une réactivité identique dans 5/11 (45.5 %) cas. Conclusions Même si le recomLine contient des protéines dérivées de l'HEV génotype 3, sa sensibilité est inférieure à l'EIA de Fortress dans les cas d'hépatite E aiguë de génotype 3. De plus, chez environ 45 % des patients, le recomLine ne parvient pas à identifier une infection comme étant causé par un virus du génotype 3. Dans la population de donneurs de sang, nous avons observe de grandes variations dans les séroprévalences mesurées, allant de 4.2 % à 21.8 % selon les tests sérologiques employés.

Audit report of the financial statements of the governmental activities, the business type activities, the aggregate discretely presented component units, each major fund and the aggregate remaining fund information of the State of Iowa as of and for the year ended June 30, 2014

Audit report of the financial statements of the governmental activities, the business type activities, the aggregate discretely presented component units, each major fund and the aggregate remaining fund information of the State of Iowa as of and for the year ended June 30, 2014

An evolutionary analysis of the relationship between spite and altruism.

We investigate the selective pressures on a social trait when evolution occurs in a population of constant size. We show that any social trait that is spiteful simultaneously qualifies as altruistic. In other words, any trait that reduces the fitness of less related individuals necessarily increases that of related ones. Our analysis demonstrates that the distinction between "Hamiltonian spite" and "Wilsonian spite" is not justified on the basis of fitness effects. We illustrate this general result with an explicit model for the evolution of a social act that reduces the recipient's survival ("harming trait"). This model shows that the evolution of harming is favoured if local demes are of small size and migration is low (philopatry). Further, deme size and migration rate determine whether harming evolves as a selfish strategy by increasing the fitness of the actor, or as a spiteful/altruistic strategy through its positive effect on the fitness of close kin.

Structure-function analysis of the human TFIIB-related factor II protein reveals an essential role for the C-terminal domain in RNA polymerase III transcription.

The transcription factors TFIIB, Brf1, and Brf2 share related N-terminal zinc ribbon and core domains. TFIIB bridges RNA polymerase II (Pol II) with the promoter-bound preinitiation complex, whereas Brf1 and Brf2 are involved, as part of activities also containing TBP and Bdp1 and referred to here as Brf1-TFIIIB and Brf2-TFIIIB, in the recruitment of Pol III. Brf1-TFIIIB recruits Pol III to type 1 and 2 promoters and Brf2-TFIIIB to type 3 promoters such as the human U6 promoter. Brf1 and Brf2 both have a C-terminal extension absent in TFIIB, but their C-terminal extensions are unrelated. In yeast Brf1, the C-terminal extension interacts with the TBP/TATA box complex and contributes to the recruitment of Bdp1. Here we have tested truncated Brf2, as well as Brf2/TFIIB chimeric proteins for U6 transcription and for assembly of U6 preinitiation complexes. Our results characterize functions of various human Brf2 domains and reveal that the C-terminal domain is required for efficient association of the protein with U6 promoter-bound TBP and SNAP(c), a type 3 promoter-specific transcription factor, and for efficient recruitment of Bdp1. This in turn suggests that the C-terminal extensions in Brf1 and Brf2 are crucial to specific recruitment of Pol III over Pol II.

Molecular Analysis of the PTEN Gene in a Choroidal Schwannoma in the Context of a Hamartomatous Syndrome

Purpose: To investigate the molecular involvement of PTEN, a tumor suppressor gene, in a case of cellular pigmented choroidal Schwannoma in a patient with hamartomatous syndrome due to heterozygous PTEN germline mutation. Methods: Histopathological, immunohistochemical, and electron microscopy analyses were performed by standard procedures. Paraffin-embedded samples of normal and tumor eye tissues were collected and DNA was extracted. A 145 bp region flanking the heterozygous c.406T>C mutation in exon 5 of PTEN was amplified by PCR and sequenced. To evaluate the allelic status of PTEN in the tumor sample, we cloned different PCR products in E. coli using a TA cloning procedure. Results: Histopathology demonstrated a posterior choroidal mass measuring 1.3 x 1.6 x 1.4 cm. The tumor was composed by fascicles of spindle cells with wavy cytoplasm. No Verrocay bodies could be identified. Scattered histiocytes with clear cytoplasm were present. By immunohistochemistry, the cells were expressing S100 and focally Melan A proteins. Pericellular type IV collagen could be demonstrated. Interlacing cytoplasmic processes covered by thick basement membrane could be found by electron microscopy as well as few premelanosomes. Moderate PTEN expression by immunohistochemistry was identified in some cells. As expected, the germline mutation could be detected by DNA sequencing in both the paraffin-embedded normal and tumor eye tissues. Analysis of 33 E. coli colonies bearing clones from the tumor eye tissue DNA surprisingly revealed that most of them contained the PTEN wild-type allele (29 vs. 4, Fisher's test p-value = 0.002). Conclusions: This is the first reported case of choroidal cellular Schwannoma arising in the context of a PTEN hamartomatous syndrome. Allelic analysis of PTEN in the tumor suggests a statistically-significant partial loss of heterozygozity in favor of the wild-type allele. Our findings are in clear contrast with what is usually observed in cancer tissues, for which mutated alleles of tumor suppressor genes are usually brought to homozygosity. Similar results were previously reported in human non-Hodgkin's lymphomas, displaying an overexpression of the wild-type form of the tumor suppressor gene p53. We are in the process of investigating additional DNA derived from other fresh and paraffin-embedded tissues from the patient, in order to gain insights on the molecular bases of PTEN involvement in this rare choroidal Schwannoma.

Integrative analysis of the Regulatory Region of the FGFR3 Oncogene

The study of transcriptional regulation often needs the integration of diverse yet independent data. In the present work, sequence conservation, predic-tion of transcription factor binding sites (TFBS) and gene expression analysis have been applied to the detection of putative transcription factor (TF) modules in the regulatory region of the FGFR3 oncogene. Several TFs with conserved binding sites in the FGFR3 regulatory region have shown high positive or negative corre-lation with FGFR3 expression both in urothelial carcinoma and in benign nevi. By means of conserved TF cluster analysis, two different TF modules have been iden-tified in the promoter and first intron of FGFR3 gene. These modules contain acti-vating AP2, E2F, E47 and SP1 binding sites plus motifs for EGR with possible repressor function.

Psychodynamic interventions in cancer care II: a qualitative analysis of the therapists' reports.

BACKGROUND: To investigate the focus of psychodynamic-oriented interventions in cancer patients by means of a qualitative analysis of the therapists' reports. METHODS: One hundred thirty-five reports collected within a controlled psychotherapy trial were analyzed; the themes addressed during the intervention were classified in categories reflecting the focus of the intervention and correlated with sociodemographic and medical data and type of intervention. RESULTS: Twenty main themes were identified and classified in two categories: category 1 corresponded to interventions based on expression and support, and category 2 to interventions based on introspection, with subcategory 2.1 focusing on the patient's psychological functioning and subcategory 2.2 focusing on his way to engage and communicate in relationships. While the most frequently addressed theme was related to the diagnosis of cancer (N = 102/576; 22.6%), the majority of themes were related to other concerns (N = 446/576; 77.4%). Half of the interventions (50.4%) were classified in category 1, 27.4% in category 2.1, and 9.6% in category 2.2. Patients of category 1 entered less often brief psychotherapy (step 2 of the intervention) and more frequently suffered from advances disease. CONCLUSIONS: A wide variety of themes are addressed in psychodynamic interventions in the oncology setting, illustrating that cancer is not the only focus of therapy. Other themes reflect different psychological difficulties triggered by the disease. This study illustrates that cancer patients have different needs, which surpass the event of the disease. Early clarification and comprehension of the demand may therefore be beneficial to adjust the therapeutic approach. Copyright © 2013 John Wiley & Sons, Ltd.

Cytogenetic and molecular analysis of the Pantaneiro cattle breed

The objective of this work was to characterize Pantaneiro cattle genetically through its paternal ancestry by the morphology of the Y chromosome, whether submetacentric or acrocentric, as well as to identify the maternal ancestry through mitochondrial DNA. The karyotype and mitochondrial DNA of 12 bulls of Pantaneiro breed were analyzed. The Y chromosome was analyzed in lymphocyte metaphases and the mitochondrial DNA by diagnosing its haplotype (Bos taurus and Bos indicus). Among Pantaneiro animals analyzed three had a taurine (submetacentric) Y and nine had a zebuine (acrocentric) Y chromosome, suggesting breed contamination by Zebu cattle, once Pantaneiro is considered to be of European origin. The mitochondrial DNA was exclusively of taurine origin, indicating that the participation of zebuines in the formation of the breed occurred entirely through the paternal line.

Analysis of the contribution of the beta-oxidation auxiliary enzymes in the degradation of the dietary conjugated linoleic acid 9-cis-11-trans-octadecadienoic acid in the peroxisomes of Saccharomyces cerevisiae.

Beta-oxidation of the conjugated linoleic acid 9-cis,11-trans-octadecadienoic acid (rumenic acid) was analyzed in vivo in Saccharomyces cerevisiae by monitoring polyhydroxyalkanoate production in the peroxisome. Polyhydroxyalkanoate is synthesized by the polymerization of the beta-oxidation intermediates 3-hydroxyacyl-CoAs via a bacterial polyhydroxyalkanoate synthase targeted to the peroxisome. The amount of polyhydroxyalkanaote synthesized from the degradation of rumenic acid was found to be similar to the amount synthesized from the degradation of 10-trans,12-cis-octadecadienoic acid, oleic acid or 10-cis-heptadecenoic acid. Furthermore, the degradation of 10-cis-heptadecenoic acid was found to be unaffected by the presence of rumenic acid in the media. Efficient degradation of rumenic acid was found to be independent of the Delta(3,5),Delta(2,4)-dienoyl-CoA isomerase but instead relied on the presence of Delta(3),Delta(2)-enoyl-CoA isomerase activity. The presence of the unsaturated monomer 3-hydroxydodecenoic acid in polyhydroxyalkanoate derived from rumenic acid degradation was found to be dependent on the presence of a Delta(3),Delta(2)-enoyl-CoA isomerase activity. Together, these data indicate that rumenic acid is mainly degraded in vivo in S. cerevisiae through a pathway requiring only the participation of the auxiliary enzymes Delta(3),Delta(2)-enoyl-CoA isomerase, along with the enzyme of the core beta-oxidation cycle.