SYNTHESIS OF POLYCYCLIC AROMATIC HYDROCARBONS: STUDIES OF ARYNE CYCLOADDITION, ACID-CATALYZED REARRANGEMENT, AND COUPLING PATHWAYS

Various synthetic routes towards polycyclic aromatic hydrocarbons dibenzo[g,p]chrysene (DBC), chrysene, zethrene, and their derivatives were studied. All of these compounds are not readily available and the literature lacks facile, efficient, and scalable syntheses. Microwave flash pyrolysis (MFP) was used for the synthesis of benzyne and phenanthryne, both of which have the ability to undergo a Diels-Alder reaction at the bay region of polycyclic aromatic hydrocarbons. Phthalic anhydride was used as a benzyne precursor and 9,10-dicarboxyphenanthrene anhydride as a phenanthryne precursor. DBC was observed after the MFP of biphenyl and 9,10-dicarboxyphenanthrene anhydride, signifying phenanthryne generation. Fluoride-induced elimination and Grignard pathways were also explored for phenanthryne formation, but no indication of phenanthryne was seen. DBC was efficiently prepared via a synthetic sequence that is the functional equivalent of the Stone-Wales rearrangement. This sequence is referred to as the pinacol-pinacolone Stone-Wales sequence, which provides DBC in high yield under mild reaction conditions. This is one of the most efficient and scalable syntheses of DBC with all of the steps providing high yields in short reaction times. Calculations for the rearrangement steps using density functional theory (DFT) further support the conclusion of a very efficient synthetic pathway. The same conditions were not successful for the synthesis of chrysene, however treatment of 1-indanopinacol with polyphosphoric acid (PPA) did provide chrysene, suggesting an alternative mechanism from the pinacol-pinacolone Stone-Wales route. For the synthesis of zethrene, the pinacol-pinacolone Stone-Wales sequence was applied to 1-acenaphthenopinacol, but like 1-indanopinacol, no pinacolone structure was observed. Treatment of 1-acenaphthenopinacol with PPA in a microwave reactor generated a small amount of zethrene. This suggests that the reaction between aromatic pinacols and PPA is an alternative and simple route towards polycyclic aromatic hydrocarbons. Other pathways for zethrene synthesis were also studied. Although further work needs to be completed to optimize the syntheses of chrysene and zethrene, these reactions show promise as mild, simple pathways towards these compounds

Cavernous malformation hemorrhage due to trans-mural pressure alterations after cerebrospinal fluid diversion: a case report

Background Cavernous malformations are rare cerebral pseudo-vascular lesions with annualized bleeding rates of 0.5–3% in most studies. Of the various explored risk factors for bleeding to date, only prior hemorrhage has shown significant correlation. Case presentation In this case, we describe a 65-year old man with a peri-ventricular atrial cavernous malformation that hemorrhaged after CSF diversion via ventriculoperitoneal shunting. Serial imaging showed that bleeding continued until the shunt was revised with a programmable valve set at maximum resistance with the addition of a gravitational unit, thereby lowering the trans-mural pressure differential across the cavernous malformation. Conclusions Given that other vascular lesions are subject to hemorrhage from alterations in trans-mural pressure dynamics, we hypothesize that cavernous malformations are similarly affected by trans-mural pressure gradients as they are composed of primitive vascular elements. This hypothesis is corroborated by the temporal correlation of interventions, imaging, and exam findings in the present case, and suggests a potentially important risk factor for hemorrhage in CM patients that affects prognostication and management

The effects of light and temperature on grazing patterns of Douglas Lake snails.

General EcologyThe purpose of this study was to determine if varying light or temperature conditions influence the grazing rates of Elimia livescens. We expected to see increased grazing rates with greater temperatures and with greater light exposure. E. livescens were collected from the littoral zone in South Fishtail Bay of Douglas Lake near Pellston, Michigan, and individually placed into pint sized jars with lake water and one algae-covered rock. We used environmental chambers to simulate six 24-hour light and temperature treatments. Statistical tests between the mean area grazed in light treatments, as well as temperature treatments, showed significant results. Additional tests also yielded significant results, showing that E. livescens were more likely to be found grazing at the end of the 24-hour period in longer light periodicities and higher temperatures. From these results, we were able to conclude that E. livescens grazed the most in settings with longer light exposure and higher temperatures. We were also able to determine that in darker and colder conditions E. livescens are less likely to graze.http://deepblue.lib.umich.edu/bitstream/2027.42/95918/1/Fate_Fey_Hoffman_Sudheendra_2012.pd

Dysbiosis in a canine model of human fistulizing Crohn\u27s disease

Crohn\u27s disease (CD) is a chronic immune-mediated inflammatory condition caused by the loss of mucosal tolerance toward the commensal microbiota. On average, 29.5% and 42.7% CD patients experience perianal complications at 10 and 20 y after diagnosis, respectively. Perianal CD (pCD) result in high disease burden, diminished quality of life, and elevated health-care costs. Overall pCD are predictors of poor long-term outcomes. Animal models of gut inflammation have failed to fully recapitulate the human manifestations of fistulizing CD. Here, we evaluated dogs with spontaneous canine anal furunculosis (CAF), a disease with clinical similarities to pCD, as a surrogate model for understanding the microbial contribution of human pCD pathophysiology. By comparing the gut microbiomes between dogs suffering from CAF (CAF dogs) and healthy dogs, we show CAF-dog microbiomes are either very dissimilar (dysbiotic) or similar (healthy-like), yet unique, to healthy dog\u27s microbiomes. Compared to healthy or healthy-like CAF microbiomes, dysbiotic CAF microbiomes showed an increased abundance of Bacteroides vulgatus and Escherichia coli and a decreased abundance of Megamonas species and Prevotella copri. Our results mirror what have been reported in previous microbiome studies of patients with CD; particularly, CAF dogs exhibited two distinct microbiome composition: dysbiotic and healthy-like, with determinant bacterial taxa such as E. coli and P. copri that overlap what it has been found on their human counterpart. Thus, our results support the use of CAF dogs as a surrogate model to advance our understanding of microbial dynamics in pCD

Pitt Political Review: GSPIA Edition (Spring 2011, Volume 3)

This volume of the Pitt Political Review: GSPIA Edition includes "Legal and Societal Injustice: Gender Inequality and Land Rights in Tanzania" and "The Transformation of Philanthropy in Sub-Saharan Africa: from Traditional Practices to the Establishment of Grantmaking Foundations." The aim of "Legal and Societal Injustice: Gender Inequality and Land Rights in Tanzania" is to increase awareness of the problems surrounding land rights and gender inequality in Tanzania's Karagwe District. "The Transformation of Philanthropy in Sub-Saharan Africa: from Traditional Practices to the Establishment of Grantmaking Foundations" discusses the effectiveness of African foundations in development over the long-term

A proangiogenic signaling axis in myeloid cells promotes malignant progression of glioma

Tumors are capable of coopting hematopoietic cells to create a suitable microenvironment to support malignant growth. Here, we have demonstrated that upregulation of kinase insert domain receptor (KDR), also known as VEGFR2, in a myeloid cell sublineage is necessary for malignant progression of gliomas in transgenic murine models and is associated with high-grade tumors in patients. KDR expression increased in myeloid cells as myeloid-derived suppressor cells (MDSCs) accumulated, which was associated with the transformation and progression of low-grade fibrillary astrocytoma to high-grade anaplastic gliomas. KDR deficiency in murine BM-derived cells (BMDCs) suppressed the differentiation of myeloid lineages and reduced granulocytic/monocytic populations. The depletion of myeloid-derived KDR compromised its proangiogenic function, which inhibited the angiogenic switch necessary for malignant progression of low-grade to high-grade tumors. We also identified inhibitor of DNA binding protein 2 (ID2) as a key upstream regulator of KDR activation during myeloid differentiation. Deficiency of ID2 in BMDCs led to downregulation of KDR, suppression of proangiogenic myeloid cells, and prevention of low-grade to high-grade transition. Tumor-secreted TGF-β and granulocyte-macrophage CSF (GM-CSF) enhanced the KDR/ID2 signaling axis in BMDCs. Our results suggest that modulation of KDR/ID2 signaling may restrict tumor-associated myeloid cells and could potentially be a therapeutic strategy for preventing transformation of premalignant gliomas.This study was supported by the Department of Defense Con- gressionally Directed Medical Research Programs (DOD CDMRP, CA120318 to Y. Huang), Elizabeth’s Hope (J. Greenfield), the Starr Foundation, the Paduano Foundation, the Champalimaud Foun- dation, the Malcolm Hewitt Wiener Foundation, the POETIC Foundation, the Sohn Foundation, the Hartwell Foundation, and the Children’s Cancer and Blood Foundation (all to D. Lyden). Address correspondence to: David Lyden, Department of Pediatrics, Weill Medical Medicine, 413 E. 69th Street, Box 284, New York, New York 10021, USA. Phone: 646.962.6238; E-mail: [email protected]. Or to: Jeffrey P. Greenfield, Department of Neurological Surgery, Weill Cornell Medicine, 525 E 68th Street, Box 99, New York, New York 10065, USA. Phone: 212.746.2363; E-mail: [email protected]. HP’s present address is: Microenvironment and Metastasis Group, Department of Molecular Oncology, Spanish National Cancer Research Center (CNIO), Madrid, Spain.S

Self organising maps for visualising and modelling

The paper describes the motivation of SOMs (Self Organising Maps) and how they are generally more accessible due to the wider available modern, more powerful, cost-effective computers. Their advantages compared to Principal Components Analysis and Partial Least Squares are discussed. These allow application to non-linear data, are not so dependent on least squares solutions, normality of errors and less influenced by outliers. In addition there are a wide variety of intuitive methods for visualisation that allow full use of the map space. Modern problems in analytical chemistry include applications to cultural heritage studies, environmental, metabolomic and biological problems result in complex datasets. Methods for visualising maps are described including best matching units, hit histograms, unified distance matrices and component planes. Supervised SOMs for classification including multifactor data and variable selection are discussed as is their use in Quality Control. The paper is illustrated using four case studies, namely the Near Infrared of food, the thermal analysis of polymers, metabolomic analysis of saliva using NMR, and on-line HPLC for pharmaceutical process monitoring

Deletion of Fibroblast Growth Factor Receptor 2 from the Peri-Wolffian Duct Stroma Leads to Ureteric Induction Abnormalities and Vesicoureteral Reflux

Purpose: Pax3cre-mediated deletion of fibroblast growth factor receptor 2 (Fgfr2) broadly in renal and urinary tract mesenchyme led to ureteric bud (UB) induction defects and vesicoureteral reflux (VUR), although the mechanisms were unclear. Here, we investigated whether Fgfr2 acts specifically in peri-Wolffian duct stroma (ST) to regulate UB induction and development of VUR and the mechanisms of Fgfr2 activity. Methods: We conditionally deleted Fgfr2 in ST (Fgfr2 ST-/- ) using Tbx18cre mice. To look for ureteric bud induction defects in young embryos, we assessed length and apoptosis of common nephric ducts (CNDs). We performed 3D reconstructions and histological analyses of urinary tracts of embryos and postnatal mice and cystograms in postnatal mice to test for VUR. We performed in situ hybridization and real-time PCR in young embryos to determine mechanisms underlying UB induction defects. Results: We confirmed that Fgfr2 is expressed in ST and that Fgfr2 was efficiently deleted in this tissue in Fgfr2 ST-/- mice at embryonic day (E) 10.5. E11.5 Fgfr2 ST-/- mice had randomized UB induction sites with approximately 1/3 arising too high and 1/3 too low from the Wolffian duct; however, apoptosis was unaltered in E12.5 mutant CNDs. While ureters were histologically normal, E15.5 Fgfr2 ST-/- mice exhibit improper ureteral insertion sites into the bladder, consistent with the ureteric induction defects. While ureter and bladder histology appeared normal, postnatal day (P) 1 mutants had high rates of VUR versus controls (75% versus 3%, p = 0.001) and occasionally other defects including renal hypoplasia and duplex systems. P1 mutant mice also had improper ureteral bladder insertion sites and shortened intravesicular tunnel lengths that correlated with VUR. E10.5 Fgfr2 ST-/- mice had decreases in Bmp4 mRNA in stromal tissues, suggesting a mechanism underlying the ureteric induction and VUR phenotypes. Conclusion: Mutations in FGFR2 could possibly cause VUR in humans. © 2013 Walker et al

Factores asociados al consumo de drogas ilícitas en estudiantes de secundaria, universitarios y población general en Colombia

Tesis doctoralSegún los estudios poblacionales que se realizan en Colombia desde 1992, el consumo de drogas ilegales crece en Colombia de manera sostenida. Tales estudios presentan análisis descriptivos, distribuciones porcentuales y prevalencias, sin que se ahonde en el escrutinio de los factores que están incidiendo en las cifras de consumo. Con el interés de ahondar en la comprensión de éste fenómeno, facilitar su predicción y contribuir con su atención integral, en esta investigación se propone identificar factores individuales, familiares y del contexto, asociados al consumo de drogas ilegales en Colombia. Para alcanzar dichos propósitos se realizan dos investigaciones: 1) una revisión sistemática sobre los factores que inciden en el consumo de drogas ilegales y 2) la formulación de tres modelos de factores asociados al consumo de drogas ilegales en Colombia y la clasificación del tipo de consumidores, a partir de los factores identificados previamente. Se analizaron las bases de datos de estudios nacionales realizados con población general, estudiantes de secundaria y estudiantes universitarios, en las cuales se utilizó la metodología del Sistema Interamericano de Datos Uniformes sobre Consumo de Drogas. Inicialmente se establecieron en cada uno de los tres grupos analizados, los factores relacionados con el consumo de sustancias ilícitas y las clases latentes de consumidores, los cuales permitieron plantear tres modelos de factores asociados al consumo, uno para cada población. Se encontró que el consumo de drogas ilícitas en el último año, se asoció en las tres poblaciones, con tener amigos y familiares consumidores de drogas ilícitas; haber iniciado el consumo de tabaco y alcohol, y tener una baja percepción del riesgo con respecto al uso de marihuana. Por su parte, con el análisis de clases latentes se identificaron tres clases entre los consumidores de drogas ilícitas en la población general, seis clases entre escolares y cuatro clases entre universitarios. Los resultados indican factores que pueden ser considerados para orientar la prevención del consumo de drogas ilegales y su atención integral.1. INTRODUCCIÓN 2. JUSTIFICACIÓN Y PLANTEAMIENTO DEL PROBLEMA 3. OBJETIVOS 4. ESTUDIO 1: REVISIÓN SISTEMÁTICA SOBRE LOS FACTORES ASOCIADOS AL RIESGO DEL CONSUMO DE DROGAS ILEGALES 5. ESTUDIO 2: FORMULACIÓN DE MODELOS DE CONSUMO DE DROGAS ILÍCITAS EN COLOMBIA, CON ESTUDIANTES DE SECUNDARIA, UNIVERSITARIOS Y POBLACIÓN GENERAL 6.REFERENCIAS 7. ANEXOSDoctoradoDoctor en Psicologí