cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Nonclassical folate analogs as inhibitors of dihydrofolate reductase and thymidylate synthase
Creators: name: Francom, Paula
Publisher: name: University of Utah
Year: 2012
Subjects: subject: Therapeutic Use
subject: Organic Chemistry
subject: FOS: Chemical sciences

description: The principal goal of this work has been to design exceptionally potent inhibitors of the folate dependent enzymes dihydrofolate reductase (DHFR) and thymidylate synthase (TS) which are at the same time selective enough to have reduced host toxicity.  Toward this end, the synthesis and evaluation of a series of five novel 2,4-diamino-pyrido[3,2-d]pyrimidine inhibitors of dihydrofolate reductase (DHFR) and of two novel 10-deaza flexible folate" inhibitors of thymidylate synthase (TS) have been accomplished.  The five 2,4-diaminopyrido (3,2-d) pyrimidine inhibitors displayed potent nM level inhibition of DHFRs from P. carinii, T. gondii, human and rat liver. Inhibition of DHFR from T. gondii was approximately equipotent with that observed for the clinically approved agent trimetrexate. Though potent inhibitors, these new agents offered no significant improvement in selectivity for the P. carinii or T. gondii DHFR.  Cocrystallization of a previously characterized "flexible folate" multisubstrate analog inhibitor (MAI) in the TS active site and resolution of the structure by difference Fourier analysis demonstrated that linkage of the MAI's folate and nucleotide moieties by means of a methylene bridge to an $sp\sp2$ hybridized carbon at position C-5 of the nucleotide's pyrimidine ring prevents irreversible inhibition of TS. The crystallographic and molecular modeling studies served as a basis for the subsequent design of two novel 10-deaza "flexible folate" inhibitors of TS. No inhibitory activity was observed for either compound against TS enzymes from P. carinii. T. gondii, human rat liver or Trypanosoma cruzii. The lack of biological activity of these inhibitors emphasizes the important contribution of entropic factors to the free energy of ligand binding. For conformationally flexible inhibitors which lack functional groups capable of participating in hydrogen bonding networks and/or forming strong electrostatic interactions with the enzyme, entropic factors may predominate in the energetics of ligand binding and must be given careful consideration.  The findings presented herein reemphasize the necessity of adopting an integrated approach to structure-based drug design in which successive cycles of crystallographic resolution of enzyme-ligand complexes, ligand design, synthesis and biological evaluation are required for optimization of inhibitor potency and selectivity.
Evolution of chemical dependence in a sample of Utah and Colorado nurses
Creators: name: Bittle, Sheila Peterson
Publisher: name: University of Utah
Year: 2012
Subjects: Utah
Drug Effects

description: The purpose of this research was to describe and explore the characteristics and patterns of substance use, abuse, experiences and consequences of addictive illness of a sample of substance-dependent nurses through personal indepth interviews.  Experiences with substance abuse were examined within the context of the nurses' personal and professional lives.  The overall concern was:  What does the nursing profession need to know and understand about this complex problem among nurses to plan effective education, prevention, and intervention approaches?  Twenty-one nurses who live in Utah and Colorado participated in indepth tape-recorded interviews with the researcher.  This research has identified baseline information useful for future research on a relatively unexplored phenomenon.  Quantitative data described the substance dependent nurses' background and characteristics and consequences of their addition.  Qualitative analysis described the circumstances and experiences of nurses in the four evolutionary phases of the addiction process:  Beginning phase, Addictive phase, Out of Control phase, and Recovery.  Although various patterns were described in each phase, a notable finding was that nearly half of these participants were experiencing problems with substance abuse while they were nursing students, and all had serious problems while they were employed as registered nurses.  Their lack of knowledge about substance abuse, distorted self-perceptions, negative attitudes and problems with personal and professional relationships were significant barriers to their recognizing their problem and seeking help.  Prior to their recovery, they sought help several times, both for the addition and for medical complication or systems of their substance abuse and addiction.  Their lack of success in earlier attempts to seek help was described as the failure of nurse participants and health professionals to identify and address the substance abuse in treatment.  Consequences to substance abuse were described as the potential for suicide, hospitalizations, dual addiction, and professional employment and licensure sanctions.  Recovery was achieved only after nurses reached a late stage in the addiction process which was described a being out of control.  Once they accepted their need for help, they sought help from a variety of treatment modalities and had attained their current level of sobriety.  They perceived support groups like AA and peer support as a valuable adjunct to their recovery and continued sobriety.  They recommended that peer support groups assist addicted nurses with legal, practice, ethical, and support issues, and prevention, education and intervention strategies.
Sonnenfleckenzeichnung Nr. 23339.
Zeichnung von Flecken und Fackelflächen zur Ermittlung der Sonnenaktivität am 08.05.1970, erstellt von Fritz Riesen
Creators: name: [s.n.]
Publisher: name: [s.n.]
Year: 1970

description: Bleistiftzeichnung mit Tinte und Farbstift überschrieben, erstellt als Projektionsbildzeichnung in der Eidgenössischen Sternwarte Zürich. Instrument: Zeiss Coudé-Refraktor (150/2250 mm).
Die Beobachtungen zu Einzelflecken und zu Sonnenfleckengruppen wurden mit Bleistift auf einem Vordruck eingetragen. Später wurden ergänzende Angaben aufgrund auswärtiger Beobachtungen direkt auf der Fleckenzeichnung hinzugefügt. Zusätzlich notiert: Tabelle mit statistischen Angaben – mit Vermerk der Werte Gr, f und g, wobei die Bestimmung der Fleckenrelativzahl nach wie auf visueller Beobachtung und anderer Instrumentierung beruhte (und dafür das entsprechende Registerblatt (in Teilbestand acht) ausgefüllt wurde). Zusammen mit den täglichen Werten oft Angabe der Resultate der Flächenmessungen der Flecken (F und F -o) in Millionsteln der Scheibe bzw. der Halbkugel
Dor Crónica em Pediatria: Orientações Para os Profissionais de Saúde
Creators: name: Santos, Susana
name: Santos, Elsa Andrade
name: Lacerda, Ana Forjaz
Publisher: name: Portuguese Journal of Pediatrics
Year: 2018

description: A realidade da pediatria passa cada vez mais pelo acompanhamento da criança com doença crónica, com necessidades de saúde complexas. Assim, para além do contacto com a dor associada à doença aguda e/ou realização de procedimentos, são frequentes para o pediatra as situações de dor recorrente ou persistente em diversos contextos de doença. Apesar do avanço em conhecimentos e intervenções disponíveis, persiste uma inadequada prevenção e alívio da dor na criança, com importantes consequências negativas imediatas e futuras a nível biológico, psicológico e social, facto reconhecido pela Organização Mundial da Saúde em 2012. Neste trabalho é feita uma revisão bibliográfica sobre a abordagem da dor pediátrica, com ênfase particular para a dor na doença crónica complexa, não dispensando a necessidade de recorrer a outras consultas e apoio de profissionais com experiência nesta área.
description: Portuguese Journal of Pediatrics, Vol. 49 No. 2 (2018)
Factores ambliogénicos em idade pré-escolar – rastreio no âmbito dos cuidados de saúde primários de uma área urbana
Creators: name: Amaral, Joana
name: Machado, Marta
name: Azenha, Cátia
name: Monteiro, Ana Madalena
name: Castela, Rui
name: Fernandes, Lívia
Publisher: name: Portuguese Journal of Pediatrics
Year: 2018

description: Introdução: A ambliopia é a principal causa de perda de visão monocular em idade pediátrica, uma condição prevenível e reversível quando detetada e tratada atempadamente. O erro refrativo é a causa mais comum de ambliopia na infância e a sua deteção não se pode limitar à avaliação tradicional da visão feita nos cuidados primários. A aplicação de dispositivos de foto-rastreio apresenta elevado valor preditivo positivo (73%). Métodos: Análise prospetiva de fatores ambliogénicos em crianças com idades compreendidas entre os 12 meses e os 6 anos numa área urbana da região centro de Portugal, recorrendo a equipamento de foto-rastreio (Plusoptix®S04). Resultados: Foram rastreadas 409 crianças em idade pré-escolar. Destas, 49 (12%) apresentavam critérios para referenciação, 15 já eram seguidas em consulta de oftalmologia. Das 27 crianças que compareceram à consulta 19 (70,4%) foram diagnosticadas, sendo o diagnóstico de astigmatismo em oito, aniso-astigmatismo cinco, aniso-hipermetropia em quatro, miopia em uma e aniso-miopia em uma. Este método de rastreio demonstrou ter um valor preditivo positivo de 70%. Durante os 13,8 ± 6,8 meses de seguimento, todas as crianças melhoraram a acuidade visual com correção ótica. Discussão: Nenhuma criança mostrava sintomatologia que sugerisse perturbação da visão, o que se explica pelo facto dos sinais de diminuição da acuidade visual nestas idades passarem frequentemente despercebidos. O principal fator de risco para ambliopia foi o astigmatismo. A deteção de erros refrativos em idade pré-escolar não se pode limitar à observação tradicional em cuidados de saúde primários. O foto-rastreio demonstrou ser um excelente método de rastreio, respeitando todos os princípios estabelecidos pela Organização Mundial de Saúde.
description: Portuguese Journal of Pediatrics, Vol. 49 No. 2 (2018)
Mechanisms for increasing epidermal growth factor receptor activity following receptor amplification
Creators: name: Schooler, Kevin Patrick
Publisher: name: University of Utah
Year: 2012
Subjects: Oncogenesis
Ligand

description: Amplification of the Epidermal Growth Factor Receptor (EGF-R) is closely associated with oncogenesis. We attempted to elucidate the mechanism used by receptor amplified cells to increase EGF-R signaling levels and/or duration. Constitutive EGF-R associated phosphotyrosine (PY), on a per cell basis, increases with receptor amplification. Moreover, PY levels appear to increase linearly with receptor level. We found that the simultaneous application of the EGF-R antagonistic antibody 225 and metalloprotease inhibitors, which block ligand production, resulted in a synergistic attenuation of this PY. Therefore, most, if not all, of the constitutive PY is ligand dependent. However, by measuring the concentration of Transforming Growth Factor Alpha (TGF?) secreted into the media, we showed that this ligand dependent increase in constitutive PY was not due to an increase in autocrine ligand expression. Furthermore, we found that cell lines can capture most of the autocrine ligand they produce regardless of receptor expression level. Using a modified pulse-chase assay, we determined that ligand was recaptured more efficiently following recycling in cells displaying receptor amplification. This increased capture efficiency at least partially explains the increased level of constitutive PY observed following receptor amplification. In another series of experiments, we found that the regulatory apparatus of cells with receptor amplification was more than adequate to handle the ligand levels those cells would see under physiological conditions. Therefore, a limited capacity of these regulatory systems is unlikely to account for the increased constitutive PY. However, PY was removed faster than EGF-R protein was degraded in cells with low receptor numbers while PY is removed at a rate similar to receptor degradation in amplified cells. We found that the number of intracellular EGF-Rs activated was larger than the number of available ligand molecules in the amplified lines. This result indicates a degree of signal amplification. However, this effect is not observed in the low receptor number expressing cell lines. We propose that unoccupied, intracellular EGF-R contribute to the increased receptor activity we observe in receptor amplified cell lines by a "ligand echo" effect.
Trombocitopenia Neonatal Aloimune: Um Diagnóstico a Ter em Mente
Creators: name: Teixeira, Ana Teresa
name: Barradas, Anabela
name: Trindade, Cristina
name: Barroso, Rosalina
Publisher: name: Portuguese Journal of Pediatrics
Year: 2018

description: A trombocitopenia aloimune neonatal é das principais causas de trombocitopenia grave no recém-nascido, estimando-se que afete um em 1000-10000 nados vivos, estando provavelmente subdiagnosticada. Deve-se à transferência placentar de anticorpos maternos contra antigénios presentes nas plaquetas do feto mas ausentes nas plaquetas da mãe. A trombocitopenia é de início precoce, podendo ser grave com complicações como a hemorragia intracraniana, que pode ocorrer antes ou após o nascimento. Descreve-se o caso de um recém-nascido filho de pais naturais da China com uma trombocitopenia grave de início precoce de causa aloimune por incompatibilidade do antigénio HPA-3b. Esta é uma causa rara de trombocitopenia aloimune (os antigénios mais frequentes são o HPA-1a e HPA-5b), com poucos casos descritos na literatura. O diagnóstico colocou dificuldades acrescidas, uma vez que os anticorpos maternos são lábeis, tendo a genotipagem plaquetária sido importante para o esclarecimento da incompatibilidade.
description: Portuguese Journal of Pediatrics, Vol. 49 No. 2 (2018)
Sonnenfleckenzeichnung Nr. 23488.
Zeichnung von Flecken und Fackelflächen zur Ermittlung der Sonnenaktivität am 19.10.1970, erstellt von Werner Scheidegger
Creators: name: [s.n.]
Publisher: name: [s.n.]
Year: 1970

description: Bleistiftzeichnung mit Tinte und Farbstift überschrieben, erstellt als Projektionsbildzeichnung in der Eidgenössischen Sternwarte Zürich. Instrument: Zeiss Coudé-Refraktor (150/2250 mm).
Die Beobachtungen zu Einzelflecken und zu Sonnenfleckengruppen wurden mit Bleistift auf einem Vordruck eingetragen. Zusätzlich notiert: Tabelle mit statistischen Angaben – mit Vermerk der Werte Gr, f und g, wobei die Bestimmung der Fleckenrelativzahl nach wie auf visueller Beobachtung und anderer Instrumentierung beruhte (und dafür das entsprechende Registerblatt (in Teilbestand acht) ausgefüllt wurde). Zusammen mit den täglichen Werten oft Angabe der Resultate der Flächenmessungen der Flecken (F und F -o) in Millionsteln der Scheibe bzw. der Halbkugel. Es sind Angaben zu Protuberanzen vermerkt
title: Δημιουργία κυβερνοφυσικού συστήματος για τη γεωργία
title: Creation of a cyberphysical system for agriculture
titleType: AlternativeTitle
Creators: name: Αθανασίου, Παναγιώτης
Publisher: name: Πανεπιστήμιο Δυτικής Αττικής
Year: 2021
Subjects: Κυβερνοφυσικά συστήματα
Cyberphysical systems
Ανάπτυξη διαδικτυακών εφαρμογών
Βάσεις δεδομένων
Μικροϋπηρεσίες
Γεωργία
Rest API
Διακομιστής
.NET Framework
Raspberry Pi
Κόμβος
Apache CouchDB

description: Δημιουργία λογισμικού και υλικολογισμικού με στόχο την αυτοματοποίηση και ανύψωση της γεωργίας στον κυβερνοχώρο. Πιο συγκεκριμένα, αφορά για την δημιουργία μιας συνολικής λύσης εφαρμογής μικρό υπηρεσιών για την ομαδοποίηση, τη παρακολούθηση και τον αυτόματο πολισμό φυτών.
No Limiar Da Viabilidade: Casuística de Dez Anos Num Hospital de Apoio Perinatal Diferenciado
Creators: name: Rodrigues, Marlene
name: Machado, Clara
name: Silva, Nicole
name: Sá, Carla
name: Silva, Albina
name: Abreu, Eduarda
name: Pinheiro, Liliana
name: Pereira, Almerinda
name: Costa, Miguel
Publisher: name: Portuguese Journal of Pediatrics
Year: 2018

description: Introdução: Nas últimas décadas, os avanços na tecnologia, cuidados obstétricos e neonatais têm possibilitado a sobrevivência de recém-nascidos pré-termo com idades gestacionais cada vez menores. Aumentar a sobrevivência, sem aumentar a morbilidade e sequelas, é dos maiores desafios da medicina perinatal. Este trabalho pretendeu analisar a morbilidade e mortalidade nos nados-vivos nascidos entre as 23 e 25 semanas e seis dias de idade gestacional e determinar o limiar de viabilidade, num hospital de apoio perinatal diferenciado. Métodos: Estudo retrospetivo abrangendo o período de 1 de junho de 2006 e 31 de maio de 2016. Avaliaram-se dados demográficos, morbilidade, mortalidade e evolução, incluindo fatores de morbilidade major e sequelas graves do neurodesenvolvimento aos 24-30 meses. Resultados: Estudaram-se 28 recém-nascidos, seis com 23 semanas, 12 com 24 semanas e 10 com 25 semanas, com mediana de peso ao nascer de 631,5 g. A mortalidade global foi 68% e o limiar de viabilidade foi as 25 semanas. Constatou-se que a idade gestacional e o peso ao nascimento foram os únicos fatores associados a morte. Todos os recém-nascidos com peso superior 800 g sobreviveram e todos eles tinham 25 semanas de idade gestacional. Não se encontrou associação estatisticamente significativa entre as variáveis avaliadas e o desenvolvimento de sequelas graves. Todos os sobreviventes com 24 semanas apresentaram um ou mais fatores adicionais de morbilidade major e 67% apresentaram sequelas graves; com 25 semanas, 50% não apresentaram fatores adicionais de morbilidade major nem sequelas graves. Discussão: A morbilidade e mortalidade foram elevadas e o limiar de viabilidade foi as 25 semanas de idade gestacional.
description: Portuguese Journal of Pediatrics, Vol. 49 No. 2 (2018)
Lesões Nodulares na Face: Estreita Fronteira Diagnóstica Entre a Autoimunidade e a Malignidade
Creators: name: Moeda, Sofia
name: Boto, Ana
name: Vale, Esmeralda
name: Freitas, Isabel
name: Cabral, Marta
Publisher: name: Portuguese Journal of Pediatrics
Year: 2018

description: A paniculite lúpica é uma forma rara de lúpus eritematoso cutâneo crónico. Deve diferenciar-se de outras entidades inflamatórias crónicas, infeciosas e neoplásicas. Descreve-se o caso de uma criança do sexo feminino, 7 anos, com placas pétreas, eritemato-violáceas e indolores na face, com três anos de evolução. Sem sintomas sistémicos. Sem leucocitose ou citopénias, proteína C reativa 0,06 mg/dL, velocidade de sedimentação 19 mm/h. Foi avaliada por dermatologia, tendo sido colocadas as hipóteses diagnósticas de paniculite lúpica / linfoma paniculítico de células T subcutâneo. Realizou biópsia cutânea. A avaliação oftalmológica, ecografia abdominal e radiografia torácica não revelaram alterações, imunoglobulina G 20,1 g/dL, componentes do complemento C3, C4, CH50 e C1q normais, auto-anticorpos negativos. Exame imunohistoquímico e estudo molecular favoreceram o diagnóstico de paniculite lúpica. Evolução favorável sob hidroxicloroquina e corticóide sistémico, e posteriormente metotrexato. Atualmente em remissão clínica completa. A vigilância e monitorização de compromisso sistémico ou evolução para malignidade são essenciais.
description: Portuguese Journal of Pediatrics, Vol. 49 No. 2 (2018)
Sonnenfleckenzeichnung Nr. 23418.
Zeichnung von Flecken und Fackelflächen zur Ermittlung der Sonnenaktivität am 01.08.1970, erstellt von Antoine Zelenka
Creators: name: [s.n.]
Publisher: name: [s.n.]
Year: 1970

description: Bleistiftzeichnung mit Tinte und Farbstift überschrieben, erstellt als Projektionsbildzeichnung in der Eidgenössischen Sternwarte Zürich. Instrument: Zeiss Coudé-Refraktor (150/2250 mm).
Die Beobachtungen zu Einzelflecken und zu Sonnenfleckengruppen wurden mit Bleistift auf einem Vordruck eingetragen. Später wurden ergänzende Angaben aufgrund auswärtiger Beobachtungen direkt auf der Fleckenzeichnung hinzugefügt. Zusätzlich notiert: Tabelle mit statistischen Angaben – mit Vermerk der Werte Gr, f und g, wobei die Bestimmung der Fleckenrelativzahl nach wie auf visueller Beobachtung und anderer Instrumentierung beruhte (und dafür das entsprechende Registerblatt (in Teilbestand acht) ausgefüllt wurde). Zusammen mit den täglichen Werten oft Angabe der Resultate der Flächenmessungen der Flecken (F und F -o) in Millionsteln der Scheibe bzw. der Halbkugel
Dor Abdominal em Pré-Adolescente
Creators: name: Carvalho, Tânia
name: Tavares, Madalena
name: Simões, Mafalda
name: Lito, David
Publisher: name: Portuguese Journal of Pediatrics
Year: 2018

description: O hímen imperfurado é a malformação obstrutiva mais comum do trato genital feminino. Quando não identificado em idade precoce, provocará manifestações clínicas, nomeadamente na adolescência. Apresenta-se um caso de adolescente com dor e massa abdominal provocada por hímen imperfurado. A colaboração entre especialidades é crucial para a orientação da dor abdominal em pré adolescente.
description: Portuguese Journal of Pediatrics, Vol. 49 No. 2 (2018)
Alternative methods to fabricate and evaluate copper zinc tin sulfide based absorber layers on transparent conducting electrodes
Creators: name: Sarswat, Prashant Kumar
Publisher: name: University of Utah
Year: 2015

description: This study is focused on fabrication and characterization of Cu2ZnSnS4 (CZTS) films on transparent conducting substrate. CZTS films were synthesized using solution based methods. A specially designed sequential and single stage electrochemical method as well as spin coating method was used to grow layers of precursors. Deposition of constituent metallic layers was carried out on SnO2/F (Fluorinated tin oxide or FTO) coated glass substrates. The electrodeposited/spin coated layers were annealed in a sulfur environment to obtain CZTS. Structural, morphological and optical characterization experiments were performed using several techniques including x-ray diffraction, Raman and UV-visible spectroscopy, scanning electron microscopy, and atomic force microscopy. All characterization experiments indicated the films are single phase with a measured direct band gap of ~1.5 eV. Photocurrent response of CZTS film grown on FTO substrate was measured using alternating front illumination and rear illumination in a Eu3+/Eu2+ solution environment. The photoelectrochemical response exhibited during rear illumination is comparable to that obtained for front illumination. The promising photocurrent data for CZTS films suggest these films have potential application in a variety of photovoltaic devices. A comparative study revealed that photoelectrochemical response exhibited by the films grown on molybdenum substrate is greater than that obtained for film grown on FTO substrate. A modified form of the Gartner model to explain J-V characteristics for CZTS-electrolyte solution has been proposed. Fundamental information such as energy band gap-temperature relationship and temperature dependent study of Raman ‘A' mode for CZTS thin films were also investigated in this research.
Preditores clínico-analíticos da doença de Kawasaki refratária à Imunoglobulina endovenosa
Creators: name: Rangel, Maria Adriana
name: Soares, Diana
name: Santos, Helena
name: Rodrigues, Lúcia
name: Carriço, Ana
name: Moreira, Diana
Publisher: name: Portuguese Journal of Pediatrics
Year: 2018

description: Introdução: A doença de Kawasaki refratária à imunoglobulina endovenosa ocorre em 10% a 20% dos casos, condicionando maior risco de anomalias das artérias coronárias. O objetivo deste estudo foi determinar fatores preditivos de doença de Kawasaki refratária à imunoglobulina endovenosa. Métodos: Estudo retrospetivo analítico dos doentes com doença de Kawasaki que realizaram imunoglobulina endovenosa num hospital do norte de Portugal, entre 2006-2016. Os doentes foram divididos em dois grupos consoante a resposta à imunoglobulina endovenosa, refratária e não refratária. Resultados: Foram incluídos 23 doentes, 73,9% sexo masculino, mediana da idade 19 meses, dos quais seis (26,1%) foram considerados refratários. Os grupos não diferiram quanto ao género e manifestações clínicas. Identificaram-se diferenças significativas quanto à idade > 4 anos (66,7% vs 17,6%; p < 0,04), duração da febre à data de diagnóstico e administração imunoglobulina endovenosa (5 vs 9 dias; p < 0,01), linfócitos na admissão (1400 vs 4400 células/μL, p = 0,01), plaquetas na admissão (255 000 vs 432 000 células/μL, p < 0,01), mínimo de hemoglobina (7,3 vs 9,9 g/dL, p < 0,01) e mínimo de albumina (2,4 vs 3,4g/dL, p = 0,01). Ocorreram alterações ecocardiográficas em 34,8% (anomalias das artérias coronárias em 8,7%). Embora sem atingir a significância estatística, uma proporção superior de doentes na doença de Kawasaki refratária apresentou ecocardiograma alterado na fase aguda (66,7% vs 25,0%). Discussão: Os fatores preditivos de doença de Kawasaki refratária identificados foram sobreponíveis aos descritos na literatura, excetuando a idade e os linfócitos na admissão. A diversidade de fatores preditivos nos estudos publicados em diferentes grupos étnicos, salientam a necessidade de um estudo multicêntrico português para a validação destes fatores na nossa população, que poderão condicionar a abordagem terapêutica inicial.
description: Portuguese Journal of Pediatrics, Vol. 49 No. 2 (2018)
Síndrome de Ehler-Danlos: Uma Criança com Pele de Veludo
Creators: name: Moreira, Ana Raquel Silva
name: Lopes, Susana
name: Martins, Cecília
name: Vieira, Clara
Publisher: name: Portuguese Journal of Pediatrics
Year: 2018

description: A síndrome de Ehler-Danlos é um distúrbio hereditário raro do tecido conjuntivo, que se caracteriza por hipermobilidade articular, hiperextensibilidade e fragilidade cutânea. Relata-se o caso clínico de uma criança de 6 anos, seguida em consulta por pele aveludada, hiperextensível e frágil, associada a equimoses e hematomas frequentes e persistentes, com formação de cicatrizes atróficas. Tinha antecedentes pessoais de anemia ferropénica e má evolução estaturo-ponderal. Era suspeita de ser vítima de maus tratos devido às cicatrizes exageradas. No exame objetivo não tinha dismorfias evidentes e a pele era suave, aveludada ao toque, hiperextensível (prega abdominal > 2 cm) com equimoses associadas a nódulos subcutâneos e hipermobilidade articular (9/9 score Beighton). O diagnóstico da síndrome clássica é clínico. Habitualmente com bom prognóstico, tem um risco de recorrência na descendência de 50%.
description: Portuguese Journal of Pediatrics, Vol. 49 No. 2 (2018)
The total synthesis and biological evaluation of Bryostatin 1 and its analogues
Creators: name: Poudel, Yam Bahadur
Publisher: name: University of Utah
Year: 2012
Subjects: Bryostatin
Synthesis
Marine pharmacology
Bugula neritina

description: Bryostatin 1 is a complex natural product isolated from the marine bryozon Bugula neritina by Pettit and coworkers whose structure was reported in 1982. This  highly oxygenated macrolide has complex and unprecedented architectural features. In addition, bryostatin 1 has exhibited a remarkable biological profile including anticancer activity, synergetic effect with other anticancer agents, reversal of multidrug resistance,  stimulation of the immune system, improvement of learning and memory, neuroprotection after stroke, reduction of amyloid plaque formation, and activity against HIV. The anticancer activity of bryostatin 1 has resulted in some 80 phase I and II clinical trials and a clinical trial against Alzheimer's disease is underway.  Despite having potential as a therapeutic drug, the availability of bryosatin 1 from natural as well as other sources is extremely limited. Synthesis of simplified analogues of bryostatin 1 provides an alternative way to solve the supply problem. With an aim of practical synthesis of simplified bryostatin 1 analogues, our group started the study of structure activity relationship of bryostatin 1 using a newly discovered pyran annulation  methodology.   The work presented in this dissertation focuses on the synthesis, computational study and biological evaluation of bryostatin 1 analogues modified in the A and B ring region. Specifically, the role of three substituents in the A and B ring region has been investigated by  synthesizing C30-decarbomethoxy bryostatin 1, C9-deoxy bryostatin 1 and a C8-gemdimethyl analogue. This study suggested that these three groups do not by themselves serve as functional switches between the PMA versus bryostatin 1 like activity of bryostatin analogues. Moreover, analogues with more polar groups in the A, B ring region tend to behave like bryostatin 1 as opposed to PMA and vice versa.   In addition to bryostatin analogues, the first total synthesis of bryostatin 1 was accomplished in 30 steps for longest linear sequence from commercially available starting material. The synthesis involved a highly convergent union of fully functionalized A and C rings by pyran annulation. The route developed to bryostatin 1 is also applicable for the synthesis of bryostatin 7, bryostatin 9 and bryostatin 15 as well as numerous bryostatin analogues.
Reception of classical mythology in Woody Allen's dramas: Crimes and Misdemeanors, Match Point, and Cassandra's Dream
Creators: name: Savenkova, Olga Sergeyevna
Publisher: name: University of Utah
Year: 2013
Subjects: Cassandra's Dream
Classical Mythology
Crimes and Misdemeanors
Drama
Match Point
Woody Allen

description: The thesis explores the reception of classical mythology in three dramas by Woody Allen: Crimes and Misdemeanors (1989), Match Point (2005), and Cassandra's Dream (2007). These films are studied as contemporary interpretations of the ancient stories of Oedipus, Narcissus, and Orestes. Allen's films use mythic patterns to meditate on such ancient themes as illusion versus reality, status, alienation and self-identity, the tragedy of love, human conscience, moral choice and responsibility, fate and revenge, crime and punishment. The purpose of this study is to show how Woody Allen's dramas originate from ancient mythology and how the study of Greek tragedy and Roman poetry sheds light on the problems centered in his movies, which are neglected by most critics. The comparative study of Allen's dramas in the context of classical mythology is based on a dialogic relation between ancient and modern narratives proposed by Vladimir Bibler. In this dialogue, every work of art contributes to the deeper understanding of one another. The interpretation of film and text in this thesis is based on close reading analysis. The study of Crimes and Misdemeanors in the context of Sophocles's Oedipus Rex discovers the film as an intertext and a metatext concerned with art's capacities for representation of reality. The study of Match Point in the context of Ovid's Narcissus reveals the problem of self-identification as a significant dimension of both narratives. A comparative analysis of Cassandra's Dream and Aeschylus's The Oresteia results in the insight about the film's title and main conflict. Eventually, the study provides an example of a dialogic approach to comparative literature in practice.
Exploiting example structure in multiple instance learning
Creators: name: Pokkunuri, Rama Krishna Sandeep
Publisher: name: University of Utah
Year: 2012
Subjects: Cutting plane optimization
Machine learning
Multiple instance learning
Structured prediction

description: Multiple Instance Learning (MIL) is a type of supervised learning with missing data. Here, each example (a.k.a. bag) has one or more instances. In the training set, we have only labels at bag level. The task is to label both bags and instances from the test set. In most practical MIL problems, there is a relationship between the instances of a bag. Capturing this relationship may help learn the underlying concept better. We present an algorithm that uses the structure of bags along with the features of instances. The key idea is to allow  a structured support vector machine (SVM) to "guess" at the true underlying structure, so long as it is consistent with the bag labels. This idea is formalized and a new cutting plane algorithm is proposed for optimization.  To verify this idea, we implemented our algorithm for a particular kind of structure - hidden markov models. We performed experiments on three datasets and found this  algorithm to work better than the existing algorithms in MIL. We present the details of these experiments and the effects of varying different hyperparameters in detail. The key contribution from our work is a very simple loss function with only one hyperparameter that needs to be tuned using a small portion of the training set.  The thesis of this work is that it is possible and desirable to exploit the structural relationship between instances in a bag, even though that structure is not observed at  training time (i.e., correct labels for all the instances are unknown). Our work opens a new direction to solving the MIL problem. We suggest a few ideas to further our work in this direction.
Acidente Vascular Cerebral Isquémico Neonatal no Registo Nacional da Unidade de Vigilância Pediátrica: Como Estão Estas Crianças Seis Anos Depois?
Creators: name: Fraga, Beatriz
name: Monteiro, José Paulo
Publisher: name: Portuguese Journal of Pediatrics
Year: 2018

description: Introdução: Pretendeu-se avaliar uma coorte de recém-nascidos com acidente vascular cerebral isquémico neonatal sintomático, incluindo o seguimento até aos 5-7 anos. Métodos: Estudo de coorte prospetivo e descritivo, baseado em dados retirados do registo nacional de acidente vascular cerebral neonatal, entre 2009-2011. Foram incluídos os casos de acidente vascular cerebral isquémico neonatal sintomático confirmados por ressonância magnética crânio-encefálica. Resultados: Analisaram-se 21 recém-nascidos, 12 do sexo masculino, mediana da idade gestacional 39 semanas e do peso ao nascer 3389 g. Apresentaram antecedentes obstétricos ou perinatais significativos 18 recém-nascidos, salientando-se reanimação neonatal (n = 9), encefalopatia hipóxico-isquémica (n = 2), parto traumático (n = 1), sépsis precoce (n = 2), cardiopatia congénita (n = 4) e potenciais fatores de risco protrombóticos (n = 8). Todos apresentaram convulsões entre as 6-72 horas de vida (focais em 18), associando-se hipotonia (n = 11), apneia (n = 5) e dificuldade alimentar (n = 4). O diagnóstico foi confirmado por ressonância magnética crânio-encefálica, sendo realizada angiografia por ressonância magnética em três recém-nascidos. O hemisfério esquerdo foi o mais afetado (n = 13). Foi possível obter dados de seguimento aos 2-3 anos em 18 crianças: 10 tinham défice motor, quatro atraso global de desenvolvimento, duas epilepsia e oito sem sequelas. Dos 11 casos com seguimento mais longo (5-7 anos), sete apresentaram défice motor, três atraso global do desenvolvimento e perturbações da linguagem, uma epilepsia e quatro sem sequelas. Discussão: O seguimento longitudinal das crianças com acidente vascular cerebral neonatal é fundamental, uma vez que as sequelas se tornam evidentes a médio / longo prazo. Apesar da existência de fatores de risco significativos nos recém-nascidos com acidente vascular cerebral, a determinação de fatores agudos preditivos da evolução é ainda difícil.
description: Portuguese Journal of Pediatrics, Vol. 49 No. 2 (2018)
Sonnenfleckenzeichnung Nr. 23491.
Zeichnung von Flecken und Fackelflächen zur Ermittlung der Sonnenaktivität am 23.10.1970, erstellt von Antoine Zelenka
Creators: name: [s.n.]
Publisher: name: [s.n.]
Year: 1970

description: Bleistiftzeichnung mit Tinte und Farbstift überschrieben, erstellt als Projektionsbildzeichnung in der Eidgenössischen Sternwarte Zürich. Instrument: Zeiss Coudé-Refraktor (150/2250 mm).
Die Beobachtungen zu Einzelflecken und zu Sonnenfleckengruppen wurden mit Bleistift auf einem Vordruck eingetragen. Zusätzlich notiert: Tabelle mit statistischen Angaben – mit Vermerk der Werte Gr, f und g, wobei die Bestimmung der Fleckenrelativzahl nach wie auf visueller Beobachtung und anderer Instrumentierung beruhte (und dafür das entsprechende Registerblatt (in Teilbestand acht) ausgefüllt wurde). Zusammen mit den täglichen Werten oft Angabe der Resultate der Flächenmessungen der Flecken (F und F -o) in Millionsteln der Scheibe bzw. der Halbkugel
Doxorubicin-loaded red blood cells reduced cardiac toxicity and preserved anticancer activity
Creators: name: Lucas, Alfredo
name: Lam, Dawn
name: Cabrales, Pedro
Publisher: name: Taylor & Francis
Year: 2019
Subjects: subject: Biochemistry
subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Physiology
subject: Pharmacology
subject: Biotechnology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: 69999 Biological Sciences not elsewhere classified
subject: Cancer

description: Doxorubicin (DOX) is one of the most widely used anticancer agents. DOX is known for inducing cardiotoxicity, resulting in the long-term development of heart failure. Intravascular delivery of DOX may benefit from the carriage by red blood cells (RBCs), as they can limit the systemic toxicity while delivering the DOX to the tumor. This study proposes a methodology for the synthesis of electrophoretically DOX-loaded red blood cells (RBC-DOX), as well as the assessment of its antitumorigenic effects in human colon cancer cells (HT-29), and in colon cancer xenograft models. In addition, healthy mice without tumors were dosed with RBC-DOX to assess cardiotoxicity via assessment of indexes of cardiac function after multiple doses of RBC-DOX. The HT-29 IC50 was found to be lower for RBC-DOX compared to free DOX. Tumor volume for the RBC-DOX group was smaller than the free DOX groups in HT-29 xenografts models. Statistically higher concentrations of DOX were found in the liver, spleen, and lungs for the RBC-DOX group compared to the free DOX group. However, the heart and the skin had statistically lower DOX concentrations for the RBC-DOX group compared to the free DOX group, with no significant differences in tumor biodistribution. All hemodynamic and cardiac function parameters were closer to control parameters for the RBC-DOX treated compared to for the free DOX-treated mice. These results suggest that RBC-DOX can be an alternative to prolong treatments with DOX, with superior antitumorigenic effects, decreased myelosuppression, and limited cardiac toxicity compared to equivalent doses of free DOX.
Sonnenfleckenzeichnung Nr. 23510.
Zeichnung von Flecken und Fackelflächen zur Ermittlung der Sonnenaktivität am 15.11.1970, erstellt von Werner Scheidegger
Creators: name: [s.n.]
Publisher: name: [s.n.]
Year: 1970

description: Bleistiftzeichnung mit Tinte und Farbstift überschrieben, erstellt als Projektionsbildzeichnung in der Eidgenössischen Sternwarte Zürich. Instrument: Zeiss Coudé-Refraktor (150/2250 mm).
Die Beobachtungen zu Einzelflecken und zu Sonnenfleckengruppen wurden mit Bleistift auf einem Vordruck eingetragen. Später wurden ergänzende Angaben aufgrund auswärtiger Beobachtungen direkt auf der Fleckenzeichnung hinzugefügt. Zusätzlich notiert: Tabelle mit statistischen Angaben – mit Vermerk der Werte Gr, f und g, wobei die Bestimmung der Fleckenrelativzahl nach wie auf visueller Beobachtung und anderer Instrumentierung beruhte (und dafür das entsprechende Registerblatt (in Teilbestand acht) ausgefüllt wurde). Zusammen mit den täglichen Werten oft Angabe der Resultate der Flächenmessungen der Flecken (F und F -o) in Millionsteln der Scheibe bzw. der Halbkugel
Hyaluronian-based synthetic extracellular matrices: syntheses and applications
Creators: name: Serban, Monica A.
Publisher: name: University of Utah
Year: 2012
Subjects: Fibroblast
Lysophosphatidic Acid

description: In mammalian tissues, cells are surrounded by the extracellular matrix (ECM) - a complex network of proteins, glycosaminoglycans (GAGs) and proteoglycans (PGs).  The ECM regulates numerous crucial processes such as cell proliferation, differentiation, migrations, and a variety of signaling events.  Synthetic extracellular matrices (sECMs) were developed in an attempt to mimic the properties of natural ECMs, specifically for tissue engineering applications.  Several sECMs are not commercially available.  We compared these materials side by side in a representative array of assays, to test their biological performances and user-friendliness.  Our results indicate that the ECM composition and compliance greatly influence cell behavior.  Based on these data, we underline the need for a paradigm shift from classical two-dimensional (2D) culturing to the more relevant, in vivo-like three-dimensional (3D) techniques especially for applications directly translatable to clinical applications.  Haloacetate-modified hyaluronan (HA) polymers were synthesized and characterized in an effort to provide a greater variety of  sECM components.  A novel approach was employed that yielded "chemically-reversed," electrophilic HA polymers that could be readily crosslinked with a variety of available nucleophiles.  The new haloacetate-modified hyaluronan materials show dose-dependent mild cytotoxic effects and appear promising for adhesion prevention or medical device coating.  A novel thiol-modified hyaluronan polymer (HASH) was also synthesized.  These biomaterials are not crosslinkable, are well tolerated by cell and shows promising results in a rat arthritis model, by slowing down the disease progression rate.  sECMs emerged to be particularly suitable for application such as drug screening.  To this end, Extracel ™, a hyaluronan and gelatin-based crosslinked hydrogel was used to examine the effect of alpha-substituted lysophosphatidic acid (LPA) analogs.  LPA and its synthesizing enzyme autotaxin (ATX) were associated in numerous studies with aberrant cellular behavior, mostly associated with cancer and tumorigenicity.  The compounds tested show cell-line dependent and LPA receptor-specific effect in cell proliferation assays.  Further studies that address modulation of cellular invasiveness and metastatic potential are needed for a complete profiling of these chemicals.
Proinflammatory Immune Response and Puerperal Group A Streptococcal Sepsis
Creators: name: Spargen, Petrine Florence
Publisher: name: University of Utah
Year: 2014

description: Group A streptococcus (GAS) is a severe, and potentially fatal, cause of postpartum infection. Bacterial virulence factors influence pathogenesis but do not effectively predict disease susceptibility or severity. Our objective was to determine if an altered maternal innate immune response is associated with puerperal group A streptococcus sepsis. We stimulated peripheral blood mononuclear cells from patients with previous postpartum puerperal GAS infection and compared cytokine/inflammatory marker production to age, parity, and racially matched controls. Concentrations of 13 cytokines/inflammatory markers including IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-α, IL-2r, and soluble CD40 ligand were measured in mononuclear cell cultures from patients and controls in response to heat-killed emm1 and emm28 group A streptococci, the M-serotypes most closely associated with puerperal morbidity. Samples from ten controls, ten severe cases, and six mild cases were analyzed. In response to stimulation, IL-1β, IL-6, IL-2r, IL-10, IL-13, and CD40L cytokine production were significantly increased in severe and mild cases combined, compared to control samples (IL-1β mean response 1143.3 vs. 502.3 pg/ml, p<0.01; IL-13 mean response 8.8 pg/ml vs. 5.7 pg/ml pg/ml, p<0.05; and CD40L mean response 131.7 vs. 69.2 pg/ml, <0.0001). IL-4 concentrations in patients were not statistically different from controls. When stratified, severe cases also had a significant response when compared to mild cases. IL-5, IL-2, and IL-12 stratified cases also showed a more robust response in the severe groups when compared to mild groups, but were not statistically significant. Puerperal group A streptococcal sepsis is associated with altered maternal innate inflammatory immune responses. The increased production of inflammatory cytokines many contribute to susceptibility and severity of puerperal group A streptococcal disease.
Genetic analysis of the adenovirus DNA binding protein
Creators: name: Rice, Stephen Anthony
Publisher: name: University of Utah
Year: 2012
Subjects: Adenovirdae
DBP Function
Genetic Analysis

description: The 72 kilodalton DNA protein (DBP) of human adenovirus is a multifunctional polypeptide involved in several aspects of vital replication.  In order to better understand DBP, adenovirus mutants containing alterations in DBP were isolated and analyzed.  Ad2ta400 is an adenovirus type 2 mutant containing three DBP mutations.  Two of the mutations map to the amino-terminal domain of DBP and confer a cold-resistant host range phenotype which allows the virus to grow efficiently in monkey cells at 32.5?C.  The third mutation maps in the carboxyl-terminal domain of DBP and causes a temperature-sensitive, DNA replication negative phenotype at 39.5?C in both human and monkey cells.  At 39.5?C, Ad2ts400 is capable of enhancing viral growth in monkey cells, indicating that this activity of DBP is independent of the role of the protein in viral DNA replication.  A genetic system was developed which allows the isolation of DBP mutants of any desired genotype.  The mutations are first engineered into a cloned DBP gene using techniques of in vitro, site-directed mutagenesis.  The mutated genes are then introduced into the viral chromosome by homologous recombination in vivo.  Mutant virus are propagated by growth in human cell lines which express DBP and thus complement DBP-defective virus.  The systems was used to construct five adenovirus type 5 DBP deletion mutants designated Ad5d1801 through Ad5d1805.  All five mutants fare completely defective of growth in normal human cell lines.  The mutant Ad5d1804 encodes a truncated protein which contains the entire amino-terminal domain of DBP including the histidine-to-tyrosine alteration at amino acid 130 which normally enhances viral growth in monkey cells.  The truncated protein, however, failed to enhance late viral gene expression in monkey cells.  The mutant Ad5d1802, which encodes no detectable DBP or DBP fragment, was used to study the role of DPB in early gene regulation of human cells.  Contrary to previously published results, the absence of DBP function had no apparent effect on either process.