Algumas tendências das publicações relacionadas à Astronomia em periódicos brasileiros de ensino de Física nas últimas décadas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Propriedades mecânicas, físico-químicas e biológica de adesivo experimental com incorporação de epigalocatequina-3-galato

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cold Shock Genes cspA and cspB from Caulobacter crescentus Are Posttranscriptionally Regulated and Important for Cold Adaptation

Cold shock proteins (CSPs) are nucleic acid binding chaperones, first described as being induced to solve the problem of mRNA stabilization after temperature downshift. Caulobacter crescentus has four CSPs: CspA and CspB, which are cold induced, and CspC and CspD, which are induced only in stationary phase. In this work we have determined that the synthesis of both CspA and CspB reaches the maximum levels early in the acclimation phase. The deletion of cspA causes a decrease in growth at low temperature, whereas the strain with a deletion of cspB has a very subtle and transient cold-related growth phenotype. The cspA cspB double mutant has a slightly more severe phenotype than that of the cspA mutant, suggesting that although CspA may be more important to cold adaptation than CspB, both proteins have a role in this process. Gene expression analyses were carried out using cspA and cspB regulatory fusions to the lacZ reporter gene and showed that both genes are regulated at the transcriptional and posttranscriptional levels. Deletion mapping of the long 5'-untranslated region (5'-UTR) of each gene identified a common region important for cold induction, probably via translation enhancement. In contrast to what was reported for other bacteria, these cold shock genes have no regulatory regions downstream from ATG that are important for cold induction. This work shows that the importance of CspA and CspB to C. crescentus cold adaptation, mechanisms of regulation, and pattern of expression during the acclimation phase apparently differs in many aspects from what has been described so far for other bacteria.

Mimosine and Cyclophosphamide: a Potential New Combination Therapy Used to Prevent Tumor Development

The effects of mimosine (MI), which is an amino acid that is derived from Leucaena leucocephala, were evaluated on the growth of ascitic Ehrlich tumors, and the effects of the combination treatment of MI and cyclophosphamide (CY) on tumor growth were also assessed. Mice were divided into groups that received the following treatments over the course of 20 days: phosphate buffer solution (CO), MI, Ehrlich cells (E), E plus CY (EC), E plus MI (EM) and E plus MI and CY (EMC). No signs of toxicity were detected in the mice from the MI group. The mice from the EMC group showed reductions in body weights when compared with those from the E group. The animals from the EC, EM and EMC groups showed reductions in ascitic volume compared with those from the E group. The mice from the EMC group showed reductions in total cell numbers of ascitic fluid compared with those from the E, EC and EM groups. The combination of MI and CY was the most effective treatment for Ehrlich tumor ascites.

O uso da Classificação Internacional de Funcionalidade, Incapacidade e Saúde para acompanhamento de pacientes usuários de Implante Coclear.

Purpose: To characterize the profile of patients with cochlear implant as proposed by the International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY). Methods: This is a descriptive, crosssectional retrospective study, which examined 30 medical records of patients using the cochlear implant of Centro de Pesquisas Audiológicas. To characterize the profile of the patients, the ICF-CY was used. Regarding the assessment, researchers relied on procedures performed in clinical routine, besides information registered in the medical record. After reviewing the information, it was related to codes from the ICF-CY; with the addition of a qualifier afterwards. Results: Overall, 55 codes from the ICF were related to the instruments to characterize this population. Regarding the Body Functions field, most participants did not have disabilities related to reception and expression of oral language and auditory functions, with only written language disabilities being found. These same findings were observed in the Activity and Participation Field. Regarding environmental factors, noise and the non-availability of technology resources to assist in the auditory comprehension of noise were characterized as a barrier, as well as the absence of speech therapy. Conclusion: This study concluded that most of the participating children showed no deficiency in the body functions, with difficulties being only reported in relation to school performance. Environmental factors (noise, non-availability of technological resources, absence of speech therapy) were characterized as a barrier. The need to expand assessments in the clinical routine was also noted.

Mimosine and cyclophosphamide: a potential new combination therapy used to prevent tumor development

The effects of mimosine (MI), which is an amino acid that is derived from Leucaena leucocephala, were evaluated on the growth of ascitic Ehrlich tumors, and the effects of the combination treatment of MI and cyclophosphamide (CY) on tumor growth were also assessed. Mice were divided into groups that received the following treatments over the course of 20 days: phosphate buffer solution (CO), MI, Ehrlich cells (E), E plus CY (EC), E plus MI (EM) and E plus MI and CY (EMC). No signs of toxicity were detected in the mice from the MI group. The mice from the EMC group showed reductions in body weights when compared with those from the E group. The animals from the EC, EM and EMC groups showed reductions in ascitic volume compared with those from the E group. The mice from the EMC group showed reductions in total cell numbers of ascitic fluid compared with those from the E, EC and EM groups. The combination of MI and CY was the most effective treatment for Ehrlich tumor ascites.

Il trapianto di midollo osseo aploidentico nelle patologie oncoematologiche: studio clinico

L’argomento della presente tesi di dottorato riguarda lo studio clinico del trapianto di cellule staminali emopoietiche aploidentiche nelle patologie oncoematologiche. Nel periodo di tempo compreso tra 1/12/2005 ed il 30/10/2007 sono stati arruolati 10 pazienti (6 LAM, 3 LAL, 1 LMC in crisi blastica mieloide) nell’ambito di uno studio clinico che prevedeva il trapianto di midollo osseo aploidentico per pazienti affetti da patologia oncoematologica in prima o successiva recidiva, per i quali non fosse disponibile un donatore di midollo osseo consanguineo o da banca. Lo schema di condizionamento al trapianto di midollo osseo utilizzato era il seguente: Fludarabina 150/m2, Busulfano orale 14mg/kg, Tiothepa 10mg/kg e Ciclofosfamide 160mg/kg. Per la profilassi della malattia da trapianto contro l’ospite è stata somministrata timoglobulina antilinfocitaria (ATG) al dosaggio complessivo di 12.5 mg/kg, short course metotrexate (+1, +3 e +11), cortisone e ciclosporina con tapering precoce al + 60. I pazienti hanno reinfuso una megadose di cellule CD34+ mediana pari a 12.8x106/kg. Tre pazienti non sono valutabili per l’attecchimento a causa di rigetto (1/3) o morte precoce (2/3). Sette pazienti sono valutabili per l’attecchimento; per questi pazienti il tempo mediano a 500 PMN/mmc e a 20 x 109/l piastrine è stato rispettivamente di 17 e 20 giorni. Quattro pazienti su 7 hanno svillupato una Graft versus Host Disease (GVHD) acuta di grado II-IV, mentre soltanto 1/7 ha sviluppato una GVHD cronica. Sette pazienti su 10 trapiantati hanno ottenuto una remissione completa successivamente al trapianto. Di questi, attualmente 2 pazienti sono vivi in remissione completa, mentre gli altri 5 sono ricaduti e successivamente deceduti. In conclusione, il trapianto aploidentico è una procedura fattibile ed efficace. Tale procedura è in grado di garantire un 20% di lungo sopravviventi in un setting di pazienti a prognosi estremamente infausta.

Biochemische Charakterisierung des O 2-Sensors NreB aus Staphylococcus carnosus

Staphylococcus carnosus wird in der Lebensmittelindustrie als Starterkultur in der Rohwurstfermentation eingesetzt. Das Gram-positive Bakterium ist fakultativ anaerob und kann unter anaeroben Bedingungen Nitrat und Nitrit zu Ammonium reduzieren. Die Expression der Gene der Nitrat-, Nitritreduktase und des potentiellen Nitrattrans-porters, wird vom NreBC Zwei-Komponentensystem reguliert. NreB ist eine cy-toplasmatische Sensor-Histidinkinase, die Ähnlichkeiten zu HämB-bindenden PAS-Domänen aufweist. NreB reagiert auf Sauerstoff und kontrolliert zusammen mit dem Response-Regulator NreC die Expression der Gene der Nitrat/Nitrit-Atmung. Die Gene nreBC wurden in Staphylococcus Arten, Bacillus clausii und anderen Bacil-lus Arten gefunden. Anaerob präpariertes NreB von S. carnosus enthält ein diamag-netisches [4Fe-4S]2+-Zentrum, das durch Mössbauer-Spektroskopie identifiziert wur-de. Nach Luftexposition wurde das [4Fe-4S]2+-Zentrum mit einer Halbwertszeit von 2,5 Minuten zu nicht an das Protein gebundenem γ-FeOOH oxidiert. Mit EPR- und Mössbauer-Spektroskopie konnten keine signifikanten Mengen von Zwischenstufen detektiert werden. Photoreduktion mit Deazaflavin lieferte kleine Mengen von [4Fe-4S]1+, die aber nicht stabil waren und sofort wieder zerfielen. Das magnetische Mössbauer-Spektrum des [4Fe-4S]2+-Zentrums wies eine hohe Symmetrie auf, wor-aus man auf eine vollständige Delokalisation der Elektronen und dieselben Liganden für alle Eisenionen schließen kann. In Übereinstimmung mit ihrer Rolle als Liganden des FeS-Zentrums inaktivierte der Austausch der einzelnen Cysteinreste (Cys59, Cys62, Cys74, Cys77) gegen Alanin oder Serin die Funktion von NreB in vivo. Die [4Fe-4S]2+-enthaltende Form von NreB besaß eine hohe Kinaseaktivität. Luftexposition erniedrigte den Gehalt an [4Fe-4S]2+-Zentrum und die Kinaseaktivität mit ähnlichen Halbwertszeiten von 2,5 min. Die Sensor-Domäne von NreB ist eine neuartige PAS-Domäne, die einen FeS-haltigen Co-Faktor (in diesem Fall ein [4Fe-4S]2+-Zentrum) zur Reizperzeption be-sitzt. Das O2-sensitive [4Fe-4S]2+-Zentrum von NreB ist dem [4Fe-4S]2+-Zentrum des DNA-bindenden FNR Proteins aus Escherichia coli ähnlich und kommt möglicherwei-se in anderen O2-wahrnehmenden bakteriellen Proteinen vor. Daraus kann man schließen, dass der Mechanismus der Sauerstoffwahrnehmung über O2-sensitive [4Fe-4S]2+-Zentren in der Evolution mehrfach und unabhängig voneinander in ver-schiedenen bakteriellen O2-Sensoren entstanden ist.

On differential operators of Calabi-Yau type

This thesis is devoted to the study of Picard-Fuchs operators associated to one-parameter families of $n$-dimensional Calabi-Yau manifolds whose solutions are integrals of $(n,0)$-forms over locally constant $n$-cycles. Assuming additional conditions on these families, we describe algebraic properties of these operators which leads to the purely algebraic notion of operators of CY-type. rnMoreover, we present an explicit way to construct CY-type operators which have a linearly rigid monodromy tuple. Therefore, we first usernthe translation of the existence algorithm by N. Katz for rigid local systems to the level of tuples of matrices which was established by M. Dettweiler and S. Reiter. An appropriate translation to the level of differential operators yields families which contain operators of CY-type. rnConsidering additional operations, we are also able to construct special CY-type operators of degree four which have a non-linearly rigid monodromy tuple. This provides both previously known and new examples.

Towards antibody-mediated targeting of dendritic cells for cancer immunotherapy with multivalent polymer-antigen conjugates

Der Fokus dieser Arbeit lag auf der definierten Synthese multifunktioneller Polymer-Konjugate zur Anwendung in der Krebs-Immunotherapie. Durch gezielte Variation der Kon-jugationsbedingungen wurde Zusammensetzung, Größe und Aggregationsverhalten in Zell-medium sowie in humanem Serum untersucht. Nach definierter physikalisch-chemischer Charakterisierung wurde dann die induzierte Antigen-Präsentation zur Aktivierung der T-Zellproliferation analysiert.rnDafür wurden zwei verschiedene polymere Carrier-Systeme gewählt, lineares Poly-L-lysin und eine Polylysinbürste (PLL-Bürste). Es wird vermutet, dass die PLL-Bürste aufgrund der anisotropen Form eine bessere Verteilung im Körper und eine verlängerte Zirkulationsdauer zeigen wird. Die zu konjugierenden biologisch aktiven Komponenten waren der antiDEC205-Antikörper (aDEC205) für die gezielte Adressierung CD8-positiver dendritischer Zellen (DC), ein Ovalbumin (OVA)-spezifisches Antigen mit der Kernsequenz SIINFEKL für die Spezifität der Immunantwort gegen Krebszellen, die dieses Antigen tragen, und ein immunaktivieren-der TLR9-Ligand, CpG1826. Die Effizienz dieses Konjugates dendritische Zellen zu aktivieren, welche wiederum eine Immunantwort gegen OVA-exprimierende Krebszellen induzieren, wurde durch die Konjugation aller Komponenten am identischen Trägermolekül deutlich höher erwartet.rnLineares Poly-L-lysin diente als Modellsystem um die Konjugationschemie zu etablieren und dann auf die zylindrische Polylysinbürste zu übertragen. Anhand dieser polymeren Träger wurde das Verhalten der verschiedenen Topologien des Knäuels und der Bürste im Hinblick auf den Einfluss struktureller Unterschiede sowohl auf Konjugationsreaktionen als auch auf das in situ und in vitro Verhalten untersucht.rnFluoreszenzmarkiertes Antigen und der CpG Aktivator konnten jeweils aufgrund einer Thiol-Modifizierung an die Thiol-reaktive Maleimidgruppe des heterobifunktionellen Linkers Sulfo-SMCC an PLL-AlexaFluor48 konjugiert werden. Anschließend wurde aDEC205-AlexaFluor647 an PLL gekoppelt, entweder durch Schiff Base-Reaktion des oxidierten Antikörpers mit PLL und anschließender Reduzierung oder durch Click-Reaktion des PEG-Azids modifizierten An-tikörpers mit Dicyclobenzylcyclooctin (DIBO)-funktionalisiertem PLL. Die Konjugation der biologisch aktiven Komponenten wurde mit Durchflusszytometrie (FACS) und konfokaler Laser Scanning Mikroskopie (CLSM) untersucht und die Zusammensetzung des Konjugatesrnmittels UV/Vis-Spektroskopie bestimmt. Die PLL-Bürste alleine zeigte eine hohe Zytotoxizität bei HeLa und JAWS II Zelllinien, wohingegen lineares PLL und PLL-Konjugate sowie die PLL Bürsten-Konjugate keine ausgeprägte Zytotoxizität aufwiesen. Die Polymer-Konjugate wie-sen keine Aggregation in Zellmedium oder humanem Serum auf, was mittels winkelabhängi-ger dynamischer Lichtstreuung bestimmt wurde. CLSM Aufnahmen zeigten Kolokalisation der an die einzelnen Komponenten gebundenen Fluoreszenzfarbstoffe in dendritischen Zel-len, was die erfolgreiche Konjugation und Internalisierung der Konjugate in die Zellen bele-gen konnte. FACS Messungen ergaben eine geringfügig erhöhte Aufnahme des adressierten PLL-Antigen-Antikörper-Konjugates verglichen mit dem PLL-Antigen-Konjugat. Experimente mit dem „Specific Hybridization Internalization Sensor“ (SHIP) zeigten jedoch nur Aufnahme der PLL-Konjugate in CD8+ unreife DC, nicht in reife DC, die nicht mehr unspezifisch, sondern nur noch über Rezeptoren internalisieren. Dies bewies die unspezifische Aufnahme des Kon-jugates, da Antikörper-Konjugation keine Rezeptor-vermittelte Endozytose in reife DC indu-zieren konnte. T-Zell-Proliferationsassays ergaben eine Aktivierung von CD8+ T-Zellen indu-ziert durch Antigen-tragende Konjugate, wohingegen Konjugate ohne Antigen als Negativ-kontrollen dienten und keine T-Zell-Proliferation erzielten. Es konnte jedoch kein Unter-schied zwischen adressierten und nicht adressierten Konjugaten aufgrund der unspezifischen Aufnahme durch das Polymer beobachtet werden. Lösliches SIINFEKL alleine bewirkte schon bei geringeren Konzentrationen eine T-Zell-Proliferation.rnEs war somit möglich, drei biologischen Komponenten an einen polymeren Träger zu konju-gieren und diese Konjugate im Hinblick auf Zusammensetzung, Größe, Internalisierung in dendritische Zellen und Aktivierung der T-Zell-Proliferation zu untersuchen. Außerdem wur-de die Konjugationschemie erfolgreich von dem Modellsystem des linearen PLL auf die PLL-Bürste übertragen. Die Polymer-Konjugate werde unspezifisch in DC aufgenommen und in-duzieren T-Zellproliferation, die mit Antigen-Präsentationsassays nachgewiesen wird. Es konnte jedoch durch Konjugation des Antikörpers keine Rezeptor-vermittelte Aufnahme in CD8+ DC erzielt werden.rnDiese Studien stellen einen erfolgsversprechenden ersten Schritt zur Entwicklung neuer Na-nomaterialien für die Anwendung in Krebs-Immuntherapie dar.

Synthetic-echo time postprocessing technique for generating images with variable T2-weighted contrast: diagnosis of meniscal and cartilage abnormalities of the knee

To assess the feasibility and accuracy of a synthetic-echo time (TE) magnetic resonance (MR) postprocessing technique for the diagnostic evaluation of abnormalities of menisci and articular cartilage in the knee.

The role of autophagy in anticancer therapy: promises and uncertainties

Autophagy (literally self-eating) is a catabolic mechanism involved in the recycling and turnover of cytoplasmic constituents. Although often referred to as type II programmed cell death, autophagy is primarily a survival rather than a cell death mechanism in response to different stress stimuli. Autophagy is a process in which part of the cytoplasm or entire organelles are sequestered into double-membrane vesicles, called autophagosomes, which ultimately fuse with lysosomes to degrade their contents. Studies show that autophagy is associated with a number of pathological conditions, including cancer, infectious diseases, myopathies and neurodegenerative disorders. With respect to cancer, it has been suggested that the early stages of tumourigenesis are associated with downregulation of autophagy-related (ATG) genes. Indeed, several ATG genes display tumour suppressor function, including Beclin1, which is frequently hemizygously deleted in breast cancer cells. Conversely, in advanced stages of tumourigenesis or during anticancer therapy, autophagy may promote survival of tumour cells in adverse environmental conditions. Therefore, a thorough understanding of autophagy in different cancer types and stages is a prerequisite to determine an autophagy-activating or autophagy-inhibiting treatment strategy.

Früherkennung von Psychosen bei Kindern und Adoleszenten - Sind entwicklungsbezogene Besonderheiten ausreichend berücksichtigt

The early detection and treatment of persons at risk for psychosis is currently regarded as a promising strategy in fighting the devastating consequences of psychotic disorders. The two current favored at-risk approaches, i.e., the «ultra high risk» and the «basic symptom» criteria, were developed mainly using adult samples. Initial evidence suggests, however, that they cannot simply be applied to children and adolescents. For «ultra-high risk» criteria, there is indication of some attenuated psychotic symptoms being potentially nonspecific in adolescents, and of brief limited intermittent symptoms being difficult to clinically classify in children when observable behavioral correlates are missing. For basic symptoms, too, only a preliminary indication of their usefulness in children and adolescents exists. Since developmental peculiarities in the assessment of basic symptoms should be considered, a child and youth version of the Schizophrenia Proneness Instrument (SPI-CY) was developed. In conclusion, research on the clinical-prognostic validity of the at-risk criteria and their potential adaption to the special needs of children and adolescents is needed. If a «Prodromal Risk Syndrome for Psychosis» or «Attenuated Psychotic Symptoms Syndrome» are included in the upcoming DSM-5, it should be highlighted that its suitability for children and adolescents is only insufficiently known.

Evaluation of pulmonary vein stenosis after pulmonary vein isolation using a novel circular mapping and ablation catheter (PVAC)

Background—Pulmonary vein stenosis (PVST) is a well-known complication of pulmonary vein isolation (PVI). Specific anatomically designed ablation catheters for antral PVI have not been evaluated with regard to the incidence of PVST. We investigated the incidence, severity, and characteristics of PVST after PVI with the Pulmonary Vein Ablation Catheter (PVAC) and phased radiofrequency technology. Methods and Results A total of 100 patients (55 men) underwent PVI for atrial fibrillation using the PVAC. PVI was guided by selective angiography of each pulmonary vein (PV) in 70 (70%) patients and by reconstructed 3D atriography (ATG) in 30 (30%) patients. Gadolinium-enhanced MRI or multidetector CT was performed in all patients before treatment and 93±78 days after PVI. PVST was classified as follows: insignificant (<25%), mild (25%–50%), moderate (50%–75%), or severe (>75%). A total of 410 PVs were analyzed. Cardiac imaging demonstrated a detectable narrowing of the PV diameter in 23 (23%) patients and in 28 (7%) PVs. In detail, insignificant PVST was observed in 12 (2.9%) PVs, mild PVST in 15 (3.7%), and moderate PVST in 1 (0.2%). No instances of severe PVST were observed. The use of 3D-ATG was associated with a lower incidence of PVST (0.8% [95% CI, 0.0%–2.2%] versus 5.4% [95% CI, 2.7%–8.1%], P=0.027). Conclusions To our knowledge, this study is the first to report the incidence of PVST using the PVAC. In this regard, the PVAC seems to be safe if used in an experienced center. In addition, the use of 3D-ATG may decrease the risk of PVST.

Challenges in the early detection of psychosis in children and adolescents

The early detection and treatment of persons at-risk for psychosis is currently regarded a promising strategy in fighting the devastating consequences of psychotic disorders. The two current at-risk approaches, i.e., the "ultra high risk" and the "basic symptom" criteria, were mainly developed on adult samples. Initial evidence suggests, however, that they cannot simply be applied to children and adolescents. For ultra high risk criteria, there is indication of some attenuated psychotic symptoms being potentially non-specific in adolescents and of brief limited intermittent symptoms being difficult to clinically classify in children when observable behavioral correlates are missing. For basic symptoms, too, only preliminary indication of their usefulness in children and adolescents exists. Since developmental peculiarities in the assessment of basic symptoms should be considered, a child and youth version of the Schizophrenia Proneness Instrument (SPI-CY) was developed. In conclusion, research on the clinical-prognostic validity of the at-risk criteria and their potential adoption to the special needs of children and adolescents is needed. If a Prodromal Risk Syndrome for Psychosis or Attenuated Psychotic Symptoms Syndrome will be included into DSM-V, it has to be highlighted that its suitability for children and adolescents is only insufficiently known.