Origens dos empresários da indústria de máquinas e equipamentos em São Paulo, 1870-1900

O objetivo específico deste artigo é identificar as origens dos empresários, como nacionalidade e gênese do capital para o início da atividade, na indústria de máquinas e equipamentos em São Paulo, e a evolução do setor no período de 1870 a 1900. Tentamos identificar os empreendimentos na indústria e sua relação com o comércio importador e exportador, com os fazendeiros de produtos para exportação (principalmente o café), com os imigrantes comerciantes e com os que possuíam algum conhecimento técnico.

Multilaminati piezoelettrici a gradiente funzionale

Aim of this thesis was the production of porosity-graded piezoelectric ceramics for ultrasonic applications by tape casting and screen printing. The study and optimization of each single step of the tape casting process allowed to produce flat and crack-free multilayers of Pb0.988(Zr0.52Ti0.48)0.976Nb0.024O3 (PZTN) of uniform and graded porosity. The multilayers of thickness ranging between 400 and 800 µm were produced stacking optimized green layers with different amount of pore former. The functionally graded materials showed porosity ranging between 10 and 30% with piezoelectric properties suitable for the specific ultrasonic applications. Screen printing inks of PZTN for deposition onto four different substrates were studied and optimized. Thick films with thickness ranging between 4 and 20 µm were produced tailoring the screen printing parameters and number of depositions.

Johann Schöffer, Buchdrucker zu Mainz

Die Arbeit beschriebt das Leben und Wirken Johann Schöffers, des Erben der Mainzer Druckerei Johannes Fusts und Peter Schöffer d.Ä. Im Mittelpunkt stehen die 315 heute noch nachweisbaren Drucke. Neben der bibliographischen Erfassung der Titel, die ergänzt werden durch Hinweise zur Illustration und zur Typographie, wird versucht anhand dieser die Entwicklung und die Veränderungen in der Werkstatt aufzuzeigen. Von Interesse ist dabei, dass sich die historischen Ereignisse und religiösen Strömungen teilweise parallel, teilweise zeitlich versetzt im Verlagsprogramm widerspiegeln.

Meccanizzazione dei vigneti allevati a doppia cortina e a cordone libero

La ricerca svolta ha voluto approfondire le possibilità offerte dai sistemi di allevamento dei vigneti a Doppia Cortina (GDC) e a Cordone Libero nei riguardi della meccanizzazione. La ricerca ha considerato gli interventi di potatura invernale, di gestione della chioma (spollonatura, cimatura, defogliazione e pettinatura della doppia cortina) e di vendemmia. Un’operazione particolarmente seguita è stata la potatura invernale realizzando differenti livelli di meccanizzazione. Tutti gli interventi sono stati eseguiti sia manualmente che meccanicamente, confrontando i tempi d’impiego, la qualità del lavoro svolto e gli impegni di manodopera. I risultati sono stati sintetizzati in una valutazione economica, ipotizzando differenti livelli di costo della manodopera impiegata, per ottenere giudizi di convenienza per i singoli interventi e per costruire una valutazione completa e più organica della linea di lavoro proposta. Nelle due forme d’allevamento la meccanizzazione della potatura invernale e della gestione della chioma hanno rispettato pienamente gli obbiettivi tecnici prefissati, dimostrando di essere un valido mezzo per ridurre tempi e costi di gestione. Per questi interventi l’acquisto delle macchine risulta conveniente anche per vigneti di piccola dimensione. Ancor più evidenti in queste due forme d’allevamento sono i vantaggi economici offerti dalla vendemmia meccanica, realizzata con pochi maltrattamenti e perdite di prodotto. La tendenza a meccanizzare integralmente gli interventi di gestione del ciclo colturale della vite, può essere nei prossimi anni un motivo di interesse e di scelta nella realizzazione di nuovi impianti con queste due forme di allevamento, che hanno dimostrato di essere un’espressione completa di sinergia tra macchina e pianta.

Analisi acustica di una finestra forata: modellazione numerica mediante COMSOL multiphysics

“Immaginate di potervi rilassare a casa in una giornata d’estate tenendo le finestre aperte per lasciare passare la brezza ma senza essere disturbati dai rumori della città, oggi è possibile”. Quello che voglio fare attraverso questa tesi è di studiare la fattibilità per la realizzazione di una finestra che permetta il passaggio dell’aria ma non dei rumori. L’idea di questa particolare finestra silenziosa mi è stata fornita dallo studio fatto dal professor Sang-Hoon Kim del Mokpo National University maritime e dal professor Seong-Hyun Lee del Korea Institute of Machinery and Materials in Corea del Sud. Essi hanno utilizzato i metamateriali acustici per risolvere il problema dell’inquinamento sonoro in città. Queste finestre hanno il vantaggio di tenere i rumori fuori dalla nostra abitazione ma permettere il passaggio dell’aria attraverso dei fori aventi dimensioni e posizioni adeguate da garantire questo particolare fenomeno. I principi su cui si basano queste finestre sono: la diffrazione e i risonatori di Helmholtz, che analizzeremo nel dettaglio nei capitoli 1 e 2 di questa tesi. Dopo aver analizzato i due principi attraverso simulazione fatte mediante il programma COMSOL multiphysics, sono passata all’analisi della finestra vera e propria: ovvero alla realizzazione delle dimensioni adeguate dei risonatori di Helmholtz utilizzati, alle dimensioni dei rispettivi fori d’ingresso e alla combinazione di questi risonatori per ricavare la miglior finestra silenziosa, che trattenesse al suo esterno il maggior numero di dB.

Improving gene silencing of siRNAs via tricyclo-DNA modification

;Small interfering RNAs (siRNAs) can be exploited for the selective silencing of disease-related genes via the RNA interference (RNAi) machinery and therefore raise hope for future therapeutic applications. Especially chemically modified siRNAs are of interest as they are expected to convert lead siRNA sequences into effective drugs. To study the potential of tricyclo-DNA (tc-DNA) in this context we systematically incorporated tc-DNA units at various positions in a siRNA duplex targeted to the EGFP gene that was expressed in HeLa cells. Silencing activity was measured by FACS, mRNA levels were determined by RT-PCR and the biostability of the modifed siRNAs was determined in human serum. We found that modifications in the 3'-overhangs in both the sense and antisense strands were compatible with the RNAi machinery leading to similar activities compared to wild type (wt) siRNA. Additional modifications at the 3'-end, the 5'- end and in the center of the sense (passenger) strand were also well tolerated and did not compromise activity. Extensive modifications of the 3'- and the 5'-end in the antisense (guide) strand, however, abolished RNAi activity. Interestingly, modifications in the center of the duplex on both strands, corresponding to the position of the cleavage site by AGO2, increased efficacy relative to wt by a factor of 4 at the lowest concentrations (2 nM) investigated. In all cases, reduction of EGFP fluorescence was accompanied with a reduction of the EGFP mRNA level. Serum stability analysis further showed that 3'-overhang modifications only moderately increased stability while more extensive substitution by tc-DNA residues significantly enhanced biostability.

Cathepsin S dominates autoantigen processing in human thymic dendritic cells

The interaction of developing thymocytes with peptide-MHC complexes on thymic antigen presenting cells (APC) is crucial for T cell development, both for positive selection of "useful" thymocytes as well as negative selection of autoreactive thymocytes to prevent autoimmunity. The peptides presented on MHC II molecules are generated by lysosomal proteases such as the cathepsins. At the same time, lysosomal proteases will also destroy other potential T cell epitopes from self-antigens. This will lead to a lack of presentation on negatively selecting thymic antigen presenting cells and consequently, escape of autoreactive T cells recognizing these epitopes. In order to understand the processes that govern generation or destruction of self-epitopes in thymic APC, we studied the antigen processing machinery and epitope processing in the human thymus. We find that each type of thymic APC expresses a different signature of lysosomal proteases, providing indirect evidence that positive and negative selection of CD4(+) T cells might occur on different sets of peptides, in analogy to what has been proposed for CD8(+) T cells. We also find that myeloid dendritic cells (DC) are more efficient in processing autoantigen than plasmacytoid DC. In addition, we observed that cathepsin S plays a central role in processing of the autoantigens myelin basic protein and proinsulin in thymic dendritic cells. Cathepsin S destroyed a number of known T cell epitopes, which would be expected to result in lack of presentation and consequently, escape of autoreactive T cells. Cathepsin S therefore appears to be an important factor that influences selection of autoreactive T cells.

Is virtuality close enough to reality? A comparison of the effectiveness of simulations with traditional laboratory activities in a high school biology class

Some schools do not have ideal access to laboratory space and supplies. Computer simulations of laboratory activities can be a cost-effective way of presenting experiences to students, but are those simulations as effective at supplementing content concepts? This study compared the use of traditional lab activities illustrating the principles of cell respiration and photosynthesis in an introductory high school biology class with virtual simulations of the same activities. Additionally student results were analyzed to assess if student conceptual understanding was affected by the complexity of the simulation. Although all student groups posted average gain increases between the pre and post-tests coupled with positive effect sizes, students who completed the wet lab version of the activity consistently outperformed the students who completed the virtual simulation of the same activity. There was no significant difference between the use of more or less complex simulations. Students also tended to rate the wet lab experience higher on a motivation and interest inventory.

Planung und Risikobewertung projektspezifischer Produktionsnetzwerke

Bei Einzel‐ und Kleinserienfertigung müssen sowohl langfristige Kooperationspartner als auch auftrags-spezifische, internationale Partner und Lieferanten in die Produktion komplexer Investitionsgüter einbezogen werden. Zunehmend sind kleine und mittlere Unternehmen (KMU) herausgefordert nicht nur technische Komponenten zu liefern, sondern die komplette Projektplanung zu realisieren. Im Forschungsprojekt „PIP“ soll ein Verfahren entwickelt werden, das gerade KMU des Maschinen- und Anlagenbaus bei der aufwandsmi-nimierten Partner- und Lieferantenauswahl sowie der Einschätzung möglicher Projektrisiken unterstützt. Der vorliegende Artikel beschreibt Rahmenbedingungen beim Aufbau projektspezifischer Produktionsnetzwerke sowie Lösungsansätze zu deren verbesserter Planung und Risikobewertung.

Blended Learning: Integrating an e-Learning Component for Competency Validation

Introduction: Emergency care providers are required to demonstrate competency in the management of life-threatening situation. The care provider’s ability to manage an emergency situation depends upon his/her knowledge and skills in basic CPR; and the use of emergency equipment and supplies. The education department at our healthcare facility is responsible for CPR/Emergency Management competency validation of over 2500 employees annually. Historically each employee was scheduled to attend 4 hours of class every year to review the content, complete the post-test and demonstrate skills. It was resource-intensive, time consuming, stressful and often difficult to schedule the 24/7 employees for the sessions. [See PDF for complete abstract]

THE UBIQUITIN LIGASE UBE4B IS REQUIRED FOR EFFICIENT EPIDERMAL GROWTH FACTOR RECEPTOR DEGRADATION

The length of time that integral membrane proteins reside on the plasma membrane is regulated by endocytosis, a process that can inactivate these proteins by removing them from the membrane and may ultimately result in their degradation. Proteins are internalized and pass through multiple distinct intracellular compartments where targeting decisions determine their fate. Membrane proteins initially enter early endosomes, and subsequently late endosomes/multivesicular bodies (MVBs), before being degraded in the lysosome. The MVB is a subset of late endosomes characterized by the appearance of small vesicles in its luminal compartment. These vesicles contain cargo proteins sorted from the limiting membrane of the MVB. Proteins not sorted into luminal vesicles remain on the MVB membrane, from where they may be recycled back to the plasma membrane. In the case of receptor tyrosine kinases (RTKs), such as epidermal growth factor (EGF) receptor, this important sorting step determines whether a protein returns to the surface to participate in signaling, or whether its signaling properties are inactivated through its degradation in the lysosome. Hrs is a protein that resides on endosomes and is known to recruit sorting complexes that are vital to this sorting step. These sorting complexes are believed to recognize ubiquitin as sorting signals. However, the link between MVB sorting machinery and the ubiquitination machinery is not known. Recently, Hrs was shown to recruit and bind an E3 ubiquitin ligase, UBE4B, to endosomes. In an assay that is able to measure cargo movement, the disruption of the Hrs-UBE4B interaction showed impaired sorting of EGF receptor into MVBs. My hypothesis is that UBE4B may be the connection between MVB sorting and ubiquitination. This study addresses the role of UBE4B in the trafficking and ubiquitination of EGF receptor. I created stable cell lines that either overexpresses UBE4B or expresses a UBE4B with no ligase activity. Levels of EGF receptor were analyzed after certain periods of ligand-induced receptor internalization. I observed that higher expression levels of UBE4B correspond to increased degradation of EGF receptor. In an in vitro ubiquitination assay, I also determined that UBE4B mediates the ubiquitination of EGF receptor. These data suggest that UBE4B is required for EGFR degradation specifically because it ubiquitinates the receptor allowing it to be sorted into the internal vesicles of MVBs and subsequently degraded in lysosomes.

EVALUATION OF THE QUANTITATIVE ACCURACY OF A COMMERCIALLY-AVAILABLE POSITRON EMISSION MAMMOGRAPHY SCANNER

Objective: The PEM Flex Solo II (Naviscan, Inc., San Diego, CA) is currently the only commercially-available positron emission mammography (PEM) scanner. This scanner does not apply corrections for count rate effects, attenuation or scatter during image reconstruction, potentially affecting the quantitative accuracy of images. This work measures the overall quantitative accuracy of the PEM Flex system, and determines the contributions of error due to count rate effects, attenuation and scatter. Materials and Methods: Gelatin phantoms were designed to simulate breasts of different sizes (4 – 12 cm thick) with varying uniform background activity concentration (0.007 – 0.5 μCi/cc), cysts and lesions (2:1, 5:1, 10:1 lesion-to-background ratios). The overall error was calculated from ROI measurements in the phantoms with a clinically relevant background activity concentration (0.065 μCi/cc). The error due to count rate effects was determined by comparing the overall error at multiple background activity concentrations to the error at 0.007 μCi/cc. A point source and cold gelatin phantoms were used to assess the errors due to attenuation and scatter. The maximum pixel values in gelatin and in air were compared to determine the effect of attenuation. Scatter was evaluated by comparing the sum of all pixel values in gelatin and in air. Results: The overall error in the background was found to be negative in phantoms of all thicknesses, with the exception of the 4-cm thick phantoms (0%±7%), and it increased with thickness (-34%±6% for the 12-cm phantoms). All lesions exhibited large negative error (-22% for the 2:1 lesions in the 4-cm phantom) which increased with thickness and with lesion-to-background ratio (-85% for the 10:1 lesions in the 12-cm phantoms). The error due to count rate in phantoms with 0.065 μCi/cc background was negative (-23%±6% for 4-cm thickness) and decreased with thickness (-7%±7% for 12 cm). Attenuation was a substantial source of negative error and increased with thickness (-51%±10% to -77% ±4% in 4 to 12 cm phantoms, respectively). Scatter contributed a relatively constant amount of positive error (+23%±11%) for all thicknesses. Conclusion: Applying corrections for count rate, attenuation and scatter will be essential for the PEM Flex Solo II to be able to produce quantitatively accurate images.

Dealing with damage: Plasma membrane repair mechanisms.

Eukaryotic cells have developed repair mechanisms, which allow them to reseal their membrane in order to prevent the efflux of cytoplasmic constituents and the uncontrolled influx of calcium. After injury, the Ca(2+)-concentration gradient fulfils a dual function: it provides guidance cues for the repair machinery and directly activates the molecules, which have a repair function. Depending on the nature of injury, the morphology of the cell and the severity of injury, the membrane resealing can be effected by lysosomal exocytosis, microvesicle shedding or a combination of both. Likewise, exocytosis is often followed by the endocytic uptake of lesions. Additionally, since plasmalemmal resealing must be attempted, even after extensive injury in order to prevent cell lysis, the restoration of membrane integrity can be achieved by ceramide-driven invagination of the lipid bilayer, during which the cell is prepared for apoptotic disposal. Plasmalemmal injury can be contained by a surfeit of plasma membrane, which serves as a trap for toxic substances: either passively by an abundance of cellular protrusions, or actively by membrane blebbing.

TimX, a novel player in protein import across the inner mitochondrial membrane of T. brucei

Mitochondrial protein import is an essential function of the unique mitochondrion in T. brucei as roughly 1000 different nuclear encoded proteins need to be correctly localized to their mitochondrial subcompartment. For this reason the responsible import machinery is expected to be similarly complex as in other Eukaryotes. This was recently demonstrated for the translocation machinery in the outer mitochondrial membrane. In contrast, the composition of the inner membrane import machinery and the exact molecular pathway(s) taken by various substrates are still ill-defined. To elucidate this further, we performed a pulldown analysis of epitope tagged TbTim17 in combination with quantitative mass spectrometry. By this we identified novel components of the mitochondrial import machinery in trypanosomes. One of these, TimX, is an essential mitochondrial membrane protein of 42 kDa that is unique to kinetoplastids. This protein migrates on Blue Native PAGE in a high molecular weight complex similar to TbTim17. Ablation of either of the two proteins leads to a destabilization of the complex containing the other protein. Furthermore, its involvement in protein import could be demonstrated by in vivo and in vitro protein import assays. This corroborates that TimX together with TbTim17 forms a protein import complex in the inner mitochondrial membrane. As TbTim17 the TimX protein was subjected to pulldown analysis in combination with quantitative mass spectrometry. The overlap of candidates defined by these two sets of IPs likely defines further components of the inner membrane translocase which are presently being analyzed. In summary our study on novel components of the trypanosome mitochondrial protein import system gives us fascinating new insights into evolution of the mitochondrion.

Involvement of histone H3 methylation in Tup1-Ssn6 repression

The Tup1-Ssn6 complex regulates the expression of diverse classes of genes in Saccharomyces cerevisiae including those regulated by mating type, DNA damage, glucose, and anaerobic stress. The complex is recruited to target genes by sequence-specific repressor proteins. Once recruited to particular promoters, it is not completely clear how it functions to block transcription. Repression probably occurs through interactions with both the basal transcriptional machinery and components of chromatin. Tup1 interactions with chromatin are strongly influenced by acetylation of histories H3 and H4. Tup1 binds to underacetylated histone tails and requires multiple histone deacetylases (HDACs) for its repressive functions. Like acetylation, histone methylation is involved in regulation of gene expression. The possible role of histone methylation in Tup1 repression is not known. Here we examined possible roles of histone methyltransferases in Tup1-Ssn6 functions. We found that like other genes, Tup1-Ssn6 target genes exhibit increases in the levels of histone H3 lysine 4 methylation upon activation. However, deletion of individual or multiple histone methyltransferases (HMTs) and other SET-domain containing genes has no apparent effect on Tup1-Ssn6 mediated repression of a number of well-defined targets. Interestingly, we discovered that Ssn6 interacts with Set2. Since deletion of SET2 does not affect Tup1-Ssn6 repression, Ssn6 may utilize Set2 in other contexts to regulate gene repression. In order examine if the two components of the Tup1-Ssn6 complex have independent functions in the cell, we identified genes differentially expressed in tup1Δ and ssn6Δ mutants using DNA microarrays. Our data indicate that ∼4% of genes in the cell are regulated by Ssn6 independently of Tup1. In addition, expression of genes regulated by Tup1-Ssn6 seems to be differently affected by deletion of Ssn6 and deletion of Tup1, which indicates that these components might have separate functions. Our data shed new light on the classical view of Tup1-Ssn6 functions, and indicate that Ssn6 might have repressive functions as well. ^