Mutations in the rotated abdomen locus affect muscle development and reveal an intrinsic asymmetry in Drosophila.

In bilateral animals, the left and right sides of the body usually present asymmetric structures, the genetic bases of whose generation are still largely unknown [CIBA Foundation (1991) Biological Asymmetry and Handedness, CIBA Foundation Symposium 162 (Wiley, New York), pp. 1-327]. In Drosophila melanogaster, mutations in the rotated abdomen (rt) locus cause a clockwise helical rotation of the body. Even null alleles are viable but exhibit defects in embryonic muscle development, rotation of the whole larval body, and helical staggering of cuticular patterns in abdominal segments of the adult. rotated abdomen is expressed in the embryonic mesoderm and midgut but not in the ectoderm; it encodes a putative integral membrane glycoprotein (homologous to key yeast mannosyltransferases). Mesodermal cells defective in O-glycosylation lead to an impaired larval muscular system. We propose that the staggering of the adult abdominal segments would be a consequence of the relaxation of intrinsic rotational torque of muscle architecture, preventing the colateral alignment of the segmental histoblast cells during their proliferation at metamorphosis.

Polynitrosylated proteins: characterization, bioactivity, and functional consequences.

Chemical modification of proteins is a common theme in their regulation. Nitrosylation of protein sulfhydryl groups has been shown to confer nitric oxide (NO)-like biological activities and to regulate protein functions. Several other nucleophilic side chains -- including those with hydroxyls, amines, and aromatic carbons -- are also potentially susceptible to nitrosative attack. Therefore, we examined the reactivity and functional consequences of nitros(yl)ation at a variety of nucleophilic centers in biological molecules. Chemical analysis and spectroscopic studies show that nitrosation reactions are sustained at sulfur, oxygen, nitrogen, and aromatic carbon centers, with thiols being the most reactive functionality. The exemplary protein, BSA, in the presence of a 1-, 20-, 100-, or 200-fold excess of nitrosating equivalents removes 0.6 +/- 0.2, 3.2 +/- 0.4, 18 +/- 4, and 38 +/- 10, respectively, moles of NO equivalents per mole of BSA from the reaction medium; spectroscopic evidence shows the proportionate formation of a polynitrosylated protein. Analogous reaction of tissue-type plasminogen activator yields comparable NO protein stoichiometries. Disruption of protein tertiary structure by reduction results in the preferential nitrosylation of up to 20 thus-exposed thiol groups. The polynitrosylated proteins exhibit antiplatelet and vasodilator activity that increases with the degree of nitrosation, but S-nitroso derivatives show the greatest NO-related bioactivity. Studies on enzymatic activity of tissue-type plasminogen activator show that polynitrosylation may lead to attenuated function. Moreover, the reactivity of tyrosine residues in proteins raises the possibility that NO could disrupt processes regulated by phosphorylation. Polynitrosylated proteins were found in reaction mixtures containing interferon-gamma/lipopolysaccharide-stimulated macrophages and in tracheal secretions of subjects treated with NO gas, thus suggesting their physiological relevance. In conclusion, multiple sites on proteins are susceptible to attack by nitrogen oxides. Thiol groups are preferentially modified, supporting the notion that S-nitrosylation can serve to regulate protein function. Nitrosation reactions sustained at additional nucleophilic centers may have (patho)physiological significance and suggest a facile route by which abundant NO bioactivity can be delivered to a biological system, with specificity dictated by protein substrate.

Differential recognition of the type I interferon receptor by interferons tau and alpha is responsible for their disparate cytotoxicities.

Interferon tau (IFN tau), originally identified as a pregnancy recognition hormone, is a type I interferon that is related to the various IFN alpha species (IFN alpha s). Ovine IFN tau has antiviral activity similar to that of human IFN alpha A on the Madin-Darby bovine kidney (MDBK) cell line and is equally effective in inhibiting cell proliferation. In this study, IFN tau was found to differ from IFN alpha A in that is was > 30-fold less toxic to MDBK cells at high concentrations. Excess IFN tau did not block the cytotoxicity of IFN alpha A on MDBK cells, suggesting that these two type I IFNs recognize the type I IFN receptor differently on these cells. In direct binding studies, 125I-IFN tau had a Kd of 3.90 x 10(-10) M for receptor on MDBK cells, whereas that of 125I-IFN alpha A was 4.45 x 10(-11) M. Consistent with the higher binding affinity, IFN alpha A was severalfold more effective than IFN tau in competitive binding against 125I-IFN tau to receptor on MDBK cells. Paradoxically, the two IFNs had similar specific antiviral activities on MDBK cells. However, maximal IFN antiviral activity required only fractional occupancy of receptors, whereas toxicity was associated with maximal receptor occupancy. Hence, IFN alpha A, with the higher binding affinity, was more toxic than IFN tau. The IFNs were similar in inducing the specific phosphorylation of the type I receptor-associated tyrosine kinase Tyk2, and the transcription factors Stat1 alpha and Stat2, suggesting that phosphorylation of these signal transduction proteins is not involved in the cellular toxicity associated with type I IFNs. Experiments using synthetic peptides suggest that differences in the interaction at the N terminal of IFN tau and IFN alpha with the type I receptor complex contribute significantly to differences in high-affinity equilibrium binding of these molecules. It is postulated that such a differential recognition of the receptor is responsible for the similar antiviral but different cytotoxic effects of these IFNs. Moreover, these data imply that receptors are "spare'' with respect to certain biological properties, and we speculate that IFNs may induce a concentration-dependent selective association of receptor subunits.

Innovative analytical strategies for the development of sensor devices and mass spectrometry methods

Il lavoro presentato in questa tesi di Dottorato è incentrato sullo sviluppo di strategie analitiche innovative basate sulla sensoristica e su tecniche di spettrometria di massa in ambito biologico e della sicurezza alimentare. Il primo capitolo tratta lo studio di aspetti metodologici ed applicativi di procedure sensoristiche per l’identificazione e la determinazione di biomarkers associati alla malattia celiaca. In tale ambito, sono stati sviluppati due immunosensori, uno a trasduzione piezoelettrica e uno a trasduzione amperometrica, per la rivelazione di anticorpi anti-transglutaminasi tissutale associati a questa malattia. L’innovazione di questi dispositivi riguarda l’immobilizzazione dell’enzima tTG nella conformazione aperta (Open-tTG), che è stato dimostrato essere quella principalmente coinvolta nella patogenesi. Sulla base dei risultati ottenuti, entrambi i sistemi sviluppati si sono dimostrati una valida alternativa ai test di screening attualmente in uso per la diagnosi della celiachia. Rimanendo sempre nel contesto della malattia celiaca, ulteriore ricerca oggetto di questa tesi di Dottorato, ha riguardato lo sviluppo di metodi affidabili per il controllo di prodotti “gluten-free”. Il secondo capitolo tratta lo sviluppo di un metodo di spettrometria di massa e di un immunosensore competitivo per la rivelazione di prolammine in alimenti “gluten-free”. E’ stato sviluppato un metodo LC-ESI-MS/MS basato su un’analisi target con modalità di acquisizione del segnale selected reaction monitoring per l’identificazione di glutine in diversi cereali potenzialmente tossici per i celiaci. Inoltre ci si è focalizzati su un immunosensore competitivo per la rivelazione di gliadina, come metodo di screening rapido di farine. Entrambi i sistemi sono stati ottimizzati impiegando miscele di farina di riso addizionata di gliadina, avenine, ordeine e secaline nel caso del sistema LC-MS/MS e con sola gliadina nel caso del sensore. Infine i sistemi analitici sono stati validati analizzando sia materie prime (farine) che alimenti (biscotti, pasta, pane, etc.). L’approccio sviluppato in spettrometria di massa apre la strada alla possibilità di sviluppare un test di screening multiplo per la valutazione della sicurezza di prodotti dichiarati “gluten-free”, mentre ulteriori studi dovranno essere svolti per ricercare condizioni di estrazione compatibili con l’immunosaggio competitivo, per ora applicabile solo all’analisi di farine estratte con etanolo. Terzo capitolo di questa tesi riguarda lo sviluppo di nuovi metodi per la rivelazione di HPV, Chlamydia e Gonorrhoeae in fluidi biologici. Si è scelto un substrato costituito da strips di carta in quanto possono costituire una valida piattaforma di rivelazione, offrendo vantaggi grazie al basso costo, alla possibilità di generare dispositivi portatili e di poter visualizzare il risultato visivamente senza la necessità di strumentazioni. La metodologia sviluppata è molto semplice, non prevede l’uso di strumentazione complessa e si basa sull’uso della isothermal rolling-circle amplification per l’amplificazione del target. Inoltre, di fondamentale importanza, è l’utilizzo di nanoparticelle colorate che, essendo state funzionalizzate con una sequenza di DNA complementare al target amplificato derivante dalla RCA, ne permettono la rivelazione a occhio nudo mediante l’uso di filtri di carta. Queste strips sono state testate su campioni reali permettendo una discriminazione tra campioni positivi e negativi in tempi rapidi (10-15 minuti), aprendo una nuova via verso nuovi test altamente competitivi con quelli attualmente sul mercato.

Multi-agent system for control of robots inspired on the distributed activity and hormonal regulation of humans

Robotics is an emerging field with great activity. Robotics is a field that presents several problems because it depends on a large number of disciplines, technologies, devices and tasks. Its expansion from perfectly controlled industrial environments toward open and dynamic environment presents a many new challenges. New uses are, for example, household robots or professional robots. To facilitate the low cost, rapid development of robotic systems, reusability of code, its medium and long term maintainability and robustness are required novel approaches to provide generic models and software systems who develop paradigms capable of solving these problems. For this purpose, in this paper we propose a model based on multi-agent systems inspired by the human nervous system able to transfer the control characteristics of the biological system and able to take advantage of the best properties of distributed software systems. Specifically, we model the decentralized activity and hormonal variation.

Subsidence damage assessment of a Gothic church using differential interferometry and field data

The Santas Justa and Rufina Gothic church (fourteenth century) has suffered several physical, mechanical, chemical, and biochemical types of pathologies along its history: rock alveolization, efflorescence, biological activity, and capillary ascent of groundwater. However, during the last two decades, a new phenomenon has seriously affected the church: ground subsidence caused by aquifer overexploitation. Subsidence is a process that affects the whole Vega Baja of the Segura River basin and consists of gradual sinking in the ground surface caused by soil consolidation due to a pore pressure decrease. This phenomenon has been studied by differential synthetic aperture radar interferometry techniques, which illustrate settlements up to 100 mm for the 1993–2009 period for the whole Orihuela city. Although no differential synthetic aperture radar interferometry information is available for the church due to the loss of interferometric coherence, the spatial analysis of nearby deformation combined with fieldwork has advanced the current understanding on the mechanisms that affect the Santas Justa and Rufina church. These results show the potential interest and the limitations of using this remote sensing technique as a complementary tool for the forensic analysis of building structures.

Financial bills and receipts, 1781

One-page account between William and Joseph Croswell for board and supplies.

Copy of William Watson's account for painting and glazing of Holden Chapel, September 1801

Contains an itemized list of costs for painting and glazing tasks to be completed and supplies needed by Watson for Holden Chapel. Tasks include painting Doctor Warren's room twice, painting window sashes and shutters, transporting glass from Boston, and setting each window pane. Supplies needed include oil, white lead, and putty.

College Book 6, 1726-1790

College Book 6 is often referred to as the Hollis book, reflecting its contents. It was created following an April 4, 1726 Corporation vote that "Mr. Treasurer procure a Book, into which shall be transmitted, and a Register kept of, Mr Hollis's Rules, orders, Gifts & Bounties past & to come; together with ye Names & age, & Charecter of his Scholars, ye time of their Entry and Dismission; and also all ye Votes of ye Overseers & Corporation from time to time relating to ye said orders, Bounties & Scholars of the said Mr Hollis." Entries are primarily in Benjamin Wadsworth's hand and record donations from Thomas Hollis and his descendants, with transcriptions of related Corporation minutes. They also provide detailed information about the allocation of Hollis funds and scholarships, and the rules governing the Hollis Professorship of Divinity (established in 1721) and the Hollis Professorship of Mathematics and Natural Philosophy (established in 1727). The volume also contains inventories of books in the official library of the Hollis Professor of Divinity and two inventories – created in 1779 and in 1790 – of the mathematical and philosophical apparatus purchased with Hollis funds. Many entries related to the purchase of scientific instruments and supplies include the cost in sterling of each item. Also included are entries related to financial accounts and expenditures, as well as copies of letters from Nathaniel Hollis.

John Winthrop's proposal respecting electrical globes and jars, ca. 1758

In this proposal, John Winthrop explains the need to replace damaged "electric globes" used in the College's collection of scientific apparatus. He states that Benjamin Franklin, at the time residing in London, was willing to seek replacement globes for the College's collection. Winthrop then proceeds to assert that the College should acquire "square bottles, of a moderate size, fitted in a wooden box, like what they call case bottles for spirits" instead of the large jars included in the scientific apparatus, because those jars cracked frequently.

(Table1) Sedimentation rates and age-control points form ODP Hole 152-919A

Planktic d18O and d13C records and point count records of biogenic, volcanic, and nonvolcanic terrigenous [ice-rafted debris (IRD)] sediment components from Hole 919A in the Irminger basin, northern North Atlantic provide a comprehensive dataset from which a paleoceanographic reconstruction for the last 630 kyr has been developed. The paleoceanographic evolution of the Irminger basin during this time contains both long-term patterns and significant developmental steps. One long-term pattern observed is the persistent deposition of hematite-stained ice-rafted debris. This record suggests that the modern and late Pleistocene discharges of icebergs from northern redbed regions to the Irminger Sea lie in the low end of the range observed over the last 630 kyr. In addition, Arctic front fluctuations appear to have been the main controlling factor on the long-term accumulation patterns of IRD and planktic biogenic groups. The Hole 919A sediment record also contains a long-term association between felsic volcanic ash abundances and light d18O excursions in both interglacial and glacial stages, which suggests a causal link between deglaciations and explosive Icelandic eruptions. A significant developmental step in the paleoceanographic reconstruction based on benthic evidence was for diminished supply of Denmark Strait Overflow Water (DSOW) beginning at ~380 ka, possibly initiated by the influx of meltwater from broad-scale iceberg discharges along the east Greenland coast. There is also planktic evidence of a two-step cooling of sea surface conditions in the Irminger basin, first at ~338-309 ka and later at ~211-190 ka, after which both glacials and interglacials were colder as the Arctic front migrated southeast of Site 919. In addition to offering these findings, this reconstruction provides a longer-term geologic context for the interpretation of more recent paleoceanographic events and patterns of deposition from this region.

Polyaromatic hydrocarbons in sediments from the Barents and White Seas

Polycyclic aromatic hydrocarbons (PAHs) are common environmental contaminants which can be derived from anthropogenic sources, such as combustion and discharges from extraction and transport, and natural processes, including leakage and erosion of fossil carbon. Natural PAH sources contribute, along with biological activities and terrestrial run-off, to the organic carbon content in sediments.The Barents Sea region is far from many anthropogenic sources of PAH, but production and trans-shipment of hydrocarbons is increasing. We present data for polycyclic aromatic hydrocarbon (PAH) concentrations in bottom sediments from 510 stations in the Barents and White Seas, and along the northern coast of Norway.

Summary of boron isotope and Mg/Ca data

Biological productivity and carbon export in the equatorial Atlantic are thought to have been dramatically higher during the last glacial period than during the Holocene. Here we reconstruct the pH and CO2 content of surface waters from the eastern equatorial Atlantic Ocean over the past ~30 k.y. using the boron isotope composition of Globigerinoides ruber (a mixed-layer-dwelling planktic foraminifera). Our new record, combined with previously published data, indicates that during the last glacial, in contrast to today, a strong west to east gradient existed in the extent of air:sea equilibrium with respect to pCO2 (DeltapCO2), with the eastern equatorial Atlantic acting as a significant source of CO2 (+100 µatm) while the western Atlantic remained close to equilibrium (+25 µatm). This pattern suggests that a fivefold increase in the upwelling rate of deeper waters drove increased Atlantic productivity and large-scale regional cooling during the last glacial, but the higher than modern DeltapCO2 in the east indicates that export production did not keep up with enhanced upwelling of nutrients. However, the downstream decline of DeltapCO2 provides evidence that the unused nutrients from the east were eventually used for biologic carbon export, thereby effectively negating the impact of changes in upwelling on atmospheric CO2 levels. Our findings indicate that the equatorial Atlantic exerted a minimal role in contributing to lower glacial-age atmospheric CO2.

The care of books : an essay on the development of libraries and their fittings, from the earliest times to the end of the eighteenth century /

Includes bibliographical references.

Reliability stress and failure rate data for electronic equipment.

Cover title.