Prediction of outcome in patients with low-grade squamous intraepithelial lesions by fluorescence in situ hybridization analysis of human papillomavirus, TERC, and MYC

BACKGROUND Cytology is an excellent method with which to diagnose preinvasive lesions of the uterine cervix, but it suffers from limited specificity for clinically significant lesions. Supplementary methods might predict the natural course of the detected lesions. The objective of the current study was to test whether a multicolor fluorescence in situ hybridization (FISH) assay might help to stratify abnormal results of Papanicolaou tests. METHODS A total of 219 liquid-based cytology specimens of low-grade squamous intraepithelial lesions (LSIL), 49 atypical squamous cells of undetermined significance (ASCUS) specimens, 52 high-grade squamous intraepithelial lesion (HSIL) specimens, and 50 normal samples were assessed by FISH with probes for the human papillomavirus (HPV), MYC, and telomerase RNA component (TERC). Subtyping of HPV by polymerase chain reaction (PCR) was performed in a subset of cases (n=206). RESULTS There was a significant correlation found between HPV detection by FISH and PCR (P<.0001). In patients with LSILs, the presence of HPV detected by FISH was significantly associated with disease progression (P<.0001). An increased MYC and/or TERC gene copy number (>2 signals in>10% of cells) prevailed in 43% of ASCUS specimens and was more frequent in HSIL (85%) than in LSIL (33%) (HSIL vs LSIL: P<.0001). Increased TERC gene copy number was significantly correlated with progression of LSIL (P<.01; odds ratio, 7.44; area under the receiver operating characteristic curve, 0.73; positive predictive value, 0.30; negative predictive value, 0.94) CONCLUSIONS: The detection of HPV by FISH analysis is feasible in liquid-based cytology and is significantly correlated with HPV analysis by PCR. The analysis of TERC gene copy number may be useful for risk stratification in patients with LSIL.

Retrospective study of indications for and outcome of perineal urethrostomy in cats

OBJECTIVES: To evaluate indications for and outcome of perineal urethrostomy in cats. METHODS: The medical records of 59 cats that had undergone perineal urethrostomy were evaluated. Short-term follow up information (for a period of four weeks following surgery) was available for all of the cats. Long-term follow up information (for a period of at least four months) was available for 39 cats. RESULTS: Early complications occurred in 25.4 per cent of cats and late complications were observed in 28.2 per cent of cats. The most frequent late complication was recurring bacterial urinary tract Infection. CLINICAL SIGNIFICANCE: Despite frequent complications and recurring signs of lower urinary tract disease, 32.2 per cent of the cats had a disease-free long-term outcome (mean four years, median 3.9 years), and 88.6 per cent of clients interviewed thought that their cats had a good quality of life after surgery.

Determination of sulfite and manganese in sediments from the K/T boundary

The solid-state-physics technique of electron spin resonance (ESR) has been employed in an exploratory study of marine limestones and impact-related deposits from Cretaceous-Tertiary (KT) boundary sites including Spain (Sopelana and Caravaca), New Jersey (Bass River), the U.S. Atlantic continental margin (Blake Nose, ODP Leg 171B/1049/A), and several locations in Belize and southern Mexico within -600 km of the Chicxulub crater. The ESR spectra of SO3(1-) (a radiation-induced point defect involving a sulfite ion substitutional for CO3(2-) which has trapped a positive charge) and Mn(2+) in calcite were singled out for analysis because they are unambiguously interpretable and relatively easy to record. ESR signal strengths of calcite-related SO3(1-) and Mn(2+) have been studied as functions of stratigraphic position in whole-rock samples across the KT boundary at Sopelana, Caravaca, and Blake Nose. At all three of these sites, anomalies in SO3(1-) and/or Mn(2+) intensities are noted at the KT boundary relative to the corresponding background levels in the rocks above and below. At Caravaca, the SO3(1-) background itself is found to be lower by a factor of 2.7 in the first 30,000 years of the Tertiary relative to its steady-state value in the last 15,000 years of the Cretaceous, indicating either an abrupt and quasi-permanent change in ocean chemistry (or temperature) or extinction of the marine biota primarily responsible for fixing sulfite in the late Cretaceous limestones. An exponential decrease in the Mn(2+) concentration per unit mass calcite, [Mn(2+)], as the KT boundary at Caravaca is approached from below (1/e characteristic length =1.4 cm) is interpreted as a result of post-impact leaching of the seafloor. Absolute ESR quantitative analyses of proximal impact deposits from Belize and southern Mexico group naturally into three distinct fields in a twodimensional [SO3(1-)]-versus-[Mn(2+)] scatter plot. These fields contain (I) limestone ejecta clasts, (II) accretionary lapilli, and (III) a variety of SO3(1-) -depleted/Mn(2+) enriched impact deposits. Data for the investigated non-impact-related Cretaceous and Tertiary marine limestones (Spain and Blake Nose) fall outside of these three fields. With reference to thes enon-impact deposits, fields I, II, and III can be respectively characterized as Mn(2+) -depleted, SO3(1-) -enhanced, and SO3(1-) -depleted. It is proposed that (1) field I represents calcites from the Yucatin Platform, and that the Mn(2+) -depleted signature can be used as an indicator of primary Chicxulub ejecta in deep marine environments and (2) field II represents calcites that include a component formed in the vapor plume, either from condensation in the presence of CO2/SO3(1-) -rich vapors, or reactions between CaO and CO2/SO3 rich vapors, and that this SO3(1-) -enhanced signature can be used as an indicator of impact vapor plume deposits. Given these two propositions, the ESR data for the Blake Nose deposits are ascribed to the presence of basal coarse calcitic Chicxulub ejecta clasts, while the finer components that are increasingly represented toward the top are interpreted to contain high- SO3(1-) calcite from the vapor plume. The apparently-undisturbed Bass River deposit may contain even higher concentrations of vapor-plume calcite. None of the three components included in field III appear to be represented at distal, deep marine KT-boundary sites; this field may include several types of impact-related deposits of diverse origins and diagenetic histories.

European sea bass, Dicentrarchus labrax, in a changing ocean

Ocean acidification, caused by rising concentrations of carbon dioxide (CO2), is widely considered to be a major global threat to marine ecosystems. To investigate the potential effects of ocean acidification on the early life stages of a commercially important fish species, European sea bass (Dicentrarchus labrax), 12 000 larvae were incubated from hatch through metamorphosis under a matrix of two temperatures (17 and 19 °C) and two seawater pCO2 levels (ambient and 1,000 µatm) and sampled regularly for 42 days. Calculated daily mortality was significantly affected by both temperature and pCO2, with both increased temperature and elevated pCO2 associated with lower daily mortality and a significant interaction between these two factors. There was no significant pCO2 effect noted on larval morphology during this period but larvae raised at 19 °C possessed significantly larger eyes and lower carbon:nitrogen ratios at the end of the study compared to those raised under 17 °C. Similarly, when the incubation was continued to post-metamorphic (juvenile) animals (day 67-69), fish raised under a combination of 19 °C and 1000 µatm pCO2 were significantly heavier. However, juvenile D. labrax raised under this combination of 19 °C and 1000 µatm pCO2 also exhibited lower aerobic scopes than those incubated at 19 °C and ambient pCO2. Most studies investigating the effects of near-future oceanic conditions on the early life stages of marine fish have used incubations of relatively short durations and suggested that these animals are resilient to ocean acidification. Whilst the increased survival and growth observed in this study supports this view, we conclude that more work is required to investigate whether the differences in juvenile physiology observed in this study manifest as negative impacts in adult fish.

BR3: a biologically inspired fish-like robot actuated by SMA-based artificial muscles

Los peces son animales, donde en la mayoría de los casos, son considerados como nadadores muy eficientes y con una alta capacidad de maniobra. En general los peces se caracterizan por su capacidad de maniobra, locomoción silencioso, giros y partidas rápidas y viajes de larga distancia. Los estudios han identificado varios tipos de locomoción que los peces usan para generar maniobras y natación constante. A bajas velocidades la mayoría de los peces utilizan sus aletas pares y / o impares para su locomoción, que ofrecen una mayor maniobrabilidad y mejor eficiencia de propulsión. A altas velocidades la locomoción implica el cuerpo y / o aleta caudal porque esto puede lograr un mayor empuje y aceleración. Estas características pueden inspirar el diseo y fabricación de una piel muy flexible, una aleta caudal mórfica y una espina dorsal no articulada con una gran capacidad de maniobra. Esta tesis presenta el desarrollo de un novedoso pez robot bio-inspirado y biomimético llamado BR3, inspirado en la capacidad de maniobra y nado constante de los peces vertebrados. Inspirado por la morfología de los peces Micropterus salmoides o también conocido como lubina negra, el robot BR3 utiliza su fundamento biológico para desarrollar modelos y métodos matemáticos precisos que permiten imitar la locomoción de los peces reales. Los peces Largemouth Bass pueden lograr un nivel increíble de maniobrabilidad y eficacia de la propulsión mediante la combinación de los movimientos ondulatorios y aletas morficas. Para imitar la locomoción de los peces reales en una contraparte artificial se necesita del análisis de tecnologías de actuación alternativos, como arreglos de fibras musculares en lugar de servo actuadores o motores DC estándar, así como un material flexible que proporciona una estructura continua sin juntas. Las aleaciones con memoria de forma (SMAs) proveen la posibilidad de construir robots livianos, que no emiten ruido, sin motores, sin juntas y sin engranajes. Asi es como un pez robot submarino se ha desarrollado y cuyos movimientos son generados mediante SMAs. Estos actuadores son los adecuados para doblar la espina dorsal continua del pez robot, que a su vez provoca un cambio en la curvatura del cuerpo. Este tipo de arreglo estructural está inspirado en los músculos rojos del pescado, que son usados principalmente durante la natación constante para la flexión de una estructura flexible pero casi incompresible como lo es la espina dorsal de pescado. Del mismo modo la aleta caudal se basa en SMAs y se modifica para llevar a cabo el trabajo necesario. La estructura flexible proporciona empuje y permite que el BR3 nade. Por otro lado la aleta caudal mórfica proporciona movimientos de balanceo y guiada. Motivado por la versatilidad del BR3 para imitar todos los modos de natación (anguilliforme, carangiforme, subcarangiforme y tunniforme) se propone un controlador de doblado y velocidad. La ley de control de doblado y velocidad incorpora la información del ángulo de curvatura y de la frecuencia para producir el modo de natación deseado y a su vez controlar la velocidad de natación. Así mismo de acuerdo con el hecho biológico de la influencia de la forma de la aleta caudal en la maniobrabilidad durante la natación constante se propone un control de actitud. Esta novedoso robot pescado es el primero de su tipo en incorporar sólo SMAs para doblar una estructura flexible continua y sin juntas y engranajes para producir empuje e imitar todos los modos de natación, así como la aleta caudal que es capaz de cambiar su forma. Este novedoso diseo mecatrónico presenta un futuro muy prometedor para el diseo de vehículos submarinos capaces de modificar su forma y nadar mas eficientemente. La nueva metodología de control propuesto en esta tesis proporcionan una forma totalmente nueva de control de robots basados en SMAs, haciéndolos energéticamente más eficientes y la incorporación de una aleta caudal mórfica permite realizar maniobras más eficientemente. En su conjunto, el proyecto BR3 consta de cinco grandes etapas de desarrollo: • Estudio y análisis biológico del nado de los peces con el propósito de definir criterios de diseño y control. • Formulación de modelos matemáticos que describan la: i) cinemática del cuerpo, ii) dinámica, iii) hidrodinámica iv) análisis de los modos de vibración y v) actuación usando SMA. Estos modelos permiten estimar la influencia de modular la aleta caudal y el doblado del cuerpo en la producción de fuerzas de empuje y fuerzas de rotación necesarias en las maniobras y optimización del consumo de energía. • Diseño y fabricación de BR3: i) estructura esquelética de la columna vertebral y el cuerpo, ii) mecanismo de actuación basado en SMAs para el cuerpo y la aleta caudal, iii) piel artificial, iv) electrónica embebida y v) fusión sensorial. Está dirigido a desarrollar la plataforma de pez robot BR3 que permite probar los métodos propuestos. • Controlador de nado: compuesto por: i) control de las SMA (modulación de la forma de la aleta caudal y regulación de la actitud) y ii) control de nado continuo (modulación de la velocidad y doblado). Está dirigido a la formulación de los métodos de control adecuados que permiten la modulación adecuada de la aleta caudal y el cuerpo del BR3. • Experimentos: está dirigido a la cuantificación de los efectos de: i) la correcta modulación de la aleta caudal en la producción de rotación y su efecto hidrodinámico durante la maniobra, ii) doblado del cuerpo para la producción de empuje y iii) efecto de la flexibilidad de la piel en la habilidad para doblarse del BR3. También tiene como objetivo demostrar y validar la hipótesis de mejora en la eficiencia de la natación y las maniobras gracias a los nuevos métodos de control presentados en esta tesis. A lo largo del desarrollo de cada una de las cinco etapas, se irán presentando los retos, problemáticas y soluciones a abordar. Los experimentos en canales de agua estarán orientados a discutir y demostrar cómo la aleta caudal y el cuerpo pueden afectar considerablemente la dinámica / hidrodinámica de natación / maniobras y cómo tomar ventaja de la modulación de curvatura que la aleta caudal mórfica y el cuerpo permiten para cambiar correctamente la geometría de la aleta caudal y del cuerpo durante la natación constante y maniobras. ABSTRACT Fishes are animals where in most cases are considered as highly manoeuvrable and effortless swimmers. In general fishes are characterized for his manoeuvring skills, noiseless locomotion, rapid turning, fast starting and long distance cruising. Studies have identified several types of locomotion that fish use to generate maneuvering and steady swimming. At low speeds most fishes uses median and/or paired fins for its locomotion, offering greater maneuverability and better propulsive efficiency At high speeds the locomotion involves the body and/or caudal fin because this can achieve greater thrust and accelerations. This can inspire the design and fabrication of a highly deformable soft artificial skins, morphing caudal fins and non articulated backbone with a significant maneuverability capacity. This thesis presents the development of a novel bio-inspired and biomimetic fishlike robot (BR3) inspired by the maneuverability and steady swimming ability of ray-finned fishes (Actinopterygii, bony fishes). Inspired by the morphology of the Largemouth Bass fish, the BR3 uses its biological foundation to develop accurate mathematical models and methods allowing to mimic fish locomotion. The Largemouth Bass fishes can achieve an amazing level of maneuverability and propulsive efficiency by combining undulatory movements and morphing fins. To mimic the locomotion of the real fishes on an artificial counterpart needs the analysis of alternative actuation technologies more likely muscle fiber arrays instead of standard servomotor actuators as well as a bendable material that provides a continuous structure without joins. The Shape Memory Alloys (SMAs) provide the possibility of building lightweight, joint-less, noise-less, motor-less and gear-less robots. Thus a swimming underwater fish-like robot has been developed whose movements are generated using SMAs. These actuators are suitable for bending the continuous backbone of the fish, which in turn causes a change in the curvature of the body. This type of structural arrangement is inspired by fish red muscles, which are mainly recruited during steady swimming for the bending of a flexible but nearly incompressible structure such as the fishbone. Likewise the caudal fin is based on SMAs and is customized to provide the necessary work out. The bendable structure provides thrust and allows the BR3 to swim. On the other hand the morphing caudal fin provides roll and yaw movements. Motivated by the versatility of the BR3 to mimic all the swimming modes (anguilliform, caranguiform, subcaranguiform and thunniform) a bending-speed controller is proposed. The bending-speed control law incorporates bend angle and frequency information to produce desired swimming mode and swimming speed. Likewise according to the biological fact about the influence of caudal fin shape in the maneuverability during steady swimming an attitude control is proposed. This novel fish robot is the first of its kind to incorporate only SMAs to bend a flexible continuous structure without joints and gears to produce thrust and mimic all the swimming modes as well as the caudal fin to be morphing. This novel mechatronic design is a promising way to design more efficient swimming/morphing underwater vehicles. The novel control methodology proposed in this thesis provide a totally new way of controlling robots based on SMAs, making them more energy efficient and the incorporation of a morphing caudal fin allows to perform more efficient maneuvers. As a whole, the BR3 project consists of five major stages of development: • Study and analysis of biological fish swimming data reported in specialized literature aimed at defining design and control criteria. • Formulation of mathematical models for: i) body kinematics, ii) dynamics, iii) hydrodynamics, iv) free vibration analysis and v) SMA muscle-like actuation. It is aimed at modelling the e ects of modulating caudal fin and body bend into the production of thrust forces for swimming, rotational forces for maneuvering and energy consumption optimisation. • Bio-inspired design and fabrication of: i) skeletal structure of backbone and body, ii) SMA muscle-like mechanisms for the body and caudal fin, iii) the artificial skin, iv) electronics onboard and v) sensor fusion. It is aimed at developing the fish-like platform (BR3) that allows for testing the methods proposed. • The swimming controller: i) control of SMA-muscles (morphing-caudal fin modulation and attitude regulation) and ii) steady swimming control (bend modulation and speed modulation). It is aimed at formulating the proper control methods that allow for the proper modulation of BR3’s caudal fin and body. • Experiments: it is aimed at quantifying the effects of: i) properly caudal fin modulation into hydrodynamics and rotation production for maneuvering, ii) body bending into thrust generation and iii) skin flexibility into BR3 bending ability. It is also aimed at demonstrating and validating the hypothesis of improving swimming and maneuvering efficiency thanks to the novel control methods presented in this thesis. This thesis introduces the challenges and methods to address these stages. Waterchannel experiments will be oriented to discuss and demonstrate how the caudal fin and body can considerably affect the dynamics/hydrodynamics of swimming/maneuvering and how to take advantage of bend modulation that the morphing-caudal fin and body enable to properly change caudal fin and body’ geometry during steady swimming and maneuvering.

Proline and pyrrolidine derivatives: new drug cadidates for hepatitis C treatment

The more advantageous hepatitis C virus (HCV) inhibitors (most of them incorporating polysubstituted prolines or pyrrolidines) are detailed in this paper. The improvement of current treatments by combination of antiviral drugs is the driving force of this race to reduce the fast proliferation of this virus. The enhancement of efficiency in short periods of treatment is crucial in the economical point of view and for the hope of all infected people. New protease or polymerase inhibitors have been recently developed in order to substitute the traditional highly toxic PEG-interferon α-2b/ribavirin tandem. The contribution of our group in this field concerns the elaboration of the first and second generation GSK polymerase inhibitors through enantioselective processes based on silver(I)- and gold(I)-catalyzed 1,3-dipolar cycloadditions of azomethine ylides.

Algercum munita metropolis Regni Algeriani : in littore Africano Barbariæ in monte declivi Amphitheatri instar quadrata forma extructa, cum portu Commodissimo Sedes est Bassæ Turcici et ob piraticam per orbem famosissima =: Algier die Befestigte Haupt-Statt des Königr. Algier, Auf die Africanischen Küsten in der Barbarey auf einem abhängigen Berg wie ein Amphiteatrum in gevierten form gebauet samt dem bequemen hasen. Ift die Residenz des Türkischen Bassa u: wegen ihrer Secrauberey Welt berussen

cura et sumptibus Matth. Seutteri.

(Table 1) Main constituents of coccolith size fractions expressed as carbonate contribution at Bass River during the PETM

Coccoliths, calcite plates produced by the marine phytoplankton coccolithophores, have previously shown a large array of carbon and oxygen stable isotope fractionations (termed "vital effects"), correlated to cell size and hypothesized to reflect the varying importance of active carbon acquisition strategies. Culture studies show a reduced range of vital effects between large and small coccolithophores under high CO2, consistent with previous observations of a smaller range of interspecific vital effects in Paleocene coccoliths. We present new fossil data examining coccolithophore vital effects over three key Cenozoic intervals reflecting changing climate and atmospheric partial pressure of CO2 (pCO2). Oxygen and carbon stable isotopes of size-separated coccolith fractions dominated by different species from well preserved Paleocene-Eocene thermal maximum (PETM, ~56 Ma) samples show reduced interspecific differences within the greenhouse boundary conditions of the PETM. Conversely, isotope data from the Plio-Pleistocene transition (PPT; 3.5-2 Ma) and the last glacial maximum (LGM; ~22 ka) show persistent vital effects of ~2 per mil. PPT and LGM data show a clear positive trend between coccolith (cell) size and isotopic enrichment in coccolith carbonate, as seen in laboratory cultures. On geological timescales, the degree of expression of vital effects in coccoliths appears to be insensitive topCO2 changes over the range ~350 ppm (Pliocene) to ~180 ppm (LGM). The modern array of coccolith vital effects arose after the PETM but before the late Pliocene and may reflect the operation of more diverse carbon acquisition strategies in coccolithophores in response to decreasing Cenozoic pCO2.

Kleine theoretisch-praktische Gesangschule : enthaltend ein-, zwei,- drei- und vierstimmige Uebungen für ersten und zweiten Tenor und ersten und zweiten Bass zur Ausbildung des vierstimmigen Männergesanges in Seminarien, Bräparandenanstalten und Liederstafeln entworfen /

Mode of access: Internet.

One hundredth anniversary of the consecration of the Rt. Rev. Edward Bass, D. D., as the first Bishop of Massachusetts, May 7, 1797-May 7, 1897.

Cover title: Centennial celebration of the consecration of the Rt. Rev. Edward Bass, D. D., as the first Bishop of Massachussetts, 1897-1897.

40 songs and airs /

v. 1. Soprano -- v. 2-3-4. Soprano and Tenor -- v. 6 Contralto. Bass.