Sensitivity and Fragmentation Calibration of the ROSINA Reflectron-type Time-Of-Flight Mass Spectrometer

The goal of this work was to increase the performance and to calibrate one of the ROSINA sensors, the Reflectron-type Time-Of-Flight mass spectrometer, currently flying aboard the ESA Rosetta spacecraft. Different optimization techniques were applied to both the lab and space models, and a static calibration was performed using different gas species expected to be detected in the vicinity of comet 67P/Churyumov-Gerasimenko. The database thus created was successfully applied to space data, giving consistent results with the other ROSINA sensors.

Sensitivity and fragmentation calibration of the ROSINA double focusing mass spectrometer

The goal of this work has been to calibrate sensitivities and fragmentation pattern of various molecules as well as further characterize the lab model of the ROSINA Double Focusing Mass Spectrometer (DFMS) on board ESA’s Rosetta spacecraft bound to comet 67P/Churyumov-Gerasimenko. The detailed calibration and characterization of the instrument is key to understand and interpret the results in the coma of the comet. A static calibration was performed for the following species: Ne, Ar, Kr, Xe, H2O, N2, CO2, CH4, C2H6, C3H8, C4H10, and C2H4. The purpose of the calibration was to obtain sensitivities for all detectors and emissions, the fragmentation behavior of the ion source and to show the capabilities to measure isotopic ratios at the comet. The calibration included the recording of different correction factors to evaluate the data, including a detailed investigation of the detector gain. The quality of the calibration that could be tested for different gas mixtures including the calibration of the density inside the ion source when calibration gas from the gas calibration unit is introduced. In conclusion the calibration shows that DFMS meets the design requirements and that DFMS will be able to measure the D/H at the comet and help shed more light on the puzzle about the origin of water on Earth.

UPM Activities on Sensitivity and Uncertainty Analysis of Assembly Depletion

UPM Activities on Sensitivity and Uncertainty Analysis of Assembly Depletion

Complejidad Esencial: Un argumento por la complementariedad entre ciencia y sensibilidad = Essential Complexity: An argument for complementarity between science and sensibility

Esta investigación recoge un cúmulo de intereses en torno a un modo de generar arquitectura muy específico: La producción de objetos con una forma subyacente no apriorística. Los conocimientos expuestos se apoyan en condiciones del pensamiento reciente que impulsan la ilusión por alimentar la fuente creativa de la arquitectura con otros campos del saber. Los tiempos del conocimiento animista sensible y el conocimiento objetivo de carácter científico son correlativos en la historia pero casi nunca han sido sincrónicos. Representa asimismo un intento por aunar los dos tipos de conocimiento retomando la inercia que ya se presentía a comienzos del siglo XX. Se trata por tanto, de un ensayo sobre la posible anulación de la contraposición entre estos dos mundos para pasar a una complementariedad entre ambos en una sola visión conjunta compartida. Como meta final de esta investigación se presenta el desarrollo de un sistema crítico de análisis para los objetos arquitectónicos que permita una diferenciación entre aquellos que responden a los problemas de manera completa y sincera y aquellos otros que esconden, bajo una superficie consensuada, la falta de un método resolutivo de la complejidad en el presente creativo. La Investigación observa tres grupos de conocimiento diferenciados agrupados en sus capítulos correspondientes: El primer capítulo versa sobre el Impulso Creador. En él se define la necesidad de crear un marco para el individuo creador, aquel que independientemente de las fuerzas sociales del momento presiente que existe algo más allá que está sin resolver. Denominamos aquí “creador rebelde” a un tipo de personaje reconocible a lo largo de la Historia como aquel capaz de reconocer los cambios que ese operan en su presente y que utiliza para descubrir lo nuevo y acercarse algo al origen creativo. En el momento actual ese tipo de personaje es el que intuye o ya ha intuido hace tiempo la existencia de una complejidad creciente no obviable en el pensamiento de este tiempo. El segundo capítulo desarrolla algunas Propiedades de Sistemas de actuación creativa. En él se muestra una investigación que desarrolla un marco de conocimientos científicos muy específicos de nuestro tiempo que la arquitectura, de momento, no ha absorbido ni refleja de manera directa en su manera de crear. Son temas de presencia casi ya mundana en la sociedad pero que se resisten a ser incluidos en los procesos creativos como parte de la conciencia. La mayoría de ellos hablan de precisión, órdenes invisibles, propiedades de la materia o la energía tratados de manera objetiva y apolítica. La meta final supone el acercamiento e incorporación de estos conceptos y propiedades a nuestro mundo sensible unificándolos indisociablemente bajo un solo punto de vista. El último capítulo versa sobre la Complejidad y su capacidad de reducción a lo esencial. Aquí se muestran, a modo de conclusiones, la introducción de varios conceptos para el desarrollo de un sistema crítico hacia la arquitectura de nuestro tiempo. Entre ellos, el de Complejidad Esencial, definido como aquella de carácter inevitable a la hora de responder la arquitectura a los problemas y solicitaciones crecientes a los que se enfrenta en el presente. La Tesis mantiene la importancia de informar sobre la imposibilidad en el estado actual de las cosas de responder de manera sincera con soluciones de carácter simplista y la necesidad, por tanto, de soluciones necesarias de carácter complejo. En este sentido se define asimismo el concepto de Forma Subyacente como herramienta crítica para poder evaluar la respuesta de cada arquitectura y poder tener un sistema y visión crítica sobre lo que es un objeto consistente frente a la situación a la que se enfrenta. Dicha forma subyacente se define como aquella manera de entender conjuntamente y de manera sincrónica aquello que percibimos de manera sensible inseparable de las fuerzas ocultas, creativas, tecnológicas, materiales y energéticas que sustentan la definición y entendimiento de cualquier objeto construido. ABSTRACT This research includes a cluster of interests around a specific way to generate architecture: The production of objects without an a priori underlying form. The knowledge presented is based on current conditions of thought promoting the illusion to feed the creative source of architecture with other fields of knowledge. The sensible animist knowledge and objective scientific knowledge are correlative in history but have rarely been synchronous. This research is also an attempt to combine both types of knowledge to regain the inertia already sensed in the early twentieth century. It is therefore an essay on the annulment of the opposition between these two worlds to move towards complementarities of both in a single shared vision. The ultimate goal of this research is to present the development of a critical analysis system for architectural objects that allows differentiation between those who respond to the problems sincerely and those who hide under an agreed appearance, the lack of a method for solving the complexity of the creative present. The research observes three distinct groups of knowledge contained in their respective chapters: The first chapter deals with the Creative Impulse. In it is defined the need to create a framework for the creative individual who, regardless of the current social forces, forebodes that there is something hidden beyond which is still unresolved. We define the "rebel creator" as a kind of person existing throughout history who is able to recognize the changes operating in its present and use them to discover something new and get closer to the origin of creation. At present, this type of character is the one who intuits the existence of a non obviable increasing complexity in society and thought. The second chapter presents some systems, and their properties, for creative performance. It describes the development of a framework composed of current scientific knowledge that architecture has not yet absorbed or reflected directly in her procedures. These are issues of common presence in society but are still reluctant to be included in the creative processes even if they already belong to the collective consciousness. Most of them talk about accuracy, invisible orders, properties of matter and energy, always treated from an objective and apolitical perspective. The ultimate goal pursues the approach and incorporation of these concepts and properties to the sensible world, inextricably unifying all under a single point of view. The last chapter deals with complexity and the ability to reduce it to the essentials. Here we show, as a conclusion, the introduction of several concepts to develop a critical approach to analyzing the architecture of our time. Among them, the concept of Essential Complexity, defined as one that inevitably arises when architecture responds to the increasing stresses that faces today. The thesis maintains the importance of reporting, in the present state of things, the impossibility to respond openly with simplistic solutions and, therefore, the need for solutions to complex character. In this sense, the concept of Underlying Form is defined as a critical tool to evaluate the response of each architecture and possess a critical system to clarify what is an consistent object facing a certain situation. The underlying form is then defined as a way to synchronously understand what we perceive sensitively inseparable from the hidden forces of creative, technological, material and energetic character that support the definition and understanding of any constructed object.

Transfer of the HIV-1 cyclophilin-binding site to simian immunodeficiency virus from Macaca mulatta can confer both cyclosporin sensitivity and cyclosporin dependence

HIV-1 specifically incorporates the peptidyl prolyl isomerase cyclophilin A (CyPA), the cytosolic receptor for the immunosuppressant cyclosporin A (CsA). HIV-1 replication is inhibited by CsA as well as by nonimmunosuppressive CsA analogues that bind to CyPA and interfere with its virion association. In contrast, the related simian immunodeficiency virus SIVmac, which does not interact with CyPA, is resistant to these compounds. The incorporation of CyPA into HIV-1 virions is mediated by a specific interaction between the active site of the enzyme and the capsid (CA) domain of the HIV-1 Gag polyprotein. We report here that the transfer of HIV-1 CA residues 86–93, which form part of an exposed loop, to the corresponding position in SIVmac resulted in the efficient incorporation of CyPA and conferred an HIV-1-like sensitivity to a nonimmunosuppressive cyclosporin. HIV-1 CA residues 86–90 were also sufficient to transfer the ability to efficiently incorporate CyPA, provided that the length of the CyPA-binding loop was preserved. However, the resulting SIVmac mutant required the presence of cyclosporin for efficient virus replication. The results indicate that the presence or absence of a type II tight turn adjacent to the primary CyPA-binding site determines whether CyPA incorporation enhances or inhibits viral replication. By demonstrating that CyPA-binding-site residues can induce cyclosporin sensitivity in a heterologous context, this study provides direct in vivo evidence that the exposed loop between helices IV and V of HIV-1 CA not merely constitutes a docking site for CyPA but is a functional target of this cellular protein.

Alternative splicing, muscle calcium sensitivity, and the modulation of dragonfly flight performance

Calcium sensitivity of myosin cross-bridge activation in striated muscles commonly varies during ontogeny and in response to alterations in muscle usage, but the consequences for whole-organism physiology are not well known. Here we show that the relative abundances of alternatively spliced transcripts of the calcium regulatory protein troponin T (TnT) vary widely in flight muscle of Libellula pulchella dragonflies, and that the mixture of TnT splice variants explains significant portions of the variation in muscle calcium sensitivity, wing-beat frequency, and an index of aerodynamic power output during free flight. Two size-distinguishable morphs differ in their maturational pattern of TnT splicing, yet they show the same relationship between TnT transcript mixture and calcium sensitivity and between calcium sensitivity and aerodynamic power output. This consistency of effect in different developmental and physiological contexts strengthens the hypothesis that TnT isoform variation modulates muscle calcium sensitivity and whole-organism locomotor performance. Modulating muscle power output appears to provide the ecologically important ability to operate at different points along a tradeoff between performance and energetic cost.

Sensitivity and rapidity of vegetational response to abrupt climate change

Rapid climate change characterizes numerous terrestrial sediment records during and since the last glaciation. Vegetational response is best expressed in terrestrial records near ecotones, where sensitivity to climate change is greatest, and response times are as short as decades.

Changes in voltage activation, Cs+ sensitivity, and ion permeability in H5 mutants of the plant K+ channel KAT1.

KAT1 is a voltage-dependent inward rectifying K+ channel cloned from the higher plant Arabidopsis thaliana [Anderson, J. A., Huprikar, S. S., Kochian, L. V., Lucas, W. J. & Gaber, R. F. (1992) Proc. Natl. Acad. Sci. USA 89, 3736-3740]. It is related to the Shaker superfamily of K+ channels characterized by six transmembrane spanning domains (S1-S6) and a putative pore-forming region between S5 and S6 (H5). The 115 region between Pro-247 and Pro-271 in KAT1 contains 14 additional amino acids when compared with Shaker [Aldrich, R. W. (1993) Nature (London) 362, 107-108]. We studied various point mutations introduced into H5 to determine whether voltage-dependent plant and animal K+ channels share similar pore structures. Through heterologous expression in Xenopus oocytes and voltage-clamp analysis combined with phenotypic analysis involving a potassium transport-defective Saccharomyces cerevisiae strain, we investigated the selectivity filter of the mutants and their susceptibility toward inhibition by cesium and calcium ions. With respect to electrophysiological properties, KAT1 mutants segregated into three groups: (i) wild-type-like channels, (ii) channels modified in selectivity and Cs+ or Ca2+ sensitivity, and (iii) a group that was additionally affected in its voltage dependence. Despite the additional 14 amino acids in H5, this motif in KAT1 is also involved in the formation of the ion-conducting pore because amino acid substitutions at Leu-251, Thr-256, Thr-259, and Thr-260 resulted in functional channels with modified ionic selectivity and inhibition. Creation of Ca2+ sensitivity and an increased susceptibility to Cs+ block through mutations within the narrow pore might indicate that both blockers move deeply into the channel. Furthermore, mutations close to the rim of the pore affecting the half-activation potential (U1/2) indicate that amino acids within the pore either interact with the voltage sensor or ion permeation feeds back on gating.

Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G1 arrest.

The tumor suppressor p53 contributes to maintaining genome stability by inducing a cell cycle arrest or apoptosis in response to conditions that generate DNA damage. Nuclear injection of linearized plasmid DNA, circular DNA with a large gap, or single-stranded circular phagemid is sufficient to induce a p53-dependent arrest. Supercoiled and nicked plasmid DNA, and circular DNA with a small gap were ineffective. Titration experiments indicate that the arrest mechanism in normal human fibroblasts can be activated by very few double strand breaks, and only one may be sufficient. Polymerase chain reaction assays showed that end-joining activity is low in serum-arrested human fibroblasts, and that higher joining activity occurs as cells proceed through G1 or into S phase. We propose that the exquisite sensitivity of the p53-dependent G1 arrest is partly due to inefficient repair of certain types of DNA damage in early G1.

Long-term oral sensitivity and feeding skills of low-risk pre-term infants

This study examined the oral sensitivity and feeding skills of low-risk pre-term infants at 11-17 months corrected age. Twenty pre-term infants (PT) born between 32 and 37 weeks at birth without any medical comorbidities were assessed. All of this PT group received supplemental nasogastric (NG) tube feeds during their birth-stay in hospital. A matched control group of 10 healthy full-term infants (FT) was also assessed. Oral sensitivity and feeding skills were assessed during a typical mealtime using the Royal Children's Hospital Oral Sensitivity Checklist (OSC) and the Pre-Speech Assessment Scale (PSAS). Results demonstrated that, at 11-17 months corrected age, the PT group displayed significantly more behaviours suggestive of altered oral sensitivity and facial defensiveness, and a trend of more delayed feeding development than the FT group. Further, results demonstrated that, relative to the FT group, pre-term infants who received greater than 3 weeks of NG feeding (PT>3NG) displayed significantly more facial defensive behaviour, and displayed significant delays across more aspects of their feeding development than pre-term infants who received less than 2 weeks of NG feeding (PT

Hearing sensitivity and bone mineral density in older adults: the Health, Aging and Body Composition Study

Bone mineral density (BMD) may be associated with hearing loss in older adults. Demineralization of the cochlear capsule has been associated with hearing loss in those with Paget's disease of the bone and otosclerosis. Osteoporosis may also result in cochlear capsule demineralization. We hypothesized that lower hip BMD and lower heel ultrasound measurements would be associated with hearing loss in a population-based sample of 2,089 older black and white men and women. Bone parameters and hearing function were measured at the fourth clinical follow-up visit. Audiometric threshold testing was used to measure air- and bone-conduction hearing sensitivity. BMD of the hip and its subregions was measured using dual-energy X-ray absorptiometry. Calcaneal bone measurements [broadband ultrasound attenuation (BUA), speed of sound (SOS) and the quantitative ultrasound index (QUI)] were obtained using heel ultrasound. After adjusting for known hearing loss risk factors, no association was found between hearing and any of the bone measurements in whites and black women. In black men, however, lower hip BMD was associated with higher odds of hearing loss; for each standard deviation decrease in total hip BMD, the odds of hearing loss were 1.41 (95% confidence interval 1.08, 1.83), 1.39 (95% CI 1.07, 1.82) for femoral neck BMD and 1.65 (95% CI 1.26, 2.16) for trochanter BMD. Conductive hearing loss was associated with lower heel ultrasound measurements, though only among white men. The results of this study are mixed and inconclusive. Lower BMD of the hip and its subregions was associated with hearing loss among black men, but not among whites or black women. Lower measurements on heel ultrasound were associated with conductive hearing loss, though only among white men. These results suggest that axial and appendicular bone parameters may be modestly associated with hearing loss in older men, but not in women.

Detection sensitivity and quantitation of Plasmodium falciparum var gene transcripts by real-time RT-PCR in comparison with conventional RT-PCR

Antigenic variation in Plasmodium falciparum erythrocyte membrane protein 1, caused by a switch in transcription of the encoding var gene, is an important feature of malaria. In this study, we quantified the relative abundance of var gene transcripts present in P. falciparum parasite clones using real-time reverse transcription-polymerase chain reaction (RT-PCR) and conventional RT-PCR combined with cloning and sequencing, with the aim of directly comparing the results obtained. When there was sufficient abundance of RNA for the real-time RT-PCR assay to be operating within the region of good reproducibility, RT-PCR and real-time RT-PCR tended to identify the same dominant transcript, although some transcript-specific issues were identified. When there were differences in the estimated relative amounts of minor transcripts, the RT-PCR assay tended to produce higher estimates than real-time RT-PCR. These results provide valuable information comparing RT-PCR and real-time RT-PCR analysis of samples with small quantities of RNA as might be expected in the analysis of field or clinical samples.

A multilevel analysis of BIS sensitivity and negative affect during skill acquisition

This Study examined the muldlevel reladonships among negadve affect Behavioural Inhibidon System (BIS) Sensidvit)' and performance. It also invesdgated whether the reladonship among these variables changed across pracdce. Pardcipants performed muldple trials of a simulated air traffic control task, A single measure of BIS was taken before pracdce, while negadve affect and performance were measured at repeated intervals. As expected, negadve affect was detrimental to performance at both a between-person and withinperson level, BIS was also found to be detrimental to performance. Contrary' to expectadons, the reladonship between BIS and performance was not mediated by overall levels of negadve affect. As predicted, the effects of overall levels of negadve affect and BIS strengthened across pracdce as pardcipants gained task knowledge and skill. The findings of this study are interpreted using resource allocadon theor}' and the implicadons for skiU acquisidon discussed.