Two-way traveltimes of internal layers and ice thickness between Dome C - Vostok - Dome A

Chinese scientists will start to drill a deep ice core at Kunlun station near Dome A in the near future. Recent work has predicted that Dome A is a location where ice older than 1 million years can be found. We model flow, temperature and the age of the ice by applying a three-dimensional, thermomechanically coupled full-Stokes model to a 70 × 70 km**2 domain around Kunlun station, using isotropic non-linear rheology and different prescribed anisotropic ice fabrics that vary the evolution from isotropic to single maximum at 1/3 or 2/3 depths. The variation in fabric is about as important as the uncertainties in geothermal heat flux in determining the vertical advection which in consequence controls both the basal temperature and the age profile. We find strongly variable basal ages across the domain since the ice varies greatly in thickness, and any basal melting effectively removes very old ice in the deepest parts of the subglacial valleys. Comparison with dated radar isochrones in the upper one third of the ice sheet cannot sufficiently constrain the age of the deeper ice, with uncertainties as large as 500 000 years in the basal age. We also assess basal age and thermal state sensitivities to geothermal heat flux and surface conditions. Despite expectations of modest changes in surface height over a glacial cycle at Dome A, even small variations in the evolution of surface conditions cause large variation in basal conditions, which is consistent with basal accretion features seen in radar surveys.

DNA alignment and Bayesian trees of partial sequences of COI, COIII and the haemocyanin functional unit f-g of 28 octopod species

Background: Octopods have successfully colonised the world's oceans from the tropics to the poles. Yet, successful persistence in these habitats has required adaptations of their advanced physiological apparatus to compensate impaired oxygen supply. Their oxygen transporter haemocyanin plays a major role in cold tolerance and accordingly has undergone functional modifications to sustain oxygen release at sub-zero temperatures. However, it remains unknown how molecular properties evolved to explain the observed functional adaptations. We thus aimed to assess whether natural selection affected molecular and structural properties of haemocyanin that explains temperature adaptation in octopods. Results: Analysis of 239 partial sequences of the haemocyanin functional units (FU) f and g of 28 octopod species of polar, temperate, subtropical and tropical origin revealed natural selection was acting primarily on charge properties of surface residues. Polar octopods contained haemocyanins with higher net surface charge due to decreased glutamic acid content and higher numbers of basic amino acids. Within the analysed partial sequences, positive selection was present at site 2545, positioned between the active copper binding centre and the FU g surface. At this site, methionine was the dominant amino acid in polar octopods and leucine was dominant in tropical octopods. Sites directly involved in oxygen binding or quaternary interactions were highly conserved within the analysed sequence. Conclusions: This study has provided the first insight into molecular and structural mechanisms that have enabled octopods to sustain oxygen supply from polar to tropical conditions. Our findings imply modulation of oxygen binding via charge-charge interaction at the protein surface, which stabilize quaternary interactions among functional units to reduce detrimental effects of high pH on venous oxygen release. Of the observed partial haemocyanin sequence, residue 2545 formed a close link between the FU g surface and the active centre, suggesting a role as allosteric binding site. The prevalence of methionine at this site in polar octopods, implies regulation of oxygen affinity via increased sensitivity to allosteric metal binding. High sequence conservation of sites directly involved in oxygen binding indicates that functional modifications of octopod haemocyanin rather occur via more subtle mechanisms, as observed in this study.

Mies van der Rohe's Illinois Institute of Technology: Analysis and History of a Compositive Development = El IIT de Mies van der Rohe: análisis e historia de un proceso compositivo

The Illinois Institute of Technology (iit) campus, Chicago, by architect Ludwig Mies van der Rohe, is often considered as a transitional work, usually acknowledged as significant for the reorientation of his professional career after he emigrated to the United States. Moreover, its favorable recognition today is somehow indicative of its relevance as a model for urban intervention in the contemporary American city and for contemporary city planning in general, not to mention the profound impact that it had on the cityscape of Chicago. However, today we know it was rather the result of a close collaboration between he and Ludwig Hilberseimer —later on, to be completed with Alfred Caldwell— who merged their personal ideas and expertise in the design for the first time. In addition to this, when one tries to locate the design within its own historical context and evaluate the sources of its approach to it, some contradictions arise. The major impact of the images produced by Mies to promote its realization —widely disseminated in most contemporary architectural periodicals— probably outshined the particular circumstances in which the design was conceived. In fact, it would never be materialized as originally presented, but it was, instead, continuously reworked according to land availability in the site —a circumstance often ignored by subsequent architectural critic, that enthusiastically praised the design even before it was fully completed. One of the main consequences of looking at iit from such a standpoint is that, when historically contextualized, one can appreciate that, due to the urban scale of its implementation process, the design had to face a complex reality very different to that initially planned by the architect, often far from his actual possibilities of intervention. Such approach is in contradiction with the common description of the design as a ‘tabula rasa’ that allegedly would have been formulated on the basis of a full denial of its context. On the contrary, the ever-changing circumstances of the design motivated a necessary re-interpretation of the relation between its executed fragments, in order to keep the original identity of the whole in an ever-changing context. This situation implied a continuous transformation of the design by means of a steady re-composition of its elements: as the number of completed buildings increased in its successive stages, their relation to their site-specific context changed, in a very particular process that these lines try to delineate. Requiring decades to be erected, neither of its authors would ever see the design finished as planned, partially because of the difficulties in acquiring the extension of land that it required. Considering the study of this process as able to provide a valuable gateway to understand the urban discourse that the architects entailed, the aim of these lines is to analyze the problems that the iit campus design had to face. As a starting point, a relationship between practice and theory in the activity of the authors implied in iit campus design has been assumed. Far from being interrupted during World War ii, strong historical evidence can be found to infer that both were developed in parallel. Consequently, the historical sequence of the preserved testimonies has been put into context, as well as their transformation while Mies remained in charge for the campus Master Plan. Notably, when seen from this perspective, some ideas already expressed during his previous European practice were still present during the design process. Particularly, Mies's particular understanding of certain architectural concepts — such as those of ‘order’ and ‘structure’—can be traced paralleling the theories about urban planning from his collaborators, a fact that possibly facilitated the campus successful development. The study of the way these ideas were actually redeveloped and modified in the American urban context, added to the specific process of the implementation of iit campus design, sheds a new light for a critical interpretation of the reasons that made it possible, and of the actual responsibility of Mies's collaborators in its overall development and final completion. RESUMEN El campus del Illinois Institute of Technology (iit) de Chicago, obra del arquitecto Ludwig Mies van der Rohe, es a menudo considerado como una obra de transición que, por lo general, ha venido siendo reconocida como relevante para la reorientación de su carrera profesional posterior a su exilio en los Estados Unidos. El reconocimiento del que goza el proyecto es indicativo, de algún modo, de su importancia como modelo para la intervención urbana en la ciudad norteamericana contemporánea y el planeamiento de la ciudad contemporánea en general, sin olvidar el profundo impacto que ha tenido sobre el paisaje urbano de Chicago. Sin embargo, hoy sabemos que el resultado se benefició de su estrecha colaboración con Ludwig Hilberseimer y se completaría más tarde con la de Alfred Caldwell, quienes unieron sus ideas y experiencia profesional en el proyecto por primera vez. Asimismo, cuando se intenta ubicar el proyecto dentro de su propio contexto histórico y evaluar los criterios de su manera de abordarlo, surgen algunas contradicciones. El considerable impacto de las imágenes producidas por Mies para impulsar su ejecución —ampliamente difundidas en la mayoría de publicaciones de arquitectura de la época— probablemente eclipsó las particulares circunstancias en las que el proyecto fue concebido. De hecho, nunca llegó a materializarse tal y como fue inicialmente presentado. Por contra, fue reelaborado de manera continua, de acuerdo a la disponibilidad de suelo en el emplazamiento; una circunstancia a menudo ignorada por la crítica posterior, que elogió con entusiasmo el proyecto antes siquiera de que fuese terminado. Una de las principales consecuencias de contemplar el iit desde semejante punto de vista es que, una vez contextualizada históricamente su puesta en obra, se puede apreciar que el arquitecto tuvo que enfrentarse a una compleja realidad urbana muy diferente a la inicialmente prevista —probablemente debido a la escala del proyecto— a menudo lejos de sus posibilidades reales de intervención. Este enfoque contradice la descripción habitual del proyecto como una ‘tabula rasa’, que supuestamente se habría formulado sobre la base de una negación completa de su contexto. Por el contrario, las circunstancias cambiantes del proyecto obligaron una necesaria reinterpretación de la relación entre sus frag mentos ejecutados, con el fin de mantener la identidad original del conjunto en un contexto en constante cambio. Esta situación implicó una continua transformación del proyecto por medio de una permanente re-composición de sus elementos: según se incrementaba el número de edificios construidos en las etapas sucesivas de desarrollo del conjunto, variaba su relación con el contexto específico en que se emplazaban, en un proceso muy particular que estas líneas tratan de perfilar. Al necesitar décadas para ser levantado, ninguno de sus autores vería el conjunto terminado según lo planificado, en parte debido a las dificultades para la adquisición de la extensión de suelo que demandaba. Asumiendo que el estudio de este proceso es capaz de proporcionar una valiosa puerta de entrada para elucidar el discurso urbano asumido por los Mies, el objetivo de estas líneas es analizar los problemas a los que el proyecto del campus del iit tuvo que enfrentarse. Como punto de partida, se ha supuesto una relación entre la práctica y la teoría en la actividad de los autores implicados en el proyecto del campus del iit. Lejos de interrumpirse durante la Segunda Guerra Mundial, existen evidencias históricas sólidas para deducir que ambas vertientes se desarrollaron en paralelo. En consecuencia, se ha contextualizado la secuencia histórica de los testimonios conservados, así como su transformación durante el periodo en que Mies estuvo a cargo del Plan General del campus. Significativamente, al ser contempladas bajo esta perspectiva, algunas ideas ya expresadas durante su práctica europea anterior resultan aún presentes durante la redacción del proyecto. En concreto, se puede trazar un paralelismo entre la comprensión particular de Mies de ciertos conceptos arquitectónicos —como los de ‘orden’ y ‘estructura’— y las teorías sobre el urbanismo de sus colaboradores, hecho que posiblemente facilitó el exitoso desarrollo del proyecto. El estudio de la manera en que estas ideas fueron reelaboradas y modificadas en el contexto urbano estadounidense, sumado al proceso específico de su aplicación en el proyecto del campus del iit, arroja una nueva luz para una interpretación crítica tanto de las razones que lo hicieron posible, como del papel real que los colaboradores de Mies tuvieron en su desarrollo y ejecución final.

Exhibit: Men of Vision: United States Colored Troops, Regiments No. 62 and 65

https://bluetigercommons.lincolnu.edu/pli/1005/thumbnail.jpg

Fission yeast orb6, a ser/thr protein kinase related to mammalian rho kinase and myotonic dystrophy kinase, is required for maintenance of cell polarity and coordinates cell morphogenesis with the cell cycle

The molecular mechanisms that coordinate cell morphogenesis with the cell cycle remain largely unknown. We have investigated this process in fission yeast where changes in polarized cell growth are coupled with cell cycle progression. The orb6 gene is required during interphase to maintain cell polarity and encodes a serine/threonine protein kinase, belonging to the myotonic dystrophy kinase/cot1/warts family. A decrease in Orb6 protein levels leads to loss of polarized cell shape and to mitotic advance, whereas an increase in Orb6 levels maintains polarized growth and delays mitosis by affecting the p34cdc2 mitotic kinase. Thus the Orb6 protein kinase coordinates maintenance of cell polarity during interphase with the onset of mitosis. orb6 interacts genetically with orb2, which encodes the Pak1/Shk1 protein kinase, a component of the Ras1 and Cdc42-dependent signaling pathway. Our results suggest that Orb6 may act downstream of Pak1/Shk1, forming part of a pathway coordinating cell morphogenesis with progression through the cell cycle.

ARF Is Required for Maintenance of Yeast Golgi and Endosome Structure and Function

ADP ribosylation factor (ARF) is thought to play a critical role in recruiting coatomer (COPI) to Golgi membranes to drive transport vesicle budding. Yeast strains harboring mutant COPI proteins exhibit defects in retrograde Golgi to endoplasmic reticulum protein transport and striking cargo-selective defects in anterograde endoplasmic reticulum to Golgi protein transport. To determine whether arf mutants exhibit similar phenotypes, the anterograde transport kinetics of multiple cargo proteins were examined in arf mutant cells, and, surprisingly, both COPI-dependent and COPI-independent cargo proteins exhibited comparable defects. Retrograde dilysine-mediated transport also appeared to be inefficient in the arf mutants, and coatomer mutants with no detectable anterograde transport defect exhibited a synthetic growth defect when combined with arf1Δ, supporting a role for ARF in retrograde transport. Remarkably, we found that early and medial Golgi glycosyltransferases localized to abnormally large ring-shaped structures. The endocytic marker FM4–64 also stained similar, but generally larger ring-shaped structures en route from the plasma membrane to the vacuole in arf mutants. Brefeldin A similarly perturbed endosome morphology and also inhibited transport of FM4–64 from endosomal structures to the vacuole. Electron microscopy of arf mutant cells revealed the presence of what appear to be hollow spheres of interconnected membrane tubules which likely correspond to the fluorescent ring structures. Together, these observations indicate that organelle morphology is significantly more affected than transport in the arf mutants, suggesting a fundamental role for ARF in regulating membrane dynamics. Possible mechanisms for producing this dramatic morphological change in intracellular organelles and its relation to the function of ARF in coat assembly are discussed.

Mechanisms of Human Mitochondrial DNA Maintenance: The Determining Role of Primary Sequence and Length over Function

Although the regulation of mitochondrial DNA (mtDNA) copy number is performed by nuclear-coded factors, very little is known about the mechanisms controlling this process. We attempted to introduce nonhuman ape mtDNA into human cells harboring either no mtDNA or mutated mtDNAs (partial deletion and tRNA gene point mutation). Unexpectedly, only cells containing no mtDNA could be repopulated with nonhuman ape mtDNA. Cells containing a defective human mtDNA did not incorporate or maintain ape mtDNA and therefore died under selection for oxidative phosphorylation function. On the other hand, foreign human mtDNA was readily incorporated and maintained in these cells. The suicidal preference for self-mtDNA showed that functional parameters associated with oxidative phosphorylation are less relevant to mtDNA maintenance and copy number control than recognition of mtDNA self-determinants. Non–self-mtDNA could not be maintained into cells with mtDNA even if no selection for oxidative phosphorylation was applied. The repopulation kinetics of several mtDNA forms after severe depletion by ethidium bromide treatment showed that replication and maintenance of mtDNA in human cells are highly dependent on molecular features, because partially deleted mtDNA molecules repopulated cells significantly faster than full-length mtDNA. Taken together, our results suggest that mtDNA copy number may be controlled by competition for limiting levels of trans-acting factors that recognize primarily mtDNA molecular features. In agreement with this hypothesis, marked variations in mtDNA levels did not affect the transcription of nuclear-coded factors involved in mtDNA replication.

Investigation by Parkinson’s Disease Research Group of United Kingdom into excess mortality seen with combined levodopa and selegiline treatment in patients with early, mild Parkinson’s disease: further results of randomised trial and confidential inquiry

Objective: To determine whether the excess mortality observed in patients who received both levodopa and selegiline in a randomised trial could be explained by revised diagnosis of Parkinson’s disease, autonomic or cardiovascular effects, more rapid disease progression, or drug interactions.

Russia's Clandestine War against the United States: The Resurrection of the KGB and Russian Organized Crime Post 9/11

As American leadership has narrowly focused on fighting global terror in Iraq and Afghanistan, the modern version of the KGB, now known as the FSB, has been conducting continuous clandestine warfare operations against the United States. These warfare operations include strategic economic and political partnerships with anti-American entities worldwide and direct embedding of double agents in the US intelligence community. This paper investigates the role of Russia's cultural history leading to the merger of the Russian Federal Security Service (FSB) and Russian Organized Crime (ROC). This paper concludes that the FSB is the most pervasive security threat to the United States and that employing Russian native and heritage speakers of Russian in the US intelligence community compromises US national security.

Optimization of test and maintenance of ageing components consisting of multiple items and addressing effectiveness

There are many models in the literature that have been proposed in the last decades aimed at assessing the reliability, availability and maintainability (RAM) of safety equipment, many of them with a focus on their use to assess the risk level of a technological system or to search for appropriate design and/or surveillance and maintenance policies in order to assure that an optimum level of RAM of safety systems is kept during all the plant operational life. This paper proposes a new approach for RAM modelling that accounts for equipment ageing and maintenance and testing effectiveness of equipment consisting of multiple items in an integrated manner. This model is then used to perform the simultaneous optimization of testing and maintenance for ageing equipment consisting of multiple items. An example of application is provided, which considers a simplified High Pressure Injection System (HPIS) of a typical Power Water Reactor (PWR). Basically, this system consists of motor driven pumps (MDP) and motor operated valves (MOV), where both types of components consists of two items each. These components present different failure and cause modes and behaviours, and they also undertake complex test and maintenance activities depending on the item involved. The results of the example of application demonstrate that the optimization algorithm provide the best solutions when the optimization problem is formulated and solved considering full flexibility in the implementation of testing and maintenance activities taking part of such an integrated RAM model.