Small area densitometry utilizing fiber optics

A transmission densitometer utilizing fiber optics for the efflux geometry was designed, constructed, and tested with several black and white films, and one color film. The system was semi-specularly illuminated and used semi-specular collection. The system demonstrates the feasibility of using fiber optic bundles in sensitometric equipment. Scattering properties of silver emulsions, color dye infra-red radiation transmission, and assorted electronic factors which introduce error in densitometric values are observed and discussed

Will PAXgene substitute formalin? A morphological and molecular comparative study using a new fixative system

Formalin fixation and paraffin embedding present the standard procedures for conserving clinical tissues for histological analysis. However, molecular analysis is impaired by the cross linking properties of formalin. The PAXgene tissue system (PreAnalytix, Switzerland) is a new formalin-free tissue collection device. AIMS: In this study we aimed to evaluate this new tissue preservation technique in comparison with formalin fixation and fresh frozen tissue samples. METHODS: 12 melanoma biopsy samples were divided and fixed simultaneously with formalin, PAXgene or fresh frozen in liquid nitrogen and analysed with regard to morphology, immunohistochemistry,  DNA and RNA content and quality. Markers of melanocytic differentiation and tumour cell proliferation were used. RESULTS: Morphology was well preserved in PAXPE samples. However, 5 out of 11 immunohistochemical markers showed significantly lower overall staining and staining intensity with PAXPE tissues in comparison with formalin-fixed, paraffin-embedded (FFPE). Increasing membrane permeability through adding a detergent did proportionally increase staining intensity in PAXPE samples. Amplification of different mRNA amplicons showed a direct relationship with the size of the amplicon with greater template integrity observed in PAXPE samples. Sequencing and mutational analysis of DNA samples were comparable for all the different fixation methods, while the level of DNA fragmentation seemed to be lower in PAXPE compared with FFPE tissues. CONCLUSIONS: The switch from formalin to PAXgene fixation would require a re-evaluation of immunohistochemical markers and staining procedures originally developed for FFPE tissues. Our data demonstrate that PAXPE fixation offers some advantages concerning molecular analysis. However, these advantages would not justify substituting formalin fixation in any routine pathology laboratory

Affected Experiencers

Numerous languages permit an NP that is not selected by the verb to be added to a clause, with several different possible interpretations. We divide such non-selected arguments into possessor, benefactive, attitude holder, and affected experiencer categories, on the basis of syntactic and semantic differences between them. We propose a formal analysis of the affected experiencer construction. In our account, a syntactic head Aff(ect) introduces the experiencer argument, and adds a conventional implicature to the effect that any event of the type denoted by its syntactic sister is the source of the experiencer’s psychological experience. Hence, our proposal involves two tiers of meaning: the at-issue meaning of the sentence, and some not-at-issue meaning (an implicature). A syntactic head can introduce material on both tiers. Additionally, we allow two parameters of variation: (i) the height of the attachment of Aff, and (ii) how much of the semantics is at-issue and how much is an implicature. We show that these two parameters account for the attested variation across our sample of languages, as well as the significant commonalities among them. Our analysis also accounts for significant differences between affected experiencers and the other types of non-selected arguments, and we also note a generalization to the effect that purely not-at-issue non-selected arguments can only be weak or clitic pronouns

Meeting Report: Aging Research and Drug Discovery

Aging is the single largest risk factor for most chronic diseases, and thus possesses large socioeconomic interest to continuously aging societies. Consequently, the field of aging research is expanding alongside a growing focus from the industry and investors in aging research. This year's 8th Annual Aging Research and Drug Discovery ARDD) meeting was organized as a hybrid meeting from August 30th to September 3rd 2021 with more than 130 attendees participating on-site at the Ceremonial Hall at University of Copenhagen, Denmark, and 1800 engaging online. The conference comprised of presentations from 75 speakers focusing on new research in topics including mechanisms of aging and how these can be modulated as well as the use of AI and new standards of practices within aging research. This year, a longevity workshop was included to build stronger connections with the clinical community

Improving snowfall forecasting by accounting for the climatological variability of snow density

ABSTRACT Accurately forecasting snow depth is a challenge. In particular, one poorly understood component of snow-depth forecasting is determining the snow ratio. The snow ratio is the ratio of snow depth to liquid equivalent and is inversely proportional to the snow density. In a previous paper, an artificial neural network was developed to predict snow ratios probabilistically in three classes: heavy (1:1 < ratio < 9:1), average (9:1<=ratio<=15:1), and light (ratio>15:1). A web-based application for the probabilistic prediction of snow ratio in these three classes based on operational forecast model soundings and the neural networks is now available. The goal of this paper is to explore the statistical characteristics of the snow ratio to determine how temperature, liquid equivalent, and wind speed can be used to provide additional guidance (quantitative, wherever possible) for forecasting snow depth, especially for extreme values of snow ratio. Snow ratio tends to increase as the low-level (surface to roughly 850 mb) temperature decreases. Snow ratio tends to increase strongly as the liquid equivalent decreases, leading to a nomogram for probabilistic forecasting snow depth, given a forecasted value of liquid equivalent. The surface wind speed cannot be used as a sole discriminator for snow ratios. At Buffalo, New York, and Sault Ste. Marie, Michigan, locations susceptible to lake-effect snowstorms, wind speeds greater than 6 m s , however, only small differences exist between lake-effect and nonlake-effect events. Although previous research has shown simple relationships to determine the snow ratio are difficult to obtain, this note helps to clarify some situations where such relationships are possible.

Improving Snowfall Forecasting by Accounting for the Climatological Variability of Snow Density

ABSTRACT Accurately forecasting snow depth is a challenge. In particular, one poorly understood component of snow-depth forecasting is determining the snow ratio. The snow ratio is the ratio of snow depth to liquid equivalent and is inversely proportional to the snow density. In a previous paper, an artificial neural network was developed to predict snow ratios probabilistically in three classes: heavy (1:1 < ratio < 9:1), average (9:1<=ratio<=15:1), and light (ratio>15:1). A web-based application for the probabilistic prediction of snow ratio in these three classes based on operational forecast model soundings and the neural networks is now available. The goal of this paper is to explore the statistical characteristics of the snow ratio to determine how temperature, liquid equivalent, and wind speed can be used to provide additional guidance (quantitative, wherever possible) for forecasting snow depth, especially for extreme values of snow ratio. Snow ratio tends to increase as the low-level (surface to roughly 850 mb) temperature decreases. Snow ratio tends to increase strongly as the liquid equivalent decreases, leading to a nomogram for probabilistic forecasting snow depth, given a forecasted value of liquid equivalent. The surface wind speed cannot be used as a sole discriminator for snow ratios. At Buffalo, New York, and Sault Ste. Marie, Michigan, locations susceptible to lake-effect snowstorms, wind speeds greater than 6 m s , however, only small differences exist between lake-effect and nonlake-effect events. Although previous research has shown simple relationships to determine the snow ratio are difficult to obtain, this note helps to clarify some situations where such relationships are possible.

Meta-analysis of global metabolomic data identifies metabolites associated with life-span extension

The manipulation of distinct signaling pathways and transcription factors has been shown to influence life span in a cell-non-autonomous manner in multicellular model organisms such as Caenorhabditis elegans. These data suggest that coordination of whole-organism aging involves endocrine signaling, however, the molecular identities of such signals have not yet been determined and their potential relevance in humans is unknown. Here we describe a novel metabolomic approach to identify molecules directly associated with extended life span in C. elegans that represent candidate compounds for age-related endocrine signals. To identify metabolic perturbations directly linked to longevity, we developed metabolomic software for meta-analysis that enabled intelligent comparisons of multiple different mutants. Simple pairwise comparisons of long-lived glp-1, daf-2, and isp-1 mutants to their respective controls resulted in more than 11,000 dysregulated metabolite features of statistical significance. By using meta-analysis, we were able to reduce this number to six compounds most likely to be associated with life-span extension. Mass spectrometry-based imaging studies suggested that these metabolites might be localized to C. elegans muscle. We extended the metabolomic analysis to humans by comparing quadricep muscle tissue from young and old individuals and found that two of the same compounds associated with longevity in worms were also altered in human muscle with age. These findings provide candidate compounds that may serve as age-related endocrine signals and implicate muscle as a potential tissue regulating their levels in humans

Whole Transcriptome Amplification for Gene Expression Profiling and Development of Molecular Archives

Expression profiling of clinically obtainable tumor specimens has been hindered by the need for microgram quantities of RNA. In vitro transcription (IVT)-based amplifications are most commonly used to amplify small quantities of RNA for microarray analysis. However, significant drawbacks exist with IVT-based amplification, and the need for alternative amplification methods remains. Herein, we validate whole transcriptome amplification (WTA), an exponential amplification technique that produces cDNA libraries and amplified target in 3 to 4 hours from nanogram quantities of total RNA using a combination of cDNA microarrays and quantitative polymerase chain reaction (PCR). We demonstrate that WTA material can serve as a “molecular archive” because a WTA cDNA library can be faithfully amplified through multiple rounds of PCR amplification, allowing it to serve as a bankable and distributable resource. To demonstrate applicability, WTA was combined with laser capture microdissection to profile frozen prostate tissues. Unlike most IVT-based and exponential amplification techniques, WTA does not depend on the presence of a poly-A tail. Thus, we demonstrate that WTA is compatible with artificially degraded RNA and RNA isolated from formalin-fixed paraffin-embedded tissues. Taken together, WTA represents a versatile approach to profile and archive cDNA from minute tumor samples and is compatible with partially degraded RNA

Cloning, Assembly, and Modification of the Primary Human Cytomegalovirus Isolate Toledo by Yeast-Based Transformation-Associated Recombination

A pesar de que la arquitectura actual parece tener una tendencia general hacia lo mediático, aproximándose cada vez más a convertirse en un producto de consumo del mercado del arte, aún existen unos pocos arquitectos que conservan unos valores y una forma de pensar y hacer arquitectura considerados ya por muchos obsoletos. Uno de estos arquitectos es el madrileño Víctor López Cotelo y con este trabajo se pretende estudiar su obra para tratar de mostrar no sólo que no se trata de valores obsoletos, sino que suponen el mejor camino para llegar a la verdadera arquitectura y por ello estarán siempre vigentes, sin importar los cambios que haya en las modas. Para estudiar la obra de este arquitecto se realiza un recorrido por tres de sus edificios, situados en la ribera del río Sarela, en Santiago de Compostela. Tres obras (Ponte Sarela, la Vaquería y Pontepedriña) que parten de ruinas de piedra y variadas topografías para llegar a tres magníficos edificios en los que el tiempo es el protagonista, el pasado y el presente se dan la mano y la arquitectura se pone al servicio de la vida, con el objetivo de mejorar la de quienes la habitan