Testing the Integrity of Liquid Containing Hermetically Sealed Containers by the Use of Radioactive Markers

A method for detecting leaky ampules filled with a liquid such as a parenteral solution. The ampules to be tested are immersed in a solution containing a short-lived radionuclide, and a pressure differential is imposed between the solution containing the radionuclide and the parenteral solution or other liquid contained in the ampules. The ampules are then removed from solution, decontaminated to remove any solution adhering to the outer surface and pores thereof, dried, and finally examined for electromagnetic radiation, preferably gamma radiation, emanating from the interior of the ampules which would indicate a leaky condition thereof

Computational immunogenetics in allogeneic immunotherapy

[no abstract

PB1-F2 Finder: scanning influenza sequences for PB1-F2 encoding RNA segments

<p>Abstract</p> <p>Background</p> <p>PB1-F2 is a major virulence factor of influenza A. This protein is a product of an alternative reading frame in the PB1-encoding RNA segment 2. Its presence of is dictated by the presence or absence of premature stop codons. This virulence factor is present in every influenza pandemic and major epidemic of the 20th century. Absence of PB1-F2 is associated with mild disease, such as the 2009 H1N1 (“swine flu”).</p> <p>Results</p> <p>The analysis of 8608 segment 2 sequences showed that only 8.5% have been annotated for the presence of PB1-F2. Our analysis indicates that 75% of segment 2 sequences are likely to encode PB1-F2. Two major populations of PB1-F2 are of lengths 90 and 57 while minor populations include lengths 52, 63, 79, 81, 87, and 101. Additional possible populations include the lengths of 59, 69, 81, 95, and 106. Previously described sequences include only lengths 57, 87, and 90. We observed substantial variation in PB1-F2 sequences where certain variants show up to 35% difference to well-defined reference sequences. Therefore this dataset indicates that there are many more variants that need to be functionally characterized.</p> <p>Conclusions</p> <p>Our web-accessible tool PB1-F2 Finder enables scanning of influenza sequences for potential PB1-F2 protein products. It provides an initial screen and annotation of PB1-F2 products. It is accessible at <url>http://cvc.dfci.harvard.edu/pb1-f2</url>.</p

A comparison of curated gene sets versus transcriptomics-derived gene signatures for detecting pathway activation in immune cells

Background: Despite the significant contribution of transcriptomics to the fields of biological and biomedical research, interpreting long lists of significantly differentially expressed genes remains a challenging step in the analysis process. Gene set enrichment analysis is a standard approach for summarizing differentially expressed genes into pathways or other gene groupings. Here, we explore an alternative approach to utilizing gene sets from curated databases. We examine the method of deriving custom gene sets which may be relevant to a given experiment using reference data sets from previous transcriptomics studies. We call these data-derived gene sets, "gene signatures" for the biological process tested in the previous study. We focus on the feasibility of this approach in analyzing immune-related processes, which are complicated in their nature but play an important role in the medical research. Results: We evaluate several statistical approaches to detecting the activity of a gene signature in a target data set. We compare the performance of the data-derived gene signature approach with comparable GO term gene sets across all of the statistical tests. A total of 61 differential expression comparisons generated from 26 transcriptome experiments were included in the analysis. These experiments covered eight immunological processes in eight types of leukocytes. The data-derived signatures were used to detect the presence of immunological processes in the test data with modest accuracy (AUC = 0.67). The performance for GO and literature based gene sets was worse (AUC = 0.59). Both approaches were plagued by poor specificity. Conclusions: When investigators seek to test specific hypotheses, the data-derived signature approach can perform as well, if not better than standard gene-set based approaches for immunological signatures. Furthermore, the data-derived signatures can be generated in the cases that well-defined gene sets are lacking from pathway databases and also offer the opportunity for defining signatures in a cell-type specific manner. However, neither the data-derived signatures nor standard gene-sets can be demonstrated to reliably provide negative predictions for negative cases. We conclude that the data-derived signature approach is a useful and sometimes necessary tool, but analysts should be weary of false positives. © 2020 The Author(s)

Mammalian kinetochores count attached microtubules in a sensitive and switch-like manner.

The spindle assembly checkpoint (SAC) prevents anaphase until all kinetochores attach to the spindle. Each mammalian kinetochore binds many microtubules, but how many attached microtubules are required to turn off the checkpoint, and how the kinetochore monitors microtubule numbers, are not known and are central to understanding SAC mechanisms and function. To address these questions, here we systematically tune and fix the fraction of Hec1 molecules capable of microtubule binding. We show that Hec1 molecules independently bind microtubules within single kinetochores, but that the kinetochore does not independently process attachment information from different molecules. Few attached microtubules (20% occupancy) can trigger complete Mad1 loss, and Mad1 loss is slower in this case. Finally, we show using laser ablation that individual kinetochores detect changes in microtubule binding, not in spindle forces that accompany attachment. Thus, the mammalian kinetochore responds specifically to the binding of each microtubule and counts microtubules as a single unit in a sensitive and switch-like manner. This may allow kinetochores to rapidly react to early attachments and maintain a robust SAC response despite dynamic microtubule numbers

Caratterizzazione fisiografica, geomorfologica e bionomica della <i>Rias</i> di Santa Teresa di Gallura: Sardegna nord-orientale = Physiographic, geomorphological and bionomic characterization of the Santa Teresa di Gallura <i>Rias</i> (N.E. Sardinia)

An underwater survey in the Rias of S. Teresa di Gallura was made to characterize the benthic environment by integrating three methods: Side Scan Sonar, ROV, SCUBA diving. The main bionomic features at different depths were described and mapped. The presence of Savalia savaglia, a rare Mediterranean species contributed to enhance the environmental value of the study area

Nutrient stripping: the global disparity between food security and soil nutrient stocks

1. The Green Revolution successfully increased food production but in doing so created a legacy of inherently leaky and unsustainable agricultural systems. Central to this are the problems of excessive nutrient mining. If agriculture is to balance the needs of food security with the delivery of other ecosystem services, then current rates of soil nutrient stripping must be reduced and the use of synthetic fertilisers made more efficient. 2. We explore the global extent of the problem, with specific emphasis on the failure of macronutrient management (e.g. nitrogen, phosphorus) to deliver continued improvements in yield and the failure of agriculture to recognise the seriousness of micronutrient depletion (e.g. copper, zinc, selenium). 3. Nutrient removals associated with the relatively immature, nutrient-rich soils of the UK are contrasted with the mature, nutrient-poor soils of India gaining insight into the emerging issue of nutrient stripping and the long-term implications for human health and soil quality. Whilst nutrient deficiencies are rare in developed countries, micronutrient deficiencies are commonly increasing in less-developed countries. Increasing rates of micronutrient depletion are being inadvertently accomplished through increasing crop yield potential and nitrogen fertiliser applications. 4. Amongst other factors, the spatial disconnects caused by the segregation and industrialisation of livestock systems, between rural areas (where food is produced) and urban areas (where food is consumed and human waste treated) are identified as a major constraint to sustainable nutrient recycling. 5. Synthesis and applications. This study advocates that agricultural sustainability can only be accomplished using a whole-systems approach that thoroughly considers nutrient stocks, removals, exports and recycling. Society needs to socially and environmentally re-engineer agricultural systems at all scales. It is suggested that this will be best realised by national-scale initiatives. Failure to do so will lead to an inevitable and rapid decline in the delivery of provisioning services within agricultural systems

Universality of rain event size distributions

We compare rain event size distributions derived from measurements in climatically different regions, which we find to be well approximated by power laws of similar exponents over broad ranges. Differences can be seen in the large-scale cutoffs of the distributions. Event duration distributions suggest that the scale-free aspects are related to the absence of characteristic scales in the meteorological mesoscale