The Board Border

Skateboard culture is a lot like high school—cliques rule. You have your technical skaters, your punk skaters blah blah and so on. Certain skateboarders fi t into these cliques and stay within them. When an individual does something diff erent—let’s say longboarding, for example—an openminded few may accept that person, but most will ostracize him or her

Natural language processing in CLIME, a multilingual legal advisory system

This paper describes CLIME, a web-based legal advisory system with a multilingual natural language interface. clime is a 'proof-of-concept' system which answers queries relating to ship-building and ship-operating regulations. Its core knowledge source is a set of such regulations encoded as a conceptual domain model and a set of formalised legal inference rules. The system supports retrieval of regulations via the conceptual model, and assessment of the legality of a situation or activity on a ship according to the legal inference rules. The focus of this paper is on the natural language aspects of the system, which help the user to construct semantically complex queries using wysiwym technology, allow the system to produce extended and cohesive responses and explanations, and support the whole interaction through a hybrid synchronous/asynchronous dialogue structure. Multilinguality (English and French) is viewed simply as interface localisation: the core representations are languageneutral, and the system can present extended or local interactions in either language at any time. The development of clime featured a high degree of client involvement, and the specification, implementation and evaluation of natural language components in this context are also discussed

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Board Border

Skateboard culture is a lot like high school—cliques rule. You have your technical skaters, your punk skaters blah blah and so on. Certain skateboarders fi t into these cliques and stay within them. When an individual does something diff erent—let’s say longboarding, for example—an openminded few may accept that person, but most will ostracize him or her.</p

Effects of drought on the abundance and distribution of non-breeding shorebirds in central California, USA.

Conservation of migratory species requires anticipating the potential impacts of extreme climatic events, such as extreme drought. During drought, reduced habitat availability for shorebirds creates the potential for changes in their abundance and distribution, in part because many species are highly mobile and rely on networks of interior and coastal habitats. Understanding how shorebirds responded to a recent drought cycle that peaked from 2013 to 2015 in central California, USA, will help optimize management of wetlands and fresh water for wildlife. In the Central Valley, a vast interior region that is characterized by a mosaic of wetlands and agricultural lands, we found 22% and 29% decreases in the annual abundance of shorebirds during periods of 3-year drought (2013-2015) and 2-year extreme drought (2014-2015), respectively, when compared to non-drought years. Lower abundance of shorebirds coincided with significant decreases in the mean proportion flooded of survey units (7% and 9%, respectively) that were reliant on fresh water. Drought was associated with lower abundance within both the interior Central Valley and coastal San Francisco Bay for greater and lesser yellowlegs (Tringa melanoleuca and T. flavipes) and long- and short-billed dowitchers (Limnodromus scolopaceus and L. griseus). Only dunlins (Calidris alpina) had patterns of abundance that suggested substantial shifts in distribution between the Central Valley and coastal regions of San Francisco Bay and Point Reyes. Our results indicate that drought has the potential to reduce, at least temporally, shorebird populations and flooded habitat in the Central Valley, and the ability to respond to drought by taking advantage of nearby coastal habitats may limit the long-term effects of drought on some species. Successful conservation strategies must balance the impacts of reduced habitat availability at interior sites with the ability of some migratory shorebirds to adapt rapidly to shifting distributions of resources

The increased incidence of congenital hypothyroidism: fact or fancy?

OBJECTIVE: The incidence of congenital hypothyroidism (CH) detected by newborn screening in the US has increased significantly since the early 1990s. We defined the characteristics associated with the increased incidence. PATIENTS: A cohort of children with CH born during an earlier period of low incidence (1991-94) was compared with a cohort born during a later period when the incidence of CH had doubled (2001-04). MEASUREMENTS: Screening was performed with T4 as the primary marker and thyroid stimulating hormone (TSH) on selected specimens. Follow-up on hypothyroid children determined whether they had permanent or transient hypothyroidism. Cases were classified based on laboratory results: initial TSH \u3e/=100 mU/l was \u27severe,\u27 initial TSH /l but \u3e/=20 mU/l was \u27mild\u27 and initial TSH /l with subsequent abnormal TSH was \u27delayed\u27. RESULTS: The overall incidence of CH almost doubled between the two time periods, from 1:3010 to 1:1660. Excess cases were found in the mild and delayed categories, with no increase in severe cases. The proportion of transient cases was CONCLUSION: The rising incidence of CH in Massachusetts is confined to mild and delayed cases. Our findings suggest that this rise is attributable to enhanced detection rather than an absolute increase in numbers

Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field