A First Principles Theory of Nuclear Magnetic Resonance J-Coupling in solid-state systems

A method to calculate NMR J-coupling constants from first principles in extended systems is presented. It is based on density functional theory and is formulated within a planewave-pseudopotential framework. The all-electron properties are recovered using the projector augmented wave approach. The method is validated by comparison with existing quantum chemical calculations of solution-state systems and with experimental data. The approach has been applied to verify measured J-coupling in a silicophosphate structure, Si5O(PO4)6Comment: 9 page

Neurophysiology

Contains reports on four research projects.Bell Telephone Laboratories, Inc.U.S. Air Force (Aeronautical Systems Division) under Contract AF 33(615)-1747National Aeronautics and Space Administration (Grant NsG-496)National Institutes of Health (Grant MH-04737-05)National Science Foundation (Grant GP-2495)The Teagle Foundation, Inc

Expression of phosphorylcholine-specific B cells during murine development

The TEPC 15 (T15) clonotype, a putatively germline antibody specificity, does not appear in the neonatal B-cell repertoire until approximately 1 wk of age. This report extends this observation by the demonstration that (a) the T15 clonotype follows similar kinetics of appearance in germfree as well as conventionally-reared mice; (b) maternal influences and genetic background play a minor role in the development of the T15 clonotype since CBFI neonates raised by C57BL/6 or BALB/c mothers acquire the T15 clonotype at the same time in ontogeny as BALB/c neonates; (c) the lack of phosphorylcholine (PC)-specific B cells shortly after birth is reflected in a dearth of PC-binding cells in the neonate as well; and (d) no PC-specifc B cells are found in 19-day fetal liver or in bone marrow until 7 days of life, coincident with their appearance in the spleen. These findings, along with a previous report that PC-specific splenic B cells are tolerizable as late as day 10 after birth, confirm the invariant, late occurrence of the T15 clonotype and support a highly- ordered, rigorously predetermined mechanism for the acquisition of the B- cell repertoire. The results are discussed in light of other studies on the ontogeny of B-cell specificity, and in terms of the implications on the mechanism by which antibody diversity is generated

Speeding disease gene discovery by sequence based candidate prioritization

BACKGROUND: Regions of interest identified through genetic linkage studies regularly exceed 30 centimorgans in size and can contain hundreds of genes. Traditionally this number is reduced by matching functional annotation to knowledge of the disease or phenotype in question. However, here we show that disease genes share patterns of sequence-based features that can provide a good basis for automatic prioritization of candidates by machine learning. RESULTS: We examined a variety of sequence-based features and found that for many of them there are significant differences between the sets of genes known to be involved in human hereditary disease and those not known to be involved in disease. We have created an automatic classifier called PROSPECTR based on those features using the alternating decision tree algorithm which ranks genes in the order of likelihood of involvement in disease. On average, PROSPECTR enriches lists for disease genes two-fold 77% of the time, five-fold 37% of the time and twenty-fold 11% of the time. CONCLUSION: PROSPECTR is a simple and effective way to identify genes involved in Mendelian and oligogenic disorders. It performs markedly better than the single existing sequence-based classifier on novel data. PROSPECTR could save investigators looking at large regions of interest time and effort by prioritizing positional candidate genes for mutation detection and case-control association studies

New horizons in frailty: the contingent, the existential and the clinical

In the past decade, frailty research has focused on refinement of biomedical tools and operationalisations, potentially introducing a reductionist approach. This article suggests that a new horizon in frailty lies in a more holistic approach to health and illness in old age. This would build on approaches that view healthy ageing in terms of functionality, in the sense of intrinsic capacity in interplay with social environment, whilst also emphasising positive attributes. Within this framework, frailty is conceptualised as originating as much in the social as in the biological domain; as co-existing with positive attributes and resilience, and as situated on a continuum with health and illness. Relatedly, social science-based studies involving interviews with, and observations of, frail, older people indicate that the social and biographical context in which frailty arises might be more impactful on the subsequent frailty trajectory than the health crisis which precipitates it. For these reasons, the article suggests that interpretive methodologies, derived from the social sciences and humanities, will be of particular use to the geriatrician in understanding health, illness and frailty from the perspective of the older person. These may be included in a toolkit with the purpose of identifying how biological and social factors jointly underpin the fluctuations of frailty and in designing interventions accordingly. Such an approach will bring clinical approaches closer to the views and experiences of older people who live with frailty, as well as to the holistic traditions of geriatric medicine itself

Neurophysiology

Contains reports on eight research projects.Bell Telephone Laboratories, Inc.Teagle Foundation, Inc.National Science Foundation (Grant GP-2495)National Institutes of Health (Grants MH-04737-04)National Institutes of Health (NB-04985-01)U. S. Air Force. Aeronautical Systems Division (Contract AF 33(615)-1747)U. S. Air Force. Cambridge Research Laboratories (Contract AF19(628)-3807)U. S. Air Force. Electronic Systems Division (Contract AF19(628)-4147)National Aeronautics and Space Administration (Grant NsG-496

An introduction to crowdsourcing for language and multimedia technology research

Language and multimedia technology research often relies on large manually constructed datasets for training or evaluation of algorithms and systems. Constructing these datasets is often expensive with significant challenges in terms of recruitment of personnel to carry out the work. Crowdsourcing methods using scalable pools of workers available on-demand offers a flexible means of rapid low-cost construction of many of these datasets to support existing research requirements and potentially promote new research initiatives that would otherwise not be possible