Two-versus one photon excitation laser scanning microscopy: Critical importance of excitation wavelength

It is often anticipated that two-photon excitation (TPE) laser scanning microscopy should improve cell survival and tissue penetration relative to conventional one-photon excitation (OPE) confocal scanning laser microscopy (CLSM). However few studies have directly compared live cell imaging using one- vs two-photon laser scanning microscopy. We have used calcein-loaded in situ chondrocytes within cartilage as a model for quantitatively comparing these techniques. TPE reduced photo-bleaching and improved cell viability compared to OPE. Using improved detection sensitivity coupled with increased tissue penetration of the near infra-red TPE laser, it was possible to capture images deeper within the cartilage. However, the advantages of TPE vs OPE were strongly dependent on excitation wavelength. We conclude that optimising TPE conditions is essential if the full benefits of this approach are to be realised

Polar distortions in hydrogen bonded organic ferroelectrics

Although ferroelectric compounds containing hydrogen bonds were among the first to be discovered, organic ferroelectrics are relatively rare. The discovery of high polarization at room temperature in croconic acid [Nature \textbf{463}, 789 (2010)] has led to a renewed interest in organic ferroelectrics. We present an ab-initio study of two ferroelectric organic molecular crystals, 1-cyclobutene-1,2-dicarboxylic acid (CBDC) and 2-phenylmalondialdehyde (PhMDA). By using a distortion-mode analysis we shed light on the microscopic mechanisms contributing to the polarization, which we find to be as large as 14.3 and 7.0\,$\mu$C/cm$^{2}$ for CBDC and PhMDA respectively. These results suggest that it may be fruitful to search among known but poorly characterized organic compounds for organic ferroelectrics with enhanced polar properties suitable for device applications.Comment: Submitte

Tidal Wave II, Community Colleges, and Student Financial Aid

Article examining the impact of "Tidal Wave II" (a bulge of high school graduates wanting access to higher education) on public community colleges for the five-year period from 2000-2001 to 2005-2006

Caenorhabditis elegans Maintains Highly Compartmentalized Cellular Distribution of Metals and Steep Concentration Gradients of Manganese

Bioinorganic chemistry is critical to cellular function. Homeostasis of manganese (Mn), for example, is essential for life. A lack of methods for direct in situ visualization of Mn and other biological metals within intact multicellular eukaryotes limits our understanding of management of these metals. We provide the first quantitative subcellular visualization of endogenous Mn concentrations (spanning two orders of magnitude) associated with individual cells of the nematode, Caenorhabditis elegans

PhotoAffinity bits : a photoaffinity-based fragment screening platform for efficient identification of protein ligands

Advances in genomic analyses enable the identification of new proteins that are associated with disease. To validate these targets, tool molecules are required to demonstrate that a ligand can have a disease-modifying effect. Currently, as tools are reported for only a fraction of the proteome, platforms for ligand discovery are essential to leverage insights from genomic analyses. Fragment screening offers an efficient approach to explore chemical space, however, it remains challenging to develop techniques that are both sufficiently high-throughput and sensitive. We present a fragment screening platform, termed PhABits (PhotoAffinity Bits), which utilises a library of photoreactive fragments to covalently capture fragment-protein interactions. Hits can be profiled to determine potency and site of crosslinking, and subsequently developed as reporters in a competitive displacement assay to identify novel hit matter. We envision that the PhABits will be widely applicable to novel protein targets, identifying starting points in the development of therapeutic

Andean drought and glacial retreat tied to Greenland warming during the last glacial period

Abrupt warming events recorded in Greenland ice cores known as Dansgaard-Oeschger (DO) interstadials are linked to changes in tropical circulation during the last glacial cycle. Corresponding variations in South American summer monsoon (SASM) strength are documented, most commonly, in isotopic records from speleothems, but less is known about how these changes affected precipitation and Andean glacier mass balance. Here we present a sediment record spanning the last ~50 ka from Lake Junín (Peru) in the tropical Andes that has sufficient chronologic precision to document abrupt climatic events on a centennial-millennial time scale. DO events involved the near-complete disappearance of glaciers below 4700 masl in the eastern Andean cordillera and major reductions in the level of Peru’s second largest lake. Our results reveal the magnitude of the hydroclimatic disruptions in the highest reaches of the Amazon Basin that were caused by a weakening of the SASM during abrupt arctic warming. Accentuated warming in the Arctic could lead to significant reductions in the precipitation-evaporation balance of the southern tropical Andes with deleterious effects on this densely populated region of South America

Andean drought and glacial retreat tied to Greenland warming during the last glacial period

Abrupt warming events recorded in Greenland ice cores known as Dansgaard-Oeschger (DO) interstadials are linked to changes in tropical circulation during the last glacial cycle. Corresponding variations in South American summer monsoon (SASM) strength are documented, most commonly, in isotopic records from speleothems, but less is known about how these changes affected precipitation and Andean glacier mass balance. Here we present a sediment record spanning the last ~50 ka from Lake Junín (Peru) in the tropical Andes that has sufficient chronologic precision to document abrupt climatic events on a centennial-millennial time scale. DO events involved the near-complete disappearance of glaciers below 4700 masl in the eastern Andean cordillera and major reductions in the level of Peru’s second largest lake. Our results reveal the magnitude of the hydroclimatic disruptions in the highest reaches of the Amazon Basin that were caused by a weakening of the SASM during abrupt arctic warming. Accentuated warming in the Arctic could lead to significant reductions in the precipitation-evaporation balance of the southern tropical Andes with deleterious effects on this densely populated region of South America

The Challenge of Spoken Language Systems: Research Directions for the Nineties

A spoken language system combines speech recognition, natural language processing and human interface technology. It functions by recognizing the person's words, interpreting the sequence of words to obtain a meaning in terms of the application, and providing an appropriate response back to the user. Potential applications of spoken language systems range from simple tasks, such as retrieving information from an existing database (traffic reports, airline schedules), to interactive problem solving tasks involving complex planning and reasoning (travel planning, traffic routing), to support for multilingual interactions. We examine eight key areas in which basic research is needed to produce spoken language systems: (1) robust speech recognition; (2) automatic training and adaptation; (3) spontaneous speech; (4) dialogue models; (5) natural language response generation; (6) speech synthesis and speech generation; (7) multilingual systems; and (8) interactive multimodal systems. In each area, we identify key research challenges, the infrastructure needed to support research, and the expected benefits. We conclude by reviewing the need for multidisciplinary research, for development of shared corpora and related resources, for computational support and far rapid communication among researchers. The successful development of this technology will increase accessibility of computers to a wide range of users, will facilitate multinational communication and trade, and will create new research specialties and jobs in this rapidly expanding area

The Challenge of Spoken Language Systems: Research Directions for the Nineties

A spoken language system combines speech recognition, natural language processing and human interface technology. It functions by recognizing the person's words, interpreting the sequence of words to obtain a meaning in terms of the application, and providing an appropriate response back to the user. Potential applications of spoken language systems range from simple tasks, such as retrieving information from an existing database (traffic reports, airline schedules), to interactive problem solving tasks involving complex planning and reasoning (travel planning, traffic routing), to support for multilingual interactions. We examine eight key areas in which basic research is needed to produce spoken language systems: (1) robust speech recognition; (2) automatic training and adaptation; (3) spontaneous speech; (4) dialogue models; (5) natural language response generation; (6) speech synthesis and speech generation; (7) multilingual systems; and (8) interactive multimodal systems. In each area, we identify key research challenges, the infrastructure needed to support research, and the expected benefits. We conclude by reviewing the need for multidisciplinary research, for development of shared corpora and related resources, for computational support and far rapid communication among researchers. The successful development of this technology will increase accessibility of computers to a wide range of users, will facilitate multinational communication and trade, and will create new research specialties and jobs in this rapidly expanding area

Relationships between plasma lipids species, gender, risk factors and Alzheimer’s disease

Background: Lipid metabolism is altered in Alzheimer’s disease (AD); however, the relationship between AD risk factors (age, APOE ɛ4, and gender) and lipid metabolism is not well defined. Objective: We investigated whether altered lipid metabolism associated with increased age, gender, and APOE status may contribute to the development of AD by examining these risk factors in healthy controls and also clinically diagnosed AD individuals. Methods: We performed plasma lipidomic profiling (582 lipid species) of the Australian Imaging, Biomarkers and Lifestyle flagship study of aging cohort (AIBL) using liquid chromatography-mass spectrometry. Linear regression and interaction analysis were used to explore the relationship between risk factors and plasma lipid species. Results: We observed strong associations between plasma lipid species with gender and increasing age in cognitively normal individuals. However, APOE ɛ4 was relatively weakly associated with plasma lipid species. Interaction analysis identified differential associations of sphingolipids and polyunsaturated fatty acid esterified lipid species with AD based on age and gender, respectively. These data indicate that the risk associated with age, gender, and APOE ɛ4 may, in part, be mediated by changes in lipid metabolism. Conclusion: This study extends our existing knowledge of the relationship between the lipidome and AD and highlights the complexity of the relationships between lipid metabolism and AD at different ages and between men and women. This has important implications for how we assess AD risk and also for potential therapeutic strategies involving modulation of lipid metabolic pathways