The putative role of some conserved water molecules in the structure and function of human transthyretin

Human transthyretin (hTTR) is a multifunctional protein that is involved in several neurodegenerative diseases. Besides the transportation of thyroxin and vitamin A, it is also involved in the proteolysis of apolipoprotein A1 and A beta peptide. Extensive analyses of 32 high-resolution X-ray and neutron diffraction structures of hTTR followed by molecular-dynamics simulation studies using a set of 15 selected structures affirmed the presence of 44 conserved water molecules in its dimeric structure. They are found to play several important roles in the structure and function of the protein. Eight water molecules stabilize the dimeric structure through an extensive hydrogen-bonding network. The absence of some of these water molecules in highly acidic conditions (pH <= 4.0) severely affects the interfacial hydrogen-bond network, which may destabilize the native tetrameric structure, leading to its dissociation. Three pairs of conserved water molecules contribute to maintaining the geometry of the ligand-binding cavities. Some other water molecules control the orientation and dynamics of different structural elements of hTTR. This systematic study of the location, absence, networking and interactions of the conserved water molecules may shed some light on various structural and functional aspects of the protein. The present study may also provide some rational clues about the conserved water-mediated architecture and stability of hTTR.

Falcon: A Graph Manipulation Language for Heterogeneous Systems

Graph algorithms have been shown to possess enough parallelism to keep several computing resources busy-even hundreds of cores on a GPU. Unfortunately, tuning their implementation for efficient execution on a particular hardware configuration of heterogeneous systems consisting of multicore CPUs and GPUs is challenging, time consuming, and error prone. To address these issues, we propose a domain-specific language (DSL), Falcon, for implementing graph algorithms that (i) abstracts the hardware, (ii) provides constructs to write explicitly parallel programs at a higher level, and (iii) can work with general algorithms that may change the graph structure (morph algorithms). We illustrate the usage of our DSL to implement local computation algorithms (that do not change the graph structure) and morph algorithms such as Delaunay mesh refinement, survey propagation, and dynamic SSSP on GPU and multicore CPUs. Using a set of benchmark graphs, we illustrate that the generated code performs close to the state-of-the-art hand-tuned implementations.

The value handbook: getting the most from your buildings and spaces.

The Value Handbook is a practical guide, showing how public sector organisations can get the most from ther buildings and spaces in their area. It brings together essential evidence about the benefits of good design, and demonstrates how understanding the different types of value created by the built environment (exchange value, use value, image value,social value, environmental value, and cultural value)is the key to realising its full potential.

Facilitated advocacy: supporting farmers to have a voice in policy making and the development of service provision

Listening to people, especially those who are poor, and involving them in policy making and decisions about service delivery processes are logical steps in building better services and improving policies aimed at poverty alleviation. This case describes a facilitated advocacy that helped to negotiate and support a role for poor people who farm and fish, to contribute recommendations for changes in services and policies that impact on their lives. The national Government of India’s Department of Animal Husbandry and Dairying and the Indian Council for Agricultural Research, both in the capital Delhi, have been linking with farmers and fishers and state government officials in the eastern states of Jharkhand, Orissa and West Bengal, in partnership with the STREAM Initiative of the intergovernmental Network of Aquaculture Centers in Asia Pacific and with the support of the UK Government Department for International Development, Natural resources Systems Program supporting farmers to have a voice(13 p.)

Assessment of Atlantic Red Drum for 1999: Northern and southern regions

An assessment of the status of the Atlantic stock of red drum is conducted using recreational and commercial data from 1986 through 1998. This assessment updates data and analyses from the 1989, 1991, 1992 and 1995 stock assessments on Atlantic coast red drum (Vaughan and Helser, 1990; Vaughan 1992; 1993; 1996). Since 1981, coastwide recreational catches ranged between 762,300 pounds in 1980 and 2,623,900 pounds in 1984, while commercial landings ranged between 60,900 pounds in 1997 and 422,500 pounds in 1984. In weight of fish caught, Atlantic red drum constitute predominantly a recreational fishery (ranging between 85 and 95% during the 1990s). Commercially, red drum continue to be harvested as part of mixed species fisheries. Using available length-frequency distributions and age-length keys, recreational and commercial catches are converted to catch in numbers at age. Separable and tuned virtual population analyses are conducted on the catch in numbers at age to obtain estimates of fishing mortality rates and population size (including recruitment to age 1). In tum, these estimates of fishing mortality rates combined with estimates of growth (length and weight), sex ratios, sexual maturity and fecundity are used to estimate yield per recruit, escapement to age 4, and static (or equilibrium) spawning potential ratio (static SPR, based on both female biomass and egg production). Three virtual analysis approaches (separable, spreadsheet, and FADAPT) were applied to catch matrices for two time periods (early: 1986-1991, and late: 1992-1998) and two regions (Northern: North Carolina and north, and Southern: South Carolina through east coast of Florida). Additional catch matrices were developed based on different treatments for the catch-and-release recreationally-caught red drum (B2-type). These approaches included assuming 0% mortality (BASEO) versus 10% mortality for B2 fish. For the 10% mortality on B2 fish, sizes were assumed the same as caught fish (BASEl), or positive difference in size distribution between the early period and the later period (DELTA), or intermediate (PROP). Hence, a total of 8 catch matrices were developed (2 regions, and 4 B2 assumptions for 1986-1998) to which the three VPA approaches were applied. The question of when offshore emigration or reduced availability begins (during or after age 3) continues to be a source of bias that tends to result in overestimates of fishing mortality. Additionally, the continued assumption (Vaughan and Helser, 1990; Vaughan 1992; 1993; 1996) of no fishing mortality on adults (ages 6 and older), causes a bias that results in underestimates of fishing mortality for adult ages (0 versus some positive value). Because of emigration and the effect of the slot limit for the later period, a range in relative exploitations of age 3 to age 2 red drum was considered. Tuning indices were developed from the MRFSS, and state indices for use in the spreadsheet and FADAPT VPAs. The SAFMC Red Drum Assessment Group (Appendix A) favored the FADAPT approach with catch matrix based on DELTA and a selectivity for age 3 relative to age 2 of 0.70 for the northern region and 0.87 for the southern region. In the northern region, estimates of static SPR increased from about 1.3% for the period 1987-1991 to approximately 18% (15% and 20%) for the period 1992-1998. For the southern region, estimates of static SPR increased from about 0.5% for the period 1988-1991 to approximately 15% for the period 1992-1998. Population models used in this assessment (specifically yield per recruit and static spawning potential ratio) are based on equilibrium assumptions: because no direct estimates are available as to the current status of the adult stock, model results imply potential longer term, equilibrium effects. Because current status of the adult stock is unknown, a specific rebuilding schedule cannot be determined. However, the duration of a rebuilding schedule should reflect, in part, a measure of the generation time of the fish species under consideration. For a long-lived, but relatively early spawning, species as red drum, mean generation time would be on the order of 15 to 20 years based on age-specific egg production. Maximum age is 50 to 60 years for the northern region, and about 40 years for the southern region. The ASMFC Red Drum Board's first phase recovery goal of increasing %SPR to at least 10% appears to have been met. (PDF contains 79 pages)

Combined Fluorescent-Chromogenic In Situ Hybridization for Identification and Laser Microdissection of Interphase Chromosomes

Chromosome territories constitute the most conspicuous feature of nuclear architecture, and they exhibit non-random distribution patterns in the interphase nucleus. We observed that in cell nuclei from humans with Down Syndrome two chromosomes 21 frequently localize proximal to one another and distant from the third chromosome. To systematically investigate whether the proximally positioned chromosomes were always the same in all cells, we developed an approach consisting of sequential FISH and CISH combined with laser-microdissection of chromosomes from the interphase nucleus and followed by subsequent chromosome identification by microsatellite allele genotyping. This approach identified proximally positioned chromosomes from cultured cells, and the analysis showed that the identity of the chromosomes proximally positioned varies. However, the data suggest that there may be a tendency of the same chromosomes to be positioned close to each other in the interphase nucleus of trisomic cells. The protocol described here represents a powerful new method for genome analysis

Harmful algal research and response: A human dimensions strategy

Harmful Algal Research and Response: A Human Dimensions Strategy (HARR-HD) justifies and guides a coordinated national commitment to human dimensions research critical to prevent and respond to impacts of harmful algal blooms (HABs). Beyond HABs, it serves as a framework for developing hu-man dimensions research as a cross-cutting priority of ecosystem science supporting coastal and ocean management, including hazard research and mitigation planning. Measuring and promoting commu-nity resilience to hazards require human dimensions research outcomes such as effective risk commu-nication strategies; assessment of community vulnerability; identification of susceptible populations; comprehensive assessment of environmental, sociocultural, and economic impacts; development of effective decision support tools; and improved coordination among agencies and stakeholders. HARR-HD charts a course for human dimensions research to achieve these and other priorities through co-ordinated implementation by the Joint Subcommittee on Ocean Science and Technology (JSOST) In-teragency Working Group on HABs, Hypoxia and Human Health (IWG-4H); national HAB funding programs; national research and response programs; and state research and monitoring programs. (PDF contains 72 pages)

State of Technology for In Situ Measures of Salinity Using Conductive Temperature Sensors, Savannah, Georgia, December 3-5, 2007: workshop proceedings

This Alliance for Coastal Technologies (ACT) workshop was convened to assess the availability and state of development of conductivity-temperature sensors that can meet the needs of coastal monitoring and management communities. Rased on the discussion, there are presently a number of commercial sensor options available, with a wide range of package configurations suitable for deployment in a range of coastal environments. However, some of the central questions posed in the workshop planning documents were left somewhat unresolved. The workshop description emphasized coastal management requirements and, in particular, whether less expensive, easily deployed, lower-resolution instruments might serve many management needs. While several participants expressed interest in this class of conductivity-temperature sensors, based on input from the manufacturers, it is not clear that simply relaxing the present level of resolution of existing instruments will result in instruments of significantly lower unit cost. Conductivity-temperature sensors are available near or under the $1,000 unit cost that was operationally defined at the workshop as a breakpoint for what might be considered to be a "low cost" sensor. For the manufacturers, a key consideration before undertaking the effort to develop lower cost sensors is whether there will be a significant market. In terms of defining "low cost," it was also emphasized that the "life cycle costs" for a given instrument must be considered (e.g., including personnel costs for deployment and maintenance). An adequate market survey to demonstrate likely applications and a viable market for lower cost sensors is needed. Another topic for the workshop was the introduction to the proposed ACT verification for conductivity-temperature sensors. Following a summary of the process as envisioned by ACT, initial feedback was solicited. Protocol development will be pursued further in a workshop involving ACT personnel and conductivity-temperature sensor manufacturers.[PDF contains 28 pages]

Growth responses and yield of heterotis (Heterotis niloticus) on artificial diet

The growth responses and yield of Heterotis niloticus on artificial diets of varying protein levels were studied in a bid to assess the implication of feeding Heterotis in intensive fish production venture for a rearing period of 84 days. One hundred and twenty juvenile H.niloticus were fed for 12 weeks on 28%, 31%, 34% and 37% dietary crude protein levels. The fish were reared in 4 concrete tanks stocked at the rate of 10 fish per M super(2) 100,00/hectare). Consequently, the weight gain, food conversion ratio, serum protein and albumin-globulin ratio were determined to assess the growth and state of health of the fish. The yield was appraised through economic considerations of cost of production of fish and diets (feed). The varying crude protein levels significantly influenced mean weight gain, percentage weight gain and food conversion ratio however, the 37% crude protein in diet produced the best growth. The serum protein was highest in fish raised on 31% crude protein diet while the highest value was recorded for albumin-globulin ratio on diet containing 34% crude protein. The yield from treatments 1, 2, 3, and 4 were 114.38 of/84 days 571.9kg/g hect);146.79g/84 days 733.95kg/hect), respectively. However, treatment 3 recorded the highest value for profit index

Building a sustainable community of coastal leaders to deal with sea level rise and inundation

Sea level rise and inundation were stated to be the highest priorities in the community-developed Ocean Research Priorities Plan and Implementation Strategy in 2005. Although they remain stated priorities, very few resources have been allocated towards this challenge. Inundation poses a substantial risk to many coastal communities, and the risk is projected to increase because of continued development, changes in the frequency and intensity of inundation events, and acceleration in the rate of sea-level rise along our vulnerable shorelines. (PDF contains 4 pages) There is an increasing urgency for federal and state governments to focus on the local and regional levels and consistently provide the information, tools, and methods necessary for adaptation. Calls for action at all levels acknowledge that a viable response must engage federal, state and local expertise, perspectives, and resources in a coordinated and collaborative effort. A workshop held in December 2000 on coastal inundation and sea level rise proposes a shared framework that can help guide where investments should be made to enable states and local governments to assess impacts and initiate adaptation strategies over the next decade.

The development of the South Carolina Coastal Information Network and portal site: Bringing training opportunities and educational resources to coastal community officials and the public

The South Carolina Coastal Information Network (SCCIN) emerged as a result of a number of coastal outreach institutions working in partnership to enhance coordination of the coastal community outreach efforts in South Carolina. This organized effort, led by the S.C. Sea Grant Consortium and its Extension Program, includes partners from federal and state agencies, regional government agencies, and private organizations seeking to coordinate and/or jointly deliver outreach programs that target coastal community constituents. The Network was officially formed in 2006 with the original intention of fostering intra-and inter- agency communication, coordination, and cooperation. Network partners include the S.C. Sea Grant Consortium, S.C. Department of Health and Environmental Control – Office of Ocean and Coastal Resource Management and Bureau of Water, S.C. Department of Natural Resources – ACE Basin National Estuarine Research Reserve, North Inlet-Winyah Bay National Estuarine Research Reserve, Clemson University Cooperative Extension Service and Carolina Clear, Berkeley-Charleston-Dorchester Council of Governments, Waccamaw Regional Council of Governments, Urban Land Institute of South Carolina, S.C. Department of Archives and History, the National Oceanic and Atmospheric Administration – Coastal Services Center and Hollings Marine Laboratory, Michaux Conservancy, Ashley-Cooper Stormwater Education Consortium, the Coastal Waccamaw Stormwater Education Consortium, the S.C. Chapter of the U.S. Green Building Council, and the Lowcountry Council of Governments. (PDF contains 3 pages)

The political econmoy of state government debt : an analysis of constitutional limitations (1961-1990)

Over the past decade, scholarly interest concerning the use of limitations to constrain government spending and taxing has noticeably increased. The call for constitutional restrictions can be credited, in part, to Washington's apparent inability to legislate any significant reductions in government expenditures or in the size of the national debt. At the present time, the federal government is far from instituting any constitutional limitations on spending or borrowing; however, the states have incorporated many controls on revenues and expenditures, the oldest being strictures on full faith and credit borrowing. This dissertations examines the efficacy of these restrictions on borrowing across the states (excluding Alaska) for the period dating from 1961 to 1990 and also studies the limitations on taxing and spending synonymous with the Tax Revolt.

We include socio-economic information in our calculations to control for factors other than the institutional variables that affect state borrowing levels. Our results show that certain constitutional restrictions (in particular, the referendum requirement and the dollar debt limit) are more effective than others. The apparent ineffectiveness of other limitations, such as the flexible debt limit, seem related to the bindingness of the limitations in at least half of the cases. Other variables, such as crime rates, number of schoolage children, and state personal income do affect the levels of full faith and credit debt, but not as strongly as the limitations. While some degree of circumvention can be detected (the amount of full faith and credit debt does inversely affect the levels of nonguaranteed debt), it is so small when compared to the effectiveness of the constitutional restrictions that it is almost negligible. The examination of the tax revolt era limitations yielded quite similar conclusions, with the additional fact that constitutional restrictions appear more binding than statutory ones. Our research demonstrates that constitutional limitations on borrowing can be applied effectively to constrain excessive borrowing, but caution must be used. The efficacy of these restrictions decrease dramatically as the number of loopholes increase.

Electrical and optical interconnects for high-performance computing

Technology scaling has enabled drastic growth in the computational and storage capacity of integrated circuits (ICs). This constant growth drives an increasing demand for high-bandwidth communication between and within ICs. In this dissertation we focus on low-power solutions that address this demand. We divide communication links into three subcategories depending on the communication distance. Each category has a different set of challenges and requirements and is affected by CMOS technology scaling in a different manner. We start with short-range chip-to-chip links for board-level communication. Next we will discuss board-to-board links, which demand a longer communication range. Finally on-chip links with communication ranges of a few millimeters are discussed.

Electrical signaling is a natural choice for chip-to-chip communication due to efficient integration and low cost. IO data rates have increased to the point where electrical signaling is now limited by the channel bandwidth. In order to achieve multi-Gb/s data rates, complex designs that equalize the channel are necessary. In addition, a high level of parallelism is central to sustaining bandwidth growth. Decision feedback equalization (DFE) is one of the most commonly employed techniques to overcome the limited bandwidth problem of the electrical channels. A linear and low-power summer is the central block of a DFE. Conventional approaches employ current-mode techniques to implement the summer, which require high power consumption. In order to achieve low-power operation we propose performing the summation in the charge domain. This approach enables a low-power and compact realization of the DFE as well as crosstalk cancellation. A prototype receiver was fabricated in 45nm SOI CMOS to validate the functionality of the proposed technique and was tested over channels with different levels of loss and coupling. Measurement results show that the receiver can equalize channels with maximum 21dB loss while consuming about 7.5mW from a 1.2V supply. We also introduce a compact, low-power transmitter employing passive equalization. The efficacy of the proposed technique is demonstrated through implementation of a prototype in 65nm CMOS. The design achieves up to 20Gb/s data rate while consuming less than 10mW.

An alternative to electrical signaling is to employ optical signaling for chip-to-chip interconnections, which offers low channel loss and cross-talk while providing high communication bandwidth. In this work we demonstrate the possibility of building compact and low-power optical receivers. A novel RC front-end is proposed that combines dynamic offset modulation and double-sampling techniques to eliminate the need for a short time constant at the input of the receiver. Unlike conventional designs, this receiver does not require a high-gain stage that runs at the data rate, making it suitable for low-power implementations. In addition, it allows time-division multiplexing to support very high data rates. A prototype was implemented in 65nm CMOS and achieved up to 24Gb/s with less than 0.4pJ/b power efficiency per channel. As the proposed design mainly employs digital blocks, it benefits greatly from technology scaling in terms of power and area saving.

As the technology scales, the number of transistors on the chip grows. This necessitates a corresponding increase in the bandwidth of the on-chip wires. In this dissertation, we take a close look at wire scaling and investigate its effect on wire performance metrics. We explore a novel on-chip communication link based on a double-sampling architecture and dynamic offset modulation technique that enables low power consumption and high data rates while achieving high bandwidth density in 28nm CMOS technology. The functionality of the link is demonstrated using different length minimum-pitch on-chip wires. Measurement results show that the link achieves up to 20Gb/s of data rate (12.5Gb/s/$\mu$m) with better than 136fJ/b of power efficiency.

Intramolecular conflict : conformation and self-assembly of architecturally complex macromolecules in solution

The solution behavior of linear polymer chains is well understood, having been the subject of intense study throughout the previous century. As plastics have become ubiquitous in everyday life, polymer science has grown into a major field of study. The conformation of a polymer in solution depends on the molecular architecture and its interactions with the surroundings. Developments in synthetic techniques have led to the creation of precision-tailored polymeric materials with varied topologies and functionalities. In order to design materials with the desired properties, it is imperative to understand the relationships between polymer architecture and their conformation and behavior. To meet that need, this thesis investigates the conformation and self-assembly of three architecturally complex macromolecular systems with rich and varied behaviors driven by the resolution of intramolecular conflicts. First we describe the development of a robust and facile synthetic approach to reproducible bottlebrush polymers (Chapter 2). The method was used to produce homologous series of bottlebrush polymers with polynorbornene backbones, which revealed the effect of side-chain and backbone length on the overall conformation in both good and theta solvent conditions (Chapter 3). The side-chain conformation was obtained from a series of SANS experiments and determined to be indistinguishable from the behavior of free linear polymer chains. Using deuterium-labeled bottlebrushes, we were able for the first time to directly observe the backbone conformation of a bottlebrush polymer which showed self-avoiding walk behavior. Secondly, a series of SANS experiments was conducted on a homologous series of Side Group Liquid Crystalline Polymers (SGLCPs) in a perdeuterated small molecule liquid crystal (5CB). Monodomain, aligned, dilute samples of SGLCP-b-PS block copolymers were seen to self-assemble into complex micellar structures with mutually orthogonally oriented anisotropies at different length scales (Chapter 4). Finally, we present the results from the first scattering experiments on a set of fuel-soluble, associating telechelic polymers. We observed the formation of supramolecular aggregates in dilute (≤0.5wt%) solutions of telechelic polymers and determined that the choice of solvent has a significant effect on the strength of association and the size of the supramolecules (Chapter 5). A method was developed for the direct estimation of supramolecular aggregation number from SANS data. The insight into structure-property relationships obtained from this work will enable the more targeted development of these molecular architectures for their respective applications.

A (re)valorização do patrimônio e as transformações da paisagem: o exemplo do Estado do Rio de Janeiro

Este trabalho apresenta as principais perspectivas estabelecidas a partir da utilização do patrimônio herdado da atividade canavieira no desenvolvimento da atividade turística, na região norte do estado do Rio de Janeiro. Para isso, discutiremos os principais conceitos que permitem entender como áreas consideradas rurais ou marcadas por uma história vinculada a alguma atividade agrícola passam por um processo de transformação e são inseridas em uma nova fase. Essas transformações são percebidas nos espaços chamados de rurais e aparecem hoje com uma nova perspectiva de utilização, antes eram destinados exclusivamente às atividades agrícolas. Outro aspecto verificado é que paisagens singulares acabam se constituindo em patrimônios culturais, na medida em que se tornam representações sociais. A paisagem então acaba sendo relacionada à memória e à identidade local. Nos municípios estudados ela é marcada pelas tradicionais plantações de cana-de-açúcar, que ao longo de mais de um século influenciou a vida e o cotidiano daquela porção do espaço fluminense, permitindo uma arquitetura e uma paisagem peculiar. Desta forma, nosso objetivo é entender como a paisagem é utilizada no desenvolvimento da atividade turística como recurso a ser explorado, além de tentarmos visualizar os principais agentes que promovem as iniciativas de (re)valorização patrimonial e como o espaço é modificado com tal atividade.