Crystal Structure and Prediction

The notion of structure is central to the subject of chemistry. This review traces the development of the idea of crystal structure since the time when a crystal structure could be determined from a three-dimensional diffraction pattern and assesses the feasibility of computationally predicting an unknown crystal structure of a given molecule. Crystal structure prediction is of considerable fundamental and applied importance, and its successful execution is by no means a solved problem. The ease of crystal structure determination today has resulted in the availability of large numbers of crystal structures of higher-energy polymorphs and pseudopolymorphs. These structural libraries lead to the concept of a crystal structure landscape. A crystal structure of a compound may accordingly be taken as a data point in such a landscape.

Catalytic pathway, substrate binding and stability in SAICAR synthetase: A structure and molecular dynamics study

The de novo purine biosynthesis is one of the highly conserved pathways among all organisms and is essential for the cell viability. A clear understanding of the enzymes in this pathway would pave way for the development of antimicrobial and anticancer drugs. Phosphoribosylaminoimidazole-succinocar boxamide (SAICAR) synthetase is one of the enzymes in this pathway that catalyzes ATP dependent ligation of carboxyaminoimidazole ribotide (CAIR) with L-aspartate (ASP). Here, we describe eight crystal structures of this enzyme, in C222(1) and H3 space groups, bound to various substrates and substrate mimics from a hyperthermophilic archaea Pyrococcus horikoshii along with molecular dynamics simulations of the structures with substrates. Complexes exhibit minimal deviation from its apo structure. The CAIR binding site displays a preference for pyrimidine nucleotides. In the ADP.TMP-ASP complex, the ASP binds at a position equivalent to that found in Saccharomyces cerevisiae structure (PDB: 2CNU) and thus, clears the ambiguity regarding ASP's position. A possible mode for the inhibition of the enzyme by CTP and UTP, observed earlier in the yeast enzyme, is clearly illustrated in the structures bound to CMP and UMP. The ADP.Mg2+.PO4.CD/MP complex having a phosphate ion between the ATP and CAIR sites strengthens one of the two probable pathways (proposed in Escherichia coli study) of catalytic mechanism and suggests the possibility of a phosphorylation taking place before the ASP's attack on CAIR. Molecular dynamic simulations of this enzyme along with its substrates at 90 degrees C reveal the relative strengths of substrate binding, possible antagonism and the role of Mg2+ ions. (C) 2015 Elsevier Inc. All rights reserved.

Effect of Rock Mass Structure and Block Size on the Slope Stability-Physical Modeling and Discrete Element Simulation

This paper studies the stability of jointed rock slopes by using our improved three-dimensional discrete element methods (DEM) and physical modeling. Results show that the DEM can simulate all failure modes of rock slopes with different joint configurations. The stress in each rock block is not homogeneous and blocks rotate in failure development. Failure modes depend on the configuration of joints. Toppling failure is observed for the slope with straight joints and sliding failure is observed for the slope with staged joints. The DEM results are also compared with those of limit equilibrium method (LEM). Without considering the joints in rock masses, the LEM predicts much higher factor of safety than physical modeling and DEM. The failure mode and factor of safety predicted by the DEM are in good agreement with laboratory tests for any jointed rock slope.

Formation, microstructure and development of the localized shear deformation in low-carbon steels

An investigation has been made into the effect of microstructural parameters on the propensity for forming shear localization produced during high speed torsional testing by split Hopkinson bar with different average rates of 610, 650 and 1500 s(-1) in low carbon steels. These steels received the quenched, quenched and tempered as well as normalized treatments that provide wide microstructural parameters and mechanical properties. The results indicate that the occurrence of the shear localization is susceptible to the strength of the steels. In other words, the tendency of the quenched steel to form a shear band is higher than that of the other two steels. It is also found that there is a critical strain at which the shear localization occurs in the steels. The critical strain value is strongly dependent on the strength of the steels. Before arriving at this point, the material undergoes a slow work-hardening. After this point, the material suffers work-softening, corresponding to a process during which the deformation is gradually localized and eventually becomes spatially correlated to form a macroscopic shear band. Examinations by SEM reveal that the shear localization within the band involves a series of sequential crystallographic and non-crystallographic events including the change in crystal orientation, misorientation, generation and even perhaps damage in microstructures such as the initiation, growth and coalescence of the microcracks. It is expected that the sharp drop in the load-carrying capacity is associated with the growth and coalescence of the microcracks rather than the occurrence of the shear localization, but the shear localization is seen to accelerate the growth and coalescence of the microcracks. The thin foil observations by TEM reveal that the density of dislocations in the band is extremely high and the tangled arrangement and cell structure of dislocations tends to align along the shear direction. The multiplication and interaction of dislocations seems to be responsible for work-hardening of the steels. The avalanche of the dislocation cells corresponds to the sharp drop in shear stress at which the deformed specimen is broken. Double shear bands and kink bands are also observed in the present study. The principal band develops first and its width is narrower than that of the secondary band.

Livelihood analysis and development of a planning support for the poor in aquaculture and aquatic resource management. Workshop proceedings. 13-15 February 2001, Thai Nguyen, Vietnam

The workshop was organized to understand and describe the livelihoods of poor people who manage aquatic resources for planning support. The purpose was to support field workers to carry out livelihood analysis and how to use this information. (PDF contains 13 pages)

Improving coastal livelihoods through sustainable aquaculture practices – the case of Tubigon, Bohol, Philippines: a report to the collaborative APEC Grouper Research and Development Network

This case study is part of STREAM’s four-country research project, which is exploring how recent advances in sustainable aquaculture have helped and can help improve coastal livelihoods and prevent unsustainable fishing practices in reef fisheries. (Pdf contains 65 pages).

Improving coastal livelihoods through sustainable aquaculture practices in Hon Mun marine protected area, Nha Trang Bay, Vietnam: a report to the collaborative APEC Grouper Research and Development Network

This case study describes the present status and trends, and provides recommendations for the improvement of aquatic resources management within Hon Mun Marine Protected Area (MPA), Nha Trang Bay, Khanh Hoa Province, Vietnam. The case study also evaluates options for improving the livelihoods of local villagers through the development of ecologically sustainable aquaculture and fisheries, which include diversification following careful selection and trial of appropriate culture species, and application of “best practice” culture methods. (Pdf contains 43 pages).

Improving coastal livelihoods through sustainable aquaculture practices - a report to the collaborative APEC Grouper Research and Development Network

Wild-harvest fisheries for live reef fish are largely over-exploited or unsustainable because of over-fishing and the widespread use of destructive fishing practices such as blast and cyanide fishing. Sustainable aquaculture – such as that of groupers – is one option for meeting the strong demand for reef fish, as well as potentially maintaining or improving the livelihoods of coastal communities. This report from a short study by the STREAM Initiative draws on secondary literature, media sources and four diverse case studies from at-risk reef fisheries, to frame a strategy for encouraging sustainable aquaculture as an alternative to destructive fishing practices. It was undertaken as a component of the APEC-funded project Collaborative Grouper Research and Development Network (FWG/01/2001) to better understand how recent technical advances in grouper culture and other complementary work – including that of the Asia-Pacific Marine Finfish Aquaculture Network (APMFAN) hosted by NACA – could better support the livelihoods of poor coastal communities. (PDF contains 49 pages)

Reforming state-level coastal management and development policies: strategic retreat as an innovative, proactive and equitable coastal environmental management strategy

Atlantic and Gulf Coast shorelines include some of the most unique and biologically rich ecosystems in the United States that provide immeasurable aesthetic, habitat and economic benefits. Natural coastal ecosystems, however, are under increasing threat from rampant and irresponsible growth and development. Once a boon to local economies, complex natural forces – enhanced by global climate change and sea level rise - are now considered hazards and eroding the very foundation upon which coastal development is based. For nearly a century, beach restoration and erosion control structures have been used to artificially stabilize shorelines in an effort to protect structures and infrastructure. Beach restoration, the import and emplacement of sand on an eroding beach, is expensive, unpredictable, inefficient and may result in long-term environmental impacts. The detrimental environmental impacts of erosion control structures such as sea walls, groins, bulkheads and revetments include sediment deficits, accelerated erosion and beach loss. These and other traditional responses to coastal erosion and storm impacts- along with archaic federal and state policies, subsidies and development incentives - are costly, encourage risky development, artificially increase property values of high-risk or environmentally sensitive properties, reduce the post-storm resilience of shorelines, damage coastal ecosystems and are becoming increasingly unsustainable. Although communities, coastal managers and property owners face increasingly complex and difficult challenges, there is an emerging public, social and political awareness that, without meaningful policy reforms, coastal ecosystems and economies are in jeopardy. Strategic retreat is a sustainable, interdisciplinary management strategy that supports the proactive, planned removal of vulnerable coastal development; reduces risk; increases shoreline resiliency and ensures long term protection of coastal systems. Public policies and management strategies that can overcome common economic misperceptions and promote the removal of vulnerable development will provide state and local policy makers and coastal managers with an effective management tool that concomitantly addresses the economic, environmental, legal and political issues along developed shorelines. (PDF contains 4 pages)

Reforming state-level coastal management and development policies: strategic retreat as an innovative, proactive and equitable coastal environmental management strategy

Atlantic and Gulf Coast shorelines include some of the most unique and biologically rich ecosystems in the United States that provide immeasurable aesthetic, habitat and economic benefits. Natural coastal ecosystems, however, are under increasing threat from rampant and irresponsible growth and development. Once a boon to local economies, complex natural forces – enhanced by global climate change and sea level rise - are now considered hazards and eroding the very foundation upon which coastal development is based. For nearly a century, beach restoration and erosion control structures have been used to artificially stabilize shorelines in an effort to protect structures and infrastructure. Beach restoration, the import and emplacement of sand on an eroding beach, is expensive, unpredictable, inefficient and may result in long-term environmental impacts. The detrimental environmental impacts of erosion control structures such as sea walls, groins, bulkheads and revetments include sediment deficits, accelerated erosion and beach loss. These and other traditional responses to coastal erosion and storm impacts- along with archaic federal and state policies, subsidies and development incentives - are costly, encourage risky development, artificially increase property values of high-risk or environmentally sensitive properties, reduce the post-storm resilience of shorelines, damage coastal ecosystems and are becoming increasingly unsustainable. Although communities, coastal managers and property owners face increasingly complex and difficult challenges, there is an emerging public, social and political awareness that, without meaningful policy reforms, coastal ecosystems and economies are in jeopardy. Strategic retreat is a sustainable, interdisciplinary management strategy that supports the proactive, planned removal of vulnerable coastal development; reduces risk; increases shoreline resiliency and ensures long term protection of coastal systems. Public policies and management strategies that can overcome common economic misperceptions and promote the removal of vulnerable development will provide state and local policy makers and coastal managers with an effective management tool that concomitantly addresses the economic, environmental, legal and political issues along developed shorelines. (PDF contains 4 pages)

Functional genomic studies of the structure and regulation of eukaryotic transcriptomes

The main focus of this thesis is the use of high-throughput sequencing technologies in functional genomics (in particular in the form of ChIP-seq, chromatin immunoprecipitation coupled with sequencing, and RNA-seq) and the study of the structure and regulation of transcriptomes. Some parts of it are of a more methodological nature while others describe the application of these functional genomic tools to address various biological problems. A significant part of the research presented here was conducted as part of the ENCODE (ENCyclopedia Of DNA Elements) Project.

The first part of the thesis focuses on the structure and diversity of the human transcriptome. Chapter 1 contains an analysis of the diversity of the human polyadenylated transcriptome based on RNA-seq data generated for the ENCODE Project. Chapter 2 presents a simulation-based examination of the performance of some of the most popular computational tools used to assemble and quantify transcriptomes. Chapter 3 includes a study of variation in gene expression, alternative splicing and allelic expression bias on the single-cell level and on a genome-wide scale in human lymphoblastoid cells; it also brings forward a number of critical to the practice of single-cell RNA-seq measurements methodological considerations.

The second part presents several studies applying functional genomic tools to the study of the regulatory biology of organellar genomes, primarily in mammals but also in plants. Chapter 5 contains an analysis of the occupancy of the human mitochondrial genome by TFAM, an important structural and regulatory protein in mitochondria, using ChIP-seq. In Chapter 6, the mitochondrial DNA occupancy of the TFB2M transcriptional regulator, the MTERF termination factor, and the mitochondrial RNA and DNA polymerases is characterized. Chapter 7 consists of an investigation into the curious phenomenon of the physical association of nuclear transcription factors with mitochondrial DNA, based on the diverse collections of transcription factor ChIP-seq datasets generated by the ENCODE, mouseENCODE and modENCODE consortia. In Chapter 8 this line of research is further extended to existing publicly available ChIP-seq datasets in plants and their mitochondrial and plastid genomes.

The third part is dedicated to the analytical and experimental practice of ChIP-seq. As part of the ENCODE Project, a set of metrics for assessing the quality of ChIP-seq experiments was developed, and the results of this activity are presented in Chapter 9. These metrics were later used to carry out a global analysis of ChIP-seq quality in the published literature (Chapter 10). In Chapter 11, the development and initial application of an automated robotic ChIP-seq (in which these metrics also played a major role) is presented.

The fourth part presents the results of some additional projects the author has been involved in, including the study of the role of the Piwi protein in the transcriptional regulation of transposon expression in Drosophila (Chapter 12), and the use of single-cell RNA-seq to characterize the heterogeneity of gene expression during cellular reprogramming (Chapter 13).

The last part of the thesis provides a review of the results of the ENCODE Project and the interpretation of the complexity of the biochemical activity exhibited by mammalian genomes that they have revealed (Chapters 15 and 16), an overview of the expected in the near future technical developments and their impact on the field of functional genomics (Chapter 14), and a discussion of some so far insufficiently explored research areas, the future study of which will, in the opinion of the author, provide deep insights into many fundamental but not yet completely answered questions about the transcriptional biology of eukaryotes and its regulation.

The structure and margins of the Lake Chilwa fisheries in Malawi: a value chain analysis

Small freshwater pelagic fisheries in closed lakes are very important to millions of people in sub-Saharan Africa providing livelihoods and nutritional security. However, returns from these fisheries have been shown to �uctuate in response to climatic variability. In order to understand the impact of these fluctuations on the livelihoods of people dependant on these fisheries, there is a need for information on how the fish value chain is organized and how it functions in response to variation in supplies. The results will feed into strategies that build resilience in fishing households against the uncertainties arising from unstable ecosystems. The Lake Chilwa fishery value chain is composed of fishers, processors, traders, fish transporters, boat owners, owners of fish processing shades, fisheries associations, gear owners, gear makers, firewood sellers, and traders of fishing gear and equipment. The value chain employs many people and local authorities can consider using this information in the design of rural development strategies for employment generation in small-scale fishing communities. The findings from this study have a number of implications for the improvement of the livelihood of fishers and enhancing their capacity to mitigate against the effects of climate change.

Synthesis of aquaculture policy and development approaches in Africa

The WorldFish Center was tasked to undertake a study to access, collate and develop background materials to produce an internationally linked and Africa-wide perspective on sectorally relevant policy issues. The specific objective of the study was to assess and define conditions and impact pathways, in Africa or elsewhere, where markets, policies, resources and technologies have combined to promote steady and sustainable growth of aquaculture, and where have been clear direct impacts on food supply, income, employment and consumption opportunities, as well as increase in supply that has led to stabilised prices. The study was also aimed at providing guidelines for scaling up the implementation of the synthesis study via Afri-FishNet (CAADP Fish Expert Pools) at the national and regional levels.

Structure and anti-HIV activity of micrandilactones B and C, new nortriterpenoids possessing a unique skeleton from Schisandra micrantha

Two new highly oxygenated nortriterpenoids with a unique norcycloartane skeleton, micrandilactones B and C (1-2), were isolated from Schisandra micrantha; micrandilactone C ( 2) exhibited an EC50 value of 7.71 mu g/mL (SI > 25.94) against HIV-1 replication with minimal cytotoxicity, and the potent anti-HIV-1 activity and unique structural features of 2 make it a promising lead for therapeutic development of a new generation of anti-HIV drug.

Vegetation structure and faunal composition of Wathurana wetland ecosystem Tebuwana, Kalutara, Sri Lanka

A study was conducted in Tebuwana Wathurana Wetland ecosystem to understand its vegetation structure and faunal composition in order to assess its conservation needs. As there are no published records on the flora and fauna of Wathurana Wetlands in Tebuwana, it is necessary to understand the ecological and other relevant features in order to develop strategies to conserve this wetland. These objectives were pursued by surveying the vegetation of the wetland and by identifying fish and bird species present. A total of 66 species of flora and 61 species of fauna were identified in the survey. Of the 27 fish species recorded from the Tebuwana Wetland, 9 species were endemic and 17 species belonged to the indigenous category. With regard to the flora in the wetlands, the dominant families were Rubaceae, Fabaceae and Arecaceae. The 66 species belonged to 39 families and 61 genera while 12 species were endemic and 4 species were considered highly threatened. These flora were found in four layers. Of the 22 species of birds recorded, two species were endemic. This study revealed that these Wathurana Wetlands have a high species diversity but that they face many threats including encroachments, extraction of forest products mainly as timber, land filling, mining and occurrence of invasive species. It is essential to minimize the exploitation of natural resources from this wetland in the future and in particular to mark the boundary, conduct awareness programmes and continue research.