Fast and accurate fitting of relaxation dispersion data using the flexible software package GLOVE

Relaxation dispersion spectroscopy is one of the most widely used techniques for the analysis of protein dynamics. To obtain a detailed understanding of the protein function from the view point of dynamics, it is essential to fit relaxation dispersion data accurately. The grid search method is commonly used for relaxation dispersion curve fits, but it does not always find the global minimum that provides the best-fit parameter set. Also, the fitting quality does not always improve with increase of the grid size although the computational time becomes longer. This is because relaxation dispersion curve fitting suffers from a local minimum problem, which is a general problem in non-linear least squares curve fitting. Therefore, in order to fit relaxation dispersion data rapidly and accurately, we developed a new fitting program called GLOVE that minimizes global and local parameters alternately, and incorporates a Monte-Carlo minimization method that enables fitting parameters to pass through local minima with low computational cost. GLOVE also implements a random search method, which sets up initial parameter values randomly within user-defined ranges. We demonstrate here that the combined use of the three methods can find the global minimum more rapidly and more accurately than grid search alone.     

Septic Shock

Septic shock may be defined as hypotension caused by bacteremia and accompanied by decreased peripheral blood flow, evidenced by oliguria. Clinically, a shaking chill is the warning signal. The immediate cause of hypotension is pooling of blood in the periphery, leading to decreased venous return: later, peripheral resistance falls and cardiac failure may occur. Irreversible shock is comparable to massive reactive hyperemia. Reticuloendothelial failure, histamine release, and toxic hypersensitivity may be factors in the pathogenesis of septic shock. Adrenal failure does not usually occur, but large doses of corticosteroid are employed therapeutically to counteract the effect of histamine release or hypersensitivity to endotoxin. The keys to successful therapy are time, antibiotics, vasopressors, cortisone and correction of acidosis.     

The Functional Role of Balinese Water Temples: A Response to Critics

In earlier publications we have proposed a model to explain the functional role of water temple networks in the agro-ecology of wet rice irrigation on the island of Bali. We argued that the key ecological effects of temple networks are best understood as emergent properties of a complex adaptive system. This argument implies that important aspects of the temple system are largely opaque from the perspective of conventional social science. We proposed that the Green Revolution created a real-world test of our model, by effectively removing the temple networks from their functional role in ecological management. The idea that water temple networks represent a hitherto-unknown kind of institution has been met with appropriate skepticism by other social scientists, who have run a fine-toothed comb through our evidence. Here we evaluate their critiques.     

Balinese "Water Temples" and the Management of Irrigation

Bali has figured prominently in debates on the question of whether irrigation centralizes state power. New evidence shows that irrigation is actually organized by networks of "water temples" that constitute an institutional system separate from the state. Earlier attempts to identify a discrete system of irrigation management misconceived the problem. For most crops, irrigation simply provides water for the plant's roots. But in a Balinese rice terrace, water is used to construct a complex, pulsed artificial ecosystem. Water temples manipulate the states of the system, at ascending levels in regional hierarchies. The permanence of water temple networks contrasts sharply with the instability of the traditional Balinese states. Since the water temples are real, perhaps it is the Balinese "state" that is chimerical.     

Waste treatment and biogas quality in small-scale agricultural digesters

Seven low-cost digesters in Costa Rica were studied to determine the potential of these systems to treat animal wastewater and produce renewable energy. The effluent water has a significantly lower oxygen demand (COD decreased from 2968 mg/L to 472 mg/L) and higher dissolved nutrient concentration (NH₄-N increased by 78.3% to 82.2 mg/L) than the influent water, which increases the usefulness of the effluent as an organic fertilizer and decreases its organic loading on surface waters. On average, methane constituted 66% of the produced biogas, which is consistent with industrial digesters. Through principle component analysis, COD, turbidity, NH₄-N, TKN, and pH were determined to be the most useful parameters to characterize wastewater. The results suggest that the systems have the ability to withstand fluctuations in the influent water quality. This study revealed that small-scale agricultural digesters can produce methane at concentrations useful for cooking, while improving the quality of the livestock wastewater.     

A Polynesian motif on the Y chromosome: population structure in remote Oceania

The Polynesian motif, a mitochondrial DNA marker of ancestral Polynesian communities, has filled a critical role in reconstructions of remote Oceanic history. Although the motif provides an effective narrative for Polynesian females, no equivalent male history is available from paternal lineages. Here, we describe a Y-chromosome binary polymorphism with absolute Polynesian affinity. We illustrate its unique spatial and temporal connections to early Polynesian communities, and through an analysis of associated short tandem repeat variation, we describe the first clear genealogic structure within Polynesia. Unlike the eastern and western regions advocated by archeology, we identify a tripartite structure comprising interaction spheres in the west (Tonga and Samoa), center (Tahiti), and east (Rapanui/Easter Island). Such patterning, a product of early regional contact and subsequent isolation, signals the conflicting roles of mobility and seclusion in Polynesian prehistory.     

Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding

A series of thiophene PLK1 inhibitors was optimized for increased solubility and reduced protein binding through the appendage of basic amine functionality. Interesting selectivity between PLK1 and PLK3 was also obtained through these modifications.     

Molecular phylogeny of the springhare, Pedetes capensis, based on mitochondrial DNA sequences

The phylogenetic position of the Pedetidae, represented by a single species Pedetes capensis, is controversial, reflecting in part the retention of both Hystricomorphous and Sciurognathous characteristics in this rodent. In an attempt to clarify the species evolutionary relationships, mtDNA gene sequences from 10 rodent species (representing seven families) were analyzed using phenetic, parsimony, and maximum-likelihood methods of phylogenetic inference; the rabbit, Oryctolagus cuniculus (Order Lagomorpha), and cow, Bos taurus (Order Artiodactyla), were used as outgroups. Investigation of 714 base pairs of the protein-coding cytochrome b gene indicate strong base bias at the third codon position with significant rate heterogeneity evident between the three structural domains of this gene. Similar analyses conducted on 816 base pairs of the 12S rRNA gene revealed a transversion bias in the loop sections of all taxa. The cytochrome b gene sequences proved useful in resolving associations between closely related species but failed to produce consistent tree topologies at the family level. In contrast, phylogenetic analysis of the 12S rRNA gene resulted in strong support for the clustering of Pedetidae/Heteromyidae/Geomyidae and Muridae in one clade to the exclusion of the Hystricidae/Thryonomyidae and Sciuridae, a finding which is concordant with studies of rodent fetal membranes as well as reproductive and other anatomical features.