Distributional Learning of Appearance

Opportunities for associationist learning of word meaning, where a word is heard or read contemperaneously with information being available on its meaning, are considered too infrequent to account for the rate of language acquisition in children. It has been suggested that additional learning could occur in a distributional mode, where information is gleaned from the distributional statistics (word co-occurrence etc.) of natural language. Such statistics are relevant to meaning because of the Distributional Principle that ‘words of similar meaning tend to occur in similar contexts’. Computational systems, such as Latent Semantic Analysis, have substantiated the viability of distributional learning of word meaning, by showing that semantic similarities between words can be accurately estimated from analysis of the distributional statistics of a natural language corpus. We consider whether appearance similarities can also be learnt in a distributional mode. As grounds for such a mode we advance the Appearance Hypothesis that ‘words with referents of similar appearance tend to occur in similar contexts’. We assess the viability of such learning by looking at the performance of a computer system that interpolates, on the basis of distributional and appearance similarity, from words that it has been explicitly taught the appearance of, in order to identify and name objects that it has not been taught about. Our experiment tests with a set of 660 simple concrete noun words. Appearance information on words is modelled using sets of images of examples of the word. Distributional similarity is computed from a standard natural language corpus. Our computation results support the viability of distributional learning of appearance.     

Irreversible Heavy Chain Transfer to Hyaluronan Oligosaccharides by Tumor Necrosis Factor-stimulated Gene-6

The covalent transfer of heavy chains (HCs) from inter-α-inhibitor (IαI) to hyaluronan (HA) via the protein product of tumor necrosis factor-stimulated gene-6 (TSG-6) forms the HC-HA complex, a pathological form of HA that promotes the adhesion of leukocytes to HA matrices. The transfer of HCs to high molecular weight (HMW) HA is a reversible event whereby TSG-6 can shuffle HCs from one HA molecule to another. Therefore, HMW HA can serve as both an HC acceptor and an HC donor. In the present study, we show that transfer of HCs to low molecular weight HA oligosaccharides is an irreversible event where subsequent shuffling does not occur, i.e. HA oligosaccharides from 8 to 21 monosaccharide units in length can serve as HC acceptors, but are unable to function as HC donors. We show that the HC-HA complex is present in the synovial fluid of mice subjected to systemic and monoarticular mouse models of rheumatoid arthritis. Furthermore, we demonstrate that HA oligosaccharides can be used, with TSG-6, to irreversibly shuffle HCs from pathological, HMW HC-HA to HA oligosaccharides, thereby restoring HC-HA matrices from the inflamed joint to their normal state, unmodified with HCs. This process was also effective for HC-HA in the synovial fluid of human rheumatoid arthritis patients (in vitro).     

Computational and Functional Analyses of a Small-Molecule Binding Site in ROMK

The renal outer medullary potassium channel (ROMK, or Kir1.1, encoded by KCNJ1) critically regulates renal tubule electrolyte and water transport and hence blood volume and pressure. The discovery of loss-of-function mutations in KCNJ1 underlying renal salt and water wasting and lower blood pressure has sparked interest in developing new classes of antihypertensive diuretics targeting ROMK. The recent development of nanomolar-affinity small-molecule inhibitors of ROMK creates opportunities for exploring the chemical and physical basis of ligand-channel interactions required for selective ROMK inhibition. We previously reported that the bis-nitro-phenyl ROMK inhibitor VU591 exhibits voltage-dependent knock-off at hyperpolarizing potentials, suggesting that the binding site is located within the ion-conduction pore. In this study, comparative molecular modeling and in silico ligand docking were used to interrogate the full-length ROMK pore for energetically favorable VU591 binding sites. Cluster analysis of 2498 low-energy poses resulting from 9900 Monte Carlo docking trajectories on each of 10 conformationally distinct ROMK comparative homology models identified two putative binding sites in the transmembrane pore that were subsequently tested for a role in VU591-dependent inhibition using site-directed mutagenesis and patch-clamp electrophysiology. Introduction of mutations into the lower site had no effect on the sensitivity of the channel to VU591. In contrast, mutations of Val¹⁶⁸ or Asn¹⁷¹ in the upper site, which are unique to ROMK within the Kir channel family, led to a dramatic reduction in VU591 sensitivity. This study highlights the utility of computational modeling for defining ligand-ROMK interactions and proposes a mechanism for inhibition of ROMK.     

Comparison of the carbon-sequestering abilities of pineapple leaf residue chars produced by controlled combustion and by field burning

This study was undertaken to compare the chemical properties and yields of pineapple leaf residue (PLR) char produced by field burning (CF) with that produced by a partial combustion of air-dried PLR at 340 °C for 3 h in a furnace (CL). Higher total C, lignin content, and yield from CL as well as the presence of aromatic compounds in the Fourier Transform Infrared spectra of the char produced from CL suggest that the CL process was better in sequestering C than was the CF process. Although the C/N ratio of char produced from CL was low indicating a high N content of the char, the C in the char produced from CL was dominated by lignin suggesting that the decomposition of char produced from CL would be slow. To sequester C by char application, the PLR should be combusted in a controlled process rather than by burning in the field.     

The effect of maternal multiple micronutrient supplementation on cognition and mood during pregnancy and postpartum in Indonesia: a randomized trial

Maternal caregiving capacity, which is affected in part by cognition and mood, is crucial for the health of mothers and infants. Few interventions aim to improve maternal and infant health through improving such capacity. Multiple micronutrient (MMN) supplementation may improve maternal cognition and mood, since micronutrients are essential for brain function. We assessed mothers who participated in the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT), a double-blind cluster-randomized trial in Indonesia comparing MMN supplementation to iron and folic acid (IFA) during pregnancy and until three months postpartum. We adapted a set of well-studied tests of cognition, motor dexterity, and mood to the local context and administered them to a random sample of 640 SUMMIT participants after an average of 25 weeks (SD = 9) of supplementation. Analysis was by intention to treat. Controlling for maternal age, education, and socio-economic status, MMN resulted in a benefit of 0.12 SD on overall cognition, compared to IFA (95%CI 0.03-0.22, p = .010), and a benefit of 0.18 SD on reading efficiency (95%CI 0.02-0.35, p = .031). Both effects were found particularly in anemic (hemoglobin<110 g/L; overall cognition: B = 0.20, 0.00-0.41, p = .055; reading: B = 0.40, 0.02-0.77, p = .039) and undernourished (mid-upper arm circumference<23.5 cm; overall cognition: B = 0.33, 0.07-0.59, p = .020; reading: B = 0.65, 0.19-1.12, p = .007) mothers. The benefit of MMN on overall cognition was equivalent to the benefit of one year of education for all mothers, to two years of education for anemic mothers, and to three years of education for undernourished mothers. No effects were found on maternal motor dexterity or mood. This is the first study demonstrating an improvement in maternal cognition with MMN supplementation. This improvement may increase the quality of care mothers provide for their infants, potentially partly mediating effects of maternal MMN supplementation on infant health and survival. The study is registered as an International Standard Randomized Controlled Trial, number ISRCTN34151616. http://www.controlled-trials.com/ISRCTN34151616.     

Constructions of expression vectors of polyhydroxybutyrate-co-hydroxyvalerate (PHBV) and transient expression of transgenes in immature oil palm embryos

Polyhydroxybutyrate-co-hydroxyvalerate (PHBV) is a polyhydroxyalkanoate (PHA) bioplastic group with thermoplastic properties is thus high in quality and can be degradable. PHBV can be produced by bacteria, but the process is not economically competitive with polymers produced from petrochemicals. To overcome this problem, research on transgenic plants has been carried out as one of the solutions to produce PHBV in economically sound alternative manner. Four different genes encoded with the enzymes necessary to catalyze PHBV are bktB, phaB, phaC and tdcB. All the genes came with modified CaMV 35S promoters (except for the tdcB gene, which was promoted by the native CaMV 35S promoter), nos terminator sequences and plastid sequences in order to target the genes into the plastids. Subcloning resulted in the generation of two different orientations of the tdcB, pLMIN (left) and pRMIN (right), both 17.557 and 19.967 kb in sizes. Both plasmids were transformed in immature embryos (IE) of oil palm via Agrobacterium tumefaciens. Assays of GUS were performed on one-week-old calli and 90% of the calli turned completely blue. This preliminary test showed positive results of integration. Six-months-old calli were harvested and RNA of the calli were isolated. RT-PCR was used to confirm the transient expression of PHBV transgenes in the calli. The bands were 258, 260, 315 and 200 bp in size for bktB, phaB, phaC and tdcB transgenes respectively. The data obtained showed that the bktB, phaB, phaC and tdcB genes were successfully integrated and expressed in the oil palm genome.     

Dry-reagent gold nanoparticle-based lateral flow biosensor for the simultaneous detection of Vibrio cholerae serogroups O1 and O139

Cholera is a communicable disease caused by consumption of contaminated food and water. This potentially fatal intestinal infection is characterised by profuse secretion of rice watery stool that can rapidly lead to severe dehydration and shock, thus requiring treatment to be given immediately. Epidemic and pandemic cholera are exclusively associated with Vibrio cholerae serogroups O1 and O139. In light of the need for rapid diagnosis of cholera and to prevent spread of outbreaks, we have developed and evaluated a direct one-step lateral flow biosensor for the simultaneous detection of both V. cholerae O1 and O139 serogroups using alkaline peptone water culture. Serogroup specific monoclonal antibodies raised against lipopolysaccharides (LPS) were used to functionalize the colloidal gold nanoparticles for dual detection in the biosensor. The assay is based on immunochromatographic principle where antigen-antibody reaction would result in the accumulation of gold nanoparticles and thus, the appearance of a red line on the strip. The dry-reagent dipstick format of the biosensor ensure user-friendly application, rapid result that can be read with the naked eyes and cold-chain free storage that is well-suited to be performed at resource-limited settings.     

Tropical Soil Bacterial Communities in Malaysia: pH Dominates in the Equatorial Tropics Too

The dominant factors controlling soil bacterial community variation within the tropics are poorly known. We sampled soils across a range of land use types--primary (unlogged) and logged forests and crop and pasture lands in Malaysia. PCR-amplified soil DNA for the bacterial 16S rRNA gene targeting the V1-V3 region was pyrosequenced using the 454 Roche machine. We found that land use in itself has a weak but significant effect on the bacterial community composition. However, bacterial community composition and diversity was strongly correlated with soil properties, especially soil pH, total carbon, and C/N ratio. Soil pH was the best predictor of bacterial community composition and diversity across the various land use types, with the highest diversity close to neutral pH values. In addition, variation in phylogenetic structure of dominant lineages (Alphaproteobacteria, Beta/Gammaproteobacteria, Acidobacteria, and Actinobacteria) is also significantly correlated with soil pH. Together, these results confirm the importance of soil pH in structuring soil bacterial communities in Southeast Asia. Our results also suggest that unlike the general diversity pattern found for larger organisms, primary tropical forest is no richer in operational taxonomic units of soil bacteria than logged forest, and agricultural land (crop and pasture) is actually richer than primary forest, partly due to selection of more fertile soils that have higher pH for agriculture and the effects of soil liming raising pH.     

Fibroblasts From Type 1 Diabetics Exhibit Enhanced Ca2+ Mobilization after TNF or Fat Exposure

The effects of cytokine and fatty acid treatment on signal transduction in dermal fibroblasts from type 1 diabetics and matched controls were compared. Chronic exposure to TNF, accentuated Ca²⁺ mobilization in response to bradykinin (BK) in cells from both controls and diabetics; responses were three-fold greater in cells from diabetics than in controls. Similarly, with chronic exposure to IL-1β, BK-induced Ca²⁺ mobilization was accentuated in cells from type 1 diabetics compared to the controls. Pretreatment with the protein synthesis inhibitor cycloheximide or the protein kinase C inhibitor calphostin C prior to the addition of TNF completely abrogated the TNF-induced increment in peak bradykinin response. Ca²⁺ transients induced by depleting endoplasmic reticulum (ER) Ca²⁺ with thapsigargin were also greater in TNF treated fibroblasts than in untreated cells, with greater increases in cells from diabetics. Exposing fibroblasts for 48 hours to 2 mM oleate also increased both the peak bradykinin response and the TNF-induced increment in peak response, which were significantly greater in diabetics than controls. These data indicate that cells from diabetic patients acquire elevated ER Ca²⁺ stores in response to both cytokines and free fatty acids,and thus exhibit greater sensitivity to environmental inflammatory stimuli and elevated lipids.