A computerized methodology for structural synthesis of kinematic chains: Part 3 - application to the new case of 10-link, three- freedom chains

The unified computer program for structural synthesis and analysis developed in Part 1 has been employed to derive the new and complete collection of 97 10-link, three-freedom simple-jointed kinematic chains. The program shows that of these chains, 3 have total freedom, 70 have partial freedom and the remaining 24 have fractionated freedom and that the 97 chains yield a total of 676 distinct mechanisms.

Side Chain Structure Determines Unique Physiologic and Therapeutic Properties of norUrsodeoxycholic Acid in Mdr2(-/-) Mice

24-norursodeoxycholic acid (norUDCA), a side chain-modified ursodeoxycholic acid derivative, has dramatic therapeutic effects in experimental cholestasis and may be a promising agent for the treatment of cholestatic liver diseases. We aimed to better understand the physiologic and therapeutic properties of norUDCA and to test if they are related to its side chain length and/or relative resistance to amidation. For this purpose, Mdr2-/- mice, a model for sclerosing cholangitis, received either a standard diet or a norUDCA-, tauro norursodeoxycholic acid (tauro- norUDCA)-, or di norursodeoxycholic acid (di norUDCA)-enriched diet. Bile composition, serum biochemistry, liver histology, fibrosis, and expression of key detoxification and transport systems were investigated. Direct choleretic effects were addressed in isolated bile duct units. The role of Cftr for norUDCA-induced choleresis was explored in Cftr-/- mice. norUDCA had pharmacologic features that were not shared by its derivatives, including the increase in hepatic and serum bile acid levels and a strong stimulation of biliary HCO3- -output. norUDCA directly stimulated fluid secretion in isolated bile duct units in a HCO3- -dependent fashion to a higher extent than the other bile acids. Notably, the norUDCA significantly stimulated HCO 3- -output also in Cftr-/- mice. In Mdr2-/- mice, cholangitis and fibrosis strongly improved with norUDCA, remained unchanged with tauro- norUDCA, and worsened with di norUDCA. Expression of Mrp4, Cyp2b10, and Sult2a1 was increased by norUDCA and di norUDCA, but was unaffected by tauro- norUDCA. Conclusion:The relative resistance of norUDCA to amidation may explain its unique physiologic and pharmacologic properties. These include the ability to undergo cholehepatic shunting and to directly stimulate cholangiocyte secretion, both resulting in a HCO3- -rich hypercholeresis that protects the liver from cholestatic injury.

In quest of a reliable and efficient computational test for detection of isomorphism in kinematic chains

The test based on comparison of the characteristic coefficients of the adjancency matrices of the corresponding graphs for detection of isomorphism in kinematic chains has been shown to fail in the case of two pairs of ten-link, simple-jointed chains, one pair corresponding to single-freedom chains and the other pair corresponding to three-freedom chains. An assessment of the merits and demerits of available methods for detection of isomorphism in graphs and kinematic chains is presented, keeping in view the suitability of the methods for use in computerized structural synthesis of kinematic chains. A new test based on the characteristic coefficients of the “degree” matrix of the corresponding graph is proposed for detection of isomorphism in kinematic chains. The new test is found to be successful in the case of a number of examples of graphs where the test based on characteristic coefficients of adjancency matrix fails. It has also been found to be successful in distinguishing the structures of all known simple-jointed kinematic chains in the categories of (a) single-freedom chains with up to 10 links, (b) two-freedom chains with up to 9 links and (c) three-freedom chains with up to 10 links.

Studies on tryptophan residues of Abrus agglutinin Stopped-flow kinetics of modification and fluorescence-quenching studies

The presence of two essential tryptophan residues/molecule was implicated in the binding site of Abrus agglutinin [Patanjali, Swamy, Anantharam, Khan & Surolia (1984) Biochem. J. 217, 773-781]. A detailed study of the stopped-flow kinetics of the oxidation of tryptophan residues revealed three classes of tryptophan residues in the native protein. A discrete reorganization of tryptophan residues into two phases was observed upon ligand binding. The heterogeneity of tryptophan exposure was substantiated by quenching studies with acrylamide, succinimide and Cs+. Our study revealed the microenvironment of tryptophan residues to be hydrophobic, and also the presence of acidic amino acid residues in the vicinity of surface-localized tryptophan residues.

Adoption of environmental assurance in pastoral industry supply chains - Market failure and beyond

This paper describes adoption rates of environmental assurance within meat and wool supply chains, and discusses this in terms of market interest and demand for certified 'environmentally friendly' products, based on phone surveys and personal interviews with pastoral producers, meat and wool processors, wholesalers and retailers, and domestic consumers. Members of meat and wool supply chains, particularly pastoral producers, are both aware of and interested in implementing various forms of environmental assurance, but significant costs combined with few private benefits have resulted in low adoption rates. The main reason for the lack of benefits is that the end user (the consumer) does not value environmental assurance and is not willing to pay for it. For this reason, global food and fibre supply chains, which compete to supply consumers with safe and quality food at the lowest price, resist public pressure to implement environmental assurance. This market failure is further exacerbated by highly variable environmental and social production standards required of primary producers in different countries, and the disparate levels of government support provided to them. Given that it is the Australian general public and not markets that demand environmental benefits from agriculture, the Australian government has a mandate to use public funds to counter this market failure. A national farm environmental policy should utilise a range of financial incentives to reward farmers for delivering general public good environmental outcomes, with these specified and verified through a national environmental assurance scheme.

Self-Organization of n-Alkane Chains in Water: Length Dependent Crossover from Helix and Toroid to Molten Globule

We demonstrate a chain length dependent crossover in the structural properties of linear hydrocarbon (n-alkane) chains using detailed atomistic simulations in explicit water. We identify a number of exotic structures of the polymer chain through energy minimization of representative snapshots collected from molecular dynamics trajectory. While the collapsed state is ring-like (circular) for small chains (CnH2n+2; n <= 20) and spherical for very long ones (n = 100), we find the emergence of ordered helical structures at intermediate lengths (n similar to 40). We find different types of disordered helices and toroid-like structures at n = 60. We also report a sharp transition in the stability of the collapsed state as a function of the chain length through relevant free energy calculations. While the collapsed state is only marginally metastable for C20H42, a clear bistable free energy surface emerges only when the chain is about 30 monomers long. For n = 30, the polymer exhibits an intermittent oscillation between the collapsed and the coil structures, characteristic of two stable states separated by a small barrier.

Obverse side of tombstone of Jeanette Molling (possibly Arthur Molling); Strangriede Cemetery; Hannover Cemeteries Tombs

Digital Image

Obverse side of tombstone of Jeanette Molling (possibly Arthur Molling); Strangriede Cemetery; Hannover Cemeteries Tombs

Digital Image

Side-band intensities in the deuterium magnetic resonance spectra of oriented molecules spinning near the magic angle

The appearance of spinning side bands in the 2H NMR spectra of oriented molecules is investigated. A theoretical interpretation of the side-band intensities is carried out. Information derived on the director orientation and distribution as a function of spinning speedis reported.

Stimulation of liver tryptophan pyrrolase during heat exposure

Exposure of rats to heat (39 +/- 1 degree C) stimulated liver tryptophan pyrrolase 2-fold between 3 and 48 h. Plasma corticosterone increased 2-fold after 1 h of heat exposure and decreased to a low value of 50% by 16 h. The effect of heat exposure on the enzyme was obtained in adrenalectomized animals. Stimulation by cortisol and tryptophan of the enzyme was also obtained in heat exposure, and the effects seemed to be additive. The concentration of tryptophan in the liver remained unchanged, and that in the plasma decreased to about 50% at 8 h exposure to heat and reverted to normal by 46 h. Simultaneous administration of noradrenaline to heat-exposed rats had no effect, whereas that of thyroxine partly prevented the stimulation of the enzyme activity. Hypothyroid conditions obtained by thyroidectomy or treatment with propylthiouracil significantly stimulated the enzyme activity. Cycloheximide treatment of heat-exposed rats did not prevent the stimulation of the enzyme activity. The results indicate that the effect of heat exposure on liver tryptophan pyrrolase is obtained, due to the accompanying hypothyroid condition, by increasing the activity of the existing protein by a mechanism possibly different from those known at present.

The scientific basis and development of a matrix metalloproteinase (MMP) -8 specific chair-side test for monitoring of periodontal health and disease from gingival crevicular fluid

Matrix metalloproteinase (MMP) -8, collagenase-2, is a key mediator of irreversible tissue destruction in chronic periodontitis and detectable in gingival crevicular fluid (GCF). MMP-8 mostly originates from neutrophil leukocytes, the first line of defence cells which exist abundantly in GCF, especially in inflammation. MMP-8 is capable of degrading almost all extra-cellular matrix and basement membrane components and is especially efficient against type I collagen. Thus the expression of MMP-8 in GCF could be valuable in monitoring the activity of periodontitis and possibly offers a diagnostic means to predict progression of periodontitis. In this study the value of MMP-8 detection from GCF in monitoring of periodontal health and disease was evaluated with special reference to its ability to differentiate periodontal health and different disease states of the periodontium and to recognise the progression of periodontitis, i.e. active sites. For chair-side detection of MMP-8 from the GCF or peri-implant sulcus fluid (PISF) samples, a dip-stick test based on immunochromatography involving two monoclonal antibodies was developed. The immunoassay for the detection of MMP-8 from GCF was found to be more suitable for monitoring of periodontitis than detection of GCF elastase concentration or activity. Periodontally healthy subjects and individuals suffering of gingivitis or of periodontitis could be differentiated by means of GCF MMP-8 levels and dipstick testing when the positive threshold value of the MMP-8 chair-side test was set at 1000 µg/l. MMP-8 dipstick test results from periodontally healthy and from subjects with gingivitis were mainly negative while periodontitis patients sites with deep pockets ( 5 mm) and which were bleeding on probing were most often test positive. Periodontitis patients GCF MMP-8 levels decreased with hygiene phase periodontal treatment (scaling and root planing, SRP) and even reduced during the three month maintenance phase. A decrease in GCF MMP-8 levels could be monitored with the MMP-8 test. Agreement between the test stick and the quantitative assay was very good (κ = 0.81) and the test provided a baseline sensitivity of 0.83 and specificity of 0.96. During the 12-month longitudinal maintenance phase, periodontitis patients progressing sites (sites with an increase in attachment loss ≥ 2 mm during the maintenance phase) had elevated GCF MMP-8 levels compared with stable sites. General mean MMP-8 concentrations in smokers (S) sites were lower than in non-smokers (NS) sites but in progressing S and NS sites concentrations were at an equal level. Sites with exceptionally and repeatedly elevated MMP-8 concentrations during the maintenance phase were clustered in smoking patients with poor response to SRP (refractory patients). These sites especially were identified by the MMP-8 test. Subgingival plaque samples from periodontitis patients deep periodontal pockets were examined by polymerase chain reaction (PCR) to find out if periodontal lesions may serve as a niche for Chlamydia pneumoniae. Findings were compared with the clinical periodontal parameters and GCF MMP-8 levels to determine the correlation with periodontal status. Traces of C. pneumoniae were identified from one periodontitis patient s pooled subgingival plaque sample by means of PCR. After periodontal treatment (SRP) the sample was negative for C. pneumoniae. Clinical parameters or biomarkers (MMP-8) of the patient with the positive C. pneumoniae finding did not differ from other study patients. In this study it was concluded that MMP-8 concentrations in GCF of sites from periodontally healthy individuals, subjects with gingivitis or with periodontitis are at different levels. The cut-off value of the developed MMP-8 test is at an optimal level to differentiate between these conditions and can possibly be utilised in identification of individuals at the risk of the transition of gingivitis to periodontitis. In periodontitis patients, repeatedly elevated GCF MMP-8 concentrations may indicate sites at risk of progression of periodontitis as well as patients with poor response to conventional periodontal treatment (SRP). This can be monitored by MMP-8 testing. Despite the lower mean GCF MMP-8 concentrations in smokers, a fraction of smokers sites expressed very high MMP-8 concentrations together with enhanced periodontal activity and could be identified with MMP-8 specific chair-side test. Deep periodontal lesions may be niches for non-periodontopathogenic micro-organisms with systemic effects like C. pneumoniae and possibly play a role in the transmission from one subject to another.

Improved domestic profitability and export competitiveness of selected fruit value chains in the southern Philippines and Australia program

The goal of the Program is to contribute to economic growth in the Philippines through increased income and improved livelihoods of tropical fruit growers in southern Philippines. The purpose of the Program is to improve the smallholder and industry profitability and export competitiveness of selected tropical fruits industries in the southern Philippines. Fruit crops to be targeted are mango, papaya, durian and jackfruit. The primary audience for the outcomes of this Program are medium to large scale commercial fruit growers and farmers predominantly in the regions of Leyte (VIII), northern Mindanao/Cagayan de Oro (X) and southern Mindanao/Davao (XI).

Computer-aided analysis of the structure of kinematic chains

Using the link-link incidence matrix to represent a simple-jointed kinematic chain algebraic procedures have been developed to determine its structural characteristics such as the type of freedom of the chain, the number of distinct mechanisms and driving mechanisms that can be derived from the chain. A computer program incorporating these graph theory based procedures has been applied successfully for the structural analysis of several typical chains.

Preferred conformations and flexibility of aminoacyl side chain of penicillins

Possible conformations of penicillin G; d and l isomers of ampicillin; α-amino-α-methyl-benzyl penicillins and 3- pyridyl methyl penicillin have been studied by an energy minimization procedure using empirical potential functions. The preferred conformations of these antibiotics have been correlated with their biological activity. The conformational requirement of the antibiotic to be active against Gram-positive and Gram-negative (β-lactamase-negative) bacterial strains seems to be the same. The reduced activity of penicillin G against Gram-negative bacteria has been attributed to its lower ability to permeate the outer membrane. The flexibility of the sidechains of these antibiotics is also shown to be important for the desired biological activity.