Revisiting Digital Straight Segment Recognition

This paper presents new results about digital straight segments, their recognition and related properties. They come from the study of the arithmetically based recognition algorithm proposed by I. Debled-Rennesson and J.-P. Reveill\`es in 1995 [Debled95]. We indeed exhibit the relations describing the possible changes in the parameters of the digital straight segment under investigation. This description is achieved by considering new parameters on digital segments: instead of their arithmetic description, we examine the parameters related to their combinatoric description. As a result we have a better understanding of their evolution during recognition and analytical formulas to compute them. We also show how this evolution can be projected onto the Stern-Brocot tree. These new relations have interesting consequences on the geometry of digital curves. We show how they can for instance be used to bound the slope difference between consecutive maximal segments

128Xe and 130Xe: Testing He-shell burning in AGB stars

The s-process branching at 128I has been investigated on the basis of new, precise experimental (n,g) cross sections for the s-only isotopes 128Xe and 130Xe. This branching is unique, since it is essentially determined by the temperature- and density-sensitive stellar decay rates of 128I and only marginally affected by the specific stellar neutron flux. For this reason it represents an important test for He-shell burning in AGB stars. The description of the branching by means of the complex stellar scenario reveals a significant sensitivity to the time scales for convection during He shell flashes, thus providing constraints for this phenomenon. The s-process ratio 128Xe/130Xe deduced from stellar models allows for a (9+-3)% p-process contribution to solar 128Xe, in agreement with the Xe-S component found in meteoritic presolar SiC grains.Comment: 24 pages, 9 figures, accepted for publication in Astophysical Journa

Accelerating the LSTRS Algorithm

In a recent paper [Rojas, Santos, Sorensen: ACM ToMS 34 (2008), Article 11] an efficient method for solvingthe Large-Scale Trust-Region Subproblem was suggested which is based on recasting it in terms of a parameter dependent eigenvalue problem and adjusting the parameter iteratively. The essential work at each iteration is the solution of an eigenvalue problem for the smallest eigenvalue of the Hessian matrix (or two smallest eigenvalues in the potential hard case) and associated eigenvector(s). Replacing the implicitly restarted Lanczos method in the original paper with the Nonlinear Arnoldi method makes it possible to recycle most of the work from previous iterations which can substantially accelerate LSTRS

Characterization of the Cholesterol Biosynthetic Pathway in Dioscorea Transversa

Cholesterol is the precursor of bioactive plant metabolites such as steroidal saponins. An Australian plant, Dioscorea transversa, produces only two steroidal saponins: 1β-hydroxyprotoneogracillin and protoneogracillin. Here, we used D. transversa as a model in which to elucidate the biosynthetic pathway to cholesterol, a precursor to these compounds. Preliminary transcriptomes of D. transversa rhizome and leaves were constructed, annotated, and analyzed. We identified a novel sterol side-chain reductase as a key initiator of cholesterol biosynthesis in this plant. By complementation in yeast, we determine that this sterol side-chain reductase reduces Δ24,28 double bonds required for phytosterol biogenesis as well as Δ24,25 double bonds. The latter function is believed to initiate cholesterogenesis by reducing cycloartenol to cycloartanol. Through heterologous expression, purification, and enzymatic reconstitution, we also demonstrate that the D. transversa sterol demethylase (CYP51) effectively demethylates obtusifoliol, an intermediate of phytosterol biosynthesis and 4-desmethyl-24,25-dihydrolanosterol, a postulated downstream intermediate of cholesterol biosynthesis. In summary, we investigated specific steps of the cholesterol biosynthetic pathway, providing further insight into the downstream production of bioactive steroidal saponin metabolites

Probing Plasmodium falciparum sexual commitment at the single-cell level

Background: Malaria parasites go through major transitions during their complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel the program inducing sexual differentiation in Plasmodium falciparum. Parasites have to make this essential life-cycle decision in preparation for human-to-mosquito transmission. Methods: By combining transcriptional profiling with quantitative imaging and genetics, we defined a transcriptional signature in sexually committed cells. Results: We found this transcriptional signature to be distinct from general changes in parasite metabolism that can be observed in response to commitment-inducing conditions. Conclusions: This proof-of-concept study provides a template to capture transcriptional diversity in parasite populations containing complex mixtures of different life-cycle stages and developmental programs, with important implications for our understanding of parasite biology and the ongoing malaria elimination campaign

TB/HIV integration at primary care level: A quantitative assessment at 3 clinics in Johannesburg, South Africa

Background. In 2004 the World Health Organization (WHO) released the Interim Policy on Collaborative TB/HIV activities. According to the policy, for people living with HIV (PLWH), activities include intensified case finding, isoniazid preventive therapy (IPT) and infection control. For TB patients, activities included HIV counselling and testing (HCT), prevention messages, and cotrimoxazole preventive therapy (CPT), care and support, and antiretroviral therapy (ART) for those with HIV-associated TB. While important progress has been made in implementation, targets of the WHO Global Plan to Stop TB have not been reached. Objective. To quantify TB/HIV integration at 3 primary healthcare clinics in Johannesburg, South Africa. Methods. Routinely collected TB and HIV data from the HCT register, TB ‘suspect’ register, TB treatment register, clinic files and HIV electronic database, collected over a 3-month period, were reviewed. Results. Of 1 104 people receiving HCT: 306 (28%) were HIV-positive; a CD4 count was documented for 57%; and few received TB screening or IPT. In clinic encounters among PLWH, 921 (15%) had documented TB symptoms; only 10% were assessed by smear microscopy, and few asymptomatic PLWH were offered IPT. Infection control was poorly documented and implemented. HIV status was documented for 155 (75%) of the 208 TB patients; 90% were HIV-positive and 88% had a documented CD4 count. Provision of CPT and ART was poorly documented. Conclusion. The coverage of most TB/HIV collaborative activities was below Global Plan targets. The lack of standardised recording tools and incomplete documentation impeded assessment at facility level and limited the accuracy of compiled data

Calibration of the channel that determines the omega-hydroxylation regiospecificity of cytochrome P4504A1 - Catalytic oxidation of 12-halododecanoic acids

The fatty acid omega-hydroxylation regiospecificity of CYP4 enzymes may result from presentation of the terminal carbon to the oxidizing species via a narrow channel that restricts access to the other carbon atoms. To test this hypothesis, the oxidation of 12-iodo-, 12-bromo-, and 12-chlorododecanoic acids by recombinant CYP4A1 has been examined. Although all three 12-halododecanoic acids bind to CYP4A1 with similar dissociation constants, the 12-chloro and 12-bromo fatty acids are oxidized to 12-hydroxydodecanoic acid and 12-oxododecanoic acid, whereas the 12-iodo analogue is very poorly oxidized. Incubations in (H2O)-O-18 show that the 12-hydroxydodecanoic acid oxygen derives from water, whereas that in the aldehyde derives from O-2. The alcohol thus arises from oxidation of the halide to an oxohalonium species that is hydrolyzed by water, whereas the aldehyde arises by a conventional carbon hydroxylation-elimination mechanism. No irreversible inactivation of CYP4A1 is observed during 12-halododecanoic acid oxidation. Control experiments show that CYP2E1, which has an omega-1 regiospecificity, primarily oxidizes 12-halododecanoic acids to the omega-aldehyde rather than alcohol product. Incubation of CYP4A1 with 12,12-[H-2](2)-12-chlorododecanoic acid causes a 2-3-fold increase in halogen versus carbon oxidation. The fact that the order of substrate oxidation (Br > Cl >> I) approximates the inverse of the intrinsic oxidizability of the halogen atoms is consistent with presentation of the halide terminus via a channel that accommodates the chloride and bromide but not iodide atoms, which implies an effective channel diameter greater than 3.90 angstrom but smaller than 4.30 angstrom

CYP199A4 catalyses the efficient demethylation and demethenylation of para-substituted benzoic acid derivatives

The cytochrome P450 enzyme CYP199A4, from Rhodopseudomonas palustris strain HaA2, can efficiently demethylate 4-methoxybenzoic acid via hemiacetal formation and subsequent elimination of formaldehyde. Oxidative demethylation of a methoxy group para to the carboxyl moiety is strongly favoured over reaction at one in the ortho or meta positions. Dimethoxybenzoic acids containing a para-methoxy group were also efficiently demethylated exclusively at the para position. The presence of additional methoxy substituents reduces the substrate binding affinity and the activity compared to 4-methoxybenzoic acid. The addition of the smaller hydroxy group to the ortho or meta positions or of a nitrogen heteroatom in the aromatic ring of the 4-methoxybenzoate skeleton was better tolerated by the enzyme and these analogues were also readily demethylated. There was no evidence of methylenedioxy ring formation with 3-hydroxy-4-methoxybenzoic acid, an activity which is observed with certain plant CYP enzymes with analogous substrates. CYP199A4 is also able to deprotect the methylenedioxy group of 3,4-(methylenedioxy)benzoic acid to yield 3,4-dihydroxybenzoic acid and formic acid. This study defines the substrate range of CYP199A4 and reveals that substrates without a para substituent are not oxidised with any significant activity. Therefore para-substituted benzoic acids are ideal substrate scaffolds for the CYP199A4 enzyme and will aid in the design of optimised probes to investigate the mechanism of this class of enzymes. They also allow an assessment of the potential of CYP199A4 for synthetic biocatalytic processes involving selective oxidative demethylation or demethenylation.Tom Coleman, Rebecca R. Chao, John B. Bruning, James J. De Voss and Stephen G. Bel

Dynamic Scaling of Magnetic Flux Noise Near the KTB Transition in Overdamped Josephson Junction Arrays

We have used a dc Superconducting QUantum Interference Device to measure the magnetic flux noise generated by the equilibrium vortex density fluctuations associated with the Kosterlitz-Thouless-Berezinskii (KTB) transition in an overdamped Josephson junction array. At temperatures slightly above the KTB transition temperature, the noise is white for $f<f_\xi$ and scales as $1/f$ for $f>f_\xi$. Here $f_\xi\propto\xi^{-z}$, where $\xi$ is the correlation length and $z$ is the dynamic exponent. Moreover, when all frequencies are scaled by $f_\xi$, data for different temperatures and frequencies collapse on to a single curve. In addition, we have extracted the dynamic exponent $z$ and found $z=1.98\pm0.03$.Comment: 5 pages, LaTeX (REVTeX) format, requires epsfig and amstex style files. 3 figures included. Tentatively scheduled for publication in Physical Review Letters, 18 March, 199