PLP - A Package for Parametric Programming

This paper is one of the series of 11 Working Papers presenting the software for interactive decision support and software tools for developing decision support system. These products constitute the outcome of the contracted study agreement between the System and Decision Sciences Program at IIASA and several Polish scientific institutions. The theoretical part of these results is presented in the IIASA Working Paper WP-88-071 entitled "Theory, Software and Testing Examples in Decision Support Systems" which contains the theoretical and methodological backgrounds of the software systems developed within the project. This paper presents the PLP package for parametric linear programming. This package constitutes the extension to MINOS, the well known linear and nonlinear programming code developed at Stanford University, and uses the MINOS as the solver of optimization problems. The PLP gives a complete parametric programming analysis for one, or more, of the following vectors: cost, rhs and bounds. In the same run several problems of this kind can be solved and for each, the starting point may be the original optimal solution obtained in the last problem. This property makes the PLP especially interesting for multiple criteria analysis using the reference point approach

G Protein-Coupled Odorant Receptors: from sequence to structure

Odorant receptors (ORs) are the largest sub-family within Class-A G Protein-Coupled Receptors (GPCRs). No experimental structural data of any OR is available to date and atomic-level insights are likely to be obtained by means of molecular modeling. In this article, we critically align sequences of ORs with those GPCRs for which a structure is available. Here, an alignment consistent with available site-directed mutagenesis data on various ORs is proposed. Using this alignment, the choice of the template is deemed rather minor for identifying residues that constitute the wall of the binding cavity or those involved in G-protein recognition

Visible camera cryostat design and performance for the SuMIRe Prime Focus Spectrograph (PFS)

We describe the design and performance of the SuMIRe Prime Focus Spectrograph (PFS) visible camera cryostats. SuMIRe PFS is a massively multi-plexed ground-based spectrograph consisting of four identical spectrograph modules, each receiving roughly 600 fibers from a 2394 fiber robotic positioner at the prime focus. Each spectrograph module has three channels covering wavelength ranges 380~nm -- 640~nm, 640~nm -- 955~nm, and 955~nm -- 1.26~um, with the dispersed light being imaged in each channel by a f/1.07 vacuum Schmidt camera. The cameras are very large, having a clear aperture of 300~mm at the entrance window, and a mass of $\sim$280~kg. In this paper we describe the design of the visible camera cryostats and discuss various aspects of cryostat performance

Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated Topoisomerase I to promote genome stability

Peer reviewedPublisher PD

Analysis of sex steroids in human tears using LC-MS and GC-MS: considerations and developments to improve method sensitivity and accuracy

Sex steroids play a role in regulation of tear film function and may exert their action locally at the ocular surface. However, measurement of sex steroids in tears is difficult due to small-volume tear samples and very low concentrations of the hormones. This short communication highlights what has been achieved to date in the analysis of tear sex steroids using ultra-performance LC-MS (UPLC-MS) as previously published, and reports further and more recent investigations toward optimising mass spectrometry method sensitivity and accuracy. The published UPLC-MS method successfully measured progesterone, androsterone glucuronide and 5α-androstane-3α,17β-diol in pooled basal tears of postmenopausal women, and fourteen sex steroid standards in methanol. Limitations included sub-optimal limits of detection (LOD) and lower limits of quantification (LLOQ) for some analytes (particularly oestrogens), exclusion of sample matrix effects and no use of internal standards. This update reports on further experiments carried out to improve sensitivity and accuracy. Sample matrix effects, internal standard spiking, and derivatisation with dansyl chloride and oximes were investigated. Dansylation significantly improved the LOD and LLOQ of oestrogens and their metabolites, by a factor of 10 for oestradiol and a factor of 5 for oestrone, but sensitivity of this updated method is not sufficient however for analysis of these oestrogens in human tears. Using gas chromatography-mass spectrometry (GC-MS) as an alternative technique to LC-MS, improved sensitivity for derivatised oestradiol is reported. This work demonstrates the need to develop higher sensitivity methods and points researchers towards specific MS ionisation techniques for future analysis of sex steroids in tears, in order to progress current understanding of the role of sex steroids in tear function and dry eye

Mapping the Corneal Sub-Basal Nerve Plexus in Orthokeratology Lens Wear Using in vivo Laser Scanning Confocal Microscopy

PURPOSE. This study was designed to map the sub-basal nerve plexus (SBNP) in the cornea of orthokeratology (OK) lens wearers. METHODS. Laser scanning confocal microscopy (LSCM) was performed in vivo on three subjects: a non-lens wearer and two OK lens wearers. Scans were performed on the right eye while the left eye fixated a moving target. A total of 575, 430, and 676 contiguous images of the SBNP were taken from the non-lens wearing and the OK lens wearing subjects, respectively, and used to construct maps of the central to midperipheral SBNP. RESULTS. In the non-lens wearing eye, nerves radiated towards a whorl-like complex centered nasally and inferiorly in an overall pattern consistent with previously reported studies. In the OK lens wearing eyes, this whorl pattern was absent, replaced by a tortuous network of nerve fibers centrally, and thicker curvilinear fibers mid-peripherally, particularly in the nasal, inferior, and temporal regions. CONCLUSIONS. This study maps the corneal SBNP in OK lens wearers and provides compelling evidence that OK lens wear alters the normal SBNP distribution observed in healthy, nonlens wearing eyes. (Invest Ophthalmol Vis Sci

Paving the way for research findings: writers' rhetorical choices in education and applied linguistics

Notwithstanding the existence of previous investigations into how research results are presented in different academic disciplines, fewer studies have looked into how authors pave the way for their results, the interdisciplinary differences in ‘result pavements’, and the interconnections between their communicative functions and linguistic choices. Using the techniques of genre analysis, I have analyzed two corpora of research reports in applied linguistics and education in order to identify the possible ways in which experienced writers schematically pave the way for their findings. Using evidence based on authentic research articles, this study demonstrates how writers set the stage for their research results by (i) demonstrating their control of the structure and flow of result-related information, (ii) connecting past research with a current finding while furnishing pertinent background elements that lead the readership progressively to specific findings, (iii) regenerating readers’ interest in their initial research purposes, and (iv) deploying locatives to embed results in a ‘space-saving strategy’ aimed at presenting an abridged Results section. I have also analyzed interdisciplinary differences in the frequencies of these rhetorical steps and the range of intricate linguistic mechanisms employed by authors as communicative resources in each step to establish a smooth rhetorical transition that sets the stage for their research results

Targeting of SUMO substrates to a Cdc48-Ufd1-Npl4 segregase and STUbL pathway in fission yeast

In eukaryotes, the conjugation of proteins to the small ubiquitin-like modifier (SUMO) regulates numerous cellular functions. A proportion of SUMO conjugates are targeted for degradation by SUMO-targeted ubiquitin ligases (STUbLs) and it has been proposed that the ubiquitin-selective chaperone Cdc48/p97-Ufd1-Npl4 facilitates this process. However, the extent to which the two pathways overlap, and how substrates are selected, remains unknown. Here we address these questions in fission yeast through proteome-wide analyses of SUMO modification sites. We identify over a thousand sumoylated lysines in a total of 468 proteins and quantify changes occurring in the SUMO modification status when the STUbL or Ufd1 pathways are compromised by mutations. The data suggest the coordinated processing of several classes of SUMO conjugates, many dynamically associated with centromeres or telomeres. They provide new insights into subnuclear organization and chromosome biology, and, altogether, constitute an extensive resource for the molecular characterization of SUMO function and dynamics

First record of Rhabdoceras suessi (Ammonoidea, Late Triassic) from the Transylvanian Triassic Series of the Eastern Carpathians (Romania) and a review of its biochronology, paleobiogeography and paleoecology

Abstract The occurrence of the heteromorphic ammonoid Rhabdoceras suessi Hauer, 1860, is recorded for the first time in the Upper Triassic limestone of the Timon-Ciungi olistolith in the Rarău Syncline, Eastern Carpathians. A single specimen of Rhabdoceras suessi co-occurs with Monotis (Monotis) salinaria that constrains its occurrence here to the Upper Norian (Sevatian 1). It is the only known heteromorphic ammonoid in the Upper Triassic of the Romanian Carpathians. Rhabdoceras suessi is a cosmopolitan species widely recorded in low and mid-paleolatitude faunas. It ranges from the Late Norian to the Rhaetian and is suitable for high-resolution worldwide correlations only when it co-occurs with shorter-ranging choristoceratids, monotid bivalves, or the hydrozoan Heterastridium. Formerly considered as the index fossil for the Upper Norian (Sevatian) Suessi Zone, by the latest 1970s this species lost its key biochronologic status among Late Triassic ammonoids, and it generated a controversy in the 1980s concerning the status of the Rhaetian stage. New stratigraphic data from North America and Europe in the subsequent decades resulted in a revised ammonoid biostratigraphy for the uppermost Triassic, the Rhaetian being reinstalled as the topmost stage in the current standard timescale of the Triassic. The geographic distribution of Rhabdoceras is compiled from published worldwide records, and its paleobiogeography and paleoecology are discussed

Environmental chemical stressors as epigenome modifiers:a new horizon in assessment of toxicological effects

In eukaryotic cells, chromatin transformation from euchromatin into heterochromatin as a means of controlling gene expression and replication has been known as the ?accessibility hypothesis?. The interplay of epigenetic changes including histone modifications, DNA methylation, RNA interference (RNAi) and other functional epigenetic components are intricate. It is believed that these changes are well-programmed, inherited and can be modified by environmental contaminant stressors. Environmentally-driven epigenetic alterations during development, e.g. embryonic, foetal or neonatal stage, may influence disease susceptibility in adulthood. Therefore, understanding how epigenome modifications develop in response to environmental chemicals and, how epigenetic-xenobiotic interactions influence human health will shed new insights into gene-environment interactions in the epidemiology of several diseases including cancer. In this review, we consider studies of chemical modifiers including nutritional and xenobiotic effects on epigenetic components in vitro or in vivo. By examining the most-studied epigenome modifications and how their respective roles are interlinked, we highlight the central role of xenbiotic-modified epigenetic mechanisms. A major requirement will be to study and understand effects following environmentally-relevant exposures. We suggest that the study of epigenetic toxicology will open up new opportunities to devise strategies for the prevention or treatment of at-risk populations