Discovery of Novel Receptors for Lipid Mediators - a study leading to the identification of receptors involved in metabolism and the immune system

Intercellular communication is of crucial importance in regulating physiology and G-protein coupled receptors (GPCRs) have evolved as an important mechanism in this process. Of the approximately 800 human GPCRs, about 160 are still considered to be “orphan” receptors for which an endogenous ligand remains to be identified. Since an estimated 50% of all clinical drugs act on 30 known GPCRs, the remaining orphan receptors provide excellent, potential new drug targets. Orphan receptors were selected using known receptor sequences as templates and subsequently cloned into expressing plasmids that were then stably transfected into luciferase-based reporter cells. An orphan receptor was found to be the second GPCR, BLT2, activated by the pro-inflammatory molecule leukotriene B4. Through use of a library of orphan receptors, potential ligands were screened for activity by applying reversed pharmacology. This approach led to the discovery of the novel receptor (FFA1R) for medium- to long-chain free fatty acids, previously known as the orphan receptor GPR40. Significantly, this receptor was found to be expressed on e.g. pancreatic beta-cells and to mediate the fatty acid augmentation of glucose stimulated insulin secretion. The clinically used anti-diabetic drugs, thiazolidinediones, also activate FFA1R expressed on reporter cells. It was discovered that FFA2R and FFA3R (GPR43 and GPR41) are activated by short-chain fatty acids (SCFAs). Being abundantly expressed on blood leukocytes, FFA2R may act as the mediator in SCFA-induced immune suppression in the intestinal tract. A recent proposal links FFA3R to leptin secretion by adipose tissue

The Twisted String Vertex Algorithm Applied to the Z2Z_2-Twisted Scalar String Four Vertex

Recently an algorithm was found by means of which one can calculate terms at arbitrary oscillator level in the four-Ramond vertex obtained by sewing. Here we show that this algorithm is applicable also to the case of ${\bf Z}_2$-twisted scalars and derive the full propagator for scalars on the Riemann sphere with two branch cuts. The relation to similar results previously derived in the literature by other means is discussed briefly.Comment: 18 pages (LaTeX), G\"oteborg ITP 94-

An Algorithm for Computing Four-Ramond Vertices at Arbitrary Level

We perform the sewing of two (dual) Ramond reggeon vertices and derive an algorithm by means of which the so obtained four-Ramond reggeon vertex may be explicitly computed at arbitrary oscillator (mass) level. A closed form of the four-vertex is then deduced on the basis of a comparison to all terms obtained by sewing that contain only level zero and one oscillators. Results are presented for both complex fermions and for the previously studied case of real fermions.Comment: 31 pages, Latex, Goteborg ITP 92-5

Skogliga grunddata

Skogliga grunddata är digitala raster-kartor som beskriver tillståndet i skog och mark. De skogliga variablerna är i huvudsak framtagna genom en sambearbetning av laserdata från Lantmäteriets nationella laserskanning och provytor från Riksskogstaxeringen. De digitala kartorna som beskriver skogsmarken är till stor hjälp för privata skogsägare, skogstjänstemän, myndigheter, m fl. Data är dels tillgängligt för gratis nedladdning, men det finns även möjligheter att titta på kartorna med hjälp av interaktiva webverktyg. Lantmäteriets laserskanning påbörjades 2009 och fortgår än idag. Endast delar av fjällkedjan återstår. Grundtanken med laserskanningen var att få en bra höjdmodell över landet. En bra höjdmodell ger stor nytta vid all samhällsplanering, men är även till hjälp vid klimatanpassning. Riksskogstaxeringen samlar årligen in data om Sveriges skogstillstånd med permanenta och tillfälliga provytor. Dessa provytor är koordinatsatta och är väl spridda över hela landet. I detta projekt har provytor från Riksskogstaxeringen kombinerats med laserdata för att ta fram rasterkartor med uppgifter om virkesvolym, grundyta, medelhöjd, medeldiameter och trädbiomassa

Evolutionary prediction of medicinal properties in the genus <i>Euphorbia </i>L.

The current decrease of new drugs brought to the market has fostered renewed interest in plant-based drug discovery. Given the alarming rate of biodiversity loss, systematic methodologies in finding new plant-derived drugs are urgently needed. Medicinal uses of plants were proposed as proxy for bioactivity, and phylogenetic patterns in medicinal plant uses have suggested that phylogeny can be used as predictive tool. However, the common practice of grouping medicinal plant uses into standardised categories may restrict the relevance of phylogenetic predictions. Standardised categories are mostly associated to systems of the human body and only poorly reflect biological responses to the treatment. Here we show that medicinal plant uses interpreted from a perspective of a biological response can reveal different phylogenetic patterns of presumed underlying bioactivity compared to standardised methods of medicinal plant use classification. In the cosmopolitan and pharmaceutically highly relevant genus Euphorbia L., identifying plant uses modulating the inflammatory response highlighted a greater phylogenetic diversity and number of potentially promising species than standardised categories. Our interpretation of medicinal plant uses may therefore allow for a more targeted approach for future phylogeny-guided drug discovery at an early screening stage, which will likely result in higher discovery rates of novel chemistry with functional biological activity

State machine-based architecture to control system processes in a hybrid fuel cell electric vehicle

This paper presents the development and implementation of a system supervisory controller in a hydrogen-based fuel cell electric vehicle. The controller's primary function is to ensure the safe control of the fuel cell system processes while facilitating coordination among various subsystems, including the balance of plant subsystems, vehicle control unit, diagnosis unit, and powertrain. The supervisory controller comprises of three primary parts: a State Machine, an Optimal Setpoint Generator, and a Power Limit Calculator. The State Machine, which serves as the central part of the supervisory controller, coordinates the fuel cell system's different operational states, including the complex processes of start-up and shutdown. To maximize the fuel cell system's efficiency and minimize the stack's degradation, the Optimal Setpoint Generator produces the subsystem's setpoints by solving an optimization problem and considering the manufacturer's requirements. The Power Limit Calculator assesses the stack's power output capability and calculates the current setpoint for the DC/DC converter. It then provides this data to the Energy Management System (EMS), which oversees the distribution of power between the fuel cell system and the batteries. The proposed fuel cell system supervisory controller is verified using the Worldwide Harmonized Light Vehicles Test Cycles (WLTC) in a real-world car. The designed control structure is implemented in a prototype hydrogen-based electric car at both PowerCell and CEVT facilities under the framework of the INN-BALANCE Horizon 2020 European project

Challenging claims in the study of migratory birds and climate change

Recent shifts in phenology in response to climate change are well established but often poorly understood. Many animals integrate climate change across a spatially and temporally dispersed annual life cycle, and effects are modulated by ecological interactions, evolutionary change and endogenous control mechanisms. Here we assess and discuss key statements emerging from the rapidly developing study of changing spring phenology in migratory birds. These well-studied organisms have been instrumental for understanding climate-change effects, but research is developing rapidly and there is a need to attack the big issues rather than risking affirmative science. Although we agree poorly on the support for most claims, agreement regarding the knowledge basis enables consensus regarding broad patterns and likely causes. Empirical data needed for disentangling mechanisms are still scarce, and consequences at a population level and on community composition remain unclear. With increasing knowledge, the overall support (‘consensus view’) for a claim increased and between-researcher variability in support (‘expert opinions') decreased, indicating the importance of assessing and communicating the knowledge basis. A proper integration across biological disciplines seems essential for the field's transition from affirming patterns to understanding mechanisms and making robust predictions regarding future consequences of shifting phenologies