Organization of ventral tegmental area projections to the ventral tegmental area-nigral complex in the rat

The ventral tegmental area (VTA) is a nodal link in reward circuitry. Based on its striatal output, it has been subdivided in a caudomedial part which targets the ventromedial striatum, and a lateral part which targets the ventrolateral striatum [Ikemoto S (2007) Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex. Brain Res Rev 56:27-78]. Whether these two VTA parts are interconnected and to what extent the VTA innervates the substantia nigra compacta (SNc) and retrorubral nucleus (RR) are critical issues for understanding information processing in the basal ganglia. Here, VTA projections to the VTA-nigral complex were examined in rats, using Phaseolus vulgaris leucoagglutinin (PHA-L) as anterograde tracer. The results show that the dorsolateral VTA projects to itself, as well as to the dorsal tier of the SNc and RR, largely avoiding the caudomedial VTA. The ventrolateral VTA innervates mainly the interfascicular nucleus. The components of the caudomedial VTA (the interfascicular, paranigral and caudal linear nuclei) are connected with each other. In addition, the caudomedial VTA (especially the paranigral and caudal linear nuclei) innervates the lateral VTA, and, to a lesser degree, the SNc and RR. The caudal pole of the VTA sends robust, bilateral projections to virtually all the VTA-nigral complex, which terminate in the dorsal and ventral tiers. Modest inputs from the medial supramammillary nucleus to ventromedial parts of the VTA-nigral complex were also identified. In double-immunostained sections, PHA-L-labeled varicosities were sometimes found apposed to tyrosine hydroxylase-positive neurons in the ventral mesencephalon. Overall, the results underscore that VTA projections to the VTA-nigral complex are substantial and topically organized. In general, these projections, like the spiralated striato-nigro-striatal loops, display a medial-to-lateral organization. This anatomical arrangement conceivably permits the ventromedial striatum to influence the activity of the lateral striatum. The caudal pole of the VTA appears to be a critical site for a global recruitment of the mesotelencephalic system. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression

Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology is poorly understood. We hypothesized that the circadian clock within the cardiomyocyte influences diurnal variations in myocardial biology. We, therefore, generated a cardiomyocyte-specific circadian clock mutant (CCM) mouse to test this hypothesis. At 12 wk of age, CCM mice exhibit normal myocardial contractile function in vivo, as assessed by echocardiography. Radiotelemetry studies reveal attenuation of heart rate diurnal variations and bradycardia in CCM mice (in the absence of conduction system abnormalities). Reduced heart rate persisted in CCM hearts perfused ex vivo in the working mode, highlighting the intrinsic nature of this phenotype. Wild-type, but not CCM, hearts exhibited a marked diurnal variation in responsiveness to an elevation in workload (80 mmHg plus 1 mu M epinephrine) ex vivo, with a greater increase in cardiac power and efficiency during the dark (active) phase vs. the light (inactive) phase. Moreover, myocardial oxygen consumption and fatty acid oxidation rates were increased, whereas cardiac efficiency was decreased, in CCM hearts. These observations were associated with no alterations in mitochondrial content or structure and modest mitochondrial dysfunction in CCM hearts. Gene expression microarray analysis identified 548 and 176 genes in atria and ventricles, respectively, whose normal diurnal expression patterns were altered in CCM mice. These studies suggest that the cardiomyocyte circadian clock influences myocardial contractile function, metabolism, and gene expression.

Inhibition of C6 rat glioma proliferation by [Ru(2)Cl(Ibp)(4)] depends on changes in p21, p27, Bax/Bcl2 ratio and mitochondrial membrane potential

The ruthenium compound [Ru(2)Cl(Ibp)(4)] (or RuIbp) has been reported to cause significantly greater inhibition of C6 glioma cell proliferation than the parent HIbp. The present study determined the effects of 0-72 h exposure to RuIbp upon C6 cell cycle distribution, mitochondrial membrane potential, reactive species generation and mRNA and protein expression of E2F1, cyclin D1, c-myc, pRb, p21, p27, p53, Ku70, Ku80, Bax, Bcl2, cyclooxygenase 1 and 2 (COX1 and COX2). The most significant changes in mRNA and protein expression were seen for the cyclin-dependent kinase inhibitors p21 and p27 which were both increased (p<0.05). The marked decrease in mitochondrial membrane potential (p<0.01) and modest increase in apoptosis was accompanied by a decrease in anti-apoptotic Bcl2 expression and an increase in pro-apoptotic Bax expression (p<0.05). Interestingly, COX1 expression was increased in response to a significant loss of prostaglandin E(2) production (p<0.001), most likely due to the intracellular action of Ibp. Future studies will investigate the efficacy of this novel ruthenium-ibuprofen complex in human glioma cell lines in vitro and both rat and human glioma cells growing under orthotopic conditions in vivo. (C) 2010 Elsevier Inc. All rights reserved.

The Thyroid Hormone Receptor (TR) beta-Selective Agonist GC-1 Inhibits Proliferation But Induces Differentiation and TR beta mRNA Expression in Mouse and Rat Osteoblast-Like Cells

Previous studies showed anabolic effects of GC-1, a triiodothyronine (T3) analogue that is selective for both binding and activation functions of thyroid hormone receptor (TR) beta 1 over TR alpha 1, on bone tissue in vivo. The aim of this study was to investigate the responsiveness of rat (ROS17/2.8) and mouse (MC3T3-E1) osteoblast-like cells to GC-1. As expected, T3 inhibited cellular proliferation and stimulated mRNA expression of osteocalcin or alkaline phosphatase in both cell lineages. Whereas equimolar doses of T3 and GC-1 equally affected these parameters in ROS17/2.8 cells, the effects of GC-1 were more modest compared to those of T3 in MC3T3-E1 cells. Interestingly, we showed that there is higher expression of TR alpha 1 than TR beta 1 mRNA in rat (similar to 20-90%) and mouse (similar to 90-98%) cell lineages and that this difference is even higher in mouse cells, which highlights the importance of TR alpha 1 to bone physiology and may partially explain the modest effects of GC-1 in comparison with T3 in MC3T3-E1 cells. Nevertheless, we showed that TR beta 1 mRNA expression increases (similar to 2.8- to 4.3-fold) as osteoblastic cells undergo maturation, suggesting a key role of TR beta 1 in mediating T3 effects in the bone forming cells, especially in mature osteoblasts. It is noteworthy that T3 and GC-1 induced TR beta 1 mRNA expression to a similar extent in both cell lineages (similar to 2- to 4-fold), indicating that both ligands may modulate the responsiveness of osteoblasts to T3. Taken together, these data show that TR beta selective T3 analogues have the potential to directly induce the differentiation and activity of osteoblasts.

Age and geochemistry of mantle peridotites and diorite dykes from the Baldissero body: Insights into the Paleozoic-Mesozoic evolution of the Southern Alps

Trace element and isotopic data obtained for mantle spinel Iherzolites and diorite dykes from the Baldissero massif (Ivrea-Verbano Zone, Western Italy) provide new, valuable constraints on the petrologic and geodynamic evolution of the Southern Alps in Paleozoic to Mesozoic times. Whole rock and mineral chemistry indicates that Baldissero Iherzolites can be regarded as refractory mantle residues following limited melt extraction. In particular, the Light Rare Earth Elements (LREE)-depleted and fractionated compositions of whole rock and clinopyroxene closely match modelling results for refractory residues after low degrees (similar to 4-5%) of near-fractional melting of depleted mantle, possibly under garnet-facies conditions. Following this, the peridotite sequence experienced subsolidus re-equilibration at lithospheric spinel-facies conditions and intrusion of several generations of dykes. However, Iherzolites far from dykes show very modest metasomatic changes, as evidenced by the crystallisation of accessory titanian pargasite and the occurrence of very slight enrichments in highly incompatible trace elements (e.g. Nb). The Re-Os data for Iherzolites far from the dykes yield a 376 Ma (Upper Devonian) model age that is considered to record a partial melting event related to the Variscan orogenic cycle s.l. Dioritic dykes cutting the mantle sequence have whole rock, clinopyroxene and plagioclase characterised by high radiogenic Nd and low radiogenic Sr, which point to a depleted to slightly enriched mantle source. Whole rock and mafic phases of diorites have high Mg# values that positively correlate with the incompatible trace element concentrations. The peridotite at the dyke contact is enriched in orthopyroxene, iron and incompatible trace elements with respect to the Iherzolites far from dykes. Numerical simulations indicate that the geochemical characteristics of the diorites can be explained by flow of a hydrous, silica-saturated melt accompanied by reaction with the ambient peridotite and fractional crystallisation. The composition of the more primitive melts calculated in equilibrium with the diorite minerals show tholeiitic to transitional affinity. Internal Sm-Nd, three-point isochrons obtained for two dykes suggest an Upper Triassic-Lower Jurassic emplacement age (from 204 31 to 198 29 Ma). Mesozoic igneous events are unknown in the southern Ivrea-Verbano Zone (IVZ), but the intrusion of hydrous melts, mostly silica-saturated, have been well documented in the Finero region, i.e. the northernmost part of IVZ and Triassic magmatism with calc-alkaline to shoshonitic affinity is abundant throughout the Central-Eastern Alps. The geochemical and chronological features of the Baldissero diorites shed new light on the geodynamic evolution of the Southern Alps before the opening of the Jurassic Tethys. (C) 2010 Elsevier B.V. All rights reserved.

A two-component system, an anti-sigma factor and two paralogous ECF sigma factors are involved in the control of general stress response in Caulobacter crescentus

The extracytoplasmic function sigma factor sigma(T) is the master regulator of general stress response in Caulobacter crescentus and controls the expression of its paralogue sigma(U). In this work we showed that PhyR and NepR act, respectively, as positive and negative regulators of sigma(T) expression and function. Biochemical data also demonstrated that NepR directly binds sigma(T) and the phosphorylated form of PhyR. We also described the essential role of the histidine kinase gene CC3474, here denominated phyK, for expression of sigma(T)-dependent genes and for resistance to stress conditions. Additionally, in vivo evidence of PhyK-dependent phosphorylation of PhyR is presented. This study also identified a conserved cysteine residue (C95) located in the periplasmic portion of PhyK that is crucial for the function of the protein. Furthermore, we showed that PhyK, PhyR and sigma(T) regulate the same set of genes and that sigma(T) apparently directly controls most of its regulon. In contrast, sigma(U) seems to have a very modest contribution to the expression of a subset of sigma(T)-dependent genes. In conclusion, this report describes the molecular mechanism involved in the control of general stress response in C. crescentus.

C-glycosyl flavones from Peperomia blanda

The methanol extract from aerial parts of the Peperomia blanda (Piperaceae) yielded two C-glycosyl-flavones. Their structures were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR, chemical transformation and comparison with the related known compounds. The structure of the new flavonoids were established as 4`-methoxy-vitexin 7-O-beta-D-xylopyranoside (1) (7-O-beta-D-xylopyranosyl-8-C-beta-D-glucopyranosyl-4`-methoxy-apigenin) and vicenin-2 (2). The antioxidant activity of both compounds was investigated using the DPPH assay. Both compounds showed only modest activity, with IC50 values of 357.2 mu M for 1, and 90.5 mu M for 2. (C) 2008 Elsevier B.V. All rights reserved.

Al-Mahdi - Gestalt och budskap : En litteraturstudie jämförande sudanesisk Mahdi och indisk Mahdi inom islam

Followers of three world religions, Judaism, Christianity and Islam are waiting for the Messiah. Muslims are even waiting for aspiritual leader al-Mahdi. Two different persons claimed the title of al-Mahdi, at the end of the nineteenth century. Theyappeared almost at the same time, at the totally different places of the earth, with a completely different message and underthe rule of the British colonial power. The aim of the study is to compare the both religious figures, Mirza Ghulam Ahmadfrom India and Muhammad Ahmad from Sudan regarding their different messages, to illustrate the social, political andreligious factors that lead to the entirely different profile and image of these two men and how their organizations havedeveloped after their death up till today. The result shows that the Sudanese Mahdi Muhammad Ahmad claimed hisMahdiship in the year 1881. He became a political leader in a time when Sudan was under the rule of a colonial power. Hetook advantage of the religion for personal purposes and tried to liberate his native country Sudan. The contemporaryMuslim clergy criticized him for his claim because the content of the Hadith traditions did not support his claim ofMahdiship. He maintained his sole right for the interpretation of religion and of the laws of Sharia. He made changes even inthe chief pillars of Islam by asserting that Jehad with sword was more imperative than the pilgrimage journey to Mecca. Heasserted that the Prophet Muhammad himself had entrusted him to launch the holy war against the non-believers. He hadimmense ambitions which were never fulfilled since he suddenly died four years after his claim for Mahdiship, in June 1885.This day his followers are organized as a political party in Sudan with a modest roll in the Sudanese politics. The IndianMahdi Mirza Ghulam Ahmad claimed in 1889 to be Mahdi, Mujaddid, Muhaddas, Messiah and a Prophet at a time of socialand political peace, though Islam as a religion was firmly pushed by the Hindu and Christian missionaries. He had no politicalambitions at all and was utterly loyal to the British colonial power. His mission was to crush the Cross and to demonstrateIslam’s excellence over all the religions of the world through overwhelming arguments. He proclaimed that Jesus was humanand a Prophet and not the son of God. Jesus survived from the cross and died a natural death after he had lived for manyyears. Ahmad claimed that God had commanded him to put stop to the religious wars. The contemporary Muslim clergyblamed him for being an imposter, melancholic and hypochondriac who had self invented the divine revelations. He died year1908, nineteen years after his claim and the communion he found is established today in more than hundred countries of theworld. Reasons for the breakdown of mission of the Sudanese Mahdi were that his objectives were political and he challengedthe colonial power with the sword. Another decisive factor was his sudden death merely four years after the beginning of hismission. Reasons for the success of Indian Mahdi were that his objectives were purely religious and he was wholly loyal to theforeign government. He survived nineteen years after the beginning of his mission which made it possible for him to create acommunion based on solid grounds. His followers continued on the same path and never engaged in local politics where everthey lived. For further studies it will be of great interest to study the life of Mirza Ghulam Ahmad and objectively examine thearguments he presented in support of his divine appointment. Furthermore it is enriching to study the organization andactivities of the Ahmadiyya Muslim community to explore if they are in accordance with the basic principles of Ahmad.

Estetiska lärprocesser och Skapande skola : Intervjustudie med verksamhetsledare, pedagoger och kulturarbetare

Syftet med studien har varit att undersöka om en nationellt stödd satsning som Skapande skola-projekt integrerar estetiska lärprocesser i skolans verksamhet? Likaså är syftet att få en djupare insikt om vad estetiska lärprocesser är i skolans kontext.Studien bygger på intervjuer med verksamhetsledare, pedagoger och kulturarbetare som arbetat med Skapande skola-projekt i tre olika kommuner. Litteraturstudier belyser tidigare forskning om estetiska lärprocesser, där modest och radikal estetik är två begrepp som är centrala i studien. Det empiriska materialet består av nio intervjuer.Resultatet visar att Skapande skola-projekt kan integrera estetiska lärprocesser i skolan. Analysen genomfördes med en specifik analysmodell som prövades och utvecklades, i avsikt att visa hur Skapande skola-projekten positionerar sig i skolan. Resultatet problematiseras utifrån tidigare forskning och visar också att innebörden i begreppet estetiska lärprocesser är diffust och att tolkningen av begreppet omfattar både en modest och radikal syn på estetiken.Studien visar också ett antal viktiga faktorer för att möjliggöra en fortsatt utveckling i arbetet med att integrera estetiska lärprocesser i skolan. Dessa faktorer är ämnesövergripande arbete, tydliga målformuleringar utifrån lärandeperspektiv och tid för att planera och organisera arbetet. Dessutom ger nationellt initierade satsningar som Skapande skola ekonomiska förutsättningar i utvecklingsarbetet.

Utbrändhet som arbetsskada och motståndsberättelse

Burnout as occupational injury and narrative of resistance During the last years of the 1990s and the first years of the 2000s, burnout was a common diagnosis for sick listing in Sweden. That burnout is directly related to working life was acknowledged by medical experts as well as in the public debate. The number of applications for occupational compensation due to social and organizational factors in work rose from a very modest degree to nearly a forth of the claims among occupational diseases. In this article 48 individual claims for compensation in cases of burnout as occupational disease are analyzed as narratives of resistance. In this respect they are seen as alternative accounts of risk in working life, but also as narratives about resistance. The concept, narratives of resistance, is used to understand the claimants’ argumentation for rights to compensation, as well as how the claimants draw upon public narratives of societal transformation to understand how they themselves have become ill from occupations that normally are not thought to be hazardous. One conclusion from the analysis is that the claimants regard their illness as the resistance of the body against changes in society and working life. 

Wickedness, Governance and Collective Sanctions: : Can Corruption be Tamed?

Tackling a problem requires mostly, an ability to read it, conceptualize it, represent it, define it, and then applying the necessary mechanisms to solve it. This may sound self-evident except when the problem to be tackled happens to be “complex, “ “ill-structured,” and/or “wicked.” Corruption is one of those kinds of problems. Both in its global and national manifestations it is ill-structured. Where it is structural in nature, endemic and pervasive, it is perhaps even wicked. Qualities of the kind impose modest expectations regarding possibilities of any definitive solution to this insidious phenomenon. If so, it may not suffice to address the problem of corruption using existing categories of law and/or good governance, which overlook the “long-term memory” of the collective and cultural specific dimensions of the subject. Such socio-historical conditions require focusing on the interactive and self-reproducing networks of corruption and attempting to ‘subvert’ that phenomenon’s entire matrix. Concepts such as collective responsibility, collective punishment and sanctions are introduced as relevant categories in the structural, as well as behavioral, subversion of some of the most prevalent aspects of corruption. These concepts may help in the evolving of a new perspective on corruption fighting strategies.

Determinants and effects of central bank independence reforms

This thesis consists of four empirically oriented papers on central bank independence (CBI) reforms.    Paper [1] is an investigation of why politicians around the world have chosen to give up power to independent central banks, thereby reducing their ability to control the economy. A new data-set, including the possible occurrence of CBI-reforms in 132 countries during 1980-2005, was collected. Politicians in non-OECD countries were more likely to delegate power to independent central banks if their country had been characterized by high variability in inflation and if they faced a high probability of being replaced. No such effects were found for OECD countries.    Paper [2], using a difference-in-difference approach, studies whether CBI reform matters for inflation performance. The analysis is based on a dataset including the possible occurrence of CBI-reforms in 132 countries during the period of 1980-2005. CBI reform is found to have contributed to bringing down inflation in high-inflation countries, but it seems unrelated to inflation performance in low-inflation countries.    Paper [3] investigates whether CBI-reforms are important in reducing inflation and maintaining price stability, using a random-effects random-coefficients model to account for heterogeneity in the effects of CBI-reforms on inflation. CBI-reforms are found to have reduced inflation on average by 3.31 percent, but the effect is only present when countries with historically high inflation rates are included in the sample. Countries with more modest inflation rates have achieved low inflation without institutional reforms that grant central banks more independence, thus undermining the time-inconsistency theory case for CBI. There is furthermore no evidence that CBI-reforms have contributed to lower inflation variability    Paper [4] studies the relationship between CBI and a suggested trade-off between price variability and output variability using data on CBI-levels, and data the on implementation dates of CBI-reforms. The results question the existence of such a trade-off, but indicate that there may still be potential gains in stabilization policy from CBI-reforms.

Existential issues in surgical care : Nurses’ experiences and attitudes in caring for patients with cancer

The overall aim of this thesis was to explore surgical nurses’ experiences of being confronted with patients’ existential issues when caring for patients with cancer, and to examine whether an educational intervention may support nurses in addressing existential needs when caring for patients with cancer. Previously recorded discussions from supervision sessions with eight healthcare professionals were analysed (I), written descriptions of critical incidents were collected from 10 nurses, and interviews with open questions were conducted (II). An educational intervention on existential issues was pilot tested and is presented in Studies III and IV. The intervention was the basis of a pilot study with the purpose of testing whether the whole design of the educational intervention, including measurements instruments, is appropriate. In Study III and IV interviews with 11 nurses were conducted and 42 nurses were included in the quantitative measurements of four questionnaires, which were distributed and collected. Data was analysed using qualitative secondary analysis (I), hermeneutical analysis (II), and mixed methods using qualitative content analysis and statistical analyses (III-IV). Results in all studies show that existential issues are part of caring at surgical wards. However, although the nurses were aware of them, they found it difficult to acknowledge these issues owing to for example insecurity (I-III), a strict medical focus (II) and/or lacking strategies (I-III) for communicating on these issues. Modest results from the pilot study are reported and suggest beneficial influences of a support in communication on existential issues (III). The results indicate that the educational intervention may enhance nurses’ understanding for the patient’s situation (IV), help them deal with own insecurity and powerlessness in communication (III), and increase the value of caring for severely ill and dying patients (III) in addition to reducing work-related stress (IV). An outcome of all the studies in this thesis was that surgical nurses consider it crucial to have time and opportunity to reflect on caring situations together with colleagues. In addition, descriptions in Studies III and IV show the value of relating reflection to a theory or philosophy in order for attitudes to be brought to awareness and for new strategies to be developed.

Corruption, governance and collective sanctions: : can a wicked problem be tamed?

Tackling a problem requires mostly, an ability to read it, conceptualize it, represent it, define it, and then applying the necessary mechanisms to solve it. This may sound self-evident except when the problem to be tackled happens to be “complex, “ “ill-structured,” and/or “wicked.” Corruption is one of those kinds of problems. Both in its global and national manifestations it is ill-structured. Where it is structural in nature, endemic and pervasive, it is perhaps even wicked. Qualities of the kind impose modest expectations regarding possibilities of any definitive solution to this insidious phenomenon. If so, it may not suffice to address the problem of corruption using existing categories of law and/or good governance, which overlook the “long-term memory” of the collective and cultural specific dimensions of the subject. Such socio-historical conditions require focusing on the interactive and self-reproducing networks of corruption and attempting to ‘subvert’ that phenomenon’s entire matrix. Concepts such as collective responsibility, collective punishment and sanctions are introduced as relevant categories in the structural, as well as behavioral, subversion of some of the most prevalent aspects of corruption. These concepts may help in the evolving of a new perspective on corruption fighting strategies.

Role of dietary fats in modulating cardiometabolic risk during moderate weight gain : a randomized double-blind overfeeding trial (LIPOGAIN study)

BACKGROUND: Whether the type of dietary fat could alter cardiometabolic responses to a hypercaloric diet is unknown. In addition, subclinical cardiometabolic consequences of moderate weight gain require further study. METHODS AND RESULTS: In a 7-week, double-blind, parallel-group, randomized controlled trial, 39 healthy, lean individuals (mean age of 27±4) consumed muffins (51% of energy [%E] from fat and 44%E refined carbohydrates) providing 750 kcal/day added to their habitual diets. All muffins had identical contents, except for type of fat; sunflower oil rich in polyunsaturated fatty acids (PUFA diet) or palm oil rich in saturated fatty acids (SFA diet). Despite comparable weight gain in the 2 groups, total: high-density lipoprotein (HDL) cholesterol, low-density lipoprotein:HDL cholesterol, and apolipoprotein B:AI ratios decreased during the PUFA versus the SFA diet (-0.37±0.59 versus +0.07±0.29, -0.31±0.49 versus +0.05±0.28, and -0.07±0.11 versus +0.01±0.07, P=0.003, P=0.007, and P=0.01 for between-group differences), whereas no significant differences were observed for other cardiometabolic risk markers. In the whole group (ie, independently of fat type), body weight increased (+2.2%, P<0.001) together with increased plasma proinsulin (+21%, P=0.007), insulin (+17%, P=0.003), proprotein convertase subtilisin/kexin type 9, (+9%, P=0.008) fibroblast growth factor-21 (+31%, P=0.04), endothelial markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin (+9, +5, and +10%, respectively, P<0.01 for all), whereas nonesterified fatty acids decreased (-28%, P=0.001). CONCLUSIONS: Excess energy from PUFA versus SFA reduces atherogenic lipoproteins. Modest weight gain in young individuals induces hyperproinsulinemia and increases biomarkers of endothelial dysfunction, effects that may be partly outweighed by the lipid-lowering effects of PUFA. CLINICAL TRIAL REGISTRATION URL: http://ClinicalTrials.gov. Unique identifier: NCT01427140.