Showing papers by "Lund University published in 2002"

Neuronal replacement from endogenous precursors in the adult brain after stroke

Abstract: In the adult brain, new neurons are continuously generated in the subventricular zone and dentate gyrus, but it is unknown whether these neurons can replace those lost following damage or disease. Here we show that stroke, caused by transient middle cerebral artery occlusion in adult rats, leads to a marked increase of cell proliferation in the subventricular zone. Stroke-generated new neurons, as well as neuroblasts probably already formed before the insult, migrate into the severely damaged area of the striatum, where they express markers of developing and mature, striatal medium-sized spiny neurons. Thus, stroke induces differentiation of new neurons into the phenotype of most of the neurons destroyed by the ischemic lesion. Here we show that the adult brain has the capacity for self-repair after insults causing extensive neuronal death. If the new neurons are functional and their formation can be stimulated, a novel therapeutic strategy might be developed for stroke in humans.

Identity regulation as organizational control: Producing the appropriate individual

Abstract: This paper takes the regulation of identity as a focus for examining organizational control. It considers how employees are enjoined to develop self-images and work orientations that are deemed congruent with managerially defined objectives. This focus on identity extends and deepens themes developed within other analyses of normative control. Empirical materials are deployed to illustrate how managerial intervention operates, more or less intentionally and in/effectively, to influence employees' self-constructions in terms of coherence, distinctiveness and commitment. The processual nature of such control is emphasized, arguing that it exists in tension with other intra. and extra-organizational claims upon employees' sense of identity in a way that can open a space for forms of micro-emancipation. (Less)

European prospective investigation into cancer and nutrition (EPIC): study populations and data collection

Abstract: The European Prospective Investigation into Cancer and Nutrition (EPIC) is an ongoing multi-centre prospective cohort study designed to investigate the relationship between nutrition and cancer, with the potential for studying other diseases as well. The study currently includes 519 978 participants (366 521 women and 153 457 men, mostly aged 35-70 years) in 23 centres located in 10 European countries, to be followed for cancer incidence and cause-specific mortality for several decades. At enrollment, which took place between 1992 and 2000 at each of the different centres, information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire addressing usual diet. Anthropometric measurements were performed and blood samples taken, from which plasma, serum, red cells and buffy coat fractions were separated and aliquoted for long-term storage, mostly in liquid nitrogen. To calibrate dietary measurements, a standardised, computer-assisted 24-hour dietary recall was implemented at each centre on stratified random samples of the participants, for a total of 36 900 subjects. EPIC represents the largest single resource available today world-wide for prospective investigations on the aetiology of cancers (and other diseases) that can integrate questionnaire data on lifestyle and diet, biomarkers of diet and of endogenous metabolism (e.g. hormones and growth factors) and genetic polymorphisms. First results of case-control studies nested within the cohort are expected early in 2003. The present paper provides a description of the EPIC study, with the aim of simplifying reference to it in future papers reporting substantive or methodological studies carried out in the EPIC cohort.

Regional Innovation Systems: The Integration of Local ‘Sticky’ and Global ‘Ubiquitous’ Knowledge

Abstract: The paper examines how firms in three regional clusters in Norway dominated by shipbuilding, mechanical engineering and electronics industry, respectively exploit both place-specific local resources as well as external, world-class knowledge to strengthen their competitiveness. From these case-studies we make four points: (1) Ideal-typical regional innovation systems, i.e., regional clusters ‘surrounded’ by supporting local organisations, is rather uncommon in Norway. (2) External contacts, outside of the local industrial milieu, are crucial in innovation processes also in many SMEs. (3) Innovation processes may nevertheless be regarded as regional phenomena in regional clusters, as regional resources and collaborative networks often have decisive significance for firms' innovation activity. (4) Regional resources include in particular place-specific, contextual knowledge of both tacit and codified nature, that, in combination, is rather geographically immobile.

A review of the production of ethanol from softwood

Abstract: Ethanol produced from various lignocellulosic materials such as wood, agricultural and forest residues has the potential to be a valuable substitute for, or complement to, gasoline One of the major resources in the Northern hemisphere is softwood This paper reviews the current status of the technology for ethanol production from softwood, with focus on hemicellulose and cellulose hydrolysis, which is the major problem in the overall process Other issues of importance, eg overall process configurations and process economics are also considered

Links between worlds: unraveling migratory connectivity

Abstract: Migration is the regular seasonal movement of animals from one place to another, often from a breeding site to a nonbreeding site and back. Because the act of migration makes it difficult to follow individuals and populations year round, our understanding of the ecology and evolution of migrating organisms, particularly birds, has been severely impeded. Exciting new advances in satellite telemetry, genetic analyses and stable isotope chemistry are now making it possible to determine the population and geographical origin of individual birds. Here, we review these new approaches and consider the relevance of understanding migratory connectivity to ecological, evolutionary and conservation issues.

Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein.

Abstract: Parkinson's disease is a devastating neurological condition that affects at least four million people. A striking feature of this disorder is the preferential loss of dopamine-producing neurons in the midbrain. Several aetiological triggers have been linked to Parkinson's disease, including genetic mutations and environmental toxins, but the pathway that leads to cell death is unknown. Recent developments have shed light on the pathogenic mechanisms that underlie the degeneration of these cells. We propose that defective sequestration of dopamine into vesicles, leading to the generation of reactive oxygen species in the cytoplasm, is a key event in the demise of dopaminergic neurons in Parkinson's disease, and might represent a common pathway that underlies both genetic and sporadic forms of the disorder.

Balancing the activation state of the endothelium via two distinct TGF‐β type I receptors

Abstract: The generation of mice lacking specific components of the transforming growth factor‐β (TGF‐β) signal tranduction pathway shows that TGF‐β is a key player in the development and physiology of the cardiovascular system. Both pro‐ and anti‐angiogenic properties have been ascribed to TGF‐β, for which the molecular mechanisms are unclear. Here we report that TGF‐β can activate two distinct type I receptor/Smad signalling pathways with opposite effects. TGF‐β induces phosphorylation of Smad1/5 and Smad2 in endothelial cells and these effects can be blocked upon selective inhibition of ALK1 or ALK5 expression, respectively. Whereas the TGF‐β/ALK5 pathway leads to inhibition of cell migration and proliferation, the TGF‐β/ALK1 pathway induces endothelial cell migration and proliferation. We identified genes that are induced specifically by TGF‐β‐mediated ALK1 or ALK5 activation. Id1 was found to mediate the TGF‐β/ALK1‐induced (and Smad‐dependent) migration, while induction of plasminogen activator inhibitor‐1 by activated ALK5 may contribute to the TGF‐β‐induced maturation of blood vessels. Our results suggest that TGF‐β regulates the activation state of the endothelium via a fine balance between ALK5 and ALK1 signalling.

Autologous Chondrocyte Transplantation Biomechanics and Long-Term Durability

Abstract: We evaluated the durability of autologous chondrocyte transplantation grafts in 61 patients treated for isolated cartilage defects on the femoral condyle or the patella and followed up for a mean of 7.4 years (range, 5 to 11). Durability was determined by comparing the clinical status at the long-term follow-up with that found 2 years after the transplantation. After 2 years, 50 of the 61 patients had good or excellent clinical results, and 51 of 61 had good or excellent results at 5 to 11 years later. Grafted areas from 11 of the patients were evaluated with an electromechanical indentation probe during a second-look arthroscopy procedure (mean follow-up, 54.3 months; range, 33 to 84); stiffness measurements were 90% or more of those of normal cartilage in eight patients. Eight of twelve 2-mm biopsy samples taken from these patients showed hyaline characteristics with safranin O staining and a homogeneous appearance in polarized light. Three fibrous and eight hyaline biopsy specimens stained positive to aggrecan and to cartilage oligomeric matrix protein. Hyaline-like specimens stained positive for type II collagen, and fibrous, for type I collagen. Autologous chondrocyte transplantation for the treatment of articular cartilage injuries has a durable outcome for as long as 11 years.

Random matrix approach to cross correlations in financial data.

Abstract: We analyze cross correlations between price fluctuations of different stocks using methods of random matrix theory (RMT). Using two large databases, we calculate cross-correlation matrices C of returns constructed from (i) 30-min returns of 1000 US stocks for the 2-yr period 1994-1995, (ii) 30-min returns of 881 US stocks for the 2-yr period 1996-1997, and (iii) 1-day returns of 422 US stocks for the 35-yr period 1962-1996. We test the statistics of the eigenvalues lambda(i) of C against a "null hypothesis" - a random correlation matrix constructed from mutually uncorrelated time series. We find that a majority of the eigenvalues of C fall within the RMT bounds [lambda(-),lambda(+)] for the eigenvalues of random correlation matrices. We test the eigenvalues of C within the RMT bound for universal properties of random matrices and find good agreement with the results for the Gaussian orthogonal ensemble of random matrices-implying a large degree of randomness in the measured cross-correlation coefficients. Further, we find that the distribution of eigenvector components for the eigenvectors corresponding to the eigenvalues outside the RMT bound display systematic deviations from the RMT prediction. In addition, we find that these "deviating eigenvectors" are stable in time. We analyze the components of the deviating eigenvectors and find that the largest eigenvalue corresponds to an influence common to all stocks. Our analysis of the remaining deviating eigenvectors shows distinct groups, whose identities correspond to conventionally identified business sectors. Finally, we discuss applications to the construction of portfolios of stocks that have a stable ratio of risk to return. (Less)

Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus

Abstract: BACKGROUND Multiple laboratory tests are used to diagnose and manage patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these tests varies substantially. APPROACH An expert committee compiled evidence-based recommendations for the use of laboratory testing for patients with diabetes. A new system was developed to grade the overall quality of the evidence and the strength of the recommendations. Draft guidelines were posted on the Internet and presented at the 2007 Arnold O. Beckman Conference. The document was modified in response to oral and written comments, and a revised draft was posted in 2010 and again modified in response to written comments. The National Academy of Clinical Biochemistry and the Evidence-Based Laboratory Medicine Committee of the American Association for Clinical Chemistry jointly reviewed the guidelines, which were accepted after revisions by the Professional Practice Committee and subsequently approved by the Executive Committee of the American Diabetes Association. CONTENT In addition to long-standing criteria based on measurement of plasma glucose, diabetes can be diagnosed by demonstrating increased blood hemoglobin A 1c (HbA 1c ) concentrations. Monitoring of glycemic control is performed by self-monitoring of plasma or blood glucose with meters and by laboratory analysis of HbA 1c . The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of autoantibodies, urine albumin, insulin, proinsulin, C-peptide, and other analytes are addressed. SUMMARY The guidelines provide specific recommendations that are based on published data or derived from expert consensus. Several analytes have minimal clinical value at present, and their measurement is not recommended.

Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation.

Abstract: Helicobacter pylori adherence in the human gastric mucosa involves specific bacterial adhesins and cognate host receptors. Here, we identify sialyl-dimeric-Lewis x glycosphingolipid as a receptor for H. pylori and show that H. pylori infection induced formation of sialyl-Lewis x antigens in gastric epithelium in humans and in a Rhesus monkey. The corresponding sialic acid-binding adhesin (SabA) was isolated with the "retagging" method, and the underlying sabA gene (JHP662/HP0725) was identified. The ability of many H. pylori strains to adhere to sialylated glycoconjugates expressed during chronic inflammation might thus contribute to virulence and the extraordinary chronicity of H. pylori infection.

A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans

Abstract: Systemic lupus erythematosus (SLE, OMIM 152700) is a complex autoimmune disease that affects 0.05% of the Western population, predominantly women. A number of susceptibility loci for SLE have been suggested in different populations, but the nature of the susceptibility genes and mutations is yet to be identified. We previously reported a susceptibility locus (SLEB2) for Nordic multi-case families. Within this locus, the programmed cell death 1 gene (PDCD1, also called PD-1) was considered the strongest candidate for association with the disease. Here, we analyzed 2,510 individuals, including members of five independent sets of families as well as unrelated individuals affected with SLE, for single-nucleotide polymorphisms (SNPs) that we identified in PDCD1. We show that one intronic SNP in PDCD1 is associated with development of SLE in Europeans (found in 12% of affected individuals versus 5% of controls; P = 0.00001, r.r. (relative risk) = 2.6) and Mexicans (found in 7% of affected individuals versus 2% of controls; P = 0.0009, r.r. = 3.5). The associated allele of this SNP alters a binding site for the runt-related transcription factor 1 (RUNX1, also called AML1) located in an intronic enhancer, suggesting a mechanism through which it can contribute to the development of SLE in humans.

One-dimensional steeplechase for electrons realized

Abstract: We report growth of one-dimensional semiconductor nanocrystals, nanowhiskers, in which segments of the whisker with different composition are formed, illustrated by InAs whiskers containing segments of InP. Our conditions for growth allow the formation of abrupt interfaces and heterostructure barriers of thickness from a few monolayers to 100s of nanometers, thus creating a one-dimensional landscape along which the electrons move. The crystalline perfection, the quality of the interfaces, and the variation in the lattice constant are demonstrated by high-resolution transmission electron microscopy, and the conduction band off-set of 0.6 eV is deduced from the current due to thermal excitation of electrons over an InP barrier.

Enzyme dynamics during catalysis.

Abstract: Internal protein dynamics are intimately connected to enzymatic catalysis. However, enzyme motions linked to substrate turnover remain largely unknown. We have studied dynamics of an enzyme during catalysis at atomic resolution using nuclear magnetic resonance relaxation methods. During catalytic action of the enzyme cyclophilin A, we detect conformational fluctuations of the active site that occur on a time scale of hundreds of microseconds. The rates of conformational dynamics of the enzyme strongly correlate with the microscopic rates of substrate turnover. The present results, together with available structural data, allow a prediction of the reaction trajectory.

Climatic control of the high-latitude vegetation greening trend and Pinatubo effect

Abstract: A biogeochemical model of vegetation using observed climate data predicts the high northern latitude greening trend over the past two decades observed by satellites and a marked setback in this trend after the Mount Pinatubo volcano eruption in 1991. The observed trend toward earlier spring budburst and increased maximum leaf area is produced by the model as a consequence of biogeochemical vegetation responses mainly to changes in temperature. The post-Pinatubo decline in vegetation in 1992-1993 is apparent as the effect of temporary cooling caused by the eruption. High-latitude CO(2) uptake during these years is predicted as a consequence of the differential response of heterotrophic respiration and net primary production.

Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system.

Abstract: Recombinant adeno-associated viral vectors display efficient tropism for transduction of the dopamine neurons of the substantia nigra. Taking advantage of this unique property of recombinant adeno-associated viral vectors, we expressed wild-type and A53T mutated human α-synuclein in the nigrostriatal dopamine neurons of adult rats for up to 6 months. Cellular and axonal pathology, including α-synuclein-positive cytoplasmic inclusions and swollen, dystrophic neurites similar to those seen in brains from patients with Parkinson9s disease, developed progressively over time. These pathological alterations occurred preferentially in the nigral dopamine neurons and were not observed in other nondopaminergic neurons transduced by the same vectors. The degenerative changes were accompanied by a loss of 30–80% of the nigral dopamine neurons, a 40–50% reduction of striatal dopamine, and tyrosine hydroxylase levels that was fully developed by 8 weeks. Significant motor impairment developed in those animals in which dopamine neuron cell loss exceeded a critical threshold of 50–60%. At 6 months, signs of cell body and axonal pathology had subsided, suggesting that the surviving neurons had recovered from the initial insult, despite the fact that α-synuclein expression was maintained at a high level. These results show that nigral dopamine neurons are selectively vulnerable to high levels of either wild-type or mutant α-synuclein, pointing to a key role for α-synuclein in the pathogenesis of Parkinson9s disease. Targeted overexpression of α-synuclein in the nigrostriatal system may provide a new animal model of Parkinson9s disease that reproduces some of the cardinal pathological, neurochemical, and behavioral features of the human disease.

Quantum control of energy flow in light harvesting.

Abstract: Coherent light sources have been widely used in control schemes that exploit quantum interference effects to direct the outcome of photochemical processes. The adaptive shaping of laser pulses is a particularly powerful tool in this context: experimental output as feedback in an iterative learning loop refines the applied laser field to render it best suited to constraints set by the experimenter. This approach has been experimentally implemented to control a variety of processes, but the extent to which coherent excitation can also be used to direct the dynamics of complex molecular systems in a condensed-phase environment remains unclear. Here we report feedback-optimized coherent control over the energy-flow pathways in the light-harvesting antenna complex LH2 from Rhodopseudomonas acidophila, a photosynthetic purple bacterium. We show that phases imprinted by the light field mediate the branching ratio of energy transfer between intra- and intermolecular channels in the complex's donor acceptor system. This result illustrates that molecular complexity need not prevent coherent control, which can thus be extended to probe and affect biological functions.

Introduction to galectins

Abstract: Good evidence suggest roles of galectins in cancer, immunity and inflammation, and development, but a unifying picture of their biological function is lacking. Instead galectins appear to have a particularly diverse, bewildering but intriguing array of activities both inside and outside cells—“clear truths and mysteries are inextricably twined”. Fortunately this has not discouraged but rather enthused a large number of good galectin researchers, some of which have contributed to this special issue of Glycoconjugate Journal to provide a personal, critical status of the field. Here we will give a brief introduction to the galectins as a protein family with some comments on nomenclature. Published in 2004.

HRPT2, encoding parafibromin, is mutated in hyperparathyroidism–jaw tumor syndrome

Abstract: We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors.

Pharmacological validation of behavioural measures of akinesia and dyskinesia in a rat model of Parkinson's disease.

Abstract: In an attempt to define clinically relevant models of akinesia and dyskinesia in 6-hydroxydopamine (6-OHDA)-lesioned rats, we have examined the effects of drugs with high (L-DOPA) vs. low (bromocriptine) dyskinesiogenic potential in Parkinson's disease on three types of motor performance, namely: (i) abnormal involuntary movements (AIMs) (ii) rotational behaviour, and (iii) spontaneous forelimb use (cylinder test). Rats with unilateral 6-OHDA lesions received single daily i.p. injections of L-DOPA or bromocriptine at therapeutic doses. During 3 weeks of treatment, L-DOPA but not bromocriptine induced increasingly severe AIMs affecting the limb, trunk and orofacial region. Rotational behaviour was induced to a much higher extent by bromocriptine than L-DOPA. In the cylinder test, the two drugs initially improved the performance of the parkinsonian limb to a similar extent. However, L-DOPA-treated animals showed declining levels of performance in this test because the drug-induced AIMs interfered with physiological limb use, and gradually replaced all normal motor activities. L-DOPA-induced axial, limb and orolingual AIM scores were significantly reduced by the acute administration of compounds that have antidyskinetic efficacy in parkinsonian patients and/or nonhuman primates (-91%, yohimbine 10 mg/kg; -19%, naloxone 4-8 mg/kg; -37%, 5-methoxy 5-N,N-dimethyl-tryptamine 2 mg/kg; -30%, clozapine 8 mg/kg; -50%, amantadine 40 mg/kg). L-DOPA-induced rotation was, however, not affected. The present results demonstrate that 6-OHDA-lesioned rats do exhibit motor deficits that share essential functional similarities with parkinsonian akinesia or dyskinesia. Such deficits can be quantified using novel and relatively simple testing procedures, whereas rotometry cannot discriminate between dyskinetic and antiakinetic effects of antiparkinsonian treatments.

On the correlation between heterozygosity and fitness in natural populations

Abstract: Three primary hypotheses currently prevail for correlations between heterozygosity at a set of molecular markers and fitness in natural populations. First, multilocus heterozygosity-fitness correlations might result from selection acting directly on the scored loci, such as at particular allozyme loci. Second, significant levels of linkage disequilibrium, as in recently bottlenecked-and-expanded populations, might cause associations between the markers and fitness loci in the local chromosomal vicinity. Third, in partially inbred populations, heterozygosity at the markers might reflect variation in the inbreeding coefficient and might associate with fitness as a result of effects of homozygosity at genome-wide distributed loci. Despite years of research, the relative importance of these hypotheses remains unclear. The screening of heterozygosity at polymorphic DNA markers offers an opportunity to resolve this issue, and relevant empirical studies have now emerged. We provide an account of the recent progress on the subject, and give suggestions on how to distinguish between the three hypotheses in future studies.

First stars. I. The extreme r-element rich, iron-poor halo giant CS 31082-001 - Implications for the r-process site(s) and radioactive cosmochronology

Abstract: We present a high-resolution (R = 75 000, S/N 500) spectroscopic analysis of the bright (V = 11.7), extreme halo giant CS 31082-001 ((Fe/H) = 2.9), obtained in an ESO-VLT Large Programme dedicated to very metal-poor stars. We nd CS 31082-001 to be extremely rich in r-process elements, comparable in this respect only to the similarly metal-poor, but carbon-enriched, giant CS 22892-052. As a result of the extreme overabundance of the heaviest r-process elements, and negligible blending from CH and CN molecular lines, a reliable measurement is obtained of the U II line at 386 nm, for the rst time in a halo star, along with numerous lines of Th II, as well as lines of 25 other r-process elements. Abundance estimates for a total of 43 elements (44 counting Hydrogen) are reported in CS 31082-001, almost half of the entire periodic table. The main atmospheric parameters of CS 31082- 001 are as follows: Te = 4825 50 K, logg =1 :5 0: 3( cgs), (Fe/H) = 2.9 0:1 (in LTE), and microturbulence 1.8 0.2 km s 1 . Carbon and nitrogen are not signicantly enhanced relative to iron. As usual in giant stars, Li is depleted by dilution (log(Li/H) = 0.85). The -elements show the usual enhancements with respect to iron, with (O/Fe) = 0:6 0:2 (from (O I) 6300 A), (Mg/Fe) = 0:45 0:16, (Si/Fe) = 0:24 0:1, and (Ca/Fe) = 0:41 0:08, while (Al/Fe) is near 0.5. The r-process elements show unusual patterns: among the lightest elements (Z 40), Sr and Zr follow the Solar r-element distribution, but Ag is down by 0.8 dex. All elements with 56 Z 72 follow the Solar r-element pattern, reduced by about 1.25 dex. Accordingly, the (r/Fe) enhancement is about +1.7 dex (a factor of 50), very similar to that of CS 22892-052. Pb, in contrast, seems to be below the shifted Solar r-process distribution, possibly indicating an error in the latter, while thorium is more enhanced than the lighter nuclides. In CS 31082-001, log(Th/Eu) is 0:22 0:07, higher than in the Solar System ( 0.46) or in CS 22892-052 ( 0.66). If CS 31082-001 and CS 22892-052 have similar ages, as expected for two extreme halo stars, this implies that the production ratios were dierent by about 0.4 dex for the two objects. Conversely, if the Th/Eu production ratio were universal, an age of 15 Gyr for CS 22892-052 would imply a negative age for CS 31082-001. Thus, while a universal production ratio for the r-process elements seems to hold in the interval 56 Z 72, it breaks down in the actinide region. When available, the U/Th is thus preferable to Th/Eu for radioactive dating, for two reasons: (i) because of its faster decay rate and smaller sensitivity to observational errors, and (ii) because the inital production ratio of the neighboring nuclides 238 Ua nd 232 Th is more robustly predicted than the 151 Eu/ 232 Th ratio. Our current best estimate for the age of CS 31082-001 is 14:0 2: 4G yr. However, the computed actinide production ratios should be veried by observations of daughter elements such as Pb and Bi in the same star, which are independent of the subsequent history of star formation and nucelosynthesis in the Galaxy.