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Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.

Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.

Determination of the electronic energy spectrum of a trigonal-symmetry mononuclear Yb3+single-molecule magnet (SMM) by high-resolution absorption and luminescence spectroscopies reveals that the first excited electronic doublet is placed nearly 500 cm–1above the ground one. Fitting of the paramagnetic relaxation times of this SMM to a thermally activated (Orbach) model {τ = τ0× exp[ΔOrbach/(kBT)]} affords an activation barrier, ΔOrbach, of only 38 cm–1. This result is incompatible with the spectroscopic observations. Thus, we unambiguously demonstrate, solely on the basis of experimental data, that Orbach relaxation cannot a prioribe considered as the main mechanism determining the spin dynamics of SMMs. This study highlights the fact that the general synthetic approach of optimizing SMM behavior by maximization of the anisotropy barrier, intimately linked to the ligand field, as the sole parameter to be tuned, is insufficient because of the complete neglect of the interaction of the magnetic moment of the molecule with its environment. The Orbach mechanism is expected dominant only in the cases in which the energy of the excited ligand field state is below the Debye temperature, which is typically low for molecular crystals and, thus, prevents the use of the anisotropy barrier as a design criterion for the realization of high-temperature SMMs. Therefore, consideration of additional design criteria that address the presence of alternative relaxation processes beyond the traditional double-well picture is required.

Records on groups of individuals could be valuable for predicting breeding values when a trait is difficult or costly to measure on single individuals, such as feed intake and egg production. Adding genomic information has shown improvement in the accuracy of genetic evaluation of quantitative traits with individual records. Here, we investigated the value of genomic information for traits with group records. Besides, we investigated the improvement in accuracy of genetic evaluation for group-recorded traits when including information on a correlated trait with individual records. The study was based on a simulated pig population, including three scenarios of group structure and size. The results showed that both the genomic information and a correlated trait increased the accuracy of estimated breeding values (EBVs) for traits with group records. The accuracies of EBV obtained from group records with a size 24 were much lower than those with a size 12. Random assignment of animals to pens led to lower accuracy due to the weaker relationship between individuals within each group. It suggests that group records are valuable for genetic evaluation of a trait that is difficult to record on individuals, and the accuracy of genetic evaluation can be considerably increased using genomic information. Moreover, the genetic evaluation for a trait with group records can be greatly improved using a bivariate model, including correlated traits that are recorded individually. For efficient use of group records in genetic evaluation, relatively small group size and close relationships between individuals within one group are recommended.

We present a simple procedure to make an augmented reality app to visualize any chemical 3D model. The molecular structure may be based on crystallographic data or from computational modeling. This guide is made in such a way that no programming skills are needed, and the procedure uses free software and provides a way to visualize 3D structures that are normally difficult to comprehend in the 2D space of paper. The process can be applied to make a 3D representation of any 2D object, and we envisage the app to be useful when visualizing simple stereochemical problems, when presenting a complex 3D structure on a poster presentation or even in audio-visual presentations. The method works for all molecules including small molecules, supramolecular structures, MOFs, and biomacromolecules.

The aim of this study was to examine (i) the genetic variation in macro-environmental sensitivity (macro-ES) for ADG in Danish Duroc pigs, (ii) the genetic heterogeneity among sexes, and (iii) residual variance heterogeneity among herds. Record of ADG for 32,297 boars (19 herds) and 42,724 gilts (16 herds) was used for analysis. The data were provided by the National Danish Pig Research Centre. The analysis was performed by fitting univariate reaction norm models with the herd-year-month on test (HYM) effect as environmental covariates and herd-specific residual variance for boars and gilts separately under a Bayesian setting. The environmental covariate was inferred simultaneously with other parameters of the model. Gibbs sampling was used to sample model dispersion and location parameters. The posterior means and highest posterior density intervals of the additive genetic variance, genetic correlations for ADG, and heritability were calculated over the continuous environmental range of −3σhto +3σh(SD of the HYM effect). The coheritability of ADG at the average environmental level and ADG in the environments along the −3σhto +3σhenvironmental gradient were also calculated. The analysis showed significant variation in macro-ES, revealing genotype by environment interactions (G × E) for ADG. The presence of G × E resulted in changes in additive genetic variance and heritability across the −3σhto +3σhrange. The genetic correlations were high and positive between ADG in environments differing by 1σhunits or less and decreased to moderately positive between ADG in the extreme environments in both sexes. The coheritability of ADG in the environment at the average level and the −3σhenvironment for boars were greater than the heritability in the environment at the average level, while it was less for gilts. The coheritability of ADG in the environment at the average level and the +3σhenvironment for boars was less than heritability in the environment at the average level, while it was either the same or greater for gilts, depending on the residual variance. Boars had larger additive genetic and residual variances than gilts. Heterogeneity of residual variances across herds was shown for both sexes. In conclusion, this study shows the presence of macro-ES, genetic variance heterogeneity among sexes for ADG in pigs, and residual variance heterogeneity across herds.

Coronary atherosclerosis is a leading cause of mortality. New technological developments in computed tomography (CT), including dual energy, iterative reconstructions and high definition scanning, could significantly improve the non-invasive identification of atherosclerosis plaques. Here, a new method for optimising cardiac coronary CT with optical coherence tomography (OCT) and histopathology is presented.

Feed conversion ratio (FCR) is an economically important trait in pigs, and feed accounts for a significant proportion of the costs involved in pig production. In this study we used a high-density SNP chip panel, Porcine SNP60 BeadChip, to identify the association between FCR and SNP markers and to study the genetic architecture of the trait. After quality control, a total of 30,847 SNP that could be mapped to the 18 porcine autosomes (SSC) using the pig genome assembly 10.2 were used in the analyses. Deregressed estimated breeding value was used as the response variable. A total of 3,071 Duroc pigs had both FCR data and genotype data. The linkage disequilibrium (r(2)) between adjacent markers was 0.56. Two association mapping approaches were used: a linear mixed model (LMM) based on single-locus regression analysis and a Bayesian variable selection approach (BVS). A total of 79 significant (P < 0.0001) SNP associations on 6 chromosomes were identified by LMM analyses. Out of these, 10 SNP crossed the genome-wide significance threshold. These 10 SNP were all located on SSC 4 and 14. In the BVS analysis, a total of 44 SNP located on 12 chromosomes had posterior probability more than or equal to 0.05 (i.e., Bayes factor ≥ 10). Thirteen SNP were identified by both LMM and BVS. These 13 SNP were located on 4 chromosomes: SSC 4, 7, 8, and 14. Hypoxia inducible factor 1, alpha subunit inhibitor (HIF1AN) and ladybird homeobox 1 (LBX1) are 2 possible candidate genes affecting FCR on SSC 4 and 14, respectively. The study provides a list of SNP associated with FCR and also offers valuable information on the genetic architecture and candidate genes for this trait.

The NorSIKT project is carried out in cooperation between all Nordic countries (Sweden, Denmark, Island, Finland and Norway) and is financed by the NordFOU Research Cooperation (ministered by the Director Generals in each country). The main objective of the NorSIKT project is to standardize the system for classification of motor vehicles in the Nordic countries in order.In the first phase of the project a detailed survey of the traffic data system in the Nordic countries was carried out. The state-of-the-art report presents the situation in terms of current definitions for the classification of vehicles and describes the traffic counting systems in each country. The state-of-the-art report has furthermore been used as a basis for developing a preliminary vehicle classification system introducing some new principles where vehicles can be classified from different types of properties like length, weight, number of axels, type of fuel, etc. Each country can adopt the classification properties that best meet the needs in the country. In the second and ongoing phase different type of registration equipment on the Nordic market will be tested to investigate how different type of equipment meets different classification principles.

Abstract: Thielavia terrestris is a soil-borne thermophilic fungus whose molecular/cellular biology is poorly understood. Only a few genes have been cloned from the Thielavia genus. We detected an extracellular glucoamylase in culture filtrates of T. terrestris and cloned the corresponding glaA gene. The coding region contains five introns. Based on the amino acid sequence, the glucoamylase was 65% identical to Neurospora crassa glucoamylase. Sequence comparisons suggested that the enzyme belongs to the glycosyl hydrolase family 15. The T. terrestris glaA gene was expressed in Aspergillus oryzae under the control of an A. oryzae α-amylase promoter and an Aspergillus niger glucoamylase terminator. The 75-kDa recombinant glucoamylase showed a specific activity of 2.8 μmol/(minmg) with maltose as substrate. With maltotriose as a substrate, the enzyme had an optimum pH of 4.0 and an optimum temperature of 60C. The enzyme was stable at 60C for 30 min. The K m and k cat of the enzyme for maltotriose were determined at various pHs and temperatures. At 20C and pH 4.0, the enzyme had a K m of 0.330.07 mM and a k cat of (5.50.5)103 min−1 for maltotriose. The temperature dependence of k cat /K m indicated an activation free energy of 2.8 kJ/mol across the range of 20–70C. Overall, the enzyme derived from the thermophilic fungus exhibited properties comparable with that of its homolog derived from mesophilic fungi.

In DMSOsolution 2amino4Hthiazolo5,4bindole is converted into a complex mixture of colored products. The three major conversion endproducts, of which two are inhibitors of protein tyrosine phosphatases PTPs, were isolated by chromatographic methods and their structures characterized by spectroscopic analysis, including NMR and MS combined with computer assisted structure elucidation, and, finally, confirmed by independent chemical synthesis. Synthesis of 2amino4Hthiazolo5,4bindole as well as its Nacetyl derivatives prepared from either oxindole or 2bromo12nitrophenylethanone is described.

Objectives 1. To determine the prevalence of endometrial hyperplasia in postmenopausal women taking standard proprietary regimens of sequential oestrogen/progestogen; 2. to determine the effects of nine months treatment with an oral continuous combined regimen of 2 mg 17ß‐oestradiol and 1 mg norethisterone acetate (Kliofem [Kliogest outside the UK]; Novo Nordisk, Denmark) on endometrial histology in postmenopausal women.

SummaryThe rapid FTIR (Fourier transform infrared) spectroscopy technique was used to indirectly measure the lignin content of Sitka spruce wood samples.A model was constructed to relate FTIR data to lignin content measured in wood by chemical analysis (i.e. the modified acetyl bromide method), through the application of the principal component regression (PCR) approach to a set of calibration observations. The acetyl bromide method provided lignin determinations ranging from 24% to 34% with a measurement error of 0.6%. A residual standard deviation of 0.8% and an average prediction error of 0.9% were calculated for lignin content when employing the selected PCR model (based on a normalized infrared data set, obtained using the band at 1374 cm−1as a reference) to indirectly measure this wood property. Furthermore, a large portion of the variability in lignin content was explained by the two principal components retained in the selected calibration model, as indicated by the magnitude (i.e. 0.93) of the coefficient of multiple determination.The model was subsequently employed to predict the lignin content of wood samples collected in a clonal experiment. Two multivariate diagnostic measures were applied to assess the quality of the individual predictions, and the results indicated that the spectral information contained in the new sample vectors was suitable for use with the selected calibration model.

Preliminary investigations suggested the importance of an evaluation of different tissue preparation methods frequently used for immunohistochemical analysis of human or murine monoclonal antibodies on human tissue. Colon adenocarcinomas and adjacent morphologically normal colon epithelia were analyzed with an indirect immunoperoxidase technique. Duplicate tissue specimens were (1) snap frozen and fixed in acetone, (2) formalin fixed and paraffin embedded, with or (3) without ensuing treatment with pronase, or (4) alcohol fixed and paraffin embedded. Three different human monoclonal anti-colon cancer IgM antibodies, COU-1, D4213, and F10279, were used in the present study. Endogenous immunoglobulin and the secretory-component-mediated IgM binding were blocked on frozen sections with Fab' anti-IgM and anti-SC antibody. Bound monoclonal antibody was detected with horseradish peroxidase-anti-IgM. COU-1 was found to stain frozen sections of all 25 cancer and adjacent normal colon epithelia. In contrast, on formalin-fixed, paraffin-embedded tissue, only 80% (20/25) of the colon cancer and 44% (11/25) of the adjacent normal colon epithelia were positive. After treatment of the formalin-fixed sections with pronase, all cancers and normal adjacent epithelia were stained, but the cancer cells were more intensely stained than the normal colon epithelial cells. On alcohol-fixed tissues, intense staining was found in all the colon carcinomas analyzed, whereas no staining was found of the adjacent normal colon epithelia, except for a few cells in some of the sections investigated. Antibody F10279 stained none of the frozen, acetone-fixed tissues or the alcohol-fixed and paraffin-embedded tissues analyzed, whereas it stained 71% (5/7) of the formalin-fixed adenocarcinomas and 43% (3/7) of the adjacent normal epithelia. Pronase treatment enhanced the staining intensity. Antibody D4213 showed similar staining of all cancers and normal colon epithelia analyzed with all the four preparation techniques. Procedures for the fixation and processing of human tissue for the immunohistochemical screening of human monoclonal antibodies are critical. Our results demonstrate the necessity of examining several tissue preparation techniques for the analysis of the tissue reactivity of monoclonal antibodies, and indicate that alcohol fixation may advantageously be included. Destruction or masking of antigens, unspecific binding of antibodies, or other technical problems may lead to erroneous conclusions concerning the antigen distribution or the specificity or selectivity of the antibody.

Summary The present study aimed to examine possible changes in keratin expression during neoplastic transformation of the uterine mucosa and possible differences in keratin expression between endocervical and endometrial adenocarcinomas. Routinely processed specimens with normal morphology or neoplastic changes were stained immunohistochemically using 5 commercial antibodies to keratinfilaments of molecular weight 39–58 kD: CAM 5.2, RCK 102, MCA 144, PKE and PRE.

This paper describes a new method for improving the control of air temperature in greenhouses. The proposed controller is an extended version of the generalized predictive controller (GPC). The prediction of air temperature is facilitated by a continuous time stochastic state space model identified for the heat dynamics of the greenhouse. A simulation study illustrates that the proposed GPC gives a more active controller with less control error than the implemented PID controller.

In an attempt to increase uniformity and unambiguity of evaluation through rating scales of schizophrenia and schizophrenialike psychosis, the 5-step edition of the Brief Psychiatric Rating Scale (BPRS) is used. In this edition of BPRS the 18 symptoms and the symptom grading are expressed in explicit item definitions. Symptoms in the Hamilton Depression Scale and in the Beigel Mania Scale which correlate with BPRS have been incorporated as far as possible. Despite wide international application of BPRS, only few reliability and validity studies have been made, the fact notwithstanding that the scale is used as a reference when new scales are introduced.This interim statement includes weekly co-rating of in-patients on the BPRS. The studies were commenced in August 1984. The rating procedure takes place between 8.15 and 9.00 a.m. and each patient is examined only once. The maximum number of raters is six but varies between three and six per rating procedure. The evaluated patients all comply with DSM-III criteria for schizophrenia.Reliability is expressed by intra-class correlation R = 0.78, p. < 0.001, for the total scale. When considering degree of severity the global estimate (validity) showed a correlation of R = 0.66, p. < 0.01. After 18 weeks of co-ratings all other schizophrenic in-patients - a total of 17 - were rated as a control group. There was no difference between the two populations of schizophrenic patients, t = 0.92, p = 0.36.

In the rather extensive litterature concerning electroconvulsive therapy, ECT, little attention has been paid to relapse problems. Therefore a case-referent study was done at Frederiksberg Hospital. All patients receiving ECT in 1982 were retrospectively followed for 6 months after treatment.The therapy was found effective in all 38 patients with major affective disorders but insignificant in other cases. An overall relapse rate of 45% was found. In contrast to other reports no significant effect of pharmacological continuation therapy could be demonstrated in this study.It is to be concluded that ECT is effective in producing a full remission of acute psychopathology in patients with major depressive disorder but a relapse rate of 45% after ECT is unacceptably high. To improve this, further prospective studies are needed which should include biological markers in order to analyse the pathophysiology of the disorders and to monitor the therapeutic effect of ECT and the follow-up treatment.

The pathogenesis and the mechanism of accelerated graft rejection in concordant xenotransplantation are unclear. The histopathological features and kinetics neither fulfill the criteria of classic hyperacute rejection nor resemble an accelerated type of first-set allograft reaction. The aim of this study was to investigate the mechanism of concordant xenograft rejection in relation to the early morphological changes in hamster hearts transplanted to unmodified rat recipients by sequential, immunohistological analysis of grafts, regional lymph nodes, and spleens and to correlate these results to the production of antidonor antibodies, as determined by a flow cytometric assay. Histopathological features were characterized by a gradually increasing myocytolysis with fragmentation and loss of myofilaments. The first slight signs were observed a few hours after transplantation. Later, vascular changes developed, evolving into a leukocytoclastic type of vasculitis, eventually with thrombosis. No significant interstitial lymphocyte infiltration was present, but neutrophilic granulocytes and macrophages appeared. In addition, a distinct increase in B cells in spleens and lymph nodes was noted. Low levels of preformed antidonor antibodies did not increase during the first 48 h; however, significant amounts of species-, but not donor-, specific antibodies were demonstrated at the time of rejection. These data, together with the morphological observations, indicate a primarily humoral xenograft rejection in this model. Minor damage to graft myocytes a few hours after transplantation, progressing to vascular changes within 24–48 h, further suggests that preformed antidonor antibodies directed against endothelial or myocyte determinants may play an initiating role in the pathogenesis of unmodified, concordant xenograft rejection.

A case of delirium acutum in the course of a schizofrenic exacerbation is reported. A short review of the literature dealing with nosological and patophysiological aspects of delirium acutum is given. In this case the patient was treated with neuroleptics and diazepaminfusion for some days, but since his clinical condition rapidly deteriorated electrocovulsive therapy (ECT) was commenced, and after several treatments the patient finally improved. Possible mechanisms for the failure of diazepam in the treatment is discussed. It is concluded that ECT is the treatment of first choice in the case of threatening or fully developed delirium acutum.

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Longevity in commercial sows is often selected for through stayability traits measured in purebred animals. However, this may not be justifiable because longevity and stayability may be subject to both genotype by environment interaction (G × E) and genotype by genotype interaction (G × G). This study tested the hypothesis that stayability to service after first parity is more strongly genetically correlated with longevity in commercial herds when stayability is measured in commercial herds rather than multiplier herds. The analysis was based on farrowing- and service-records from 470,824 sows (189,263 multiplier; 281,561 commercial) and 300 herds (156 multiplier; 144 commercial sows). Multiplier sows were either purebred Landrace or Yorkshire and commercial sows were mainly rotationally crossbreds between the two breeds. Commercial longevity was defined as age in days when culled (LongC), and stayability to service after first parity was defined for both commercial sows (StayC) and multiplier sows (StayM). The genetic correlations between LongC, StayC, and StayM were estimated by restricted maximum likelihood using linear mixed models. Genetic parameters were estimated separately for Landrace and Yorkshire. In Landrace, the genetic correlations between LongC and StayC, LongC and StayM, and StayC and StayM were 0.86 ± 0.02, 0.24 ± 0.05, and 0.34 ± 0.06, respectively. In Yorkshire, the genetic correlations between LongC and StayC, LongC and StayM, and StayC and StayM were 0.81 ± 0.03, 0.17 ± 0.05, and 0.18 ± 0.7, respectively. Conclusively, longevity in commercial herds is more strongly correlated with stayability when stayability is measured in commercial herds rather than multiplier herds.

A patient who developed bilateral angle-closure glaucoma during treatment with nortriptylene is presented. The differential diagnoses are given and precautions suggested

Hamster hearts were transplanted to rats, and the effects of combinations of total lymphoid irradiation (TLI), cyclophosphamide, cyclosporine A (CyA) and monoclonal antibodies (MAB) were investigated, Controls not immunosuppressed rejected their xenograft in 3 to 5 days, while combination immunosuppression including MABs against CD4 or IL-2-receptors extended graft survival significantly, In one case, the graft was still functioning 180 days after transplantation, which is the longest survival seen in this model. The use of specific MABs may open a new era for both xeno- and allo-transplantation.

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