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When I was a child, we didn't have a matched set of china. Maybe there had been one before I was born, but pieces had broken or just plain disappeared [...]

My thanks to John Burgess for giving us a glimpse into the thoughts of ordinary Russians in these conflicted times ('What my Russian friends are saying,' September). I'm grateful that [...]

This article discusses four ways of understanding the concept of humor: 1) in terms of necessary and sufficient conditions, as 2) a cluster concept, 3) an interpretive concept, and 4) a dual character concept. We peruse both historical and contemporary research on humor, but instead of asking “What is humor?,” we draw conclusions regarding what humor research tells us of the ways to conceptualize humor. The main merits and shortcomings of different approaches are explicated. We suggest that the increased awareness of conceptual options will help the field of humor research to construct ever better theories on the elusive subject matter.

Insulin regulates heart metabolism through the regulation of insulin-stimulated glucose uptake. Studies have indicated that insulin can also regulate mitochondrial function. Relevant to this idea, mitochondrial function is impaired in diabetic individuals. Furthermore, the expression of Opa-1 and mitofusins, proteins of the mitochondrial fusion machinery, is dramatically altered in obese and insulin-resistant patients. Given the role of insulin in the control of cardiac energetics, the goal of this study was to investigate whether insulin affects mitochondrial dynamics in cardiomyocytes. Confocal microscopy and the mitochondrial dye MitoTracker Green were used to obtain three-dimensional images of the mitochondrial network in cardiomyocytes and L6 skeletal muscle cells in culture. Three hours of insulin treatment increased Opa-1 protein levels, promoted mitochondrial fusion, increased mitochondrial membrane potential, and elevated both intracellular ATP levels and oxygen consumption in cardiomyocytes in vitro and in vivo. Consequently, the silencing of Opa-1 or Mfn2 prevented all the metabolic effects triggered by insulin. We also provide evidence indicating that insulin increases mitochondrial function in cardiomyocytes through the Akt-mTOR-NFκB signaling pathway. These data demonstrate for the first time in our knowledge that insulin acutely regulates mitochondrial metabolism in cardiomyocytes through a mechanism that depends on increased mitochondrial fusion, Opa-1, and the Akt-mTOR-NFκB pathway. Diabetes 2014;63:75-88 | DOI: 10.2337/db13-0340, The heart requires a constant supply of metabolic substrates and oxygen. Although in the adult heart nearly 70% of energy requirements are met by free fatty acid oxidation, cardiomyocytes have [...]

The study analyses how students' growing understanding of the topic and search experience were related to their choice of search tactics and terms while preparing a research proposal for a small empirical study. In addition to that, the findings of the study are used to test Vakkari's (2001) theory of task-based IR. The research subjects were 22 students of psychology attending a seminar for preparing the proposal. They made a search for their task in PsychINFO database at the beginning and end of the seminar. Data were collected in several ways. A pre- and post-search interview was conducted in both sessions. The students were asked to think aloud in the sessions. This was recorded as were the transaction logs. The results show that search experience was slightly related to the change of facets. Although the students' vocabulary of the topic grew generating an increased use of specific terms between the sessions, their use of search tactics and operators remained fairly constant. There was no correlation between the terms and tactics used and the total number of useful references found. By comparing these results with the findings of relevant earlier studies the conclusion was drawn that domain knowledge has an impact on searching assuming that users have a sufficient command of the system used. This implies that the tested theory of task-based IR is valid on condition that the searchers are experienced. It is suggested that the theory should be enriched by including search experience in its scope. Keywords: Task-based information searching; Search terms; Search tactics; Search success; Relevance

While renewable energies locally installed in buildings are increasing, there is a potential or even a need to store them to promote their self-consumption. Being efficient, modular, and scalable, reversible Solid Oxide Cell (rSOC) technology can play a key role. Works undertaken in the frame of the REFLEX European project are presented, starting with the optimization of each individual component, ie. cells, stacks, and BoP components such as power electronics. With the support of modelling activities, the rSOC based system, made of 3 modules of 4 stacks each, coupled with a battery storage, has been designed in such a way to ensure achieving maximum efficiency, while still operating the system in safe and lifetime-optimal conditions. The site where the system will be installed has been prepared. Furthermore, techno-economic simulations have been carried out to evaluate market driven requirements on system sizing and costs to be competitive with other storage solutions.

Declining carbon (C) content in agricultural soils threatens soil fertility and makes soil prone to erosion, which could be rectified with organic soil amendments. In a 4‐yr field trial, we made a single application of three different organic sludges from the pulp and paper industry and studied their effects on cereal yield, soil C content, and fungal and bacterial composition. In laboratory rainfall simulations, we also studied the effects of the soil amendments on susceptibility to erosion and nutrient mobilization of a clay‐textured soil by measuring the quality of percolation water passing through 40‐cm intact soil monoliths during 2‐d rainfall simulations over four consecutive years after application. A nutrient‐poor fiber sludge reduced wheat yield in the first growing season, but there were no other significant effects on cereal yield or grain quality. An input of ∼8 Mg ha−1C with the soil amendments had only minor effects on soil C content after 4 yr, likely because of fast microbe‐mediated turnover. The amendments clearly changed the fungal and bacterial community composition. All amendments significantly reduced suspended solids (SS) and total phosphorus (TP) concentrations in percolation water. The effect declined with time, but the reduction in SS and TP was still >25% 4 yr after application. We attributed the lower tendency for particle detachment in rain simulations to direct interactions of soil minerals with the added particulate organic matter and microbe‐derived compounds that stabilize soil aggregates. In soils with low organic matter content, pulp and paper industry by‐products can be a viable measure for erosion mitigation.

A novel coronavirus (COVID-19) reached pandemic levels by March 11th, 2020, with a destructive impact across socioeconomic domains and all facets of global health, but little is known of its impact on sexual health.

Angiotensin-(1–9) is a peptide from the noncanonical renin-angiotensin system with anti-hypertrophic effects in cardiomyocytes via an unknown mechanism. In the present study we aimed to elucidate it, basing us initially on previous work from our group and colleagues who proved a relationship between disturbances in mitochondrial morphology and calcium handling, associated with the setting of cardiac hypertrophy. Our first finding was that angiotensin-(1–9) can induce mitochondrial fusion through DRP1 phosphorylation. Secondly, angiotensin-(1–9) blocked mitochondrial fission and intracellular calcium dysregulation in a model of norepinephrine-induced cardiomyocyte hypertrophy, preventing the activation of the calcineurin/NFAT signaling pathway. To further investigate angiotensin-(1–9) anti-hypertrophic mechanism, we performed RNA-seq studies, identifying the upregulation of miR-129 under angiotensin-(1–9) treatment. miR-129 decreased the transcript levels of the protein kinase A inhibitor (PKIA), resulting in the activation of the protein kinase A (PKA) signaling pathway. Finally, we showed that PKA activity is necessary for the effects of angiotensin-(1–9) over mitochondrial dynamics, calcium handling and its anti-hypertrophic effects.

The analysis of students' information needs in terms of conceptual understanding is focused and its consequences for the search process and outcome are analyzed. During the preparation of research proposal, different features of the studentEs conceptual structure were connected to the search process.

A decision support system with damage stability analysis has been recognized as an important tool for passenger ships. Various software applications have been developed and taken into use over the years, without a direct link to any compelling requirement, set forth in the international regulatory framework. After the Costa Concordia accident, new regulations have been established, setting minimum requirements for a decision support system, as an extension to a loading computer. Yet, more advanced systems have been developed recently, aiming at providing valuable additional information on the predicted development of the stability of the damaged ship. This paper presents these alternative decision support systems with damage stability analysis methods for flooding emergencies on passenger ships. The technical background, usability, and usefulness of the various approaches are compared and discussed, taking into account the important statutory approval point of view. In addition, practical examples, including past accidents, are presented and discussed.

Nasal spray formulations of naloxone, a mu-opioid receptor (MOR) antagonist, are currently used for the treatment of opioid overdose. They may have additional therapeutic utility also in the absence of opioid agonist drugs, but the onset and duration of action at brain MORs have been inadequately characterized to allow such projections. This study provides initial characterization of brain MOR availability at high temporal resolution following intranasal (IN) naloxone administration to healthy volunteers in the absence of a competing opioid agonist. Fourteen participants were scanned twice using positron emission tomography (PET) and [11C]carfentanil, a selective MOR agonist radioligand. Concentrations of naloxone in plasma and MOR availability (relative to placebo) were monitored from 0 to 60 min and at 300–360 min post naloxone. Naloxone plasma concentrations peaked at ~20 min post naloxone, associated with slightly delayed development of brain MOR occupancy (half of peak occupancy reached at ~10 min). Estimated peak occupancies were 67 and 85% following 2 and 4 mg IN doses, respectively. The estimated half-life of occupancy disappearance was ~100 min. The rapid onset of brain MOR occupancy by IN naloxone, evidenced by the rapid onset of its action in opioid overdose victims, was directly documented in humans for the first time. The employed high temporal-resolution PET method establishes a model that can be used to predict brain MOR occupancy from plasma naloxone concentrations. IN naloxone may have therapeutic utility in various addictions where brain opioid receptors are implicated, such as gambling disorder and alcohol use disorder.

Adrenocortical carcinoma (ACC) is a rare endocrine carcinoma with poor 5-year survival rates of < 40%. According to the literature, ACC is rarely an incidental imaging finding. However, presentation, treatment and outcome may differ in modern series. We studied all patients (n= 47, four children) from a single centre during years 2002–2018. We re-evaluated radiologic and histopathological findings and assessed treatments and outcome. We searched for possible TP53gene defects and assessed nationwide incidence of ACC. In adults, incidental radiologic finding led to diagnosis in 79% at median age of 61 years. ENSAT stage I, II, III and IV was 19%, 40%, 19% and 21%, respectively. Nonenhanced CT demonstrated > 20 Hounsfield Units (HU) for all tumours (median 34 (21–45)), median size 92 mm (20–196), Ki67 17% (1–40%), Weiss score 7 (4–9) and Helsinki score 24 (4–48). ACC was more often found in the left than the right adrenal (p< 0.05). One child had Beckwith-Wiedemann and one a TP53mutation. In adults, the primary tumour was resected in 88 and 79% received adjuvant mitotane therapy. Median hospital stay was significantly shorter in the laparoscopic vs. open surgery group (4 (3–7) vs. 8 (5–38) days, respectively; p< 0.001). In 3/4 patients, prolonged remission of > 5 to > 10 years was achieved after repeated surgery of metastases. Overall 5-year survival was 67%, and 96% vs. 26% for ENSAT stage I–II vs. III–IV (p< 0.0001). ENSAT stage and Ki67 predicted survival, type of surgery did not. Mitotane associated with better survival. Contemporary ACC predominantly presents as an incidental imaging finding, characterised by HU > 20 on nonenhanced CT but variable tumour size (20–196 mm). Malignancy cannot be ruled out by small tumour size only. The 5-year survival of 96% in ENSAT stage I–III compares favourably to previous studies.

PLAYING GREAT GUITAR INVOLVES more than monster technique, but developing physical skills is an important part of the game. One effective way to hone your chops is to isolate and [...]

AimsWidespread use of high-resolution imaging techniques and thus increased prevalence of adrenal lesions has made diagnostics of adrenocortical tumours an increasingly important clinical issue. In non-metastatic tumours, diagnosis is based on histology. New or enhanced information for clinicopathological diagnosis, revealing the malignant potential of the tumour, could emerge by means of biomarkers. The connection of proto-oncogene c-myc to adrenocortical neoplasias is poorly known, although the Wnt/beta-catenin pathway, one of the signalling pathways leading to induction of c-myc expression, has been connected to development of adrenocortical neoplasias. We studied c-myc expression in adrenocortical tumours and investigated molecules associated with the signalling pathway of c-myc, including cell cycle-related proteins p27, cyclin E and cyclin D1.MethodsWe studied 195 consecutive adult patients with 197 primary adrenocortical tumours. Histopathological diagnosis was determined by Weiss score and the novel Helsinki score. C-myc, cyclin D1, cyclin E and p27 expressions were determined by immunohistochemistry.ResultsBenign adenomas showed prominent nuclear c-myc expression comparable to that of normal adrenocortical cells, whereas carcinomas showed increased cytoplasmic expression. Strong cytoplasmic and weak nuclear c-myc expressions associated with malignancy and adverse outcome. C-myc staining did not correlate with cyclin E. Cyclin D1 correlated with cytoplasmic c-myc expression and to a lesser extent with nuclear c-myc. P27 correlated with cytoplasmic c-myc, but not with nuclear c-myc. P27 correlated with cyclin E.ConclusionsStrong cytoplasmic c-myc expression and weak nuclear expression in adrenocortical tumours associated with malignancy and shorter survival.

We investigated the interaction between fungal communities of soil and dead wood substrates. For this, we applied molecular species identification and stable isotope tracking to both soil and decaying wood in an unmanaged boreal Norway spruce-dominated stand. Altogether, we recorded 1990 operational taxonomic units, out of which more than 600 were shared by both substrates and 589 were found to exclusively inhabit wood. On average the soil was more species-rich than the decaying wood, but the species richness in dead wood increased monotonically along the decay gradient, reaching the same species richness and community composition as soil in the late stages. Decaying logs at all decay stages locally influenced the fungal communities from soil, some fungal species occurring in soil only under decaying wood. Stable isotope analyses suggest that mycorrhizal species colonising dead wood in the late decay stages actively transfer nitrogen and carbon between soil and host plants. Most importantly, Piloderma sphaerosporum and Tylospora sp. mycorrhizal species were highly abundant in decayed wood. Soil- and wood-inhabiting fungal communities interact at all decay phases of wood that has important implications in fungal community dynamics and thus nutrient transportation.

Sarco/endoplasmic reticulum–mitochondria communication and mitochondrial dynamics are essential regulators of mitochondrial function, cellular metabolism, and calcium homeostasisSarco/endoplasmic reticulum–mitochondria contacts and mitochondrial dynamics modulate myocardial contractility and vascular smooth muscle cell differentiationAlterations in sarco/endoplasmic reticulum–mitochondria communication and in mitochondrial network morphology are implicated in several cardiovascular pathologies, including heart failure, coronary artery disease, and pulmonary hypertensionMore studies are required to define the role that alterations in sarco/endoplasmic–mitochondria contacts and mitochondrial dynamics have in the pathogenesis of cardiovascular diseases

To establish environmentally friendly small-scale CHP units, a concept with serial connection of two SOFC stacks and an electrical efficiency of up to 50 % was developed. The underlying idea of the STAGE-SOFC concept is to couple a small exothermal CPOX stage with a larger endothermal steam reforming stage. This complete new system layout was validated by system modelling, CFD simulations of single components, experimental investigation of reformer performance and testing of a complete 5 kW prototype system for more than 600 hours under various parameters and loads. On basis of these results an improved second prototype was designed for long-term tests under real operating conditions.

Silver birch (Betula pendula) is a pioneer boreal tree that can be induced to flower within 1 year. Its rapid life cycle, small (440-Mb) genome, and advanced germplasm resources make birch an attractive model for forest biotechnology. We assembled and chromosomally anchored the nuclear genome of an inbred B. pendula individual. Gene duplicates from the paleohexaploid event were enriched for transcriptional regulation, whereas tandem duplicates were overrepresented by environmental responses. Population resequencing of 80 individuals showed effective population size crashes at major points of climatic upheaval. Selective sweeps were enriched among polyploid duplicates encoding key developmental and physiological triggering functions, suggesting that local adaptation has tuned the timing of and cross-talk between fundamental plant processes. Variation around the tightly-linked light response genes PHYC and FRS10 correlated with latitude and longitude and temperature, and with precipitation for PHYC. Similar associations characterized the growth-promoting cytokinin response regulator ARR1, and the wood development genes KAK and MED5A.

Biogas produced from anaerobic digestion (AD) of sewage sludge and organic wastes at wastewater treatment plants (WWTPs) can present an important energy contribution to a sustainable society. Raw AD biogas contains 50-65 molar% methane (CH4) and 50-35 molar% carbon dioxide (CO2) and can be upgraded to biomethane (with over 98 molar% CH4). During the CO2separation step of biomethane upgrading, substantial amounts of CO2are emitted to the atmosphere. A methanation unit can convert this CO2into sustainable Synthetic Natural Gas (SNG) and replace the conventional CO2separation unit for biomethane upgrading, but needs addition of hydrogen from water electrolysis. The water electrolysis can be built as a novel high-performance reversible Solid Oxide Electrolysis (rSOC), as demonstrated in the European H2020 project BALANCE. To highlight the zero-emission potential of the rSOC, this paper emphasizes author’s earlier results from the European H2020 project DEMOSOFC, demonstrating zero-local emission SOFC using raw biogas from WWTP sewage sludge and organic wastes. In this paper, profitability estimations for optimal rSOC and methanation investment and operation strategies at a modern city level WWTP in Finland, Europe, are presented. Power used in rSOC electrolysis mode (SOEC) origins from intermittent wind power, while power produced in rSOC fuel cell mode (SOFC) uses raw AD biogas. A dedicated Power-to-X optimization model is used, optimizing power market operations, dimensions of renewable power sources, plant dimensions and operational scheduling. High profitability is shown using European energy crisis market data 2021-2022, resulting in sustainable biomethane net production costs of 30-70 €/MWh.

In the version of this article initially published, there was a mistake in the calculation of the nucleotide mutation rate per site per generation: 1 × 10−9mutations per site per generation was used, whereas 9.5 × 10−9was correct. This error affects the interpretation of population-size changes over time and their possible correspondence with known geological events, as shown in the original Fig. 4 and supporting discussion in the text, as well as details in the Supplementary Note. Neither the data themselves nor any other results are affected. Figure 4 has been revised accordingly. Images of the original and corrected figure panels are shown in the correction notice.

SOMETIMES IT'S HARD TO GET off the ground when the radar says 'modal zone.' When that happens, try chord-tone arpeggios. You can cover all of the C major modes with […]

•The model predicts consumers’ intentions to buy plant-based drinkable snacks.•The model includes food choice motives, health-related value and likelihood of buying.•The model is validated with survey data sets from the Netherlands, Germany and France.•Health, naturalness and free-from motives predict value perception.•Value perception mediates the relationship between some motives and likelihood of buying.

Objective Some drugs have adverse effects on glucose metabolism, but it is unknown whether prescription drugs used prior to conception influence the future risk of gestational diabetes mellitus (GDM). Our study evaluated whether the purchase of prescription drugs 6 months prior to conception was associated with the occurrence of GDM.Methods This cohort study enrolled women with a Finnish background who delivered between 2009 and 2015 in the city of Vantaa, Finland (N = 10,455). Data on maternal characteristics and prescription drug purchases were obtained from national health registers. The use of a unique personal identification number enabled us to combine the register data on an individual level.Results Six months prior to conception, women who had pregnancies complicated by GDM purchased more prescription drugs than women without GDM (1.38 ± 2.04 vs. 1.11 ± 1.80). The GDM risk was higher in women with higher numbers of prescription purchases and those with more than three deliveries.Conclusions Multiparous women who purchase several prescription drugs should be given personalized counseling to prevent GDM.

Having read your question-and-answer column in the January/ February 2006 issue ("Ditching SUVs and Breeding Beefalos," Earth Talk), I was wondering something about the U.S. auto industry. If smaller cars […]

Decorin is generally recognized as a tumor suppressing molecule. Nevertheless, although decorin has been shown to be differentially expressed in malignant tissues, it has often remained unclear whether, in addition to non-malignant stromal cells, cancer cells also express it. Here, we first used two publicly available databases to analyze the current information about decorin expression and immunoreactivity in normal and malignant human colorectal tissue samples. The analyses demonstrated that decorin expression and immunoreactivity may vary in cancer cells of human colorectal tissues. Therefore, we next examined decorin expression in normal, premalignant and malignant human colorectal tissues in more detail using both in situ hybridization and immunohistochemistry for decorin. Our results invariably demonstrate that malignant cells within human colorectal cancer tissues are devoid of both decorin mRNA and immunoreactivity. Identical results were obtained for cells of neuroendocrine tumors of human colon. Using RT-qPCR, we showed that human colon cancer cell lines are also decorin negative, in accordance with the above in vivo results. Finally, we demonstrate that decorin transduction of human colon cancer cell lines causes a significant reduction in their colony forming capability. Thus, strategies to develop decorin-based adjuvant therapies for human colorectal malignancies are highly rational.

Mitochondria are key organelles for ATP production in cardiomyocytes, which is regulated by processes of fission and fusion. We hypothesized that the mitochondria fusion protein dynamin-related protein 1 (Drp1) inhibition, attenuates ischemia-reperfusion (IR) injury through modifications in mitochondrial metabolism. Rats were subjected to IR through coronary artery ligation, and isolated cardiomyocytes were treated with an ischemia-mimicking solution. In vivo, cardiac function, myocardial infarction area, and mitochondrial morphology were determined, whereas in vitro, viability, mitochondrial membrane potential, intracellular ATP levels, and oxygen consumption rate (OCR) were assessed. In both models, an adenovirus expressing Drp1 dominant-negative K38A (Drp1K38A) was used to induce Drp1 loss-of-function. Our results showed that IR stimulated mitochondrial fission. Myocardial infarction size and cell death induced by IR were significantly reduced, whereas cardiac function after IR was improved in Drp1K38A-treated rats compared with controls. Drp1K38A-transduced cardiomyocytes showed lower OCR with no decrease in intracellular ATP levels, and on IR, a larger decrease in OCR with a smaller reduction in intracellular ATP level was observed. However, proton leak-associated oxygen consumption was comparatively higher in Drp1K38A-treated cardiomyocytes, suggesting a protective mitochondrial uncoupling effect against IR. Collectively, our results show that Drp1 inhibition triggers cardioprotection by reducing mitochondrial metabolism during IR.

Multivariable linear regression (MLR) models are developed for the estimation of the maximum temperature and the temperature difference over a cell inside a solid oxide fuel cell (SOFC) stack. Empirical test data from both long-term tests (3500 hours) and a full three-factor designed experiment on a 10 kW SOFC system are utilized in the work. It is shown that accurate estimation can be carried out effectively based on systematic short-term experiments and by using simple and reliable measurements even under the effects of stack performance degradation. After proper data is obtained, selection of suitable MLR model regressors is crucial to obtaining good estimates. The cathode outlet temperature was found useful for the estimation of the stack maximum temperature and the stack voltage for the estimation of the temperature difference over a cell. Also, analysis of the measurement data shows that the experiment design can be considerably reduced without significant reduction in obtained information. The importance of using both long-term testing data as well as short-term designed experiments from an invariant system as the basis for modeling is underlined.

GUITARISTS OFTEN ASK, 'How do you play outside?' Here's a basic, yet effective, technique for momentarily shifting away from the tonal center to create tension and release. The concept is […]

JANUARY'S LICK CHAMP IS KEIJO Pennanen from Helsinski, Finland. 'The lick is played entirely on the second strin,' he reveals, 'to facilitate hammer-ons and pull-offs. Pick only the accented notes […]

The behavior of the maximum temperature measured inside a SOFC stack with respect to three independent input variables (stack current, air flow and air inlet temperature) is examined by using a full factorial screening experiment, following the design of experiments methodology. The experiments were carried out with a complete 10 kWe SOFC system. Multivariate regression models are developed to estimate said temperatures and a statistical analysis is carried out on the model parameters.

The aqueous solution of the Ni2+ion was investigated using a first principles molecular dynamics (FPMD) simulation based on periodic density-functional theory (DFT) calculations. Statistical averages of the magnetic properties corresponding to the triplet spin state of the ion, the hyperfine coupling, gand zero-field splitting tensors, as well as the resulting paramagnetic nuclear magnetic resonance (pNMR) shielding terms were calculated using DFT from instantaneous simulation snapshots extracted from the FPMD trajectory. We report comprehensive tests of the reliability of systematically selected DFT functionals for the properties. The isotropic nuclear shielding of the 17O nuclei can be obtained with good predictive power. The accuracy of the calculated 1H shieldings is limited by the fact that the spin-density on the proton sites is not reproduced reliably with the tested functionals, rendering the dominant Fermi contact isotropic shielding term less well-defined. On the other hand, the dominant spin-dipole term of the shielding anisotropy, which gives a practically vanishing isotropic contribution, can be obtained with good reliability for both the 1H and 17O nuclei. The anisotropic shielding tensor can be thus utilized reliably in the calculation of Curie-type paramagnetic relaxation. We discuss the evolution of the pNMR properties through the first and second solvation shells of the ion, toward the bulk solvent. The magnetic properties of the dominant, six-coordinated solution are compared to those of the metastable, 5-fold coordinated intermediate occurring in the dissociative exchange process.

Abstract: This paper presents a computational framework for cash-flow based valuation of insurance liabilities in incomplete markets. It accounts for the risks associated with both insurance claims and investment returns until maturity in accordance with modern principles of asset-liability management. The valuation framework is market consistent in the sense that it takes into account the investment opportunities available to the insurer at the time of valuation. The framework is easily adapted to different lines of insurance and it can effectively employ advanced tools for strategic portfolio management. As an application, we value the insurance portfolio of the Finnish private sector occupational pension system where the liabilities extend over 82 years.

Abstract: We study the problem of diversifying a given initial capital over a finite number of investment funds that follow different trading strategies. The investment funds operate in a market where a finite number of underlying assets may be traded over finite discrete time. We present a numerical procedure for finding a diversification that is optimal in the sense of a given convex risk measure. The procedure is illustrated on an asset-liability management problem where the liabilities correspond to a pension insurance portfolio.

Abstract: This paper proposes a general approach to stochastic mortality modelling. The logit transforms of annual survival probabilities are modelled by a linear combination of user-specified basis function of age. The model is easy to calibrate using the maximum likelihood method. The flexible construction and tangible interpretation of the underlying risk factors allows for an easy incorporation of population-specific characteristics and user views into the model. We fit two versions of the model into Finnish adult (18–100 years) population and mortality data, and present simulations for the future development of life spans.

Las mitocondrias son organelos dinámicos, capaces de intercambiar su morfología entre redes elongadas e interconectadas y arreglos fragmentados y desconectados mediante los procesos de fusión y fisión mitocondrial, respectivamente. Estos eventos permiten la transmisión de moléculas de señalización y el intercambio de metabolitos dentro de la célula y participan en una amplia variedad de procesos biológicos, que incluyen el desarrollo embrionario, el metabolismo, la apoptosis y la autofagia. Aunque la mayoría de estos estudios se han realizado en células no cardiacas, la evidencia emergente indica que los cambios en la morfología mitocondrial participan en el desarrollo cardiaco, la respuesta al daño por isquemia-reperfusión, la insuficiencia cardiaca y la diabetes mellitus. En este artículo se revisa cómo la dinámica mitocondrial se altera en diversas enfermedades cardiacas, con especial énfasis en la insuficiencia cardiaca, y cómo este conocimiento podría proporcionar nuevos blancos terapéuticos para su tratamiento.

The aim of this study was to investigate the health effects induced by exposure to the fungicide mancozeb in Italian vineyard workers. Ninety-three Italian subjects entered the study - 48 vine-growers intermittently exposed to mancozeb and 45 healthy controls. The subjects were investigated three times: before the seasonal application of pesticides (T0), 30 days after the beginning of the application period (T30), and 45 days after T0 (T45). At T0 the comparison between agricultural workers and controls showed a higher prevalence of cold or flu symptoms, a statistically significant lower percentage of monocytes, higher absolute count of T lymphocytes, CD4 and natural killer cells, and lower plasma levels of IgA and IgM in workers. Such differences were not confirmed at T30 and T45. In fact at T30 in exposed workers, besides a significant increase of urinary ethylenethiourea, confirming mancozeb exposure, T lymphocytes, CD4 and natural killer cells, IgA and IgM returned to values comparable to those observed in controls. Moreover, no other differences in clinical signs, haematological, and immune parameters, such as the immune functional capability evaluated as a response to hepatitis B vaccination, was observed. Altogether the differences between exposed and controls were not consistently correlated to any clinical impairment and suggest that the seasonal application of mancozeb does not pose a significant health risk to exposed subjects.

To assess whether subarachnoid hemorrhage (SAH) and its treatment is followed by volume loss in temporomesial structures.

Summary. The simplest and the best-known method for numerical approximation of high-dimensional integrals is the Monte Carlo method (MC), i.e. random sampling. MC has also become the most popular method for constructing numerically solvable approximations of stochastic programs. However, certain modern integration quadratures are often superior to crude MC in high-dimensional integration, so it seems natural to try to use them also in discretization of stochastic programs. This paper derives conditions that guarantee the epi-convergence of the resulting objectives to the original one. Our epi-convergence result is closely related to some of the existing ones but it is easier to apply to discretizations and it allows the feasible set to depend on the probability measure. As examples, we prove epi-convergence of quadrature-based discretizations of three different models of portfolio management and we study their behavior numerically. Besides MC, our discretizations are the only existing ones with guaranteed epi-convergence for these problem classes. In our tests, modern quadratures seem to result in faster convergence of optimal values than MC.

We describe a method for the isolation of free DNA from ductal lavage (DL) and nipple aspirate fluid (NAF), and its evaluation for the presence of LOH at the BRCA1and FHITgenes and for mitochondrial DNA (mtDNA) mutations at the D310 marker, to improve early detection of breast cancer. We evaluated 26 DL and six NAF samples from 14 women of known BRCA1status, who have no clinical evidence of breast tumors: nine mutation carriers and five non-carriers. LOH studies at the BRCA1locus were possible in 19/26 DL samples, and at the FHITlocus in 16/26 samples. In 4/9 mutation carriers we found LOH at the BRCA1allele, and in two of these we also found LOH at the FHITallele. In one of the mutation carriers with BRCA1LOH, invasive breast cancer was subsequently detected, and the tumor showed the same LOH as the DL. In one of the true negatives, BRCA1and FHITLOH were detected. The mitochondrial studies were possible in all 26 DL samples and a somatic mutation was found in 3/9 carriers, two of whom also had LOH at the BRCA1locus, and in none of the non-carriers. mtDNA mutation evaluation was possible in 4/6 NAF samples. The NAF and DL results were concordant. One NAF sample from a BRCA1patient showed a mtDNA mutation. Our data demonstrates the feasibility of performing molecular studies using the free DNA present in the ductal fluid, while the intact cells can be used for cytologic studies.

Due to their high abundance and ubiquitous existence, microbes are considered to be efficient colonisers of newly established habitats. To shed light on the dispersal mechanisms of soil microbes, a controlled microcosm experiment was established. In these microcosms, the dispersal of microbes from a source humus patch to originally sterile humus patches (embedded in a mineral soil matrix) was followed for 16 months, applying 16S and 18S ribosomal DNA-based PCR-DGGE molecular methods. Specifically, the role of enchytraeid worms and habitat (humus) corridors as possible facilitators of microbe dispersal was studied. The results showed that enchytraeid worms function efficiently as vectors for horizontal dispersal of saprophytic fungi in soil. Some of the fungi also proved to disperse through the corridors by vegetative growth, although this dispersal was inefficient as compared to dispersal with the enchytraeids. Virtually no saprophytic fungi were able to disperse through the mineral soil matrix in the absence of both enchytraeid worms and corridors. Unlike soil fungi, the dispersal of soil bacteria was not affected by any of the studied factors. The results of the present experiment provide direct evidence of the crucial role of soil fauna in aiding the horizontal dispersal of soil fungi. The role of enchytraeids as a functionally important species in boreal forest soils is further emphasized, since bringing microbes into contact with new resources is likely to enhance the rate of decomposition in soils.

As the inclusion criteria for breast conservation therapy have continued to evolve to include lower quadrant tumors, very large breasts, and central tumors, the potential for significant disfigurement after breast conservation therapy has also increased. This has led some centers to develop coordinated oncologyplastic surgery approaches to ensure both adequated cancer resection and aesthetic appearance to the breasts. The authors applied this principle to a specific group of breast cancer patients—women with macromastia—who would benefit from reduction mammaplasty. Eleven women were identified from the senior author's S.L.S. reconstructive practice who underwent breast conservation therapy followed by breast reconfiguration and bilateral reduction mammaplasty. Preoperative brassiere sizes ranged from 34D to 46D. All women had immediate reduction after frozen sections from the lumpectomypartial mastectomy margins were determined to be negative. A total of 22 reduction mammaplasties were performed eight freenipple grafts, five inferior pedicle flaps, seven superomedial pedicle flaps, and two superolateral flaps and an average of 1085 g was removed per breast. All patients underwent radiation therapy postoperatively. There were eight minor complications in six patients one hematoma, one keloid, one radiation burn, two cases of nipple hypopigmentation, and three cases of fat necrosis. After an average of 24 months' followup, there were no local recurrences and one death from distant metastasis. Seven of the 11 patients were available and agreed to rate their aesthetic satisfaction on the basis of a scale from 1 to 4, with 4 being the best. The mean satisfaction score was 3.3. Aesthetic outcomes before radiation therapy and after radiation therapy were evaluated by a panel of plastic surgery residents blinded to the purpose of the study. Using a scale of 1 to 4, the aesthetic mean before radiation therapy was 2.9 and the aesthetic mean after radiation therapy was 3.03. By combining breast conservation therapy with breast reconfiguration or reduction in largebreasted women, multiple benefits are derived. Larger segmental or partial mastectomies can be performed without disfigurement risk, ensuring adequate surgical margins. Immediate reconfiguration of the breast with reduction of the contralateral side creates symmetric, aesthetically pleasing breasts allows contralateral breast tissue to be evaluated and spares women from undergoing a second operative procedure. Such a coordinated program gives women an important boost, both physically and psychologically, during management of their breast cancer.

The steroid hormone progesterone is known to have profound effects on growth and differentiation of normal and malignant breast epithelial cells. The biologic actions of progesterone are exerted through the nuclear progesterone receptor-mediated control of target gene transcription. We utilized differential display polymerase chain reaction (DD-RT-PCR) to identify genes whose expression is altered in response to progestins in cultured breast cancer cells. Here we report identification of a gene encoding a member of the MAGUK protein family, hDlg5 (also known as KIAA0583 and P-dlg), as being the primary progestin target gene in MCF-7 breast cancer cells. Quantitative real-time RT-PCR analysis showed a rapid and strong upregulation of hDlg5 mRNA in cells treated with synthetic progestin medroxyprogesterone acetate (MPA) in the presence of estrogen in MCF-7, T47D and ZR-75-1 cells. The induction was abrogated by antiprogestin RU486. hDlg5 mRNA was also upregulated by progesterone, R5020 and dexamethasone. Protein synthesis inhibitor cycloheximide failed to block progestin-mediated induction of the hDlg5 gene. hDlg5 is a member of the growing family of MAGUKs (membrane-associated guanylate kinase homologs) and is to our knowledge the first member of the family reported to be hormonally regulated. hDlg5 is one of the human homologs of the Drosophila gene dlg [lethal(1)discs-large], which was initially identified as a tumor suppressor gene. The Dlg has a well-established role in cell growth control and maintenance of cell adhesion and cell polarity. Domain profile analysis revealed that hDlg5 has 2 additional PDZ domains than previously reported. © 2002 Wiley-Liss, Inc.

Occupational Exposure to Indoor Allergens in Finnish Trained Home-Helpers: a Pilot Study: Sirpa Pennanen, et al.Kuopio Regional Institute of Occupational Health—The presence of allergies, respiratory symptoms and skin-prick reactions was evaluated in trained home-helpers (THH), and indoor allergen levels were measured at their work sites. A questionnaire was answered by 118 THHs and forty THHs consented to skin-prick tests. The indoor allergen levels in the settled house dust from the clients’ homes of 17 prick tested THHs were determined by two-site monoclonal antibody ELISA methods. Forty- eight percent of the THHs had one or more symptoms at least weekly. The presence of respiratory symptoms and atopy was not particularly high in THHs. Prick tests revealed that 11 THHs (28%) had positive reactions to one or more of the allergens tested. A significant correlation was observed between the frequency of reported symptoms and positive prick reactions. Fel d 1 was found in 98% and Can f 1 in 96% of the dust samples, but Der p 1 in only 21% of the samples, though the levels remained rather low. The sensitization threshold suggested for cat allergen (1 µg/g) was exceeded in 26%, and that for dog allergen (2 µg/g) in 32% of the sites studied. These results showed that THHs are occupationally exposed to allergen levels sufficient to result in sensitization.