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The Treaty of Amsterdam introduced data protection, the core principles of which were developed in the 1970s, in the EC Treaty, and the Article 286(2) EC transposes the concept of an independent supervisory body (the EDPS) as introduced in Community law by Directive 95/46. The EDPS has elements of an institution, an agency, a regulator, an ombudsman and a judicial body, which gives a face to data protection and provides for independence, expertise and power.

Hepatocellular carcinoma (HCC)—the most common form of liver cancer—is an aggressive malignancy with few effective treatment options1. Lenvatinib is a small-molecule inhibitor of multiple receptor tyrosine kinases that is used for the treatment of patients with advanced HCC, but this drug has only limited clinical benefit2. Here, using a kinome-centred CRISPR–Cas9 genetic screen, we show that inhibition of epidermal growth factor receptor (EGFR) is synthetic lethal with lenvatinib in liver cancer. The combination of the EGFR inhibitor gefitinib and lenvatinib displays potent anti-proliferative effects in vitro in liver cancer cell lines that express EGFR and in vivo in xenografted liver cancer cell lines, immunocompetent mouse models and patient-derived HCC tumours in mice. Mechanistically, inhibition of fibroblast growth factor receptor (FGFR)  by lenvatinib treatment leads to feedback activation of the EGFR–PAK2–ERK5 signalling axis, which is blocked by EGFR inhibition. Treatment of 12 patients with advanced HCC who were unresponsive to lenvatinib treatment with the combination of lenvatinib plus gefitinib (trial identifier NCT04642547) resulted in meaningful clinical responses. The combination therapy identified here may represent a promising strategy for the approximately 50% of patients with advanced HCC who have high levels of EGFR.

Acromegaly is characterized by an excess of growth hormone (GH) and insulin-like growth factor 1 (IGF1). Cardiovascular disease (CVD) risk factors are common in acromegaly and often persist after treatment. Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Therefore, we hypothesized that inflammation persists in treated acromegaly and may contribute to CVD risk.In this cross-sectional study, we assessed cardiovascular structure and function, and inflammatory parameters in treated acromegaly patients. Immune cell populations and inflammatory markers were assessed in peripheral blood from 71 treated acromegaly patients (with controlled or uncontrolled disease) and 41 matched controls. Whole blood (WB) was stimulated with Toll-like receptor ligands. In a subgroup of 21 controls and 33 patients with controlled disease, vascular ultrasound measurements were performed.Leukocyte counts were lower in patients with controlled acromegaly compared to patients with uncontrolled acromegaly and controls. Circulating IL18 concentrations were lower in patients; concentrations of other inflammatory mediators were comparable with controls. In stimulated WB, cytokine production was skewed toward inflammation in patients, most pronounced in those with uncontrolled disease. Vascular measurements in controlled patients showed endothelial dysfunction as indicated by a lower flow-mediated dilatation/nitroglycerine-mediated dilatation ratio. Surprisingly, pulse wave analysis and pulse wave velocity, both markers of endothelial dysfunction, were lower in patients, whereas intima-media thickness did not differ.Despite treatment, acromegaly patients display persistent inflammatory changes and endothelial dysfunction, which may contribute to CVD risk and development of CVD.

The content of (1→3, 1→4)‐β‐glucan (BG) in barley (Hordeum vulgareL.) has become a breeding target due to the human health benefits of BG. More than 20,000 barley accessions from the USDA National Small Grains Collection (NSGC) have been assayed for BG content and the data recorded in the Germplasm Resources Information Network (GRIN). This study classified barley accessions as high or low BG content using the GRIN data, analyzed the relationship of BG content with the geographic origin of accessions and other barley descriptors, and verified the analysis with two replicated field experiments using a total of 829 accessions. Content of BG varied with geographic origin and spike‐row type. Accessions from Asia and Africa had higher frequencies of high‐BG‐content accessions and those from Europe and the Americas had higher frequencies of low‐BG‐content accessions. Two‐row accessions were more often classified as high BG content than six‐row types. There was no significant relationship between accession improvement status (e.g., landrace vs. either cultivar or breeding line) and BG content. The geographic differences among barley accessions likely correspond to the ecogeographic classification of barley and end‐use needs, such as malting vs. food barley, that vary by origin. Genebank databases should be expanded to include classification of relative BG content to make the data more readily useful to plant breeders.

We compared five methods for applying crop models to predict yield potential.A global weather database was divided into training and test sites.Metamodels and weather generation approaches performed best.Nearest neighbor interpolation can be replaced by superior and computationally efficient methods. Opportunities for and constraints to crop production can be assessed with crop growth simulation models. Most crop simulation models require daily weather data as input but such data are generally not available at a high spatial resolution. Several approaches have been developed to estimate yield potential (Yp) at locations without daily weather data (weather stations) but these have not been compared. We used two crop simulation models (WOFOST and LINTUL) to compute Yp for two crops for the entire world. A global weather database was divided into 856 training and 12,808 testing sites. We predicted Yp at the testing sites by using five main methods (eight methods if one considers within‐method variants): (i) weather interpolation followed by simulation; (ii) nearest neighbor interpolation; (iii) thin plate spline interpolation, either with or without covariates; (iv) Random Forest‐based metamodels with either climatic or bioclimatic variables; and (v) weather generation from either climate data or interpolated climate data, followed by simulation. The metamodel with bioclimatic variables performed best [average root mean square error (RMSE) = 667 ± 111 kg ha−1], followed by weather generation from climate data, weather interpolation, and spatial interpolation of yield with climatic covariables. The most commonly used method, nearest neighbor interpolation, performed worst (RMSE = 1763 ± 472 kg ha−1). The optimal method for a particular study will depend on the simulation model, the region, weather station density, and other variables but these results suggest that for estimating Yp, alternatives to nearest neighbor interpolation should be considered.

Current treatment for advanced stage ovarian clear cell cancer is severely hampered by a lack of effective systemic therapy options, leading to a poor outlook for these patients. Sequencing studies revealed that ARID1Ais mutated in over 50% of ovarian clear cell carcinomas. To search for a rational approach to target ovarian clear cell cancers with ARID1Amutations, we performed kinome-centered lethality screens in a large panel of ovarian clear cell carcinoma cell lines. Using the largest OCCC cell line panel established to date, we show here that BRD2 inhibition is predominantly lethal in ARID1Amutated ovarian clear cell cancer cells. Importantly, small molecule inhibitors of the BET (bromodomain and extra terminal domain) family of proteins, to which BRD2 belongs, specifically inhibit proliferation of ARID1Amutated cell lines, both in vitro and in ovarian clear cell cancer xenografts and patient-derived xenograft models. BET inhibitors cause a reduction in the expression of multiple SWI/SNF members including ARID1B, providing a potential explanation for the observed lethal interaction with ARID1Aloss. Our data indicate that BET inhibition may represent a novel treatment strategy for a subset of ARID1Amutated ovarian clear cell carcinomas.

Background: Increased cardiovascular disease risk and prevalence associated with overweight and obesity is due, in part, to heightened inflammatory burden. The mechanisms underlying adiposity-related amplification of inflammation are not fully understood. Alterations in regulators of inflammatory processes such as microRNAs (miRs), however, are thought to play a pivotal role. Objective: The aim of this study was to determine the influence of overweight and obesity, independent of other cardiovascular risk factors, on circulating expression of miR-34a, miR-126, miR-146a, miR-150 and miR-181b. Methods: Forty-five sedentary, middle-aged (47-64 years) adults were studied: 15 were normal weight (8M/7F; BMI: 23.3 ± 0.3 kg/m2); 15 were overweight (8M/7F; 28.2 ± 0.3 kg/m2); and 15 were obese (7M/8F; 32.3 ± 0.5 kg/m2). All subjects were non-smokers, normotensive and free of overt cardiometabolic disease. Circulating levels of the following inflammation-related miRs: miR-34a, miR-126, miR-146a, miR-150 and miR-181b were determined in plasma using standard RT-PCR techniques. miR expression was normalized to exogenous C. elegans miR-39 and reported as relative expression (AU). Results: Circulating miR-34a was ~200% higher (P < 0.05) in the obese as compared with normal weight and overweight groups. Whereas, miR-126, miR-146a and miR-150 were significantly lower (~65%) in both the obese and overweight groups than the normal weight group. There were no significant group differences in circulating expression of miR-181b. miR-34a was positively related (r = 0.43; P < 0.05); whereas, miR-126 (r = -0.48), miR-146a (r = -0.33) and miR-150 (r = -0.43) levels were significantly inversely related to BMI. Conclusion: Overweight and obesity, independent of other cardiometabolic risk factors, negatively influences circulating inflammation-related miRs. Dysregulation of circulating miRs may contribute mechanistically to the heightened inflammatory state associated with overweight and obesity.

microRNAs (miRNAs) have a key role in regulating inflammation, vascular health and in turn, cardiovascular disease. Specifically, altered circulating expression of miR-17, miR-21, miR-34a, miR-92a, miR-126, miR-145, miR-146a, and miR-150 has been linked with the pathogenesis and progression of cardiovascular disease. The aim of this study was to determine whether the circulating profile of these vascular-related miRNAs is disrupted with hypertension. Thirty sedentary, middle-aged adults were studied: 15 normotensive (10M/5F; age: 56 ± 1 year; BP: 113/71 ± 2/1 mmHg) and 15 hypertensive (10M/5F; 56 ± 2 year; 140/87 ± 2/2 mmHg). All subjects were non-obese and free of other cardiometabolic disorders. Circulating miRNAs were determined in plasma using standard RT-PCR techniques with miRNA primers of interest. Expression was normalized to exogenous C. elegansmiR-39 and reported as relative expression in arbitrary units (AU). Circulating expression of miR-34a (9.18 ± 0.94 vs 5.33 ± 0.91 AU) was higher (~170%; P< 0.01) whereas the expression of miR-21 (1.32 ± 0.25 vs 2.50 ± 0.29 AU), miR-126 (0.85 ± 0.10 vs 1.74 ± 0.27 AU) and miR-146a (1.50 ± 0.20 vs 3.10 ± 0.50 AU) were markedly lower (~50%, ~55%, and ~55% respectively; P< 0.05) in the hypertensive vs normotensive groups. Moreover, circulating levels of miR-34a, miR-21, and miR-126 were significantly related to systolic blood pressure (r= 0.48, r= −0.38; r= −0.48); whereas, miR-146a was significantly related to both systolic (r= −0.58) and diastolic (r= −0.55) blood pressure. There were no significant group differences in circulating miR-17, miR-92a, miR-145, and miR-150. In summary, these results suggest that hypertension, independent of other cardiometabolic risk factors, adversely affects the circulating profile of a subset of vascular-related miRNAs that have been link to CVD risk and development.

Crop phenology models that use constant temperature parameters across developmental stages may be less accurate and have temperature-dependent systematic prediction error (bias). Using the DD10 model, we evaluated default and optimized (DD_Opt) temperature parameters using data from seven California rice (Oryza sativaL.) cultivars grown in six locations over 3 yr (2012–2014). Furthermore, we evaluated the effect of using stage-dependent temperature parameters on model performance using two- and three-stage optimization approaches. Optimized temperature parameters, or DD_Opt (RMSE: 2.3–5.4 d), performed better than DD10 (RMSE: 2.9–7.3 d). A temperature sensitivity analysis indicated that the time from planting to panicle initiation was most sensitive to temperature (every 1°C increase decreased days to panicle initiation by 1.8 d) while time from heading to R7 (marked by the appearance of one yellow hull on the main stem panicle) was not affected by temperature. Optimized temperature parameters varied between stages, with base temperature decreasing and optimum temperature increasing with plant development. Compared to the DD_Opt, two-stage optimization (planting–heading and heading–R7) reduced the RMSE by 0.8 d and the systematic error by 0.6 d °C-1. Three-stage optimization (planting–panicle initiation, panicle initiation–heading, and heading–R7) further reduced RMSE by 1.1 d and systematic error by 1.4 d °C-1for preheading. These results demonstrate the importance of using stage-dependent parameters to improve accuracy of phenological models, which may be important when models are used to study the crop response to climate change, field management options, ecosystem productivity, breeding, and yield gap analysis.

Dirk Bouts, born about 1410 in Haarlem, moved to Louvain (Belgium) before 1448, where he died in 1475. His painting 'Ecce Agnus Dei', in which John the Baptist recognises Christ [...]

Colloidal 2D semiconductor nanocrystals, the analogue of solid-state quantum wells, have attracted strong interest in material science and physics. Molar quantities of suspended quantum objects with spectrally pure absorption and emission can be synthesized. For the visible region, CdSe nanoplatelets with atomically precise thickness and tailorable emission have been (almost) perfected. For the near-infrared region, PbS nanosheets (NSs) hold strong promise, but the photoluminescence quantum yield is low and many questions on the crystallinity, atomic structure, intriguing rectangular shape, and formation mechanism remain to be answered. Here, we report on a detailed investigation of the PbS NSs prepared with a lead thiocyanate single source precursor. Atomically resolved HAADF-STEM imaging reveals the presence of defects and small cubic domains in the deformed orthorhombic PbS crystal lattice. Moreover, variations in thickness are observed in the NSs, but only in steps of 2 PbS monolayers. To study the reaction mechanism, a synthesis at a lower temperature allowed for the study of reaction intermediates. Specifically, we studied the evolution of pseudo-crystalline templates toward mature, crystalline PbS NSs. We propose a self-induced templating mechanism based on an oleylamine-lead-thiocyanate (OLAM-Pb-SCN) complex with two Pb-SCN units as a building block; the interactions between the long-chain ligands regulate the crystal structure and possibly the lateral dimensions.

In geriatric medical practice and in epidemiological surveys doctors rely heavily on the information obtained from the medical history. In elderly subjects the accuracy of this information is questionable because [...]

An increase in glucose uptake driving aerobic glycolysis is a robust hallmark of immune cell activation. The glycolytic response supports functional alterations of the innate immune cells including the production and release of cytokines. Large inter-individual differences in the magnitude of this cytokine response are known to exist. In addition, the presence of disease is known to impact on immune cell function. Whether variation in metabolic responses of immune cells exist between individuals during health or disease is currently unknown. Here, we explore inter-individual differences in the glycolytic rate of immune cells using lactate production as readout upon activation using a variety of different stimuli. Glycolytic responses are subsequently associated to functional immune cell responses in healthy humans. In addition, we determined the glycolytic rate of immune cells and its association with immune function using patients diagnosed with diabetes mellitus. Based on the relative increase in lactate production after activation, distinct clusters of low, intermediate, and high responders could be identified, illustrating the existence of variation in glycolytic responses in healthy subjects. Interestingly, the production of cytokines mirrored these high-, intermediate-, and low-lactate patterns after pathogenic stimulation. In patients with diabetes mellitus, a reduced correlation was found between lactate and cytokine production, specifically for IL-6. Furthermore, based on the relative increase in lactate production, variability in the glycolytic response was reduced compared to healthy subjects. In conclusion, our results show a specific association between the glycolytic rate and function in human immune cells after stimulation with different pathogens. In addition to demonstrating the existence of glycolytic variability and specificity depending on the type of stimulus, the association between glycolysis and function in innate immune cells is altered during the presence of diabetes.

Proteinuria is an important cause of tubulointerstitial damage. Anti-proteinuric interventions are not always successful, and residual proteinuria often leads to renal failure. This indicates the need for additional treatment modalities by targeting the harmful downstream consequences of proteinuria. We previously showed that proteinuria triggers renal lymphangiogenesis before the onset of interstitial inflammation and fibrosis. However, the interrelationship of these interstitial events in proteinuria is not yet clear. To this end, we specifically blocked lymphangiogenesis (anti-VEGFR3 antibody), monocyte/macrophage influx (clodronate liposomes) or lymphocyte and myofibroblast influx (S1P agonist FTY720) separately in a rat model to investigate the role and the possible interaction of each of these phenomena in tubulointerstitial remodeling in proteinuric nephropathy. Proteinuria was induced in 3-month old male Wistar rats by adriamycin injection. After 6 weeks, when proteinuria has developed, rats were treated for another 6 weeks by anti-VEGFR3 antibody, clodronate liposomes or FTY720 up to week 12. In proteinuric rats, lymphangiogenesis, influx of macrophages, T cells and myofibroblasts, and collagen III deposition and interstitial fibrosis significantly increased at week 12 vs week 6. Anti-VEGFR3 antibody prevented lymphangiogenesis in proteinuric rats, however, without significant effects on inflammatory and fibrotic markers or proteinuria. Clodronate liposomes inhibited macrophage influx and partly reduced myofibroblast expression; however, neither significantly prevented the development of lymphangiogenesis, nor fibrotic markers and proteinuria. FTY720 prevented myofibroblast accumulation, T-cell influx and interstitial fibrosis, and partially reduced macrophage number and proteinuria; however, it did not significantly influence lymphangiogenesis and collagen III deposition. This study showed that proteinuria-induced interstitial fibrosis cannot be halted by blocking lymphangiogenesis or the influx of macrophages. On the other hand, FTY720 treatment did prevent T-cell influx, myofibroblast accumulation and interstitial fibrosis, but not renal lymphangiogenesis and proteinuria. We conclude that tubulointerstitial fibrosis and inflammation are separate from lymphangiogenesis, at least under proteinuric conditions.

An analytical framework is described for assessing the nutritional adequacy of national food supplies and the potential for addressing micronutrient gaps by increased crop production and crop diversity. The micronutrient contents of national food supplies of three countries (Bangladesh, Senegal, and Cameroon) were estimated using data from national food balance sheets. Population-adjusted nutrient requirements and identified nutrient short-falls, defined as not meeting the requirements of at least 80 % of the population, were also estimated. Linear programming models were used to determine a mix of crops that could meet the gaps the deficits of several nutrients while minimizing the use of additional agricultural land. Out of eight micronutrients included in the present analysis, six were identified as inadequate in Bangladesh and Senegal (vitamins A and C, riboflavin, folate, calcium, and zinc) and three were inadequate in Cameroon (vitamin A, calcium, and zinc). Adequacy of vitamins A and C could be met by increasing production of a few crops that are particularly dense in these nutrients (e.g., carrots or guava), which would necessitate only a small addition of agricultural land. Folate adequacy could be improved with increased production of legumes and green leafy vegetables, but with a greater requirement for agricultural land. Some micronutrient gaps, however, would probably have to be met by other means, such as enhanced livestock production, food fortification, biofortification, or imports. Despite the limitations of agriculture to meet the entire nutrient needs of a population, agricultural policy should consider the potential to improve nutrient adequacy with the crops currently available and by crop diversification.

To meet the growing demand for rice and to ease the pressure on mountain ecosystems in northern Laos, it has been proposed to reduce upland rice cultivation and to expand the area under paddy rice. We used Random Forest, a classification and decision-tree-based method, to characterize the areas currently under paddy cultivation, and to predict which areas are suitable for paddy. Topographic variables and accessibility to villages and roads were the most important predictors for the presence of paddy cultivation. There appears to be much land available that is suitable for expanding paddy areas in central and southern Laos but not in the north, where more than 40% of the rice area is on sloping land, and much less area is suitable. We conclude that expanding paddy-based rice production will be difficult in most parts of northern Laos.

The article reports on the growth of piracy activities in the high seas of Somalia. It describes several factors that contributed to the success of attacks including the expansion of the area of operation by the pirates and the use of large merchant vessels as mother ships. It discusses some anti-piracy operations carried out by public and private sectors.

Abstract:It was long thought that Sol Invictus was a Syrian sun-god, and that Aurelian imported his cult into Rome after he had vanquished Zenobia and captured Palmyra. This sun-god, it was postulated, differed fundamentally from the old Roman sungod Sol Indiges, whose cult had long since disappeared from Rome. Scholars thus tended to postulate a hiatus in the first centuries of imperial rule during which there was little or no cult of the sun in Rome. Recent studies, however, have shown that Aurelian’s Sol Invictus was neither new nor foreign, and that the cult of the sun was maintained in Rome without interruption from the city’s earliest history until the demise of Roman religion(s). This continuity of the Roman cult of Sol sheds a new light on the evidence for priests and temples of Sol in Rome. In this article I offer a review of that evidence and what we can infer from it about the Roman cult of the sun. A significant portion of the article is devoted to a temple of Sol in Trastevere, hitherto misidentified. Résumé:Durant longtemps, on a cru que Sol Invictus était un dieu-soleil syrien, dont Aurélien aurait importé le culte à Rome, après avoir vaincu Zénobie et pris Palmyre. Ce dieusoleil, supposément, différait fondamentalement de l’ancien dieu-soleil romain, Sol Indiges, dont le culte avait depuis longtemps disparu de Rome. Les chercheurs tendaient ainsi à postuler que les premiers siècles du régime impérial avaient connu un hiatus, durant lequel il n’y aurait eu que peu ou pas de culte du soleil à Rome. Des études récentes ont toutefois montré que le Sol Invictus d’Aurélien n’était ni nouveau ni étranger et que le culte du soleil s’était maintenu à Rome sans interruption, depuis les débuts de la cité jusqu’à la disparition de la (des) religion(s) romaine(s). Cette continuité dans le culte romain de Sol jette un éclairage nouveau sur les témoignages relatifs aux prêtres et aux temples de Sol à Rome. Dans cet article, je propose d’examiner ces témoignages et ce que nous pouvons en déduire sur le culte romain du soleil. Une partie significative de cet article est consacrée à un temple de Sol dans le Trastevere, jusque-là mal identifié

Around fifteen years before the chemical substance alumina (aluminium oxide) could be decomposed in the laboratory, it was identified as a compound and predicted to contain a new element called ‘aluminium’. Using this episode from early nineteenth-century chemistry as a case study for the use of analogical reasoning in science, this paper examines how chemists relied on chemical classifications for the prediction of aluminium. I argue that chemists supplemented direct evidence of chemical decomposition with analogical inferences in order to evaluate the composition of substances. Since they were established on the basis of relevant similarities in chemical properties, classifications were taken to reflect so-called ‘chemical analogies’ between substances. In combination with the knowledge that analogous properties indicated similarities in composition, this enabled chemists to infer the composition of experimentally indecomposable substances by analogy. The trust in such analogical inferences, even if they could not be confirmed through experiment, was justified by pragmatic considerations. Whereas the possibility of decomposing a substance depended on the available laboratory techniques, chemical analogies were thought to last independently of internal composition. It was therefore more practical to keep well-established classes of substances together rather than separate them on the basis of experimental results that might evolve as new techniques were developed. Besides highlighting the links between analogical reasoning and classification, this paper also illustrates the importance of analogy in the evaluation of elementary nature in the early nineteenth century.

Coconut Coir Pith (CCP) is a relatively unexplored type of lignocellulosic waste from the coconut industry. As a feedstock that is highly enriched in lignin (Klason lignin content of 40.9 wt % found in this study), CCP is a potential source for renewable lignin-derived materials. We have performed a systematic study on the characterization and valorization of lignin from CCP. We have investigated two different valorization approaches: reductive catalytic fractionation (RCF) and soda pulping followed by catalytic hydrodeoxygenation. During RCF, the lignin was converted into monomeric products in 7.6 wt %. Using soda pulping conditions, we were able to isolate lignin from CCP in 74% yield. Subsequent hydrotreatment of the lignin over a Pt/MoO3/TiO2catalyst resulted in the formation of hydrogenated oil in 43 wt % yield, suitable for the production of biobased diesel fuels and lubricant base oils.

Wheat stem rust, caused by Puccinia graminisPers.:Pers f. sp. triticiEriks. & Henn., is of renewed concern due to the emergence of a new virulent race in East Africa. Landrace accessions of common wheat (Triticum aestivumL. subsp. aestivum) and durum wheat (T. turgidumL. subsp. durum) from the National Small Grains Collection (NSGC) could be sources of new stem rust resistance genes. In an effort to better target the screening of NSGC landrace accessions against the new race, data from the NSGC were analyzed for the geographic distribution of resistance. We used data from U.S. screening trials for 5700 landrace accessions of common wheat and 2719 of durum wheat. Areas with a high incidence of stem rust resistance were found in Ethiopia, Chile, Turkey, Bosnia and Herzegovina, and adjacent areas of the former Yugoslavia. Resistance to multiple races at the seedling stage was most frequent in accessions from Ethiopia and Turkey. Resistance in durum wheat was more frequent than resistance in common wheat. The distribution of the areas with high incidence of resistant durum landraces was similar to that for common wheat landraces. A logistic regression model predicting resistance in common wheat accessions (n= 3607) from 10 traits identified 192 previously untested accessions with a greater than 50% chance of being resistant. Based on this model and on the identification of geographic centers for resistance, accessions will be prioritized for future screening against new stem rust races.

We present new results on an optical implementation of Grover's quantum search algorithm. This extends previous work in which the transverse spatial mode of a light beam oscillates between a broad initial input shape and a highly localized spike, which reveals the position of the tagged item. The spike reaches its maximum intensity after ∼√N round trips in a cavity equipped with two phase plates, where N is the ratio of the surface area of the original beam and the area of the phase spot or tagged item. In our redesigned experiment the search space is now two dimensional. In the time domain, we demonstrate for the first time a multiple-item search where the items appear directly as bright spots on the images of a gated camera. In a complementary experiment we investigate the searching cavity in the frequency domain. The oscillatory nature of the search algorithm can be seen as a splitting of cavity eigenmodes, each of which concentrates up to 50% of its power in the bright spot corresponding to the solution.

Recently, the upstream stimulatory factor 1 gene (USF1) was proposed as a candidate gene for familial combined hyperlipidemia (FCH). In this study, we examined the previously identified risk haplotype of USF1 with respect to FCH and its related phenotypes in 36 Dutch FCH families. The diagnosis of FCH was based on both the traditional diagnostic criteria and a nomogram. The two polymorphisms, USF1s1 and USF1s2, were in complete linkage disequilibrium. No association was found for the individual single nucleotide polymorphisms (SNPs) with FCH defined by the nomogram (USF1s1, P = 0.53; USF1s2, P = 0.53), whereas suggestive associations were found when using the traditional diagnostic criteria for FCH (USF1s1, P = 0.08; USF1s2, P = 0.07). USF1 was associated with total cholesterol (USF1s1, P = 0.05; USF1s2, P = 0.04) and apolipoprotein B (USF1s1, P = 0.06; USF1s2, P = 0.04). Small dense LDL showed a suggestive association (USF1s1, P = 0.10; USF1s2, P = 0.09). The results from the haplotype analyses supported the results obtained for the individual SNPs. In conclusion, the previously identified risk haplotype of USF1 showed a suggestive association with FCH and contributed to the related lipid traits in our Dutch FCH families.

Landrace accessions of wheat (Triticum aestivumL. subsp. aestivum) from the USDA‐ARS National Small Grains Collection (NSGC) have been tested systematically for the past 25 yr for disease resistance. We analyzed the resistance of 10 759 common wheat accessions to common bunt (CB) caused by Tilletia tritici(Bjerk.) Wint. and T. laevisKühn, and 8167 to dwarf bunt (DB) caused by T. controversaKühn with respect to geographic origin, relationship to color of awn, glume, and kernel of accessions, and phenotypic variation within areas of high frequency of resistance. A clear center of concentration was evident for CB resistance extending from Serbia and Montenegro through Macedonia, Turkey, and Iran with the highest frequency of resistance occurring in Kosovo province in Serbia and Montenegro (36%) and Bakhtaran province in Iran (40.8%). Compared to CB resistance (5.5% of total tested), DB resistance was more rare (1.3% of total tested). DB resistance was concentrated in accessions from Iran, Turkey, and Serbia and Montenegro with the highest frequency (58%) occurring in Hakkari province in southeastern Turkey. CB resistance was positively associated with lightly pigmented kernels and negatively associated with lightly pigmented awns and glumes. Analysis of accessions from areas with unusually high frequency of resistance suggested that DB resistant accessions from Hakkari are genetically diverse, whereas CB resistant accessions from Bakhtaran may be much less so.

Proinflammatory cytokines, such as interleukin-1ββ(IL-1ββ), IL-6, and tumor necrosis factor-αα(TNF-αα), are suggested to have an important role in the process of atherosclerosis. Patients with heterozygous familial hypercholesterolemia (FH) have a marked elevation in the plasma level of low-density lipoproteins (LDL), and they show early development of atherosclerosis. The aim of the present study was to test with a whole blood culture system if hyperlipoproteinemia is associated with increased cytokine production capacity in these patients and if treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors influences this production capacity of blood cells, at both the protein and mRNA levels. The capacity of blood cells in a whole blood culture to produce IL-1ββ, IL-6, TNF-αα, IL-12, IL-18, and IL-1 receptor antagonist (IL-1Ra) in response to lipopolysaccharide (LPS) appeared to be similar for heterozygous FH patients and healthy volunteers. Furthermore, the capacity to produce IL-1ββ, IL-6, and TNF-ααin response to LPS was not modified by cholesterol synthesis inhibitors at the level of mRNA expression or at the level of release. On the other hand, the release of IL-1Ra was significantly increased after treatment with HMG-CoA reductase inhibitors, although only at the protein level. This suggests a possible beneficial anti-inflammatory role for this therapy.

In many European countries the question of cultural identity has gained special importance due to the increase of globalization, the position of the United States, and the European unification. How can political leaders deal with these developments without alienating their people? In what ways do they express national identity in popular communication? Is nationalism a characteristic of their rhetoric? These questions are asked in regard to thirty-six New Year's speeches held by the last five French presidents. By answering these questions we will develop a perspective on the concepts of national identity and nationalism.Discourse analysis shows a typical discourse for every president, in which nationalist rhetoric appears to play a role. Above all, differences between three structures of significance, or frames, are distinguished, which can be described as ‘sense of belonging’ or ‘paternal protection’, ‘the myth of French values’, and ‘the significant other’.

Although originally domesticated in tropical America, the sweetpotato [Ipomoea batatas(L.) Lam.] has a long history of cultivation in the Pacific region. While the post-Columbus dispersal of sweetpotato to Asia and the Pacific is well documented, the hypothesis that there was a prehistoric transfer of sweetpotato by Peruvian or Polynesian voyagers from Peru to Oceania has long been a controversial issue. The objective of this study was to assess the genetic diversity and interrelationships of sweetpotato landraces from the Pacific region and Latin America, and test the hypothesis of human transfer of this crop to the Pacific Island in prehistoric times. Seventy-five sweetpotato landraces from Peru, Ecuador, Mexico, the Philippines, Papua New Guinea (PNG) and 5 Oceania countries were analyzed using amplified fragment length polymorphism (AFLP). Multidimensional scaling (MDS) and analysis of molecular variance (AMOVA) revealed a large genetic variation in the Oceania gene pool, far greater than that in Peru-Ecuador. The Mexican cultivars were grouped together with those of Oceania. In contrast, there is little association between the Peru-Ecuador germplasm and that of Oceania. These results suggest that Peru-Ecuador may not be the source of the Oceania sweetpotato germplasm. Natural dispersal from Mesoamerica is an alternative explanation, to the ‘Kumara hypothesis’, for the origin of the Oceania sweetpotato.

The effect of climate change on global potato production was assessed. Potential yields were calculated with a simulation model and a grid with monthly climate data for current (1961–1990) and projected (2010–2039 and 2040–2069) conditions. The results were mapped and summarized for countries. Between 1961–1990 and 2040–2069 the global (terrestrial excluding Antarctica) average temperature is predicted to increase between 2.1 and 3.2 C, depending on the climate scenario. The temperature increase is smaller when changes are weighted by the potato area and particularly when adaptation of planting time and cultivars is considered (a predicted temperature increase between 1 and 1.4 C). For this period, global potential potato yield decreases by 18% to 32% (without adaptation) and by 9% to 18% (with adaptation). At high latitudes, global warming will likely lead to changes in the time of planting, the use of later-maturing cultivars, and a shift of the location of potato production. In many of these regions, changes in potato yield are likely to be relatively small, and sometimes positive. Shifting planting time or location is less feasible at lower latitudes, and in these regions global warming could have a strong negative effect on potato production. It is shown that heat-tolerant potato cultivars could be used to mitigate effects of global warming in (sub)tropical regions.

Abstract:Ce n’est qu’au IVesiècle que s’est instaurée la tradition de célébrer l’anniversaire du Christ le 25 décembre, le jour exact de sa naissance étant de fait inconnu. Aujourd’hui, les spécialistes se rangent à la théorie de Hermann Usener (fin du XIXesiècle) selon laquelle l’église primitive aurait choisi cette date dans le but de supplanter une importante fête païenne en l’honneur de Sol Invictus. Mais l’importance de cette fête a été exagérée, et les témoignages indiquent que la raison de ce choix réside plutôt dans la valeur symbolique attribuée au solstice d’hiver (traditionnellement le 25 décembre).

Native LDL (nLDL) increases expression of adhesion molecules on endothelial cells through induction of Ca(2+) mobilization. Ca(2+) mobilization is also involved in the induction of proinflammatory cytokines, important mediators involved in atherogenesis. The aim of the study was to evaluate the capacity of nLDL to affect spontaneous and lipopolysaccharide (LPS)-stimulated cytokine production. Preincubation of human peripheral blood mononuclear cells (PBMC) with nLDL for 24 h did not influence spontaneous production of tumor necrosis factor alpha (TNF alpha) or interleukin-8 (IL-8), but significantly potentiated LPS-induced production of these cytokines. nLDL preincubation of PBMC did not increase the expression of the LPS receptors Toll-like receptor-4, CD14, or CD11c/CD18. Potentiation of cytokine production by nLDL was mediated through induction of Ca(2+) mobilization, because: a) nLDL induced a sustained pattern of repetitive Ca(2+) transients in human PBMC; b) the Ca(2+) chelator fura 2-acetoxymethyl ester, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, an intracellular Ca(2+) chelator, inhibited the potentiating effect of nLDL on LPS-induced cytokine synthesis; c) induction of Ca(2+) mobilization by thapsigargin potentiated LPS-induced cytokine production. nLDL are able to potentiate LPS-induced production of cytokines by human PBMC, and this effect is probably mediated through induction of Ca(2+) mobilization. This may represent an important pathogenetic mechanism in atherogenesis induced by hyperlipoproteinemia.

AbstractThis article aims to examine existential meaning constructions from an action theoretical perspective in a specific Internet environment: the personal homepage. Personal homepages are on-line multi-media documents addressing the question Who am I? Authors of personal homepages provide information on both their personal and public identity. These identity constructions sometimes include reflections on the meaning of life. Answers to questions on the meaning of life reflect the way in which individuals assign ultimate meanings to human life, and consist of three key components: orientation (goals and objectives), beliefs, and experience. This paper aims to examine existential meaning constructions from a action theoretical perspective in a specific Internet environment: the personal homepage. Findings are reported of a qualitative content analysis of answers to the meaning of life provided in a sample of 42 personal homepages. We found that most answers to the meaning of life could be interpreted either as divine/religious, experience centered, cosmic, or social utopian. The answers provided on the homepages showed similarities with findings reported in other studies on existential meaning. In addition, we found that this Internet environment offers new venues for expressing orientation (goals and objectives), beliefs, and experience reflecting answers to the meaning of life.

The global distribution of potato area is described using country-level statistics and a new geo-referenced database. There are two main peaks in global potato distribution by latitude. The major peak is between 45°N and 57°N and represents potato production zones in the temperate climates where potato is a summer crop. The other peak is between 23°N and 34°N, and mainly represents production zones in the subtropical lowlands, where potato is a winter crop. Between 1950 and 1998 potato production area increased at low latitudes and decreased at high latitudes, particularly around 53°N (this zone includes parts of Belarus, Germany, Poland, Russia, and Ukraine). The northern limit of potato production coincides with the boundaries of agriculture and the presence of human population. The peak between 23°N and 34°N coincides with the area of highest population density (per area of land and per area of arable land). About 25% of the global potato area is in the highlands (above 1000 m).

This paper reviews the systematics of wild potatoes over the past 11 years, in reference to the latest comprehensive taxonomic treatment by Hawkes (1990. The potato: evolution, biodiversity and genetic resources. Belhaven Press, Washington, D.C.). Included here is information on monographs and floras, new germplasm collections made since 1988 compared to total potato distributional data, new taxonomic changes (including synonymy and new species descriptions), ingroup and outgroup relationships, intraspecific studies, diversity studies, and fingerprinting. In addition, data supporting taxonomic changes and phylogeny from ploidy levels, Endosperm Balance Numbers, and morphological studies of taxonomically important characters are reviewed. A revised list of 206 species is presented (from 232 in Hawkes) that incorporates recent synonymy of names, recognition of new names, and new species descriptions. New germplasm collections of 58 potato taxa were collected that did not occur in genebanks before 1988.

Peru contains about half of the described wild potato taxa, and many of these are not yet preserved in genebanks. This paper reports results of the second of a series of five planned collecting expeditions to Peru. Collections were made in the central Peruvian departments of Ancash, Huancavelica, La Libertad, and Lima, from March 8 to April 25,1999. They follow collections in 1998 in the southern Peruvian departments of Apurimac, Arequipa, Cusco, Moquegua, Puno, and Tacna. We collected 101 germplasm accessions, including first germplasm collections of the following 22Solanumtaxa:Solanum amayanum, S. anamatophilum, S. arahuayum(lost in germplasm increase),S. augustii, S. bill- hookeri, S. cantense, S. chavinense, S. chomatophilum var. subnivale, S. chrysoflorum, S. gracilifrons, S. hapalos um, S. huarochiriense, S. hypacrarthrum, S.jalcae, S. moniliforme, S. multiinterruptum f. longipilosum, S. multiinterruptum var. machaytambinum, S. peloquinianum, S. rhombilanceolatum, S. simplicissimum, S. taulisense(lost in germplasm increase), andS. wittmackii. In addition, new collections were made of the under-collected speciesS. hastiforme(three collections). The above taxonomy is that used in planning our expedition, that we compare to a new treatment of Peruvian wild potatoes published by C. Ochoa in 1999. This paper reports the collection and new species identifications of the 1999 collections, and germplasm conservation and survival of the 1998 and 1999 collections. In addition, chromosome counts are provided for 134 accessions from the 1998 and 1999 expeditions, including first reports forS. chomatophilum var. subnivale(2n = 2x = 24),S. megistacrolobumsubsp.purpureum(2n = 2x = 24), andS. multiinterruptumvar.multiinterruptumf.albiflorum(2n = 2x = 24); we also report the first triploid count of an accession ofS. immite.

Background:Aging is associated with a progressive increase in risk and prevalence of cardiovascular disease (CVD). Endothelial cell dysfunction is considered to be a central mechanism underlying the age-related increase in vascular risk and disease. However, the direct, and indirect, effects of aging on endothelial cell biology are diverse and not completely understood.Clinical interest in circulating extracellular vesicles, particularly endothelial cell-derived microvesicles (EMVs), has intensified due to their involvement in the development and progression of endothelial dysfunction and CVD. The purpose of this study was to determine: 1) if circulating EMV levels increase with age, independent of other cardiometabolic risk factors; and if so, 2) whether circulating EMVs are associated with age-related endothelial vasodilator dysfunction.Methods:Thirty-six healthy, non-obese, normotensive, sedentary men were studied: 12 young (age: 27+1 yr); 12 middle-aged (51+1 yr) and 12 older (67+2 yr). EMV identification (CD31+/42b-) and concentration in peripheral blood was determined by flow cytometry. Forearm blood flow (FBF: via plethysmography) was assessed in response to intra-arterial infusions of acetylcholine (4.0, 8.0 and 16.0 μg/100 mL tissue/min) and sodium nitroprusside (1.0, 2.0 and 4.0 μg/100 mL tissue/min) in 8 young, 8 middle-aged and 8 older men.Results:Circulating EMV levels were significantly and progressively higher across the young, middle-aged and older groups (57+5 vs 102+9 vs 134+16 EMV/μL, respectively). FBF response to acetylcholine was significantly and progressively lower (~35%) in the young (from 5.2±0.4 to 17.2±1.8 mL/100 mL tissue/min) vs middle-aged (4.5±0.3 to 13.2±1.2 mL/100 mL tissue/min) vs older (4.2±0.3 to 11.3±0.8 mL/100 mL tissue/min) group. Circulating EMVs were positively associated with age (r=0.67; P<0.01) and inversely associated with the vasodilator response to acetylcholine (r=-0.43; P<0.01).Conclusions:Aging, independent of other cardiometabolic risk factors, is associated with progressive elevated circulating levels of EMVs. Circulating EMVs may serve as a biomarker of, and contributor to, age-related endothelial dysfunction and vascular disease risk.

The potato crop originated in the Andean highlands where numerous farmer's varieties and non-cultivated wild species exist. An Andean potato collection is held in trust at the International Potato Center (CIP) to preserve the biodiversity of this crop and ensure the supply of germplasm for potato improvement worldwide. A core collection representing the biodiversity of the Andean potato germplasm is under construction using morphological, molecular, and geographic data. One of the eight cultivated potato species, Solanum phureja, has been genotyped using the RAPD technique. A protocol suitable for large germplasm collection genotyping has been developed to process numerous samples at reasonable costs. From 106 RAPD primers evaluated, we have selected 12 primers yielding 102 polymorphic markers, which unambiguously discriminated all 128 accessions but 2 that are possible duplicates. The S. phureja germplasm collected throughout the Andean countries appears to have a homogeneous genetic constitution. There was no clear geographic pattern as indicated by cluster analysis of the RAPD data. A sub-group of 20 accessions has been identified on the basis of the marker data and selected to maximize molecular (RAPD) variance and polymorphism. The probability of capturing equal amounts of marker polymorphism in this sub-group of 20 accessions by random sampling is less than 40%. This set accessions represents our first group of accessions that may constitute a core of the S. phureja collection. This tentative core will be challenged for diversity content by alternate markers and agronomic traits. Hence, the methodology for sampling less than 10% of the base collection, proposed for core collections by Brown (1989), can be based on molecular marker data provided cost-efficient fingerprints are developed.

Peru has 103 taxa of wild potatoes (species, subspecies, varieties, and forms) according to Hawkes (1990; modified by us by a reduction of species in theSolanum brevicaulecomplex) and including taxa described by C. Ochoa since 1989. Sixty-nine of these 103 taxa (67% ) were unavailable from any of the world’s genebanks and 85 of them (83%) had less than three germplasm accessions. We conducted a collaborative Peru (INIA), United States (NRSP-6), and International Potato Center (CIP) wild potato (Solanumsect.Petota)collecting expedition in Peru to collect germplasm and gather taxonomic data. This is the first of a series of planned expeditions from 1998–2002. We collected from February 18 to April 18, 1998, in the southern departments of Apurímac, Arequipa, Cusco, Moquegua, Puno, and Tacna. We made 57 germplasm collections, including 14 taxa that are the first available as germplasm for any country (Solanum aymaraesense, S. chillonanum, S. incasicum, S. megistacrolobumsubsp.megistacrolobum f. purpureum, S. longiusculus, S. multiflorum,S. pillahuatense, S. sawyeri, S. sandemanii, S. tacnaense, S. tarapatanum, S. urubambae, S. velardei, S. villuspetalum), and two additional taxa that are the first available for Peru but with germplasm from Bolivia (S. megistacrolobumsubsp.toralapanum, S. yungasense).Collections also were made for the rare taxaS. acroscopicum, S. buesii, S. limbaniense, andS. santolallae.Our collections suggest the following minimum synonymy may be needed for Peruvian potatoes:S. sawyerias a synonym ofS. tuberosum;S. hawkesiiandS. incasicumas synonyms ofS. raphanifolium;S. multiflorumandS. villuspetalumas synonyms ofS. urubambae.

The geographic co-ordinates of the locations where germplasm accessions have been collected are usually documented in genebank databases. However, the co-ordinate data are often incomplete and may contain errors. This paper describes procedures to check for errors, to determine the cause of these errors and to assign new co-ordinates, using Geographical Information Systems (GIS). These procedures can assist in improving the quality of genebank databases, and with that, increase the capability for analysis and use of crop genetic diversity.

The product of the c‐myc proto‐oncogene, c‐Myc, is a sequence‐specific DNA binding protein with an N‐terminal transactivation domain and a C‐terminal DNA binding domain. Several lines of evidence indicate that c‐Myc activity is essential for normal cell cycle progression. Since the abundance of c‐Myc during the cell cycle is constant, c‐Myc's activity may be regulated at a post‐translational level. We have shown previously that the N‐terminus of c‐Myc can form a specific complex with the product of the retinoblastoma gene, pRb, in vitro. These data suggested a model in which pRb, or pRb‐related proteins, regulate c‐Myc activity through direct binding. We show here that the pRb‐related protein p107, but not pRb itself, forms a specific complex with the N‐terminal transactivation domain of c‐Myc in vivo. Binding of p107 to c‐Myc causes a significant inhibition of c‐Myc transactivation. Expression of c‐Myc releases cells from a p107‐induced growth arrest, but not from pRb‐induced growth arrest. Our data suggest that p107 can control c‐Myc activity through direct binding to the transactivation domain and that c‐Myc is a target for p107‐mediated growth suppression.

Hairy cell leukemia (HCL) is a usually chronic B cell lymphoproliferative disorder. To evaluate the prognostic significance of the various heavy and light chain determinants of the surface immunoglobulins (slg), we analyzed the clinical data and immunologic phenotype of 64 patients with HCL. Sixty-two of the 64 patients showed slg, which was invariably of only one light chain type (kappa 33, lambda 29). The actuarial survival of the cases expressing kappa-light chains was significantly better than those with lambda-light chains (p less than 0.002). This difference persisted when only cases with gamma or alpha gamma heavy chains were considered. No differences between the kappa and lambda-subgroups were discovered with respect to parameters of clinical importance. The various heavy chain classes of slg did not correlate significantly with the survival time. These results suggest that the immunologic phenotype, in particular the light chain type, may be a prognostic factor in patients with HCL.

We discuss the experimental and theoretical aspects of absorption spectroscopy of cold atomic hydrogen gas in a magnetostatic trap using a pulsed narrow-band source (bandwidth ˜ 100 MHz) at the Lyman-a wavelength (121.6 nm). A careful analysis of the measured absorption spectra enables us to determine non-destructively the temperature and the density of the trapped gas. The development of this diagnostic technique is important for future attempts to reach Bose-Einstein condensation in trapped atomic hydrogen.