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Contains fulltext : 231651.pdf (Publisher’s version ) (Open Access) In vitro neuronal models are essential for studying neurological physiology, disease mechanisms and potential treatments. Most in vitro models lack controlled vasculature, despite its necessity in brain physiology and disease. Organ-on-chip models offer microfluidic culture systems with dedicated micro-compartments for neurons and vascular cells. Such multi-cell type organs-on-chips can emulate neurovascular unit (NVU) physiology, however there is a lack of systematic data on how individual cell types are affected by culturing on microfluidic systems versus conventional culture plates. This information can provide perspective on initial findings of studies using organs-on-chip models, and further optimizes these models in terms of cellular maturity and neurovascular physiology. Here, we analysed the transcriptomic profiles of co-cultures of human induced pluripotent stem cell (hiPSC)-derived neurons and rat astrocytes, as well as one-day monocultures of human endothelial cells, cultured on microfluidic chips. For each cell type, large gene expression changes were observed when cultured on microfluidic chips compared to conventional culture plates. Endothelial cells showed decreased cell division, neurons and astrocytes exhibited increased cell adhesion, and neurons showed increased maturity when cultured on a microfluidic chip. Our results demonstrate that culturing NVU cell types on microfluidic chips changes their gene expression profiles, presumably due to distinct surface-to-volume ratios and substrate materials. These findings inform further NVU organ-on-chip model optimization and support their future application in disease studies and drug testing.

In this paper, a wire detection algorithm is proposed for synthetic aperture radar (SAR) images. The algorithm is specifically designed for SAR images generated from an agile, drone-mounted, omnidirectional radar array to be used for the detection of improvised explosive devices (IEDs). A multistage approach consisting of denoising, constant false alarm rate (CFAR) thresholding, feature extraction, and automated detection using the Radon transform, is proposed and applied to a set of SAR images with multiple aspect angles. At each detection step, the look-angles of individual pixels are used to remove false alarms, and improve detection accuracy. The algorithm is tested using measured data and provides an acceptable detection performance on straight wire segments even in the presence of a strong background clutter.

Summary: Epilepsy, intellectual and cortical sensory deficits, and psychiatric manifestations are the most frequent manifestations of mitochondrial diseases. How mitochondrial dysfunction affects neural structure and function remains elusive, mostly because of a lack of proper in vitro neuronal model systems with mitochondrial dysfunction. Leveraging induced pluripotent stem cell technology, we differentiated excitatory cortical neurons (iNeurons) with normal (low heteroplasmy) and impaired (high heteroplasmy) mitochondrial function on an isogenic nuclear DNA background from patients with the common pathogenic m.3243A > G variant of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). iNeurons with high heteroplasmy exhibited mitochondrial dysfunction, delayed neural maturation, reduced dendritic complexity, and fewer excitatory synapses. Micro-electrode array recordings of neuronal networks displayed reduced network activity and decreased synchronous network bursting. Impaired neuronal energy metabolism and compromised structural and functional integrity of neurons and neural networks could be the primary drivers of increased susceptibility to neuropsychiatric manifestations of mitochondrial disease. : Using human-inducible-pluripotent-stem-cell-derived neurons with high levels of m.3243A > G heteroplasmy, Klein Gunnewiek et al. show neuron-specific mitochondrial dysfunction as well as structural and functional impairments ranging from reduced dendritic complexity and fewer synapses and mitochondria to reduced neuronal activity and impaired network synchronicity. Keywords: MELAS, mitochondrial disease, mitochondria, neuron, induced pluripotent stem cells, network activity, neurodevelopment, micro-electrode array, m.3243A > G

Objective The peroxisome proliferator-activated receptor-γ coactivator-1α1 (PGC-1α1) regulates genes involved in energy metabolism. Increasing adipose tissue energy expenditure through PGC-1α1 activation is potentially beneficial for systemic metabolism. Pharmacological PGC-1α1 activators could be valuable tools in the fight against obesity and metabolic disease. Finding such compounds has been challenging partly because PGC-1α1 is a transcriptional coactivator with no known ligand-binding properties. While, PGC-1α1 activation is regulated by several mechanisms, protein stabilization is a crucial limiting step due to its short half-life under unstimulated conditions. Methods We designed a cell-based high-throughput screening system to identify PGC-1α1 protein stabilizers. Positive hits were tested for their ability to induce endogenous PGC-1α1 protein accumulation and activate target gene expression in brown adipocytes. Select compounds were analyzed for their effects on global gene expression and cellular respiration in adipocytes. Results Among 7,040 compounds screened, we highlight four small molecules with high activity as measured by: PGC-1α1 protein accumulation, target gene expression, and uncoupled mitochondrial respiration in brown adipocytes. Conclusions We identify compounds that induce PGC-1α1 protein accumulation and show that this increases uncoupled respiration in brown adipocytes. This screening platform establishes the foundation for a new class of therapeutics with potential use in obesity and associated disorders., Graphical abstract, Highlights • A high-throughput platform to identify PGC-1α1 activators. • PGC-1α1 protein stabilizers work as activators in brown adipocytes. • Small molecule PGC-1α1 activators induce Ucp1 expression and cellular respiration.

SummaryEpilepsy, intellectual and cortical sensory deficits and psychiatric manifestations are among the most frequent manifestations of mitochondrial diseases. Yet, how mitochondrial dysfunction affects neural structure and function remains largely elusive. This is mostly due to the lack of a properin vitrotranslational neuronal model system(s) with impaired energy metabolism. Leveraging the induced pluripotent stem cell technology, from a cohort of patients with the common pathogenic m.3243A>G variant of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), we differentiated excitatory cortical neurons (iNeurons) with normal (low heteroplasmy) and impaired (high heteroplasmy) mitochondrial function on an isogenic nuclear DNA background. iNeurons with high levels of heteroplasmy exhibited mitochondrial dysfunction, delayed neural maturation, reduced dendritic complexity and fewer functional excitatory synapses. Micro-electrode array recordings of neuronal networks with high heteroplasmy displayed reduced network activity and decreased synchronous network bursting. The impaired neural energy metabolism of iNeurons compromising the structural and functional integrity of neurons and neural networks, could be the primary driver of increased susceptibility to neuropsychiatric manifestations of mitochondrial disease.

Background Skeletal muscle mass and strength are crucial determinants of health. Muscle mass loss is associated with weakness, fatigue, and insulin resistance. In fact, it is predicted that controlling muscle atrophy can reduce morbidity and mortality associated with diseases such as cancer cachexia and sarcopenia. Methods We analyzed gene expression data from muscle of mice or human patients with diverse muscle pathologies and identified LMCD1 as a gene strongly associated with skeletal muscle function. We transiently expressed or silenced LMCD1 in mouse gastrocnemius muscle or in mouse primary muscle cells and determined muscle/cell size, targeted gene expression, kinase activity with kinase arrays, protein immunoblotting, and protein synthesis levels. To evaluate force, calcium handling, and fatigue, we transduced the flexor digitorum brevis muscle with a LMCD1-expressing adenovirus and measured specific force and sarcoplasmic reticulum Ca2+ release in individual fibers. Finally, to explore the relationship between LMCD1 and calcineurin, we ectopically expressed Lmcd1 in the gastrocnemius muscle and treated those mice with cyclosporine A (calcineurin inhibitor). In addition, we used a luciferase reporter construct containing the myoregulin gene promoter to confirm the role of a LMCD1-calcineurin-myoregulin axis in skeletal muscle mass control and calcium handling. Results Here, we identify LIM and cysteine-rich domains 1 (LMCD1) as a positive regulator of muscle mass, that increases muscle protein synthesis and fiber size. LMCD1 expression in vivo was sufficient to increase specific force with lower requirement for calcium handling and to reduce muscle fatigue. Conversely, silencing LMCD1 expression impairs calcium handling and force, and induces muscle fatigue without overt atrophy. The actions of LMCD1 were dependent on calcineurin, as its inhibition using cyclosporine A reverted the observed hypertrophic phenotype. Finally, we determined that LMCD1 represses the expression of myoregulin, a known negative regulator of muscle performance. Interestingly, we observed that skeletal muscle LMCD1 expression is reduced in patients with skeletal muscle disease. Conclusions Our gain- and loss-of-function studies show that LMCD1 controls protein synthesis, muscle fiber size, specific force, Ca2+ handling, and fatigue resistance. This work uncovers a novel role for LMCD1 in the regulation of skeletal muscle mass and function with potential therapeutic implications.

Embryogenic cultures of soybean [Glycine max (L.) Merr. cv. Jack and Asgrow A2872] were established in liquid Finer and Nagasawa medium, maintained by transfer to fresh medium at biweekly intervals, and subjected to microprojectile bombardment over time. Cultures were not amenable to transformation until they were at least 6 months old. Over time, different cell lines of the same genotype acquired very different culture phenotypes. Histological analysis of cell lines differing in transformation ability showed that the most transformable cultures had cytoplasmic-rich cells in the outermost layers of the tissue. In contrast, the outer layers of less transformable cultures contained cells with prominent vacuoles. Although fresh weight accumulation of the cultures was curvilinear during the 2-week subculture period, a burst of mitotic activity was evident shortly after transfer to fresh medium. This activity usually lasted from the 2nd to the 6th day following subculture, and peaked on the 4th day. Tissues at or near this stage always produced more transient expression of a reporter gene than did bombardments at other times. In addition, the cell lines most amenable to transformation also exhibited the highest mitotic index. Thus any treatment to increase the mitotic index, especially when the cell lines are less than 6 months old, may facilitate the transformation of cell lines from which efficient recovery of transgenic plants is still possible.

Contains fulltext : 196125.pdf (Publisher’s version ) (Closed access) The biological background and consequences of serotonin transporter polymorphism-glucocorticoid relationship in individual differences in stress reactivity has been a major interest in neuropsychiatry research. Individual differences in glucocorticoid release have long been implicated in vulnerability to stress-related psychopathologies, like depression and anxiety in various species. Yet, it is largely elusive to what extent results from non-human primates and rodents translate to human findings. Based on our structured, comprehensive and non-hypothesis driven overview of this topic, we conclude that although gene-environment interaction studies have highlighted the importance of serotonin transporter polymorphism in modulating glucocorticoid release, there is compelling evidence that age, gender and ethnicity are significant factors too contributing to the equation. We conclude too that the way early life events modulate an individual's stress reactivity as a function of serotonin transporter polymorphism is comparable between species. These data provide a rationale for the design of new, prospective translational studies into sex-specific gene-environment interactions across the lifespan with the goal of improving preventative efforts and optimizing (personalized) treatment in stress-related psychopathologies.

Modern 5-axis machining centers enable the development and use of new machining kinematics and grinding strategies to grind workpieces with superabrasives mounted points. One of these technologies is the oscillating surface grinding (OSG), which can improve the surface characteristics and the tribological properties of machined surfaces. In the current contribution could be observed that the resultant surface roughness values by OSG are not constant within a wavelength of oscillation of the grinding tool. This leads to further studies of the kinematics involved in this process, resulting in the development of a new grinding strategy: the tilt surface grinding (TSG). By using TSG, workpiece surfaces with similar characteristics as OSG could be obtained even without aid of oscillation. In this study, experimental tests are carried out to investigate the influence of parameters involved in these strategies. A significant parameter is the tilt angle α t, which can be simplified as an angle between the directions of the feed rate in tangential direction v ft and the feed rate in axial direction v fa of the grinding tool. The tilt angle α t is responsible for changes occurred on the OSG when compared to conventional surface grinding. Increasing the tilt angle α t, a reduction up to 50 % of the roughness values could be achieved. This paper aims to complement and expand the knowledge of the OSG, explaining how the aid of the oscillation tool changes the grinding kinematic, in order to optimize the grinding process.

Isolated spinal leptomeningeal metastases (LMM) without brain metastases are infrequent, accounting for about 1% of all solid tumors. In LMM, cerebrospinal fluid (CSF) analyses are mostly abnormal. Demonstrations of intrathecal tumor markers are highly suggestive, but only a positive cytology is diagnostic. The initial CSF cytology can give a false negative result in up to 40-50% of patients with pathologically proven LMM on autopsy. We report a case of intrahepatic cholangiocarcinoma with spinal LMM confirmed using cytokeratin7 and pancytokeratin (AE1/AE3) immunocytochemical studies on paucicellular cerebrospinal fluid cytospin preparation. Given the paucicellularity of the smears and difficult morphologic categorization, immunocytochemistry is vital for confirmatory diagnosis and can help reduce false negative results. To the best of our knowledge this is the first case report of cytologically confirmed LMM from an intrahepatic cholangiocarcinoma while the patient was undergoing treatment.

This paper presents an approach for the development and optimization of the NC-form grinding technology for an efficient machining of carbon fibre reinforced silicon carbide composite (C/SiC). The C/SiC properties, the importance and the necessity of the application of a high performance grinding process for the machining of this innovative composite material are introduced first. Then, the methodologies and the experimental investigations of NC-form grinding with the application of several machining parameters and three distinct bond types (vitrified, metal and synthetic resin) of diamond mounted points for the abrasive machining of C/SiC are presented. In order to monitor and analyze the process, grinding forces, surface integrity of ground workpieces and grinding wheel wear are investigated. The results of this paper provide new information regarding the wear behavior of grinding tools and the optimized conditions for grinding of C/SiC

The development of tools which ensure the desired level of transgene expression in plastids is a prerequisite for the effective utilization of these plant organelles for the deployment of bioactive proteins. High-level accumulation of target proteins is considered as a positive feature of transplastomic plants, but excessive accumulation of foreign proteins may have deleterious effects on host plants. On the other hand, expression at low levels can result in ineffective phenotypes. We compared the effectiveness of different 5'-regulatory sequences in driving the expression of a reporter gene, β-glucuronidase (uidA), in tobacco chloroplasts. To achieve varying expression levels, we have chosen heterologous 5'-regulatory sequences which either differ significantly from their homologous counterparts or depend on specific nuclear encoded factors. The Medicago truncatula psbA promoter/5'-UTR supported the highest levels of protein accumulation, surpassing the other tested sequences by two to three orders of magnitude. The heterologous regulatory sequence of Phaseolus vulgaris rbcL gene was as efficient in tobacco chloroplasts as the corresponding homologous promoter/5'-UTR. The Arabidopsis thaliana ndhF promoter/5'-UTR supported as high reporter activity levels as the rbcL 5'-sequences, whereas the effectiveness of A. thaliana psbN promoter/5'-UTR was three fold lower. The characterized regulatory sequences can be utilized to establish transplastomic lines with desirable levels of target protein accumulation. The ability to control transgene expression should be useful for achieving appropriate levels of protein accumulation and thereby avoid their negative impacts on host plant physiology.

Endurance and resistance exercise training induces specific and profound changes in the skeletal muscle transcriptome. Peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α) coactivators are not only among the genes differentially induced by distinct training methods, but they also participate in the ensuing signaling cascades that allow skeletal muscle to adapt to each type of exercise. Although endurance training preferentially induces PGC-1α1 expression, resistance exercise activates the expression of PGC-1α2, -α3, and -α4. These three alternative PGC-1α isoforms lack the arginine/serine-rich (RS) and RNA recognition motifs characteristic of PGC-1α1. Discrete functions for PGC-1α1 and -α4 have been described, but the biological role of PGC-1α2 and -α3 remains elusive. Here we show that different PGC-1α variants can affect target gene splicing through diverse mechanisms, including alternative promoter usage. By analyzing the exon structure of the target transcripts for each PGC-1α isoform, we were able to identify a large number of previously unknown PGC-1α2 and -α3 target genes and pathways in skeletal muscle. In particular, PGC-1α2 seems to mediate a decrease in the levels of cholesterol synthesis genes. Our results suggest that the conservation of the N-terminal activation and repression domains (and not the RS/RNA recognition motif) is what determines the gene programs and splicing options modulated by each PGC-1α isoform. By using skeletal muscle-specific transgenic mice for PGC-1α1 and -α4, we could validate, in vivo, splicing events observed in in vitro studies. These results show that alternative PGC-1α variants can affect target gene expression both quantitatively and qualitatively and identify novel biological pathways under the control of this system of coactivators.

The Armed Forces Health Surveillance Center (AFHSC), Division of Global Emerging Infections Surveillance and Response System conducts disease surveillance through a global network of US Department of Defense research laboratories and partnerships with foreign ministries of agriculture, health and livestock development in over 90 countries worldwide. In 2010, AFHSC supported zoonosis survey efforts were organized into four main categories: (i) development of field assays for animal disease surveillance during deployments and in resource limited environments, (ii) determining zoonotic disease prevalence in high-contact species which may serve as important reservoirs of diseases and sources of transmission, (iii) surveillance in high-risk human populations which are more likely to become exposed and subsequently infected with zoonotic pathogens and (iv) surveillance at the human-animal interface examining zoonotic disease prevalence and transmission within and between human and animal populations. These efforts have aided in the detection, identification and quantification of the burden of zoonotic diseases such as anthrax, brucellosis, Crimean Congo haemorrhagic fever, dengue fever, Hantaan virus, influenza, Lassa fever, leptospirosis, melioidosis, Q fever, Rift Valley fever, sandfly fever Sicilian virus, sandfly fever Naples virus, tuberculosis and West Nile virus, which are of military and public health importance. Future zoonotic surveillance efforts will seek to develop local capacity for zoonotic surveillance focusing on high risk populations at the human-animal interface.

Summary The role of tryptophan-kynurenine metabolism in psychiatric disease is well established, but remains less explored in peripheral tissues. Exercise training activates kynurenine biotransformation in skeletal muscle, which protects from neuroinflammation and leads to peripheral kynurenic acid accumulation. Here we show that kynurenic acid increases energy utilization by activating G protein-coupled receptor Gpr35, which stimulates lipid metabolism, thermogenic, and anti-inflammatory gene expression in adipose tissue. This suppresses weight gain in animals fed a high-fat diet and improves glucose tolerance. Kynurenic acid and Gpr35 enhance Pgc-1α1 expression and cellular respiration, and increase the levels of Rgs14 in adipocytes, which leads to enhanced beta-adrenergic receptor signaling. Conversely, genetic deletion of Gpr35 causes progressive weight gain and glucose intolerance, and sensitizes to the effects of high-fat diets. Finally, exercise-induced adipose tissue browning is compromised in Gpr35 knockout animals. This work uncovers kynurenine metabolism as a pathway with therapeutic potential to control energy homeostasis.

RESUMO – Os trocadores de calor do tipo Casco e Tubo sao um dos trocadores mais utilizados no meio industrial. Dessa forma, e importante o estudo dos fenomenos fisicos que ocorrem no seu interior, principalmente em seu casco, onde o escoamento tortuoso do fluido pelos tubos e chicanas e de dificil modelagem. O presente trabalho apresenta o projeto e analise, com fluidodinâmica computacional (CFD), de um trocador de calor Casco e Tubo. Nesse trocador, ha oleo escoando no casco a fim de ser aquecido, enquanto agua de utilidade quente escoa nos tubos. Para o projeto do trocador, utilizou-se o software HTRI 6.0, o qual fornece o perfil de temperatura ao longo dos tubos e do casco. O primeiro foi utilizado na simulacao com CFD para especificar a temperatura nos tubos como funcao da posicao ao longo do eixo longitudinal do trocador. Foram consideradas geometrias com e sem as folgas diametrais, as quais sao responsaveis pela formacao de correntes de fuga, de modo a comprovar sua importância para correta predicao do escoamento e troca termica. Foram testados os modelos de turbulencia k-e e SST, sendo o ultimo o modelo que forneceu melhores predicoes. Os resultados obtidos com CFD mostraram boa compatibilidade com os resultados do perfil de temperatura e pressao obtidos com o HTRI. Alem disso, as correntes de fuga foram quantificadas e comparadas com as estimadas pelo HTRI, obtendo-se resultados bastante proximos.

Para melhorar a eficiencia desse processo, e necessario levar em consideracao, no projeto e na operacao destes equipamentos, a turbulencia criada pela movimentacao relativa da plataforma. Neste trabalho, foi analisada a influencia do movimento angular periodico de rotacao sobre o eixo principal (jogo) na eficiencia de separadores gravitacionais, atraves de simulacoes com fluidodinâmica computacional. Devido a complexidade do escoamento e ao tamanho do equipamento, uma malha com 2.604.813 elementos e 659.883 nos foi utilizada em simulacoes no CFX 15.1 da ANSYS.

Resume Objectif Le signal FSH intercycle initie le recrutement folliculaire au debut du cycle menstruel. Il survient generalement au troisieme jour du cycle. Son amplitude est faible, et peut varier d'un cycle a l'autre. Sa mesure dans le serum (FSHs) requiert donc des prises de sang quotidiennes. Nous avons cherche a determiner si le dosage de la FSH dans l'urine (FSHu) pouvait etre une alternative non invasive au dosage serique, en utilisant un modele ou le signal FSH intercycle est controle par une prise ponctuelle d'estradiol (E2). Patientes et methodes Il s'agit d'une etude pilote prospective, chez 21 femmes infertiles ayant recu de l'E2 du vingt-cinquieme jour du cycle precedent au premier vendredi apres les regles. Les echantillons de sang et d'urine ont ete recoltes des le dernier jour sous E2, pour doser la FSH et la creatinine urinaire. Une echographie a ete effectuee pour la recherche de follicules de taille superieure a 12 mm. Resultats La FSHu et FSHu/Cr montrent une bonne correlation avec la FSHs ( r = 0,52 et 0,63, p p Discussion et conclusion Le dosage la FSHu permet d'identifier le signal FSH intercycle. C'est une methode non invasive et fine pour evaluer la physiologie ovarienne.

Relationships between residual feed intake (RFI) and other performance variables were determined using 54 purebred Angus steers. Individual feed intake and BW gain were recorded during a 70-d post-weaning period to calculate RFI. After the 70-d post-weaning test, steers were fed a finishing ration to a similar fat thickness (FT), transported to a commercial facility, and slaughtered. A subsample of carcasses (n = 32) was selected to examine the relationships among RFI, meat quality, and palatability. Steers were categorized into high (> 0.5 SD above the mean; n = 16), medium (mid; +/- 0.5 SD from the mean; n = 21), and low (< 0.5 SD below the mean; n = 17) RFI groups. No differences were detected in ADG, initial BW, and d 71 BW among the high, mid, and low RFI steers. Steers from the high RFI group had a greater DMI (P = 0.004) and feed conversion ratio (FCR; DMI:ADG; P = 0.002) compared with the low RFI steers. Residual feed intake was positively correlated with DMI (r = 0.54; P = 0.003) and FCR (r = 0.42; P = 0.002), but not with initial BW, d 71 BW, d 71 ultrasound FT, initial ultrasound LM area, d 71 ultrasound LM area, or ADG. The FCR was positively correlated with initial BW (r = 0.46; P = 0.0005), d 71 BW (r = 0.34; P = 0.01), and DMI (r = 0.40; P = 0.003) and was negatively correlated with ADG (r = -0.65; P = 0.001). There were no differences among RFI groups for HCW, LM area, FT, KPH, USDA yield grade, marbling score, or quality grade. Reflectance color b* scores of steaks from high RFI steers were greater (P = 0.02) than those from low RFI steers. There was no difference between high and low RFI groups for LM calpastatin activity. Warner-Bratzler shear force and sensory panel tenderness and flavor scores of steaks were similar across RFI groups. Steaks from high RFI steers had lower (P = 0.04) off-flavor scores than those from low RFI steers. Cook loss percentages were greater (P = 0.005) for steaks from low RFI steers than for those from mid RFI steers. These data support current views that RFI is independent of ADG, but is correlated with DMI and FCR. Importantly, the data also support the hypothesis that there is no relationship between RFI and beef quality in purebred Angus steers.

The potential tumor seeking MRI contrast agent MnTPPS(4) was labelled with the positron emitting nuclide (51)Mn in no-carrier-added (n.c.a.) form. The complex formation kinetics were investigated and the apparent rate constants were determined under pseudo-first-order conditions. The derived bimolecular rate constants gave the Arrhenius parameters E(A)=84 kJ mol(-1) and A=2 x 10(12)s(-1)M(-1). Optimum labelling conditions were derived (radiochemical yields >99% possible, effective yields about 32%). Separation and purification of n.c.a. (51)MnTPPS(4) were performed for potential human use. All impurities were

Two experiments investigated the joint effect of need for cognitive closure (induced by mental fatigue) and similarity of perspective on empathic responding. Results indicated that when participants felt similar to a distressed target, no differences in empathy emerged across fatigue conditions. When they felt dissimilar, participants in the high (vs. low) mental fatigue condition were less likely to accept the target's response as appropriate and reported less empathic concern for the target. Furthermore, when motivated to learn more about the target because of an outcome dependency manipulation (introduced in Experiment 2) the reduced empathy observed under fatigue was corrected. The results imply that fatigue-induced need for cognitive closure acts as a motivational boundary condition of empathic responding.

Summary In connection with the production of 46.2 min 51Mn via the 50Cr(d, n)-process, several separation techniques such as ion exchange chromatography, solid phase extraction, liquid–liquid extraction and co-precipitation have been investigated; the aim was to separate no-carrier-added radiomanganese from the bulk target chromium. Among the separation systems *MnII/CrIII, *MnII/CrVI and *MnIV/CrVI, the latter applying the co-precipitation of *MnIV with FeIII hydroxide was found to be the optimum; the removal of chromium was rapid and quantitative (remaining content *Mn). For production purposes, a sandwiched pellet of the chemical composition Al4·50CrCl3 was developed as a new target. This allowed a quick dissolution after irradiation, thus enabling a fast separation of 51Mn and its production on a MBq scale. A 1 h irradiation at 3 µA (wobbled beam) over an effective deuteron energy range of E d = 12.8 → 7.9 MeV yielded 107 MBq 51Mn. Simultaneously formed nuclides of other elements, such as 38Cl, 24Na, 48V and 51Cr were quantitatively separated using the proposed procedure. Only the shorter-lived radioisotope 52mMn, formed via the 52Cr(d, 2n)52mMn reaction, was present at a low level of 2%, if the enrichment of 50Cr was 95% (with ∼5% 52Cr).

Competing labelling of solvent dimethyl sulfoxide (DMSO) can occur during the 11 C-methylation of amine precursors. A kinetic analysis of the methylation reaction of DMSO with n.c.a. [ 11 C]CH 3 I was performed at 120°C resulting in rate constants. The rate constant for the formation of the intermediate, methylated DMSO ([ 11 C]DMSO-M), is compared to the reaction of [ 11 C]CH 3 I with two tertiary amines, namely Dexetimide and Desmethyloxotremorine-M. The specific activity of the labelled product is reduced due to partial 12 C-methylation of the precursor amines by [ 11 C]DMSO-M in cases of significant DMSO labelling as side reaction.

This report describes Trocara virus, a newly recognized member of the genus Alphavirus, that has been isolated from Aedes serratus mosquitoes collected at two widely separated sites in the Amazon Basin. Biological, antigenic and genetic characteristics of the new virus are given. Results of these studies indicate that Trocara virus is the first member of a newly discovered antigenic complex within the family Togaviridae genus Alphavirus. The public health and veterinary importance of Trocara virus is still unknown.

Two experiments examined whether the type of information that determines persuasion varies as a function of the message recipients' chronic motivation for cognitive closure. Results of Study 1 indicated that individuals relatively high in dispositional need for closure processed a persuasive message according to heuristic cues and failed to attend systematically to the message content. In contrast, individuals relatively low in dispositional need for closure scrutinized the message content, presumably due to a greater motivation to process information. Study 2 tested the hypothesis that individuals high in dispositional need for closure may process a message systematically if a heuristic cue was unavailable to provide an easy means for closure. The data supported this hypothesis. These findings suggest that the interaction between the motivation for closure and the type of information available moderates the route to persuasion pursued.

The positron emitter 51Mn (t1/2 = 46.2 min, Iβ+ = 97%) is of potential interest in positron emission tomography (PET). With a view to optimizing its production route, excitation functions for deuteron induced nuclear reactions on isotopically enriched (~95%) 50Cr were determined radiochemically over the energy range of 3 to 13 MeV and for proton induced nuclear reactions on natCr in the range of 18 to 38 MeV. Cross sections are presented for the reactions: 50Cr(d,2n) 50mMn, 50Cr(d,n) 51Mn, 50Cr(d,t)49Cr, 50Cr(d,p)51Cr, 50Cr(d,a)48V, 52Cr(d,2p)52V, natCr(p,x) 51Mn, natCr(p,x)52Mn, natCr(p,x)52mMn, natCr(p,x)54Mn, natCr(p,x)48Cr, natCr(p,x)49Cr, natCr(p,x) 51Cr, natCr(p,x)48V and natCr(p,x)45Ti. In the case of proton induced reactions on natCr, the isomeric cross section ratio for the isomeric pair 52m,gMn was also determined. The results are interpreted in terms of the spins of the two isomers concerned. Theoretical thick target yields were derived from the corresponding excitation functions. The maximum achievable thick target yield of 51Mn is 1.1 GBq/μAh in the case of the 50Cr(d,n) 51Mn reaction at Ed = 14 → 3 MeV, and 3.2 GBq/μAh in the case of the natCr(p,x)51Mn process for Ep = 40 → 20 MeV. The 50Cr(d,n) 51Mn process is the favourable production route for 51Mn, since the radioisotopic purity is high and a small-sized medical cyclotron is adequate to produce this positron emitter in sufficient quantities.

Batch electrodeposition based on very dilute (0.14 M) hexavalent chromium electrolyte (2 mL) was optimized in order to produce thin isotopically enriched (e.g., 50 Cr) hard chromium layers on gold backings for use as targets in charged particle irradiations at accelerators. Deposition parameters were systematically investigated. The enriched chromium layers achieve a thickness of about 6 μm after 10 min of electrolysis. The chromium contents of both the deposit and the electrolyte were determined via UV-photometric Cr VI analysis in acid media. A pH range between I and 4 gives an absorption plateau for the two peaks at 257 and 348 nm of acid chromate, thus allowing a precise chromium determination without an exact pH adjustment. Gravimetrically determined deposition yields, especially for long deposition times, were found to differ significantly from the photometrically determined yields. The kinetics of development of the disturbing Cr II content in the electrolyte was investigated using high performance liquid chromatography-based ion-chromatography. The trivalent species was found to accumulate, reaching an absolute maximum of about 10% after 15 min. A chemical pathway is described to produce and to reprocess the hexavalent electrolyte.

Human growth hormone (hGH) binds to its receptor (hGHr) in a three-body interaction: one molecule of the hormone and two identical monomers of the receptor form a trimer. Curiously, the hormone-receptor interactions in the trimer are not equivalent and the formation of the complex occurs in a specific kinetic order (Cunningham BC, Ultsch M, De Vos AM, Mulkerrin MG, Clauser KR, Wells JA, 1991, Science 254:821-825). In this paper, we model the recognition of hGH to the hGHr using shape complementarity of the three-dimensional structures and macromolecular docking to explore possible binding modes between the receptor and hormone. The method, reported previously (Hendrix DK, Kuntz ID, 1998, Pacific symposium on biocomputing 1998, pp 1234-1244), is based upon matching complementary-shaped strategic sites on the molecular surface. We modify the procedure to examine three-body systems. We find that the order of binding seen experimentally is also essential to our model. We explore the use of mutational data available for hGH to guide our model. In addition to docking hGH to the hGHr, we further test our methodology by successfully reproducing 16 macromolecular complexes from X-ray crystal structures, including enzyme-inhibitor, antibody-antigen, protein dimer, and protein-DNA complexes.

Some of the transgenic soybean [Glycine max (L.) Merr.] plants produced by bombarding embryogenic suspension cultures with DNA-coated particles exhibit morphological aberrations, including stunted plant growth, leathery dark green leaves and partialto-total seed sterility. In general, cultures from two Asgrow soybean lines (A2242, A2872) that were maintained for 8 months or longer produced primary transformants with reduced fertility. Cytological examination (mitotic pro-metaphase to metaphase chromosomes) of cells of suspension cultures, of roots from germinating somatic embryos, and of plants (R0 and R1) derived from A2242, revealed, besides diploidy (2n=40), various chromosomal aberrations such as deletions, duplications, trisomics and tetraploidy. Diploid transgenic plants with a normal karyotype from A2242 generally exhibited good fertility. No chromosomal abnormalities were observed in A2872-derived plants. However, plants regenerated from relatively old cultures of A2872 (more than 1 year in culture) showed a range of phenotypic abnormalities although they all contained 2n=40 chromosomes. These results indicate that soybean genotypes differ in their susceptibility to chromosomal instability induced by tissue culture. Therefore, chromosome analysis of cell cultures and the plants derived from them can help eliminate chromosomally and genetically abnormal material from gene-transfer experiments.

The monoclonal-antibody production of an immobilized hybridoma cell line cultivated in a fluidized-bed reactor was monitored on-line for nearly 900 h. The monoclonal antibody concentration was determined by an immuno affinity-chromatography method (ABICAP). Antibodies directed against the product, e.g. IgG, were immobilized on a micro-porous gel and packed in small columns. After all IgG present in the sample was bound to the immobilized antibodies, unbound proteins were removed by rinsing the column. Elution of the bound antibodies followed and the antibodies were determined by fluorescence. The analytical procedure was automated with a robotic device to enable on-line measurements. The correlation between the on-line determined data and antibody concentrations measured by HPLC was linear.A sampling system was constructed, which was based on a pneumatically actuated in-line membrane valve integrated into the circulation loop of the reactor. Separation of the cells from the sample stream was achieved by a depth filter made of glass-fibre, situated outside the reactor. Rapid obstruction of the filter by cells or cell debris and contamination of the sample system was avoided by intermittent rinsing of the sample system with a chemical solution. The intermittent rinsing of the filter, which had a surface of 4.8 cm(2), resulted in an operational capacity of up to 40 samples (1.0 l total sample volume). Both the sampling system and the analytical device functioned without failure during this long-term culture.The culture temperature was varied between 34 and 40 °C. Raising the temperature from 34 up to 37 °C resulted in a simultaneous increase of growth and specific antibody production rate. Specific metabolic rates of glucose, lactate, glutamine and ammonium stayed constant in this temperature range. A further enhancement of temperature up to 40 °C had a negative effect on the growth rate, whereas the specific monoclonal antibody production rate showed a small increase. The other specific metabolic rates also increased in the temperature range between 38 to 40 °C.

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Hafnium oxide dielectric thin films were deposited by metalorganic chemical vapor deposition with Hf (IV) t-butoxide and either an O2, N2, or N2O plasma in a 1:1 ratio with helium. Films approximately 5nm thick were analyzed using angle-resolved x-ray photoelectron spectroscopy (XPS) and variable angle ellipsometry before and after heat treatment in an ultrahigh vacuum up to 470°C. Interdiffusion and/or reaction of the film with the silicon substrate, as measured by an increase in thickness and an increase in Si-O type bonding at the interface was most apparent with O2 plasma deposited films and least observed with N2 plasma deposited films. Also, the Hf(4f) XPS peak shifts toward higher binding energy after anneals for the N2 and N2O plasma deposited films indicates further oxidation of the film. In contrast, oxygen plasma deposited films do not exhibit a Hf(4f) peak shift. These results provide evidence that high-κ film∕substrate stability may be controlled by applying appropriate plasma chemistry.

Composite materials in terms of fiber-reinforced plastics (FRP) are used as lightweight materials in various products for example airplanes or helicopters. The manufacturing of high performance carbon fiber-reinforced plastic (CFRP) parts in the aeronautics industry often relies on preimpregnated fibers (prepregs) which are cured in an autoclave. In this context, the production output mainly is determined by the autoclave being a bottleneck in production. To address this issue, we present a novel approach to model a batch optimization problem in the context of composites manufacturing and then introduce a batch optimization algorithm based on the principle of a genetic algorithm. Furthermore, a simulation study, which is used to assess the performance of the proposed algorithm, is described.