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The production of natural gas in Tanzania has contributed to national socioeconomic development. It is responsible for about 57% of the total generated electricity in the country. Despite a growing body of literature in this sector, little intellectual attention has been given to how local community members participate in and profit from this sector through an articulated engagement mechanism, employment and other benefits. Using a mix of qualitative research methods, we studied two gas-producing locations of Msimbati and Songosongo in southeastern Tanzania. Findings suggest inadequate local community participation. Belated and fast local community engagement by the government and gas companies resulted in unmanageable expectations to local communities. Hopes for more local employment opportunities dwindled as gas projects entered the production phase that required skilled workers. Stakeholders were unprepared without a gas sector institutional framework. Local communities have failed to tap the potential to produce and supply foodstuffs to gas companies. This has further restrained their potentially meaningful participation in this sector. Benefits emanating from gas activities have appeared inequitably shared among stakeholders. We call for well thought local community engagement approaches, equitable benefit-sharing modalities and local community preparedness to promote meaningful local community participation in the natural gas sector.

Hurricane Sandy greatly disrupted the New York City (NYC) region’s transportation systems, electric power systems, work locations, and schools in 2012. This study uses survey responses from NYC Metropolitan Area residents to develop an agent-based model that depicts commuter travel behavior and adaptation after the disruption. Six scenarios were tested to quantify which systems were more critical to recover for an earlier return to productivity - defined as the ability to work for one’s employer. The recommended system restoration order depends on the pattern of normal commuting behavior. In the NYC Metropolitan Area, a larger share of commuters use transit to commute than in any other US metropolitan area. This resulted in the model indicating the subway/rail system recovery as the most important factor for returning the most people to productivity. The second most important factor is widespread power restoration itself, which allows residents to telework while waiting for the transportation system to recover. The next most important factor is the reopening of schools and daycares (with associated infrastructure systems), freeing parents to commute. The remaining expedited system recovery scenarios tested using the agent-based model resulted in a faster return to productivity than the baseline, but to a lesser degree than the subway/rail, power, and childcare systems scenarios. Additional analysis of recovery shows that households with higher annual income benefit more from power recovery compared to those with lower incomes. Moreover, the effectiveness of recovery scenarios can differ based on residential location and the extent of disruption in that location.

Objective: Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) transports Ca2+ from the cytosol into the endoplasmic retitculum (ER) and is essential for appropriate regulation of intracellular Ca2+ homeostasis. The objective of this study was to test the hypothesis that SERCA pumps are involved in the regulation of white adipocyte hormone secretion and other aspects of adipose tissue function and that this control is disturbed in obesity-induced type-2 diabetes. Methods: SERCA expression was measured in isolated human and mouse adipocytes as well as in whole mouse adipose tissue by Western blot and RT-qPCR. To test the significance of SERCA2 in adipocyte functionality and whole-body metabolism, we generated adipocyte-specific SERCA2 knockout mice. The mice were metabolically phenotyped by glucose tolerance and tracer studies, histological analyses, measurements of glucose-stimulated insulin release in isolated islets, and gene/protein expression analyses. We also tested the effect of pharmacological SERCA inhibition and genetic SERCA2 ablation in cultured adipocytes. Intracellular and mitochondrial Ca2+ levels were recorded with dualwavelength ratio imaging and mitochondrial function was assessed by Seahorse technology. Results: We demonstrate that SERCA2 is downregulated in white adipocytes from patients with obesity and type-2 diabetes as well as in adipocytes from diet-induced obese mice. SERCA2-ablated adipocytes display disturbed Ca2+ homeostasis associated with upregulated ER stress markers and impaired hormone release. These adipocyte alterations are linked to mild lipodystrophy, reduced adiponectin levels, and impaired glucose tolerance. Interestingly, adipocyte-specific SERCA2 ablation leads to increased glucose uptake in white adipose tissue while the glucose uptake is reduced in brown adipose tissue. This dichotomous effect on glucose uptake is due to differently regulated mitochondrial function. In white adipocytes, SERCA2 deficiency triggers an adaptive increase in fibroblast growth factor 21 (FGF21), increased mitochondrial uncoupling protein 1 (UCP1) levels, and increased oxygen consumption rate (OCR). In contrast, brown SERCA2 null adipocytes display reduced OCR despite increased mitochondrial content and UCP1 levels compared to wild type controls. Conclusions: Our data suggest causal links between reduced white adipocyte SERCA2 levels, deranged adipocyte Ca2+ homeostasis, adipose tissue dysfunction and type-2 diabetes. (c) 2022 The Author(s). Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Funding Agencies|Swedish Research Council [2013-07107, 2017-00792, 2019-01239, 2020-01463]; Magnus Bergvall Foundation [2016-01711]; Novo Nordisk Foundation [NNF19OC0056601]; Swedish Diabetes Foundation [DIA2016-127, DIA2018-358, DIA2019-419, DIA2014-074, DIA2015-062, DIA2017- 273, DIA2018-354]

White adipocyte adiponectin exocytosis is triggered by cAMP and a concomitant increase of cytosolic Ca

This paper used survey data from 397 commuters in the New York City area to determine the transportation-related disruptions and socio-demographic characteristics associated with the duration of home to work commute travel changes after Hurricane Sandy in 2012. The durations examined included those associated with working schedule/location alterations, home-to-work trip delays, telecommuting time, and the alteration of commuting patterns. Accelerated failure time fully parametric duration models, based on the Weibull distribution were used. The models’ significant variables differed. Commuters with higher income or who were highly educated were more likely to prolong the time to return to normal working schedules and increase telecommuting duration. Longer commutes under normal circumstances (based on trip time) prolonged trip delays and the number of days that the commute was changed. Prolonged service recovery periods increased the duration of commute changes and delays, emphasizing the importance of timely transit service restoration. Policies like gas purchase restrictions were found to have trade-offs, since they can prolong the duration of commute changes and create queues at gas stations. Telecommuting can allow commuters to keep their productivity levels high during post-disaster periods.

Resistin, and its closely related homologs, the resistin-like molecules (RELMs) have been implicated in metabolic dysregulation, inflammation, and cancer. Specifically, RELMβ, expressed predominantly in the goblet cells in the colon, is released both apically and basolaterally, and is hence found in both the intestinal lumen in the mucosal layer as well as in the circulation. RELMβ has been linked to both the pathogenesis of colon cancer and type 2 diabetes. RELMβ plays a complex role in immune system regulation, and the impact of loss of function of RELMβ on colon cancer and metabolic regulation has not been fully elucidated. We therefore tested whether Retnlβ (mouse ortholog of human RETNLβ) null mice have an enhanced or reduced susceptibility for colon cancer as well as metabolic dysfunction. We found that the lack of RELMβ leads to increased colonic expression of T helper cell type-2 cytokines and IL-17, associated with a reduced ability to maintain intestinal homeostasis. This defect leads to an enhanced susceptibility to the development of inflammation, colorectal cancer, and glucose intolerance. In conclusion, the phenotype of the Retnlβ null mice unravels new aspects of inflammation-mediated diseases and strengthens the notion that a proper intestinal barrier function is essential to sustain a healthy phenotype.

The Washington, DC Metrorail collision in 2009 presents a rare opportunity to study rapid transit passengers’ responses to a highly publicized rail incident entailing injuries and fatalities. To investigate behavioral responses to the accident, particularly mode shifts, we conducted a web-based survey of approximately 300 commuters traveling on Metrorail after the accident who had used Metrorail in the 6 months prior to the collision. The most common response to the accident was avoidance of the first and last train cars. Some respondents substituted some Metrorail trips with other modes or took fewer Metrorail trips. To investigate factors influencing these behavioral responses, we employ multinomial logit models to explore the statistical association between respondent and travel characteristics and the choice among the options of (1) making no changes, (2) avoiding certain seating locations, (3) changing modes of transportation, and (4) changing both seating locations and modes of transportation. Results suggest that travel inertia, specifically mode inertia, exists, in that respondents generally prefer not to make mode or travel choice changes. However, some mode characteristics, such as cost differences and frequent delays have a statistically significant association with mode switching. Gender and the presence of children in the household correlate with the option selected.

Nearly every state in the United States has developed a voluntary land cleanup program to support an alternative, more decentralized approach to the revitalization of contaminated and underperforming land. Yet, despite the ubiquity of such programs and the thousands of properties enrolled in them, we know relatively little about their formation and attractiveness. This paper reports results from interviews of officials in voluntary cleanup program in all fifty states, and from a survey of program participants in one state. It seeks to characterize attitudes about the desirability and performance of voluntary cleanup programs and to motivate further research into policies to improve their efficacy. Results suggest the primacy of economic redevelopment in motivating state officials to develop voluntary cleanup program, with improving environmental quality, promoting regulatory reform, easing political pressures, and improving the cleanup process also playing roles. Program participants in the state examined in detail indicated that gaining liability protection, decreasing cleanup costs, and facilitating property sales constitute the most important potential benefits of enrolling properties in voluntary cleanup programs.

Highlights ► We characterized the mutator phenotype of a very early onset rectal cancer. ► High frequency of C:G>T:A or G:C>A:T transitions at methylated CpG sites was found. ► A somatic TDG mutation was found associated with TDG expression loss in the tumor. ► 1st in vivo evidence that TDG acts against deleterious 5-methylcytosine deamination., Cells with DNA repair defects have increased genomic instability and are more likely to acquire secondary mutations that bring about cellular transformation. We describe the frequency and spectrum of somatic mutations involving several tumor suppressor genes in the rectal carcinoma of a 13-year-old girl harboring biallelic, germline mutations in the DNA mismatch repair gene PMS2. Apart from microsatellite instability, the tumor DNA contained a number of C:G → T:A or G:C → A:T transitions in CpG dinucleotides, which often result through spontaneous deamination of cytosine or 5-methylcytosine. Four DNA glycosylases, UNG2, SMUG1, MBD4 and TDG, are involved in the repair of these deamination events. We identified a heterozygous missense mutation in TDG, which was associated with TDG protein loss in the tumor. The CpGs mutated in this patient's tumor are generally methylated in normal colonic mucosa. Thus, it is highly likely that loss of TDG contributed to the supermutator phenotype and that most of the point mutations were caused by deamination of 5-methylcytosine to thymine, which remained uncorrected owing to the TDG deficiency. This case provides the first in vivo evidence of the key role of TDG in protecting the human genome against the deleterious effects of 5-methylcytosine deamination.

Metabolically healthy individuals effectively adapt to changes in nutritional state. Here, we focus on the effects of the adipocyte-derived secretory molecule adiponectin on adipose tissue in mouse models with genetically altered adiponectin levels. We found that higher adiponectin levels increased sensitivity to the lipolytic effects of adrenergic receptor agonists. In parallel, adiponectin-overexpressing mice also display enhanced clearance of circulating fatty acids and increased expansion of subcutaneous adipose tissue with chronic high fat diet (HFD) feeding. These adaptive changes to the HFD were associated with increased mitochondrial density in adipocytes, smaller adipocyte size, and a general transcriptional up-regulation of factors involved in lipid storage through efficient esterification of free fatty acids. The physiological response to adiponectin overexpression resembles in many ways the effects of chronic exposure to beta3-adrenergic agonist treatment, which also results in improvements in insulin sensitivity. In addition, using a novel computed tomography-based method for measurements of hepatic lipids, we resolved the temporal events taking place in the liver in response to acute HFD exposure in both wild-type and adiponectin-overexpressing mice. Increased levels of adiponectin potently protect against HFD-induced hepatic lipid accumulation and preserve insulin sensitivity. Given these profound effects of adiponectin, we propose that adiponectin is a factor that increases the metabolic flexibility of adipose tissue, enhancing its ability to maintain proper function under metabolically challenging conditions.

Both the disproportionate loss of adipose tissue in the case of lipodystrophies and the disproportionate gain of adipose tissue in obesity are frequently associated with an increase in insulin resistance and its complications. Leptin replacement is a very promising therapeutic approach for the management of the complications of lipodystrophy. In contrast, leptin treatment for the reversal of obesity-related metabolic disorders has not proven to be successful. There is a need to better understand both of these phenomena. Mouse models of lipodystrophy may provide us with new pharmaceutical targets for the treatment and prevention of metabolic disturbances related to dysfunctional adipose tissue both in the context of lipodystrophy and obesity.

This paper provides a survey of existing research on agent-based approaches to transportation and traffic management. A framework for describing and assessing this work will be presented and systematically applied. We are mainly adopting a logistical perspective, thus focusing on freight transportation. However, when relevant, work of traffic and transport of people will be considered. A general conclusion from our study is that agent-based approaches seem very suitable for this domain, but that this still needs to be verified by more deployed system.

The problem domain in this work is a three-dimensional simulation of an underwater vehicle (AUV) that must navigate through obstacles towards a stationary goal point. The AUV has a limited set of sensors, including sonar, and can set its speed and direction each decision cycle. We wish to learn a strategy that is expressed as a set of reactive rules, (i.e. stimulus-response rules) that map sensor readings to actions to be performed at each decision time step. Note that the system does not learn a specific path, but a set of rules that reactively decide a move at each time step allowing the vehicle to reach its goal and avoid the obstacles.

Vascular endothelial growth factors (VEGFs) regulate the development and growth of the blood and lymphatic vascular systems. Of the three VEGF receptors (VEGFR), VEGFR-1 and -2 are expressed on blood vessels; VEGFR-2 is found also on lymphatic vessels. VEGFR-3 is expressed mainly on lymphatic vessels but it is also up-regulated in tumor angiogenesis. Although VEGFR-3 is essential for proper lymphatic development, its signal transduction mechanisms are still incompletely understood. Trans-phosphorylation of activated, dimerized receptor tyrosine kinases is known to be critical for the regulation of kinase activity and for receptor interaction with signal transduction molecules. In this study, we have identified five tyrosyl phosphorylation sites in the VEGFR-3 carboxyl-terminal tail. These sites were used both in VEGFR-3 overexpressed in 293 cells and when the endogenous VEGFR-3 was activated in lymphatic endothelial cells. Interestingly, VEGF-C stimulation of lymphatic endothelial cells also induced the formation of VEGFR-3/VEGFR-2 heterodimers, in which VEGFR-3 was phosphorylated only at three of the five sites while the two most carboxyl-terminal tyrosine residues appeared not to be accessible for the VEGFR-2 kinase. Our data suggest that the carboxyl-terminal tail of VEGFR-3 provides important regulatory tyrosine phosphorylation sites with potential signal transduction capacity and that these sites are differentially used in ligand-induced homo- and heterodimeric receptor complexes.

We have previously demonstrated that ligand-stimulation of c-Kit induces phosphorylation of Tyr568 and Tyr570 in the juxtamembrane region of the receptor, leading to recruitment, phosphorylation and activation of members of the Src family of tyrosine kinases. In this paper, we demonstrate that members of the Src family of tyrosine kinases are able to phosphorylate c-Kit selectively on one particular tyrosine residue, Tyr900, located in the second part of the tyrosine kinase domain. In order to identify potential docking partners of Tyr900, a synthetic phosphopeptide corresponding to the amino acid sequence surrounding Tyr900 was used as an affinity matrix. By use of MALDI-TOF mass spectrometry, CrkII was identified as a protein that specifically bound to Tyr900 in a phosphorylation dependent manner, possibly via the p85 subunit of PI3-kinase. Expression of a mutant receptor where Tyr900 had been replaced with a phenylalanine residue (Y900F) resulted in a receptor with reduced ability to phosphorylate CrkII. Together these data support a model where c-Src phosphorylates the receptor, thereby creating docking sites for SH2 domain containing proteins, leading to recruitment of Crk to the receptor.

Linoleate diol synthase is a homotetrameric ferric hemeprotein, which catalyzes dioxygenation of linoleic acid to (8R)-hydroperoxylinoleate and isomerization of the hydroperoxide to (7S,8S)-dihydroxylinoleate. Ferryl intermediates and a tyrosyl radical are formed in the reaction. Linoleate diol synthase was digested with endoproteinase Lys-C, and internal peptides were sequenced. The sequence information was used for reverse transcription-polymerase chain reaction analysis, and a cDNA probe was obtained. Northern blot analysis of linoleate diol synthase suggested a 3.7-kilobase pair (kb) mRNA. A full-length clone of the linoleate diol synthase gene was obtained by screening of a genomic lambda-ZAP II library of the fungus Gaeumannomyces graminis. The 5'-untranslated region contained CAAT- and TATA-like boxes. The gene contained three short introns and spanned over 3.2-kb. The deduced open reading frame consisted of 2.9-kb, which corresponded to 978 amino acids and a molecular subunit mass of 108,000. Data base analysis with the gapped BLAST algorithm showed that 391 residues of linoleate diol synthase was 23-24% identical and 36-37% positive with the catalytic domain of mammalian prostaglandin H (PGH) synthase-2. Based on homology with PGH synthases, the proximal heme ligand of linoleate diol synthase was tentatively identified as His-379 and the important tyrosine for catalysis as residue 376 (apparent consensus EFNXXXYXWH). The distal heme ligand was tentatively identified as His-203 (apparent consensus THXXFXT). We conclude from catalytic and structural similarities that linoleate diol synthase and PGH synthases likely share common ancestry and may belong to a gene family of fatty acid heme dioxygenases.

The linking of cleanups at contaminated sites in the US to the sites’ expected land uses may offer a more rational and cheaper cleanup process, economic development in the local communities that host such sites, and more community control of cleanups. Interviews with national-level stakeholders, information from a large database of contaminated sites, and a detailed case study suggest these presumed benefits are problematic. Misunderstandings about the current role of land use in cleanup, the likelihood of economic development at contaminated sites, the viability of institutional controls, the willingness of communities to accept partial cleanups, and public involvement warrant more attention.

Receptor tyrosine phosphorylation is crucial for signal transduction by creating high affinity binding sites for Src homology 2 domain-containing molecules. By expressing the intracellular domain of Flt-1/vascular endothelial growth factor receptor-1 in the baculosystem, we identified two major tyrosine phosphorylation sites at Tyr-1213 and Tyr-1242 and two minor tyrosine phosphorylation sites at Tyr-1327 and Tyr-1333 in this receptor. This pattern of phosphorylation of Flt-1 was also detected in vascular endothelial growth factor-stimulated cells expressing intact Flt-1. In vitro protein binding studies using synthetic peptides and immunoblotting showed that phospholipase C-gamma binds to both Y(p)1213 and Y(p)1333, whereas Grb2 and SH2-containing tyrosine protein phosphatase (SHP-2) bind to Y(p)1213, and Nck and Crk bind to Y(p)1333 in a phosphotyrosine-dependent manner. In addition, unidentified proteins with molecular masses around 74 and 27 kDa bound to Y(p)1213 and another of 75 kDa bound to Y(p)1333 in a phosphotyrosine-dependent manner. SHP-2, phospholipase C-gamma, and Grb2 could also be shown to bind to the intact Flt-1 intracellular domain. These results indicate that a spectrum of already known as well as novel phosphotyrosine-binding molecules are involved in signal transduction by Flt-1.

Prothymosin alpha (PTA) stimulates in a dose-dependent manner the phosphorylation of a 105-kDa protein (p105) in cell extracts from different cell types. Protein sequencing and immunological analysis indicated that this protein is elongation factor 2 (EF-2). We propose that calcium/calmodulin-dependent protein kinase III is responsible for the PTA-dependent EF-2 phosphorylation based on the following lines of evidence: (a) Ca2+ is required for the effect; (b) calmodulin enhances the reaction, and calmodulin inhibitors block the phosphorylation; and (c) no phosphorylation is seen in cell extracts depleted of calmodulin-binding proteins. To obtain a strong phosphorylated EF-2 band, we found it necessary to add PTA to cytosolic extracts from synchronized dividing cells in various phases of the cell cycle except in mitosis. Since PTA is a nuclear protein everywhere in the cell cycle except in mitosis, when it is found in the cytoplasm, we hypothesize that, if PTA activates EF-2 phosphorylation in vivo, as present data suggest, its presence in the cytoplasm during mitosis could explain why EF-2 phosphorylation is mainly restricted to that phase of the cell cycle. Moreover, other bands in addition to EF-2 were phosphorylated in a calmodulin- and PTA-dependent manner, and several of them (in a range between 50 and 60 kDa) have similar Mr to those that conform to the holoenzyme calcium/calmodulin dependent protein kinase II, suggesting that PTA could have a more general function modulating the activity of various Ca2+/CaM-dependent enzymes along the cell cycle.

Hormone-sensitive lipase (HSL) is the rate-limiting enzyme in lipolysis. Stimulation of rat adipocytes with isoproterenol results in phosphorylation of HSL and a 50-fold increase in the rate of lipolysis. In this study, we used site-directed mutagenesis and two-dimensional phosphopeptide mapping to show that phosphorylation sites other than the previously identified Ser-563 are phosphorylated in HSL in response to isoproterenol stimulation of 32P-labeled rat adipocytes. Phosphorylation of HSL in adipocytes in response to isoproterenol and in vitro phosphorylation of HSL containing Ser --> Ala mutations in residues 563 and 565 (S563A, S565A) with protein kinase A (PKA), followed by tryptic phosphopeptide mapping resulted in two tryptic phosphopeptides. These tryptic phosphopeptides co-migrated with the phosphopeptides released by the same treatment of F654HPRRSSQGVLHMPLYSSPIVK675 phosphorylated with PKA. Analysis of the phosphorylation site mutants, S659A, S660A, and S659A,S660A disclosed that mutagenesis of both Ser-659 and Ser-660 was necessary to abolish the activation of HSL toward a triolein substrate after phosphorylation with PKA. Mutation of Ser-563 to alanine did not cause significant change of activation compared with wild-type HSL. Hence, our results demonstrate that in addition to the previously identified Ser-563, two other PKA phosphorylation sites, Ser-659 and Ser-660, are present in HSL and, furthermore, that Ser-659 and Ser-660 are the major activity controlling sites in vitro.

We have compared 70-kDa heat shock cognate protein (Hsc70) isolated from bovine brain with recombinant wild type protein and mutant E543K protein (previously studied as wild type in our laboratory). Wild type bovine and recombinant protein differ by posttranslational modification of lysine 561 but interact similarly with a short peptide (fluorescein-labeled FYQLALT) and with denatured staphylococcal nuclease-(Delta135-149). Mutation E543K results in 4. 5-fold faster release of peptide and lower stability of complexes with staphylococcal nuclease-(Delta135-149). ATP hydrolysis rates of the wild type proteins are enhanced 6-10-fold by the addition of peptide. The E543K mutant has a peptide-stimulated hydrolytic rate similar to that of wild type protein but a higher unstimulated rate, yielding a mere 2-fold enhancement. All three versions of Hsc70 possess similar ATP-dependent conformational shifts, and all show potassium ion dependence. These data support the following model: (i) in the presence of K+, Mg2+, and ATP, the peptide binding domain inhibits the ATPase; (ii) binding of peptide relieves this inhibition; and (iii) the E543K mutation significantly attenuates the inhibition by the peptide binding domain and destabilizes Hsc70-peptide complexes.

Members of the Smad family of intracellular signal transducers are essential for transforming growth factor-beta (TGF-beta) to exert its multifunctional effects. After activation of TGF-beta receptors, Smad2 and Smad3 become phosphorylated and form heteromeric complexes with Smad4. Thereafter, these activated Smad complexes translocate to the nucleus, where they may direct transcriptional responses. Here we report that TGF-beta mediates phosphorylation of Smad2 at two serine residues in the C terminus, i.e. Ser465 and Ser467, which are phosphorylated in an obligate order; phosphorylation of Ser465 requires that Ser467 be phosphorylated. Transfection of Smad2 with mutation of Ser465 and/or Ser467 to alanine residues into Mv1Lu cells resulted in dominant-negative inhibition of TGF-beta signaling. These Smad2 mutants were found to stably interact with an activated TGF-beta receptor complex, in contrast to wild-type Smad2, which interacts only transiently. Mutation of Ser465 and Ser467 in Smad2 abrogated complex formation of this mutant with Smad4 and blocked the nuclear accumulation not only of Smad2, but also of Smad4. Thus, heteromeric complex formation of Smad2 with Smad4 is required for nuclear translocation of Smad4. Moreover, peptides from the C terminus of Smad2 containing phosphorylated Ser465 and Ser467 were found to bind Smad4 in vitro, whereas the corresponding unphosphorylated peptides were less effective. Thus, phosphorylated Ser465 and Ser467 in Smad2 may provide a recognition site for interaction with Smad4, and phosphorylation of these sites is a key event in Smad2 activation.

This paper presents an hierarchical fuzzy control strategy of an autonomous mobile robot in unknown environments. Controlling a mobile robot in an unknown environment requires different types of reactive behaviour which can be implemented and coordinated by fuzzy rules and fuzzy sets. To combine the main tasks of mobile robot control, target steering and collision avoidance, a new hierarchical fuzzy control strategy was developed. The idea was to divide the whole control tasks in two fuzzy systems, a superior one for obstacle avoidance and a subordinated fuzzy system for target steering. This method simplifies the design of the fuzzy rules and results in a good robot behaviour in unknown environments. To locate the robot position without external sensors a mathematical model was designed, which calculates the robot path at every sample step.

Genetic evidence suggests a role for apolipoprotein E (apoE) in Alzheimer's disease (AD) amyloidogenesis. Here, amyloid-associated apoE from 32 AD patients was purified and characterized. We found that brain amyloid-associated apoE apparently exists not as free molecules but as complexes with polymers of the amyloid beta peptide (A beta). Brain A beta-apoE complexes were detected irrespective of the apoE genotype, and similar complexes could be mimicked in vitro. The fine structure of purified A beta-apoE complexes was fibrillar, and immunogold labeling revealed apoE immunoreactivity along the fibrils. Thus, we conclude that A beta-apoE complexes are principal components of AD-associated brain amyloid and that the data presented here support a role for apoE in the pathogenesis of AD.

The Columbia River Basin, one of the world′s most complex developed hydropower systems, is also the spawning area for over 100 stocks of salmon, 3 of which have recently been listed under the U.S. Endangered Species Act. Electricity ratepayers in the basin have spent over a billion dollars since 1980 to increase salmon populations. This paper describes simulation and optimization models developed to analyze the cost-effectiveness of salmon recovery measures, as required by the 1980 Northwest Power Planning Act. The results suggest that the combination of optimization and simulation is useful for analyzing the system-wide cost-effectiveness of mitigation measures.

Runs of salmon in the Columbia Basin in the north-western United States have declined dramatically over the past 50 years, due to hydropower development, habitat degradation, over-harvest and other causes. This article describes a suite of models that analyze the biological effectiveness and financial costs of strategies designed to meet harvest and escapement goals for nearly 80 stocks of salmon simultaneously. Results suggest that finding a cost-effective solution requires that all aspects of the salmon life-cycle must be analyzed simultaneously. Policy implications and difficulties in using this modeling approach to inform regional decision-making also are discussed.

We have isolated and partially characterized a 32-kDa membrane-associated protein (p32), which forms a complex with p63, an abundant membrane protein in bovine retinal pigment epithelium. The sequence of a cDNA clone for p32 revealed an open reading frame encoding 318 amino acid residues. Several hydrophobic regions could be identified, suggesting that p32 is an integral membrane protein. A search of data bases identified p32 as a member of the superfamily of short chain alcohol dehydrogenases. Transcripts for p32 were specifically expressed in retinal pigment epithelium. Overexpression of p32 in Cos cells produced a membrane-bound stereospecific 11-cis retinol dehydrogenase, active in the presence of NAD + as cofactor but not in the presence of NADP. We propose that p32 is the stereospecific 11-cis retinol dehydrogenase, which catalyzes the final step in the biosynthesis of 11-cis retinaldehyde, the universal chromophore of visual pigments.

In this paper a new approach to optimal design of fuzzy controllers for robotics, under consideration of friction, will be presented and discussed. As a first model a linear robotic mechanism with position- and force control is discussed. The system’s friction is evaluated and modelled in a new developed software tool. This software package allows the optimization of the controller using performance criterions after the definition of the fuzzy- controller’s parameters. During the optimization process a test of the system’s stability is possible. A second example deals with the control of a transport robot in a high shelf store where changing numbers of wagons occur. In a third application a robot arm is position controlled.

Milk was obtained from a woman with acute postpartum psychosis and with ongoing lactation. Defatted samples were subjected to micropurification and collected fractions were analyzed by means of their beta-casomorphin-8 immunoreactivity. Immunoreactive material with the same chromatographic properties as synthetic human beta-casomorphin-8 was determined by amino acid sequence analysis to be Tyr-Pro-Phe-Val-Glu-Pro-Ile-Pro. Its molecular mass was determined by fast atom bombardment-mass spectrometry to be 962.3 Da. These determinations, which ultimately identify the immunoreactive material as human beta-casomorphin-8, represent the first structural identification of a beta-casomorphin peptide from a body fluid.

Retinol, a metabolic precursor of retinal and retinoic acid, is transported in plasma by the plasma retinol-binding protein (RBP). The cellular uptake of retinol from RBP is believed to involve a specific membrane receptor for RBP. In retinal pigment epithelium the RBP receptor appears to be an oligomeric protein complex, and we have previously identified a 63-kDa membrane protein as part of this receptor. The 63-kDa protein (p63) has now been isolated, and we have cloned the corresponding cDNA. In a data base search no sequences similar to p63 were identified. Hydropathy analyses of the 533 amino acids deduced from the cDNA sequence did not indicate an N-terminal signal sequence or obvious transmembrane regions. In vitro translation of synthetic mRNA encoding p63, in the presence of heterologous microsomes, verified that p63 does not become cotranslationally membrane-inserted. Transcripts for p63 are abundantly expressed in retinal pigment epithelium with no detectable expression in several other tissues. Southern blotting analysis of bovine and human genomic DNA revealed several hybridizing fragments suggesting a complex organization of the corresponding genes.

We have previously identified and purified transforming growth factor-beta 1 (TGF-beta 1)-binding proteins from porcine uterus membranes (Ichijo, H., Ronnstrand, L., Miyagawa, K., Ohashi, H., Heldin, C.-H., and Miyazono, K. (1991) J. Biol. Chem. 266, 22459-22464). One of these TGF-beta 1-binding proteins, with a molecular weight of 40,000, was purified to homogeneity and subjected to amino acid sequence analysis. The amino acid sequences obtained were used to isolate two closely related cDNA clones from a porcine uterus cDNA library. The deduced amino acid sequences revealed that both cDNAs encoded proteins that were mainly composed of fibrinogen-like and collagen-like domains. Therefore, they were denoted ficolin-alpha and ficolin-beta. Expression of ficolin-alpha and -beta cDNA in mammalian cells revealed that ficolin forms dimers, trimers, and several higher order of oligomers, whose molecular weights fit well with those of the purified TGF-beta 1-binding proteins from porcine uterus. Moreover, immunoblotting analysis using a peptide anti-serum against ficolin indicated that the TGF-beta 1-binding proteins identified in porcine uterus are ficolin-alpha, -beta, and their oligomers or closely related molecules. However, recombinant ficolin-alpha and -beta did not bind TGF-beta 1, despite the similarities in molecular weights and immunoreactivity with the material from the natural source. It is possible that a specific posttranslational modification of ficolin or interaction with another component is needed for TGF-beta 1 binding. Analysis by Northern blotting revealed that the expression of ficolin-alpha mRNA is relatively restricted and most abundant in placenta and lung. On the other hand, ficolin-beta was mainly expressed in skeletal muscle. The in vivo functions of ficolin will be discussed.

Nearly every state in the United States has developed one or more voluntary cleanup programs (VCPs) to support an alternative approach to cleanup of contaminated sites. Thousands of sites have entered into these programs. Yet, despite the ubiquity of VCPs and the number of enrolled properties, we know little about the factors that influence voluntary action at these sites. This paper reports results from interviews of state officials involved in VCPs in all states, and from a survey of VCP participants in several states. It has two objectives. First, at an application level, the interview and survey results can be used to help improve policy and practice in voluntary cleanup programs. Second, the paper furnishes a unique study to the general literature on environmental voluntary behavior, contributing an empirical, survey-based study of volunteers engaged in cleanup.

DIOPRAN is an interactive program package for the experimental process analysis within the scope of analysis and design problems of systems and automation engineering. It contains robust methods for primary data processing as well as signal and system modelling. A user-friendly design of the user guiding has been particulary taken into consideration. The program system runs on 16- and 32 bit computers under the operating system MS-DOS.

An opioid nonapeptide was isolated from fresh frozen human pituitaries. Its primary structure (Leu-Val-Tyr-Pro-Trp-Thr-Gln-Arg) was identical to fragment 32-40 of the beta-, delta-, gamma- and epsilon-chains of human hemoglobin. A larger peptide of about 4.5 kDa, which generated a fragment containing the nonapeptide on trypsin digestion, showed an amino acid composition similar to fragment 1-41 of the beta-chain of human hemoglobin. The nonapeptide interacted with mu-opioid receptors in rat brain homogenates using [3H]-(D-Ala2, MePhe3, Gly-ol5)-enkephalin and with sigma-receptors using (+)-[3H]-3-(3-hydroxyphenyl)-N-1-(propyl)piperidine, respectively. The affinities for mu-opioid receptors were in the same range as those observed for the structurally related beta-casomorphins. However, the isolated peptide showed markedly higher affinity at sigma-binding sites when compared to the beta-casomorphins or other opioid peptides. The opioid potency of this peptide as determined in the guinea-pig ileum myenteric plexus muscle preparation, was significant but less than that observed for the beta-casomorphins.

The consulting/expert system type DIOPRAN-EXPERT has been developed to support users who are no experts in the field of experimental process analysis and who have to solve design, diagnosis, control and prediction tasks. It contains methods of signal analysis and processing, model building, design of experiments and model vali-dation. They constitute the procedural part of DIOPRAN-EXPERT and are written in FORTRAN 77. The coupling to the knowledge-based part is realized by the logic programming language FORLOG. The knowledge base contains the expert knowledge in the form of IP "condition”, THEN "conclusion" rules, facts and methods. The facts are obtained from the present data by automated fact ascertaining and constitute the basis for the application of the rules. Thus, on the basis of the available data, a solution to the given problem is proposed to the user, and furthermore, results are presented corresponding to an expert’s experiences in the field of experimental process analysis.