Integrating process and controller models for the design of self-optimizing control

The steady-state behavior of an existing plant depends on the independent input variables, process equipment and process controllers. This paper presents a method for formulating models that represent the effects of controllers when they are included within a steady-state process flowsheet. The method replaces the controller equations with the equivalent stationarity conditions representing the relationship between the controlled variables and the implemented manipulated variables at steady state. The method is demonstrated for the centralized multivariable Dynamic Matrix Control algorithm applied to two processes, binary distillation and gasoline blending. The integrated process and control system simulation is used to design controllers that improve the profitability of processes without extensive real-time calculations; this is sometimes termed self-optimizing control. For both processes, controllers were designed that yielded higher profit than standard control methods and that approached the highest possible profit achieved by frequent real-time optimization.     

Integrated micro-Raman/infrared thermography probe for monitoring of self-heating in AlGaN/GaN transistor structures

Self-heating in AlGaN/GaN device structures was probed using integrated micro-Raman/Infrared (IR) thermography. IR imaging provided large-area-overview temperature maps of powered devices. Micro-Raman spectroscopy was used to obtain high-spatial-resolution temperature profiles over the active area of the devices. Depth scans were performed to obtain temperature in the heat-sinking SiC substrate. Limitations in temperature and spatial resolution, and relative advantages of both techniques are discussed. Results are compared to three-dimensional finite-difference simulations.     

Altered Signal Transduction in the Immune Response to Influenza Virus and S. pneumoniae or S. aureus Co-Infections

Influenza virus is a well-known respiratory pathogen, which still leads to many severe pulmonary infections in the human population every year. Morbidity and mortality rates are further increased if virus infection coincides with co-infections or superinfections caused by bacteria such as Streptococcus pneumoniae (S. pneumoniae) and Staphylococcus aureus (S. aureus). This enhanced pathogenicity is due to complex interactions between the different pathogens and the host and its immune system and is mainly governed by altered intracellular signaling processes. In this review, we summarize the recent findings regarding the innate and adaptive immune responses during co-infection with influenza virus and S. pneumoniae or S. aureus, describing the signaling pathways involved and how these interactions influence disease outcomes.     

Carbohydrate ingestion improves endurance performance during a 1 h simulated cycling time trial

We show here that limited proteolysis can probe the structural and dynamic differences between the holo and apo form of horse myoglobin (Mb). Initial nicking of the polypeptide chain of apoMb (153 amino acid residues, no disulfide bonds) by several proteases (subtilisin, thermolysin, chymotrypsin and trypsin) occurs at the level of chain segment 89-96. In contrast, holoMb is resistant to proteolytic digestion when reacted under identical experimental conditions. Such selective proteolysis implies that the F-helix of native holoMb (residues 82 to 97) is disordered in apoMb, thus enabling binding and adaptation of this chain segment at the active site of the proteolytic enzymes for an efficient peptide bond fission. That essentially only the F-helix in apoMb is largely disrupted was earlier inferred from spectroscopic measurements and molecular dynamics simulations. The results of this study provide direct experimental evidence for this and emphasize therefore that limited proteolysis is a useful and reliable method for probing structure and dynamics of proteins, complementing other experimental techniques such as NMR and X-ray crystallography.     

Occurrence of some organic UV filters in wastewater, in surface waters, and in fish from Swiss Lakes

Organic UV filters are used in personal care products such as sunscreen products, and in cosmetics, beauty creams, skin lotions, lipsticks, hair sprays, hair dyes, shampoos, and so forth. The compounds enter the aquatic environmentfrom showering, wash-off, washing (laundering), and so forth via wastewater treatment plants (WWTPs) ("indirect inputs") and from recreational activities such as swimming and bathing in lakes and rivers ("direct inputs"). In this study, we investigated the occurrence of four important organic UV filter compounds (benzophenone-3, BP-3; 4-methylbenzylidene camphor, 4-MBC; ethylhexyl methoxy cinnamate, EHMC; octocrylene, OC) in wastewater, and in water and fish from various Swiss lakes, using gas chromatographic/mass spectrometric analyses. All four UV filters were present in untreated wastewater (WWTP influent) with a maximum concentration of 19 microg L(-1) for EHMC. The data indicate a seasonal variation with influent loads higher in the warmer season (June 2002) than in the colder one (April 2002). The influent loads were in the order EHMC > 4-MBC approximately BP-3 > OC. The concentrations in treated wastewater (WWTP effluent) were considerably lower, indicating substantial elimination in the plants. 4-MBC was usually the most prevalent compound (maximum concentration, 2.7 microg L(-1)), followed by BP-3, EHMC, and OC. UV filters were also detected in Swiss midland lakes and a river (Limmat) receiving inputs from WWTPs and recreational activities. However, all concentrations were low (<2-35 ng L(-1)); no UV filters (<2 ng L(-1)) were detected in a remote mountain lake. Data from passive sampling using semipermeable membrane devices (SPMDs) supported the presence of these UV filters in the lakes and the river and suggested some potential for accumulation of these compounds in biota. SPMD-derived water concentrations increased in the order Greifensee < Zürichsee < Hüttnersee. This order is reversed from that observed for methyl triclosan, used as a chemical marker for WWTP-derived lipophilic contaminants in the lakes. This indicated inputs of UV filters from sources other than WWTPs to the lakes during summer,for example,inputs from recreational activities. Fish (white fish, Coregonus sp.; roach, Rutilus rutilus; perch, Perca fluviatilis) from these lakes contained low but detectable concentrations of UV filters, in particular, 4-MBC (up to 166 ng g(-1) on a lipid basis). 4-MBC concentrations relative to methyl triclosan were lower in fish than in SPMDs exposed in the same lakes, suggesting that 4-MBC is less bioaccumulated than expected or metabolized in fish. The lipid-based bioconcentration factor (BCF(L)) estimated from the fish (roach) data and SPMD-derived water concentrations was about 1-2.3 x 10(4) and thus approximately 1 order of magnitude lower than expected from its Kow value.     

Enhanced Inhibition of Prostate Tumor Growth by Dual Targeting the Androgen Receptor and the Regulatory Subunit Type Iα of Protein Kinase A in Vivo

Progression to castration resistance is a major problem in the treatment of advanced prostate cancer and is likely to be driven by activation of several molecular pathways, including androgen receptor (AR) and cyclic AMP-dependent protein kinase A (PKA). In this study, we examined the therapeutic efficacy of a combined inhibition of the AR and the regulatory subunit type Iα (RIα) of protein kinase A with second generation antisense oligonucleotides (ODNs) in androgen-sensitive LNCaP and castration-resistant LNCaPabl tumors in vivo. We found that targeting the AR alone inhibited LNCaP, as well as LNCaPabl tumors. Combined inhibition resulted in an improved response over single targeting and even a complete tumor remission in LNCaPabl. Western blot analysis revealed that both ODNs were effective in reducing their target proteins when administered alone or in combination. In addition, treatment with the ODNs was associated with an induction of apoptosis. Our data suggest that dual targeting of the AR and PKARIα is more effective in inhibiting LNCaP and LNCaPabl tumor growth than single treatment and may give a treatment benefit, especially in castration-resistant prostate cancers.     

Bottlenose dolphins as indicators of persistent organic pollutants in the western North Atlantic Ocean and northern Gulf of Mexico

Persistent organic pollutants (POPs) including legacy POPs (PCBs, chlordanes, mirex, DDTs, HCB, and dieldrin) and polybrominated diphenyl ether (PBDE) flame retardants were determined in 300 blubber biopsy samples from coastal and near shore/estuarine male bottlenose dolphins (Tursiops truncatus) sampled along the U.S. East and Gulf of Mexico coasts and Bermuda. Samples were from 14 locations including urban and rural estuaries and near a Superfund site (Brunswick, Georgia) contaminated with the PCB formulation Aroclor 1268. All classes of legacy POPs in estuarine stocks varied significantly (p < 0.05) among sampling locations. POP profiles in blubber varied by location with the most characteristic profile observed in bottlenose dolphins sampled near the Brunswick and Sapelo estuaries along the Georgia coast which differed significantly (p < 0.001) from other sites. Here and in Sapelo, PCB congeners from Aroclor 1268 dominated indicating widespread food web contamination by this PCB mixture. PCB 153, which is associated with non-Aroclor 1268 PCB formulations, correlated significantly to human population indicating contamination from a general urban PCB source. Factors influencing regional differences of other POPs were less clear and warrant further study. This work puts into geographical context POP contamination in dolphins to help prioritize efforts examining health effects from POP exposure in bottlenose dolphins.     

Lysine Ethylation by Histone Lysine Methyltransferases

Biomedicinally important histone lysine methyltransferases (KMTs) catalyze the transfer of a methyl group from S-adenosylmethionine (AdoMet) cosubstrate to lysine residues in histones and other proteins. Herein, experimental and computational investigations on human KMT-catalyzed ethylation of histone peptides by using S-adenosylethionine (AdoEth) and Se-adenosylselenoethionine (AdoSeEth) cosubstrates are reported. MALDI-TOF MS experiments reveal that, unlike monomethyltransferases SETD7 and SETD8, methyltransferases G9a and G9a-like protein (GLP) do have the capacity to ethylate lysine residues in histone peptides, and that cosubstrates follow the efficiency trend AdoMet>AdoSeEth>AdoEth. G9a and GLP can also catalyze AdoSeEth-mediated ethylation of ornithine and produce histone peptides bearing lysine residues with different alkyl groups, such as H3K9meet and H3K9me2et. Molecular dynamics and free energy simulations based on quantum mechanics/molecular mechanics potential supported the experimental findings by providing an insight into the geometry and energetics of the enzymatic methyl/ethyl transfer process.