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In this paper, a roadway controller is designed, analyzed and simulated for a single automated highway lane that achieves desired traffic densities along the lane. A macroscopic traffic flow model that is modified for AHS (Automated Highway Systems) operation is used for control design and analysis. The authors show that the proposed roadway controller guarantees exponential convergence of the traffic density at each section of the lane to the desired density. Simulation results are used to illustrate the effectiveness of the proposed controller and the significant benefits AHS may bring to traffic flow.

Abstract Background Lemay et al recently reported that the RNA binding protein HuR directly interacts with the ribonuclease H (RNase H) domain of HIV-1 reverse transcriptase (RT) and influences the efficiency of viral reverse transcription (Lemay et al., 2008, Retrovirology 5:47). HuR is a member of the embryonic lethal abnormal vision protein family and contains 3 RNA recognition motifs (RRMs) that bind AU-rich elements (AREs). To define the structural determinants of the HuR-RT interaction and to elucidate the mechanism(s) by which HuR influences HIV-1 reverse transcription activity in vitro, we cloned and purified full-length HuR as well as three additional protein constructs that contained the N-terminal and internal RRMs, the internal and C-terminal RRMs, or the C-terminal RRM only. Results All four HuR proteins were purified and characterized by biophysical methods. They are well structured and exist as monomers in solution. No direct protein-protein interaction between HuR and HIV-1 RT was detected using NMR titrations with 15N labeled HuR variants or the 15N labeled RNase H domain of HIV-1 RT. Furthermore, HuR did not significantly affect the kinetics of HIV-1 reverse transcription in vitro, even on RNA templates that contain AREs. Conclusions Our results suggest that HuR does not impact HIV-1 replication through a direct protein-protein interaction with the viral RT.

Consumers in the U.S. increasingly prefer plant-based milk alternative beverages (abbreviated "plant milk") to conventional milk. This study is motivated by the need to take into consideration varied nutritional and qualitative attributes in plant milk to examine consumers' purchasing behavior and estimate demand elasticities which are achieved by a new approach combing hedonic pricing model with Barten's synthetic demand system. The method of estimation is enlightened from the common practice of companies differentiating their products in multidimensions in terms of attributes. A research dataset was uniquely created by associating the products' purchase data from Nielsen Homescan dataset with exclusive first-hand nutritional data. Estimations began with creating a multidimensional hedonic attribute space based on the qualitative information of different types of plant milk and conventional milk available to consumers and then calculating the hedonic distances by Euclidean distance measurement to reparametrize Barten's synthetic demand system. Estimation results showed that the highest own-price elasticity pertained to soy milk which was -0.25. Three plant milk types had inelastic demand. Soy milk exerted substituting effects on all types of conventional milk products and vice versa. Soy milk, rice milk and almond milk entertained complementary relationships between each other and four types of conventional milk were strong substitutes within the group.

Dairy products, especially milk play a crucial role in assuring dietary quality for U.S. households. However, due to taste, nutrition, health and environmental concerns, households increasingly prefer to consume dairy alternative beverages instead of conventional milk in the U.S. This work is motivated by the need to take into consideration of intrinsic characteristics and differences of such characteristics when analyzing the changes of consumers' purchasing behavior of and willingness to pay for dairy alternative beverages and conventional milk products. After aggregating and organizing the purchase data of Nielsen Homescan and first-hand nutrition data, this study estimates both linear and semi-log hedonic pricing models. The results show that consumers exert the highest weights and assign highest evaluation on such qualitative characteristic as nutritional attributes which include calories, protein, fat, vitamin A and vitamin D in which protein is the most valued attribute and other characteristics such as package size, multi pack and brand. The hedonic pricing order and value of these qualitative characteristic are indicative of consumers' purchasing behavior and thus provide essential information for manufacturers to better differentiated their products and develop products catering to consumer's preferred attributes., Competing Interests: We declare that we do not have any conflict of interest., (© 2020 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Systematic physical and electrochemical characterizations revealed unique positive multifunction of a polymeric salen-type nickel(II) complex, poly[Ni(CH 3 -salen)], as an additive for conventional cathodes in lithium-ion batteries. Due to its promising electrochemical and mechanical properties, combined with its unique three-dimensional weblike electron-network structure, the redox-active-organometallic polymer can eliminate conductive carbon and replace a significant portion of the poly(vinylidene fluoride) (PVdF) binder that has been used in conventional LiFePO 4 cathodes. By replacing such electrochemically inactive components (i.e., carbon and PVdF), LiFePO 4 cathodes with poly[Ni(CH 3 -salen)] deliver improved energy density compared with the conventional LiFePO 4 cathode. Facile electron transfer via large-area contact at polymer/LiFePO 4 interfaces significantly accelerates charge-transfer reactions and consequently improves the rate capability of the cathodes. In addition, unlike PVdF, poly[Ni(CH 3 -salen)] retains steady Young's modulus values after immersing in an electrolyte solvent, which enhances the mechanical integrity of the cathodes during the cycling of battery cells and thereby improves their cycle life. The unique multifunction of the poly[Ni(CH 3 -salen)] will be of broad interest for its application in next-generation energy-storage devices.

During dynamic atomic force microscopy (AFM), the deflection of a scanning cantilever generates multiple frequency terms due to the nonlinear nature of AFM tip-sample interactions. Even though each frequency term is reasonably expected to encode information about the sample, only the fundamental frequency term is typically decoded to provide topographic mapping of the measured surface. One of main reasons for discarding higher harmonic signals is their low signal-to-noise ratio. Here, we introduce a new design concept for multi-harmonic AFM, exploiting intentional nonlinear internal resonance for the enhancement of higher harmonics. The nonlinear internal resonance, triggered by the non-smooth tip-sample dynamic interactions, results in nonlinear energy transfers from the directly excited fundamental bending mode to the higher-frequency mode and, hence, enhancement of the higher harmonic of the measured response. It is verified through detailed theoretical and experimental study that this AFM design can robustly incorporate the required internal resonance and enable high-frequency AFM measurements. Measurements on an inhomogeneous polymer specimen demonstrate the efficacy of the proposed design, namely that the higher harmonic of the measured response is capable of enhanced simultaneous topography imaging and compositional mapping, exhibiting less crosstalk with an abrupt height change.

Monthly data derived from the Nielsen Homescan Panel for calendar years 1998 through 2003 are used to estimate the effects of a proposed tax on sugar-sweetened beverages (SSBs). Most arguments in describing the ramifications of a tax fail to consider demand interrelationships among various beverages. To circumvent this shortcoming we employ a variation of Quadratic Almost Ideal Demand System (QUAIDS) model. The consumption of isotonics, regular soft drinks and fruit drinks, the set of SSBs, is negatively impacted by the proposed tax, while the consumption of fruit juices, low-fat milk, coffee, and tea is positively affected. Diversion ratios are provided identifying where the volumes of the SSBs are directed as a result of the tax policy. The reduction in the body weight as a result of a 20% tax on SSBs is estimated to be between 1.54 and 2.55 lb per year. However, not considering demand interrelationships would result in higher weight loss. Unequivocally, it is necessary to consider interrelationships among non-alcoholic beverages in assessing the effect of the tax., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: Lemay et al recently reported that the RNA binding protein HuR directly interacts with the ribonuclease H (RNase H) domain of HIV-1 reverse transcriptase (RT) and influences the efficiency of viral reverse transcription (Lemay et al., 2008, Retrovirology 5:47). HuR is a member of the embryonic lethal abnormal vision protein family and contains 3 RNA recognition motifs (RRMs) that bind AU-rich elements (AREs). To define the structural determinants of the HuR-RT interaction and to elucidate the mechanism(s) by which HuR influences HIV-1 reverse transcription activity in vitro, we cloned and purified full-length HuR as well as three additional protein constructs that contained the N-terminal and internal RRMs, the internal and C-terminal RRMs, or the C-terminal RRM only., Results: All four HuR proteins were purified and characterized by biophysical methods. They are well structured and exist as monomers in solution. No direct protein-protein interaction between HuR and HIV-1 RT was detected using NMR titrations with 15N labeled HuR variants or the 15N labeled RNase H domain of HIV-1 RT. Furthermore, HuR did not significantly affect the kinetics of HIV-1 reverse transcription in vitro, even on RNA templates that contain AREs., Conclusions: Our results suggest that HuR does not impact HIV-1 replication through a direct protein-protein interaction with the viral RT.

The effect of hypothyroidism on the cardiovascular system has been well documented. Cardiac dysfunction due to hypothyroidism manifests as both systolic and diastolic dysfunction of the heart leading to cardiac arrhythmia and congestive heart failure. Its presentation in the form of refractory hypotension is rare. We describe a 52 year old man on whom Hypothyroid Cardiomyopathy manifested as cardiogenic shock responsive only to thyroxin replacement.

Introduction: Lung cancer is the leading cause of death among the cancers seen in the United States. Hypercalcemia and leukocytosis are two common paraneoplastic syndromes associated with lung cancer. Unfortunately patients presenting with Hypercalcemia- leukocytosis syndrome has a worse prognosis than patients presenting with lung cancer alone., Case Presentation: We present a 67 yr old Caucasian male with a history of active smoking presenting as pneumonia being diagnosed as cavitating squamous cell carcinoma of the lung with hypercalcemia-leukocytosis syndrome, Conclusion: There should be a high degree of suspicion to diagnose lung cancer in patients presenting with symptoms of paraneoplastic syndrome.

The resistance of HIV-1 to 3'-azido-3'-deoxythymidine (AZT) involves phosphorolytic excision of chain-terminating AZT-5'-monophosphate (AZTMP). Both pyrophosphate (PPi) and ATP act as excision substrates in vitro, but the intracellular substrate used during replication of AZT-resistant HIV is still unknown. PPi-mediated excision produces AZT-5'-triphosphate (AZTTP), which could be immediately re-used as a substrate for viral DNA chain termination. In contrast, ATP-mediated excision produces the novel compound AZT-(5')-tetraphospho-(5')-adenosine (AZTp4A). Since little is known of the interaction of AZTp4A with HIV-1 RT, we carried out kinetic and molecular modeling studies to probe this. AZTp4A was found to be a potent inhibitor of HIV-1 RT-catalyzed DNA synthesis and of both ATP- and PPi-mediated AZTMP excision. AZTp4A is in fact an excellent chain-terminating substrate for AZT-resistant RT-catalyzed DNA synthesis, better than AZTTP (k(pol)/Kd = 6.2 and 11.9 for AZTTP and AZTp4A, respectively). The affinity of AZT-resistant HIV-1 RT for AZTp4A is at least 30,000-fold greater than that for the excision substrate ATP and approximately 10-fold greater than that for AZTTP. Dissociation of newly formed AZTp4A from RT may therefore provide a significant rate-limiting step for continued HIV-1 DNA synthesis. Our studies show that the products of PPi- and ATP-mediated excision of chain-terminating AZTMP (AZTTP and AZTp4A, respectively) are both potent chain-terminating substrates for HIV-1 RT, suggesting that there is no obvious benefit to HIV using ATP instead of PPi as the excision substrate.

The rapid emergence of drug-resistant variants of human immunodeficiency virus, type 1 (HIV-1), has limited the efficacy of anti-acquired immune deficiency syndrome (AIDS) treatments, and new lead compounds that target novel binding sites are needed. We have determined the 3.15 A resolution crystal structure of HIV-1 reverse transcriptase (RT) complexed with dihydroxy benzoyl naphthyl hydrazone (DHBNH), an HIV-1 RT RNase H (RNH) inhibitor (RNHI). DHBNH is effective against a variety of drug-resistant HIV-1 RT mutants. While DHBNH has little effect on most aspects of RT-catalyzed DNA synthesis, at relatively high concentrations it does inhibit the initiation of RNA-primed DNA synthesis. Although primarily an RNHI, DHBNH binds >50 A away from the RNH active site, at a novel site near both the polymerase active site and the non-nucleoside RT inhibitor (NNRTI) binding pocket. When DHBNH binds, both Tyr181 and Tyr188 remain in the conformations seen in unliganded HIV-1 RT. DHBNH interacts with conserved residues (Asp186, Trp229) and has substantial interactions with the backbones of several less well-conserved residues. On the basis of this structure, we designed substituted DHBNH derivatives that interact with the NNRTI-binding pocket. These compounds inhibit both the polymerase and RNH activities of RT.

Background: Dementia is poorly recognized even by physicians. This study compares three instruments used to assess dementia in a community setting in Sri Lanka., Method: Translated and culturally adapted versions of the Mini Mental State Examination (MMSE), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and Clinical Dementia Rating (CDR) were administered to 363 individuals selected by stratified random sampling in a periurban community in Sri Lanka. The results on the three instruments were compared with the independent psychiatric evaluation done on a concentrated sample of 37 individuals from the study population., Results: Culturally adapted MMSE, IQCODE and CDR can be used to screen dementia in Sri Lanka. IQCODE is the best among the three instruments with a sensitivity of 71.4% and a specificity of 82.6% when 3.5 is the cut-off. In addition, IQCODE is culturally acceptable, easy to administer and can be used in those with a low level of literacy as well as in those with hearing or visual impairment., Conclusion: IQCODE was found to be more effective and culturally acceptable as a screening tool for dementia in Sri Lanka, compared with MMSE and CDR.

The electronic and steric constraints of the dopamine beta-monooxygenase (DbetaM; E.C. 1.14.17.1) active site were studied using a series of chiral bisubstrate inhibitors. The (R) and (S) enantiomers of 5-phenyl-2-thiooxazolidone were apparent bisubstrate inhibitors for DbetaM with respect to tyramine and dioxygen, but with small enantiomeric selectivity. In contrast to the substrate specificity of the enzyme, N-methylation of both inhibitors increased the potency without altering the enantiomeric selectivity. The (S) C-4-methyl substitution was more detrimental toward the inhibition potency compared to (R) C-4-methyl substitution for both the (R) and (S) series, which was also opposite of the substrate specificity of the enzyme. The high inhibition potency and apparent bisubstrate behavior of 3-phenyl-1,5-bisthioglutarimide (XVI), a probe designed to mimic two distinct binding modes for the (R) and (S) inhibitors, suggested that they may interact with the enzyme by two different modes involving both coppers in the active site. Direct support for the interaction of the thione group(s) of XVI with the reduced DbetaM copper(s) is provided by the UV-vis spectroscopic studies. The complete disappearance of the characteristic UV absorption of XVI at 336 nm in the presence of stoichiometric amounts of reduced DbetaM demonstrate that it could be an active site titrant for reduced DbetaM. The ability of the enzyme to interact with these inhibitors by more than one mode suggests that the DbetaM active site possesses high steric and electronic tolerance.

Two repetitive sequences (IpSdM and IpSdS) have been cloned and sequenced from the genome of Setaria digitata. When IpSdM (214 bp) and IpSdS (201 bp) were aligned, a high degree of homology (85%) was observed, indicating that they belong to the same family of repeats. IpSdM represents a complete repeating element while IpSdS consists of two partial repeating elements arranged in tandem. The elements are present in about 10 000 copies comprising 2.8% of the S. digitata genome. As a diagnostic probe IpSdM detects as little as 100 pg DNA of both S. digitata and S. labiato-papillosa. It can also detect a single microfilaria and a L3 larva making it a valuable tool to monitor cattle and mosquito vector populations in the prevention of cerebrospinal nematodiasis.

A series of ascorbate derivatives has been used to examine the specificity of the reduction site of ascorbate oxidase. Replacement of the 6-OH group of ascorbic acid with either hydrogen or bromine does not alter the substrate activity significantly. 6-Amino-6-deoxy-L-ascorbic acid is a weak substrate for the enzyme, suggesting that positively charged groups at the 6-position are not well tolerated by the enzyme. The modification of the 5-OH reduces the effective interaction with the enzyme and the replacement of 6-OH with 6-S-phenyl- or 6-O-phenyl groups significantly increases the affinity for the enzyme. Both 2-Amino-6-S-phenyl-L-ascorbic acid and imino-D-glucoascorbic acid are not substrates for the enzyme. The stereoelectronic properties and alternate binding modes of these molecules are being considered to explain these observations. The substrate specificity of the enzyme is compared to the specificity of the reduction site of dopamine beta-monooxygenase.

A series of ascorbate derivatives has been used to examine the specificity and the chemistry of the reduction site of dopamine beta-monooxygenase (D beta M). Replacement of the 6-OH group of ascorbic acid with either bromine or hydrogen does not alter the enzyme reduction efficiency significantly. Unexpectedly, the 6-OH modified ascorbate derivatives, 6-S-phenyl-6-thio-L-ascorbic acid and 6-O-phenyl-L-ascorbic acid were found to have much higher affinity for the enzyme than the most effective known electron donor, ascorbic acid (AscH-). The affinity of 2-amino-6-S-phenyl-L-ascorbic acid was found to be similar to that of 2-amino-L-ascorbic acid. 6-Amino-6-deoxy-L-ascorbic acid is neither a substrate nor an inhibitor for the enzyme. Although glucoascorbic acid is an excellent substrate for the enzyme, imino glucoascorbic acid was found to be an extremely potent competitive inhibitor for the enzyme. The stereoelectronic properties and alternate binding modes of these molecules have been considered in explaining the observations.