cssi/SciSciGPT-SciSciNet huggingface dataset:
Substitutions of the "bridging" aspartate 178 result in profound changes in the reactivity of the Rieske center of phthalate dioxygenase.

Phthalate dioxygenase (PDO) and its reductase (PDR) are parts of a two-component Rieske oxygenase system that initiates the aerobic breakdown of phthalate by forming cis-4,5-dihydro-4,5-dihydroxyphthalate. Aspartate D178 in PDO, which lies between the Rieske [2Fe-2S] center of one subunit and the mononuclear center of the adjacent subunit, is highly conserved among the Rieske dioxygenases. The analogous aspartate has been implicated in electron transfer in naphthalene dioxygenase and in substrate binding and oxygen reactivity in anthranilate dioxygenase. Substitution of D178 with alanine or asparagine in PDO resulted in proteins with significantly increased Fe(II) dissociation constants. The rates of oxidation of the reduced Rieske centers in D178A and D178N were decreased by more than 104-fold; only part of the loss of activity can be attributed to depletion of iron from the mononuclear centers. Reduction of PDO by reduced PDR was also slower in the D178A and D178N variants. Observed decreases in turnove...
Homotopy fixed points for LK(n)(En∧X) using the continuous action

Abstract Let K ( n ) be the n th Morava K -theory spectrum. Let E n be the Lubin–Tate spectrum, which plays a central role in understanding L K ( n ) ( S 0 ) , the K ( n ) -local sphere. For any spectrum X , define E ∨ ( X ) to be L K ( n ) ( E n ∧ X ) . Let G be a closed subgroup of the profinite group G n , the group of ring spectrum automorphisms of E n in the stable homotopy category. We show that E ∨ ( X ) is a continuous G -spectrum, with homotopy fixed point spectrum ( E ∨ ( X ) ) hG . Also, we construct a descent spectral sequence with abutment π * ( ( E ∨ ( X ) ) hG ) .
Solving Cauchy singular integral equations by using general quadrature-collocation nodes☆

Abstract We show that the specific nodes are not necessary for solving Cauchy singular integral equations by using quadrature-collocation methods. The solvability of the discrete system is proved for arbitrary selection of quadrature and collocation nodes. We also propose several special choices of these nodes. Especially, a weighted minimum norm-least square method is discussed.
Nucleosomes inhibit the initiation of transcription but allow chain elongation with the displacement of histones

Promoters were assembled in nucleosomes or ligated to nucleosomes and transcribed with SP6 RNA polymerase or with mammalian RNA polymerase II and accessory factors. Neither polymerase would initiate transcription at a promoter in a nucleosome, but once engaged in transcription, both polymerases were capable of reading through a nucleosome. In the course of readthrough transcription, the histones were displaced from the DNA, as shown by the exposure of restriction sites and by a shift of the template to the position of naked DNA in a gel. It may be true, in general, that processive enzymes will traverse regions of DNA organized in nucleosomes and displace histones.
National adverse drug reaction reporting : 1984-1989

Surveillance of adverse reactions due to pharmaceuticals is important because the drug approval process cannot totally assure safety and because new knowledge is bound to accrue after drugs enter usual medical practice. Reporting of reactions to the Food and Drug Administration increased markedly between 1985 and 1989 and totaled 261 515 reports for this period. A large part of this increase was due to new legal requirements, which ensure that manufacturers report reactions to the Food and Drug Administration. Most reaction reports originated with practicing physicians who contacted drug manufacturers. High proportions of the reports involved new drugs and serious reactions. Reaction surveillance leads to 50 to 100 important safety investigations annually and to numerous changes in product information. Health care providers must continue to report suspect adverse reactions to the Food and Drug Administration and manufacturers if pharmaceutical use and safety are to improve. ( Arch Intern Med . 1991;151:1645-1647)
Thermoradiation therapy for superficial malignant tumors

Background. Between 1980–1990, 126 patients were treated with radiation therapy (RT) and hyperthermia using 915-MHz external microwave applicators. All but 11 patients had failed to respond to previous therapy. Methods. The mean tumor volume was 73 ± 13 cm3, and the mean radiation dose delivered was 45 ± 1 Gy. Hyperthermia was administered biweekly in 83% of the fields in 5.5 ± 0.2 sessions. Lesions were stratified by depth. The predictive influence of pretreatment or treatment parameters was analyzed for the probability of response by logistic regression and for the duration of local control by proportional hazards. Results. In tumors considered potentially heatable (i.e., ± 3-cm deep), the complete response (CR) rate was 70%, whereas the CR rate for patients with tumors deeper than 3 cm was 18% (P ± 0.0001). Among superficial lesions of less than or equal to 3-cm depth that exhibited a CR, 14 recurred (26%, 8.7 ± 1.6 months), while 39 lesions were recurrence-free at last follow-up of 17.8 ± 1.4 months. The 50% tumor-effective dose was 44 Gy. For superficial lesions that received between 30–60 Gy, the CR rate was 55% when the fraction size was less than 3 Gy, whereas it was 77% when the fraction size was 3–4 Gy (P = 0.05). Multivariate logistic regression analysis indicated that the model best correlating with CR included concurrent radiation dose (P = 0.006) and tumor volume (P = 0.02; model P = 0.0001). Multivariate proportional hazard analysis indicated that the model best correlating with duration of local control included tumor histology (P = 0.004; model P 0.0007). The overall survival rate of patients with lesions of less than or equal to 3-cm depth who were treated with thermoradiation therapy was 16.1 ± 1.2 months. For patients with lesions more than 3-cm deep, survival was 8.7 ± 1.1 months (P ± 0.001). Forty-two fields were treated without any skin reactions (33%), 59 exhibited erythema (47%), and 25 experienced thermal blistering (20%). Conclusions. Treatment of superficial malignant tumors can benefit from the adjuvant use of hyperthermia delivered with external 915-MHz applicators provided tumors are less than 3 cm from the surface and the lateral margins are within the 50% specific absorption rate (SAR) on the surface.
An evaluation of garnet-clinopyroxene geothermometry in granulites

Four new formulations of the garnet-clinopyroxene geothermometer (Ellis and Green 1979; Ganguly 1979; Saxena 1979; Dahl 1980) have been evaluated in the Adirondacks and five other granulite terranes using results from 94 mineral pairs. The Saxena and Ganguly formulations give temperatures that are generally 100–150° C above those constrained by phase equilibria and other independent thermometry while the empirical calibration of Dahl gives widely scattered, erratic results. Despite some scatter in the data, the Ellis and Green calibration appears to be more accurate and precise than the others and is the most useful garnet-clinopyroxene thermometer currently available for quantitative thermometry in granulites. All four formulations are sensitive to large variations (>70–80° C) in temperature suggesting that problems with accuracy and precision can be improved with further refinement of model-based aspects of the thermometers.
The effects of oral anti‐hyperglycaemic medications on serum lipid profiles in patients with type 2 diabetes

Aim: Patients with type 2 diabetes often have dyslipidaemia, putting them at risk of cardiovascular disease, and are frequently treated with oral anti-hyperglycaemic medications (OAMs). This review compares the effects of OAMs on serum lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and free fatty acids (FFAs)] in patients with type 2 diabetes. Methods: medline was searched for entries indexed from January 1966 to November 2002; search terms included the names of OAMs and serum lipids, limited to English language and human subjects. We selected clinical studies in type 2 diabetes of OAM monotherapy that included serum lipid data, treated all patients in a treatment group with the same drug, used therapeutic OAM doses not higher than the maximum recommended in the USA, compared therapy with baseline or placebo and specified statistical tests used. One unblinded investigator selected studies for inclusion. Data reported include number of patients, study length, OAM dose, serum lipid data at baseline and endpoint, p-values and statistical tests. Results: Data on the serum lipid effects of sulphonylureas, repaglinide, nateglinide and miglitol were inconclusive. Acarbose increased HDL-C and decreased LDL-C and voglibose reduced TC. Metformin at higher doses reduced TC; data on its effects on other lipids were inconclusive. Rosiglitazone increased LDL-C, HDL-C and TC and reduced FFAs but had no effect on TGs. Pioglitazone increased HDL-C and reduced TGs and FFAs but did not affect LDL-C or TC. Conclusions: Lipid changes as a result of improved glycaemic control are not uniform findings associated with anti-diabetic therapy. Only metformin, acarbose, voglibose, rosiglitazone and pioglitazone had significant effects on the lipid profile. These effects should be considered when selecting OAMs for patients with type 2 diabetes.
Apoptosis of T cells in peripheral blood and cerebrospinal fluid is associated with disease activity of multiple sclerosis

Apoptotic elimination of pathogenic T cells is considered to be one of regulatory mechanisms in multiple sclerosis (MS). To explore the potential relationship between Fas-mediated apoptosis and the disease course of MS, we examined apoptosis, defined by annexin V (AV) binding, and Fas (CD95) expression in CD4+ and in CD8+ T cells in MS patients by using five-color flow cytometry. The percentage of AV+CD4+CD3+ cells and CD95+AV+CD4+CD3+ cells in peripheral blood and cerebrospinal fluid (CSF) were significantly decreased in active MS patients compared with inactive MS patients. A significantly lower proportion of CD95+AV+CD8+CD3+ cells in CSF was observed in active MS patients compared with inactive MS patients, but not in peripheral blood. These results indicate that the resistance of T cells to Fas-mediated apoptosis is involved in exacerbation of MS and/or that Fas-mediated apoptosis of T cells is associated with remission of MS.
High-frequency valve development for smart material electro-hydraulic actuators

This paper presents two approaches to developing improved check valves for high frequency fluid rectification in a smart material electro-hydraulic actuator: a single reed-type design and an array of miniaturized valves. The multiphysics software COMSOL was used to study the 3-D fluid-structure interaction between the valve and hydraulic fluid during pump operation, and the results were validated utilizing an instrumented valve to measure in-situ tip displacement. The added mass effect of the fluid on the valve was experimentally characterized. To improve the frequency response of the valves, an array of miniature reed valves were designed for the high frequency and high pressure environment in the pump. A fabrication method was developed for the miniaturized valves utilizing micromachining processes. The performance of the two types of valves was compared through static and dynamic experiments.
Nitric oxide donor-induced hyperpermeability of cultured intestinal epithelial monolayers: role of superoxide radical, hydroxyl radical, and peroxynitrite

Many of the cytopathic effects of nitric oxide (NO·) are mediated by peroxynitrite (PN), a product of the reaction between NO· and superoxide radical (O·−2). In the present study, we investigated the role of PN, O·−2 and hydroxyl radical (OH·) as mediators of epithelial hyperpermeability induced by the NO· donor, S-nitroso-N-acetylpenicillamine (SNAP), and the PN generator, 3-morpholinosydnonimine (SIN-1). Caco-2BBe enterocytic monolayers were grown on permeable supports in bicameral chambers. Epithelial permeability, measured as the apical-to-basolateral flux of fluorescein disulfonic acid, increased after 24 h of incubation with 5.0 mM SNAP or SIN-1. Addition of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, an NO· scavenger, or Tiron, an O·−2 scavenger, reduced the increase in permeability induced by both donor compounds. The SNAP-induced increase in permeability was prevented by allopurinol, an inhibitor of xanthine oxidase (a source of endogenous O·−2). Diethyldithiocarbamate, a superoxide dismutase inhibitor, and pyrogallol, an O·−2 generator, potentiated the increase in permeability induced by SNAP. Addition of the PN scavengers deferoxamine, urate, or glutathione, or the OH· scavenger mannitol, attenuated the increase in permeability induced by both SNAP and SIN-1. Both donor compounds decreased intracellular levels of glutathione and protein-bound sulfhydryl groups, suggesting the generation of a potent oxidant. These results support a role for PN, and possibly OH·, in the pathogenesis of NO· donor-induced intestinal epithelial hyperpermeability.
MTBE Transport Screening Analysis in Vadose Zone Risk and Liability Apportionment Assessment

Abstract The problem of allocating liability cleanup costs is an arduous task when more than one potentially responsible party has contributed to the groundwater plume. This problem is most likely to be encountered when dealing with methyl- tert -butyl-ether (MTBE) contamination, as MTBE is seen to travel large distances in underlying aquifers. There has been a significant effort in the recent past to develop liability allocation methodologies that incorporate fate and transport behavior and toxicological characteristics of the contaminants. The application of such methods often requires estimation of contaminant input from the vadose zone into the underlying aquifer. A screening level analysis is presented here to develop preliminary insights on relative mass contributions arising from different source types. The analysis illustrates how different vadose zone conceptualizations lead to vastly different contaminant loadings. Parametric studies indicate that the contaminant flux into the aquifer is very sensitive to changes in water infiltration rates. Hence, a reliable estimate of this parameter is critical for equitable allocation of remedial costs. Conceptual model formulation, should focus on identifying whether the fuel present in the aquifer can flow as a separate phase. It is also important to obtain reliable estimates for fluid saturations at the site.
Data-path synthesis of VLIW video signal processors

This paper describes a methodology for synthesizing the data-path of a Very Long Instruction Word (VLIW) based Video Signal Processor (VSP). Offering both performance and programmability, VSPs are important for their roles in digital video applications, which are omnipresent in today's world. Among many different architectures, VLIW is becoming increasingly popular and widely used due to its efficiency in exploiting high degree of parallelism inherent in multimedia applications. While architectural syntheses of embedded systems have been studied in depth, little literature has addressed similar issues for VLIW-based VSPs. Using an MPEG-2 video encoder as a case study, in this paper we present a combined application of trace-driven simulation and performance estimation in the data-path synthesis of a VLIW VSP. Results show that our estimations are quite precise and helpful, let alone that they are orders of magnitude faster than simulation.
Vortex motion and the Hall effect in type-II superconductors: A time-dependent Ginzburg-Landau theory approach

Vortex motion in type-II superconductors is studied starting from a variant of the time-dependent Ginzburg-Landau equations, in which the order-parameter relaxation time is taken to be complex. Using a method due to Gor'kov and Kopnin, we derive an equation of motion for a single vortex (B\ensuremath{\ll}${\mathit{H}}_{\mathit{c}2}$) in the presence of an applied transport current. The imaginary part of the relaxation time and the normal-state Hall effect both break ``particle-hole symmetry,'' and produce a component of the vortex velocity parallel to the transport current, and consequently a Hall field due to the vortex motion. Various models for the relaxation time are considered, allowing for a comparison to some phenomenological models of vortex motion in superconductors, such as the Bardeen-Stephen and Nozi\`eres-Vinen models, as well as to models of vortex motion in neutral superfluids. In addition, the transport energy, Nernst effect, and thermopower are calculated for a single vortex. Vortex bending and fluctuations can also be included within this description, resulting in a Langevin-equation description of the vortex motion. The Langevin equation is used to discuss the propagation of helicon waves and the diffusional motion of a vortex line. The results are discussed in light of the rather puzzling sign change of the Hall effect which has been observed in the mixed state of the high-temperature superconductors.
Does a Firm's Product-Recall Strategy Affect Its Financial Value? An Examination of Strategic Alternatives During Product-Harm Crises

Abstract Product-harm crises often result in product recalls, which can have a significant impact on a firm's reputation, sales, and financial value. In managing the recall process, some firms adopt a proactive strategy in responding to consumer complaints, while others are more passive. In this study, the authors examine the impact of these strategic alternatives on firm value using Consumer Product Safety Commission recalls during a 12-year period from 1996 to 2007. Using the event study method, the authors show that regardless of firm and product characteristics, proactive strategies have a more negative effect on firm value than more passive strategies. An explanation for this surprising result is that the stock market interprets proactive strategies as a signal of substantial financial losses to the firm. When a firm proactively manages a product recall, the stock market infers that the consequence of the product-harm crisis is sufficiently severe that the firm had no choice but to act swiftly to red...
An analysis of students’ initial statistical understandings: developing a conjectured learning trajectory

Abstract This paper reports the analysis of performance assessment tasks administered in a seventh-grade classroom. The purpose of the assessments was to obtain data on students’ current statistical understandings that would then inform future instructional design decisions in a classroom teaching experiment that focused on statistical data analysis. The tasks were designed to provide information about students’ current understandings of creating data, organizing data, and assessing the center and “spreadoutness” of data. In considering the analysis, we found that the students typically viewed the mean as a procedure that was to be used to summarize a group of numbers regardless of the task situation. Data analysis for these students meant “doing something with the numbers.” Based on this analysis, a goal that emerged as significant for the classroom teaching experiment was to support a shift in students’ reasoning towards data analysis as inquiry rather than procedure. The influence of the students’ prior experiences of doing mathematics in school was also apparent when they developed graphs. They were primarily concerned with school-taught graphical conventions rather than with what the graphs signified. In the course of the analysis we distinguished between additive and multiplicative reasoning about data. This distinction is significant given that the transition from additive to multiplicative reasoning constitutes the overriding goal of statistics instruction at the middle-school level.
Modes of continental extension in a crustal wedge

Abstract We ran numerical experiments of the extension of a crustal wedge as an approximation to extension in an orogenic belt or a continental margin. We study the effects of the strength of the lower crust and of a weak mid-crustal shear zone on the resulting extension styles. A weak mid-crustal shear zone effectively decouples upper crustal extension from lower crustal flow. Without the mid-crustal shear zone, the degree of coupling between the upper and the lower crust increases and extension of the whole crust tends to focus on the thickest part of the wedge. We identify three distinct modes of extension determined by the strength of the lower crust, which are characterized by 1) localized, asymmetric crustal exhumation in a single massif when the lower crust is weak, 2) the formation of rolling-hinge normal faults and the exhumation of lower crust in multiple core complexes with an intermediate strength lower crust, and 3) distributed domino faulting over the weak mid-crustal shear zone when the lower crust is strong. A frictionally stronger mid-crustal shear zone does not change the overall model behaviors but extension occurred over multiple rolling-hinges. The 3 modes of extension share characteristics similar to geological models proposed to explain the formation of metamorphic core complexes: 1) the crustal flow model for the weak lower crust, 2) the rolling-hinge and crustal flow models when the lower crust is intermediate and 3) the flexural uplift model when the lower crust is strong. Finally we show that the intensity of decoupling between the far field extension and lower crustal flow driven by the regional pressure gradient in the wedge control the overall style of extension in the models.
Inactivation of factor VIIa by antithrombin in vitro, ex vivo and in vivo: role of tissue factor and endothelial cell protein C receptor.

Recent studies have suggested that antithrombin (AT) could act as a significant physiologic regulator of FVIIa. However, in vitro studies showed that AT could inhibit FVIIa effectively only when it was bound to tissue factor (TF). Circulating blood is known to contain only traces of TF, at best. FVIIa also binds endothelial cell protein C receptor (EPCR), but the role of EPCR on FVIIa inactivation by AT is unknown. The present study was designed to investigate the role of TF and EPCR in inactivation of FVIIa by AT in vivo. Low human TF mice (low TF, ∼1% expression of the mouse TF level) and high human TF mice (HTF, ∼100% of the mouse TF level) were injected with human rFVIIa (120 µg kg−1 body weight) via the tail vein. At varying time intervals following rFVIIa administration, blood was collected to measure FVIIa-AT complex and rFVIIa antigen levels in the plasma. Despite the large difference in TF expression in the mice, HTF mice generated only 40–50% more of FVIIa-AT complex as compared to low TF mice. Increasing the concentration of TF in vivo in HTF mice by LPS injection increased the levels of FVIIa-AT complexes by about 25%. No significant differences were found in FVIIa-AT levels among wild-type, EPCR-deficient, and EPCR-overexpressing mice. The levels of FVIIa-AT complex formed in vitro and ex vivo were much lower than that was found in vivo. In summary, our results suggest that traces of TF that may be present in circulating blood or extravascular TF that is transiently exposed during normal vessel damage contributes to inactivation of FVIIa by AT in circulation. However, TF’s role in AT inactivation of FVIIa appears to be minor and other factor(s) present in plasma, on blood cells or vascular endothelium may play a predominant role in this process.
Coercive forms associated with elastic systems with damping

Abstract We consider the evolution equation u (t)+Au(t)+2aB u (t)=0 , where B is comparable to Aα for some 1 2 ⩽α⩽1 . This is a model for an elastic system with structural damping, and it is known that the system operator associated with this model is the infinitesimal generator of an analytic semigroup on the natural energy space. However, except for the case of so-called Kelvin–Voigt damping (α=1), this operator is neither sectorial nor associated with a coercive sesquilinear form. We show that these properties can be obtained via a different inner product on the energy space.
Isolation of two restriction endonucleases from Chloroflexus aurantiacus (CauI, CauII)

Abstract The purification and characterization of two restriction endonucleases from the photosynthetic gliding bacterium Chloroflexus aurantiacus are described.
Biochemical signature assay for use in a biosensor platform to detect bacteria in drinking water biofilms

The objective of the study was to identify the enzymatic-biochemical (enz-bio) signatures of Escherichia coli and Salmonella for rapid detection of these bacteria in drinking water biofilms. The relative potency of lipophilic, glucosidic, and proteolytic activities in biofilms containing single bacterial species and mixture of different bacterial was used to identify the enz-bio signatures of Escherichia coli and Salmonella. The enz-bio signatures identified were: Lipophilic < Glucosidic < Proteolytic (for Escherichia coli); and Glucosidic = Lipophilic < Proteolytic (for Salmonella). The enz-bio assays were performed sequentially for detecting Escherichia coli and Salmonella in pure and mixed biofilm cultures formed on the coupons incubated in a batch reactor. The results obtained were substantiated by culture-based assays indicating comparable data. The enz-bio sensing method described here is a proof of principle and the results of this study provide a platform for the fabrication of a biosensor for bacterial detection in biofilms. The detection time required for the biosensor platform versus culture methods ranged from 10 to 120 min and 24 to 48 h, respectively.
Crosslinking Kinetics Studies on Interpenetrating Polymer Network Powder Coatings

IPN powder coatings were prepared which were composed of (A) a pendant double bond-containing acrylic resin made by reacting m-isopropenyl-α-α-dimethylbenzyl isocyanate (TMI) and a hydroxyl-containing acrylic resin and (B) a bisphenol type epoxy resin of high molecular weight cured by means of a carboxylic acid-containing acrylic resin. Crosslinking kinetics studies were carried out by using a computerized differential scanning calorimeter (DSC). A computer program was designed to simulate the curing reactions of the IPN powder coatings by using the individual kinetic parameters obtained from DSC. The simulated results from the computer program are very close to the results from experimental thermograms (by DSC). Therefore, this methodology provides an efficient tool to simplify and predict kinetic studies of crosslinking reactions in current or new IPN powder coating systems.
The combinatorial-connectionist debate and the pragmatics of adjectives

Within the controversy between the combinatorial and the connectionist approaches to cognition it has been argued that our semantic and syntactic capacities provide evidence for the combinatorial approach. In this paper I offer a counter-weight to this argument by pointing out that the same type of considerations, when applied to the pragmatics of adjectives, provide evidence for connectionism.
Nonadditive Developmental Toxicity in Mixtures of Trichloroethylene, Di(2-ethylhexyl) Phthalate, and Heptachlor in a 5×5×5 Design

In order to identify nonadditive effects on development, three compounds were combined using five dosages of each agent (a 5 x 5 x 5 full-bacterial design). Trichloroethylene (TCE), di(2-ethylhexyl) phthalate (DEHP), and heptachlor (HEPT), in corn oil, were administered by gavage to Fischer-344 rats on Gestation Days 6-15. Dose levels were 0, 10.1, 32, 101, and 320 mg/kg/day for TCE; 0, 24.7, 78, 247, and 780 mg/kg/day for DEHP; and 0, 0.25, 0.8, 2.5, and 8 mg/kg/day for HEPT. The dams were allowed to deliver and their pups were weighed and examined postnatally. Maternal death showed no main effects but DEHP and HEPT were synergistic. For maternal weight gain on Gestational Days 6-8, main effects for all three agents were observed, as well as 6-8 main effects for all three agents were observed, as well as TCE-DEHP synergism, and DEHP-HEPT antagonism. Maternal weight gain on Gestational Days 6-20 adjusted for litter weight showed main effects for TCE and HEPT, but no interactions. Main effects for all three agents were evident for full-litter resorptions and prenatal loss. The HEPT main effects were unexpected and were interpreted as reflecting potentiation by HEPT of the other agents. For full-litter loss, the TCE-HEPT and DEHP-HEPT interactions were antagonistic, perhaps due to a "ceiling" effect. For prenatal loss, the TCE-DEHP interaction was synergistic. Postnatal loss showed DEHP and HEPT main effects but no interaction. Analysis of pup weights on Day 1 revealed TCE and DEHP main effects and DEHP-HEPT antagonism; on Day 6, DEHP and HEPT main effects, DEHP-HEPT antagonism, and TCE-DEHP synergism were evident. Microphthalmia and anophthalmia incidences revealed TCE and DEHP main effects but no interactions. This extensive examination of a full-factorial design elucidates the complexities of studying and interpreting mixture toxicity. The data are available for further analysis.
Intravenous regional anesthesia in isoflurane anesthetized cats: lidocaine plasma concentrations and cardiovascular effects.

Abstract Objective To determine if intravenous regional anesthesia (IVRA) can be used in cats without resulting in excessive plasma lidocaine concentrations or adverse cardiovascular effects. Study design Prospective, blinded crossover study. Animals Seven healthy male young adult cats weighing 3.96 ± 0.63 kg. Methods At 2.3% end-tidal isoflurane concentration, lidocaine (L) 3 mg kg −1 (1%) or saline (S) was injected in a distal cephalic venous catheter after application of two tourniquets to that forelimb which remained in place for 20 minutes. Heart and respiratory rates, arterial blood pressures and ECG were recorded every 5 minutes during tourniquet application and for 20 minutes following tourniquet removal. Lidocaine plasma concentrations were measured 5 minutes after injection and 0.5, 1, 2, 4, 8, 20 and 40 minutes after tourniquet removal. End tidal isoflurane concentrations were reduced to 1.5–2.0% to elicit a response to toe pinch (RTP) in the contralateral leg. The study was repeated similarly in the contralateral leg and RTP was graded for 40 minutes. Response was also tested in the leg previously injected, the differences between the two scores determined and those differences compared between the L and S treatments. The data were analyzed using anova for repeated measures comparing values to baseline. Significance was set at p Results There were no significant differences in physiologic parameters at either isoflurane concentration. Differences in RTP were significantly larger in the lidocaine treatment. The highest mean lidocaine concentrations were measured 0.5 minutes after tourniquet removal after both injections and were 2.79 ± 1.05 and 3.10 ± 1.11 μg mL −1 . The highest individual plasma concentration was 6.46 μg mL −1 . Conclusion No adverse hemodynamic effects were evident after IVRA lidocaine in any cat. The lidocaine dose studied inhibited a RTP until 20 minutes after tourniquet removal. Lidocaine concentrations varied and were measurable prior to tourniquet removal. Clinical relevance IVRA may be a suitable technique for cats undergoing surgery of the distal limbs.
Synthesis and evaluation of inhibitors of bacterial d-alanine: d-alanine ligases

Abstract Background : d-Alanine:d-alanine ligase is essential for bacterial cell wall synthesis, assembling one of the sub-units used for peptidoglycan crosslinking. The resulting aminoacyl-d-Ala-d-Ala strand is the Achilles' heel of vancomycin-susceptible bacteria; binding of vancomycin to this sequence interferes with crosslinking and blocks cell-sites. wall synthesis. A mutant enzyme (VanA) from vancomycin-resistant Enterococcus faccium has been found to incorporate α-hydroxy acids at the terminal site instead of d-Ala; the resulting depsipeptides do not bind vancomycin, yet function in the crosslinking reaction. To investigate the binding specificity of these ligases, we examined their inhibition by a series of substrate analogs. Results : Phosphinate and phosphonate dipeptide analogs (which, after phosphorylation by the enzyme, mimic intermediates in the ligation reaction) were prepared and evaluated as reversible inhibitors of the wild-type ligases DdlA and DdlB from Escherichia coli and of the mutant enzyme VanA. K i values were calculated for the first stage of inhibitor binding according to a mechanism in which inhibitor competes with d-Ala for both substrate binding sites. DdlA is potently inhibited by phosphinates but not by phosphonates, while DdlB and VanA show little discrimination; both series of compounds inhibit DdlB strongly and VanA weakly. Conclusions : VanA has greatly reduced affinity for all the ligands studied. The relative affinities of the inhibitors in the reversible binding step are not, however, consistent with the substrate specificities of the enzymes. We propose a mechanism in which proton transfer from the attacking nucleophile to the departing phosphate occurs directly, without intervention of the enzyme.
Condensations at the 6α-position of triacetic lactone via the dianion

Abstract Triacetic lactone ( 1 ) on treatment with two or more equivs of alkali amides in liquid ammonia was converted into dianion 8 . Treatment of 8 with benzyl chloride and other alkyl halides gave mixtures of 6α- and 5-alkylation products 9 and 10 . Benzophenone condensed with 8 to give 6α-aldol product 14 , which was readily dehydrated to form unsaturated pyrone 15 . 6α-Carboxylation of dilithio 8 , which had been formed in THF by treatment of 1 with lithium diisopropylamide, was also effected. Aroylation of 8 with methyl benzoate gave 6-phenacyl pyrone 17 , but acetylation of 8 was not successful. Two monomethylation ( 18 and 24 ) and three dimethylation ( 19–21 ) products of 17 were prepared and identified. Condensation of 17 with malonyl chloride gave pyranopyran 25 .
Hydrophobic binding of hydrocarbons by proteins. I. Relationship of hydrocarbon structure

Abstract 1. 1. The interactions between proteins and a variety of hydrocarbons were studied. An improved procedure was developed to determine the amount of hydrophobic substance absorbed or dissolved in the protein solution. This procedure involves the direct injection of the hydrocarbon-protein mixtures into a gas-liquid chromatographic apparatus. 2. 2. Binding studies were done with bovine serum albumin and β-lactoglobulin. With homologous alkanes, the amounts bound decreased as chain length was increased from C7 to C13, especially with β-lactoglobulin. Larger amounts of branched-chain alkanes were bound by bovine serum albumin than by β-lactoglobulin. Both alicyclic and aromatic hydrocarbons were more soluble in bovine serum albumin than in β-lactoglobulin. No preferential binding was observed for cis- versus trans-isomers of dimethylcyclohexane. Similarly, there were no marked differences in binding of o-, m-, or p- xylene . 3. 3. The procedure was used to study the effect of hydrocarbon concentration on binding by β-lactoglobulin. The reciprocal plot of the binding isotherm of n- heptane was linear and the Scatchard plot gave a value of 1.35 for the number of strong binding sites per mole of β-lactoglobulin. Plots with benzene, however, indicated that binding approached infinity at high benzene concentrations. The results demonstrate that interactions between a wide variety of hydrocarbons and proteins can be studied by the general techniques described.
Student status monitoring tool (SSM): proxy for the real world expert in online course delivery

Distance Education has entered a new era, where it is now possible for courseware to be delivered online in a very effective, efficient and appealing manner. At the Institute for Advanced Education in GeoSpatial Science (IAESG), a project funded by NASA, it is our objective to develop a repository of dynamic online coursework in the field of Geospatial Information Technology. These courses are intended to enhance the traditional university learning through visually rich content, and also through closely emulating the concept of an Expert in a virtual environment. It thus becomes imperative to address a number of pedagogical issues in the design of such a dynamic web-based course delivery system. Traditional education generally involves two main entities: an Expert, and some form of reference material such as a textbook. The Expert imparts knowledge interactively in the real world, and is in some sense the more 'active' or 'intelligent' agent, whereas the textbook is just reference since it has limited scope, and hence is the 'passive' or 'static' agent. Thus the pedagogical issue that needs the most immediate attention, while dealing with learner-centered online course delivery is the issue of how to emulate the real-world Expert in a virtual learning environment. We realize that the role, the Expert plays in knowledge transfer is multi-faceted. One of the roles of the Export is to use traditional testing methodologies like quizzes and exercise to evaluate the performance of a learner. In an online environment, the best way to achieve this continous evaluation is to get constant feedback on the performance and learning style of the student, via 'Student Status Monitoring' (SSM) tool. The research we present focuses on this pivotal aspect of effective online learning.
Golgi-associated Maturation of Very Low Density Lipoproteins Involves Conformational Changes in Apolipoprotein B, but Is Not Dependent on Apolipoprotein E

The major protein component in secreted very low density lipoproteins (VLDL) is apoB, and it is established that these particles can reach sizes approaching 100 nm. We previously employed a cell-free system to investigate the nature of the vesicles in which this large cargo exits the endoplasmic reticulum (ER) (Gusarova, V., Brodsky, J. L., and Fisher, E. A. (2003) J. Biol. Chem. 278, 48051-48058). We found that apoB-containing lipoproteins exit the ER as dense lipid-protein complexes regardless of the final sizes of the particles and that further expansion occurs via post-ER lipidation. Here, we focused on maturation in the Golgi apparatus. In three separate approaches, we found that VLDL maturation (as assessed by changes in buoyant density) was associated with conformational changes in apoB. In addition, as the size of VLDL expanded, apoE concentrated in a subclass of Golgi microsomes or Golgi-derived vesicles that co-migrated with apoB-containing microsomes or vesicles, respectively. A relationship between apoB and apoE was further confirmed in co-localization studies by immunoelectron microscopy. These combined results are consistent with previous suggestions that apoE is required for VLDL maturation. To our surprise, however, we observed robust secretion of mature VLDL when apoE synthesis was inhibited in either rat hepatoma cells or apoE(-/-) mouse primary hepatocytes. We conclude that VLDL maturation in the Golgi involves apoB conformational changes and that the expansion of the lipoprotein does not require apoE; rather, the increase in VLDL surface area favors apoE binding.
Parenteral vs Enteral Nutrition in Tumor-Bearing Rats

The development of cachexia may complicate cancer therapy, yet controversy exists concerning its nutritional management. For example, use of total parenteral nutrition (TPN) may not be appropriate because of gut atrophy, possible stimulation of tumor growth, and lack of total host protein repletion. In the present experiment, host and tumor responses were compared after identical parenteral or enteral nutritional supplementation (EN). Eighteen days after subcutaneous inoculation of adult male Fischer-344 rats with fresh methylcholanthrene-induced sarcoma (tumor-bearing [TB] rats), catheters were placed into either the external jugular vein or the stomach. Four days later, rats were started on an 11-day course of either TPN or EN with a Freamine-III-based formula (amino acids = 6%, dextrose = 21.5%, lipid = 1.5%). When the rats were killed, there was no difference in tumor weight between the various TB groups. Carcass weight was increased significantly in both the TB-TPN and TB-EN groups, and there was an elevation in gastrocnemius protein content in both groups compared with the TB-rat food group. Small intestine protein was preserved in the TB-EN group to the level observed in the control-rat food animals. Total lipids in the liver were increased in both TB-TPN and TB-EN groups; however, the magnitude of the increase was less in the TB-EN animals. Neither treatment resulted in complete protein repletion of tumor-bearing rats. EN may be more appropriate than TPN in that gut mass is preserved. The maintenance of gut mucosa may prove to be beneficial in the treatment of the depleted, immunocompromised, and metabolically stressed host.
Minireview: Development and Differentiation of Gut Endocrine Cells

For over 30 yr, it has been known that enteroendocrine cells derive from common precursor cells in the intestinal crypts. Until recently, relatively little was understood about the events that result in commitment to endocrine differentiation or the segregation of over 10 different hormone-expressing cell types in the gastrointestinal tract. The earliest cell fate decisions appear to be regulated by the Notch signaling pathway. Notch is inactive in endocrine precursor cells, allowing for expression of the proendocrine basic helix-loop-helix proteins Math1 and neurogenin3. Differentiating precursor cells activate Notch in neighboring cells to switch off expression of proendocrine factors and inhibit endocrine differentiation. Math1 is the first factor involved in endocrine specification, committing cells to become one of three secretory lineages-goblet, Paneth, and enteroendocrine. Neurogenin3 appears to be a downstream target that is essential for endocrine cell differentiation. Events that control the segregation of each mature lineage from progenitor cells have not been characterized in detail. The transcription factors Pax4, Pax6, BETA2/NeuroD, and pancreatic-duodenal homeobox 1 have all been implicated in enteroendocrine differentiation. BETA2/NeuroD appears to coordinate secretin gene expression in S-type enteroendocrine cells with cell cycle arrest as cells terminally differentiate. Powerful genetic approaches have established the murine intestine as the most important model for studying enteroendocrine differentiation. Enteroendocrine cells in the mouse are remarkably similar to those in humans, making it likely that insights learned from the mouse may contribute to both our understanding and treatment of a variety of human disorders.
Inferring gaze shifts from captured body motion

Motion-captured performances seldom include eye gaze, because capturing this motion requires eye tracking technology that is not typically part of a motion capture setup. Yet having eye gaze information is important, as it tells us what the actor was attending to during capture and it adds to the expressivity of their performance.
The 20th annual intelligent ground vehicle competition: building a generation of robotists

The Intelligent Ground Vehicle Competition (IGVC) is one of four, unmanned systems, student competitions that were founded by the Association for Unmanned Vehicle Systems International (AUVSI). The IGVC is a multidisciplinary exercise in product realization that challenges college engineering student teams to integrate advanced control theory, machine vision, vehicular electronics and mobile platform fundamentals to design and build an unmanned system. Teams from around the world focus on developing a suite of dual-use technologies to equip ground vehicles of the future with intelligent driving capabilities. Over the past 20 years, the competition has challenged undergraduate, graduate and Ph.D. students with real world applications in intelligent transportation systems, the military and manufacturing automation. To date, teams from over 80 universities and colleges have participated. This paper describes some of the applications of the technologies required by this competition and discusses the educational benefits. The primary goal of the IGVC is to advance engineering education in intelligent vehicles and related technologies. The employment and professional networking opportunities created for students and industrial sponsors through a series of technical events over the four-day competition are highlighted. Finally, an assessment of the competition based on participation is presented.
Dear Doctor Benjamin: Letters from Transsexual Youth (1963―1976)

ABSTRACT Due to his high public profile, Harry Benjamin was often the first contact for those who identified as transsexual in the 1960s and 1970s, until his retirement in 1976. Among the over 800 letters from transsexuals written to Benjamin, 21 were from youth seeking his medical assistance. These letters, written from 1963–1976, provide a rare window into the lives and subjectivities of transsexual youth before the modern transgender movement took shape. Often taking the form of short autobiographies, these pioneers wrote about the meaning of their genders and sexualities, sometimes in great detail. Narrative analyses of these letters focused on narrative explanations for their transsexual desire; how Benjamin, his colleagues, and transsexual correspondents co-constructed transsexual narratives; and the rejection of these youth by their families and peers.
Covert Intervention as a Moral Problem

Today's international community may well view covert action and democracy as mutually exclusive policies. This article examines the practice of covert action in American foreign policy in light of events of the mid-1970s and 1980s, focusing on the scandalous misuse of executive authority and lack of accountability associated with covert means. Often manipulative and sometimes anonymous, covert operations raise critical morality concerns in a democratic society. Whether “any form of accountability is likely to be sufficient to bring the unauthorized use of executive power under control” is the crucial issue to be addressed when examining the practicality of covert actions by the executive branch.
Optimization and theoretical modeling of polymer microlens arrays fabricated with the hydrophobic effect.

High-performance polymer microlens arrays were fabricated by means of withdrawing substrates of patterned wettability from a monomer solution. The f-number (f#) of formed microlenses was controlled by adjustment of monomer viscosity and surface tension, substrate dipping angle and withdrawal speed, the array fill factor, and the number of dip coats used. An optimum withdrawal speed was identified at which f# was minimized and array uniformity was maximized. At this optimum, arrays of f/3.48 microlenses were fabricated with one dip coat with uniformity of better than Δf/ f ∼ ±3.8%. Multiple dip coats allowed for production of f/1.38 lens arrays and uniformity of better than Δf/ f ∼ ±5.9%. Average f#s were reproducible to within 3.5%. A model was developed to describe the fluid-transfer process by which monomer solution assembles on the hydrophilic domains. The model agrees well with experimental trends.