cssi/SciSciGPT-SciSciNet huggingface dataset:
An in vitro model system to study gene therapy in the human inner ear.

The confined fluid-filled labyrinth of the human inner ear presents an opportunity for introduction of gene therapy reagents designed to treat hearing and balance dysfunction. Here we present a novel model system derived from the sensory epithelia of human vestibular organs and show that the tissue can survive up to 5 days in vitro. We generated organotypic cultures from 26 human sensory epithelia excised at the time of labyrinthectomy for intractable Meniere's disease or vestibular schwannoma. We applied multiply deleted adenoviral vectors at titers between 105 and 108 viral particles/ml directly to the cultures for 4–24 h and examined the tissue 12–96 h post-transfection. We noted robust expression of the exogenous transgene, green fluorescent protein (GFP), in hair cells and supporting cells suggesting both were targets of adenoviral transfection. We also transfected cultures with a vector that carried the genes for GFP and KCNQ4, a potassium channel subunit that causes dominant-progressive hearing loss when mutated. We noted a positive correlation between GFP fluorescence and KCNQ4 immunolocalization. We conclude that our in vitro model system presents a novel and effective experimental paradigm for evaluation of gene therapy reagents designed to restore cellular function in patients who suffer from inner ear disorders.
String method for the study of rare events

We present an efficient method for computing the transition pathways, free energy barriers, and transition rates in complex systems with relatively smooth energy landscapes. The method proceeds by evolving strings, i.e., smooth curves with intrinsic parametrization whose dynamics takes them to the most probable transition path between two metastable regions in configuration space. Free energy barriers and transition rates can then be determined by a standard umbrella sampling around the string. Applications to Lennard-Jones cluster rearrangement and thermally induced switching of a magnetic film are presented.
On richness and evenness within and between communities

Although there is extraordinary interest in the quantitative measurement of species diversity, published statements on the behavior of the components of species diversity are contradictory and lead to opposite conclusions. In this paper, we demonstrate that the confusion is due to two key oversights: (1) whether or not biological sampling is carried out within or between communities; and (2) determination of the statistical distribution underlying a biological community, which is crucial for the evaluation of all of the components of diversity measurement.The problem of sampling “within” a population or community is basically distinct from the equivalent integration of structure and diversity measurement “between” differing multispecies populations. “Within-community sampling” is defined as a set of biological samples from a statistical population that has a particular statistical distribution or a constant value for the associated parameter(s). As the number of individuals increases along with the number of species, for a log series distribution, the diversity measures of Shannon's H, log series or Fisher's α, and Simpson's Index 1/λ remain constant while the evenness measures of Buzas-Gibson's E and Pielou's J decrease. For a log-normal distribution, J will remain constant while E decreases and α, 1/λ, and H increase. No single measure of evenness remains constant over all statistical distributions, so if constancy as a type of independence is required, the appropriate distribution must first be determined. Each species ensemble is mathematically fixed by the applicable statistical distribution.In contrast, “between-community sampling” is defined as a set of biological samples from different statistical distributions and/or the same distribution with differing parametric values. If sampling is between communities and S increases while the number of individuals remains constant, then all the other measures considered here increase. The exception is the broken stick, for which E remains constant while H, J, α, and 1/λ increase.Herein we propose and justify the use of the log-series distribution (with regression on the information decomposition equation) as a null model for determination of community structure and demonstrate that the community structure of a Miocene bed at Calvert Cliffs, Maryland, is a log series by use of this new unified methodology.
Natural history of chronic myelomonocytic leukemia: gene sequencing identifies multiple clonal molecular abnormalities associated with rapid progression to acute myeloid leukemia

Key Clinical Message Gene panel sequencing in a CMML patient without any detectable genetic abnormality by conventional genetic studies identified four concurrent somatic mutations in three genes. Gene panel mutation analysis is a rapidly emerging clinical tool to demonstrate the clonality in hematologic malignancies, and to identify the potential targets for therapy.
Specific power analysis of thermoelectric OTEC plants

Abstract The specific power output of a real thermoelectric OTEC plant is analyzed and optimized. The thermoelectric OTEC is treated as an external and internal irreversible heat engine. The irreversibilities of the heat engine are limited to the factors of heat transfers and Joulean loss only. The specific power output of the real thermoelectric OTEC is then compared with that of the Carnot OTEC, endoreversible OTEC and external reversible thermoelectric OTEC.
Suppression of Ground-Fault Arcs on Single-Pole-Switched EHV Lines by Shunt Reactors

Arcing line-to-ground faults isolated by single-pole switching are maintained by capacitive coupling between the faulted and unfaulted phases. Such faults are difficult to extinguish on long EHV (extra-high-voltage) lines because the fault A promising remedy consists of neutralizing the capacitive coupling by shunt reactors, which are required anyhow on many lines for compensating the normal charging current.
Intelligent state space pruning for Monte Carlo simulation with applications in composite power system reliability

Abstract The probabilistic reliability evaluation of composite power systems is a complicated, computation intensive, and combinatorial task. As such evaluation may suffer from issues regarding high dimensionality that lead to an increased need for computational resources, MCS is often used to evaluate the reliability of power systems. In order to alleviate this burden, an analytical method known as state space decomposition has previously been used to prune the state space that is sampled using MCS. This paper extends the state-of-the-art by proposing a novel algorithm known as intelligent state space pruning (ISSP). This algorithm leverages the intelligence of highly modified population based metaheuristic (PBM) algorithms including genetic algorithms (GA), particle swarm optimization (PSO), ant colony optimization (ACO), and artificial immune systems (AIS) to quickly, efficiently, and intelligently prune the state space that is used during MCS. The presented PBMs are modified using domain-specific knowledge to improve their performance and fine tune their intelligence. This new algorithm leads to reductions of up to 90% in total computation time and iterations required for convergence when compared to non-sequential MCS. Results are reported using the IEEE Reliability Test Systems (RTS79/MRTS).
Law and the Pragmatics of Inclusion: Governing Domestic Violence in Trinidad and Tobago

In this article, I demonstrate some of the complexities of the "pragmatics of inclusion" that ensue when subordinated people first struggle to gain access to hegemonic institutions and then challenge those institutions to maintain their inclusion. In presenting these findings, I reconsider the meaning of agency for persons seeking legal redress from domestic abuse in Trinidad and reassess the power and limitations of domestic violence law as a symbol and instrument for social change, [domestic violence law, agency, legal processes, kinship and gender ideologies, Caribbean]
Upregulation of nitric oxide, inhibition of oxidative stress, and antihypertensive effects of statins.

To the Editor: We read with great interest the article by Strazzullo et al1 in which they report a meta-analysis of 20 randomized, controlled trials of statin therapy and show that statins slightly but significantly reduced systolic blood pressure (−1.9 mm Hg in total patients and −4.0 mm Hg in the patients with systolic blood pressure >130 mm Hg). Statins have pleiotropic effects on the vasculature, including upregulation of endothelial NO synthase expression and activity, downregulation of endothelin-1 and angiotensin II receptor subtype 1 expression, …
Mono‐N‐Methylation of 1,2,3,4‐Tetrahydro‐β‐Carbolines in Brain Cytosol: Absence of Indole Methylation

In an accompanying report we demonstrated enzyme activity in guinea pig brain cell nuclei that catalyzes S-adenosylmethionine (SAM)-dependent N-methylations of heteroaromatic beta-carbolines (BCs) on the 2[beta]-nitrogen and subsequently on the 9[indole]-nitrogen, ultimately yielding N2,N9-dimethylated BCs. Presented here are the results of a parallel study of the N-methylation of 1,2,3,4-tetrahydro-BCs (THBCs), which form endogenously via condensations of tryptophan and its derived indoles with carbonyl compounds or, like their BC oxidation products, are environmental constituents and plant alkaloids. THBCs were enzymatically methylated on the 2[beta]-nitrogen by [3H]-SAM in undialyzed homogenates of rat or guinea pig brain, but [3H]methyl transfer to the 9[indole]-nitrogen was not observed. The structure of the 2[beta]-methyl THBC product was verified with capillary gas chromatography-mass spectrometry. Furthermore, whereas BC N-methylation was largely particulate and displayed micromolar Km values for BC substrate, THBC 2[beta]-N-methylation activity was cytosolic and displayed a relatively high (millimolar) Km for THBC substrate. The N-methylation of THBCs may be due to cytosolic N-methyltransferases that others have studied using different azaheterocyclics. Our overall studies indicate that N2,N9-dimethylated BCs could be unique neurotoxic factors that are bioactivated within brain by sequential N-methylations of BCs. These results suggest the possibility of an additional route to the putative 2,9-dimethylated toxins involving, as a first step, 2[beta]-N-methylation of environmental or endogenously derived THBCs in the brain and perhaps other organs.
Neural mechanisms underlying destabilization of cortex by sensory input

Abstract A mathematical model of the mechanism of olfaction has been developed in the form of coupled nonlinear integrodifferential equations. The model was first constructed to simulate the performance of the separated bulb or cortex in response to electrical impulse stimulation of its input and output nerves. With sufficiently high internal feedback gains, the model entered a stable limit cycle state at frequencies characteristic of the EEG bursts. The instability was diminished when the connection densities and input amplitude were spatially nonuniform, though these factors could be compensated by increasing the internal gains (connection strengths). This model failed to simulate three important characteristics of olfactory activity: (1) the dependence of spatial patterns of bulbar output on internal connectivity rather than on input patterns; (2) the exquisite selective sensitivity of the bulb to learned inputs; and (3) its broad spectrum and aperiodic wave forms. The model was changed by including an asymmetric sigmoid nonlinearity, and by introducing long feedback connections from the cortex to the bulb that had dispersive delays. These changes sufficed to provide chaotic solutions of the equations, and to selectively sensitize the system to destabilization by input, thereby improving the simulations of the biological activity. The conclusion is put forth that for pattern recognition to be done, the chaotic activity of the sensory system must arise from a macroscopic attractor. Local fluctuations are everywhere damped by the distributions of return times and strengths owing to biological variability in neuron size and connection density. Thus high-dimensional local stability is combined with low-dimensional global instability, so as to emphasize the relationships among local features in a holistic sensory input pattern.
Cyclocopolymerization of p-chlorostyrene with 4-vinylcyclohexene

4-Vinylcyclohexene was polymerized by triethyl-aluminum–titanium tetrachloride catalyst (mole ratio 5.4:1). Copolymerization of 4-vinylcyclohexene with p-chlorostyrene by the same catalyst was also carried out. For these polymerization results, the Roovers-Smets equation was applied and the reactivity ratio parameters, Kc, Kc′, r2 and r3 were determined as follows: Kc = Kc/k11 = 9.1; Kc′ = kc/k12 ∼ ∞; r2 = k22/k21 = 1.45; r3 = k31/k32 ∼ 0, where subscripts 1, 2 and 3 indicate 4-vinylcyclohexene, p-chlorostyrene, and cyclized polymer anion, respectively.
Experimental study of a two-dimensional language vs. FORTRAN for first-course progammers

The variability in programming performance for a group of novice Fortran programmers was measured over a set of problems from an introductory programming text. A wide variation was observed despite the elementary nature of each problem and the relatively homogeneous subject group. The implications of these results are examined. Another experiment measured the comparative performance of programming novices using Fortran and the Klerer-May two-dimensional (2-D) language. The results indicated that the 2-D language was much more economically efficient than Fortran for the subject groups in the areas of scientific/engineering application programming.
Maintaining Interior Egg Quality by Holding Shell Eggs in a Case With a Petroleum Resin Liner

Abstract THE problem of preserving the quality of chicken eggs has been of prime concern to the poultryman and allied industry for many years. The chief method of maintaining egg quality on the farm has been a combination of rapid cooling of the eggs and the storage of the eggs in a room with proper temperature and sufficiently high humidity to reduce the moisture loss from the eggs. Recent research workers have investigated the theory that if the loss of carbon dioxide from the eggs could be slowed up, or even stopped, the interior quality of eggs could be maintained at a higher level for a longer period of time. This led to the oiling of eggs and the overwrapping or sealing of egg cartons. Cotterill and Gardner (1957) reviewed the literature relative to egg oiling and certain methods of packaging shell eggs in air tight containers. The importance of carbon…
Base-induced reactions of α,β-dihydroxysilanes: stereochemistry and mechanisms

Abstract Cyclic α,β-dihydroxysilanes undergo base-induced elimination reactions if the silicon and the β-OH can be anti; otherwise protiodesilylation predominates.
Radiative Lifetimes of Ultraviolet Transitions of Argon ii

The electron-excitation, phase-shift method of Lawrence has been applied to the determination of radiative lifetimes of Ar ii transitions. The measured levels, which are primarily those of 4p2S, 2P, 4D, were studied using transitions in the region from 1900–4500 A. The Ar ii lifetimes measured ranged from 1.2 to 10.6 nsec and involve a number of levels in which configuration interaction is present.
Inflation targeting and monetary policy in Canada: What is the impact on inflation uncertainty?

Abstract Inflation uncertainty has been demonstrated both theoretically and empirically to lower real output. This paper examines the impact of inflation targeting in Canada on inflation uncertainty, as well as persistence. Our results indicate that inflation targeting lowered inflation persistence, but actually increased uncertainty. Such an effect may be due to the failure of the previous formal target, the M1 money supply, to successfully combat inflation.
The Shuttle environment from a payload viewpoint

The paper describes the basis for current estimates of Shuttle environments. It considers available predictions of environments, uncertainties, worst-case conditions and discusses how this data base is used to derive the environmental design requirements. These requirements are assessed from a payload viewpoint, i.e., how they affect payload type, design, mission, location in Shuttle and payload classification. Finally, typical future Shuttle payloads (a pallet-mounted instrument and a spacecraft) are discussed relative to how the Shuttle environments influenced the payload design and test approach.
AFFECTION AND CONFLICT IN MARITAL AND PARENT-CHILD RELATIONSHIPS

In this study, we examined affection and conflict in marital and parent-child relationships, as reported by mothers, fathers, and 9- and 10-year-old children in a community sample of 87 families. Affection and conflict were inversely related within relationships, with mixed findings across relationships. Most reports showed an association between marital and parent-child conflict as well as between marital and parent-child affection. According to fathers, however, the association between marital affection and father-child affection is moderated by marital conflict. Clinical implications of the associations between positive and negative dimensions of family interaction and of the links between marital and parent-child relations are discussed.
Changing the bridging connectivity pattern within a heterometallic assembly: design of single-source precursors with discrete molecular structures

Three heterometallic single-source precursors with a proper Li : Co ratio for the lithium ion battery cathode material LiCoO2 are reported. The heterometallic compounds LiCoL3 (L = acac (1), tbaoac (2) or dhd (3)) were obtained on a large scale, in nearly quantitative yield using a one-step reaction that employs readily available starting reagents. The first of these precursors, heterometallic diketonate LiCo(acac)3 (1) (acac = pentane-2,4-dionate), was found to have a polymeric structure in the solid state that limits its volatility and prevents solubility in non-coordinating solvents. In order to design precursors with discrete molecular structures, we used asymmetric ligands, tert-butyl acetoacetate (tbaoac) and 2,2-dimethyl-hexanedionate (dhd), that exhibit different bridging properties at the two ends of the ligand and thus allow one to effectively change the bridging connectivity pattern within the heterometallic assembly. As a result, the heterometallic complexes LiCo(tbaoac)3 (2) and LiCo(dhd)3 (3), which consist of discrete tetranuclear molecules of Li2Co2L6, were successfully isolated and characterized. Out of the three heterometallic compounds reported in this work, LiCo(tbaoac)3 (2) appears to meet the application demands for an ideal single-source precursor. In accord with its discrete molecular structure, the complex is soluble in nearly all common solvents and retains its heterometallic structure in solution. Thus, it can be effectively used for the preparation of thin films by direct liquid injection techniques. The compound is highly volatile and exhibits a congruent sublimation with heterometallic fragments present in the gas phase. In addition, it shows the lowest decomposition temperature leading to phase-pure LiCoO2 and can be utilized for the preparation of nanoparticles of this cathode material. Importantly, single-source precursor 2 does not impose any measurable ligand extra cost on the formation of the target cathode material.
Incidence of venous thromboembolism in patients undergoing surgical treatment for malignancy by type of neoplasm: An analysis of ACS-NSQIP data from 2005 to 2010

Introduction This study investigates the incidence, relative risk, and adjusted odds ratio of venous thromboembolism (VTE) among patients with malignant neoplasms compared with those with benign neoplasms, as well as the incidence of outpatient VTE diagnosis. Methods We performed a retrospective cohort study of patients in the ACS-NSQIP database from 2005 to 2010 with a postoperative diagnosis of neoplasm. The incidence of 30-day VTE, post-VTE death, the incidence of postdischarge VTE diagnosis, and the relative risk of postoperative VTE was calculated by cancer site. Logistic regression was used to calculate an independent odds ratio for each neoplasm site, adjusting for age, gender, body mass index, and operative time. Results Of 208,200 patients, 159,752 had a malignant diagnosis of the sites of interest and 48,448 had benign/carcinoma in situ neoplasms. The incidence, relative risk, and odds ratio of 30-day VTE varied substantially by site of malignancy. The absolute incidence of outpatient VTE diagnosis varied by site and percent of VTE diagnosed as an outpatient was found to increase over time. Conclusion Recommendations for VTE prophylaxis and duration of VTE prophylaxis for patients undergoing operations may benefit from tailoring to the specific type of malignancy. The increasing percentage of VTE events diagnosed as an outpatient may impact hospitals substantially as financial penalties for readmission are enacted.
Why Should We Compensate Organ Donors When We Can Continue to Take Organs for Free? A Response to Some of My Critics

In Kidney for Sale by Owner: Human Organs, Transplantation, and the Market, I argued that the market is the most efficient and effective-and morally justified-means of procuring and allocating human organs for transplantation. This special issue of The Journal of Medicine and Philosophy publishes several articles critical of this position and of my arguments mustered in its support. In this essay, I explore the core criticisms these authors raise against my conclusions. I argue that clinging to comfortable, but unfounded, notions that human body parts are not commodities, that the physician-patient relationship transcends commercial practices, and that medicine rises above market-place morality (where "market-place morality" is presented rhetorically as a criticism) leads to a real failure adequately to appreciate the complex reality of modern medicine. Denying the illicit moral intuitions that commodification of body parts is immoral or that it necessarily violates human dignity would benefit donors and recipients alike, while also reinforcing virtuous transplantation practice and policy. Honestly acknowledging the medical marketplace would shed light on what is often a hazy and shrouded policy setting. At stake is not solely the efficiency of procuring human organs for transplantation but also the recognition of the moral authority of persons over themselves.
Evaluating the differences in cycloalkyl ether metabolism using the design parameter "lipophilic metabolism efficiency" (LipMetE) and a matched molecular pairs analysis.

We have observed previously that modification of ring size and substitution pattern may be used as a strategy to mitigate the metabolic instability of cycloalkyl ethers. In this article, we introduce a medicinal chemistry design parameter named “lipophilic metabolism efficiency” (LipMetE) that indicates that these changes in metabolic stability can be largely ascribed to changes in lipophilicity. Our matched molecular pair analysis also indicates that this finding is a general phenomenon, widely observed across different chemotypes. It is our hope that both the LipMetE design parameter and the results from our pairwise analysis will be useful tools for medicinal chemists.
Integrated coronary revascularization with drug-eluting stents: Immediate and seven-month outcome

Objective We sought to demonstrate the safety and feasibility of an integrated coronary revascularization strategy that combines minimally invasive left internal thoracic artery to left anterior descending coronary artery anastomosis with drug-eluting stent implantation to non-left anterior descending coronary artery lesions. Methods Over 18 months, 47 consecutive patients with multivessel coronary artery disease underwent thoracoscopic harvesting of the left internal thoracic artery to graft the left anterior descending coronary artery. Anastomoses were constructed by hand, off-pump, and under direct vision through a 4-cm non–rib-spreading, muscle-sparing chest incision. Non-left anterior descending coronary artery lesions were then treated percutaneously using sirolimus- or paclitaxel-eluting stents. Angiographic follow-up was performed in all patients. Results Within the first 90 days of hospitalizations, there were no deaths, myocardial infarctions, neurologic events, or wound complications. Forty patients underwent left internal thoracic artery to left anterior descending coronary artery grafting, and 7 patients underwent left internal thoracic artery to left anterior descending coronary artery/diagonal sequential grafting for a total of 54 anastomoses. Angiographic patency scores were FitzGibbon A 96.2% (52/54) and FitzGibbon A + B 100% (54/54). A total of 65 drug-eluting stents were implanted in 61 non-left anterior descending coronary artery coronary lesions of which 49.1% (30/61) were type B2 or C lesions, including 5 left main lesions. Diabetes was present in 53.2% of patients (25/47). At a mean follow-up time of 7.0 ± 4.8 months, the target lesion or vessel repeat revascularization rate was 6.6% (4/61) for drug-eluting stents and 1.9% (1/54) for left internal thoracic artery to left anterior descending coronary artery grafting. One anastomosis required balloon dilation, but no patients have required repeat coronary artery bypass grafting. Conclusions Integrated coronary revascularization using drug-eluting stents is feasible and safe. There are sufficient data to justify a randomized comparison of integrated coronary revascularization with standard coronary artery bypass grafting.
Ontogeny of leg motor output in the chick embryo: A neural analysis

The motor output of the leg of the chick embryo during hatching (20 days of incubation) was characterized using electromyographic (EMG) recordings from identified knee and ankle muscles. A highly coordinated pattern of motor output was found. It was therefore used as a standard against which to compare the motor output from younger embryos (7, 9, 13, 17 and 19 days of incubation). Despite large differences in some aspects of the EMG records from embryos of different ages, consistent patterns of muscle activation were observed. Quantitative analysis of phase and latency relationships between pairs of muscles indicated that at least some elements of the neural circuitry involved in generating the hatching motor output may be laid down very early in development. Duration vs. latency plots revealed that there is a gradual refinement in the temporal pattern of alternation between antagonist muscles during development.
Transport in a Methanol Steam Reformer as the Fuel Processor for Fuel Cell Systems

An experimental and analytical study of the reacting flow in a catalytic reactor is presented. Methanol-steam reforming may be utilized in the fuel processing system for hydrogen fuel cells. Understanding the flow and transport phenomena as well as the reaction mechanisms is essential for improving the efficiency of the reforming process as well as the quality of the processed fuel. Utilizing the results obtained, optimized conditions for fuel processing are discussed.Copyright © 2004 by ASME
Microeconomic foundations of an optimal currency area

Abstract The concept of an optimum currency area has previously been developed using macroeconomic policy results and factor mobility as the criteria for the optimum extent of a common currency area. In this paper, microeconomic foundations for an optimum currency area are set forth. These microeconomic foundations are requirements for a common currency area to exist. One can test for consistency with these microeconomic foundations. Procedures for such tests are discussed. Some preliminary results are presented from tests of whether or not the Euro Area economies constitute a common currency area. The test results tentatively suggest that the Euro Area countries may encounter problems in their attempt to establish a common currency.
Health behavior: Issues, contradictions and dilemmas.

American medicine faces many contradictions and dilemmas. This is especially the case with regard to preventive health behavior. This paper explores the effects of several issues, contradictions and dilemmas on the American experience with primary preventive health behavior. These issues include: individualism, victim blaming, therapeutic nihilism, the over abundance of health information, America as a culture of risk takers, and the dilemma of the jungle vs the zoo. Four types of health behavior are defined. The first type of health behavior is the primary prevention of disease, defect, injury or disability. The second type is detection of asymptomatic disease, injury and defect. Third, is the promotion of enhanced levels of health, wellness and quality of life. And the fourth, at a more societal level, protective behaviors to make environmental transactions safe from disease, injury, defect and disability. These four types of health behavior are each explored in relation to societal values, technology and economics to determine which of these facilitate or impede health behavior at both the individual and societal levels.
An Online Battery Impedance Measurement Method Using DC–DC Power Converter Control

This paper presents a simple online impedance measurement method for electrochemical batteries, including lithium-ion, lead-acid, and nickel–metal-hydride chemistries. By using the proposed online impedance measurement method, there is no need to disconnect the battery from the system or to interrupt system operation, and there is no need to add ac signal injection circuits, costly response measurement, and analysis circuits/devices. In practical battery-powered systems, a power converter is usually used to interface the battery with the load for voltage/current regulation purposes. In this paper, through the control of the power converter and duty-cycle perturbation, the ac impedance of the battery can be determined. The proposed method provides a low-cost and practical solution for the online measurement of the ac impedance of batteries. Moreover, the proposed method can be either continuously or periodically performed without interrupting the normal operation of the battery system and the power converter. In addition, this paper provides an example where the obtained impedance data are utilized for online state-of-charge estimation of lithium-ion batteries. The proposed online impedance measurement method is validated by experiments conducted on a 2.6-Ah 18650-size lithium-ion battery interfaced to the load via a bidirectional dc–dc boost/buck converter.
Identification of Residues Important for Ligand Binding of Thromboxane A2 Receptor in the Second Extracellular Loop Using the NMR Experiment-guided Mutagenesis Approach

The second extracellular loop (eLP2) of the thromboxane A2 receptor (TP) had been proposed to be involved in ligand binding. Through two-dimensional1H NMR experiments, the overall three-dimensional structure of a constrained synthetic peptide mimicking the eLP2 had been determined by our group (Ruan, K.-H., So, S.-P., Wu, J., Li, D., Huang, A., and Kung, J. (2001) Biochemistry 40, 275–280). To further identify the residues involved in ligand binding, a TP receptor antagonist, SQ29,548 was used to interact with the synthetic peptide. High resolution two-dimensional 1H NMR experiments, NOESY, and TOCSY were performed for the peptide, SQ29,548, and peptide with SQ29,548, respectively. Through completed 1H NMR assignment and by comparing the different spectra, extra peaks were observed on the NOESY spectrum of the peptide with SQ29,548, which implied the contacts between residues of eLP2 at Val176, Leu185, Thr186, and Leu187 with SQ29,548 at position H2, H7, and H8. Site-directed mutagenesis was used to confirm the possible ligand-binding sites on native human TP receptor. Each of the four residues was mutated to the residues either in the same group, with different structure or different charged. The mutated receptors were then tested for their ligand binding activity. The receptor with V176L mutant retained binding activity to SQ29,548. All other mutations resulted in decreased or lost binding activity to SQ29,548. These mutagenesis results supported the prediction from NMR experiments in which Val176, Leu185, Thr186, and Leu187 are the possible residues involved in ligand binding. This information facilitates the understanding of the molecular mechanism of thromboxane A2 binding to the important receptor and its signal transduction.
Supercritical processing of functionalized size selective microporous materials

Abstract A supercritical fluid silanation process is applied to effectively functionalize commercial microporous materials without blocking the pore channels. In this approach, supercritical carbon dioxide (SCCO 2 ) is used to deposit mercaptopropyl silane into the microporosity of zeolite beta. The thiol group was subsequently oxidized into sulfonic acid. The size selective catalytic properties of the SCCO 2 modified zeolite compare well with similar materials prepared by an in situ silanation process reported by Jones et al. The active functional groups were delivered to the internal pore surface of the microporous material and remain accessible to molecules that can enter the pore channels. The supercritical process provides an alternative approach to functionalize microporous materials because of the enhanced diffusivity of the functional molecules in the micropore channels and accelerated reaction kinetics. Furthermore, the supercritical process simplifies the materials preparation and may open up new opportunities for commercial zeolites.
Some properties of the simple disequilibrium model with covariance

Abstract This paper investigates two difficulties that arise in disequilibrium models with non-zero covariances between demand and supply errors. The nature of these difficulties is demonstrated analytically and some preliminary observations are made about their practical, computational significance.
Impact of Stirring on the Luminescent Dissolved Oxygen Sensor

AbstractThe impact of stirring on the response of the field YSI ProODO luminescence dissolved oxygen sensor was measured in a 300-mL biological oxygen demand (BOD) test bottle with a magnetic stirrer either on or off. With a water sample from a fish transport experiment, the dissolved oxygen dropped by 2–3 mg/L when the magnetic stirrer was turned off for 11 min. The initial rate of dissolved oxygen decline ranged from −0.39 to −1.04 mg/L per min for this water. The dissolved oxygen returned to a value projected from the oxygen uptake rate when the stirrer was turned on. A much smaller impact was observed for 18.2 MΩ high-purity water (mean: −0.11 mg/L). Acid-washing the BOD bottle/stir bar and cleaning the sensor cap reduced the decrease to −0.08 mg/L. Based on t-tests between pairs of stirring-on and stirring-off results, the lack of stirring had a significant effect on measured dissolved oxygen. The source of this effect and its potential impact on the accuracy of the optical probe under typical operat...
Novel in vitro model barriers for evaluation of the permeability of antitumor compounds, thioxanthones.

Anticancer drugs have to cross many layers of cells and the extracellular matrix to reach the tumor cells and elicit their pharmacological action. The three dimensional structure (micro-environment) of tumors poses a penetration barrier to antitumor drugs resulting in poor response. Two in vitro model barriers representing the extracellular matrix and multilayered structure of tumors were used in this study to evaluate the permeability of four structurally related antitumor compounds, thioxanthones. Matrigel® was used to represent the tumor extracellular matrix and multilayered Caco-2 cells were used to represent the multilayered confluence of solid tumor. The in vitro permeability characteristics of the thioxanthones across the model barriers were correlated to their in vivo distribution. The apparent permeability coefficients of thioxanthone analogs are in the range of 2.9 × 10−6 to 11.8 × 10−6 cm/s across matrigel and 12.6 × 10−6 to 24.5 × 10−6 cm/s across Caco-2 multilayers. This high in vitro permeability of thioxanthones across the model barriers suggested their good tissue distribution in vivo. Therefore, the use of in vitro model barriers was found to predict in vivo tissue distribution for thioxanthones.
FIR laser tangential interferometry/polarimetry on NSTX

A tangential far infrared interferometer/polarimeter system has been upgraded for the measurement of two-dimensional electron density and toroidal magnetic field profiles on the National Spherical Torus Experiment (NSTX). The system employs a three-wavelength configuration that simultaneously produces interferometric phase shift and Faraday rotation polarimetric data from a single detector for each channel. Three CH/sub 3/OH lasers (/spl lambda/=119 /spl mu/m) including Stark-tuned laser cavities are optically pumped by a CO/sub 2/ laser tuned to 9.7 /spl mu/m. For high time-resolution measurements, the modulation frequency in the heterodyne interferometer is operated at /spl sim/ 7 MHz via the Stark-tuned laser, serving as the local oscillator in this system. Unwanted phase changes introduced by mechanical vibrations originating from various sources were eliminated by extensive work including a specially designed vibration-free stand for the retroreflector. The system is designed to have a full remote control capacity using the LABVIEW program via fiber links and real time signal processing circuits with a tracking receiver technique. A high IF frequency and a low noise fringe counting system enabled the system to measure wide-band density fluctuations such as microturbulence and magnetohydrodynamics. In this paper, a comparison study of the measured electron density with Thomson scattering data and para/diamagnetism effects measured via polarimetry signal and compared with the calculated value using the EFIT equilibrium code are presented. A recent upgrade plan together with the technical details of the system development will also be described.
Estimating local backbone structural deviation in homology models.

Abstract After the atomic coordinates themselves, the most important data in a homology model are the spatial reliability estimates associated with each of the atoms (atom annotation). Recent blind homology modeling predictions have demonstrated that principally correct sequence-structure alignments are achievable to sequence identities as low as 25% [Martin, A.C., MacArthur, M.W., Thornton, J.M., 1997. Assessment of comparative modeling in CASP2. Proteins Suppl(1), 14–28]. The locations and extent of spatial deviations in the backbone between correctly aligned homologous protein structures remained very poorly estimated however, and these errors were the cause of errant loop predictions [Abagyan, R., Batalov, S., Cardozo, T., Totrov, M., Webber, J., Zhou, Y., 1997. Homology modeling with internal coordinate mechanics: deformation zone mapping and improvements of models via conformational search. Proteins Suppl(1), 29–37]. In order to derive accurate measures for local backbone deviations, we made a systematic study of static local backbone deviations between homologous pairs of protein structures. We found that ‘through space’ proximity to gaps and chain termini, local three-dimensional ‘density’, three-dimensional environment conservation, and B-factor of the template contribute to local deviations in the backbone in addition to local sequence identity. Based on these finding, we have identified the meaningful ranges of values within which each of these parameters correlates with static local backbone deviation and produced a combined scoring function to greatly improve the estimation of local backbone deviations. The optimized function has more than twice the accuracy of local sequence identity or B-factor alone and was validated in a recent blind structure prediction experiment. This method may be used to evaluate the utility of a preliminary homology model for a particular biological investigation (e.g. drug design) or to provide an improved starting point for molecular mechanics loop prediction methods.
When worlds collide

Nanotechnology has enabled the production of new materials and molecular-scale devices. Biotechnological advancements have allowed scientists to physical ly manipulate genetic pathways or engineering strains of proteins to possess novel functionalities. Informatics has served as the catalyst for organizing and understanding vast knowledge from a system point of view. The fusion of biotechnology, nanotechnology, and information science will culminate in system architectures that can rival those that have taken millions of years to come to fruition. With this comes the hope of achieving a fundamental comprehension of how to manipulate and control cells on die molecular level. It will also enable us to question just how much further we can push the envelope of human engineering.
Abrasive wear by paper

Abstract An engineering study of wear produced by data processing card stock is presented. Wear data was obtained for several different metals and geometries as well as for different loads and sliding speeds. These data were accumulated for amounts of sliding, from a few thousand feet of paper up to hundreds of miles. In addition, a model is proposed to explain some of the observed dependencies.
A Note on the Use of Short-time Trapnesting in Breeding Selection

Abstract DAILY trapnesting throughout the year for the purposes of selecting superior layers to be used in breeding constitutes an important item of expense to breeders of production stocks. Several attempts to determine the possibility of reducing this expense by trapnesting for less than a year of laying have been made. Thompson (1933) and Olsen (1939) have reviewed in full the literature on this subject, so that repetition is not necessary here. As pointed out by Olsen, two types of short-time trapnesting have been suggested: (1) trapnesting during a number of consecutive days or months and (2) trapnesting at periodic intervals. To determine the utility of short-time trapnesting all of the investigators in this field have used as standards the degree of correspondence between the short-time and the annual records reporting significant positive correlations of various magnitudes. From the breeding standpoint, however, the important consideration involved lies not so much in . . .
Program Assessment: Getting to a Practical How-To Model

The Association to Advance Collegiate Schools of Business (AACSB) International's assurance of learning (AoL) standards require that schools develop a sophisticated continuous-improvement process. The authors review various assessment models and develop a practical, 6-step AoL model based on the literature and the authors’ AoL-implementation experiences. The model creates a sound foundation for compliance with AACSB standards as well as regional accreditation and likely future assessment requirements. The authors present suggestions for successful implementation of each AoL step as well as cautions on possible pitfalls.
Electrochemical and chemical reduction of TcO4− in dithiols in alkaline aqueous media

Abstract The electrochemical reduction of [ 99 Tc]pertechnetate ion in the presence of 1,3-dimercaptopropane, 2,3-dimercaptopropanol and 2,3-dimercapto succinic-acid was carried out in alkaline aqueous media. For these experiments, the potentials imposed to the mercury pool electrode were selected from the voltammograms of TcO 4 − -ligand solution recorded at a HMDE. The coulometric experiment evolution was followed by spectrophotometry and voltammetry. The species obtained were precipitated as tetraphenylarsonium salts and characterized by u.v., visible and i.r. spectrophotometry. The results demonstrate that technetium (V)-dithiolate complexes were obtained in the electroreduction of TcO 4 − in these media. Similar results were obtained in the chemical reduction of TcO 4 − with Sn(II), in the same media.
Failure of Angiotensin II to Stimulate Increases in Concentrations of Adrenal Androgens, 17- Hydroxyprogesterone, or Adrenocorticotropin in Congenital 21-Hydroxylase Deficiency

To determine if angiotensin II stimulates an increase in the plasma concentration of androstenedione, dehydroepiandrosterone, 17-hydroxyprogesterone, or ACTH in a patient with congenital 21-hydroxylase deficiency, we measured these plasma concentrations before and after the plasma angiotensin II concentration was increased by upright posture and angiotensin II infusion in a surgically castrate XX adult patient with this disorder. The patient was studied before treatment, after treatment with 1 mg dexamethasone daily for 3 weeks, and after treatment with both dexamethasone and 0.2 mg fludrocortisone daily for 3 weeks. The plasma concentrations of androstenedione, dehydroepiandrosterone, and 17-hydroxyprogesterone did not change consistently during increases in the angiotensin II concentration. The ACTH concentration did not increase in response to raised angiotensin II concentrations before or after steroid treatment. During the infusion of angiotensin II, blood pressure increased and renin activity decrea...
Zinc transport by respiratory epithelial cells and interaction with iron homeostasis

Despite recurrent exposure to zinc through inhalation of ambient air pollution particles, relatively little information is known about the homeostasis of this metal in respiratory epithelial cells. We describe zinc uptake and release by respiratory epithelial cells and test the postulate that Zn(2+) transport interacts with iron homeostasis in these same cells. Zn(2+) uptake after 4 and 8 h of exposure to zinc sulfate was concentration- and time-dependent. A majority of Zn(2+) release occurred in the 4 h immediately following cell exposure to ZnSO(4). Regarding metal importers, mRNA for Zip1 and Zip2 showed no change after respiratory epithelial cell exposure to zinc while mRNA for divalent metal transporter (DMT)1 increased. Western blot assay for DMT1 protein supported an elevated expression of this transport protein following zinc exposure. RT-PCR confirmed mRNA for the metal exporters ZnT1 and ZnT4 with the former increasing after ZnSO(4). Cell concentrations of ferritin increased with zinc exposure while oxidative stress, measured as lipid peroxides, was decreased supporting an anti-oxidant function for Zn(2+). Increased DMT1 expression, following pre-incubations of respiratory epithelial cells with TNF-alpha, IFN-gamma, and endotoxin, was associated with significantly decreased intracellular zinc transport. Finally, incubations of respiratory epithelial cells with both zinc sulfate and ferric ammonium citrate resulted in elevated intracellular concentrations of both metals. We conclude that exposure to zinc increases iron uptake by respiratory epithelial cells. Elevations in cell iron can possibly affect an increased expression of DMT1 and ferritin which function to diminish oxidative stress. Comparable to other metal exposures, changes in iron homeostasis may contribute to the biological effects of zinc in specific cells and tissues.
A Comparison of Air Sampling Methods for Airborne Silica in the Diatomaceous Earth Industry

Abstract The purpose of this study was to derive empirical quantitative relationships from linear regression equations between standard impinger, total mass, and respirable mass sampling methods for silica dust in the diatomaceous earth industry. Dust from one diatomaceous earth processing plant was sampled simultaneously by all three sampling methods. Two areas within the plant were sampled: one area included only main flux-calcined product; the other included only bag-house flux-calcined product. The baghouse product contains a much higher percentage of small-sized particles than the main product. Results from 61 clusters of the three sampling devices indicate that the particle size distribution of the dust varies with the particle size distribution of the parent product handled in that area. Since the respirable mass method is dependent on the particle size distribution of the dust, separate relationships were derived for main product and baghouse product dust. For bag-house product dust, the relations...