cssi/SciSciGPT-SciSciNet huggingface dataset:
Halothane and isoflurane augment depolarization-induced cytosolic CA2+ transients and attenuate carbachol-stimulated CA2+ transients.

Background: Neuronal excitability is in part determined by Ca 2+ availability that is controlled by regulatory mechanisms of cytosolic Ca 2+ ([Ca 2+ ] cyt ). Alteration of any of those mechanisms by volatile anesthetics (VAs) may lead to a change in presynaptic transmission and postsynaptic excitability. Using a human neuroblastoma cell line, the effects of halothane and isoflurane on cytosolic Ca 2+ concentration ([Ca 2+ ] cyt ) in response to K + and carbachol stimulation were investigated. Methods: Volatile anesthetic (0.05-1 mM) action on stimulated [Ca 2+ ] cyt transients were monitored in suspensions of SH-SY5Y cells loaded with fura-2. Potassium chloride (KCl; 100 mM) was used to depolarize and activate Ca 2+ entry through voltage-dependent calcium channels; 1 mM carbachol was used to activate muscarinic receptor-mediated inositol triphosphate (IP 3 )-dependent intracellular Ca 2+ release. Sequential stimulations, KCl followed by carbachol and vice versa, were used to investigate interactions between intracellular Ca 2+ stores. Results: Halothane and isoflurane in clinically relevant concentrations enhanced the K + -evoked [Ca 2+ ] cyt transient whether intracellular Ca 2+ stores were full or partially depleted. In contrast, halothane and isoflurane reduced the carbachol-evoked [Ca 2+ ] cyt transient when the intracellular Ca 2+ stores were full but had no effect when the Ca 2+ stores were partially depleted by KCl stimulation. Conclusions: Volatile anesthetics acted on sites that differently affect the K + - and carbachol-evoked [Ca 2+ ] cyt transients. These data suggest the involvement of an intracellular Ca 2+ translocation from the caffeine-sensitive Ca 2+ store to the inositol triphosphate-sensitive Ca 2+ store that was altered by halothane and isoflurane.
The Stability of Self-Employment A Comparison between Japan and Korea

The persistent role of self-employment in the Japanese and Korean economies and its changing character under recent economic and industrial changes merit renewed attention to self-employment in the two countries. Using individuals’ job history data, the article compares the occupational heterogeneity of self-employment activities and stability in Japan and Korea. Korea shows a much higher prevalence of shop/restaurant owners among total self-employment than Japan, where skilled blue-collar self-employed occupy a relatively large share. The hazard models of exit from self-employment show that the overall likelihood of leaving self-employment is greater among Korean self-employed than their Japanese counterparts. In Korea, shop/restaurant owners not only comprise the majority of self-employed persons but also show a fairly high risk of exit, similar to unskilled self-employed. This pattern is contrasted to shop/restaurant owners in Japan, who show considerable stability. The study addresses how differences ...
Kinetics of inhibition of ethanol metabolism in rats and the rate-limiting role of alcohol dehydrogenase

If liver alcohol dehydrogenase were rate-limiting in ethanol metabolism, inhibitors of the enzyme should inhibit the metabolism with the same type of kinetics and the same kinetic constants in vitro and in vivo. Against varied concentrations of ethanol, 4-methylpyrazole is a competitive inhibitor of purified rat liver alcohol dehydrogenase (Kis = 0.11 microM, in 83 mM potassium phosphate and 40 mM KCl buffer, pH 7.3, 37 degrees C) and is competitive in rats (with Kis = 1.4 mumol/kg). Isobutyramide is essentially an uncompetitive inhibitor of purified enzyme (Kii = 0.33 mM) and of metabolism in vivo (Kii = 1.0 mmol/kg). Low concentrations of both inhibitors decreased the rate of metabolism as a direct function of their concentrations. Qualitatively, therefore, alcohol dehydrogenase activity appears to be a major rate-limiting factor in ethanol metabolism. Quantitatively, however, the constants may not agree because of distribution in the animal or metabolism of the inhibitors. At saturating concentrations of inhibitors, ethanol is eliminated by inhibitor-insensitive pathways, at about 10% of the total rate at a dose of ethanol of 10 mmol/kg. Uncompetitive inhibitors of alcohol dehydrogenase should be especially useful for inhibiting the metabolism of alcohols since they are effective even at saturating levels of alcohol, in contrast to competitive inhibitors, whose action is overcome by saturation with alcohol.
Laser desorption electron attachment time-of-flight mass spectrometry: a new approach to detection of involatile compounds

We report initial results of a new method for obtaining mass spectra of involatile compounds: laser desorption electron attachment time-of-flight mass spectrometry. With this approach, laser desorbed neutral molecules are entrained in a molecular beam and subsequently ionized by low energy electron attachment. Mass analysis is carried out by a linear time-of-flight. We present a description of the apparatus and a number of examples of our early results on: van der Waals condensates of SF6, Fullerenes, derivatized Fullerenes, perfluorinated polyethers, polyphenylethers, and 5-bromouracil.
Surface figure measurement based on the transmitted wavefront with reverse raytracing

A method of surface figure measurement is described based on the transmitted wavefront of an optical element obtained from a Mach-Zehnder interferometer. Given known values for the refractive index and center thickness, along with the sample's transmitted wavefront, the unknown surface profile is reconstructed in a deterministic way. The technique relies on knowledge of one of the surfaces of the element, such as an easy-to-measure plano or spherical surface, and is well suited for testing aspheric surfaces. Reverse raytracing is used to bring the transmitted wavefront from the detector to the unknown surface considering the refraction at the surfaces in the system. Reverse raytracing also removes the effects of transmission through a thick lens and the induced aberration associated with the interferometer. In the interferometer, the wavefront transmitted through the sample is tested against a plano reference. This method also has the ability to make measurements on multiplexed surfaces, such as a lenslet array, which traditionally cannot be measured without moving the sample. The surface profile of a plano-convex lens has been produced and verified against other metrology techniques for calibration purposes. Surface measurements on a cylindrical lens and a lenslet array are also presented.
Next generation lithography: Impact on device and circuit architecture and performance

Lithographic scaling has been the driver for Moore Law over multiple process generations. Through the use of more advanced imaging technology and the development of advanced photoresists that are capable of finer resolution, the microelectronics industry has sustained a remarkable trend in the increase of complexity, capability and scale that is unparalleled in human endeavor.
Comparison of theory to experiment for DNA thermal denaturation

THEORETICAL profiles of the thermal denaturation of random sequence DNA that were calculated by Frank-Kamenetskii and Vologodskii1 displayed a number of narrow subtransitions. In several ways these subtransitions resembled the thermalities observed experimentally in derivative denaturation profiles2–7. Lyubchenko et al.8 extended their theoretical work to include the known sequence of ΦX174 DNA and claim that not only the shape of prominent subtransitions, but also the number and denaturation temperatures are essentially the same for both calculated and observed denaturation profiles. We suggest that the agreement between current theory and experiment is not as satisfactory as has been implied, and that at least one critical parameter has been neglected in the theory and ignored in the discussions of Lyubchenko et al.8.
Variance reduction for a replacement process

Prediction of replacement requirements for components (such as manufacturing equipment or engines) requires analysis of a replacement process. Unfortunately, unless component lives are exponentially distributed, that analysis requires transform methods, approxima tions, or simulation. Only simulation or approxima tion may be used for prediction of replacement re quirements when the replacement process is complicat ed, when it is subdivided into several periods of time, when replacements are not all new, or when several identical components that operate simulta neously are supplied from the same stock of spares.This paper shows that in a simulation the use of complementary antithetic random variates in the generation of component lifetimes reduces the vari ance of the sample mean number of replacements in a multiple-component multiple-period replacement process in which the components may be either new or used. Reducing the variance results in more accurate predictions for fixed simulation runtimes or, alt...
Technetium-99m complexes of dimethylaminomethylene diphosphonate (DMAD)--I. Anion exchange HPLC characterization of 99mTc(NaBH4)-DMAD mixtures.

Abstract Radiopharmaceutical analogs prepared by sodium borohydride reduction of 99m TcO − 4 in the presence of DMAD have been characterized by anion exchange HPLC (high performance liquid chromatography) separation of the resulting mixture into component 99m Tc-DMAD complexes. The distribution of complexes within a radiopharmaceutical formulation can be manipulated by controlling technetium concentration, pH, presence or absence of air, and time post reaction.
A new opuntioid cactus from the Cayman Islands, B.W.I., with a discussion and key to the genus Consolea Lemaire

A new subspecies ofConsolea millspaughii is described from the eastern bluff of Cayman Brac and northern coastal terrace of Little Cayman (Cayman Islands, British West Indies). This taxon has been mistakenly identified asConsolea spinosissima since its first collection in 1938. However, the smooth surface of its stem segments, not being demarcated by a network of depressed lines, its pitted areoles, and the fairly reduced pedicellate area of the pericarpel set is apart from this Jamaican endemic. Because the novelty here described brings to three the number ofConsolea taxa that are characterized by very closely set, pitted areoles, an informal “C. millspaughii species-group” is recognized. This assemblage of Western Caribbean opuntioids includesConsolea corallicola, C. millspaughii subsp.millspaughii, andC. millspaughii subsp.caymannnsis. The new subspecies is described, illustrated, and compared withC. spinosissima and with kindred taxa within the species-group. A key to all species and subspecies ofConsolea is provided.
On an extension of Mullin and Jury's method

Actuating signal at sampling instants determined in phase plane by Mullin-Jury method for sampled data feedback containing quantizer and zero order hold circuit
USE OF PAVEMENT MANAGEMENT SYSTEM DATA FOR PAVEMENT ENGINEERING APPLICATIONS

Agencies have collected data for pavement management for many years now. These data have been used primarily to develop short- and long-range rehabilitation programs. Another valuable use of these data is improvements to engineering procedures. The Illinois Pavement Feedback System (IPFS) is a comprehensive inventory and monitoring system that was designed in 1984 to provide data for both programming and engineering uses. Over the past 10 years many engineering issues have been addressed through the use of these data. IPFS data were used to provide feedback to designers and administrators on the design of new (or original) pavements and on overlay designs. Results from a survival analysis of thousands of kilometers of original jointed reinforced concrete pavement (JRCP), continuously reinforced concrete pavement and hot-mix asphalt concrete pavements and asphalt concrete (AC) overlays of these pavements were used. Key results relate to performance variability (a wide range of performance was found for ide...
Thermal radiation relaxation times near the boundary of a semi-infinite nongray medium

Abstract The effect of a nearby boundary on thermal radiation relaxation times in a semi-infinite medium has been examined for gray and exponential band models. Noticeable variations from relaxation time in an infinite medium are confined to a region within one wavelength of the boundary. A reflecting boundary has a lesser effect than a transparent one and the asymptotic behavior of the two band models are quite distinct for optically thick waves.
Axillary Staging Prior to Neoadjuvant Chemotherapy for Breast Cancer: Predictors of Recurrence

The value of axillary staging prior to delivery of neoadjuvant chemotherapy (NEO) for breast cancer is controversial. Our goal was to analyze the prognostic and therapeutic impact of axillary staging on recurrence. The study cohort included 161 patients undergoing comprehensive evaluation by a multidisciplinary approach during the period 1996–2006. Clinicopathologic features were assessed before and after delivery of NEO. Patients with node-positive disease before NEO underwent a post-NEO axillary lymph node dissection at time of definitive breast surgery. At presentation, median age was 49 years; mean tumor size was 45 mm. The axilla was negative in 45 (28.6%) patients. Of the 114 pre-NEO node-positive patients, 65 (57%) were staged histologically. At completion of NEO, partial or complete clinical response was observed in 90.6%; complete pathologic response occurred in 23.6%. Mean residual tumor size was 10.5 mm. Of the 112 initially node-positive patients, 36 (31.6%) had no residual axillary disease post NEO. At median follow-up of 38.1 months, 21.7% patients relapsed. The pre-NEO nodal status was the strongest predictor of treatment failure. A significant risk of distant relapse was based on nodal response to NEO: 8.1% in node-negative patients, 13.9% in the downstaged group, and 22.1% in the persistently positive group (P = 0.047). Delivery of nodal irradiation decreased local recurrence in the downstaged group (12.5% versus 3.7%, P = NS). Our experience suggests that comprehensive axillary staging with ultrasound and fine-needle aspiration (FNA) and sentinel lymph node biopsy prior to NEO is both prognostically and therapeutically important in predicting those patients at higher risk of recurrence.
Prediction of early symptomatic recurrence after intestinal resection in Crohn's disease.

Objective This study was performed to identify clinical criteria that may help recognize patients with Crohn's disease who are at high risk for early symptomatic postoperative recurrence. Summary Background Data Currently, no reliable criteria are available to help recognize patients who are prone to experience early symptomatic recurrence. Methods One hundred sixty-four patients undergoing intestinal resection for Crohn's disease at The Mount Sinai Hospital between 1976 and 1989 were studied prospectively. Patients with symptomatic recurrent disease within 36 months were defined as having an early recurrence. Results Multivariate analysis revealed that the number of anastomoses was the most important prognostic indicator (p=0.001), followed by inflammation at the resection margins (p<0.05)
δ13C–δ18C covariance as a paleohydrological indicator for closed-basin lakes

The relationship between δ18O and δ13C in a closed-basin lake is a function of hydrological change, vapor exchange, lake productivity, and total CO2 (or carbonate alkalinity) concentration. Covariance of δ18O and δ13C usually occurs in lake sediments under the condition of hydrological closure for time periods of the order of 5000 yr or longer. On shorter time scales, however, certain subtleties in the use of the δ13C–δ18O covariance as a hydrology history indicator must be recognized. The covariant trend may not be found in hyper-alkaline lakes because of the insensitivity of δ13C to lake volume changes. For less alkaline closed-basin lakes, covariance of δ13C–δ18O will result from relatively rapid increase or decrease of lake volume, with the rapid-decrease condition giving rise to heavy and narrow-ranged isotopic values for both δ13C and δ18O due to the coupled evaporation-productivity effect. When the lake volume remains stable (as is the case for an over-flowing open lake), poor δ13C–δ18O covariance will ensue, due to the effect of vapor exchange with the atmosphere. We have used the measured δ13C–δ18O covariance in carbonate sediments of Mono Lake, California, to deduce paleo-hydrological and lake-water alkalinity (and salinity) variations and found the results in consonance with Holocene lake-level history derived from the δ18O and other information.
Pre-Transplant Donor-Specific HLA Antibodies (DSA) Frequently Decline Following Lung Transplantation

Purpose DSAs prior to lung transplantation (LT) have been associated with adverse outcomes, but the implications of weak DSAs detected by sensitive microarrays remain poorly understood. We examined the incidence of DSAs before transplant and immunodominant DSA (iDSA) profiles after LT. Methods and Materials LT recipients (n=66) from a single center with single antigen testing (LABScreen®) before LT, within the first 45 days after LT and at least one subsequent time point were studied. Patients were excluded if they received any desensitization or antibody directed therapy. We defined the iDSA as the DSA with the highest mean fluorescence intensity (MFI). We used iDSA levels pre-LT to categorize subjects into 3 groups: No DSA, iDSA MFI of 500-1000 MFI, and iDSA MFI >1000. Results Pre-LT, no DSAs were detected in 36 (55%) patients. Of these, 6 (17%) developed iDSA >1000 MFI post-LT (range 1685-6071 MFI). These iDSAs were initially detected 12-32 days after transplant, against HLA Class II, and accompanied by additional DSAs. At the last time point (93-560 days post-LT), the DSAs were below peak levels or were eliminated. Pre-LT iDSAs with MFI 500-1000 were observed in 12 (18%) of patients. Of these, 5 (42%) developed iDSA >1000 MFI post-LT. In 2 of these 5, the post-LT iDSA specificity was different from the pre-LT iDSA. At the last time point, DSA levels were declining or eliminated in 3 recipients. Pre-LT iDSA >1000 MFI were detected in 18 (27%) recipients (range 1023-5246 MFI; 11 Class II, 7 Class I). Post-LT, 4 had no DSA >1000 MFI. The maximum iDSA level after LT was 9659 MFI. In 13 (72%) of these recipients, iDSA specificity pre- and post-LT was identical. Of the 18 recipients, 9 (50%) had all DSA Conclusions Weak DSAs are observed in nearly half of patients pre-LT. While variable, the majority of DSAs decline post-LT. Additional study is needed to determine the impact of weak pre-LT DSAs and declining post-LT DSAs on clinical outcomes.
Lessons Learned Through Area Exercises in an Inland Region

ABSTRACT The Environmental Protection Agency (EPA) Region VIII (R8) has completed planning and exercising in seven of its designated Sub-Areas. This paper takes a brief journey through the analyzation of the results of the planning and exercising that has taken place by compiling lessons learned by profession and examines the actions taken to change and improve the response plans. A brief summary of the extensive background of activities which have occurred by constituents includes developed written plans, guidelines, and exercises for seven designated Sub-Areas of the Region.
Heart failure training: A call for an integrative, patient-focused approach to an emerging cardiology subspecialty

The coming years will see continued growth in the epidemic of heart failure (HF) and increasingly complex pharmacologic, interventional, and device-based therapies, effective in reducing HF morbidity and mortality. Highly trained clinician-specialists are needed to assist in optimally evaluating and managing patients with HF. The patient is the central element defining the skills needed within this cardiology subspecialty. Primary care education, disease management strategies, and effective communication among HF specialists and other clinicians are key systemic elements needed to deliver the increasingly complex array of treatments to the expanding population of patients with HF.
Filtering with rhythms: Application to estimation of gait cycle

The aim of this paper is to describe a coupled oscillator model for Bayesian inference. The coupled oscillator model comprises of a large number of oscillators with mean-field coupling. The collective dynamics of the oscillators are used to solve an inference problem: the empirical distribution of the population encodes a ‘belief state' (posterior distribution) that is continuously updated based on noisy measurements. In effect, the coupled oscillator model works as a particle filter. The framework is described here with the aid of a model problem involving estimation of a walking gait cycle. For this problem, the coupled oscillator particle filter is developed, and demonstrated on experimental data taken from an Ankle-foot Orthosis (AFO) device.
Encapsulating concurrency with Early-Reply

Component methods often produce their final parameter values long before the method body is ready to terminate. To minimize client blocking, Early-Reply can be used to forward invocation results to the caller as soon as they are (safely) available. After executing Early-Reply, the method remainder and the client caller can proceed concurrently, modulo synchronization constraints. The prime motivation for Early-Reply, then, is to improve performance factors such as response time and resource utilization.Early-Reply received previous attention as a construct for explicit concurrent programming. It's value for sequential programming, however, has not been widely recognized. The present research supplies a formal treatment of Early-Reply as a basis for concurrent execution of sequential programs. In particular, we reformulate Early-Reply under local proof obligations that encapsulate concurrency as a (temporal) unit of information hiding. The upshot is that software developers can use Early-Reply to exploit the performance benefits of concurrent execution, without compromising the reasoning benefits of sequential programming.
Tidal decomposition of zonal neutral and ion flows in the earth's upper equatorial thermosphere

Evidence is presented for strong coupling between the diurnal components of zonal neutral winds and ion drifts, suggesting that the relative importance of the E- and F-region dynamos be reevaluated. Measurements of zonal neutral winds in the equatorial region of the earth's thermosphere at an average altitude of about 350 km show that the nighttime zonal winds are very similar to the zonal ion-drifts. That similarity is examined, comparing the corresponding tidal components of the 24 hr variations of these two parameters. The amplitude spectrum of the neutral winds exhibits primary and secondary maxima at the diurnal and ter-diurnal frequencies respectively, while the ion-drift spectrum shows only the diurnal maximum. It is found that the simularity between neutral winds and ion-drifts is strongest in the diurnal mode where the phases differ by less than one half hour, the amplitude of the ion-drift being between 70 percent and 80 percent that of the neutral wind, suggesting a first-order relation between the two quantities. The largest difference is found in the steady component representing superrotation; under similar conditions of solar activity, the ions superrotate with a velocity of about 30 m/s and the neutrals with 10 m/s. For the ions, the steady component, the phase of the semi-diurnal component and the amplitude of the ter-diurnal component appear to be sensitive to solar activity and are responsible for the observed solar cycle variations in the times of eastward-to-westward reversals between 0400 and 0700 LT. The ion-drift diurnal amplitude and phase are relatively insensitive to changes in solar activity.
Renormalization of binary trees derived from one-dimensional unimodal maps

For one-dimensional unimodal mapsh λ(x):I →I, whereI=[x 0,x 1] when λ=λmax, a binary tree which includes all the periodic windows in the chaotic regime is constructed. By associating each element in the tree with the superstable parameter value of the corresponding periodic interval, we define a different unimodal map. After applying a certain renormalization procedure to this new unimodal map, we find the period-doubling fixed point and the scaling constant. The period-doubling fixed point depends on the details of the maph λ(x), whereas the scaling constant equals the derivative\(h'_{\lambda _{max} } \left( {x_0 } \right)\). The thermodynamics and the scaling function of the resulting dynamical system are also discussed. In addition, the total measure of the periodic windows is calculated with results in basic agreement with those obtained previously by Farmer. Up to 13 levels of the tree have been included, and the convergence of the partial sums of the measure is shown explicitly. A new scaling law has been observed, i.e., the product of the length of a periodic interval characterized by sequenceQ and the scaling constant ofQ is found to be approximately 1.
Do three α-particles make a 12C?☆

Abstract This note answers two questions: 1) What is the binding energy of three ‘elementary’ α-particles, interacting via the empirical α-α potential; and 2) why do the various previous calculations of this model of 12 C disagree?
American Holiday Postcards, 1905-1915: Imagery and Context Daniel Gifford. Jefferson, NC: McFarland, 2013.

American Holiday Postcards, 1905-1915: Imagery and Context Daniel Gifford. Jefferson, NC: McFarland, 2013.Holidays as pop culture offer a rich opportunity for libraries and other public institutions to display their collection of postcards, and the author notes in his introduction that there are multiple repositories with holiday postcards.The author, who works at the Smithsonian Institution and serves as a part-time faculty member in the Department of History and Art History, George Mason University, argues that holiday postcards circulated primarily among rural and small towns and Northern white women with Anglo-Saxon and Germanic heritages. Gifford reconsiders the postcard phenomenon as an image-based conversation among exclusive groups of Americans. From Santa Claus to Easter bunnies, flag-waving turkeys to gun-toting cupids, holiday postcards proved to be not only humorous expressions of a past era but a barometer to the deep divides within the American social fabric at the height of the Progressive Era.Gifford focuses on one period only, 1905-1915, when the makeup of the United States population was changing and postcards started to reflect a more urban design. This was actually considered the Golden Age of American postcards, which peaked in 1910 with the introduction of tariffs on German-printed postcards, and ended by 1915, when World War I ultimately disrupted the printing and import of the fine Germanprinted cards with their scenic landscapes.In fact, one of the most interesting chapters in the book is Chapter 5 ("Women and Courtship in Holiday Postcards") which brings together three distinct elements: women as a core postcard audience; the historically situated contexts of the "New Woman"; and clusters of postcard images reflecting courtship in which stereotypes abound. This chapter argues that women in the early twentieth century used postcards to advance a gender-specific agenda on courtship as Christmas and Halloween joined Valentine's Day in displays of adult, heterosexual rites. Postcards allowed women to exploit holidays to control the power structures around them.Stereotypes abound, especially in portrayals of ethnic groups which often inspired protest movements. One such postcard, issued for St. Patrick's Day, shows two men shaking hands; one of the men wears a button from the Ancient Order of Hibernians, a group that organized such protests (68).Blacks were especially ill-served on postcards of these periods. Two for Thanksgiving are both quite derogatory. One portrays an African American woman as poor and rural, performing the hard labor of plucking a turkey that her white sisters have left behind (54). The second depicts the modern white woman (this was 1912! …
Microtubule sliding in reduced‐amplitude bending waves of Ciona sperm flagella: Bending waves attenuated by lithium

The distinct damped, or attenuated, bending pattern observed when demembranated sperm flagella of the tunicate, Ciona, are reactivated in the presence of 2 mM Li+ has been analysed in detail. In these patterns, bends are initiated at the base of the flagellum, but die out after they start to propagate along the flagellum, so that little or no bending is seen in the distal half of the flagellum. A quantitative descriptive analysis shows that the distinctive feature of this attenuation of bending wave amplitude is an asymmetric interbend decay, or slippage, occuring, on average, only at the transitions between a reverse bend and the preceding principal bend. This attenuation is combined with a significant amount of synchronous sliding in the distal half of the flagellum and a decrease in propagation velocity of transitions between bends in the mid-region of the flagellum. Computer simulations demonstrate that the synchronous sliding in the distal half of these flagella can be an entirely passive consequence of the mechanical interaction between active sliding and bending in the basal third of the flagellum and viscous resistances to movement of the distal region of the flagellum through the fluid environment. The current computer models do not contain a mechanism for asymmetric interbend decay that can reproduce these attenuated bending patterns. © 1994 Wiley-Liss, Inc.
Computational Systems Biology and Dose-Response Modeling in Relation to New Directions in Toxicity Testing

The new paradigm envisioned for toxicity testing in the 21st century advocates shifting from the current animal-based testing process to a combination of in vitro cell-based studies, high-throughput techniques, and in silico modeling. A strategic component of the vision is the adoption of the systems biology approach to acquire, analyze, and interpret toxicity pathway data. As key toxicity pathways are identified and their wiring details elucidated using traditional and high-throughput techniques, there is a pressing need to understand their qualitative and quantitative behaviors in response to perturbation by both physiological signals and exogenous stressors. The complexity of these molecular networks makes the task of understanding cellular responses merely by human intuition challenging, if not impossible. This process can be aided by mathematical modeling and computer simulation of the networks and their dynamic behaviors. A number of theoretical frameworks were developed in the last century for understanding dynamical systems in science and engineering disciplines. These frameworks, which include metabolic control analysis, biochemical systems theory, nonlinear dynamics, and control theory, can greatly facilitate the process of organizing, analyzing, and understanding toxicity pathways. Such analysis will require a comprehensive examination of the dynamic properties of "network motifs"--the basic building blocks of molecular circuits. Network motifs like feedback and feedforward loops appear repeatedly in various molecular circuits across cell types and enable vital cellular functions like homeostasis, all-or-none response, memory, and biological rhythm. These functional motifs and associated qualitative and quantitative properties are the predominant source of nonlinearities observed in cellular dose response data. Complex response behaviors can arise from toxicity pathways built upon combinations of network motifs. While the field of computational cell biology has advanced rapidly with increasing availability of new data and powerful simulation techniques, a quantitative orientation is still lacking in life sciences education to make efficient use of these new tools to implement the new toxicity testing paradigm. A revamped undergraduate curriculum in the biological sciences including compulsory courses in mathematics and analysis of dynamical systems is required to address this gap. In parallel, dissemination of computational systems biology techniques and other analytical tools among practicing toxicologists and risk assessment professionals will help accelerate implementation of the new toxicity testing vision.
Examining the Effectiveness of Test Accommodation Using DIF and a Mixture IRT Model

This study examined the validity of test accommodation in third–eighth graders using differential item functioning (DIF) and mixture IRT models. Two data sets were used for these analyses. With the first data set (N = 51,591) we examined whether item type (i.e., story, explanation, straightforward) or item features were associated with item difficulty, item discrimination, or DIF. The second data set (N = 3,452) was used to investigate whether observed DIF was related to students' accommodation status, gender, race, disability, or latent academic ability. Item types and features were significantly related to item difficulty but not to DIF. Story items were not always more difficult than explanation or straightforward items. Observed DIF was partially explained by an interaction of accommodation use and academic ability. Limitations and implications of this study are discussed, and suggestions for future research are offered.
Noninvasive cardiac output by partial CO2 rebreathing after severe chest trauma.

Background: In multiple trauma patients, early continuous cardiac output (CCO) monitoring is frequently desired but is difficult to routinely employ in most emergency departments because it requires invasive procedures. Recently, a noninvasive cardiac output (NICO) technique based on the Fick principle and partial CO 2 rebreathing has shown promise under a variety of conditions. Since this method has not been tested after lung damage, we evaluated its utility in a clinically relevant model. Methods: Anesthetized, ventilated swine (n = 11, 35-45 kg) received a unilateral blunt trauma via a captive bolt gun followed by a 25% hemorrhage. After 60 min of shock, crystalloid resuscitation was given as needed to maintain heart rate 70 mm Hg. Standard CCO by thermodilution (Baxter Vigilance, Irvine, CA) was compared with NICO (Novametrix Medical Systems Inc., Wallingford, CT) for 8 hr. Results: The severity of the injury is reflected by seven deaths (average survival time = 4.25 hr). Trauma increased dead space ventilation (19%), airway resistance (30%), and lactate (3.2 mmol/L), and decreased dynamic compliance (48%) and PaO 2 /FlO 2 (54%). In these extreme conditions, the time course and magnitude of change of CCO and NICO were superimposed. Bland-Altman analysis reveal a bias and precision of 0.01 ± 0.69 liters/ min. The linear relationship between individual CCO and NICO values was significant (p < 0.0001) and was described by the equation NICO = (0.74 ± 0.1)CCO + (0.65 ± 0.16 liters/min) but the correlation coefficient (r2 = 0.541) was relatively low. The cause for the low correlation could not be attributed to increased pulmonary shunt, venous desaturation, anemia, hypercapnia, increased dead space ventilation, or hyperlactacidemia. Conclusion: NICO correlated with thermodilution CCO, but underestimated this standard by 26% in extreme laboratory conditions of trauma-induced cardiopulmonary dysfunction; 95% of the NICO values fall within 1.38 liters/min of CCO; and with further improvements, NICO may be useful in multiple trauma patients requiring emergency intubation during initial assessment and workup.
A new extension of unscented Kalman filter for structural health assessment with unknown input

A time-domain nonlinear system identification (SI)-based structural health assessment (SHA) procedure, using Unscented Kalman Filter (UKF) concept, is presented in this paper. It is a two-stage procedure. It integrates an iterative least squares technique and the unscented Kalman filter concept. The authors believe that the integrated procedure significantly improves the basic UKF concept. The procedure can assess the health of a structure using only a limited number of noise-contaminated acceleration time-histories measured only at a small part of a structure and does not need information on input excitation. The structures are represented by finite element models and the location and severity of defect(s) are assessed by tracking the changes in the stiffness properties of individual elements from their expected values. With the help of examples, it is demonstrated that the method is capable of accurately identifying defect-free and defective states of structures. Small and relatively large defects are introduced at different locations in the structure and the capability of the method to detect the health of the structure is examined. It is demonstrated that the accuracy of the method is much better than the other methods currently available for the structural health assessment. It is also superior to the extended Kalman filter. Considering the accuracy and robustness, the procedure can be used as a nondestructive structural health assessment procedure.
HOME MANAGEMENT EXPERIENCE COURSES IN THE U.S.

The formats and learning experiences employed in home management experience courses in U.S. colleges and universities have increased greatly in diversity in the past decade. Many resident courses have been terminated and replaced with nonresident courses, while others continue to be taught in non-traditional formats. The overall objective of this study is the assessment of home management experience course formats and learning activities in 1979–80. Other aspects of experience courses such as types of residences used, instructors, and majors for whom the courses are required, are also described. Current questions regarding the choice of experience course format and objectives are discussed.
Topotecan-induced topoisomerase IIα expression increases the sensitivity of the CML cell line K562 to subsequent etoposide plus mitoxantrone treatment

Purpose: A new chemotherapy regimen was designed for leukemia to improve response to therapy and elucidate the possible underlying mechanisms responsible for its efficacy. Methods: Cells of the chronic myelogenous leukemia (CML) cell line, K562, were treated singly, in combination, and in sequence with clinically equivalent dosages of topotecan, which targets topoisomerase I (Topo I), and etoposide and mitoxantrone, which target topoisomerase II (Topo II), to determine the best treatment. Apoptosis, early cell deaths, and cell cytotoxicities in drug-treated cells were determined with annexin V and propidium iodide staining and MTT assays, respectively. Confocal microscopy and RT-PCR showed the cellular locations and relative increases in Topo IIα in topotecan-treated cells. The double comet assay of individual cells showed simultaneously free Topo proteins, non-Topo-associated DNA, and Topo-DNA complexes in drug-induced DNA fragments. Results: Sequential treatment with topotecan on days 1–3, followed by etoposide+mitoxantrone on days 4, 5, 9 and 10 resulted in 100% cell death whereas treatments involving administration of drugs singly or simultaneously resulted in less cell kill. The cytotoxicity results in cells treated for fewer days with the same sequential chemotherapy regimen showed the same trend, and adequate surviving cells for the experiments on the cellular and molecular mechanisms of drug action were produced. An increase in Topo IIα mRNA from RT-PCR 1 h after topotecan treatment was observed. Observations on K562 cells treated sequentially with topotecan followed by etoposide, mitoxantrone or etoposide+mitoxantrone were as follows: (1) Topo IIα protein levels increased and relocated from the cytoplasm into the nucleus as detected by confocal microscopy, (2) Topo IIα-DNA complexes increased and were associated with fragmented DNA (positive double comets) as detected by protein-DNA double comet assay, and (3) Topo I and Topo IIβ proteins were not associated with fragmented DNA. Topotecan-induced Topo IIα protein levels correlated with increased numbers of positive double comets and reduction of cell viability. Conclusions: Our results showed that Topo IIα protein induction after Topo I-directed drug treatment enhanced the sensitivity of cells to subsequent exposure to Topo II-directed drugs. Timed sequential chemotherapy with topotecan followed by etoposide+mitoxantrone is an effective regimen to ablate CML cancer cells.
Nucleotide sequence of a Bacillus subtilis promoter recognized by Bacillus subtilis RNA polymerase containing σ37

We report the nucleotide sequence of the promoter for a Bacillus subtilis gene (spoVC) whose transcription is controlled by a 37,000 dalton species of B. subtilis sigma factor known as sigma 37 but not by the principal- sigma factor of 55,000 daltons (sigma 55). Using S1 nuclease mapping we show that the startpoint for sigma 37-directed transcription of the spoVC gene in vitro corresponded closely to the 5' terminus of in vivo synthesized spoVC RNA. The binding site for sigma 37-containing RNA polymerase extended from 43 bp to 51 bp (positions -43 to -51) upstream from the transcription startpoint to 22 bp (position +22) downstream from the startpoint. The nucleotide sequence of the spoVC promoter differed significantly from promoters whose recognition is controlled by sigma 55 but was similar to other sigma 37- controlled promoters in regions known to be important in promoter recognition. Our results are consistent with the hypothesis (Lee and Pero, J. Mol. Biol., in press) that sigma factors work by contacting specific bases in both the -35 and -10 regions of promoters.
Occupational Safety and Health Legislation: Part 1 — Public Law 91-956

Several representative State occupational health and safety acts are discussed in terms of relevant provisions of Public Law 91-596, the Occupational Safety and Health Act of 1970.
SOLVING ION CHANNEL KINETICS WITH THE QuB SOFTWARE

The ability to record the currents from single ion channels led to the need to extract the underlying kinetic model from such data. This inverse hidden Markov problem is difficult but led to the creation of a software suite called QuB utilizing likelihood optimization. This review presents the software. The software is open source and, in addition to solving kinetic models, has many generic database operations including report generation with publishable graphics, function fitting and scripting for new and repeated processing and AD/DA I/O. The core algorithms allow for constraints such as fixed rates or maintaining detailed balance in the model. All rate constants can be driven by a stimulus and the system can analyze nonstationary data. QuB also can analyze the kinetics of multichannel data where individual events cannot be discriminated, but the fitting algorithms utilize the signal variance as well as the mean to fit models. QuB can be applied to any data appropriately modeled with Markov kinetics and has been utilized to solve ion channels but also the movement of motor proteins, the sleep cycles in mice, and physics processes. Special Issue Comment: This is a review about the software QuB that can extract a model from the trajectory. It is connected with the review about treatments when solving single molecules,60 and the reviews about enzymes.61,62
Axial area and anteroposterior diameter as estimates of left atrial size using computed tomography of the chest: Comparison with 3-dimensional volume

Background Left atrial (LA) size has incremental value in risk stratification. Objectives We aimed to assess feasibility and reproducibility of 2 quick measures of LA size by chest CT (axial LA area and LA anteroposterior [AP] diameter) by using contrast-enhanced and CT scans. Methods We measured LA size in 100 contrast-enhanced 64-slice multidetector CT (MDCT) scans (randomly selected from the ROMICAT collective) by (1) axial LA area at the level of the left ventricular outflow tract and the mitral valve leaflets, (2) AP diameter in 3-chamber view, and (3) 3-dimensional (3D) LA volume by Simpson's methods. We assessed interobserver and intraobserver intraclass correlation coefficient (ICC) for axial LA area and AP diameter as well as their correlation to 3D LA volume. For axial area, feasibility and reproducibility were also determined in 100 non–contrast MDCT scans, randomly selected from the Framingham Heart Offspring collective. Results In contrast-enhanced CT, both LA axial area and AP diameter had excellent reproducibility (interobserver: axial area: ICC, 0.96, mean relative difference, 2.4% ± 7.4%; AP diameter: ICC, 0.91, 3.6% ± 7.2%; intraobserver: axial area: ICC, 0.99, 0.4% ± 5.2%; AP diameter: ICC, 0.94, 1.7% ± 5.5%). Correlations with 3D volume were better for axial area ( r =0.88) than for AP diameter ( r =0.67). In non–contrast images, axial area could be assessed with excellent reproducibility (interobserver: ICC, 0.96, 0.5% ± 8.3%; intraobserver: ICC, 0.99, 0.01% ± 4.4%). Conclusion Both AP diameter and axial LA area permit quick and reproducible estimates of LA volume in contrast-enhanced and non–contrast electrocardiographic-gated chest CT. However, LA area should be used preferably over AP diameter because of its better agreement to 3D LA volume.
Scalable and precise taint analysis for Android

We propose a type-based taint analysis for Android. Concretely, we present DFlow, a context-sensitive information flow type system, and DroidInfer, the corresponding type inference analysis for detecting privacy leaks in Android apps. We present novel techniques for error reporting based on CFL-reachability, as well as novel techniques for handling of Android-specific features, including libraries, multiple entry points and callbacks, and inter-component communication. Empirical results show that our approach is scalable and precise. DroidInfer scales well in terms of time and memory and has false-positive rate of 15.7%. It detects privacy leaks in apps from the Google Play Store and in known malware.
Stability of heroin, 6-monoacetylmorphine, and morphine in biological samples and validation of an LC-MS assay for delayed analyses of pharmacokinetic samples in rats

Degradation of heroin to 6-monoacetylmorphine (6-MAM) and then morphine happens rapidly in vivo and in vitro. The rates of heroin and 6-MAM degradation depend on the type of biological samples, and the duration and conditions of storage. In order to optimize conditions for measuring heroin and its metabolites in samples collected for pharmacokinetic studies in rats, we investigated the time course of degradation of heroin, 6-MAM, and morphine in four biological matrices: rat blood, rat brain homogenate, bovine serum, and human plasma under various conditions. Analyte concentrations were measured by LC-MS. The goal was to identify conditions that allow maximum flexibility in scheduling sample collection and analysis, as well as gain more information on the stability of heroin in blood and tissue samples. A solid-phase extraction method with ice-cold solvents, sodium fluoride (NaF) and a low pH (3.0) maintained sample stability. Quality controls were within 94.0-105% of the target value. Variability was 4.0-8.9% for all analytes within the range of 5-200 ng/mL for heroin, 5-1000 ng/mL for 6-MAM, and 10-200 ng/mL for morphine. Heroin degradation to 6-MAM was faster in rat whole blood than in plasma, and faster in rat plasma than in rat brain homogenate. Maintaining NaF at 4 mg/mL throughout processing enhanced stability; higher NaF concentrations added to whole blood caused hemolysis. Samples processed through solid phase extraction and stored as dried pellets at 80°C constituted the most stable environment for heroin, and was superior to the storing of samples in solution prior to or after extraction. Nevertheless, post-extraction heroin and 6-MAM levels declined by 6.7-8.3% over one week in rat plasma under these conditions, and by <1-4.7% in bovine serum or human plasma.