cssi/SciSciGPT-SciSciNet huggingface dataset:
Na+-independent release of Ca2+ from rat heart mitochondria. Induction by adriamycin aglycone.

The effect of adriamycin aglycones on Ca2+ retention by isolated, preloaded rat heart mitochondria was assessed. After an initial lag, which decreased with increasing drug concentration, the 7-hydroxy-aglycone (5–20 μM) triggered Ca2+ release. Aglycone-induced Ca2+ release was correlated with Ca2+ -dependent mitochondrial swelling, Ca2+-dependent collapse of the mitochondrial membrane potential, Ca2+-dependent oxidation of mitochondrial pyridine nucleotides, and a transition from the condensed to the orthodox configuration. Aglycone-induced Ca2+ release was inhibited by dibucaine, dithiothreitol, ATP, and bovine serum albumin. It can be concluded, therefore, that aglycone-induced Ca2+ release reflects the Ca2+-dependent increase in the permeability of the inner mitochondrial membrane to solutes of molecular weight < 1000 which has been observed with other triggering agents [R. A. Haworth and D. R. Hunter, Archs Biochem. Biophys.195, 460 (1979); I. Al-Nasser and M. Crompton, Biochem. J.239, 19 (1986)]. In particular, the 7-hydroxy-aglycone decreased the amount of Ca2+ required to trigger the permeability increase. No effect of the aglycone on Ca2+ uptake could be discerned. 7-Deoxy-adriamycin aglycone, the more prominent biological metabolite of adriamycin, was similarly effective in inducing Ca2+ release, and both aglycones were substantially more effective than the parent drug. Adriamycin and related anthracyclines are potent antineoplastic agents, the clinical use of which is limited by severe cardiotoxicity. These results suggest that aglycone formation and the resultant disruption of both cellular Ca2+ homeostasis and metabolite compartmentation may mediate anthracycline cardiotoxicity.
Incidence and survival of therapy related myeloid neoplasm in United States.

Abstract Background Therapy related myeloid neoplasm (t-MN) is an emerging challenge in the current era. However, real world data on its incidence and survival at the population level remains sparse. Methods Using Surveillance Epidemiology and End Results (SEER-18) database, we identified patients aged ≥20 years with pathologically confirmed t-MN diagnosed between the years 2001–2014 and actively followed. Incidence rate per 100,000 population and incidence rate ratio (IRR) were calculated. Overall survival (OS) was calculated by Kaplan-Meier method with determinants analyzed by Cox proportional hazard regression method. Results A total of 1093 patients with a median age of 65 years were identified. Overall incidence of t-MN was 0.13 cases/100,000 population and showed significant variations with age, race and the period of diagnosis. Two year OS significantly declined with increasing age (51.3% in age group 20–39, 33.9% in age group 40–59, 19.3% in age group 60–79 and 0% in age ≥ 80, p Conclusions Incidence of t-MN has significantly increased in the last decade. Although OS at the population level is improving over time, outcomes of this disorder continue to remain poor, highlighting the need for novel therapies.
Impact of direct-acting antivirals and 12-week sustained viral response on clinical outcomes in patients with hepatitis C and hepatocellular carcinoma.

397Background: To investigate the impact of direct-acting antivirals (DAA) and 12-week sustained viral response (SVR12) in patients with hepatocellular carcinoma (HCC) and hepatitis C viral infecti...
Hepatitis induced by methyldopa (aldomet). Report of a case and a review of the literature.

We have reported a patient with methyldopa-induced hepatitis who was inadvertently challenged with the drug. The histopathology of the liver was indistinguishable from that of viral hepatitis. The experience with our patient and a review of the literature indicated rapid recovery in all cases when the drug was discontinued.
Continued Fractions and Quadratic Irrationals

Most books on number theory contain a chapter or two on continued fractions, which really are indispensable in a number of areas. Nevertheless, they have not achieved a mainstream popularity and are often omitted in courses on number theory. Of course there are reasons for this; their basic construction strikes one as rather bizarre and they are notoriously impossible to manipulate with respect to the usual operations of arithmetic. Furthermore, they have no satisfactory generalization to fit into a more comprehensive framework. But, they are surprising and interesting. One of the key roles played by continued fractions is in the construction of units in real quadratic fields. In studying this topic we have found that the entire theory of units in such fields can in fact be derived via continued fractions. Also, the periods of the continued fractions associated with quadratic irrationals exhibit a certain pattern or structure when classified by discriminant, which has not been previously noted.
Assessing the Emporium Model Through Student Performance and Persistence

The mathematics emporium model (MEM) was implemented to improve student success and retention rates. The college algebra course sequence was redesigned using the emporium model to establish consistency, emphasize active learning, modularize course materials, and provide one-on-one personalized on-demand assistance from faculty and teaching assistants. The emporium model ensured consistent content coverage and learning experiences, improved course coherence, and improved quality control. This study compared the course performance of students enrolled in a college algebra and trigonometry course using the MEM and traditional, lecture method. The results on whether the MEM or traditional students performed better were mixed. Also, the course effectiveness rates, which examines the successful performance of students enrolled in two successive courses that are associated such that the first course provides the foundation for the second, were similar for both the MEM and traditional methods.
On accounting’s twenty-first century challenge: evidence on the relation between intangible assets and audit fees

We inform the policy debate arising from the dramatic shift in US firms’ balance sheets towards intangible assets that has created a challenge for market participants to estimate firm value. While accounting guidelines have failed to keep pace with this change, the auditors’ perspective on this issue remains unknown. Our study reveals that auditors also find it relatively more challenging to audit firms with higher intangible assets. Specifically, we document a strong positive relation between audit fee and the proportion of intangible assets, after controlling for standard audit fee determinants. Further, we show that firms with higher proportion of intangible assets are associated with higher auditor effort and higher litigation risk for auditors, manifesting in higher audit fee. Ex post proxies of innovation success, such as patents, citation-weighted patents and ex ante R&D expense, indicate that firms with greater likelihood of innovation success are also charged higher audit fees. We find that high intangible asset firms in concentrated patent-generating industries (i.e. with lower expected patent litigation) are charged lower audit fees than similar firms in patent-competitive industries.
Looking to Other Professions to Advance the Health Care Ethics Consultant Certification Program.

We join Horner et al. (2020) in our commitment to the ongoing professionalization of the field of Clinical Ethics Consultation. As the field has long-recognized, a sound and sustainable process by ...
A Robust Method for Collecting X-ray Diffraction Data from Protein Crystals across Physiological Temperatures

Abstract Traditional X-ray diffraction data collected at cryo-temperatures have delivered invaluable insights into the three-dimensional structures of proteins, providing the backbone of structure-function studies. While cryo-cooling mitigates radiation damage, cryo-temperatures can alter protein conformational ensembles and solvent structure. Further, conformational ensembles underlie protein function and energetics, and recent advances in room-temperature X-ray crystallography have delivered conformational heterogeneity information that is directly related to biological function. The next challenge is to develop a robust and broadly applicable method to collect single-crystal X-ray diffraction data at and above room temperatures and was addressed herein. This approach provides complete diffraction datasets with total collection times as short as ~5 sec from single protein crystals, dramatically increasing the amount of data that can be collected within allocated synchrotron beam time. Its applicability was demonstrated by collecting 1.09-1.54 A resolution data over a temperature range of 293–363 K for proteinase K, thaumatin, and lysozyme crystals. Our analyses indicate that the diffraction data is of high-quality and do not suffer from excessive dehydration or damage.
Rapid Adaptation to Changing Mechanical Load by Ordered Recruitment of Identified Motor Neurons.

As they interact with their environment and encounter challenges, animals adjust their behavior on a moment-to-moment basis to maintain task fitness. This dynamic process of adaptive motor control occurs in the nervous system, but an understanding of the body’s biomechanics is essential to properly interpret the behavioral outcomes. To study how animals respond to changing task conditions, we used a model system in which the functional roles of identified neurons and the relevant biomechanics are well understood and can be studied in intact behaving animals: feeding in the marine mollusc Aplysia. We monitored the motor neuronal output of the feeding circuitry as intact animals fed on uniform food stimuli under unloaded and loaded conditions, and we measured the force of retraction during loaded swallows. We observed a previously undescribed pattern of force generation, which can be explained within the appropriate biomechanical context by the activity of just a few key, identified motor neurons. We show that, when encountering load, animals recruit identified retractor muscle motor neurons for longer and at higher frequency to increase retraction force duration. Our results identify a mode by which animals robustly adjust behavior to their environment which is experimentally tractable to further mechanistic investigation. Significance Statement Understanding adaptive motor control requires studying the brain and body together during behavior. Studying motor control systems at the level of individual neurons in intact animals is challenging. The Aplysia feeding system has individual neurons that can be identified from animal to animal and well-studied biomechanics. Prior work showed that animals respond adaptively to changing mechanical load, but did not measure or did not find strong neural correlates. As animals generate increasing force on food, we find that the increased activity and size-ordered recruitment of identified motor neurons allows animals to adapt their behavior. This is the first demonstration of a relationship between identified motor neurons and adaptive motor behavior in intact behaving Aplysia in response to changing mechanical load.
Getting to the Bottom of Noether's Theorem

We examine the assumptions behind Noether's theorem connecting symmetries and conservation laws. To compare classical and quantum versions of this theorem, we take an algebraic approach. In both classical and quantum mechanics, observables are naturally elements of a Jordan algebra, while generators of one-parameter groups of transformations are naturally elements of a Lie algebra. Noether's theorem holds whenever we can map observables to generators in such a way that each observable generates a one-parameter group that preserves itself. In ordinary complex quantum mechanics this mapping is multiplication by $\sqrt{-1}$. In the more general framework of unital JB-algebras, Alfsen and Shultz call such a mapping a "dynamical correspondence", and show its presence allows us to identify the unital JB-algebra with the self-adjoint part of a complex C*-algebra. However, to prove their result, they impose a second, more obscure, condition on the dynamical correspondence. We show this expresses a relation between quantum and statistical mechanics, closely connected to the principle that "inverse temperature is imaginary time".
Nonlinear Control of Gradient Dynamics with Shifted Passivity

A nonlinear control framework is developed for constrained gradient dynamics in real-time convex optimization. To counter the effect of the input constraints, an existing linear controller is augmented with an artificial nonlinearity such that the equilibrium conditions of the resulting closed loop are exactly the KKT optimality conditions for the corresponding optimization problem. Global asymptotic stability of the equilibrium is established from the shifted passivity property of the modified dynamics. The utility of the proposed control algorithm for neural circuit implementation is illustrated for quadratic programming.
Sample and Average Common-Mode Feedback in a 101 nW Acoustic Amplifier

We present a Sample and Average Feedback Resistor (SAFR) for accurate and programmable common-mode feedback in capacitively coupled low-power amplifiers. Using only switches, clocks, and capacitors, we reduce the variation across process and temperature by 4.4× and 226x, respectively, compared to a traditional pseudo-resistor implementation. The SAFR was implemented in a low-power audio LNA + PGA + ADC chain, achieving a resistance of 100 TΩ and HP corner programmability from 16 mHz to 4 Hz.
Solving N + m nonlinear equations with only m nonlinear variables

We derive a method for solvingN+m nonlinear algebraic equations inN+m unknownsy≠R m andz≠R N of the formA(y)z+b(y)=0, where the(N+m) × N matrixA(y) and vectorb(y) are continuously differentiable functions ofy alone. By exploiting properties of an orthonormal basis for null(A T (y)) the problem is reduced to solvingm nonlinear equations iny only. These equations are solved by Newton's method inm variables. Details of computational implementation and results are provided.
The Effects of Horizontal Merger Operating Efficiencies on Rivals, Customers, and Suppliers

We study how operating efficiencies in horizontal mergers affect market reactions of merging firmsâ€™ rivals, customers, and suppliers. We measure operating efficiency gains using projections disclosed by merging firmsâ€™ insiders. Higher efficiency gains are associated with lower announcement returns to merging firmsâ€™ rivals (due to increased equilibrium output of merging firms), higher returns to their customers (due to lower equilibrium price of merging firmsâ€™ output), and higher returns to their suppliers (due to the merged firmâ€™s higher equilibrium demand for inputs). Our results suggest that the pass-through of efficiency gains along merging firmsâ€™ supply chains is as important as the effects of post-merger changes in market power.
Classical pilot-wave dynamics: The free particle.

We present the results of a theoretical investigation into the dynamics of a vibrating particle propelled by its self-induced wave field. Inspired by the hydrodynamic pilot-wave system discovered by Yves Couder and Emmanuel Fort, the idealized pilot-wave system considered here consists of a particle guided by the slope of its quasi-monochromatic “pilot” wave, which encodes the history of the particle motion. We characterize this idealized pilot-wave system in terms of two dimensionless groups that prescribe the relative importance of particle inertia, drag and wave forcing. Prior work has delineated regimes in which self-propulsion of the free particle leads to steady or oscillatory rectilinear motion; it has further revealed parameter regimes in which the particle executes a stable circular orbit, confined by its pilot wave. We here report a number of new dynamical states in which the free particle executes self-induced wobbling and precessing orbital motion. We also explore the statistics of the chaotic regime arising when the time scale of the wave decay is long relative to that of particle motion and characterize the diffusive and rotational nature of the resultant particle dynamics. We thus present a detailed characterization of free-particle motion in this rich two-parameter family of dynamical systems.
Load-Aware Dynamic Time Synchronization in Parallel Discrete Event Simulation

Traditional Parallel Discrete Event Simulation (PDES) systems employ a monolithic approach for choosing their thread synchronization protocol. They either implement a Time Window-based conservative synchronization or an optimistic event processing capability based on the Time Warp synchronization. In this paper, we show that this binary choice is suboptimal and unnecessary, particularly in the realistic situation where the load distribution across the simulation domain changes over time. We thus propose a new PDES synchronization scheme, called Hybrid PDES, that dynamically switches between conservative and optimistic synchronization protocols based on the simulation run time characteristics. The primary objective of Hybrid PDES is to exploit the optimistic event processing as long as it is beneficial for the system performance and scalability. We implement Hybrid PDES in Python- and Lua-based Simian PDES engines and demonstrate up to 3X performance improvements on Intel Knights Landing and AMD EPYC processors based on the Phold, La-pdes and PPT-GPU simulation applications.
Microtubules, Myelin Sheaths, and Altered Behavior.

Mice are skttish creatures that innately hide from perceived threats by staying out of open areas, freezing to avoid predators, or hiding in dark spaces when an adverse stimulus is sensed. However, after inducing a global TPPP (tubulin polymerization promoting protein) gene knock-out (KO), which results in reduced myelin length and thickness (Fu et al., 2019), Nguyen et al. (2020) found that these natural behaviors become less pronounced (Fig. 1). They also report that fear conditioning is less effective in the Tppp KO mice, indicating that their ability to learn to fear a specific event is impaired. Fear impacts many brain circuits and is critical for survival, but the contribution of non-neuronal cells in fear circuits is not well understood. This work identifies a protein that influences both innate and learned fear via its role in microtubule nucleation in oligodendrocytes. Figure 1. A ) Normal branching and myelin sheath length in oligodendrocytes in WT mice is coupled with normal fear conditioning and innate fear responses. B ) Tppp KO results in highly branched oligodendrocytes with shorter, thinner myelin sheaths. These mice have dramatically reduced fear conditioning and innate fear responses. In the cell body of most cells, microtubules are nucleated from perinuclear centrosomes. These microtubule organizing centers (MTOCs) contain centrioles and a pericentriolar matrix containing g-tubulin ring complexes (γTURCs). γTURCs are the starting point for the initiation and subsequent polymerization of α/βtubulin dimers into cytoplasmic microtubules. Golgi outposts are a different type of MTOC that nucleate microtubules outside of the cell body in …
Kinetic model development for α-amino ester hydrolase (AEH)-catalyzed synthesis of β-lactam antibiotics

Abstract α-Amino ester hydrolases (AEH) are a class of enzymes highly specific for catalyzing the synthesis and hydrolysis of amides and esters of α-amino acids. They are particularly promising catalyst candidates as an alternative to penicillin G acylase (PGA) for synthesis of a variety of β-lactam antibiotics, including cephalexin, cefadroxil, amoxicillin, and ampicillin. In this study, X. campestris pv. campestris AEH and two previously established quadruple variants designed for enhanced stability (N186D/A275P/V622I/E143G termed QVG and N186D/A275P/V622I/E143H termed QVH) were characterized in terms of their kinetic properties. AEH appears to have highest substrate specificity for cephalosporins, particularly cephalexin. The optimum pH value for activity was found to be between pH 6.5 – 6.75 for synthesis of amoxicillin, cephalexin, and cefadroxil, while synthesis selectivity consistently increased with decreasing pH value. Evidence for substrate inhibition preventing the β-lactam nucleus from binding and forming the corresponding amide is discussed. Time-course kinetic data across a wide range of substrate concentrations was found to corroborate the presence of substrate inhibition, and five possible kinetic models are derived to explain AEH-catalyzed cephalexin synthesis kinetic profiles. A best fit model that incorporates both competitive substrate inhibition and partial substrate inhibition was selected based on the Akaike Information Criterion (AIC) and quality of fit at high substrate concentration. Finally, progress of the synthesis of beta-lactams in a single CSTR was simulated using the best fit kinetic model and a Pareto optimal front was constructed for fractional yield, productivity, and substrate conversion to evaluate potential reactor configurations.
Chimeric Antigen Receptor-T Cell Therapy in Adults with B-Cell Acute Lymphoblastic Leukemia: A Systematic Review.

ABSTRACT Chimeric antigen receptor T-cell (CAR-T) therapy has transformed treatment paradigms for relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) in children and younger adults. We performed a systematic review to investigate the published literature on efficacy and toxicity of CAR-T therapy in adults with r/r B-ALL. We searched MEDLINE, Embase and Cochrane Library for prospective, interventional studies and included published studies of ≥5 patients with median age at enrollment of ≥ 18 years. Risk of bias was assessed using a modified Institute of Health Economics tool. A total of 2566 records were assessed; 16 studies involving 489 patients were included in the final analysis. The mean CR rate was 81% and MRD negative remission rate was 81% at 4 weeks post CAR-T infusion. With median follow-up across studies of 24 months the cumulative 12-month probability of PFS and OS were 37% (95% CI 26-48%) and 57% (95% CI 49-65%), respectively. Relapse occurred in 40.3%; target antigen was retained in 73.2% of relapses. Across studies, any grade of CRS occurred in 82% (95% CI 61-95%) and grade 3 or higher CRS in 27% (95% CI 18-36%). Neurotoxicity of any grade occurred in 34% (95% CI 24-47%) and grade 3 or higher in 14% (95% CI 1-25%). In summary, CAR-T therapy achieves high early remission rates in adults with r/r B-ALL and represents a significant improvement over traditional salvage chemotherapy. Relapses are common and durable response remains a challenge.
AV Autotutorial Instruction: A Review of Evaluative Research.

INTRODUCTION Autotutorial (A-T) instruction using audio recordings was first proposed and developed in 1961 by Samuel N. Postlethwait at Purdue University, primarily to meet the challenge of teaching biology to large numbers of students (Postlethwait, Novak, & Murray, 1972). Since that time, the method has been adapted to many different subject areas, class sizes, and institutions. Two brief reviews of the research aimed at measuring the effectiveness of A-T instruction have appeared. One is an unpublished report by Hinton (1970) containing largely impressionistic evaluations of autotutorial teaching in the California Community Colleges. The other is a recent paper by Mintzes (1975) reviewing 20 studies.
The effect of palmityl coenzyme A on pigeon liver fatty acid synthetase.

Abstract Because of the rather widespread interest in palmityl coenzyme A as a possible physiological inhibitor of a large number of enzymes, we have further investigated the inhibition of pigeon liver fatty acid synthetase by palmityl-CoA initially reported in 1958 by Porter and Long (1). The inhibition of the fatty acid synthetase is dependent on the presence of a critical mixed micellar concentration of palmityl-CoA and, more importantly, on the molar ratio of the CoA ester to protein. The molar ratio requirement eliminates the possibility of a site-specific inhibition of the fatty acid synthetase. It is concluded, rather, that palmityl-CoA inhibits this enzyme by virtue of its detergent nature. In support of this conclusion, data are reported which show that sodium lauryl sulfate, another strong detergent, acts in a similar way on the fatty acid synthetase. It is suggested, from the above results, that the inhibiting effect of palmityl-CoA on a number of enzymes reported in the literature may be solely or largely attributed to its detergent action. However, examination of these enzymes with respect to a possible molar ratio requirement for palmityl-CoA inhibition will be necessary before a final conclusion can be drawn.
Localized deformation and fracture due to low velocity particulate erosion of ductile metals by spherical particulates

ABSTRACT A simple cumulative damage model has been developed for the low velocity, normal incidence erosion of ductile metals by spherical particles. The model correlates the computed plastic strain distribution for different impact velocities and materials with the experimentally measured erosion rates. This paper describes the surface and sub-surface changes which occur in Cu and Cu-6wt%Al specimens during erosion testing. Scanning and transmission electron microscopy have been used to study these changes. The object of this study was to determine whether the deformed microstructures are consistent with the predictions of the model. Because the deformation due to the impact of a 50um diameter spherical particle occurs at high strain rates (106s-l) and is also highly localized, the deformation mechanisms differ slightly from bulk deformation which has been reported for low strain rates. The contribution of strain localization (adiabatic shear) and twinning will be discussed in light of the microstructural observations.
Amenorrhea in patients with Hodgkin's disease treated with antineoplastic agents

Abstract Ten young female patients with Hodgkin's disease who were treated with antineoplastic agents in an Oncology Clinic developed amenorrhea or marked oligomenorrhea shortly after treatment was begun. In 6 patients high levels of FSH and LH in blood showed the amenorrhea to be the result of primary ovarian failure. In at least 2 of the patients, ovarian function was maintained, despite the menstrual abnormalities and one of them became pregnant during treatment. Morphologic study of the ovaries of two of the patients showed a complete disappearance of oocytes. The mechanism of destruction of resting oocytes by antineoplastic agents is discussed.
Ribonucleotide Reductase Activity of Synchronized KB Cells Infected with Herpes Simplex Virus

The replication of herpes simplex virus (HSV) is unimpeded in KB cells which have been blocked in their capacity to synthesize deoxyribonucleic acid (DNA) by high levels of thymidine (TdR). Studies showed that the presence of excess TdR did not prevent host or viral DNA replication in HSV-infected cells. In fact, more cellular DNA was synthesized in infected TdR-blocked cells than in uninfected TdR-blocked cells. This implies that the event which relieved the TdR block was not specific for viral DNA synthesis but allowed some cellular DNA synthesis to occur. These results suggested that HSV has a means to insure a pool of deoxycytidylate derivatives for DNA replication in the presence of excess TdR. We postulated that a viral-induced ribonucleotide reductase was present in the cell after infection which was not inhibited by thymidine triphosphate (TTP). Accordingly, comparable studies of the ribonucleotide reductase found in infected and uninfected KB cells were made. We established conditions that would permit the study of viral-induced enzymes in logarithmically growing KB cells. A twofold stimulation in reductase activity was observed by 3 hr after HSV-infection. Reductase activity in extracts taken from infected cells was less sensitive to inhibition by exogenous (TTP) than the enzyme activity present in uninfected cells. In fact, the enzyme extracted from infected cells functioned at 60% capacity even in the presence of 2 mm TTP. These results support the idea that a viral-induced ribonucleotide reductase is present after HSV infection of KB cells and that this enzyme is relatively insensitive to inhibition by exogenous TTP.
Nowoczesność i utrata

The following text is a translation of fragment of Jonathan Flatley’s book Affective Mapping Melancholia and the Politics of Modernism. The suprising claim of Affective Mapping is that dwelling on loss and melancholia is not necessarily depressing. Flatley argues that melancholy can lead people and writers to productively re-map their relationship to the world. Modernism is an accurate portrait of these processes and related consequences.
ASIS&T annual meeting pre-conference activities: Information behavior on the move: 2013 ASIS&T SIG/USE research symposium

EDITOR'S SUMMARY The 13th Annual SIG/USE Research Symposium focused on ways mobile technologies have influenced information needs, seeking and use. In her keynote address, Caroline Haythornthwaite framed movement as changing contributorship, interactions and participation in multiple knowledge communities. A series of Ignite talks on the common theme of mobility followed, with topics ranging from mobile phones as the preferred Internet access device, credibility of mobile applications and online resources and public libraries' use of social media and mobile applications to mobile apps promoting health information literacy and supporting teleworking. Small groups brainstormed on opportunities, challenges and research ideas inspired by the theme. Annual SIG/USE awards recognized scholars for innovative work on topics including refugees' information seeking, factors influencing scholars' data sharing and drawings as visual representations of information. The symposium closed with encouragement to consider how information on the move influences perspectives and research into information behavior.
Activation of a flavoprotein by proteolysis.

Abstract Chymotryptic digestion of brain pyridoxine-5-P oxidase brings about a 4-fold enhancement of the catalytic power (Vmax/KM) using pyridoxine-5-P as substrate in the assay mixtures. The chymotrypsin-treated enzyme is less susceptible to inhibition by pyridoxal-5-P than the native enzyme. Fragments arising from limited proteolysis were separated by affinity chromatography using P-pyridoxal-Sepharose as supporting matrix. Catalytically active fractions, eluted by pyridoxine-5-P (5mM), displayed three bands when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The molecular masses of the three protein bands are considerably lower than 28 kDa, the molecular mass of monomeric pyridoxine-5-P oxidase. Spectroscopic studies, absorption, fluorescence, and circular dichroism revealed that the microenvironment surrounding the cofactor flavin mononucleotide is not perturbed by limited proteolysis.
Application of Adomian Decomposition for multi-machine power system simulation

In this paper, the merits of Adomian Decomposition Method (ADM) have been investigated for the time domain simulation of multi-machine power systems. ADM is an analytical approximation method for the solution of linear, nonlinear, deterministic and stochastic operator equations. It approximates the nonlinearities in the equations using Adomian polynomial series and that can form a rapidly convergent sequence of analytic functions. We apply the ADM approach for simulation of differential algebraic equations representing the detailed multi-machine power system. The ADM approach has been applied on the widely used IEEE 3 generator 9 bus system and IEEE 10 generator 39 bus system for 3 - ϕ fault simulations. In our simulations we found that the ADM approach is faster than the standard trapezoidal time integration method for the comparable accuracy.
Substitution Reactions Which Proceed via Radical Anion Intermediates

A new type of substition process at a saturated carbon atom is described. These reactions, which proceed via a chain sequence in which radical anions and free radicals are intermediates, are noteworthy for providing novel and powerful means of synthesis: they occur readily under mild conditions, they give excellent yields of pure products, and, in contrast to SN2 displacements, they are rather insensitive to steric hindrance. As a consequence, radical anion processes are especially valuable for the preparation of highly branched structures. Many inorganic and organic anions readily enter into these displacements and, indeed, amines are also effective. Systems which undergo substitutions via this electron transfer mechanism include benzylic, cumylic, strictly aliphatic, and heterocyclic molecules. It is of interest that a number of groups which do not behave as leaving groups in SN2 displacements are readily displaced at room temperature from a satureted carbon atom via the radical anion-free radical pathway, e.g., nitro, azide, sulfone, and ether groups.
Analysis of Thermal Diodes Enabled by Junctions of Phase Change Materials

Materials designed to undergo a phase transition at a prescribed temperature have been advanced as elements for controlling thermal flux. Such phase change materials can be used as components of reversible thermal diodes, or materials that favor heat flux in a preferred direction; however, a thorough mathematical analysis of such diodes is thus far absent from the literature. Herein, it is shown mathematically that the interface of a phase change material with a phase invariant one can function as a simple thermal diode. Design equations are derived for such phase change diodes, solving for the limits where the transition temperature falls within or outside of the temperature gradient across the device. Criteria are derived analytically for the choice of thermal conductivity of the invariant phase to maximize the rectification ratio. Finally, the model is applied to several experimental systems in the literature, providing bounds on observed performance. This model should aid in the development of materials capable of controlling heat flux.
Early-Reply Components: Concurrent Execution with Sequential Reasoning

Generic software components have a reputation for being inefficient. Parallel implementations may improve performance, but can thwart reuse by being architecture-dependent or by exposing concurrency to client-side reasoning about component interactions. To address performance, we present Early-Reply as an alternative to blocking method invocations. Component operations can be partitioned into a material computation required to satisfy the postcondition, and a residual computation required to re?stablish the component invariant, optimize its representation, etc. Early-Reply exploits opportunities for parallelism by forwarding final parameter values to the caller as soon as the material computation completes, thereby offloading the residual computation to execute in parallel with subsequent client activities. Proof obligations for Early-Reply support a synchronous calling model, so clients can still reason sequentially about component behavior. Also, since Early-Reply components do not depend on system-wide support for component synchronization, they can be deployed incrementally. Finally, Early-Reply can improve the response time of idle components by orders of magnitude; when composed hierarchically, performance benefits are magnified by the potential fan-out of concurrently executing components.
On the Implementation of Reduced Gradient methods

Until now, the implementation of reduced gradient methods had to be improvised empirically, since procedures for the truncation of the inner iterations, in the feasibility restoration stage, have not been analyzed with respect to convergence of the overall algorithm. This paper presents an implementation of one reduced gradient method. While retaining all the attractive features of the classical reduced gradient methods, this implementation incorporates, explicitly, efficient procedures for truncating the inner iterations to a finite number. In the paper, we present the properties of the restoration subalgorithm and we prove the convergence of the new algorithm under fairly general assumptions.
Role of respiratory infection in onset of asthma and chronic obstructive pulmonary disease

There is renewed interest in the possible role of events occurring during early life in determining predisposition to asthma and allergies. Among these events, respiratory illnesses associated with viral infections have been the matter of considerable research interest. There is now evidence suggesting that an immune response to viral infection in early life that is skewed toward an IgE- or an eosinophil-mediated slant is predictive of persistent wheezing symptoms up to the age of 6 years. Genetic and environmental factors (specifically bacterial infection burden) may be important determinants of the maturation of immune responses from a default ‘Th-2-like’ at birth to mature, non-Th-2-like responses. Homing of Th-2-like responses to the lung may be determined in part by inheritance of bronchial hyperresponsiveness, and in part by the progressive nature of chronic, uncontrolled airway inflammation. The main risk factor for the development of wheezing episodes in children who are not predisposed to allergic asthma is diminished airway function, which can also be detected shortly after birth. These children may stop wheezing later during childhood, but their levels of lung function track with age. It is tempting to speculate that chronic obstructive pulmonary disease may occur more frequently in these children.
Saying Meritocracy and Doing Privilege

This article describes the relationship between saying and doing. It argues that focusing on the discrepancy between participants' accounts and their actions is one of the greatest analytical stren...
Dietary calcium modulates Mycobacterium paratuberculosis infection in beige mice

A 6-month study was conducted to evaluate the effects of feeding different levels of dietary calcium (Ca) on the persistence of Mycobacterium paratuberculosis infection using a mouse model. Beige mice, averaging 8 weeks of age, were randomly assigned to one of the following dietary treatments: 1) 0.02% Ca, 2) 0.15% Ca, 3) 0.45% Ca, and 4) 1.0% Ca. Mice were infected intraperitoneally with 10(8) CFU viable M. paratuberculosis for 1, 3, and 6 month periods. Plasma Ca levels was unaffected by dietary Ca (x = 7.3 mg/dl). Plasma levels of 1,25(OH)2D3 was elevated significantly in 0.02% and 0.15% Ca groups compared to other treatments at the end of each period, with the highest levels observed for 0.02% Ca mice and intermediate values for 0.15% Ca mice. One month after infection, numbers of viable M. paratuberculosis cultured from the spleen were significantly reduced for 0.15% Ca mice, whereas the number of bacteria isolated from the liver and mesenteric lymph node (MLN) were higher for the 0.02% Ca group. There were no differences in bacterial numbers in the ileum although they tended to be higher for the 0.02% Ca group. Three months after infection, bacterial numbers in the spleen, ileum, and MLN did not differ across treatments, however, significantly lower numbers were found in the liver of 1.0% Ca mice. Reduced bacterial counts were also observed in the liver of 0.15%. 0.45%, and 1.0% Ca mice after a 6-month infection period compared to the 0.02% Ca group, with the lowest numbers isolated from the 1.0% Ca mice. Numbers of viable bacteria cultured from the ileum and MLN after 6 months of infection were also significantly reduced in 1.0% Ca mice. These results suggest that Ca metabolism is an important modulator of M. paratuberculosis infection.
Effects of temperature acclimation on the expression of hepatic cytochrome P4501A mRNA and protein in the fish Fundulus heteroclitus

Abstract Previous studies showed that hydrocarbon induction of hepatic microsomal monooxygenase activity is attenuated in the teleost fish Fundulus heteroclitus acclimated to low temperature. The basis of that attenuation, and the effects of temperature on monooxygenase activity, were examined by analyzing liver cytochrome P4501A (CYP1 A) mRNA, protein, and catalytic activity in control and β-naphthoflavone (BNF)-treated F. heteroclitus acclimated to 6 or 16 °C. There were no temperature-related differences in total P450 content, NADPH-cytochrome c (P450) reductase activity, ethoxyresorufin O -deethylase (EROD) activity, or immunoquantified CYP1A content in hepatic microsomes of untreated fish. Fish acclimated to 16 °C and given a single intraperitoneal injection of BNF exhibited a rapid rise and fall in CYP1A mRNA content and an induction of EROD activity and CYP1A protein that was undiminished over 7 days. Similarly treated fish acclimated at 6 °C showed an increase in CYP1A mRNA content greater than that in 16 °C fish, but with no significant increase in EROD activity or CYP1A content over 7 days. Examined over a longer term, microsomal EROD activity was significantly induced by BNF in fish at both temperatures; activity peaked at 5–7 days in 16 °C fish, while in 6 °C fish the activity continued to rise slowly over 25 days. However, the greatest activity reached in 6 °C fish (0.68 nmol/min/ mg) was less than half that seen in the warmer animals (1.46 nmol/min/mg). Immunodetectable CYP1A content showed the same trend as EROD activity, and the turnover number (nmol product formed/min/nmol CYP1A) for EROD activity was about the same in all groups, indicating that concentration of the catalyst alone could account for the different patterns of microsomal activity. CYP1A mRNA content was again induced to a similar degree by BNF in both the 6 and the 16 °C fish; the apparent half-life of the mRNA was substantially longer in cold-acclimated than in warm-acclimated BNF-treated fish. Comparing the levels of CYP1A mRNA and protein at the two acclimation temperatures following BNF treatment indicates that translational activity, rather than transcriptional activity, is the sensitive point in the effect of temperature on CYP1A induction in these fish.
Solvation and Aggregation of N,N′-Dialkylimidazolium Ionic Liquids: A Multinuclear NMR Spectroscopy and Molecular Dynamics Simulation Study

The solvation and aggregation of the ionic liquid (IL) 1-n-butyl-3-methylimidazolium chloride ([C4mim]Cl) in water and dimethylsulfoxide (DMSO) were examined by analysis of (1)H and (35/37)Cl chemical shift perturbations and molecular dynamics (MD) simulations. Evidence of aggregation of the IL n-butyl chains in aqueous environments at IL concentrations of 75-80 wt% was observed both in the NMR experiments and in the MD simulations. The studies also show that [C4mim]Cl behaves as a typical electrolyte in water, with both ions completely solvated at low concentrations. On the other hand, the data reveal that the interactions between the [C4mim](+) and Cl(-) ions strengthen as the DMSO content of the solutions increases, and IL-rich clusters persist in this solvent even at concentrations below 10 wt%. These results provide an experimentally supported atomistic explanation of the effects that these two solvents have on some of the macroscopic properties of [C4mim]Cl. The implications that these findings could have on the design of IL-based solvent systems are briefly discussed.
Not so selective serotonin reuptake inhibitors.

Venlafaxine norepinephrine reuptake dopamine reuptake BRAINSTORMS is a monthly section of The Journal of Clinical Psychiatry aimed at providing updates of novel concepts emerging from the neurosciences that have relevance to the practicing psychiatrist. From the Clinical Neuroscience Research Center in San Diego and the Department of Psychiatry at the University of California San Diego. Reprint requests to: Stephen M. Stahl, M.D., Ph.D., Editor, BRAINSTORMS, 8899 University Center Lane, Suite 130, San Diego, CA 92122. Not So Selective Serotonin Reuptake Inhibitors
Misapplications Reviews: Mea Culpa

An essay in authors' “mea culpa” style about airline safety and about marketing in a grocery by using coupons.
A Lagged Warm Event–Like Response to Peaks in Solar Forcing in the Pacific Region

Abstract The forced response coincident with peaks in the 11-yr decadal solar oscillation (DSO) has been shown to resemble a cold event or La Nina–like pattern during December–February (DJF) in the Pacific region in observations and two global coupled climate models. Previous studies with filtered observational and model data have indicated that there could be a lagged warm event or El Nino–like response following the peaks in the DSO forcing by a few years. Here, observations and two climate model simulations are examined, and it is shown that dynamical coupled processes initiated by the response in the tropical Pacific to peaks in solar forcing produce wind-forced ocean Rossby waves near 5°N and 5°S. These reflect off the western boundary, producing downwelling equatorial Kelvin waves that contribute to transitioning the tropical Pacific to a warm event or El Nino–like pattern that lags the peaks in solar forcing by a few years.
Why Heidegger wasn't shocked by the holocaust: Philosophy and its defense system

Apres avoir soutenu que les communautes philosophiques ne peuvent entendre ce qui les remettrait trop en question, l'A. explique la position retranchee de Heidegger sur l'holocauste nazi. Il montre que cette devastation humaine etait, pour lui, la consequence logique de la technologisation du monde, comme en temoignent deux courts textes dont un inedit
The effect of angular momentum on the unimolecular dissociation HCO→H+CO

Full dimensional wave packet calculations are performed to model the unimolecular dissociation HCO→H+CO on its ground electronic state. Results of calculations up to total (nuclear) angular momentum J=10 are reported. Most of our results are based on the recent potential surface of Werner, Keller, Schinke, and co-workers, although some comparative results with the earlier surface of Bowman, Bittman, and Harding are also presented. We focus on certain unimolecular resonances, and determine their positions, widths, and associated CO product distributions. We find good agreement with the available experimental results of Neyer et al. We also consider how rotation affects a group of states associated with the 2:1 stretch/bend resonance. Bowman’s adiabatic rotation model is found to provide a reasonable description of our results, and is also a useful tool for analysis.
Rural/Urban Differences in Child Growth and Survival in Bolivia

Using data from a national survey in Bolivia and from a regional sample of poor communities in two regions of Bolivia we model the effects of community conditions household characteristics and social relations on child health as measured by child mortality and stunted growth. Based on national data children in rural areas are twice as likely to die before the age of two than are children in large cities and about one-third of the children in rural areas are stunted. Including measures of community household and maternal characteristics accounts for at least two-thirds of the urban/rural difference in child health. We conclude that expansion of health services improvements in household and community sanitation and socioeconomic development are all needed to overcome the rural disadvantage in child health. (authors)