cssi/SciSciGPT-SciSciNet huggingface dataset:
Evidence That Antibiotics Bind to Human Mitochondrial Ribosomal RNA Has Implications for Aminoglycoside Toxicity

Aminoglycosides are a well known antibiotic family used to treat bacterial infections in humans and animals, but which can be toxic. By binding to the decoding site of helix44 of the small subunit RNA of the bacterial ribosome, the aminoglycoside antibiotics inhibit protein synthesis, cause misreading, or obstruct peptidyl-tRNA translocation. Although aminoglycosides bind helix69 of the bacterial large subunit RNA as well, little is known about their interaction with the homologous human helix69. To probe the role this binding event plays in toxicity, changes to thermal stability, base stacking, and conformation upon aminoglycoside binding to the human cytoplasmic helix69 were compared with those of the human mitochondrial and Escherichia coli helix69. Surprisingly, binding of gentamicin and kanamycin A to the chemically synthesized terminal hairpins of the human cytoplasmic, human mitochondrial, and E. coli helix69 revealed similar dissociation constants (1.3–1.7 and 4.0–5.4 μm, respectively). In addition, aminoglycoside binding enhanced conformational stability of the human mitochondrial helix69 by increasing base stacking. Proton one-dimensional and two-dimensional NMR suggested significant and specific conformational changes of human mitochondrial and E. coli helix69 upon aminoglycoside binding, as compared with human cytoplasmic helix69. The conformational changes and similar aminoglycoside binding affinities observed for human mitochondrial helix69 and E. coli helix69, as well as the increase in structural stability shown for the former, suggest that this binding event is important to understanding aminoglycoside toxicity.
Induction of Adult Neurogenesis

: Over most of the past century, it was thought that the adult brain was completely incapable of generating new neurons. However, in the last decade, the development of new techniques has resulted in an explosion of new research showing that (i) neurogenesis, the birth of new neurons, is not restricted to embryonic development, but normally also occurs in two limited regions of the adult mammalian brain (the olfactory bulb and the dentate gyrus of the hippocampus); (ii) that there are significant numbers of multipotent neural precursors in many parts of the adult mammalian brain; and (iii) that it is possible to induce neurogenesis even in regions of the adult mammalian brain, like the neocortex, where it does not normally occur, via manipulation of endogenous multipotent precursors in situ. In the neocortex, recruitment of small numbers of new neurons can be induced in a region-specific, layer-specific, and neuronal type-specific manner, and newly recruited neurons can form long-distance connections to appropriate targets. This suggests that elucidation of the relevant molecular controls over adult neurogenesis from endogenous neural precursors/stem cells may allow the development of neuronal replacement therapies for neurodegenerative disease and other central nervous system injuries that may not require transplantation of exogenous cells.
Method for Characterizing Nanoscale Wear of Atomic Force Microscope Tips

Atomic force microscopy (AFM) is a powerful tool for studying tribology (adhesion, friction, and lubrication) at the nanoscale and is emerging as a critical tool for nanomanufacturing. However, nanoscale wear is a key limitation of conventional AFM probes that are made of silicon and silicon nitride (SiNx). Here we present a method for systematically quantifying tip wear, which consists of sequential contact-mode AFM scans on ultrananocrystalline diamond surfaces with intermittent measurements of the tip properties using blind reconstruction, adhesion force measurements, and transmission electron microscopy (TEM). We demonstrate direct measurement of volume loss over the wear test and agreement between blind reconstruction and TEM imaging. The geometries of various types of tips were monitored over a scanning distance of approximately 100 mm. The results show multiple failure mechanisms for different materials, including nanoscale fracture of a monolithic Si tip upon initial engagement with the surface, film failure of a SiNx-coated Si tip, and gradual, progressive wear of monolithic SiNx tips consistent with atom-by-atom attrition. Overall, the method provides a quantitative and systematic process for examining tip degradation and nanoscale wear, and the experimental results illustrate the multiple mechanisms that may lead to tip failure.
Using the Aberrant Behavior Checklist to Assess Problem Behavior in Older Individuals

ABSTRACT The Aberrant Behavior Checklist-Community (ABC-C) was administered to four groups of older individuals (mean age = 79.35 years): those with (a) dual diagnosis of mental retardation and mental illness (n = 35); (b) mental illness only (n = 59); (c) mental retardation only (n = 20); and (d) neither mental retardation nor mental illness (n = 58). Individuals with dual diagnosis were rated significantly higher, suggesting more psychopathology, than those in the other three groups which did not differ from one another. Compared to individuals not receiving psychotropic medication, those on medication had consistently higher ratings. Younger individuals tended to be rated higher than older ones. Men were rated higher than women but only on the Hyperactivity/Noncompliance scale. There were no significant interaction effects on any of the analyses. The Lethargy/ Social Withdrawal scale was the least discriminating of the five scales with this population of older individuals. The data are consistent with ...
The effect of electron carriers and other ligands on oxygen stability of clostridial hydrogenase

The effects of various electron carriers, a substrate (H2) and a reversible inhibitor (CO) on the rate of irreversible oxygen inactivation of clostridial hydrogenase (ferredoxin: H+ oxidoreductase, EC 1.18.3.1) have been studied kinetically. Some electron carriers (e.g., clostridial ferredoxin and methyl viologen) greatly stabilize the enzyme, some (FAD, FMN) drastically reduce its stability, while others (benzyl viologen and methylene blue) only slightly alter the stability. Competitive experiments indicate that stabilizers and destabilizers do not compete with each other for binding with the active center of hydrogenase. Hydrogen and CO do not affect the rate of the oxygen inactivation. On the basis of the results obtained herein and kinetic data on hydrogenase catalysis from the literature, it is concluded that the active center of this hydrogenase comprises at least three different independent subsites. The first one (presumably an iron atom of the iron-sulfur cluster) binds H2 and CO and does not contribute to the oxygen stability. The second one binds stabilizers like methyl viologen while the third one binds destabilizers like FMN and FAD.
A kinetic study of the hydrolysis of the N-tosylalanine ester of 3-hydroxy-5-phenylpyrrole and related compounds by human leukocyte elastase.

Abstract The tosylalanine ester of 3-hydroxy-5-phenylpyrrole (HOPPy) is localized on reagent strips (Ames LEUKOSTIX) and used diagnostically to test urine for the presence of human leukocyte elastase (HLE) as an indication of urinary tract infection. We have determined the kinetic constants for the HLE-catalyzed hydrolysis of this substrate and the related substrates Tos-Ala-ONp, Cbz-Ala-OPPy, and Cbz-Ala-ONp, in solution at three different pH values. In the reagent strip matrix, diazo coupling of 4-diazo-3-hydroxy-1-napthylsulfonate[formula]with the enzymatic hydrolysis product HOPPy generates a purple color. We have also studied the kinetics of the reaction of HOPPy with[formula]and other related diazonium salts such as 4-diazo-3-hydroxy-7-nitro-1-napthylsulfonate, 4-diazo-3-hydroxy-1,7-napthyldisulfonate, and 2-methoxy-4-( N -morpholinyl)benzene diazonium chloride. Tos-Ala-OPPy is the most reactive substrate among the compounds examined and kinetic studies indicate that deacylation is rate-limiting for HLE hydrolysis. The presence of decanol accelerates the enzymatic hydrolysis of Tos-Ala-OPPy with a k cat / K M = 10 7 M −1 s −1 , which is close to the diffusion-controlled limit. For the diazo coupling reaction, the rate is affected by the substituents on the naphthalene ring and by the buffer in which the reaction occurs. This research has elucidated some important mechanistic features for the reaction of these compounds and may lead to improved methods for the detection of leukocyte elastase.
Acute and subacute toxicity of cytochalasin E in the rat.

Abstract Cytochalasin E, a minor toxic metabolite of the fungus Aspergillus clavatus, is acutely toxic to rats, mice, and guineapigs. The LD50 values for a single ip administration of cytochalasin E were: 1-day-old rats, 0.98 mg/kg; adolescent rats, 2.60 mg/kg; mice, 4.60 mg/kg, and guinea-pigs, 0.5–1.5 mg/kg. The toxicity of cytochalasin E was reduced in adolescent rats when administered orally (LD50 9.10 mg/kg) and was increased when administered by the intrathoracic route (LD50 1.30 mg/kg). Rats receiving a fatal ip dose of cytochalasin E died within 2–18 hr with 2–3 ml fluid in the peritoneal cavity. Intrathoracic administration of cytochalasin E killed rats within 2–8 hr and resulted in accumulation of 2.5–3.5 ml pleural fluid. Rats receiving the toxin orally died within 4–18 hr with 1.0–1.5 ml gastric fluid. Histopathologic examination revealed congestive degenerative changes, necrosis of liver, kidney, spleen, pancreas, and small intestine, brain edema, pulmonary hemorrhages, and injury to vascular walls.
Sustained generation of electricity by the spore-forming, Gram-positive, Desulfitobacterium hafniense strain DCB2

Desulfitobacterium hafniense strain DCB2 generates electricity in microbial fuel cells (MFCs) when humic acids or the humate analog anthraquinone-2,6-disulfonate (AQDS) is added as an electron-carrying mediator. When utilizing formate as fuel, the Gram-positive, spore-forming bacterium generated up to 400 mW/m2 of cathode surface area in a single-chamber MFC with a platinum-containing air-fed cathode. Hydrogen, lactate, pyruvate, and ethanol supported electricity generation, but acetate, propionate, and butyrate did not. Scanning electron microscopy indicated that strain DCB2 colonized the surface of a current-generating anode but not of an unconnected electrode. The electricity was recovered fully within minutes after the exchange of the medium in the anode chamber and within a week after an exposure of a colonized anode to 90°C for 20 min. Of the six strains of Desulfitobacteria tested, all of which would reduce AQDS, only D. hafniense strain DCB2 continued to reduce AQDS and generate electricity for more than 24 h, indicating that reduction of the humate analog alone is insufficient to sustain electrode reduction.
Performance functions and reinforcement learning for trading systems and portfolios

We propose to train trading systems and portfolios by optimizing objective functions that directly measure trading and investment performance. Rather than basing a trading system on forecasts or training via a supervised learning algorithm using labelled trading data, we train our systems using recurrent reinforcement learning (RRL) algorithms. The performance functions that we consider for reinforcement learning are profit or wealth, economic utility, the Sharpe ratio and our proposed differential Sharpe ratio. The trading and portfolio management systems require prior decisions as input in order to properly take into account the effects of transactions costs, market impact, and taxes. This temporal dependence on system state requires the use of reinforcement versions of standard recurrent learning algorithms. We present empirical results in controlled experiments that demonstrate the efficacy of some of our methods for optimizing trading systems and portfolios. For a long/short trader, we find that maximizing the differential Sharpe ratio yields more consistent results than maximizing profits, and that both methods outperform a trading system based on forecasts that minimize MSE. We find that portfolio traders trained to maximize the differential Sharpe ratio achieve better risk-adjusted returns than those trained to maximize profit. Finally, we provide simulation results for an S&P 500/TBill asset allocation system that demonstrate the presence of out-of-sample predictability in the monthly S&P 500 stock index for the 25 year period 1970 through 1994. Copyright © 1998 John Wiley & Sons, Ltd.
Influence of extreme hypercapnia on respiratory motor nerve activity in cats

Sedative drugs have been found to depress the respiratory activity of upper airway muscles more than that of the diaphragm. To determine whether CO2 at narcotic levels has a similar action, we recorded phrenic and hypoglossal nerve activities in decerebrate, vagotomized, paralyzed cats. T5 or T6 external intercostal nerve activity was also recorded in some animals. End-tidal CO2 concentration was raised progressively to over 30% or until depression of nerve activity was apparent. Respiratory frequency was reduced by severe hypercapnia in most cats. Hypoglossal nerve activity was consistently decreased more than that of the phrenic nerve. In most cases intercostal nerve activity was also more susceptible than phrenic nerve activity to hypercapnic depression. The results indicate that CO2 at narcotic levels interferes both with the central pattern generator for breathing movements and with the expression of the pattern in specific motor nerves.
Cholecystokinin-8-like-immunoreactive fibers in rat lumbosacral autonomic regions are sexually dimorphic and altered by a reduction of androgen receptors.

Abstract Cholecystokinin-8-like-immunoreactive (CCK-8-LI) fibers in laminae VII and X of the rat lumbosacral spinal cord demarcate the position of preganglionic autonomic neurons. This investigation reveals that adult male Sprague-Dawley, or King-Holtzman/Sprague-Dawley rats contain more CCK-8-LI fibers in lumbosacral laminae VII and X than adult females. Furthermore, testicular feminization mutation male rats (which lack 85–90% of their functional androgen receptors) contain fewer CCK-8-LI fibers than normal male or female rats, with the amount of CCK-8-LI being reduced to a greater extent in the sympathetic vs. the parasympathetic regions of the lumbosacral spinal cord. Thus, CCK-8-LI in testicular feminization mutation male rats has a distinctly female-like pattern. These results suggest that testosterone is a regulatory factor for CCK-8-LI fibers found in laminae VII and X of the lumbosacral spinal cord. Sexual dimorphism in lumbosacral CCK-8-LI fibers may contribute to modulating the final common pathway which differentially regulates the reproductive organs and stereotypic reproductive behavior, and may be involved with the sex differences described for pain.
Shock, Post-Shock Annealing, and Post-Annealing Shock in Ureilites

The thermal and shock histories of ureilites can be divided into four periods: 1) formation, 2) initial shock, 3) post-shock annealing, and 4) post-annealing shock. Period 1 occurred approx.4.55 Ga ago when ureilites formed by melting chondritic material. Impact events during period 2 caused silicate darkening, undulose to mosaic extinction in olivines, and the formation of diamond, lonsdaleite, and chaoite from indigenous carbonaceous material. Alkali-rich fine-grained silicates may have been introduced by impact injection into ureilites during this period. About 57% of the ureilites were unchanged after period 2. During period 3 events, impact-induced annealing caused previously mosaicized olivine grains to become aggregates of small unstrained crystals. Some ureilites experienced reduction as FeO at the edges of olivine grains reacted with C from the matrix. Annealing may also be responsible for coarsening of graphite in a few ureilites, forming euhedral-appearing, idioblastic crystals. Orthopyroxene in Meteorite Hills (MET) 78008 may have formed from pigeonite by annealing during this period. The Rb-Sr internal isochron age of approx.4.0 Ga for MET 78008 probably dates the annealing event. At this late date, impacts are the only viable heat source. About 36% of ureilites experienced period 3 events, but remained unchanged afterwards. During period 4, approx.7% of the ureilites were shocked again, as is evident in the polymict breccia, Elephant Moraine (EET) 83309. This rock contains annealed mosaicized olivine aggregates composed of small individual olivine crystals that exhibit undulose extinction. Ureilites may have formed by impact-melting chondritic material on a primitive body with heterogeneous O isotopes. Plagioclase was preferentially lost from the system due to its low impedance to shock compression. Brief melting and rapid burial minimized the escape of planetary-type noble gases from the ureilitic melts. Incomplete separation of metal from silicates during impact melting left ureilites with relatively high concentrations of trace siderophile elements.
TAU 2015 Contest on Incremental Timing Analysis: Incremental Timing and CPPR Analysis

Among timing analysis applications, timing-driven operations are imperative for the success of optimization flows, such as placement, routing, logic synthesis, and physical synthesis. Optimization transforms change the design, and therefore have the potential to significantly affect timing information. As such, timing must be kept current to ensure slack integrity and timing closure. For reasonable turnaround and performance, the timer should incrementally update the affected portion of the design.The aim of the TAU 2015 timing contest is to seek novel ideas for incremental timing analysis by: (i) introducing the concept and motivating the importance of incremental timing analysis, (ii) encourage novel parallelization techniques (including multi-threading), and (iii) facilitating the creation of an incremental timing analysis framework with benchmarks to further advance this research area.
Adaptive all-order femtosecond dispersion compensation and pulse combining

Adaptive holographic quantum-well films are high-sensitivity dynamic holographic media that can be used to self- compensate time-varying disturbances such as mechanical vibration in interferometers, laser speckle, fsec pulse broadening and arrival-time drift. The holograms are quasi- steady-state with a compensation bandwidth up to 1 MHz. Dispersion to all orders is compensated by forming a dynamic spectral-domain hologram of a signal pulse (that has a time- varying dispersion) referenced to a stable clock pulse. The hologram is read out using forward scattering phase conjugation to remove phase distortion to all orders, including linear order that induces drift in the time of flight. We also have used adaptive interferometry to combine two ultrashort pulses into a pulse train. The relative phase between the two pulses in the train are self-adaptively phase locked, and is immune to drifting optical path differences or delay times between the two input pulses.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Molecular specificity of the tumorigenic action of ethionine: the inactivity of S-ethylcysteine. Action on respiratory parameters.

S-Ethyl-l-cysteine (a lower homolog of ethionine) is not carcinogenic to male Wistar rats at approximately three times the dose at which ethionine produces 100% liver tumor incidence. Administration of ethionine lowers both the P/O ratio and the respiratory control index of liver mitochondria from female rats, but does not affect these parameters in males with the three substrates studied: α-ketoglutarate, β-hydroxybutyrate and succinate. The respiratory control index but not the P/O ratio is also lowered in the females when ethionine is added in vitro. With none of these substrates does S-ethyl-l-cysteine affect the P/O ratio in either of the two sexes, nor does either ethionine or S-ethyl-l-cysteine significantly alter the \(Q_{0_2 } \). The data indicate that in female rats the lowering of availability of ATP in liver tissue by the “trapping” of adenosyl moieties by ethionine is compounded by alteration of the ATP synthesizing system. The results support the view that the effect of ethionine on phosphorylation efficiency is related to its ability to induce fatty liver in females but not to its carcinogenic activity.
Aggregation and Reactivity of the Cesium Enolate of p-Phenylisobutyrophenone in Tetrahydrofuran1

Reinvestigation of the cesium enolate (CsPhIBP) of 1-biphenylyl-2-methylpropanone (p-phenylisobutyrophenone, PhIBP) in tetrahydrofuran (THF) solution at 25.0 °C shows that its UV−visible spectrum changes with concentration with λmax moving to longer wavelengths in more dilute solution. Analysis of the spectral data over a wide concentration range by singular value determination (SVD) combined with the pK measurements indicates a mixture of monomer (M), dimer (D), and tetramer (T) with equilibrium constants of K1,2 = D/M2 = 2.89 × 104 M-1 and K1,4 = T/M4 = 7.78 × 1012 M-3. The pK of the monomer is 25.08. The data are also compared with the corresponding data obtained for the lithium ion pair system reported in the following paper. We find that the cesium ion pair is more highly aggregated and much more basic than the lithium ion pair. The average aggregation number of CsPhIBP at 10-3 M is 3.2, substantially greater than the value of 2.2 reported previously; the revision arises from our taking into account ...
Effect of Molecular Weight (MW) and End-Groups on the Thermal and Lewis-Acid Catalyzed Decomposition of Fomblin Z-Type Lubricants

The high-temperature stability of disk lubricants has attracted a lot of interest in recent years because smaller head-media spacing may cause head-media contact and thus a local temperature rise. At elevated temperatures, the lubricant may either evaporate or decompose, leading to the eventual failure of the head-media interface. The decomposition might result from heating and/or may be catalyzed by the presence of a Lewis acid site at the head-disk interface (HDI). In this paper, we study how the chemical structure, namely, molecular weight (MW) and end-groups (see Fig. 1), of disk lubricants will affect the thermal and Lewis-acid catalyzed decomposition of the lubricant.Copyright © 2005 by ASME
Integrin signals, transcription factors, and monocyte differentiation.

The precise signals responsible for differentiation of circulating monocytes into tissue macrophages are incompletely defined. "Outside-in" integrin signaling has been implicated in modulating gene expression that affects cellular differentiation. This review highlights the role of transcription factors in monocyte differentiation and describes how integrin engagement orchestrates monocyte differentiation signals by regulating the expression of the forkhead transcription factor Foxp1, which functions as a transcriptional repressor of the macrophage colony-stimulating factor receptor c-fms . This represents a new pathway for integrin-dependent modulation of gene expression and control of cellular differentiation.
Subsurface contaminant monitoring by laser excitation-emission matrix/cone penetrometer

We have recently developed instrumentation capable of quickly characterizing or monitoring a site using laser-induced fluorescence (LIF) measurements made through a sapphire window near the tip of a cone penetrometer (CPT) probe as it advances through the subsurface. By incorporating ten laser wavelengths simultaneously and collecting a full three-dimensional fingerprint of the soil sample at a vertical resolution of approximately 2 cm, we have made advances in site characterization using this technique, which enjoys all the advantages of in situ measurements: no exposure to, handling, custody or generation of hazardous waste is involved, and results are available in near real time. This report presents the results of recent work at Otis Air National Guard Base. First, a simple one-dimensional measure of the fluorescence fingerprints was correlated with laboratory results for total petroleum hydrocarbons (TPH), as a potentially convenient way for an operator of our instrument to monitor the results of the LIF measurements in real time, as the probe advances. Second, and more importantly, results are presented to demonstrate the potential of the instrumentation to identify individual target species and to quantify their concentrations approximately. The samples collected on site for conventional laboratory analysis were also measured by LIF and the resulting excitation-emission matrices (EEMs) were analyzed for ten target polycyclic aromatic hydrocarbons (PAHs). Qualitative and semi-quantitative agreement between these two sets of results was obtained. The agreements were extended to the in situ LIF data taken 2 - 3 feet away.
Lattice QCD with dynamical domain wall quarks

Abstract We study lattice QCD with two flavors of dynamical domain wall quarks. With renormalization group motivated actions, we find chiral symmetry can be preserved to a high degree at lattice cut off of a −1 ∼ 2GeV even for fifth dimension size as small as L s = 12. In addition two new steps are introduced to improve the performance of the hybrid Monte Carlo simulation.
Beta process based adaptive learning for immunosignature microarray feature identification

We propose a latent feature model for immunosignature random peptide microarray data using beta process factor analysis to identify relationships between patients and infectious agents. The method uses Bayesian nonparametric adaptive learning techniques that allow for further classification if additional patient data is received, and new relationships between patients and disease states are obtained. In addition to feature discovery, this methodology can also detect biothreat agents on the fly. Using experimental immunosignature microarray data, we demonstrate the identification and classification of underlying relationships between patients with different disease states.
Peripheral pathways are pioneered by an array of central and peripheral neurones in grasshopper embryos

During embryonic development, neuronal growth cones traverse long distances along stereotyped pathways to arrive at their appropriate targets. Since Harrison's initial observations1, increasing evidence has supported the notion that axonal pathways are “pioneered” early in development when the distances are short and the terrain relatively simple; thus an axonal scaffold is erected upon which later neurones can navigate. Grasshopper embryos have emerged as an attractive preparation in which to study pathfinding because the nervous system is relatively simple, and the individual identified neurones in the periphery and central nervous system (CNS) of the embryo are large and highly accessible. How are the first axonal pathways established between the periphery and CNS? Bate2 has described a single pair of cells in the limb buds, and two pairs in the antennae, which were thought to establish the very first peripheral pathways over distances of several hundred micrometres from the periphery to CNS; he called these pairs of cells ‘pioneer neurones’. Keshishian3 confirmed this finding and also described4 a second pair of pioneers in the limb buds. We report here a further analysis of peripheral pathfinding in the grasshopper embryo using a monoclonal antibody, called I-5, which stains the cells responsible for establishing the first pathways5,6. In contrast to the earlier reports, we find a large array of peripheral cells responsible for establishing the first pathways, with both pathfinders and landmark cells spaced at short intervals along the route. Furthermore, growth cones from central motoneurones make important contributions to the first peripheral pathways6.
Inner hair cell responses to tonal stimulation in the presence of broadband noise.

The effects of broadband noise (BBN) on the tone‐evoked dc receptor potential from inner hair cells of guinea pigs were measured. The effects of the noise were: suppression of the receptor potential, no net change, or greater depolarization relative to the tone alone, evoked receptor potential. The effects appear to be consistent with a two‐tone suppression hypothesis. The time course of the suppression effect is immediate and constant in time. This observation suggests no obvious involvement of a local feedback loop in outer hair cells or one depending on the efferent nerves. Inner hair cell ‘‘sensitivity’’ is a variable in the magnitude of the suppression. Comparison of masked, tone‐evoked dc receptor potential intensity functions to responses from auditory‐nerve fibers (taken from the literature for experiments using a similar paradigm) differentiates the phenomena of suppression and adaptation in the auditory periphery.
High potency of a new bombesin antagonist (RC-3095) in inhibiting serum gastrin levels; comparison of different routes of administration.

Abstract This study was performed to evaluate the efficacy and duration of action of a new bombesin antagonist d -Tpi6,Leu13 ψ (CH2NH)Leu14-bombesin (6–14) (RC-3095), given by different routes of administration, in suppressing gastrin releasing-peptide (GRP(14–27))-stimulated gastrin release in rats. First, we showed that GRP(14–27) itself was highly active when administered by different routes. GRP(14–27), given to rats at a dose of 25 μg/100 g b.w. significantly increased serum gastrin levels 3 and 6 min after intravenous and for more than 30 min after subcutaneous administration or pulmonary inhalation. RC-3095 was then injected subcutaneously, intravenously and also delivered by pulmonary inhalation at a dose of 10 μg/100 g b.w. in each case to seven male rats 2, 30, 60 or 120 min prior to i.v. administration of 5 μg GRP(14–27). RC-3095 administered 2 min prior to GRP(14–27) decreased the gastrin response to GRP(14–27), measured as area under the curve, by 81% in the intravenously injected group and 64% in the pulmonary inhalation group in the first 6 min. When GRP(14–27), was given 30 min after administration of RC-3095, the gastrin response was decreased by 52% in the subcutaneous group, 49% in the pulmonary inhalation group and 11% in the intravenous group during the first 6 min. RC-3095 delivered subcutaneously or by pulmonary inhalation 1 h before GRP(14–27) was also able to significantly inhibit gastrin release. Analysis of the data revealed that the biovailability of RC-3095 given by the pulmonary inhalation route was about 69% of the s.c. route. Our results indicate high activity of bombesin antagonist RC-3095, administered by different in vivo routes, in suppressing serum gastrin in rats. The administration by pulmonary inhalation evaluated here in rats, may prove to be practical and useful in the clinical setting.
American Autobiography: Retrospect And Prospect

The first four essays review the major historical periods of American autobiography, placing the classic texts of American autobiographical literature from Captain John Smith to Malcolm X in the illuminating context of lesser-known contemporary narratives. Daniel B. Shea writes on colonial America, Lawrence Buell on the American Renaissance, Susanna Egan on the years after the Civil War, and Albert E. Stone on the twentieth century. The second part of American Autobiography shows the diversity of voices, forms, audiences, and modes of identity in the literature of American autobiography. Provocative essays by William Boelhower and Sau-Ling Cynthia Wong on immigrant autobiography discuss the changes in the sense of self that occur when strangers come to a strange land. Arnold Krupat writes about how American Indians conceptualize the self and about the relationship between oral and written discourse. William L. Andrews evaluates the strong body of critical theory that has grown up around African-American autobiography, showing how both the genre and its criticism have responded to contemporary historical pressures. Carol Holly explores the model of personal identity that underlies nineteenth-century women s autobiographies, and Blanche Gelfant examines the narrative and political strategies of Emma Goldman s autobiography, especially her use of popular romance and melodrama. The last essay offers a more personal perspective on contemporary autobiography: a dialogue between Robert and Jane Coles about how they developed their method of eliciting first-person oral narratives for their famous Children of Crisis and Women of Crisis series. These essays raise theoretical issues that are examined in Paul John Eakin s incisive introduction: How do we define a literary genre of protean shape and perplexing cultural multiplicity? How do we approach the special problems created by documents that are both historical and literary texts, ones that pose difficult questions about truth and representation? Most important, how is the canon of American autobiography to be constructed, and how is its history to be written? Tracing that critical history, Eakin explains how changing ideas about the mainstream and the marginal have revitalized our retrospective view of American autobiography and opened up new and exciting prospects for today s reader."
The Application of Large Capacitors for Use in Energy Storage Banks

In this paper, the explosively increasing demand for energy storage capacitor applications is discussed with particular reference to the various special characteristics required and how they affect the cost, mechanical configuration, circuitry, and protection requirements. Of particular importance at this time, there is included a discussion of means of accomplishing lower inductance and "Q" factor improvement over conventional design. A brief discussion of capacitor fundamentals contributing to the control of discharge waves is presented to illustrate the need for precise determination of circuit characteristics and electrical parameters. Several application problems are discussed, illustrating all of the factors pertinent to the design requirements, and how to obtain them. Since most of these installations represent considerable investment and frequently the need for high reliability, means for protection both against voltage overshoot and isolation in the event of unit failure is also discussed. Thus, the information presented establishes the criteria for selection of large banks of capacitors under the most favorable economic and technical comditions, along with an assurance of reliable performance without excessive unused safety factor dollars.
Methane gas release from the Storegga submarine landslide linked to earlyHolocene climate change: a speculative hypothesis

The 3000 km3 Storegga submarine landslide occurred c. 8150 years ago from an area rich in gas hydrates off the western coast of Norway. A synchronous increase of 80—100 ppb in atmospheric methane c...
Parental Interpersonal Sensitivity and Youth Social Problems: A Mediational Role for Child Emotion Dysregulation

We examined the relations between parental interpersonal sensitivity and youth social problems and explored the mediational role of child emotion dysregulation. Mothers (N = 42; M age = 39.38) and fathers (N = 41; M age = 39.38) of youth aged 7–12 (N = 42; M age = 9.12) completed measures of their own interpersonal sensitivity and reported on their child’s emotion regulation skills and social functioning. Maternal interpersonal sensitivity was positively associated with child social problems, and this relationship was fully mediated by child emotion dysregulation. A bootstrapping technique provided evidence for the significance of the mediation. For fathers, only the association between child emotion dysregulation and child social problems was significant. Our findings suggest one potential mechanism through which maternal behaviors relate to youth psychosocial functioning. Identification of such mechanisms contributes to the development of conceptual models of youth functioning and suggests specific targets for prevention and intervention efforts.
Optical Heterogeneity in Lake Champlain

Abstract Optical properties of eleven stations on Lake Champlain are described for a single survey in the late summer of 1990. Light penetration, the angular distribution of irradiance, and the spectral quality of underwater irradiance were quantified by measurements with a Secchi disc, quantum sensors, and a spectroradiometer. Estimates of absorption (a) and scattering coefficients (b) are presented, and a is partitioned according to contributing components. Microscopy-based individual particle analyses provide insights concerning the role of particles in light attenuation. Major spatial differences in the concentration and composition of attenuating components, and thereby a and b, apparently promoted by the lake's physical setting and disparate localized material loading conditions, caused substantial spatial heterogeneity in measured optical characteristics. Phytoplankton were a minor attenuating component throughout the lake during the survey. More important components were water itself, gelbstoff, and particles of terrigenous origin. The role of non-phytoplankton material and the heterogeneity of its distribution have important implications with respect to responses in clarity, due to changes in phytoplankton concentration.
Assessing the Participation of Women in Microfinance Institutions: Evidence From a Multinational Study

ABSTRACT Microfinance institutions (MFIs) typically offer small credit services with no collateral to low-income clients, particularly women microentrepreneurs. Evidence suggests that microcredit services are an effective tool for the social and financial empowerment of women and have a significant impact on maternal health, children's education, and sustainable economic growth. With multiple financial institutions offering various microfinance services, women's participation as borrowers has changed. We examine the variation in women borrowers’ participation rates in 105 developing countries by analyzing participation rates using selected determinants such as legal status, outreach, external control, and target clients. Results indicate a preference for unregulated MFIs, particularly nongovernmental organizations (NGOs), which suggests that in spite of the advent of formal financial institutions, women in developing countries are more likely to seek loans from grassroots MFIs. However, with more commerci...
Contrasting nanoparticle diffusion in branched polymer and particulate solutions: more than just volume fraction

We contrasted the diffusion of gold nanoparticles (AuNPs) in crowded solutions of a randomly branched polymer (dextran) and rigid, spherical particles (silica). The goal was to understand the roles played by the probe size and structure of the crowding agent in determining the probe diffusion. AuNPs of two different sizes (2.5 nm & 10 nm), dextran of molecular weight 70 kDa and silica particles of radius 10 nm were used. Our results indicated that the AuNP diffusion can be described using the bulk viscosity of the matrix and hydrodynamically dextran behaved similar to a soft colloid. In all situations, we observed normal diffusion except for 2.5 nm sized AuNPs in dextran solution at a higher volume fraction. This is caused by transient trapping of particles within the random branches. The results showed the importance of macromolecular architecture in determining the transport properties in intracellular matrix and in cells with spiny dendrites.
Efficacy and cost-effectiveness of autologous bone marrow transplantation in metastatic breast cancer. Estimates using decision analysis while awaiting clinical trial results.

Objective. —To assess the efficacy and cost-effectiveness of standard chemotherapy and high-dose chemotherapy with autologous bone marrow transplantation (ABMT) in metastatic breast cancer. Design. —Decision analysis model using a Markov process. Setting. —Response and recurrence rates from the published literature for standard therapy and from case series of ABMT. Costs were based on local charges and on adjusted Medicare data. Patients. —Hypothetical cohorts of women with metastatic breast cancer who had no bone marrow involvement and no comorbid illness. Intervention. —The standard chemotherapy cohort received cyclophosphamide, doxorubicin, and fluorouracil. The ABMT cohort was treated with intense induction chemotherapy, then additional high-dose chemotherapy following a remission, with ABMT support. Main Outcome Measures. —Anticipated survival, incremental cost per year of life, and incremental cost per quality-adjusted year of life gained using a 5-year time horizon. Rigorous sensitivity analyses were done, including assessing a benefit "tail" of normal life expectancy for those free of disease after 5 years. Results. —ABMT was the preferred approach under almost all assumptions, but the size of the benefit varied greatly. ABMT had a survival benefit of 6.0 months at 5 years at an incremental cost of $115 800 per year of life saved. If patients who were free of disease after 5 years had normal survival, the benefit was 18.1 months at an incremental cost of $28 600 per year. The benefit of ABMT was primarily dependent on whether the recurrence risk was constant or decreases after a finite period of time. Conclusion. —Using reasonable assumptions, ABMT provided a substantial benefit but at a cost that may be untenable. Decision analysis highlights the limitations in the currently available data and the assumptions made for the emotional question of using ABMT in metastatic breast cancer. The model supports the need for randomized clinical trials. (JAMA. 1992;267:2055-2061)
Biogeochemistry: Carbonate rocks deconstructed.

The ratios of stable isotopes, especially isotopes of carbon and oxygen, have tales to tell about Earth's history. Post-depositional alteration of the carbonate rocks being studied may radically alter the story.
Prior time uncertainty reduction of foreperiod duration under two different levels of event uncertainty in process and reactive schizophrenia.

Process and reactive schizophrenic Ss judged stimulus durations of 0.50 and 0.55 seconds. Stimulus was 1, 3 or 5 dark dots and was preceded by variable foreperiod duration of 1, 3, or 5 seconds. Judgment of stimulus duration was found to be a monotonically increasing function of foreperiod duration. When pitch of the auditory warning signal was correlated with foreperiod duration so that it functioned as prior time information, such monotonic function was eliminated for process schizophrenies only when the numerosity of dots was constant from trial to trial. The effect of prior time information that concerned foreperiod duration was negligible for both process and reactive schizophrenics when the numerosity of dots was variable from trial to trial. Uniqueness of process schizophrenia was shown to be associated with prior time uncertainty reduction of foreperiod duration in the context of minimal event uncertainty of stimulus.
Transition to turbulence in plane Poiseuille and plane Couette flow

Direct numerical solutions of the three-dimensional time-dependent Navier-Stokes equations are presented for the evolution of three-dimensional finite-amplitude disturbances of plane Poiseuille and plane Couette flows. Spectral methods using Fourier series and Chebyshev polynomial series are used. It is found that plane Poiseuille flow can sustain neutrally stable two-dimensional finite-amplitude disturbances at Reynolds numbers larger than about 2800. No neutrally stable two-dimensional finite-amplitude disturbances of plane Couette flow were found.Three-dimensional disturbances are shown to have a strongly destabilizing effect. It is shown that finite-amplitude disturbances can drive transition to turbulence in both plane Poiseuille flow and plane Couette flow at Reynolds numbers of order 1000. Details of the resulting flow fields are presented. It is also shown that plane Poiseuille flow cannot sustain turbulence at Reynolds numbers below about 500.
Impact of chronic obstructive pulmonary disease on quality of life : The role of dyspnea

Dyspnea is a common symptom that accompanies a diagnosis of chronic obstructive pulmonary disease (COPD). Dyspnea often interferes with the patient's health-related quality of life (HRQOL), yet it is often underreported by the patient and underrecognized by the clinician. Reductions in objective pulmonary function measurements, such as forced expiratory volume in 1 second, are not well correlated with the patient's perception of symptoms and HRQOL. The patient's self-reported or subjective assessment is therefore important when evaluating the intensity of dyspnea and its impact on HRQOL. This article describes several well-validated questionnaires and dyspnea assessment scales that can be effective for assessing the intensity and impact that dyspnea may have on patient-perceived HRQOL. In addition, it describes the integration of pulmonary rehabilitation and specific pharmacotherapies as well as how these interventions can positively influence and modify the severity and distress of dyspnea. Effective assessment and therapeutic management of dyspnea for the patient living with COPD are opportunities to improve the patient's overall HRQOL.
Genes for epilepsy mapped in the mouse

The neurological mutant mouse strain E1 is a model for complex partial seizures in humans. The inheritance of epileptic seizures with seven conventional chromosomal markers and over 60 endogenous proviral markers was studied by means of back-crosses of E1 with two seizure-resistant strains, DBA/2J and ABP/LeJ. The major gene responsible for this epileptic phenotype (El-1) was localized to a region distal with respect to the centromere on chromosome 9. At least one other gene, El-2, linked to proviral markers on chromosome 2, also influences the seizure phenotype. In addition, a potential modifier of seizures was detected in the DBA/2J background. The location of El-1 on distal chromosome 9 may allow identification of an epilepsy candidate gene in humans on the basis of conserved synteny with human chromosome 3.
A limit theorem for quadratic forms and its applications

We consider quadratic forms of martingale differences and establish a central limit theorem under mild and easily verifiable conditions. By approximating Fourier transforms of stationary processes by martingales, our central limit theorem is applied to the smoothed periodogram estimate of spectral density functions. Our results go beyond earlier ones by allowing a variety of nonlinear time series and by avoiding strong mixing and/or summability conditions on joint cumulants.We thank the two reviewers for their detailed comments, which led to substantial improvements. The work is supported in part by NSF grant DMS-0478704.
DNA SPECIFICITY OF THE CRE RECOMBINASE RESIDES IN THE 25 KDA CARBOXYL DOMAIN OF THE PROTEIN

The Cre protein of bacteriophage P1 is a 38.5 kDa site-specific recombinase that belongs to the Int family of recombination proteins. Cre acts by binding specifically to a 34 base-pair sequence, lox, where it carries out recombination. A limited chymotryptic digest of Cre resulted in two fragments of sizes 25 and 13.5 kDa, respectively. The sequence of the amino terminus of the purified 25 kDa peptide demonstrates that this peptide represents the carboxyl-terminal portion of the Cre protein. A truncated version of the cre gene was constructed which produces only the 25 kDa peptide. The 25 kDa peptide is capable of specific binding to the lox site, but binds at lower affinity than does wild-type Cre. Footprinting with Fe-EDTA indicates that the 25 kDa peptide protects the inverted repeats of the lox site but shows only partial protection of the spacer region. This is in contrast to the footprint obtained with wild-type Cre which protects the entire spacer region.
Collector's Guide to the Eudialyte Group

Minerals of the eudialyte group are generally rare, although eudialyte itself is relatively plentiful, occasionally produces fine crystals, and is a minor but very attractive lapidary material. The...