cssi/SciSciGPT-SciSciNet huggingface dataset:
Variability in glutathione-dependent detoxication in vivo and its relevance to detoxication of chemical mixtures

Glutathione (GSH) has multiple functions in detoxication and its depletion has been associated with an increased risk of chemical toxicity. Because GSH can be depleted by different agents, combinations of compounds in chemical mixtures are likely to enhance risk over that seen with individual chemicals. Our studies have focussed on factors affecting the status of GSH in humans. In addition, we have utilized animal models and cell culture systems to understand the role of GSH in protection against chemical injury. Results of these studies show that, while large variations in sulfur amino acid content occur in the human diet, these variations are not correlated simply with GSH levels in vivo as reflected in the blood plasma pool. However, plasma levels of GSH do vary with gender, age, race and dietary habits, and these factors could affect the risk of toxicity in individuals exposed to chemical mixtures. In animal studies, we found that extracellular pools of GSH, including the blood plasma, lung-lining fluid and small intestinal lumen can be very important in protection against chemically induced injury. These pools can function to detoxify chemicals extracellularly, supply GSH and its precursors to cells and protect the extracellular surface of the plasma membrane from damage. Finally, endogenous gene-activated mechanisms of cell death which produce the characteristic morphology of apoptosis are susceptible to thiol-disulfide redox regulation. Perturbations in GSH status induced by chemical mixtures could alter this regulation and lower the threshold for chemically induced cell death by apoptosis. Thus, in vivo GSH status could be an important determinant of toxicity from chemical mixtures and may be useful as a biomarker for such risk.
Holographic data storage in a DX-center material

We report on the optical storage of digital data in a semiconductor sample containing DX centers. The diffraction efficiency and the bit-error-rate performance of multiplexed data images are shown to agree well with a simple model of the material. Uniform storage without an exposure schedule is demonstrated. The volume sensitivity is found to be ~10^3 times that of LiNBO3:Fe. The importance of coherent addition of scattered light with diffracted light in holographic data storage is discussed.
SAS-B digitized spark chamber gamma ray telescope

Systems description of SAS-B gamma ray telescope with multilayer digitized spark chamber for gamma rays with energy exceeding 20 MeV
ISAR range measurement via complex analysis and its application to motion compensation

Standard ISAR image focusing techniques utilize the magnitude and position of range domain target signatures to achieve translational motion compensation. Alternatively, range can be determined by analyzing the slope of the unwrapped phase function associated with the frequency domain signature of a moving target. We propose a motion compensation method based on such phase slope analysis. To improve noise performance, the probability density function of additive noise corrupting the signature is modeled as a Weibull distribution to determine a threshold for constant false alarm rate filtering. Complex analysis is then utilized to determine sample intervals where noise is relatively weak, where the amplitude of the filtered signature is high above the noise interference level and the phase of the same signature is nearly linear Weighted least squares is subsequently used to estimate the target's kinematic parameters based on the phase slope measurement. Results show that parameter estimates for motion compensation obtained in this manner converge to a unique solution, thus providing focused ISAR imagery of the target.
Mass distribution in spiral galaxies

The masses of a carefully selected sample of primary disk galaxies orbited by one or more satellite systems have been calculated both from the rotation of the disks and from the kinematics of the satellites. The ratio of these two mass estimates (χobs ) is sensitive to the presence of any extended halo and for satellite-primary pairs the mass distribution is significantly different from that of binary galaxies. Our data cannot be described by the heavy halo model with circular orbits, though extended haloes are a possibility if the satellite orbits are highly eccentric.
Open Shop Scheduling to Minimize Finish Time

A linear time algorithm to obtain a minimum finish time schedule for the two-processor open shop together with a polynomial time algorithm to obtain a minimum finish time preemptive schedule for open shops with more than two processors are obtained. It is also shown that the problem of obtaining minimum finish time nonpreemptive schedules when the open shop has more than two processors is NP-complete.
A hybrid learning network for shift, orientation, and scaling invariant pattern recognition

A three-layer neural network is presented as a generic approach for visual pattern recognition invariant with respect to the geometric appearance such as translation, orientation and scale of the patterns. The invariant recognition is achieved by representing the geometric variations internally in the network by nodes in the input and middle layers, which are laterally connected and trained by a hybrid algorithm combining both competitive and Hebbian learning. As the result of the hybrid learning, each pattern will be represented by a particular subset of middle-layer nodes all specialized to respond to the same pattern but with different geometric appearances. The nodes in the output layer are then trained by competitive learning to recognize the different pattern internally represented by the middle-layer nodes, independent of their location, orientation and size. The proposed algorithm is generic and robust and can be applied to various practical recognition problems. Moreover, the network is relativel...
Dilemmas of trustworthiness in preservice teacher action research

Can preservice teachers carry out trustworthy action research? We have found that action research can be a powerful experience for preservice teachers. Yet preservice teacher action research projects involve complexities unique to a preservice teacher's position as `guest', `student', `teacher', and `researcher'. In this article, we suggest criteria for trustworthy preservice teacher action research that embraces these complexities as sources of strength. We base our criteria upon analysis of action research projects produced by students in the teacher education program where we teach. We apply trustworthiness criteria from qualitative research (Arminio & Hultgren, 2002; Kincheloe, 2003; Lather, 1991; Reason & Bradbury, 2001; Richardson, 1997) to guide our analysis, but we interpret `trustworthiness' through the lens of preservice teacher context and experience. Our intent is to honor the voices of preservice teachers telling their own stories of becoming a teacher through action research.
Investigation of Trap Spacing for the Amorphous State of Phase-Change Memory Devices

The subthreshold conduction in the amorphous state of the phase-change material is dominated by the hopping of the carriers through the trap states or localized states with the assistance of the electric field across the material. It is important to understand the nature and number of these traps to properly model the physics of the conduction, threshold switching, and drift in phase-change materials. In this paper, we present a device structure and a methodology to extract the trap spacing directly from the I-V characteristics of the device. Furthermore, the dependence of the trap spacing on the amorphous region thickness, reset voltage, and drift is also discussed. These results are then correlated with the 1/f noise measurements of the device.
Assessment of microwave-assisted enzymatic digestion by measuring glycated hemoglobin A1c by mass spectrometry

Enzymatic digestion of proteins and analysis of the resulting peptides by mass spectrometry is an established approach in proteomics and in clinical and environmental chemistry. The long digestion times of several hours prevent the fast turnover of samples and results. Qualitative applications showed that microwave radiation profoundly shortens enzymatic digestion. However, its usefulness for quantitative applications had not been assessed. In this study, the microwave-assisted enzymatic digestion of hemoglobin at different temperatures, buffer concentrations, and digestion times was assessed and compared with conventional digestion for the proteolytic enzymes trypsin and Glu-C. A microwave-assisted enzymatic digestion method optimized for digestion time and temperature was applied for the analysis of glycated hemoglobin HbA1c and compared with a reference method. Using trypsin, complete digestion was obtained at 50 degrees C within 20 min. Under these conditions, the digestion efficiency was 20% higher than with conventional trypsin digestion. These effects were not observed with Glu-C as enzyme, probably because of the decreased stability of Glu-C at elevated temperatures in comparison with the trypsin used. The comparison of the optimized microwave-assisted digestion method using trypsin with the reference method for HbA1c using Glu-C gave a close correlation in the results (R2: 0.996). A significant bias of 0.33% HbA1c was observed, with higher values obtained with the microwave-assisted tryptic digest; this finding might have resulted from the use of a different enzyme. This study showed that microwave-assisted enzymatic digestion can substantially reduce digestion times to minutes and can be used in qualitative as well as quantitative applications.
Revisiting the effect of quality of graphics on distance judgments in virtual environments: A comparison of verbal reports and blind walking

In immersive virtual environments, judgments of perceived egocentric distance are significantly underestimated, as compared with accurate performance in the real world. Two experiments assessed the influence of graphics quality on two distinct estimates of distance, a visually directed walking task and verbal reports. Experiment 1 demonstrated a similar underestimation of distances walked to previously viewed targets in both low- and high-quality virtual classrooms. In Experiment 2, participants’ verbal judgments underestimated target distances in both graphics quality environments but were more accurate in the high-quality environment, consistent with the subjective impression that high-quality environments seem larger. Contrary to previous results, we suggest that quality of graphics does influence judgments of distance, but only for verbal reports. This behavioral dissociation has implications beyond the context of virtual environments and may reflect a differential use of cues and context for verbal reports and visually directed walking.
High relatedness is necessary and sufficient to maintain multicellularity in Dictyostelium

Most complex multicellular organisms develop clonally from a single cell. This should limit conflicts between cell lineages that could threaten the extensive cooperation of cells within multicellular bodies. Cellular composition can be manipulated in the social amoeba Dictyostelium discoideum, which allows us to test and confirm the two key predictions of this theory. Experimental evolution at low relatedness favored cheating mutants that could destroy multicellular development. However, under high relatedness, the forces of mutation and within-individual selection are too small for these destructive cheaters to spread, as shown by a mutation accumulation experiment. Thus, we conclude that the single-cell bottleneck is a powerful stabilizer of cellular cooperation in multicellular organisms.
Relation of coronary artery calcium to left ventricular mass in African-Americans

Both coronary artery calcium (CAC) deposits and increased left ventricular (LV) mass are important risk factors for coronary heart disease, but the relation between these 2 factors has rarely been studied. We examined the correlation of CAC and LV mass in 159 young to middle-aged African-Americans, and found that the average LV mass indexes were bigger in the CAC-positive groups than in CAC-negative groups in both genders (p = 0.0004 in men; p = 0.08 in women).
SOME NOTES ON TIME OUT FROM REINFORCEMENT1

Pigeons produced food on a fixed-ratio schedule by pecking at one key, and an SΔ period by pecking at a second (switching) key. Switching behavior was examined as a function of (a) size of the fixed ratio, (b) whether the SΔ was of fixed duration or could be determined by the bird, (c) the introduction of a novel food SD, (d) extinction of food responding, and (e) the stimuli associated with the SD and SΔ conditions. No monotonic relationship was obtained between ratio size and switching behavior. Switching behavior was, however, influenced by many variables. The results suggest that an interpretation of switching behavior in terms of its being reinforced by the removal of aversive conditions, is open to considerable question.
Engineering nanofluid electrodes: controlling rheology and electrochemical activity of γ-Fe 2 O 3 nanoparticles

Nanofluid electrodes or nanoelectrofuels have significant potential in the field of flow batteries, as at high loadings of solid battery active nanoparticles, their energy density can be orders of magnitude higher than in traditional redox flow battery electrolytes. Nanofluid electrodes must have a manageable viscosity at high particle concentrations (i.e., easily pumpable) and exhibit good electrochemical activity toward charge and discharge reactions. Engineering of such nanofluid electrodes involves development of new and unique approaches to stabilization of nanoparticle suspensions. In this work, we demonstrate a surface modification approach that allows controlling the viscosity of nanofluids at high solid loading, while simultaneously retaining electrochemical activity of the nanoparticles. A scalable single step procedure for the surface grafting of small organic molecules onto iron (III) oxide nanoparticles (γ-Fe2O3, maghemite, 40–150 nm) is demonstrated. Modified iron oxide nanoparticles reported here have ~5 wt% of the grafting moiety on the surface, which helps forming stable dispersions with up to 40 wt% of solid loading in alkali aqueous electrolytes with a maximum viscosity of 12 cP at room temperature. The maximum particle concentration achievable in the same electrolyte with pristine nanoparticles is 15 wt%. Electrochemical testing of the pristine and modified nanomaterials in the form of solid-casted electrodes showed a maximum reversible discharge capacity of 280 and 155 mAh/g, respectively, indicating that electrochemical activity of modified nanoparticles is partially suppressed due to the surface grafted moiety.
Nesting songbirds assess spatial heterogeneity of predatory chipmunks by eavesdropping on their vocalizations

1. Information benefits organisms living in a heterogeneous world by reducing uncertainty associated with decision making. For breeding passerines, information reliably associated with nest failure, such as predator activity, can be used to adjust breeding decisions leading to higher reproductive success. 2. Predator vocalizations may provide a source of current information for songbirds to assess spatial heterogeneity in risk that enables them to make appropriate nest-site and territory placement decisions. 3. To determine whether ground-nesting passerines eavesdrop on a common nest predator, the eastern chipmunk (Tamias striatus), we conducted a playback experiment to create spatial heterogeneity in perceived predation risk. We established three types of playback plots broadcasting: (i) chipmunk vocalizations (increased risk), (ii) frog calls (procedural control) and (iii) no playback (silent control). We conducted point counts from plot centres to compare bird activity among treatments and measured the distance of two ground-nesting species' nests, ovenbird (Seiurus aurocapilla) and veery (Catharus fuscescens), from playback stations. 4. Ground-nesting birds significantly reduced their activities up to 30 m from plot centres in response to playbacks of chipmunk calls suggesting an adjustment of territory placement or a reduction of overt behaviours (e.g. singing frequency). In contrast, less vulnerable canopy-nesting species showed no effect across experimental plots. Correspondingly, veeries and ovenbirds nested significantly further from chipmunk playback stations relative to control stations. Interestingly, the magnitude of this response was more than twice as high in ovenbirds than in veeries. 5. Our findings indicate that some breeding passerines may eavesdrop on predator communication, providing an explanation for how some birds assess spatial heterogeneity in predation risk to make breeding site decisions. Thus, heterospecific eavesdropping may be a common feature of predator-prey interactions that allows birds to avoid nest predators in space and provide greater stability to predator-prey dynamics.
Low-Renin and Nonmodulating Essential Hypertension

Low-renin hypertension (LREH) accounts for an important subset of the hypertensive human population and is associated with salt-sensitivity and diuretic response and is also common in black patients. An interesting finding in LREH is the presence of normal plasma aldosterone levels.1 2 The ratio of plasma aldosterone to renin activity is used to screen for adrenal adenomas and hyperplasia3 and is usually >100 when plasma renin activity is expressed in ng/mL/hr and the aldosterone concentration is expressed in ng/dL. The plasma aldosterone/plasma renin activity ratios may be somewhat elevated in LREH (>30 but <100), which is especially relevant if the concurrent urinary sodium excretion exceeds 200 mEq/24 hours.4 It is not known what regulates aldosterone secretion in this setting or whether there is actual mineralocorticoid excess. Undue prior emphasis may have been placed on the continued suppression of plasma renin activity during severe salt restriction or volume depletion in LREH,1 and the suppression of plasma renin activity and basal aldosterone secretion5 in the elderly can also confound the analysis of LREH. Studies by Fisher et al2 focus on adrenal and pressor responsiveness to angiotensin II (Ang II) as a function of dietary salt intake in patients with LREH, normal-renin hypertension, and normal controls. Especially striking are the functional similarities between LREH and “ nonmodulating” essential hypertension with normal plasma renin activity (NMEH), including: (1) salt-sensitivity of the blood pressure; (2) blunted plasma aldosterone responses to Ang II infusion and upright posture after 5 days of rigid dietary sodium restriction; and (3) relatively low basal plasma aldosterone levels. These differences compared with normal controls and “modulating” hypertensive subjects disappeared when the dietary salt intake was increased to 200 mEq. The latter results are consistent with suppression of plasma Ang II activity during high-salt intake with …
Essentialist to some degree: beliefs about the structure of natural kind categories.

Previous research has provided conflicting evidence regarding the hypothesis that people are essentialists. Much of the evidence in favor of essentialism is based on demonstrating that categories are thought to have absolute membership. Although the hypothesis is often framed as an absolute claim about all categories of a certain type (e.g., natural kinds), it has generally been tested by making relative comparisons with a select sample. The present study assesses judgments of absolute structure across a range of categories. A further condition for essentialism is that the criteria for category identity be seen as objective rather than conventional. The results of three experiments based on these considerations do not provide support for essentialist claims. Few categories were judged to have essentialist structure, in terms of either absolute membership or objective criteria. Results are discussed in light of an alternative to the essentialist hypothesis that emphasizes a pragmatic view of categories.
Systemic and microiontophoretic administration of morphine differentially effect ventral pallidum/substantia innominata neuronal activity.

In vivo electrophysiological recording techniques were employed to examine responses of ventral pallidum/substantia innominata (VP/SI) neurons to systemic and local administration of morphine. Using a cumulative dosing protocol, intravenous administration (0.1–30 mg/kg i. v.) produced a suppression of firing in 82% of neurons tested. The suppression was dose-related and blocked by the opioid antagonist, naloxone. In contrast, microiontophoretic applications of morphine resulted in current-related suppression (32% of neurons tested) or excitation (26%). Concurrent application of naloxone attenuated or blocked both effects of local morphine applicatio. It was demonstrated that acute tolerance did not develop with repeated morphine exposures following either systemic or local administration. The present findings establish the sensitivity of VP/SI neurons to morphine and provide functional relevance at the level of a single neuron for opioid peptides and their receptors in this region. As reported for most other opioid receptive brain areas, neuronal rate suppression was the predominate response observed, and it is proposed that excitations to iontophoresed morphine reflect a disinhibitory phenomenon. The differntial morphine-induced rate changes, and number of responding neurons, observed with systemic vs. iontophoretic morphine administration suggest that extra-VP/SI regions that also are opioid sensitive can subsequently direct neuronal responsivensess to opioids within the VP/SI. © 1992 Wiley-Liss, Inc.
High precision contour tracking with a joystick sensor

High performance contour tracking is achievable with simple sensing and control. We describe a system that tracks unknown shapes with a joystick sensor mounted on an Adept SCARA robot. The joystick's limited force sensing is combined with the Adept's high positional accuracy to yield precise contact measurements. Force control is carried out with a simple feedback loop to avoid unnecessary oscillations. Due to contact friction and random sensor noise, prediction of the tangential motion from force measurements alone is unreliable. A position control strategy is devised to update the tracking direction based on a quadratic t to local turning of the contour. Fitting yields more accurate shape approximation while the use of local data keeps the computational cost low for constant updates. The result is fast tracking with hardly any loss of shape accuracy.
Humans and Old World monkeys have similar patterns of fetal globin expression

The expression of epsilon- and gamma-globin mRNA and protein has been determined in three Old World monkey species (Macaca mulatta, Macaca nemestrina, and Cercopithecus aethiops). Using RT-PCR with primers for epsilon- and gamma-globin, both mRNAs were detected in early fetal stages, whereas at 128 days (85% of full term), only gamma was expressed. High-performance liquid chromatography was used for separation and quantitation, and matrix-assisted laser desorption/ionization mass spectrometry was used for identification of globin polypeptides. An alpha-globin polymorphism was observed in all of the species examined. During fetal life, gamma-globin was the predominant expressed beta-type globin. The red blood cells of infants still contained substantial amounts of gamma-globin, which declined to negligible levels in 14 weeks as beta-globin expression reached adult values. The ratio of gamma1- to gamma2-globins (equivalent to Ggamma/Agamma in humans) was approximately 2.5, similar to the Ggamma/Agamma ratio observed in humans. Thus, gamma-globin gene expression in these Old World monkeys species has three features in common with human expression: expression of both duplicated gamma genes, the relative preponderance of gamma1 over gamma2 expression, and the delay of the switch from gamma- to beta-globin until the perinatal period. Thus, the catarrhines seem to share a common pattern of developmental switching in the beta-globin gene cluster, which is distinct from the timing of expression in either prosimians or the New World monkeys. Our results indicate that an Old World monkey, such as Rhesus, could serve as a model organism (resembling humans) for experimentally investigating globin gene expression patterns during the embryonic, fetal, and postnatal stages.
A Homolog of Voltage-Gated Ca2+ Channels Stimulated by Depletion of Secretory Ca2+ in Yeast

refill Ca 21 stores within the secretory pathway. Mutants lacking Pmr1p, a conserved Ca 21 pump in the secretory pathway, exhibit higher rates of Ca 21 influx relative to wild-type cells due to the stimulation of a high-affinity Ca 21 uptake system. Stimulation of this Ca 21 uptake system was blocked in pmr1 mutants by expression of mammalian SERCA pumps. The high-affinity Ca 21 uptake system was also stimulated in wild-type cells overexpressing vacuolar Ca 21 transporters that competed with Pmr1p for substrate. A screen for yeast mutants specifically defective in the high-affinity Ca 21 uptake system revealed two genes, CCH1 and MID1, previously implicated in Ca 21 influx in response to mating pheromones. Cch1p and Mid1p were localized to the plasma membrane, coimmunoprecipitated from solubilized membranes, and shown to function together within a single pathway that ensures that adequate levels of Ca 21 are supplied to Pmr1p to sustain secretion and growth. Expression of Cch1p and Mid1p was not affected in pmr1 mutants. The evidence supports the hypothesis that yeast maintains a homeostatic mechanism related to CCE in mammalian cells. The homology between Cch1p and the catalytic subunit of voltage-gated Ca 21 channels raises the possibility that in some circumstances CCE in animal cells may involve homologs of Cch1p and a conserved regulatory mechanism.
Treatment of chlorinated ethenes in groundwater with ozone and hydrogen peroxide

A study was conducted to enhance the performance of an advanced oxidation process in treating chlorinated ethenes in groundwater at IBM`s groundwater treatment system at its Essex Junction, Vermont facility. A model describing the reaction kinetics and mass transfer of a co-current ozone injection process is presented. This model, in conjunction with experiments, demonstrates that the treatment performance of the ozone treatment process at a given ozone/air concentration and ozone mass flowrate cannot be improved by varying process operating parameters such as number of ozone injectors utilized, use of a static mixer, or variation of groundwater flowrate through each injector. This is because dissolved ozone reaches equilibrium with the injected ozone/air mixture within two seconds of initial contact. Also, the Venturi-type ozone injection system presently in use destroys nearly half of the injected ozone. Injection of hydrogen peroxide in conjunction with ozone increases the overall tetrachloroethylene (PCE) treatment efficiency by a factor of four (in comparison to ozone alone) at a H{sub 2}O{sub 2}/O{sub 3} mass ratio of between 1 and 2. Treatment of trichloroethylene (TCE) is enhanced by a factor of two. This enhancement of the oxidative treatment process results in a reduction in solvent mass load to amore » granular activated carbon (GAC) adsorption system located downstream, thus potentially reducing the usage GAC and regeneration of spent GAC. However, residual hydrogen peroxide and/or hydroxyl free radicals from the oxidation process effluent may interact adversely with certain grades of GAC; the causes of this interaction and methods to attenuate it (i.e., the use of more resistant grades of GAC) are discussed. Overall O{sub 3}/H{sub 2}O{sub 2}/GAC system operating costs can potentially be reduced significantly (up to $20K annually). An economic analysis and system operation/cost optimization study are presented. 8 refs., 7 figs., 1 tab.« less
Male-biased nectar production in a protandrous herb matches predictions of sexual selection theory in plants

Nectar production may disproportionately benefit male relative to female pollination success. In such cases, sexual selection is often suggested as the cause of asymmetric benefits, yet sexual selection in plants—particularly plants with hermaphroditic flowers—is infrequently tested empirically. Here, I used a protandrous herb with male-biased nectar production (Chrysothemis friedrichsthaliana, Gesneriaceae) to test predictions from sexual selection theory. During three flowering seasons, I measured nectar production, pollinator visits, and male and female fecundity following different numbers of cross-pollination events. In accordance with sexual selection predictions, (1) nectar production was greater during the male phase by at least 65%; (2) visits by the main pollinator (hummingbird Phaethornis striigularis) were limiting for part of the season, indicating that plants had to compete for pollinator visits; (3) pollinators spent 53% more time per visit and made 86% more visits to male- vs. female-phase flowers, suggesting that nectar increased male more than female pollination success; and (4) female fecundity was maximized by one visit, whereas male fecundity continued to increase with additional visits. Autonomous self-pollination further reduced visit requirements for maximum female seed set. These findings match specific sexual selection predictions: they link an observable male bias in a secondary sexual trait (nectar) to positive responses of mating participants (pollinators), resulting in more mating opportunities for mate-limited males, relative to apparently resource-limited females. This field-testing of theoretical predictions provides unique evidence that sexual selection helps maintain nectar production patterns in this and, quite likely, other hermaphroditic plant species.
Skp1 Independent Function of Cdc53/Cul1 in F-box Protein Homeostasis

Abundance of substrate receptor subunits of Cullin-RING ubiquitin ligases (CRLs) is tightly controlled to maintain the full repertoire of CRLs. Unbalanced levels can lead to sequestration of CRL core components by a few overabundant substrate receptors. Numerous diseases, including cancer, have been associated with misregulation of substrate receptor components, particularly for the largest class of CRLs, the SCF ligases. One relevant mechanism that controls abundance of their substrate receptors, the F-box proteins, is autocatalytic ubiquitylation by intact SCF complex followed by proteasome-mediated degradation. Here we describe an additional pathway for regulation of F-box proteins on the example of yeast Met30. This ubiquitylation and degradation pathway acts on Met30 that is dissociated from Skp1. Unexpectedly, this pathway required the cullin component Cdc53/Cul1 but was independent of the other central SCF component Skp1. We demonstrated that this non-canonical degradation pathway is critical for chromosome stability and effective defense against heavy metal stress. More importantly, our results assign important biological functions to a sub-complex of cullin-RING ligases that comprises Cdc53/Rbx1/Cdc34, but is independent of Skp1.
La Liberalización Y El Manejo De Los Flujos De Capital: Una Visión Institucional (The Liberalization and Management of Capital Flows: An Institutional View)

Los flujos de capital han aumentado notablemente en los ultimos anos y son un aspecto clave del sistema monetario mundial. Ofrecen beneficios potenciales a los paises, pero su tamano y su volatilidad tambien pueden plantear problemas de politica. El Fondo debe estar en condiciones de proporcionar asesoria clara y coherente respecto de los flujos de capital y las politicas relacionadas. En 2011, el Comite Monetario y Financiero Internacional llamo a “seguir trabajando en un enfoque integral, flexible y equilibrado para el manejo de los flujos de capital”. En este documento se propone una vision institucional que apoye este enfoque, con base en documentos de politica anteriores, estudios analiticos y discusiones de la Junta sobre los flujos de capital.Capital flows have increased significantly in recent years and are a key aspect of the global monetary system. They offer potential benefits to countries, but their size and volatility can also pose policy challenges. The Fund needs to be in a position to provide clear and consistent advice with respect to capital flow and policies related to them. In 2011, the International Monetary and Financial Committee called for “further work on a comprehensive, flexible, and balanced approach for the management of capital flows”. This paper proposes an institutional view to underpin this approach, drawing on earlier Fund policy papers, analytical work, and Board discussions on capital flow.
Allosteric Indole Amide Inhibitors of p97: Identification of a Novel Probe of the Ubiquitin Pathway

A high-throughput screen to discover inhibitors of p97 ATPase activity identified an indole amide that bound to an allosteric site of the protein. Medicinal chemistry optimization led to improvements in potency and solubility. Indole amide 3 represents a novel uncompetitive inhibitor with excellent physical and pharmaceutical properties that can be used as a starting point for drug discovery efforts.
Cryosectioning of biofilms for microscopic examination

A method for rapid and minimally disruptive embedding and sectioning of bacterial biofilms has been developed and applied to binary population biofilms of Klebsiella pneumoniae and Pseudomonas aeruginosa grown on stainless steel surfaces in continuous flow annular reactors. Biofilms were cryoembedded using a commercial tissue embedding medium. Frozen embedded biofilms could be removed easily from the substratum by gently flexing the steel coupon. Microscopic examination of the substratum surface after biofilm removal indicated that less than a monolayer of attached cells remained. Five μm thick frozen sections were cut with a cryostat and examined by light or fluorescence microscopy. The cryoembedding technique preserved biofilm structural features including an irregular surface, water channels, local protrusions up to 500 μm thick, and a well‐defined substratum interface. The method requires minimal sample processing without dehydration or prolonged fixation, and can be completed in less than 24 h.
Some Practical Remarks on Multiple Scattering

Abstract The experimentalist's familiar formula for multiple scattering is investigated in terms of the more exact theory. A new value for the constant is suggested: Es=17.5 MeV. Convenient formulas for a thickness-dependent correction and a center-of-mass correction are given.
Five Top Stories in Thyroid Pathology

Context.— Thyroid carcinoma is the most common malignant tumor of endocrine organs, yet it only accounts for approximately 1% of all cancers in the United States with more than 35 000 new cases diagnosed each year and more than 450 000 people living with this disease. While most tumors can be diagnosed without much difficulty, a few tumor types, especially tumors with follicular pattern, sometimes pose a diagnostic challenge. Objective.— To discuss morphologic, immunohistochemical, and molecular features of thyroid tumors. We also explore the clinicopathologic features of papillary microcarcinoma and medullary microcarcinoma and how the latter is related and differentiated from C-cell hyperplasia. Finally with the ever-growing list of organ systems involved in immunoglobulin (Ig) G4–related diseases, we discuss the still not completely explored IgG-4–related thyroid disease. Data Sources.— Data were obtained from review of the pertinent peer-reviewed literature and institutional experience. Conclusions.— ...
On the Global Dimensions of D+M

This note answers affirmatively a question of the author [4, p. 456], by producing an example of an integrally closed quasi-local non valuation domain of global dimension 3, each of whose overrings is a goingdown ring. Although [4, Proposition 4.5] shows that such an example cannot be constructed by means of restrained power series, an approach via the more general D+M construction succeeds.
High-resolution electronic spectroscopy of the doorway states to intramolecular charge transfer.

Reported here are several of the ground, first, and second excited state structures and dipole moments of three benchmark intramolecular charge transfer (ICT) systems; 4-(1H-pyrrol-1-yl)benzonitrile (PBN), 4,4′-dimethylaminobenzonitrile (DMABN), and 4-(1-pyrrolidinyl)benzonitrile (PYRBN), isolated in the gas phase and probed by rotationally resolved spectroscopy in a molecular beam. The related molecules 1-phenylpyrrole (PP) and 4-aminobenzonitrile (ABN) also are discussed. We find that the S1 electronic state is of B symmetry in all five molecules. In PBN, a second excited state (S2) of A symmetry is found only ∼400 cm–1 above the presumed origin of the S1 state. The change in dipole moment upon excitation to the A state is measured to be Δμ ≈ 3.0 D, significantly smaller than the value predicted by theory and also smaller than that observed for the “anomalous” ICT band of PBN in solution. The B state dipole moments of DMABN and PYRBN are large, ∼10.6 D, slightly larger than those attributed to “normal” ...
Liver Antigens Detected by Liver Antinucleolar Antibodies

SummaryThree antigens (Ln-l-Ln-3) in extracts of normal rat liver were detected by immunodiffusion analysis using rabbit antibodies to liver nucleoli. In analyses of a series of tissues, antigens Ln-1 and Ln-3 were found only in normal and regenerating liver. Antigen Ln-2 was found in several tissues studied but not in kidney or rat serum; in kidney, an antigen was found that formed an overlapping band with antigen Ln-1 but did not exhibit identity with antigen Ln-1. In liver, approximately 99% of the antigen Ln-1 was in the cytosol and 1% was in the nuclei. In the extracts of nuclei and nucleoli, approximately 6-8% of this antigen was in the chromatin fraction from which it was extractable with 0.6 M NaCl. The antigens were purified on affinity columns which contained covalently bound liver antinucleolar antibodies. Interestingly, the bound antigen contained GC-rich RNA of approximately 200,000 MW.
P38 Appropriateness of referrals to rapid access and consultant outpatient services at a specialist paediatric cardiology centre

Introduction Since the publication of the controversial “Safe and Sustainable Standards for Specialist Surgical Centres” in 2012, care of patients with congenital heart disease has come under extreme scrutiny, with focus on the provision of safe and effective care locally where possible and centralised in specialist centres where necessary. Three years after this process began, we analysed the quality of new patient referrals with suspected congenital heart disease to outpatient services at a paediatric cardiology specialist centre. Method We reviewed referral and outcome data for all new referrals to Rapid Access and Consultant Outpatient clinics from January to March 2015 at Evelina London Children’s Hospital. Patients with pre-existing diagnoses of congenital heart disease including those referred for assessment prior to anaesthesia were excluded. Data were analysed for referral appropriateness and completeness in accordance with standards identified from available literature and local referral guidelines. Results 257 referrals (71 Rapid Access Service, 186 Consultant Outpatient Service) were analysed; 144 male (56%), 113 (44%) female. The median age range for the Rapid Access Service was 0–4 weeks and 5–12 years for the Consultant Outpatient Service. 102 referrals (40%) were received from primary care services and 155 (60%) from secondary care. Of 241 referral documents available only 81% contained a documented medical history, 55% a drug history and 47% commented on family history. For physical examination 23% documented the resting heart rate, 20% noted a blood pressure (children Conclusion New patient referrals with suspected congenital heart disease are not compliant with referral guidance, contributing to low diagnostic yields. In a cash strapped NHS, referrals to tertiary services should be considered carefully. At present, no import is given to such concerns by NHS trusts as each referral (regardless of the quality or outcome) earns income for the hospital trust. The quality of the referrals was extremely poor; affecting the ability to appropriately triage patients with subsequent implications for patient safety. Monitoring of referral standards needs to be considered centrally in order to discourage unnecessary referrals.
Characteristics of Neural Injury After Abdominoperineal Resection

Abstract A total of 13 men underwent synchronous video/pressure/flow electromyography studies after abdominoperineal resection of the rectum. All patients had diminished pressure in the proximal urethra and an incompetent vesical neck suggestive of sympathetic denervation. Five patients (38 per cent) had cystometric evidence of parasympathetic denervation and 7 (54 per cent) had electromyographic evidence of pudendal denervation. These data suggest that denervation owing to surgical injury is an important cause of persistent symptoms after abdominoperineal resection of the rectum.
Haemostatic Failure of Prothrombin Complex Concentrates during Elective Dental Procedure.

One haemophilia A patient with an inhibitor was exposed to a graded surgical procedure and treated with Prothrombin Complex Concentrates (PCC). Hemostasis was not obtained until the inhibitor was neutralized and the patient�s factor VIII level was normal. This patient is presented to emphasize that PCC are not nearly as effective as once hoped in producing hemostasis in inhibitor patients. Consequently, major decisions should not be made presuming efficacy of these products in inhibitor patients.
Homograft valve preparation and predicting viability at implantation.

An experimental study was performed using C14 proline uptake in order to: (1) assess the effects of current sterilization and storage methods on fibroblast viability, and (2) establish a control tissue that could be used to determine viability of each homograft valve at the time of implantation in the clinical setting. The results were expressed as disintegrations per minute per milligram of tissue (DPM/mg). Swine aortic (AV), pulmonary (PV), and tricuspid leaflets (TV), and adjacent AV and PV arterial wall were procured sterile and subjected to routine sterilization and storage. Thirty samples of AV were analyzed for incorporation of labeled proline at procurement (208 +/- 7 DPM/mg), following 48-hour antibiotic exposure (87 +/- 6 DPM/mg, P less than .0001), and following controlled rate cryopreservation and storage for 12 days at -80 degrees C (78 +/- 8 DPM/mg, P = .42). Proline uptake of the other tissues at the same intervals disclosed that only the TV resulted in the same degree of viability at implantation (AV 78 +/- 8, PV 68 +/- 3, TV 75 +/- 2, P = NS). The homograft valves were obtained under sterile conditions from brain dead, multiorgan donors (homovital). It has been postulated that these valves are sterile and ready for implantation. Of 17 homovital valves cultured at procurement, 9 had positive cultures within 48 hours (53%). We conclude that: (1) the TV can be processed as a control tissue with each homograft and then utilized to predict viability at the time of implantation in the clinical setting; (2) antibiotic exposure is an essential step in the preparation of all homografts, however, modification of the antibiotic solution is necessary.
Liquid-filled underwater camera lens system

A novel underwater camera lens design is presented which replaces all interstitial air spaces with a low refractive index liquid to allow pressure compensation of the system in a thinner, safer diving package. The optical design presented overcomes the loss of refractive power by the liquid in a high performance, all spherical, f/1.2 lens, which operates over a 20-degree field of view. A design modulation transfer function of 0.85 is obtained at a typical CCD frequency of 50 lp/mm.
Modern induction chemotherapy before chemoradiation for bulky locally-advanced nonsmall cell lung cancer improves survival

Background: We seek to investigate whether carboplatin-based induction chemotherapy before modern day concurrent chemoradiotherapy (CCRT) improves survival in patients with bulky, locally advanced nonsmall cell lung cancer (NSCLC). Materials and Methods: This analysis included 105 patients with Stage II and III NSCLC treated with definitive CCRT from 2003 to 2013. All patients underwent definitive treatment with weekly platinum-based doublet chemotherapy delivered concurrently with 60–66 Gy of thoracic radiotherapy. Thirty patients who received induction chemotherapy before CCRT had T4 disease, N3 disease, or gross tumor volume (GTV) of >150 cm 3. These patients were compared to those with unresectable disease who received CCRT alone without induction chemotherapy. Statistical analysis included univariate and multivariate methods. Results: Mean follow-up time was 15.6 months. Patients treated with carboplatin based induction chemotherapy demonstrated prolonged overall survival (28.2 vs. 14.2 months, P = 0.04), progression free survival (12.6 vs. 9.0 months, P = 0.02), and distant metastasis free survival (15.8 vs. 10.1months, P = 0.05) compared to those who received CCRT alone without induction chemotherapy. Univariate analysis revealed older age, larger GTV, and squamous pathology as negative prognostic factors. When controlling for these factors, Cox regression analysis indicated a trend toward significantly improved overall survival in the induction cohort (P = 0.10). Conclusion: In patients with large tumors or bulky nodal NSCLC, carboplatin-based induction chemotherapy may be an important addition to definitive CCRT in the modern era. Our findings strongly support further investigation induction chemotherapy in this population.
Hospital Quality and Patient Choice: An Empirical Analysis of Mitral Valve Surgery

We document a wide variation in quality among 188 surgeons at 35 hospitals in New York state that perform mitral valve surgery. Our analysis shows that patients of different demographics and levels of acuity benefit differently from elite surgeons. However, existing healthcare provider quality information is based on population averages and so does not differentiate patients of different medical conditions. This implies that patient-centric quality information, which calibrates outcome statistics by patient demographics and acuity, can increase the ability of patients to choose the most appropriate surgeon. In this paper, we develop an approach for computing patient-centric information from outcome data and evaluate the potential health benefits from using such information to guide patients to surgeons. We estimate that the total societal benefits from using patient-centric information are comparable to those achievable by enabling the best surgeons to treat 40% more patients under population-average information.
Vitamin D, calcium homeostasis and aging

Osteoporosis is characterized by low bone mass and microarchitecture deterioration of bone tissue, leading to enhanced bone fragility and consequent increase in fracture risk. Evidence is accumulating for an important role of calcium deficiency as the process of aging is associated with disturbed calcium balance. Vitamin D is the principal factor that maintains calcium homeostasis. Increasing evidence indicates that the reason for disturbed calcium balance with age is inadequate vitamin D levels in the elderly. In this article, an overview of our current understanding of vitamin D, its metabolism, and mechanisms involved in vitamin D-mediated maintenance of calcium homeostasis is presented. In addition, mechanisms involved in age-related dysregulation of 1,25(OH)2D3 action, recommended daily doses of vitamin D and calcium, and the use of vitamin D analogs for the treatment of osteoporosis (which remains controversial) are reviewed. Elucidation of the molecular pathways of vitamin D action and modifications that occur with aging will be an active area of future research that has the potential to reveal new therapeutic strategies to maintain calcium balance.