cssi/SciSciGPT-SciSciNet huggingface dataset:
Recognition of multiple drugs by a single protein: a trivial solution of an old paradox.

Multi drug-efflux transporters recognize scores of structurally dissimilar toxic compounds and expel them from cells. The broad chemical specificity of these transporters challenges some of the basic dogmas of biochemistry and remains unexplained. To understand, at least in principle, how a protein can recognize multiple compounds, we analysed the transcriptional regulator of the Bacillus subtilis multidrug transporter Bmr. This regulator, BmrR, binds multiple dissimilar hydrophobic cations and, by activating the expression of the Bmr transporter, causes their expulsion from the cell. Crystallographic analysis of the complexes of the inducer-binding domain of BmrR with some of its inducers revealed that ligands cause disordering of the surface α-helix and penetrate the hydrophobic core of the protein, where they form multiple van der Waals and stacking interactions with hydrophobic amino acids and an electrostatic bond with the buried glutamic residue. Mutational analysis of the binding site suggests that each ligand forms a unique set of atomic contacts with the protein: each tested mutation exerted disparate effects on the binding of different ligands. The example of BmrR demonstrates that a protein can bind multiple compounds with micromolar affinities by using only electrostatic and hydrophobic interactions. Its ligand specificity can be broadened by the flexibility of the binding site. It therefore seems that the commonly expressed fascination with the broad specificity of multidrug transporters is misdirected and originates from an almost exclusive familiarity with the more sophisticated processes of specific molecular recognition that predominate among existing proteins.
A 31P NMR study of the association of uridine-3'-monophosphate to ribonuclease A.

Summary The association between ribonuclease A and its product inhibitor uridine-3′-monophosphate has been studied by 31 P nmr spectroscopy. Analysis of the chemical shifts and the linewidths of the 31 P resonance of the inhibitor over a wide range of enzyme concentrations yielded the apparent dissociation rate constant of 3200 ± 300 sec −1 at 32°C for the enzyme-inhibitor complex and an activation energy of 3.5 ± 1.0 kcal/mole for this process. The chemical shift data suggest that the phosphate group of this inhibitor is simultaneously bound to two positively charged amino acid residues at the active site of the enzyme.
Neutral line chaos and phase space structure

Phase space structure and chaos near a neutral line are studied with numerical surface-of-section (SOS) techniques and analytic methods. Results are presented for a linear neutral line model with zero crosstail electric field. It was found that particle motion can be divided into three regimes dependening on the value of the conserved canonical momentum, Py, and the conserved Hamiltonian, h. The phase space structure, using Poincare SOS plots, is highly sensitive to bn = Bn/B0 variations, but not to h variations. It is verified that the slow motion preserves the action, Jz, as evaluated by Sonnerup (1971), when the period of the fast motion is smaller than the time scale of the slow motion. Results show that the phase space structure and particle chaos depend sensitively upon Py and bn, but are independent of h.
Calculation of transient photocurrents in insulators with trapped space charge

The transit times and pulse shapes of photoinjected carriers moving in the presence of trapped space charge are derived. Two distributions are considered: uniformly trapped space charge, and trapped space charge decreasing exponentially in position from the injecting electrode. The pulse shapes are in some cases similar to those arising from transient space‐charge‐limited currents. The results in the case of the exponentially trapped space charge may have application in analysis of pulses taken in the presence of space charge trapped in the excitation layer or on the surface of insulators.
Review Essay on Pleasure and the Good Life

Despite its distinguished pedigree, hedonism is now unpopular among philosophers. But Pleasure and the Good Life: Concerning the Nature, Varieties, and Plausibility of Hedonism is Fred Feldman's able and spirited defense of hedonism, at least as a view about individual welfare or well-being.1 Pleasure and the Good Life incorporates two main projects. It aims to properly characterize hedonism, so as to reveal the wealth of its possible forms. And it aims to develop a particular form of hedonism, indeed a range of forms, which can evade standard objections to such a view. These two projects are linked, since the forms of hedonism which Feldman thinks plausible involve significant modifications of traditional hedonist claims. Let me begin with the first project, with the characterization of hedonism.
Objective estimates of westward Rossby wave and eddy propagation from sea surface height analyses

[1] An objective method to estimate westward propagation of sea surface height (SSH) anomalies is introduced and compared to a subjective technique. Both approaches use time series extracted from global SSH analyses, prepared by optimal interpolation of altimeter data, as described in detail. The cost function used in the objective method calculates the mean along-slope standard deviation, where slope is the reciprocal of propagation speed and defines the angle of linear samples through the SSH time series along each transect. The along-slope standard deviation can be computed as an extension of the Radon transform, as shown. The optimum speed estimate minimizes the cost function, and speeds with mean along-slope standard deviation within 1% of the minimum define the range of uncertainty. The 1% criteria was chosen to give a seemingly reasonable uncertainty range over a variety of cases and does not imply a specific probability that the true minimum is bounded in the uncertainty range. Applied in the central Pacific, objective speed estimates increase from 1 cm s−1 or less at the highest latitudes to above 30 cm s−1 nearer the equator. Subjective speed estimates are similar to, but generally lower than, their objective counterparts, reflecting a bias in subjective interpretation that is likely to vary among different individuals. A more detailed examination of the along-slope minimization over 160°E–95°W focuses on the higher low-latitude speeds, returning estimates of 48 cm s−1 (45 cm s−1) at 5.5°N (5.5°S) over 1993–2006. The corresponding 42–55 cm s−1 (38–65 cm s−1) uncertainty ranges bound most of the predictions from sensitivity test cases with alternate preprocessing filters or different multiyear time windows, although variability is larger south of the equator. The findings are consistent with prior studies and suggest the methods may be useful for other applications over the global ocean.
Whither Evolutionary Educational Psychology

Commentators' questions about the utility of an evolutionarily informed approach to children's schooling are addressed. I begin with discussion of our knowledge of the organization of evolved folk domains and clarify my proposals as to how evolved learning and motivational biases might influence the acquisition of nonevolved academic competencies. I then provide a model of how the Darwinian mechanisms of variability, competition, and selection at the levels of brain and cognition might operate during children's cognitive and academic development, and then I turn to the question of whether evolutionary predictions are falsifiable. I close with suggestions for future directions.
Inorganic–Organic Hybrid Solar Cell: Bridging Quantum Dots to Conjugated Polymer Nanowires

Quantum dots show great promise for fabrication of hybrid bulk heterojunction solar cells with enhanced power conversion efficiency, yet controlling the morphology and interface structure on the nanometer length scale is challenging. Here, we demonstrate quantum dot-based hybrid solar cells with improved electronic interaction between donor and acceptor components, resulting in significant improvement in short-circuit current and open-circuit voltage. CdS quantum dots were bound onto crystalline P3HT nanowires through solvent-assisted grafting and ligand exchange, leading to controlled organic–inorganic phase separation and an improved maximum power conversion efficiency of 4.1% under AM 1.5 solar illumination. Our approach can be applied to a wide range of quantum dots and polymer hybrids and is compatible with solution processing, thereby offering a general scheme for improving the efficiency of nanocrystal hybrid solar cells.
Dynamic equations on time scales which can be written in factored form

In this paper, we look at solution techniques for linear dynamic equations on time scales which can be written in a factored form. This generalizes recent work by Bohner and Akin-Bohner on Euler-Cauchy dynamic equations [1, Section 2.3]. We discuss equations containing delta-derivatives, nabla-derivatives, or a combination of the two kinds of derivatives. We conclude by describing solution techniques for a constant coefficient dynamic equation which is equivalent to another equation which can be written in factored form.
Noninvasive imaging of biological tissue structure, function, and abnormalities with optical coherence tomography

Optical coherence tomography (OCT) is a novel noninvasive optical imaging technique that enables cross-sectional imaging of highly scattering biological tissues at the axial resolution of 10 micrometers or less. Technological advances in our laboratory and others have been permitted high-contrast and high-resolution OCT imaging of turbid biological tissues at depths of up to 2-3 mm, highly desirable for screening various kinds of superficial lesions and the invasion of these lesions. In this study, we will demonstrate the potential of OCT as a powerful tool of optical biopsy or optical guided biopsy for the purpose of noninvasive imaging diagnosing malignancies in these tissues. We will present ex vivo OCT images of animal urinary bladders and lesions (including cancers) in these tissues in comparison with the corresponding histologic evaluations. Based on the comparative studies between OCT and histology, we will analyze the image contrast of OCT or the patterns in OCT images in relation to the micro morphologies in these tissues and their alternations or lesions at different stages of tumorigenesis. We will also analyze the image contrast of OCT related to the blood vessels as well as other tissue functions such as fluid penetration and buildup in these tissues. Our results demonstrate the utility of OCT in high- resolution imaging to delineate the micro morphology of highly scattering tissues such as urinary bladders and the clinical relevance of OCT in diagnosing alternations or tumor growth in these tissues. Because of limitations to specificity and resolution of current techniques, OCT is presently unable to provide distinctive diagnosis of malignancies that require subcellular imaging or identification of subtle changes in nuclear morphology. However, certain characteristics associated with malignancies in bladders such as heavy vascularization and proliferation within the urothelial tissue can be clearly demonstrated.
Screening test for identifying adolescents adversely affected by a parental drinking problem.

It is believed that 28 million children nationally are affected adversely by parental alcoholism. To help them, we must identify them. A screening tool was developed and tested to identify adolescents experiencing difficulties because of a parent's drinking problem. The single question, "Has the drinking of either parent created any problem for you?", was given in a medical screening inventory at a teenage clinic. This was followed by an eight-question semistructured interview. Of the 37 patients screened, 57% had high interview scores, suggesting that a parent's drinking had created a problem for them. Their substantiating information was consistent with the literature describing the effects of alcoholics on their children. In contrast, those with low or medium scores consistently reported no problem because of a parent's drinking. High scorers had nearly twice as many somatic symptoms and health concerns as those not reporting a problem with parental drinking. Based on the high percentage of adolescents adversely affected by a parental drinking problem and the patients' responsiveness to specific direct questions, this type of semistructured interview may be useful as a teenage intake interview in a variety of settings. Such screening could allow early referral and interventions to treat the family in which there is alcohol abuse, thus promoting healthier psychosocial development. This might also decrease the adolescent's risk of abusing alcohol. Such screening may help the physician to place vague, somatic complaints in a more meaningful perspective. Our method is a quick, brief screen for a common but easily overlooked, potentially serious family problem.
A comparison of arborescent vegetation pre- (1983) and post- (2008) outbreak of the invasive species the Asian ambrosia beetle Xyleborus glabratus in a Florida maritime hammock

Background: An outbreak of the invasive species the Asian ambrosia beetle (Xyleborus glabratus) has been devastating populations of Persea borbonia in the southeastern USA. This is the first study to compare pre- and post-outbreak plant diversities in coastal hammock communities. Aims: We compared present-day patterns to those reported before the beetle outbreak. Methods: Vegetation was surveyed in the maritime hammock forest at Little Talbot Island, northeastern Florida, in June 2008. Fifteen 100 m2 quadrats were sampled for density, frequency, and diameter at breast height of arborescent vegetation. Nested within each of the 100 m2 quadrats, an 8 m2 quadrat was sampled for densities of understory taxa. Results: Quercus virginiana remained the most common canopy species when compared with the 1984 data. Juniperus virginiana var. silicicola replaced P. borbonia as the third most common species. Thirty-two percent of adult P. borbonia were dead in 2008. In the understory assemblage, Quercus spp., Sabal pal...
In vitro model systems for evaluation of smooth muscle cell response to cryoplasty.

Abstract Restenosis is a major health care problem, with approximately 40% of angioplasties resulting in restenosis. Mechanisms related to elastic recoil, cell proliferation, and extracellular matrix (ECM) synthesis are implicated. In vivo studies have demonstrated the potential for cryotherapy to combat the process of restenosis, but the mechanisms whereby freezing and/or cooling can reduce or eliminate smooth muscle cell (SMC) proliferation and ECM synthesis are not well known. While in vivo testing is ultimately necessary, in vitro models can provide important information on thermal parameters and mechanisms of injury. However, it is important to carefully choose the model system for in vitro work on cryoinjury characterization to adequately reflect the clinical situation. In this study, we examined the differences in response to cryoinjury by SMCs from different species (rat, pig, and human) and in different cellular environments (suspension vs. tissue equivalent). Tissue equivalents, composed of cells embedded in collagen or fibrin gel, provide a 3-D tissue-like environment, while allowing for controlled composition. As reported here, all SMCs showed similar trends, but rat cells appeared less sensitive to cooling at faster cooling rates in suspension, while human SMCs were less sensitive to temperatures just above freezing when embedded in collagen. In addition, the SMCs were less sensitive in suspension than they were in collagen. Cells in suspension exhibited 70% viability at −11 °C, whereas cells in the tissue equivalent model showed only 30% survival. Future studies will aim to more adequately represent the conditions in restenosis by providing inflammatory and proliferative cues to the cells.
SpHmx,a Sea Urchin Homeobox Gene Expressed in Embryonic Pigment Cells

We describe the first complete sea urchin member of the H6 subfamily of homeobox genes. A cDNA encoding the complete protein was recovered from a Strongylocentrotus purpuratus library, and sequence comparisons demonstrate that this gene belongs to the same family as the Nkx-5.1, Nkx-5.2, and H6 genes of mammals, and the GH6 and SOHo-1 genes of chicken. In accord with current nomenclature this gene is named SpHmx. The gene is present in a single copy per haploid genome. Single-strand probe excess hybridization demonstrates that a rare maternal SpHmx mRNA is present in unfertilized eggs. Strong zygotic expression begins during the blastula stage, and the transcript is present at moderately high levels until late in development. Whole mountin situhybridization reveals a remarkable pattern of expression: In midgastrula-stage embryos SpHmx is expressed throughout the archenteron, but particularly strongly in delaminating secondary mesenchyme cells. This more general expression resolves to a dramatic pigment cell-specific pattern in prism and pluteus stages. SpHmx apparently encodes a cell-type-specific transcription factor of embryonic pigment cells.
Investigation of membrane disruption in the reaction catalyzed by cholesterol oxidase.

Dye leakage experiments were undertaken to investigate the membrane disruption properties of cholesterol oxidase. Inspection of the X-ray crystal structures of cholesterol oxidase suggested that an active-site “lid” opens in order to bind substrate [Li, J., Vrielink, A., Brick, P., & Blow, D. M. (1993) Biochemistry 32, 11507−11515]. We tested whether the interaction of the putative active-site lid with the membrane was sufficiently disruptive of the membrane structure to cause leakage or lysis of the cell membrane. Vesicles (100 nm) composed of egg phosphatidylcholine, 2-palmitoyl-3-oleoyl-1-sn-phosphatidylethanolamine, and 2-palmitoyl-3-oleoyl-1-sn-phosphatidylcholine were used in this study to mimic biomembranes. To separate the effects of membrane binding from conversion of cholesterol to cholest-4-en-3-one, the active-site mutant E361Q was utilized. In the reaction catalyzed by E361Q, isomerization of the cholest-5-en-3-one intermediate is suppressed and cholest-5-en-3-one is the major product isolate...
Treatment of pain due to fibromyalgia with topical capsaicin: A pilot study

The efficacy and safety of 0.025% capsaicin cream was evaluated as a treatment for the pain associated with primary fibromyalgia. Forty-five patients received capsaicin cream or vehicle four times daily in this 4-week, double-blind, vehicle-controlled study. Capsaicin-treated patients reported significantly less tenderness in the tender points than patients who received vehicle at week 4 (P = .03). There were no statistically significant differences between groups in the visual analog scale for pain. A significant increase (P = .02) in grip strength was noted at week 2 for the capsaicin-treated patients. The most common adverse effect attributable to capsaicin was transient burning or stinging at the application site. This study suggests that capsaicin cream may be a useful therapy for pain associated with primary fibromyalgia; however, additional confirmatory studies are needed.
Heterosis for brain myelin content in mice.

Biochemical evidence of heterosis (hybrid vigor) for brain myelin content is presented. The concentrations of cerebroside and GM1 ganglioside, two glycolipids known to be abundant in myelin, were higher in the brains of (C57BL/6J × DBA/2J) F1 hybrids than in the brains of either parental strain. Furthermore, brain water content, which is known to be inversely related to myelin content, was lower in the F1 hybrids, especially during the most active period of myelin synthesis. Heterosis was not observed, however, for total brain ganglioside concentration. Additionally, the results do not substantiate a direct developmental-genetic relationship between brain myelin content and susceptibility to audiogenic seizures.
Important interaction effects in the growth of InGaN violet light emitting diodes by MOCVD

The growth of violet light emitting diodes (LEDs) was optimized using a statistical design of experiment (DOE) approach and several important interaction effects were found. The DOEs studied the effect of several variables on the well layer, the barrier layer, and the pAlGaN cladding layer. These variables included the gallium flow rate, the indium flow rate, the growth temperature, and the growth time for the well layer, the ammonia flow in the active region, the barrier growth time, and the Si doping of the barrier, as well as the growth time, growth temperature and Mg doping of the pAlGaN cladding layer. The LEDs were optimized based on combinations of several responses from photoluminescence and electroluminescence measurements. An overall process desirability was obtained, based on achieving the desired wavelength and maximizing the PL intensity and optical output power. Significant interactions between variables played a major role in the optimization of optical output power as well the emission wavelength. The understanding of these interactions led to the optimization of the LEDs both by improvements in the structure and improvements in the quality of the layers. Several of the interactions will be explained based on kinetic models of GaN growth by MOCVD.
Loss factor for short bunches in azimuthally symmetric tapered structures

We use the program ECHO to study numerically the loss factor of axisymmetric cavities and collimators with and without tapering. We consider a Gaussian driving bunch of length $\ensuremath{\sigma}$, and structures with inner radius $b$, outer radius $d$, cavity gap (or collimator inner length) $g$, and taper length $L$. In all cases we consider a short bunch with $\ensuremath{\sigma}\ensuremath{\ll}b$. For the untapered structures ($L=0$), in certain regimes, we describe our numerical results using the known expressions for a step transition and for the diffraction model. In addition, we identify new regimes where $gl\ensuremath{\sigma}$ and/or $d\ensuremath{-}bl\ensuremath{\sigma}$, for which the data must be described by new phenomenological expressions. For a tapered collimator with $d\ensuremath{-}bgb$, we present a phenomenological formula which accurately describes the dependence of the loss factor on the parameters $\ensuremath{\sigma}$, $b$, $d$, and $L$. This formula also holds for a tapered cavity with $gg{d}^{2}/\ensuremath{\sigma}$ and $d\ensuremath{-}bgb$.
The acid‐catalyzed addition of alkoxyl groups to the olefinic double bonds of soybean oil

The acid-catalyzed reaction of soybean oil with the homologous series of straight-chain alcohols: methyl, ethyl, n-propyl, n-butyl and n-hexyl in a pressurized system yielded completely transesterified products and 18-31% substituted alkyl ethers. Mass spectrometry of the hydrogenated methyl ester derivatives showed that the addition reaction occurred at one of three double bonds of the unsaturated fatty acids. The reaction with three secondary alcohols yielded only 0.1-2.5% substituted alkyl ethers.
C-terminal Domain Modulates the Nucleic Acid Chaperone Activity of Human T-cell Leukemia Virus Type 1 Nucleocapsid Protein via an Electrostatic Mechanism

Retroviral nucleocapsid (NC) proteins are molecular chaperones that facilitate nucleic acid (NA) remodeling events critical in viral replication processes such as reverse transcription. Surprisingly, the NC protein from human T-cell leukemia virus type 1 (HTLV-1) is an extremely poor NA chaperone. Using bulk and single molecule methods, we find that removal of the anionic C-terminal domain (CTD) of HTLV-1 NC results in a protein with chaperone properties comparable with that of other retroviral NCs. Increasing the ionic strength of the solution also improves the chaperone activity of full-length HTLV-1 NC. To determine how the CTD negatively modulates the chaperone activity of HTLV-1 NC, we quantified the thermodynamics and kinetics of wild-type and mutant HTLV-1 NC/NA interactions. The wild-type protein exhibits very slow dissociation kinetics, and removal of the CTD or mutations that eliminate acidic residues dramatically increase the protein/DNA interaction kinetics. Taken together, these results suggest that the anionic CTD interacts with the cationic N-terminal domain intramolecularly when HTLV-1 NC is not bound to nucleic acids, and similar interactions occur between neighboring molecules when NC is NA-bound. The intramolecular N-terminal domain-CTD attraction slows down the association of the HTLV-1 NC with NA, whereas the intermolecular interaction leads to multimerization of HTLV-1 NC on the NA. The latter inhibits both NA/NC aggregation and rapid protein dissociation from single-stranded DNA. These features make HTLV-1 NC a poor NA chaperone, despite its robust duplex destabilizing capability.
Pharmacokinetics of 2',3'-Dideoxycytidine after High-Dose Administration to Rats

Abstract The pharmacokinetics of 2',3'-dideoxycytidine (DDC) was characterized after iv administration of a high dose (500 mg/kg) of DDC to rats. The high dose was administered to optimally characterize plasma DDC concentration and urinary excretion rate versus time profiles. Drug concentrations in plasma and urine were determined by HPLC. Plasma DDC concentrations and DDC urinary excretion rates as a function of time were fitted simultaneously to a two-compartment model. Drug concentrations in plasma and urinary excretion rates declined in parallel with a terminal half-life of 1.29 ± 0.07 h (mean ± SD). Total, renal, and nonrenal clearances were 1.48 ± 0.15, 0.73 ± 0.38, and 0.75 ± 0.36 L/h/kg, respectively. Renal clearance exceeds glomerular filtration rate in the rat, indicating that DDC undergoes active renal tubular secretion. The unbound secretory intrinsic clearance for DDC renal excretion was moderate, with a value of 0.4 L/h. The steady-state volume of distribution of DDC was 1.25 ± 0.13 L/kg. Pharmacokinetic parameters after iv administration of 500 mg/kg of DDC were virtually identical to those reported previously after administration of 10–200 mg/kg of the nucleoside to rats. Thus, the disposition of DDC in the rat is independent of dose over a range of 10 to 500 mg/kg. High doses of DDC can be administered to rats to allow for complete characterization of the disposition pattern of the drug without complexities due to any nonlinearity.
Case Studies of Patients Successfully and Unsuccessfully Managed Pre- and Post-Fontan Procedure

As a result of advances and modifications in surgical procedures and the development of drugs for pulmonary arterial hypertension, many patients who have undergone Fontan procedures are able to enjoy good quality of life, without pulmonary arterial hypertension and severe complications. In Shizuoka Children's Hospital, drugs for pulmonary arterial hypertension have long been given to Fontan candidates and patients with established Fontan circulation to maintain sufficient pulmonary blood flow and suppress pulmonary arterial hypertension. We present three typical cases that were treated with anti-pulmonary hypertensive drugs before or after Fontan procedure. The first case had asplenia syndrome, and a single ventricle with major aortopulmonary collateral arteries. Anti-pulmonary hypertensive therapy permitted a Fontan procedure and maintained a good long-term quality of life. The second case was a Down syndrome patient who had progressive cyanosis after a Fontan operation. Anti-pulmonary hypertensive therapy improved cyanosis. The third case suffered from protein-losing enteropathy, for which all procedures and medical therapies were ineffective. Fontan candidates and patients with Fontan circulation have varied anatomical backgrounds and pulmonary properties. We must identify the conditions that lead to successful Fontan procedure and Fontan circulation correction, as well as conditions that result in failed Fontan procedure and poorly-controlled Fontan circulation.
Ontogeny of VEGF, IGF-I, and GH in neonatal rat serum, vitreous fluid, and retina from birth to weaning.

PURPOSE. Vascular endothelial growth factor (VEGF), insulinlike growth factor (IGF)-I, and growth hormone (GH) are major regulators of physical growth, as well as normal and pathologic retinal development. Ocular tissues are protected by the blood– ocular barrier. This study was conducted to test the hypothesis that the ontogenic profiles of VEGF, IGF-I, and GH in the rat serum, vitreous fluid, and retina are compartment specific, and that the vitreous is a reservoir for retinal growth factors. METHODS. Sprague-Dawley rat pups were killed at birth (postnatal day [P]0) and at P7, P14, and P21. At death, serum, vitreous fluid, and retinal homogenates were analyzed for ontogeny of VEGF, IGF-I, and GH. RESULTS. VEGF levels were 10 times higher in the vitreous than in serum at all stages of development. Vitreous and serum VEGF levels progressively declined, with lowest concentrations at P21. Retinal VEGF levels increased with the highest concentration at P21. IGF-I levels in the vitreous decreased from P7 through P21. IGF-I levels in serum and retinal homogenates increased with advancing postnatal age. Although IGF-I levels were four times higher in the vitreous than in the retina at P0, equilibration was achieved at P21. GH levels in the vitreous were 10 times lower than serum levels, were decreased at P14 and P21, and remained unchanged from P0 through P21 in the retina. CONCLUSIONS. VEGF and IGF-I act in concert to promote retinal development with the vitreous fluid as a reservoir. The ontogenic profiles of VEGF, IGF-I and GH in the serum and ocular compartments are specific. These differences should be considered when therapies for ROP are proposed. (Invest Ophthalmol Vis Sci. 2006;47:738 –744) DOI:10.1167/iovs.05-1046
Sarbanes–Oxley Act and patterns in stock returns around executive stock option exercise disclosures

We document negative stock returns and elevated trading volumes around executives’ early option exercise disclosures post-SOX, but not pre-SOX. This stock price reaction is incomplete, and the negative stock price drift is smaller post-SOX compared to pre-SOX. We also show effects of media coverage in the stock price response to exercise disclosures in the post-SOX period. These findings provide evidence that the requirement mandated by SOX to disclose executives’ stock option exercises within two business days, and the increased media coverage, improves investors’ ability to incorporate into stock prices in a timely fashion the information conveyed by these exercises.
The Effects of Bariatric Surgery on Asthma Severity

Background Excess body weight increases both the risk and severity of asthma. Several studies indicate that bariatric surgery decreases asthma severity, but either enrolled few patients or were not focused primarily on asthma. Furthermore, none compared the effects of different bariatric surgical procedures.
Liquid chromatography–electrospray tandem mass spectrometry investigations of fragmentation pathways of biliary 4,4′-methylenedianiline conjugates produced in rats

4,4′-methylenedianiline (DAPM) is the main building block for production of 4,4′-methylenediphenyldiisocyanate that has been widely used in the manufacturing of polyurethane materials including medical devices. Although it was revealed that damage to biliary epithelial cells of the liver and common bile duct occurred upon acute exposure to DAPM, the exact mechanism of DAPM toxicity is not fully understood. Both phase I and II biotransformations of DAPM, some of which generate reactive intermediates, are characterized in detail by liquid chromatography electrospray tandem mass spectrometry. The two most prominent metabolites found in rat bile (M2 and M7) implicated glutathione, glucuronic acid, and glycine conjugations (phase II) following hydroxylation, and N-oxidation (phase I). Their decomposition pathways, as evidenced by MS n experiments, have been elucidated in detail.
Social Contract Theory Implications for Professional Ethics

Social contract theorists of the 17th and 18th centuries provide diverse accounts of human nature and the social processes that shape conflict, cooperation, and compliance. These ideas are applied to the challenges of contemporary public administration, specifically; the effort that often underlies both the search for public administration's identity and professionalization more generally: the effort to build consensus on shared values and ideals and ensure ethical practice with a minimum of external policing. A consideration of social contract theory yields a heavy dose of realism when it comes to this objective but invites neither despondency nor complacency.
True-amplitude prestack depth migration

Most current true-amplitude migrations correct only for geometric spreading. We present a new prestack depth-migration method that uses the framework of reverse-time migration to compensate for geometric spreading, intrinsic Q losses, and transmission losses. Geometric spreading is implicitly compensated by full two-way wave propagation. Intrinsic Q losses are handled by including a Q -dependent term in the wave equation. Transmission losses are compensated based on an estimation of angle-dependent reflectivity using a two-pass recursive reverse-time prestack migration. The image condition used is the ratio of receiver/source wavefield amplitudes. Two-dimensional tests using synthetic data for a dipping-layer model and a salt model show that loss-compensating prestack depth migration can produce reliable angle-dependent reflection coefficients at the target. The reflection coefficient curves are fitted to give least-squares estimates of the velocity ratio at the target. The main new result is a procedure ...
Synthesis and Characterization of Supported Cobalt–Manganese Nanoparticles as Model Catalysts for Fischer–Tropsch Synthesis

Author(s): Werner, S; Johnson, GR; Bell, AT | Abstract: Supported Co is an effective catalyst for the Fischer-Tropsch synthesis of various hydrocarbon products that can be converted to diesel. Recent studies have shown that the formation of methane can be suppressed and the formation of C5+ products enhanced by promoting Co with Mn. Because the activity and product selectivity of Co-based catalysts are dependent on the size of Co nanoparticles and the extent of Co promotion by Mn, it is desirable to understand these effects by investigating the performance of Co nanoparticles with well-defined size and elemental composition. The present study was undertaken with the aim of producing well-defined nanoparticles of Co and Co-Mn and then supporting them on silica. Co and Co-Mn particles were synthesized through the polyol reduction of Co and Mn acetylacetonates. By controlling synthesis conditions, Co particles with diameters of 7-10 nm and similarly sized Co-Mn (Mn/Co=0.1) particles were prepared. XRD and elemental mapping with scanning TEM-energy-dispersive X-ray spectroscopy and scanning TEM-electron energy loss spectroscopy studies suggested that most of the Mn species was associated with the Co particles. Ex situ prepared Co and Co-Mn nanoparticles were first supported on silica and then investigated for the catalytic activity for the Fischer-Tropsch synthesis. The turnover frequencies and product distributions obtained with silica-supported Co and Co-Mn nanoparticles were similar to those obtained with catalysts prepared by using the conventional incipient wetness impregnation method. However, the rate of CO consumption per mass of Co was much lower for the catalysts produced by supporting ex situ prepared nanoparticles. This effect was attributed to the sintering of the nanoparticles during their calcination and reduction. Magnetic interactions among nanoparticles during their immobilization and thermal pretreatment were identified as the primary cause of sintering. Balancing yin and yang energy: The immobilization of well-defined cobalt-manganese nanoparticles on porous supports leads to the formation of Fischer-Tropsch catalysts with turnover frequencies and product selectivities comparable to those of conventionally prepared catalysts. The catalytic activity per cobalt mass is found to be significantly lower owing to sintering. Magnetic interactions among nanoparticles during immobilization and thermal pretreatment are identified as the primary cause of this phenomenon.
Economics and search

They say that economists are people who are good with numbers but don’t have the personality to become accountants. I want to belie that mild-mannered image by doing something rash and even downright dangerous: I want to talk to you about some work in my subject, economics, that I think might be relevant to the work in your subject, information retrieval. I take this step with considerable trepidation, since I know that it is unlikely to be successful. It is rare that an outsider can really contribute anything useful to another subject, as I know from listening to innumerable speeches by the physicists, biologists, and mathematicians about what their subject has to say about economics. However, it is also true that such cross fertilization can be extremely stimulating. Economics has, in fact, learned a lot from physics, biology and mathematics. And even when such attempts at interdisciplinary communication fail, as they often do, it is often interesting to see how others approach the questions that are your main business. Here are three areas in economics where I think there might be some fruitful cross-fertilization:
Proteolytic Processing Yields Two Secreted Forms of Sonic hedgehog

Sonic hedgehog (Shh) is expressed in tissues with known signalling capacities, such as the notochord, the floor plate of the central nervous system, and the zone of polarizing activity in the limb. Several lines of evidence indicate that Shh is involved in floor plate induction, somite patterning, and regulation of anterior-posterior polarity in the vertebrate limb. In this report, we investigate the biochemical behavior of Shh in a variety of expression systems and embryonic tissues. Expression of mouse Shh in Xenopus oocytes, COS cells, and baculovirus-infected insect cells demonstrates that in addition to signal peptide cleavage and N-linked glycosylation, chicken and mouse Shh proteins undergo additional proteolytic processing to yield two peptides with molecular masses of approximately 19 kDa (amino terminus) and 27 kDa (carboxy terminus), both of which are secreted. In transfected COS cells, we show that the 19-kDa peptide does not accumulate significantly in the medium unless heparin or suramin is added, suggesting that this peptide associates with the cell surface or extracellular matrix. This retention appears to depend on sequences in the carboxy-terminal part of the peptide. Finally, detection of the 19-kDa product in a variety of mouse and chicken embryonic tissues demonstrates that the proteolytic processing observed in cell culture is a normal aspect of Shh processing in embryonic development. These results raise the possibility that amino- and carboxyl-terminal regions of Shh may have distinct functions in regulating cell-cell interactions in the vertebrate embryo.
Homogenizing Metal Oxide Catalysts

Abstract Metal oxide particles have been prepared which are “soluble” in hydrocarbon solvents. The reaction of either a metal (or its metal oxide) with water, mineral spirits, and a mixture of carboxylic acids can result in hydrocarbon-miscible metal oxide core particles of 20-1000A diameter sizes which are coated with a layer of hydrophobic carboxylates. This will only occur if the metal:acid ratio exceeds one. The particle size increases as the metaltacid ratio increases. The surface carboxylate groups are in equilibrium, preventing the use of colligative property measurements in determining molecular weights. Sedimentation velocity studies confirmed that particle aggregation equilibria occur which are solvent dependent. Aggregation is more serious in polar solvents. The distribution of carboxylic acids used did not effect the particle size. Cobalt and manganese oxide particles have been used in oxidations of cyclohexane, toluene, and xylenes. Cobalt oxides were used in hydroformylations of 1-pentene, N...
Characteristics of the Pupillary Light Reflex in the Macaque Monkey: Metrics

To investigate whether the simian light reflex is a reasonable model for the human light reflex, we elicited pupillary responses in three behaving rhesus macaques. We measured the change in pupilla...
The Case for Daily Physical Education

(2007). The Case for Daily Physical Education. Journal of Physical Education, Recreation & Dance: Vol. 78, No. 5, pp. 18-21.
General Versus Specific Victim Blaming

The authors investigated (a) whether victim blaming is a general variable in a person's make-up or (b) whether the extent of blaming depends on the kind of victim considered. The authors evaluated scales for blaming (a) victims in general, (b) society in general, (c) a specific kind of victim (i.e., AIDS), and (d) the society in which AIDS victims live. The general and specific scales had favorable psychometric properties, including reliability. General and specific victim blaming were significantly and positively correlated, whereas victim blaming and society blaming were not significantly correlated. Multiple regression analyses provided evidence of construct validity for the scales. All blaming variables were significantly related in the hypothesized directions to social distance, social responsibility, and discrimination (regarding persons with AIDS). The general and specific scales made significant and unique contributions. Implications for attribution theory and research are specified.
Three-Dimensional Relationships between Hippocampal Synapses and Astrocytes

Recent studies show that glutamate transporter-mediated currents occur in astrocytes when glutamate is released from hippocampal synapses. These transporters remove excess glutamate from the extracellular space, thereby facilitating synaptic input specificity and preventing neurotoxicity. Little is known about the position of astrocytic processes at hippocampal synapses. Serial electron microscopy and three-dimensional analyses were used to investigate structural relationships between astrocytes and synapses in stratum radiatum of hippocampal area CA1 in the mature rat in vivo and in slices. Only 57 +/- 11% of the synapses had astrocytic processes apposed to them. Of these, the astrocytic processes surrounded less than half (0.43 +/- 22) of the synaptic interface. Other studies suggest that astrocytes extend processes toward higher concentrations of glutamate; thus the presence of astrocytic processes at particular hippocampal synapses might signal which ones are releasing glutamate. The distance between nearest neighboring synapses was usually (approximately 95%) <1 microgram. Astrocytic processes occurred along the extracellular path between 33% of the neighboring synapses, neuronal processes occurred along the path between another 66% of the neighboring synapses, and only 1% of the synapses were close enough such that neither astrocytic nor neuronal processes occurred between them. These morphological arrangements suggest that the glutamate released at approximately two-thirds of hippocampal synapses might diffuse to other synapses, unless neuronal glutamate transporters are more effective than previously reported. The findings also suggest that physiological recordings made from hippocampal astrocytes do not uniformly sample the glutamate released from all hippocampal synapses.
Social Isolation and Labor Market Insulation: Network and Neighborhood Effects on Less-Educated Urban Workers

This study examines the influence of neighborhood poverty and social networks on labor market experiences of less-educated urban job seekers. Data come from the Multi-City Survey of Urban Inequalit...
Role of dCA3 efferents via the fimbria in the acquisition of a delay nonmatch to place task.

Dorsal CA3, but not dorsal CA1, lesioned rats are impaired in the acquisition of a delay nonmatch to place task. In this study, dorsal CA3 efferent fibers in the fimbria were transected; while taking care to spare afferent fibers from the medial septum. Neurophysiological, anatomical tracing, and histochemical data suggest that the transection was selective to dorsal CA3 efferent fibers and spared afferents from the medial septum. Rats showed a deficit for acquisition, but not for performance once learned. One possible explanation is that a small change to the cholinergic inputs to dCA3 caused by a decrease in dorsal CA3 efferent signals reaching the medial septum may impair new learning but not performance of a task once learned. © 2007 Wiley-Liss, Inc.
Helicoverpa zea CYP6B8 and CYP321A1: different molecular solutions to the problem of metabolizing plant toxins and insecticides

Under continual exposure to naturally occurring plant toxins and synthetic insecticides, insects have evolved cytochrome P450 monooxygenases (P450s) capable of metabolizing a wide range of structurally different compounds. Two such P450s, CYP6B8 and CYP321A1, expressed in Helicoverpa zea (a lepidopteran) in response to plant allelochemicals and plant signaling molecules metabolize these compounds with varying efficiencies. While sequence alignments of these proteins indicate highly divergent substrate recognition sites (SRSs), homology models developed for them indicate that the two active site cavities have essentially the same volume with distinct shapes dictated by side-chain differences in SRS1 and SRS5. CYP6B8 has a narrower active site cavity extending from substrate access channel pw2a with a very narrow access to the ferryl oxygen atom. This predicted shape suggests that bulkier molecules bind further from the ferryl oxygen at positions that are not as effectively metabolized. In contrast, CYP321A1 is predicted to have a more spacious cavity allowing larger molecules to access the heme-bound oxygen. The metabolic profiles for several plant toxins (xanthotoxin, angelicin) and insecticides (cypermethrin, aldrin and diazinon) correlate well with these predictive models. The absence of Thr in the I helix of CYP321A1 and hydroxyl groups on many of its substrates suggests that this insect P450 mediates oxygen activation by a mechanism different from that employed by CYP107A1 and CYP158A1, which are two bacterial P450s also lacking Thr in their I helix, and most other P450s that contain Thr in their I helix.
Delay Test Quality Evaluation Using Bounded Gate Delays

Conventionally, path delay tests are derived in a delay-independent manner, which causes most faults to be robustly untestable. Many non-robust tests are invalidated by hazards caused primarily due to non-zero delays of off-path circuit elements. Thus, non-robust tests are of limited value when process variations change gate delays. The authors propose a bounded gate delay model for test quality evaluation and give a novel simulation algorithm that is less pessimistic than previous approaches. The key idea is that certain time-correlations among the multiple transitions at the inputs of a gate cannot cause hazard at its output. The authors maintain "ambiguity lists" for gates. These are propagated with events, similar to fault lists in a traditional concurrent fault simulation. They are used to suppress erroneous unknown states. Experimental results for ISCAS benchmarks with gate delay variation of plusmn14% show a miscorrelation of critical path delay as much as 20%.
Total dose radiation effect simulations on a high-precision data acquisition system

A novel method to evaluate total dose radiation response on large mixed signal circuits is described. The method is based on partly behavioral, partly structural simulation on the VHDL-AMS language. Results obtained with the developed simulation method are compared to total dose testing results of an embedded high-precision data acquisition system. The system was total dose tested until functional failure in a Cobalt-60 irradiation chamber. Photoemission microscopy (PEM) analysis showed severe TID induced leakage currents inside the 1.2 kbyte SRAM memory sub-system. The SRAM sub-system was TID simulated with the developed method, and the results were compared to the irradiation test results. The simulation results suggest that the drain-to-source leakage currents inside the SRAM sub-system might not be the only cause for the system failure.