cssi/SciSciGPT-SciSciNet huggingface dataset:
Dietary Effects on Drug Metabolism and Transport

Metabolic food-drug interactions occur when the consumption of a particular food modulates the activity of a drug-metabolising enzyme system, resulting in an alteration of the pharmacokinetics of drugs metabolised by that system. A number of these interactions have been reported. Foods that contain complex mixtures of phytochemicals, such as fruits, vegetables, herbs, spices and teas, have the greatest potential to induce or inhibit the activity of drug-metabolising enzymes, although dietary macroconstituents (i.e. total protein, fat and carbohydrate ratios, and total energy intake) can also have effects. Particularly large interactions may result from the consumption of herbal dietary supplements. Cytochrome P450 (CYP) 3A4 appears to be especially sensitive to dietary effects, as demonstrated by reports of potentially clinically important interactions involving orally administered drugs that are substrates of this enzyme. For example, interactions of grapefruit juice with cyclosporin and felodipine, St John's wort with cyclosporin and indinavir, and red wine with cyclosporin, have the potential to require dosage adjustment to maintain drug concentrations within their therapeutic windows. The susceptibility of CYP3A4 to modulation by food constituents may be related to its high level of expression in the intestine, as well as its broad substrate specificity. Reported ethnic differences in the activity of this enzyme may be partly due to dietary factors. Food-drug interactions involving CYP1A2, CYP2E1, glucuronosyltransferases and glutathione S-transferases have also been documented, although most of these interactions are modest in magnitude and clinically relevant only for drugs that have a narrow therapeutic range. Recently, interactions involving drug transporters, including P-glycoprotein and the organic anion transporting polypeptide, have also been identified. Further research is needed to determine the scope, magnitude and clinical importance of food effects on drug metabolism and transport.
Vision and eye health in children 36 to <72 months: proposed data system.

ABSTRACTPurposeThis article provides a rationale for developing an integrated data system for recording vision screening and eye care follow-up outcomes in preschool-aged children. The recommendations were developed by the National Expert Panel to the National Center for Children’s Vision and Eye He
The Effects of Stock Splits on Clientele: Is Tick Size Relevant?

We explore whether the relation between stock splits and clientele is driven by binding tick sizes. We find little evidence that firms adjusted prices to maintain similarly binding tick sizes as the NYSE reduced tick sizes. Furthermore, though splits that increase the extent to which tick sizes are binding are associated with greater increases in spreads, these splits experience similar changes in measures related to clientele, including trade size, breadth of individual and institutional ownership, and analyst following. We find little evidence supporting theories, such as spread-induced sponsorship, that rely on binding tick sizes to link splits and clientele.
Cell cycle–related kinase links androgen receptor and β-catenin signaling in hepatocellular carcinoma: Why are men at a loss?

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. It is more prevalent in men than women. Related to this, recent genetic studies have revealed a causal role for androgen receptor (AR) in hepatocarcinogenesis, but the underlying molecular mechanism remains unclear. Here, we used genome-wide location and functional analyses to identify a critical mediator of AR signaling — cell cycle‐related kinase (CCRK) — that drives hepatocarcinogenesis via a signaling pathway dependent on β-catenin and T cell factor (TCF). Ligand-bound AR activated CCRK transcription and protein expression via direct binding to the androgen-responsive element of the CCRK promoter in human HCC cell lines. In vitro analyses showed that CCRK was critical in human cell lines for AR-induced cell cycle progression, hepatocellular proliferation, and malignant transformation. Ectopic expression of CCRK in immortalized human liver cells activated β-catenin/TCF signaling to stimulate cell cycle progression and to induce tumor formation, as shown in both xenograft and orthotopic models. Conversely, knockdown of CCRK decreased HCC cell growth, and this could be rescued by constitutively active β-catenin or TCF. In primary human HCC tissue samples, AR, CCRK, and βcatenin were concordantly overexpressed in the tumor cells. Furthermore, CCRK overexpression correlated with the tumor staging and poor overall survival of patients. Our results reveal a direct AR transcriptional target, CCRK, that promotes hepatocarcinogenesis through the upregulation of β-catenin/TCF signaling. COMMENTS Hepatocellular Carcinoma (HCC) is the fifth most common cancer and the third cause of cancer-related death worldwide. HCC usually occurs in the backdrop of chronic liver disease due to hepatitis of various etiologies. Men are at higher risk to develop HCC and the role of male sex hormones as tumor promoters is highly relevant (1). The Androgen Receptor is critical for the development and maintenance of the male sexual phenotype (2). It is a type of nuclear receptor that regulates gene transcription when activated by androgens. Upon activation, AR translocates to the nucleus, binds to androgen response elements (ARE) on target genes and engages crosstalk with transcription factors to eventually induce transcription of certain genes. Overexpression of AR has been reported in 60%-80% of human HCCs (3) making it a formidable player in male HCC. In addition, liver specific
Individual and Social Network Factors that Predict Entry to Drug Treatment

Prospective data were analyzed to examine individual and social network characteristics that predict entry into drug treatment among a sample of 557 heroin and cocaine users. Entering treatment was associated with being HIV positive [AOR: 2.25, 95% CI: 1.33–3.81] and a history of drug treatment [AOR: 3.41, 95% CI: 2.19–5.31]. Individuals with a greater number of social network members who were in drug treatment [AOR: 1.29, 95% CI: 1.07–1.56] and fewer network members who smoked crack [AOR: 0.86, 95% CI: 0.75–0.99] were more likely to enter treatment. Social network-based interventions that promote successful outcomes in drug treatment are needed.
Characterization of a metabolite-cytochrome P-450 complex derived from the aerobic metabolism of an insect juvenile hormone analog by rat microsomal fractions.

Abstract The juvenile hormone analog, ( E )-4-[(6,7-epoxy-3,7-dimethyl-2-nonenyl)oxyl]-1,2-(methylenedioxy)benzene (RO-20-3600), was aerobically metabolized by and formed a metabolite complex with hepatic microsomal cytochrome P 450 in vitro and in vivo . The K m for the formation of the complex with hepatic microsomal cytochrome P 450 obtained from rats pretreated with phenobarbital was 74 μ m . The complex, once formed, is stable and cannot be discharged by treatment with either CO, potassium ferricyanide, peroxide, or dithionite. The complex has two spectral forms: with oxidized cytochrome P 450 (Fe +3 ), it has a single Soret band centered at 442 nm; with reduced cytochrome P 450 (Fe +2 ), it has Soret bands centered at about 427 and 455 nm. The results obtained when the spectral properties of the metabolite complex, its rate for formation, and its effects on drug metabolism were studied suggest that the complex may be involved with and/or responsible for the juvenile hormone properties of RO-20-3600. The metabolite complex inhibits a significant amount of cytochrome P 450 and most likely prevents the metabolism of endogenous juvenile hormone in insects.
Potential for Cavitation-Mediated Tissue Damage in Shockwave Lithotripsy

Purpose: Shockwave lithotripsy (SWL) injures renal tissue, and cavitation has been reported to mediate some of these effects. Much of the work characterizing the cavitation injury of SWL has been performed in small animals or in vitro. We describe experiments that promote cavitation during SWL and estimate the spatial distribution of the resulting hemorrhagic lesion in a large-animal (porcine) model of clinical lithotripsy. Materials and Methods: The lower pole calix of the left kidney in female farm pigs was targeted for SWL with a Dornier HM3 lithotripter. Intraventricular injections of polystyrene microspheres were made before and at intervals during lithotripsy to blanket systemic circulation with cavitation nuclei. Following SWL, the abdominal viscera were inspected and the kidneys were processed for morphologic analysis. Results: Extensive surface hemorrhage occurred over both the targeted and contralateral kidneys, along with widespread petechial hemorrhage over the spleen, intestines, and peritone...
A Multi Grid Maximum Likelihood Reconstruction Algorithm For Positron Emission Tomography

The problem of reconstruction in Positron Emission Tomography (PET) is basically estimating the number of photon pairs emitted from the source. Using the concept of maximum likelihood (ML) algorithm, the problem of reconstruction is reduced to determining an estimate of the emitter density that maximizes the probability of observing the actual detector count data over all possible emitter density distributions. A solution using this type of expectation maximization (EM) algorithm with a fixed grid size is severely handicapped by the slow convergence rate, the large computation time, and the non-uniform correction efficiency of each iteration making the algorithm very sensitive to the image-pattern. An efficient knowledge-based multi-grid reconstruction algorithm based on ML approach is presented to overcome these problems.
Catalytic Dehydrogenation of Cycloalkanes to Arenes by a Dihydrido Iridium P−C−P Pincer Complex

We recently found that the iridium P-C-P pincer complex IrH{sub 2}[C{sub 6}H{sub 3}-2,6-(CH{sub 2}-PBu{sup T}{sub 2}){sub 2}] (1) is a highly active, homogeneous catalyst for the transfer dehydrogenation of cyclooctane with unusual long-term stability at temperatures as high as 200 {degree}C. This reactivity has now been extended to the catalytic transfer dehydrogenation of cycloalkanes to arenes. We report this novel catalytic activity as well as the results of an X-ray structure determination of 1. 15 refs., 1 fig., 1 tab.
Economic Evaluation of Carotid Artery Stenting Versus Carotid Endarterectomy for the Treatment of Carotid Artery Stenosis

Background The clinical effectiveness of carotid endarterectomy (CEA) is well established. But the economic impact of CEA and carotid artery stenting (CAS) is still uncertain. The objective of this study was to compare hospital costs and reimbursement for CAS and CEA. Study Design We performed a retrospective database analysis on pair-matched patients who underwent CEA (n = 31) and CAS (n = 31) at the Richard M Ross Heart Hospital in Columbus, OH. The hospital's clinical and financial databases were used to obtain patient-specific information and procedural charges. Cost data were generated by applying the hospital's ratio of cost to charges for all DRG charges. The Wilcoxon signed-rank test was used to examine the differences between costs of these procedures. Results Data are reported as mean ± SD. The mean age of patients in CAS group was 70.14 years (± 1.60 years) versus 68.64 years (± 1.75 years) for CEA patients (p Conclusions CAS is significantly more expensive than CEA, with a major portion of cost attributed to the total procedural cost. The hospital experienced significant savings from CEA procedures compared with CAS under all DRG classifications and insurers. Hospitals must develop new financial strategies and improve the efficiency of infrastructure to make CAS financially viable.
Evaluating a satellite altimeter-derived digital elevation model of Antarctica using precision kinematic GPS profiling

Abstract The Radarsat Antarctic Mapping Project Digital Elevation Model (RAMP DEM) represents the best currently available compilation of Antarctic surface topography. Satellite altimeter data provide the foundation for most of the DEM, augmented where available with other mapping and survey information. We use precision global positioning system (GPS) data collected continuously along several profiles 150–320 km long in West and East Antarctica to independently assess the performance of the DEM in capturing the shape of the ice sheet surface. Overall, the DEM performs well at representing the gross morphology of the ice sheet north of 81.4°S. South of this latitude, where the DEM is unconstrained by high-resolution altimeter data, the DEM is less capable of capturing surface topographic detail, and elevation accuracy degrades. The comparison with GPS data indicates that the horizontal resolution of the DEM over well-constrained inland portions of the ice sheet is approximately 8 km. This resolution is larger than initial estimates, meaning that many of the important topographic details of the ice sheet surface are omitted. This omission has implications for applications using the DEM to understand patterns of local accumulation rate variability or for mapping ice flow features. There also appear to be some errors in the absolute elevations, especially in regions of relatively rugged inland topography where GPS elevations differ by up to 50 m from DEM elevations.
Crystallographic site distribution and redox activity of Fe in nontronites determined by optical spectroscopy

Optical absorption spectroscopy has the potential to uncover many characteristics of Fe-bearing, redox-active smectites that have heretofore been hidden. The purpose of this study was to exploit this technique to reveal the temperature dependence of the spectra and to characterize the behavior of octahedral and tetrahedral Fe(III) under various stages of reduction. The Uley nontronites, NAu-1 and NAu-2, were compared using optical spectroscopy, which probed the crystallographic-site distribution of Fe in the clay structures as well as the resulting differences in the reduction process in the two minerals. All of the major differences in the spectra of the two minerals in the wavelength range 450–950 nm are due to the presence of a significant amount of tetrahedral Fe(III) in NAu-2. In situ observation of the optical spectra of NAu-1 suspensions as a function of the degree of reduction reveals a steady increase in the dominant intervalence charge transfer (IVCT) band and the resulting blue-green color as the Fe(II) content of the octahedral sheet increases. Although the spectrum of NAu-2 at ∼50% reduction looks nearly identical to the spectrum of NAu-1 at a similar state of reduction, the spectra corresponding to the initial stages of reduction are quite different. Stepwise reduction of NAu-2 causes a rapid decrease in the absorbance features due to crystal-field transitions of tetrahedral Fe(III) before the IVCT band appears, suggesting that tetrahedral Fe(III) is preferentially reduced before the octahedral Fe(III). The intensity of the absorbance features due to tetrahedral Fe(III) also exhibit an inverse temperature dependence, suggesting that they are enhanced due to exchange-coupling with Fe(III) ions in neighboring sites. Spectra of NAu-1 at liquid nitrogen temperature, therefore, allowed the identification of a small amount of tetrahedral Fe(III) in NAu-1 that had not been noted previously.
Identification of a region important for human monoamine oxidase B substrate and inhibitor selectivity.

Abstract Monoamine oxidase (MAO) A and B are flavoenzymes that catalyze the oxidative deamination of biogenic and xenobiotic amines. To search for domains that confer substrate and inhibitor selectivities, two chimeric proteins were constructed and expressed in yeast. The kinetic constants and IC50 values were determined for these chimeric enzymes using MAO-A/B selective substrates and inhibitors. Replacement of MAO-A amino acids 161–375 with the corresponding region of MAO-B, termed AB161–375A, converted MAO-A catalytic properties to MAO-B like ones. The specificity constants ( k cat K m ) for the oxidation of β-phenylethylamine (PEA) (1.6 × 105s−1 M−1) and benzylamine (2.4 × 104s−1 M−1) by AB161–375A were similar to wild-type MAO-B (PEA, 8 × 105s−1 M−1; benzylamine, 4.9 × 104s−1 M−1)-Serotonin (5-HT), a preferred substrate for MAO-A, was not oxidized by AB161–375A or wild-type MAO-B. Furthermore, AB161–375A was more sensitive to the MAO-B specific inhibitor deprenyl (IC50 2.7 ± 0.4 × 10−8M) than to the MAO-A specific inhibitor clorgyline (IC505.4 ± 0.8 × 10−7M). However, the reciprocal chimera in which a MAO-B segment was replaced with the corresponding region of MAO-A, termed BA151–366B, lacked catalytic activity. The lack of catalytic activity was not due to aberrant expression but rather an inactive protein as demonstrated by Western blot analysis. These results demonstrate that MAO-B amino acids 152–366 contain a domain(s) that confers substrate and inhibitor selectivity.
B-cell co-receptors: The two-headed antigen

Lymphocytes often recognize antigens using not only their antigen receptors but also 'co-receptors' that bind other molecules associated with the antigen; the co-receptors then modulate the response to antigen. This concept has been used to make chimeric antigens that are extremely potent inducers of antibody responses.
Improved nutrition after the detection and treatment of occult gastroparesis in nondiabetic dialysis patients

Abstract Malnutrition in dialysis patients is of multifactorial etiology and is associated with greatly increased morbidity and mortality. A low serum albumin level is one of the most powerful predictors of death and may persist despite optimization of the dialysis prescription. We retrospectively reviewed our experience in improving nutrition in nondiabetic patients with unexplained hypoalbuminemia. Using radionuclide solid-phase gastric emptying scans, we identified 6 patients who had occult gastroparesis. These patients (one on hemodialysis and five on peritoneal dialysis) were then treated with prokinetic medications (erythromycin elixir or metoclopramide) selected on the basis of their effectiveness in improving the scanning results after being given intravenously. Gastric emptying half-times improved from a median of 122 minutes (range, 95 to >300 minutes; normal, 0.1). We conclude that gastric emptying scans are valuable in identifying occult gastroparesis in high-risk patients and can guide the selection of prokinetic therapy, which may significantly increase serum albumin levels. (Am J Kidney Dis 1998 Jan;31(1):62-6)
Pulsed Doppler ultrasound detection of flow disturbances in arteriosclerosis.

Pulsed Doppler ultrasound blood flow detection has been used in a noninvasive manner to detect arterial abnormalities associated with arteriosclerosis. Sound spectrograms of ultrasound signals obtained from in uitro and animal studies in which flow was disturbed by obstacles placed in the flow stream showed a different distribution of energy over frequency than signals obtained from studies with no flow disturbances. Similar findings were seen clinically. A technique has been developed which can detect disturbed flow patterns resulting from partial occlusion in important superficial arteries (e.g. femoral and carotid) up to 15 cm distal to localized arterial wall abnormalities. Thirty-five arterial examinations of normal and arteriographically abnormal arteries in 12 patients revealed a sensitivity of 83 percent and a specificity of 61 percent. This study suggests that pulsed Doppler ultrasound may be useful as a screening technique for detection of arteriosclerotic lesions in major superficial arteries.
Renal Complications and Therapy in the PICU: Hypertension, CKD, AKI, and RRT

This article provides the bedside clinician an overview of the unique renal complications that are seen commonly in the pediatric intensive care unit. These sections are purposely succinct to give a quick guide to the clinician for the care of these children. We have identified four major areas that should result in discussion and cooperative care between intensive care physicians and nephrologists for the care of these children: (1) hypertension, (2) chronic kidney failure, (3) acute kidney injury, and (4) renal replacement therapy.
On the relation between surface energy, melting temperature and interatomic separation for metals

Abstract A simple relation between surface energy, bulk melting temperature, and interatomic separation is discussed and illustrated empirically for metals.
Rewriting literary history: the case of Moroccan fiction in Arabic

The article suggests that the history of modern Moroccan fiction in Arabic needs to be viewed within a longer temporal frame of reference, one that demands the use of a wider variety of literary-critical principles. Three separate ‘strands’ are identified as contributors to the development of fictional genres: importation from Europe and the West; the pre-modern tradition of indigenous narrative forms; and earlier models of Arabic fiction from the Mashriq region. Two pre-independence narratives, those of Al-Tihâmi al-Wazzâni and Muhammad ibn Abdallâh al-Muwaqqit, are briefly discussed as examples of the need for a re-examination of the role of pre-modern narratives in any discussion of the development of modern fictional genres in Morocco.
A fast algorithm for inverse kinematic analysis of robot manipulators

To solve the inverse kinematics problem, we obtain with little effort a reduced and complete set of equations by a conve nient choice of end-effector frame and application of rotation orthogonality...
Glutamate signalling and secretory phospholipase A2 modulate the release of arachidonic acid from neuronal membranes

The lipid mediators generated by phospholipases A(2) (PLA(2)), free arachidonic acid (AA), eicosanoids, and platelet-activating factor, modulate neuronal activity; when overproduced, some of them become potent neurotoxins. We have shown, using primary cortical neuron cultures, that glutamate and secretory PLA(2) (sPLA(2)) from bee venom (bv sPLA(2)) and Taipan snake venom (OS2) elicit synergy in inducing neuronal cell death. Low concentrations of sPLA(2) are selective ligands of cell-surface sPLA(2) receptors. We investigated which neuronal arachidonoyl phospholipids are targeted by glutamate-activated cytosolic calcium-dependent PLA(2) (cPLA(2)) and by sPLA(2). Treatment of (3)H-AA-labeled cortical neurons with mildly toxic concentrations of sPLA(2) (25 ng/ml, 1.78 nM) for 45 min resulted in a two- to threefold higher loss of (3)H-AA from phosphatidylcholine (PC) than from phosphatidylethanolamine (PE) and in minor changes in other phospholipids. A similar profile, although of greater magnitude, was observed 20 hr posttreatment. Glutamate (80 microM) induced much less mobilization of (3)H-AA than did sPLA(2) and resulted in a threefold greater degradation of (3)H-AA PE than of (3)H-AA PC by 20 hr posttreatment. Combining sPLA(2) and glutamate resulted in a greater degradation of PC and PE, and the N-methyl-D-aspartate receptor antagonist MK-801 only blocked glutamate effects. Thus, activation of the arachidonate cascade induced by glutamate and sPLA(2) under experimental conditions that lead to neuronal cell death involves the hydrolysis of different (perhaps partially overlapping) cellular phospholipid pools.
Phosphorylation of the cAMP-dependent protein kinase (PKA) regulatory subunit modulates PKA-AKAP interaction, substrate phosphorylation, and calcium signaling in cardiac cells.

Subcellular compartmentalization of the cAMP-dependent protein kinase (PKA) by protein kinase A-anchoring proteins (AKAPs) facilitates local protein phosphorylation. However, little is known about how PKA targeting to AKAPs is regulated in the intact cell. PKA binds to an amphipathic helical region of AKAPs via an N-terminal domain of the regulatory subunit. In vitro studies showed that autophosphorylation of type II regulatory subunit (RII) can alter its affinity for AKAPs and the catalytic subunit (PKAcat). We now investigate whether phosphorylation of serine 96 on RII regulates PKA targeting to AKAPs, downstream substrate phosphorylation and calcium cycling in primary cultured cardiomyocytes. We demonstrated that, whereas there is basal phosphorylation of RII subunits, persistent maximal activation of PKA results in a phosphatase-dependent loss of RII phosphorylation. To investigate the functional effects of RII phosphorylation, we constructed adenoviral vectors incorporating mutants which mimic phosphorylated (RIIS96D), nonphosphorylated (RIIS96A) RII, or wild-type (WT) RII and performed adenoviral infection of neonatal rat cardiomyocytes. Coimmunoprecipitation showed that more AKAP15/18 was pulled down by the phosphomimic, RIIS96D, than RIIS96A. Phosphorylation of phospholamban and ryanodine receptor was significantly increased in cells expressing RIIS96D versus RIIS96A. Expression of recombinant RII constructs showed significant effects on cytosolic calcium transients. We propose a model illustrating a central role of RII phosphorylation in the regulation of local PKA activity. We conclude that RII phosphorylation regulates PKA-dependent substrate phosphorylation and may have significant implications for modulation of cardiac function.
Nuclear structure studies in the medium mass (A ≈ 70) region

The in-beam γ-ray studies on several nuclei in A ≈ 70 region, have revealed highly collective band structures of the following types: 1) ground state band, 2) one or two even spin positive parity bands with 8+ as band head, 3) odd and even spin negative parity bands, 4) ΔJ = 1 even parity bands with 2+ as band heads, 5) deformed bands built on the first excited 0+ states. Not all these types of bands have been observed in all of the nuclei in this mass region. The even spin positive parity bands with 8+ as band head and the negative parity bands can be understood in terms of rotational alignment model. The Interacting Boson Model calculations reproduce the negative parity bands and the ΔJ = 1 even parity bands with 2+ as band head. Both these models have to be further investigated as to the validity of them in describing nuclei in the mass region A ≈ 70. Recent dynamic deformation model calculations of Kumar support the shape coexistence picture for 72Se, which explains the deformed bands built on the first excited 0+ states.
Problem-solving strategies on a partial reinforcement task: Effects of socioeconomic status and cognitive level

Abstract Differences in performance between lower- and middle-class children on partial reinforcement tasks have often been attributed to motivational differences between the groups. An alternate hypothesis suggests that different environmental experiences have resulted in differences in familiarity with problem-solving tasks. Both of these hypotheses have generated research; neither has received clear-cut support. A third hypothesis is that there is a developmental lag in the lower class so that equating the two groups on chronological age confounds the social class by cognitive-level interaction. In the present study, children were matched on cognitive abilities (preoperational, transitional, and concrete operational) and administered a partial reinforcement task. The main hypotheses that social-class differences would not be found but that cognitive level differences in success on the task and in problem-solving strategies would be found were supported. Implications were made concerning a developmental learning model that includes both qualitative and quantitative changes in abilities.
Non-Baire hyperplanes in non-separable Baire spaces

Abstract Given an infinite-dimensional Banach space E, one may ask: Does E have (1) a properly separable quotient, (2) a dense non-Baire hyperplane? [Every closed hyperplane in a Baire space is Baire.] The famous separable quotient problem (1) remains unsolved, and question (2) is question 13.1.1 of P. Perez Carreras and J. Bonet (“North-Holland Math. Stud.,” Vol. 131, North-Holland, Amsterdam, 1987 ). In 1966 Wilansky-Klee conjectured the answer to (2) is always “no”; J. Arias de Reyna denied the conjecture (Math. Ann. 249, 1980, 111–114 ), proving the answer to (2) is “yes” whenever the answer to (1) is “yes,” under assumption of c-additivity (c-A), a condition weaker than Martin's Axiom. M. Valdivia extended the result to E a Baire (2nd category in itself) topological vector space (Collect. Math. 34, 1983, 287–296). In general, (2) is non-trivial only in case E is Baire with E′ ≠ E ∗ . An extension of Valdivia's extension yields the complete answer for (2) in the general locally convex setting, affirming question 13.1.1 of Perez Carreras and Bonet (referenced above) in particular: A [not necessarily] Hausdorff locally convex space E has a dense non-Baire hyperplane if and only if [ dim (E′) = ∞ and ] E′ ≠ E ∗ . Even for E non-locally convex, ( dim (E′) = ∞ and E′ ≠ E ∗ ) suffices, but is not necessary, whereas E′ ≠ E ∗ is obviously always necessary in order that E have a dense non-Baire hyperplane. Whether E′ ≠ E ∗ suffices in the Hausdorff non-locally convex case, and whether the assumption of c-A can be omitted, we do not know. Contrastingly, any infinite-dimensional E is the union of a sequence of hyperplanes, and if E is Baire, one of the hyperplanes must be dense and Baire; and every hyperplane of E must be unordered Baire-like if E is.
Extraction and quantification of epibatidine in plasma.

Abstract Epibatidine was extracted from human and mouse plasma into a hexane–isopropanol mixture and back-extracted into a phosphate buffer, pH 2.5, then identified by HPLC isocratically using a CN column and quantified with ultraviolet detection at a fixed wavelength of 214 nm. The percent recovery of epibatidine from spiked plasma samples was 83.6% and the percent extraction was linear between 10 and 1000 ng/ml. Desipramine was used as the internal standard. For spiked control samples containing 50 and 750 ng/ml, between-day precisions were 20.8 and 7.2% (RSD%), respectively; accuracy was 87.0 and 99.1%, respectively. The limit of detection was 2 ng/ml. Using this method, an intraperitoneal dose of 0.1 mg/kg of epibatidine produced mean levels of 7.3 and 37.1 ng/ml in pooled male and female plasma samples from C57BL/10 J mice, respectively. This is a simple and straightforward procedure by which plasma samples may be analyzed for epibatidine.
A PLACEMENT FLOW FOR VERY LARGE-SCALE MIXED-SIZE CIRCUIT PLACEMENT

The very large-scale integrated circuit (VLSI) placement problem is to determine the exact location of each movable circuit element within a given region. It is a crucial process in physical design, since it affects performance, power consumption, routability, and heat distribution of a design. In this paper, we propose a VLSI placement flow to handle the large-scale mixed-size placement problem. The main idea of our placement flow is using a floorplanning algorithm to guide the placement of circuit elements. It consists of four steps: (1) With the multilevel framework, circuit elements are clustered into blocks by recursively partitioning; (2) a floorplanning algorithm is performed on every level of the blocks; (3) the macro cells are shifted by a macro shifting technique to determine their exact locations; (4) with each macro cell location fixed, a standard cell placement algorithm is applied to place the remaining objects. The proposed approach is tested on the IBM mixed-size benchmarks and the modern mixed-size (MMS) placement benchmarks. Experimental results show that our approach outperforms the state-of-the-art placers on the solution quality for most of the benchmarks.
Changes in -S-S- linked structures of the sperm tail during epididymal maturation, with comparative observations in sub-mammalian species.

Treatment of immature and mature epididymal spermatozoa with SDS and DTT reveals differences in the structural character of their respective tail organelles as a function of their maturity, which are not apparent in untreated spermatozoa. The response of mature sperm tails of rat, rabbit and other mammals to these reagents indicates that the segmented connecting pieces, the coarse outer fibers, the outer membrane of the mitochondrion and the fibrous sheath of the principal piece, as well as the relationships between these organelles, are stabilized highly by intermolecular SS crosslinks. The disruption of these structures by SDS alone in caput epididymal spermatozoa, however, implies their stabilization by disulfide bonds during sperm passage through the epididymis. Hence the pattern of flagellar beat seen typically in mature epididymal or ejaculated spermatozoa is probably determined by post-spermiation changes in the structural as well as in the metabolic properties of the tail organelles. In similar studies of a wide variety of sub-mammalian species, the sperm tails fell into two broad classes. The “simple” tail, a plasma membrane enclosing only mitochondria and microtubule doublets (teleosts, frog, chicken and pigeon), disappeared immediately in SDS, though a partial SS dependent stability was inducible in the microtubules of teleost sperm tails. In the second class, the coarse fibers, arrayed as a nine-membered ring (octopus, snake, lizard, turtle and sparrow) or otherwise (skate, newt), and the fibrous sheath (snake, lizard) also are stabilized by SS bonds, as is the undulating membrane of the urodele sperm tail. Since the sperm mitochondria in all sub-mammalian species were totally disrupted by SDS alone, an extreme SS dependent stability of the outer mitochondrial membrane may well be a feature unique to mammalian spermatozoa.
On the giant sea-salt particles in the atmosphere

The vertical distribution of giant sea-salt particles in the 10-m layer over the sea surface, where humidity, eddy diffusivity, etc., sharply change with height, is analytically studied. A steady state with no horizontal gradient and with a logarithmic distribution of wind speed is assumed, but the vertical distributions of temperature and vapor pressure are taken into account in such a way that each droplet is assumed to instantaneously attain its equilibrium salinity for the environmental air at each level, and to remain as a droplet of supersaturated salt solution when the relative humidity is lower than 75%. It is deduced that the vertical distribution of the number concentration of each class interval of mass of salt contained in a droplet should be approximately expressed by a straight line on a logarithmic diagram. Also, the logarithm of the ratio of the concentration of the particles at the sea surface and at the 10-m level is proportional to the two thirds power of the mass of salt, and inversely proportional to the wind speed at the 10-m level. The proportionality factor is approximately a function of the relative humidity at the 10-m level and a friction factor. This proportionality factor is calculated for various values of the variables and the effect of wind speed and relative humidity on the vertical distribution of particles is predicted. When this result is applied to data of the concentration and the effective production rate of sea-salt particles at the 10-m level compiled in the previous paper, complicated features disappear to give very simple patterns of the production rate or the surface concentration of sea water droplets as a function of wind force and of mass of salt. This represents predicted processes of production of sea-salt particles at the ocean surface, and gives some agreement with the author's 1961 wind flume experiment. DOI: 10.1111/j.2153-3490.1965.tb01429.x
Metastasis from Uveal Melanoma Associated with Congenital Ocular Melanocytosis: A Matched Study

Purpose To determine the rate of metastasis resulting from uveal melanoma associated with congenital ocular melanocytosis (COM) and to compare it with the rate of metastasis resulting from uveal melanoma not associated with COM. Design Matched retrospective study. Participants Fifty-seven patients with uveal melanoma associated with ocular melanocytosis (melanocytosis group). Each patient in the melanocytosis group was matched with 2 patients with uveal melanoma not associated with ocular melanocytosis (no melanocytosis group) for age, gender, location of anterior tumor margin, location of tumor epicenter, tumor basal diameter, and tumor thickness. Methods Review of medical records. Main Outcome Measures Metastasis resulting from uveal melanoma. Results The mean basal diameter and thickness of tumors in the melanocytosis group were 10 and 4.9 mm, respectively, and most were located between the macula and equator (70%). The melanocytosis and no melanocytosis groups were similar with regard to all patient, ocular, and tumor features studied. Nineteen (33%) of 57 patients in the melanocytosis group and 18 (16%) of 114 patients in the no melanocytosis group demonstrated systemic metastasis during mean follow-up periods of 77 months (range, 1–402) and 64 months (range, 1–252), respectively ( P = 0.013). The Kaplan-Meier estimates for systemic metastasis in the melanocytosis group at 5 and 15 years were 27% and 59%, respectively, compared with 15% and 33%, respectively, in the no melanocytosis group (hazard ratio, 1.99; 95% confidence interval, 1.16–3.41). Conclusions In this matched study, patients with uveal melanoma associated with COM were twice as likely to have systemic metastasis compared with patients with uveal melanoma not associated with COM. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.
THE SELECTIVE ABSORPTION OF POTASSIUM BY ANIMAL CELLS : II. THE CAUSE OF POTASSIUM SELECTION AS INDICATED BY THE ABSORPTION OF RUBIDIUM AND CESIUM.

1. Frog muscles perfused with Ringer solution in which potassium chloride has been replaced by an equivalent amount of rubidium or cesium chloride take up rubidium or cesium and incorporate them into the tissue substance in such form as to be retained during a subsequent perfusion with potassium-free Ringer solution, provided the muscles contract during the first perfusion. Retention of rubidium or cesium by a resting muscle does not occur. 2. Rats on synthetic diets, adequate in all respects except that potassium was replaced by an equivalent amount of rubidium or cesium, died after a period varying from 10 to 17 days with characteristic symptoms including tetanic spasms. Muscle, heart, liver, kidney, spleen, and lung tissues were then found to contain significant amounts of rubidium or cesium. The concentration of these metals in the muscle amounted, in some cases, as shown by a spectroscopic estimation, to about half the concentration of potassium normally found in mammallian muscle. 3. The results are regarded as tending to confirm the theory that the peculiarities in the physiological effects of potassium, including the facility with which it is "selected" by living cells in preference to sodium, are related to the electronic structure of the potassium ion as compared with that of similar ions. The possible relationship of the comparative migration velocity, a function of the electronic structure, to physiological effects is suggested.
Validating computer simulations of enantioselective catalysis; reproducing the large steric and entropic contributions in Candida Antarctica lipase B

The prospect for computer-aided refinement of stereoselective enzymes is further validated by simulating the ester hydrolysis by the wild-type and mutants of CalB, focusing on the challenge of dealing with strong steric effects and entropic contributions. This was done using the empirical valence bond (EVB) method in a quantitative screening of the enantioselectivity, considering both kcat and kcat/KM of the R and S stereoisomers. Although the simulations require very extensive sampling for convergence they give encouraging results and major validation, indicating that our approach offers a powerful tool for computer-aided design of enantioselective enzymes. This is particularly true in cases with large changes in steric effects where alternative approaches may have difficulties in capturing the interplay between steric clashes with the reacting substrate and protein flexibility. Proteins 2014; 82:1387–1399. © 2014 Wiley Periodicals, Inc.
Denosumab Treatment for Fibrous Dysplasia

Fibrous dysplasia (FD) is a skeletal disease caused by somatic activating mutations of the cyclic adenosine monophosphate (cAMP)-regulating protein, α-subunit of the Gs stimulatory protein (G(s) α). These mutations lead to replacement of normal bone by proliferative osteogenic precursors, resulting in deformity, fracture, and pain. Medical treatment has been ineffective in altering the disease course. Receptor activator of NF-κB ligand (RANKL) is a cell-surface protein involved in many cellular processes, including osteoclastogenesis, and is reported to be overexpressed in FD-like bone cells. Denosumab is a humanized monoclonal antibody to RANKL approved for treatment of osteoporosis and prevention of skeletal-related events from bone metastases. We present the case of a 9-year-old boy with severe FD who was treated with denosumab for a rapidly expanding femoral lesion. Immunohistochemical staining on a pretreatment bone biopsy specimen revealed marked RANKL expression. He was started on monthly denosumab, with an initial starting dose of 1 mg/kg and planned 0.25 mg/kg dose escalations every 3 months. Over 7 months of treatment he showed marked reduction in pain, bone turnover markers (BTMs), and tumor growth rate. Denosumab did not appear to impair healing of a femoral fracture that occurred while on treatment. With initiation of treatment he developed hypophosphatemia and secondary hyperparathyroidism, necessitating supplementation with phosphorus, calcium, and calcitriol. BTMs showed rapid and sustained suppression. With discontinuation there was rapid and dramatic rebound of BTMs with cross-linked C-telopeptide (reflecting osteoclast activity) exceeding pretreatment levels, accompanied by severe hypercalcemia. In this child, denosumab lead to dramatic reduction of FD expansion and FD-related bone pain. Denosumab was associated with clinically significant disturbances of mineral metabolism both while on treatment and after discontinuation. Denosumab treatment of FD warrants further study to confirm efficacy and determine potential morbidity, as well as to determine the mechanism of RANKL in the pathogenesis of FD and related bone marrow stromal cell diseases.
A single-cell electroporation device with integrated perfusion channels for efficient intracellular delivery

We present here a single-cell electroporation device with integrated perfusion channels to efficiently deliver impermeable substances into a cell. Each sequestered cell is subjected to an electric field to induce localized transient non-selective pores in a portion of the cell membrane. After pores are locally induced on a portion of the cell membrane, individually addressable capillary channels release pre-loaded compounds of interest into the cell. This approach conserves reagents; moreover cells remain separated from reagents until time of introduction. To demonstrate the effectiveness of our device design, we electroporate Hela (human cervical cancer) cells using low applied voltages (<1 V) and characterize permeation by measuring time dependent current traces. Subsequently, we insert cell impermeable propidium iodide and characterize its deliver/ via fluorescent intensity measurements.
Dr. Watts' “Flights of Fancy”

The year 1948 drew to a close with a spate of articles appearing in religious magazines honoring the memory of Watts. Along with the King James Version, Dr. Watts' hymns have become a symbol of Protestantism's underlying unity in a day of proliferating denominations. Around his hymns there now cluster historic associations and fond memories that endear Watts to the entire Protestant community.
Energy Metabolism in a Matched Model of Radiation Resistance for Head and Neck Squamous Cell Cancer

While radiation therapy is commonly used for treating cancer, radiation resistance can limit long-term control of the disease. In this study, we investigated the reprogramming of the energy metabolism in radiosensitive and radioresistant head and neck squamous cell carcinomas (HNSCC) using a preclinical matched model of radiation resistance. Our investigation found that radioresistant rSCC-61 cells: 1. They display increased glucose uptake and decreased fatty acid uptake; 2. They deviate from the classical Warburg effect by diverting the glycolytic flux into the pentose phosphate pathway; 3. They are more dependent on glucose than glutamine metabolism to support growth; 4. They have decreased mitochondrial oxidative phosphorylation; 5. They have enhanced fatty acid biosynthesis by increasing the expression of fatty acid synthase; and 6. They utilize endogenous fatty acids to meet the energy demands for proliferation. Inhibition of fatty acid synthase with orlistat or FASN siRNA resulted in increased cytotoxicity and sensitivity to radiation in rSCC-61 cells. These results demonstrate the potential of combination therapy using radiation and orlistat or other inhibitors of lipid and energy metabolism for treating radiation resistance in HNSCC.
Modes of instability in spiral flow between rotating cylinders

Abstract : This paper gives the results of an experimental investigation of the stability of spiral flow between rotating cylinders with respect to axisymmetric and nonaxisymmetric disturbances. Various modes of instability were detected by observing visually characteristic ink patterns in the fluid. The effect of small axial flow upon all of the modes was to give an approximately parabolic dependence of the critical Taylor number on the axial flow rate. In the case of an axisymmetric mode, agreement with the theory of Krueger and Di Prima (1964) was found to be excellent.
A study of charge trapping in PECVD PTEOS films

We have studied charge trapping in tetraethylorthosilicate (TEOS) based phosphorous doped silicon glass (PSG) films deposited by plasma enhanced chemical vapor deposition (PECVD) using electron spin resonance and capacitance voltage measurements. The results indicate that these films trap electrons and holes very well. The charges appear to be trapped in phosphorus and carbon related centers as well as in E' centers. The carbon related centers are unique to the TEOS films.
Real-time Seismic Monitoring of the Integrated Cape Girardeau Bridge Array and Recorded Earthquake Response

SUMMARY This paper introduces the state of the art, real-time and broad-band seismic monitoring network implemented for the 1206 m [3956 ft] long, cable-stayed Bill Emerson Memorial Bridge in Cape Girardeau (MO), a new Mississippi River crossing, approximately 80 km from the epicentral region of the 1811–1812 New Madrid earthquakes. The bridge was designed for a strong earthquake (magnitude 7.5 or greater) during the design life of the bridge. The monitoring network comprises a total of 84 channels of accelerometers deployed on the superstructure, pier foundations and at surface and downhole free-field arrays of the bridge. The paper also presents the high quality response data obtained from the network. Such data is aimed to be used by the owner, researchers and engineers to assess the performance of the bridge, to check design parameters, including the comparison of dynamic characteristics with actual response, and to better design future similar bridges. Preliminary analyses of ambient and low amplitude small earthquake data reveal specific response characteristics of the bridge and the free-field. There is evidence of coherent tower, cable, deck interaction that sometimes results in amplified ambient motions. Motions at the lowest tri-axial downhole accelerometers on both MO and IL sides are practically free from any feedback from the bridge. Motions at the midlevel and surface downhole accelerometers are influenced significantly by feedback due to amplified ambient motions of the bridge.