cssi/SciSciGPT-SciSciNet huggingface dataset:
An American experience of pregnancy and childbirth in Japan.

Abstract: Birth practices in modern Japan differ markedly from those currently observed in the United States and the outcomes are among the best in the world. A fundamental question is whether such practices could be exported apart from the underlying system of cultural values. While autonomy is cherished in America, birth practices in Japan directly and indirectly reflect the values of order and harmony in social groups. Strict adherence to traditional gender roles is seen as promoting the social order. I used a participant-observer approach to study this phenomenon, teaching on a maternity nursing faculty in Japan for two years, providing childbirth counseling in the foreign community, touring various birth facilities, interviewing health professionals and Ministry of Health officials, and bearing my first child in that country.
Disruption of monolayer integrity enables activation of a cystic fibrosis "bypass" channel in human airway epithelia.

Cystic fibrosis (CF) is a genetic disease characterized by marked reduction in Cl− conductance across many epithelia. Two kinds of Cl− channels have been associated with CF. One channel, termed the cystic fibrosis transmembrane conductance regulator (CFTR), is directly coded by the CF gene1–3. The other channel is an outwardly rectifying depolarization induced Cl− channel (ORDIC) that is distinguished from other outwardly rectifying chloride channels (ORCCs) because its activity is induced most reliably by patch excision and depolarization4–7. An issue in current CF research is whether ORDIC channels are indirectly activated by CFTR to contribute a significant portion of apical membrane Cl− conductance in airway cells6. We now show that ORDIC channels are readily activated in patches excised and depolarized from isolated cells, but are rarer or refractory to activation in patches from the apical membranes of confluent human airway epithelia. These findings have important implications for proposed therapies that would bypass the CFTR conductance by activating ORDIC channels.
Surface film formation in vitro by infant and therapeutic surfactants: role of surfactant protein B

Surface film formation in vitro by infant and therapeutic surfactants: role of surfactant protein B
Erosion Behaviour of CVD TiB2 Coatings on TiB2-based Ceramic Substrates in High-velocity Coal-oil Slurries*

ABSTRACT The erosion behaviour of CVD TiB2 coatings deposited on TiB2 ceramic substrates was studied via impingement of a liquid stream containing 8 wt % of coal-derived (SRC–1) solids in anthracene oil upon the CVD surface and compared with erosion of a high-density uncoated TiB2 ceramic specimen. Erosive exposure of all specimens was conducted at ~350°C for 1 h at a liquid flow velocity of 100 m/s and an incidence angle of 20° between the liquid jet and the specimen surfaces. These conditions simulate those present in pressure let-down valves in direct coal liquefaction processes. The principal materials variables included the microstructure and composition of the TiB2 ceramic substrates, while the CVD coatings were all deposited under identical conditions at 900°C from TiCl4 and BCl3. The deposited CVD coatings, which were ~50 μm thick, exhibited strong preferred orientation as determined by X-ray diffraction. Relative erosion resistance was assessed by determining the maximum depth of the erosion crater formed in the TiB2 surface at the point of jet impingement. For the four CVD coatings exposed, the maximum crater depth values were 0, 1.5, 5.5, and 5.5 μm, while the uncoated specimen had a depth of ~22 μm. Prior work had shown that only consolidated or single-crystal diamond provided zero crater depths under these conditions. The outstanding erosion resistance of the CVD coatings was apparently related to the crystallographic texture produced in them when they were deposited on the TiB2 ceramic substrates.
On Townsend's rapid-distortion model of the turbulent-wind-wave problem

Townsend's (1980) model of wind-to-wave energy transfer, which is based on a putative interpolation between an inner, viscoelastic approximation and an outer, rapid-distortion approximation and predicts an energy transfer that is substantially larger (by as much as a factor of three) than that predicted by Miles's (1957) quasi-laminar model, is revisited. It is shown that Townsend's interpolation effectively imposes a rapid-distortion approximation throughout the flow, rather than only in the outer domain, and that his asymptotic (far above the surface) solution implicitly omits one of the two admissible, linearly independent solutions of his perturbation equations. These flaws are repaired, and Townsend's dissipation function is modified to render the transport equation for the perturbation energy of the same form as those for the perturbation Reynolds stresses. The resulting wind-to-wave energy transfer is close to that predicted by Townsend's (1972) viscoelastic model and other models that incorporate the perturbation Reynolds stresses, but somewhat smaller than that predicted by the quasi-laminar model. We conclude that Townsend's (1980) predictions, although closer to observation than those of other models, rest on flawed analysis and numerical error.
SU‐E‐T‐314: Novel System for Delivery of Electron Dose From Short Lived Isotopes

Purpose: To evaluate feasibility of delivering electron dose by use of the extremely short lived isotope In‐116 undergoing beta decay. Methods of isotope creation, transport and delivery are also examined. Methods: A system consisting of natural Indium in a eutectic liquid metal was constructed to transport by peristaltic pumping in flexible tubing the isotope In‐116 between a neutron activation source and a phantom material where beta decay is measured. The In‐116 (half‐life 14.1 sec), created through thermal neutron capture on In‐115, decays with 99.98% probability by beta particle with an energy average of 1.37 MeV and endpoint energy of 3.28 MeV. The liquid metal was passed near the neutron source for 4 half‐lives, pumped to a thin window chamber (0.13mm styrene), and held stationary for 60 seconds to detect beta particles with a silicon charged particle detector. Results: The liquid nature of the eutectic allowed pumping of the material through tubing from the neutron source to the detector. By keeping the tubing narrow the mixture remained in smooth laminar flow to maintain a bolus of active material (In‐116) that reaches the detector with good uniformity. Beta decays were detected in the silicon detector with a half‐life matching that of In‐116 showing that dose can be successfully delivered to a material. Conclusion: This work indicates the potential for targeted electron dose useful for shallow lesions currently treated by electrons or low energy X‐Rays. The lack of associated gamma‐rays and pure beta source allows dose to be tightly controlled to the treatment area and the application of custom fields based on applicator shape. Rapid decay to stable Sn‐116 means no permanent isotopes are used and a reduction in shielding requirements. Future investigation includes ion chamber measurements for depth dose and the use of higher flux neutron sources to examine clinically useful doses.
Sample preparation for analyzing polycyclic aromatic hydrocarbons and polychlorinated dibenzo-p-dioxins and dibenzofurans in sediment by gas chromatography/mass spectrometry

A sample preparation technique was developed to isolate and separate two classes of combustion-produced pollutants: three- to six-ring polycyclic aromatic hydrocarbons (PAH) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F), from sediment samples for interference-free analyses by gas chromatography/mass spectrometry (GC/MS). The method involves soxhlet extraction with methylene chloride, sulfur removal with activated copper powder, gel filtration chromatography with Sephadex LH-20, polarity separations of PAH and PCDD/F with prepacked silica gel solid-phase extraction columns, and isolation of PCDD/F from polychlorinated biphenyls with microalumina columns. Stringent procedural controls were established to achieve clean isolations and recoveries of 70% or better for each step in the method. The prepared sample extracts were analyzed by capillary GC and GC/MS. Electron impact ionization was used for PAH, and negative chemical ionization with methane as a reagent gas was used for PCDD/F. Reproducible results were obtained. The method is simple and has the advantage of conserving sample consumption since two classes of compounds can be analyzed from the same sample. This can be critical in sediment core analyses where sample size is usually limited.
Coronal Images from the 1984 Solar Eclipse

We present digitized photographs of the white-light solar corona taken during the total solar eclipse of 22–23 November, 1984, on both calibrated black-and-white film and on color film. Conditions on site in Hula, Papua New Guinea, were exceptionally clear. The color image was used to produce an isophotal map of the inner corona, from which a flattening coefficient of 0.23 was measured. The black-and-white image was enhanced through a digital radial filter. Our images are the best processed images available from the 1984 eclipse and so provide important data for synoptic observations.
Reliability and reproducibility of nonstress test readings

The nonstress test is commonly used as a test of fetal well-being, despite the fact that both false-positive and false-negative results are known to occur. Although some of the errors are due to biologic variability among fetuses, some may be due to variability of reading the test. The purpose of the present study was to assess the reliability and reproducibility of nonstress test readings. Fifty nonstress test monitor strips were read by five perinatologists on two occasions, for a total of 500 readings. Nonstress tests were read as reactive, equivocal, nonreactive, or technically unsatisfactory. Of the 50 tracings, only 11 had identical readings on all 10 occasions, and readers had different readings for the first and second readings 28% of the time. Estimates of interobserver and intraobserver agreement ranged from 0.41 to 0.55. These results indicate that there is considerable interobserver and intraobserver variability that can be expected to have a serious adverse effect on the sensitivity of the nonstress test.
Perception of gait

Our ability of perceive the identity and naturalness of a human gait is examined in a series of four experiments involving computer-animated stick figures. The results indicate that the perceived naturalness of a walking or running gait can be influenced by the motion of any limb segment, but the perceived identity of these gaits is primarily determined by the movements of the lower leg (i.e., the tibia). The results also demonstrate that a perceptually salient walking gait can be transformed into running (or vice versa) by adding or subtracting a constant value to the angle of the lower leg over the entire step cycle. The size of this constant value is affected by the shape of the lower leg angle function and the motion of other limb segments.
Vibrational circular dichroism, absolute configuration and predominant conformations of volatile anesthetics: 1,2,2,2-tetrafluoroethyl methyl ether

Abstract Vibrational absorption and circular dichroism spectra of (−)-1,2,2,2-tetrafluoroethyl methyl ether have been measured in CCl4 solution in the 2000–900 cm−1 region. These spectra are compared with the ab initio predictions of absorption and VCD spectra obtained with density functional theory using B3LYP/6-31G* and B3PW91/6-311G(2d) basis sets for different conformers of (R)-1,2,2,2-tetrafluoroethyl methyl ether. The results suggest that the trans-conformer of 1,2,2,2-tetrafluoroethyl methyl ether is predominant in the solution phase and that the (−)-enantiomer has the R-configuration.
Management of hypertension: Potential trade-offs on coronary risk

The major risk factors for coronary heart disease remain high blood pressure, cigarette smoking, and abnormal serum lipid levels, including total cholesterol but more specifically elevated low-density lipoprotein cholesterol and reduced high-density lipoprotein cholesterol levels. Observations made from large-scale trials almost a decade ago suggested that commonly used antihypertensive agents, such as thiazide diuretics and beta-blockers, may adversely influence serum lipid levels. Over time, we realized that these lipid alterations persist long term and are of sufficient magnitude to potentially account for important differences in coronary heart disease risk reduction among various antihypertensive drug regimens. Considering recent National Cholesterol Education Program and Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure recommendations concerning lipid and blood pressure treatment, it is prudent and timely to rethink our approach to antihypertensive therapy in patients with abnormal serum lipid levels. Therefore, when lipids are a concern, appropriate dietary treatments should be advised and antihypertensive therapy that has a beneficial or neutral impact on serum lipid levels should be considered.
Cross-Regulation in Vibrio parahaemolyticus: Compensatory Activation of Polar Flagellar Genes by the Lateral Flagellar Regulator LafK

Gene organization and hierarchical regulation of the polar flagellar genes of Vibrio parahaemolyticus, Vibrio cholerae, and Pseudomonas aeruginosa appear highly similar, with one puzzling difference. Two sigma(54)-dependent regulators are required to direct different classes of intermediate flagellar gene expression in V. cholerae and P. aeruginosa, whereas the V. parahaemolyticus homolog of one of these regulators, FlaK, appears dispensable. Here we demonstrate that there is compensatory activation of polar flagellar genes by the lateral flagellar regulator LafK.
Origin and Development of Archival Record-Keeping in the Crown of Castile-Leon

Summary Archives were the byproducts of scribal bureaucracies which developed in the Iberian peninsula especially in the twelfth century. In the heartland Crown of Castile-Leon, the beginning of systematic record keeping can be traced as a development parallel to the growth of the monarchy from a traveling court to a network of regional capitals and coordination by the royal chanceries. The kinds of records and their formats are surveyed in this essay, with special attention to edited and published records for the study of Castile-Leon in the Middle Ages. The main foci are on the royal chancery, monastic and cathedral archives, records of the military orders, municipal archives, and the origin of royal archives. Legal sources documenting more conscientious record keeping are important, as are registers attesting actual practices. Finally, the main archival depositories of Spain are discussed, especially regarding their holdings of medieval and early modern records.
Magnetic properties of NdSb, GdSb, TbSb, DySb, HbSb and ErSb under hydrostatic pressure

Abstract The hydrostatic pressure dependence of magnetic properties are reported for antiferromagnetic RSb where R = Nd, Gd, Tb, Dy, Ho or Er. Measurements were made for pressures 0 ≤ p ≤ 10 kbar, magnetic fields 0 ≤ H0 ≤ 60 kG, and temperatures 1.4 K ≤ T ≤ 35 K. dTN/dP shows no systematic trend and ranges from -0.038 K/kbar for DySb to + 0.21 K/kbar for NdSb. The magnetic properties of DySb are strongly P-dependent, whereas those of HoSb are P-independent, but sample-dependent.
The role of interfacial layers in the enhanced thermal conductivity of nanofluids: A renovated Hamilton–Crosser model

We previously developed a renovated Maxwell model for the effective thermal conductivity of nanofluids and determined that the solid/liquid interfacial layers play an important role in the enhanced thermal conductivity of nanofluids. However, this renovated Maxwell model is limited to suspensions with spherical particles. Here, we extend the Hamilton--Crosser model for suspensions of nonspherical particles to include the effect of a solid/liquid interface. The solid/liquid interface is described as a confocal ellipsoid with a solid particle. The new model for the three-phase suspensions is mathematically expressed in terms of the equivalent thermal conductivity and equivalent volume fraction of anisotropic complex ellipsoids, as well as an empirical shape factor. With a generalized empirical shape factor, the renovated Hamilton--Crosser model correctly predicts the magnitude of the thermal conductivity of nanotube-in-oil nanofluids. At present, this new model is not able to predict the nonlinear behavior of the nanofluid thermal conductivity.
And the Noise Played on: Stochastic Gene Expression and HIV-1 Infection

Stochastic gene expression has been implicated in a variety of cellular processes, including cell differentiation and disease. In this issue of Cell, take an integrated computational-experimental approach to study the Tat transactivation feedback loop of HIV-1. They show that fluctuations in a key regulator, Tat, in an isogenic population of infected cells result in two distinct expression states corresponding to latent and productive HIV-1 infection. These findings demonstrate the importance of stochastic gene expression in molecular "decision-making."
A biomechanical comparison between anterior and transverse interbody fusion cages.

Study Design. Human cadaveric lumbar spines underwent placement of threaded fusion cages (TFCs) in either an anterior or transverse orientation. Spines underwent load testing and angular rotation measurement in the intact state, after diskectomy, after cage placement, and after fatiguing. Angular rotations were compared between cage orientations and interventions. Objective. To determine which cage orientation resulted in greater immediate stability. Summary of Background Data. There has been extensive biomechanical study of interbody fusion cages. The lateral orientation has been increasingly used for intervertebral fusion, but a direct biomechanical comparison between cages implanted either anteriorly or transversely in human cadaveric spines has not been performed. Methods. Fourteen spines were randomized into the anterior group (anterior diskectomy and dual anterior cage placement) and the lateral group (lateral diskectomy and single transverse cage placement). Pure bending moments of 1.5, 3.0, 4.5, and 6.0 Nm were applied in flexion, extension, lateral bending, and axial rotation. Load testing was performed while intact, after diskectomy, after cage placement, and after fatiguing. Angular rotation was compared between anterior and lateral groups and, within each group, among the different interventions. Results. Segmental ranges of motion were similar between spines undergoing either anterior or lateral cage implantation. Conclusions. These results demonstrate few differences between angular rotation after either anterior or lateral TFC implantation. These findings add to data that find few differences between orientation of implanted TFCs. Combined with a decreased risk of adjacent structure injury through a lateral approach, these data support a lateral approach for lumbar interbody fusion.
High Frequency Audiometry and Stapedius Muscle Reflex Thresholds in Juvenile Diabetics

Sixty-one juvenile, insulin-treated diabetics below 50 years of age with a duration of diabetes mellitus longer than 10 years underwent impedance audiometry with determination of stapedius reflex thresholds at 500 Hz, 1,2, and 4 kHz, conventional pure tone and speech audiometry, and high-frequency audiometry up to 20 kHz. The results were compared with a normative material of non diabetic subjects selected after exactly the same criteria. No significant differences in hearing or stapedius reflex thresholds were found. Among half of the subjects there was a diabetic retinopathy. A comparison between those with and those without retinopathy did not reveal any significant difference in audiological findings. Even subjects with severe diabetic complications and almost lifelong diabetes had normal hearing. Recent investigations on plasma-lipoids have discussed the possibility that insulin might prevent a premature ageing of hearing which has been reported by other authors. It is concluded that no statistical d...
Sympathetic sprouting in the central nervous system: a model for studies of axonal growth in the mature mammalian brain

Sympathetic fibers innervate many peripheral tissues but are normally confined to extracerebral structures within the cranial cavity, e.g. blood vessels. The invasion of the central nervous system by vascular sympathetic axons is a unique example of neuronal plasticity which provides new information concerning the regulation and mechanisms of neuronal sprouting in both the peripheral and central nervous systems. In this paper, the principal findings concerning the conditions under which such sprouting occurs, the mechanisms which may be involved, and the question of its possible function are reviewed. Of special interest is the fact that a nerve growth factor-like brain factor may be involved in this growth response. The principles gleaned from studies of this sprouting phenomenon may be applicable to other models of neuronal plasticity and may have clinical relevance.
Experiential Development and Mentoring Processes for Leaders for Innovation

Leading creative people is particularly challenging. Leaders of creative people must have the expertise and skill set required for creative endeavors to understand and communicate with this specifi...
Biochemical and behavioral alterations following 6-hydroxydopamine administration into brain

Publisher Summary This chapter discusses the biochemical and behavioral alterations following 6-hydroxydopamine (6-OHDA) administration into brain. Early studies with 6-OHDA indicated that depletions of brain catecholamines were not accompanied by a chronic behavioral effect. It is found that because multiple injections of 6-OHDA have been shown to produce greater depletion of brain catecholamines, two doses of 6-OHDA were given to desipramine treated rats to increase the depletion of brain DA. This procedure antagonized acquisition of the shuttle-box avoidance response as well as acquisition of a one-way avoidance task. In contrast to results after depletion of NE with intra-cisternal injections, destruction of dorsal, and ventral NE pathways with 6-OHDA did not facilitate acquisition of the avoidance task, even though NE was reduced by 85% in the forebrain. Administration of 6-OHDA into the nigro-striatal pathway as well as into the caudate was found to block acquisition of the shuttle-box avoidance response providing further evidence for the proposal that dopaminergic neurons are essential for maintaining avoidance responding.
A generic stoichiometric equation for microalgae–microorganism nexus by using clarified domestic wastewater as growth medium

AbstractStoichiometric equations for microalgae–microorganism nexus culture were established by using 18 sets of experimental data from the literature where clarified domestic wastewater (CDWW) was used as a growth media. The best correlations between observed and calculated coefficients in the equations were 0.908, 0.878, 0.838, and 0.849 for reactors R1, R2, R3, and the sum of three reactors, respectively. Then, each stoichiometric equation was generalized to quantitatively describe the reactions in each set of data for 18 different experimental conditions. By analysis, the most and second most sensitive limiting parameters were identified from the 18 stoichiometric equations. The formulas and equations were further upgraded to a generic form for a general organic growth medium (CaHbOcNdPf). Microalgae–microorganism nexus was established by using the developed coefficients to depict the limited and balanced reactions. The study showed that nitrogen and phosphorus are required as additives in CDWW in ord...
The role of computers in dentofacial research and the development of diagnostic aids

Abstract Growth studies provide data for norms and growth standards and, to some extent, make predictions possible. Since the measurements are used to construct norms, they must be derived from valid and reliable landmarks in addition to being accurate. Facial bones grow in three dimensions and therefore must be studied in three dimensions simultaneously. A three-dimensional method which satisfies all these requirements has been developed with assistance from computers. Some studies of individual bones, cranium, dentition, and occlusion using experimental and statistical methods made feasible by automatic data processing are described. The role of computers in the development of predictive methods based on complex statistical procedures is discussed. A computerized discriminant procedure distinguishing normal from abnormal is mentioned. The possibility of reading roentgenograms and photographs automatically by means of scanning devices is considered. It may be possible in the future to construct more accurate and reliable norms, develop predictive methods which are clinically useful, and process patients' records automatically, all with assistance of computers and better scanning devices.
Cross coupled wiggly line hairpin filters with high selectivity and spurious suppression

A low cost and compact microstrip bandpass filter with high selectivity and suppressed harmonic is introduced in this paper. A simple hairpin resonators filter is manipulated to obtain the desired filter performance. Line widths of the resonators are perturbated to adjust odd mode phase velocities in order to lower the higher order modes. Furthermore, by implementing a proper cross coupling from input or output to nonadjacent coupled sections, virtually a quintuplet coupling scheme is realized to improve the filter selectivity. Then the final improved hairpin filter has a sharp cut-off, a low spurious level, and still has the same compact size. The proposed combined technique is very attractive for variety of miniature filter applications. A sample filter is designed for this purpose and it can be adopted in variety of wireless subassemblies including low power radio carriers, mobile communications, and WIMAX applications.
Integrin Regulation of β-Catenin Signaling in Ovarian Carcinoma

Reversible modulation of integrin-regulated cell-matrix adhesion and epithelial (E)-cadherin-mediated cell-cell adhesion plays a critical role in the establishment of ovarian cancer metastases. In contrast to most epithelial cell-derived tumors that down-regulate E-cadherin expression during progression, acquisition of E-cadherin expression accompanies malignant transformation of the ovarian surface epithelium and is maintained in peritoneal metastases. Metastatic epithelial ovarian cancer cells are disseminated intraperitoneally and preferentially adhere via integrins to interstitial collagens in the peritoneal cavity. This study was undertaken to determine whether integrin engagement influences E-cadherin and β-catenin localization and function. The data demonstrate that multivalent integrin engagement results in increased internalization of E-cadherin, inhibition of GSK-3β, elevated levels of nuclear β-catenin, increased β-catenin-regulated promoter activation, and transcriptional activation of Wnt/β-catenin target genes. Blocking β-catenin transcriptional control with inhibitor of β-catenin and Tcf-4 reduces cellular invasion, suggesting a key role for β-catenin nuclear signaling in EOC invasion and metastasis. These studies support a model wherein cell-matrix engagement regulates the functional integrity of cell-cell contacts, leading to increased β-catenin nuclear signaling and enhanced cellular invasive activity. Furthermore, these results provide a mechanism for activation of Wnt/β-catenin signaling in the absence of activating mutations in this pathway.
Crystal Surface and State of Charge Dependencies of Electrolyte Decomposition on LiMn2O4 Cathode

First principles calculations are used to study the initial decomposition reactions of ethylene carbonate (EC) on the (111) surface of LiMn2O4 (LMO), a candidate for Li ion battery (LIB) cathode. Theoretical studies of interfacial reactions are particularly timely due to recent experiments on the effect of LMO crystal morphology on battery cyclability and interfacial film stability [J.-S. Kim, K. Kim, W. Cho, W. H. Shin, R. Kanno, and J. W. Choi, Nano Lett., 12, 6358–6365 (2012)]. We find that EC degradation is a two-step reaction. The first step is the rate determining reaction where a proton is abstracted from EC and transferred to the surface. The second step involves ring opening of the proton abstracted EC which turns out to have a smaller barrier. Both of these reactions are sensitive to the Li content, i.e. state of charge, of the model electrode. EC degradation via H-abstraction becomes a feasible reaction route when the cathode becomes more highly charged. Comparison with predictions on the (100) surface of LMO is discussed, and speculation on the growth of nanometer-thick interfacial layer on LMO despite its relatively modest operating potential are made in light of the reaction driving forces predicted in this work. © 2014 The Electrochemical Society. [DOI: 10.1149/2.009408jes] All rights reserved.
Pavlovian backward conditioned inhibition in humans: Summation and retardation tests

Two experiments using human participants investigated whether a Pavlovian backward inhibitory treatment (nonreinforced trials in phase 1 followed by reinforced trials in phase 2; i.e., AX- followed by A+) produces a stimulus which can pass summation and retardation tests for inhibition. The rationale for conducting these experiments was that previous demonstrations of Pavlovian backward inhibition informed participants about the nature of the outcome before starting the experiment. According to some theoretical views, this is a potential confound. In the present experiments we used a predictive task in which participants had no knowledge about the outcome until phase 2, when reinforcement occurred. The results of Experiment 1 (summation test) and Experiment 2 (retardation test) provide a clear demonstration of backward conditioned inhibition.
A phase I study of 5-azacytidine (NSC-102816)

5-Azacytidine was administered daily to 12 patients in a five-day schedule and to 15 patients in a weekly schedule as part of a phase I trial. The daily dose ranged from 50 mg/m2 to 158 mg/m2 and the weekly dose, from 200 mg/m2 to 633 mg/m2. The maximum total dose was 2000 mg in the daily schedule and 3775 mg in the weekly schedule. The major toxicity was gastrointestinal, with nausea and vomiting occurring in all patients in this study. Myelosuppression was less frequently encountered and appeared to be related to the increase in 5-azacytidine dose. Patients receiving 5-azacytidine in a weekly schedule of administration appeared to tolerate the drug better and to be more willing to continue their therapy.
A distal axonal cytoskeleton forms an intra-axonal boundary that controls axon initial segment assembly.

Summary AnkyrinG (ankG) is highly enriched in neurons at axon initial segments (AISs) where it clusters Na + and K + channels and maintains neuronal polarity. How ankG becomes concentrated at the AIS is unknown. Here, we show that as neurons break symmetry, they assemble a distal axonal submembranous cytoskeleton, comprised of ankyrinB (ankB), αII-spectrin, and βII-spectrin, that defines a boundary limiting ankG to the proximal axon. Experimentally moving this boundary altered the length of ankG staining in the proximal axon, whereas disruption of the boundary through silencing of ankB, αII-spectrin, or βII-spectrin expression blocked AIS assembly and permitted ankG to redistribute throughout the distal axon. In support of an essential role for the distal cytoskeleton in ankG clustering, we also found that αII and βII-spectrin-deficient mice had disrupted AIS. Thus, the distal axonal cytoskeleton functions as an intra-axonal boundary restricting ankG to the AIS.
Bisphosphonates in children with hypercalciuria and reduced bone mineral density.

Previous studies have demonstrated reduced bone mineral density (BMD) and biochemical changes of excessive bone resorption in some patients with idiopathic hypercalciuria (IH). Consequently, bisphosphonates have been successfully employed in research animals and adults with IH and reduced BMD. We evaluated the effect of treatment with bisphosphonates in seven patients ages 10–16 years with persistent IH and reduced BMD. In five children, preceding traditional therapy failed. All children received oral alendronate and one also IV Zoledronic acid for 6–18 (median 9.0, mean 10.7) months. With treatment, BMD Z scores in the lumbar spine improved from −2.0 ± 0.3 to −0.8 ± 0.8 (p = 0.002) and in the femoral neck from −1.8 ± 0.4 to −0.7 ± 0.9 (p = 0.01); urine N-telopeptides/creatinine decreased from 372 ± 289 to 72 ± 39 nmol/mmol (p = 0.05) and calcium/creatinine from 0.29 ± 0.12 to 0.13 ± 0.06 mg/mg (p = 0.009). Height Z scores, normal at baseline in all, remained unaffected, and no new stones or fractures were documented throughout the treatment period. Serum creatinine, electrolytes, calcium, phosphorus and parathyroid hormone remained normal as well. In summary, in children with IH and decreased BMD, treatment with bisphosphonates normalized urine calcium excretion, eliminated urinary symptoms, and significantly improved reduced BMD. These short-term beneficial effects indicate the need for larger prospective studies on the potential of bisphosphonates to serve as a new tool in treating children with IH and reduced BMD.
A Lipid Pathway for Ligand Binding Is Necessary for a Cannabinoid G Protein-coupled Receptor

Recent isothiocyanate covalent labeling studies have suggested that a classical cannabinoid, (−)-7′-isothiocyanato-11-hydroxy-1′,1′dimethylheptyl-hexahydrocannabinol (AM841), enters the cannabinoid CB2 receptor via the lipid bilayer (Pei, Y., Mercier, R. W., Anday, J. K., Thakur, G. A., Zvonok, A. M., Hurst, D., Reggio, P. H., Janero, D. R., and Makriyannis, A. (2008) Chem. Biol. 15, 1207–1219). However, the sequence of steps involved in such a lipid pathway entry has not yet been elucidated. Here, we test the hypothesis that the endogenous cannabinoid sn-2-arachidonoylglycerol (2-AG) attains access to the CB2 receptor via the lipid bilayer. To this end, we have employed microsecond time scale all-atom molecular dynamics (MD) simulations of the interaction of 2-AG with CB2 via a palmitoyl-oleoyl-phosphatidylcholine lipid bilayer. Results suggest the following: 1) 2-AG first partitions out of bulk lipid at the transmembrane α-helix (TMH) 6/7 interface; 2) 2-AG then enters the CB2 receptor binding pocket by passing between TMH6 and TMH7; 3) the entrance of the 2-AG headgroup into the CB2 binding pocket is sufficient to trigger breaking of the intracellular TMH3/6 ionic lock and the movement of the TMH6 intracellular end away from TMH3; and 4) subsequent to protonation at D3.49/D6.30, further 2-AG entry into the ligand binding pocket results in both a W6.48 toggle switch change and a large influx of water. To our knowledge, this is the first demonstration via unbiased molecular dynamics that a ligand can access the binding pocket of a class A G protein-coupled receptor via the lipid bilayer and the first demonstration via molecular dynamics of G protein-coupled receptor activation triggered by a ligand binding event.
The mycotoxin fumonisin B1 transiently activates nuclear factor-kappaB, tumor necrosis factor alpha and caspase 3 via protein kinase Calpha-dependent pathway in porcine renal epithelial cells.

Fumonisin B1 (FB1) is a toxic mycotoxin produced byFusarium verticillioides, predominantly present in corn. The principal biochemical responses of FB1 involve disruption of sphingolipid metabolism from the inhibition of ceramide synthesis leading to accumulation of free sphingoid bases, particularly sphinganine. The ability of FB1 to modulate signal transduction pathways plays a role in its toxicity. We recently reported that FB1 selectively and transiently activatives protein kinase Cα (PKCα) in porcine renal epithelial cells (LLC-PK1). The aim of current study was to investigate the effect of PKCα activation by FB1 on NF-κB activation and subsequently on TNFα gene expression and caspase 3 induction in LLC-PK1 cells. FB1 (1 μmol/L for 5 min) transiently activated PKCα and increased nuclear translocation of NF-κB, followed by their down-regulation at later time points. Preincubating the cells with the PKC inhibitor, calphostin C, prevented the activation of NF-κB by FB1. TNFα mRNA expression was increased after 15 min exposure to FB1 or the PKC activator, phorbol 12-myristate 13-acetate. In addition, an increase in caspase 3 activity was observed after addition of FB1 for 1 h. Calphostin C prevented both the FB1-induced increase in TNFα expression and caspase 3 activation. In summary, we hereby demonstrate that the FB1 activation of NF-κB and sequential induction of TNFα expression resulting in the subsequent increase in caspase 3 activity are all dependent on PKCα stimulation in LLC-PK1 cells.
Do extracellular matrix protein expressions change with cyclic reproductive hormones in pelvic connective tissue from women with stress urinary incontinence

Background To evaluate differential expression of transforming growth factor (TGF-beta1), latent transforming factor-binding proteins (LTBP-1, LTBP-2) and elastin microfibril components (fibrillin-1 and fibrillin-2) in vaginal tissue from women with stress urinary incontinence (SUI). Methods In this case-control study, vaginal tissue from women in both phases of the menstrual cycle was obtained. Messenger RNA (mRNA) expressions of LTBP-1, LTBP-2, fibrillin-1, fibrillin-2 and TGF-beta1 were determined by relative real-time quantification PCR. Tissue localization was analysed by immunohistochemistry, and semiquantitative protein expression was evaluated by Western blot analysis. Results Vaginal wall fibroblasts synthesized all proteins tested. LTBP-1, LTBP-2 and TGF-beta1 co-localized with elastin microfibrils, fibrillin-1 and fibrillin-2 in the extracellular matrix. LTBP-1 mRNA and protein expressions were higher in control versus women affected with SUI in the proliferative phase (P = 0.04), while in the secretory phase, mRNA expression in cases was higher (P = 0.04). Fibrillin-1 mRNA was higher in women affected by SUI versus controls in both phases, but no statistical differences in fibrillin-1 protein expression were observed between the two groups in either phase. LTBP-2 and TGF-beta1 mRNA expressions showed the same trends as LTBP-1. Conclusion LTBP-1, LTBP-2, TGF-beta1, fibrillin-1, and fibrillin-2 expressions are hormonally regulated in vaginal wall fibroblasts and differ in women affected by SUI when compared to controls. These data suggest a mechanism to regulate TGF-beta1 activity in pelvic connective tissue.
Changes in root architecture under elevated concentrations of CO2 and nitrogen reflect alternate soil exploration strategies

Summary Predicting the response of fine roots to increased atmospheric CO2 concentration has important implications for carbon (C) and nutrient cycling in forest ecosystems. Root architecture is known to play an important role in how trees acquire soil resources in changing environments. However, the effects of elevated CO2 on the fine-root architecture of trees remain unclear. We investigated the architectural response of fine roots exposed to 14 yr of CO2 enrichment and 6 yr of nitrogen (N) fertilization in a Pinus taeda (loblolly pine) forest. Root traits reflecting geometry, topology and uptake function were measured on intact fine-root branches removed from soil monoliths and the litter layer. CO2 enrichment resulted in the development of a fine-root pool that was less dichotomous and more exploratory under N-limited conditions. The per cent mycorrhizal colonization did not differ among treatments, suggesting that root growth and acclimation to elevated CO2 were quantitatively more important than increased mycorrhizal associations. Our findings emphasize the importance of architectural plasticity in response to environmental change and suggest that changes in root architecture may allow trees to effectively exploit larger volumes of soil, thereby pre-empting progressive nutrient limitations.
Context-Sensitive Solutions, Value Engineering, and Asset Management: Creating and Maintaining Value, Improving Accountability, and Reaching for Sustainability

Context-sensitive solutions, value engineering or value analysis, and asset management systems are all strategic processes or systems with common objectives, even if they have different emphases. All place a high value on customer satisfaction, stakeholder values, and the delivery or maintenance of safe facilities. All stress the efficient and effective use of resources and the alignment of investments to produce the best outcomes or the most quality for the money. All are open to a broad interpretation of the word "best," but they are challenged by the measurement of performance in areas that are more difficult to quantify. They share an emphasis on transparency, multidisciplinary teams and perspectives, and analytical, evidence-based decision making. They use processes that examine multiple alternatives to finding consensus on ultimate decisions. Especially when they are used together or in tandem, these tools and systems can be used as part of strategic and systematic approaches that have a significant...
Hypercalcaemia and haemophagocytic syndrome: rare concurrent presentations of disseminated tuberculosis in a dialysis patient

Tuberculosis remains an important cause of infection in chronic haemodialysis patients. Frequent extrapulmonary involvement, non-specific presentation and limited diagnostic tools usually make early diagnosis difficult. Herein, we report on an 83-year-old female patient who had been on regular heamodialysis therapy for 15 years, who presented with asymptomatic hypercalcaemia and pancytopenia. Haemophagocytic syndrome was documented during the admission period. Mycobacterium tuberculosis was cultured from bone marrow 1 month after her demise. This case report highlights the non-specific manifestations of extrapulmonary tuberculosis in dialysis patients and the limited value of conventional diagnostic methods. We would like to recommend aggressive intervention and early tissue aspiration from possible infectious sites when tuberculosis cannot be completely ruled out. Disseminated tuberculosis should be considered as an indication of hypercalcaemia where haemophagocytic syndrome occurs simultaneously.
THE DIALECTIC OF LIBERTY: LAW AND RELIGION IN ANGLO-AMERICAN CULTURE

The separation of church and state disguised the coordination of two very different conceptions of liberty at work in Revolutionary America, one with a religious basis in radical Protestant thought and the other with a legal basis in the secular Enlightenment. The essay combines the disciplines of law, literature, and intellectual history to investigate these contrasting formulations and their changing relationship. Cross-cultural analysis of the language of protest in both England and America gives the investigation a crucial focus. It also explains a larger movement from direct influence to refraction in Anglo-American relations.The interdisciplinary approach is critical to understanding how the same language came to mean different things. Exegesis of the common law tradition in England and close rhetorical analysis of pulpit oratory and legal pamphleteering in Revolutionary America reveal a striking shift in the meaning of liberty as legal explanation trumped religious protest in the process of national formations. Properly understood, the paradoxical role of the American lawyer was to cap revolutionary impulses through the manipulation of the language of a bible culture. Legal positivism replaced natural law as a ruling impulse in the definition of rights, and a republic based on the right of revolution became a nation state where the test of membership would be loyalty. The long-term result has been that the citizen faces a permanent and often puzzling dichotomy best understood in dialectical terms. National identity, while secular, responds to providential invocation in the American republic of laws, and protest finds its most potent voice in religious expression.
Confining flux tubes in a current algebra approach

We describe flux tubes and their interactions in a low energy \ensuremath{\sigma} model induced by SU(${\mathit{N}}_{\mathit{f}}$)\ensuremath{\rightarrow}SO(${\mathit{N}}_{\mathit{f}}$) flavor symmetry breaking in SO(${\mathit{N}}_{\mathit{c}}$) QCD. Unlike standard QCD, this model allows gauge confinement to manifest itself in the low energy theory, which has unscreened spinor color sources and global ${\mathit{Z}}_{2}$ flux tubes. We construct the flux tubes and show how they mediate the confinement of spinor sources. We further examine the flux tubes' quantum stability, spectrum, and interactions. We find that flux tubes are Alice strings, despite ambiguities in defining parallel transport. Furthermore, twisted loops of flux tube support Skyrmion number, just as gauged Alice strings form loops that support monopole charge. This model, while phenomenologically unviable, thus affords a perspective on both the dynamics of confinement and on subtleties which arise for global Alice strings.
Scaling of Precipitation Extremes over a Wide Range of Climates Simulated with an Idealized GCM

Extremes of precipitation are examined in a wide range of climates simulated with an idealized aquaplanet GCM. The high percentiles of daily precipitation increase as the climate warms. Their fractional rate of increase with global-mean surface temperature is generally similar to or greater than that of mean precipitation, but it is less than that of atmospheric (column) water vapor content. A simple scaling is introduced for precipitation extremes that accounts for their behavior by including the effects of changes in the moist-adiabatic lapse rate, the circulation strength, and the temperature when the extreme events occur. The effects of changes in the moist-adiabatic lapse rate and circulation strength on precipitation extremes are important globally, whereas the difference in the mean temperature and the temperature at which precipitation extremes occur is important only at middle to high latitudes.