cssi/SciSciGPT-SciSciNet huggingface dataset:
Phase II evaluation of three-day topotecan in recurrent platinum-sensitive ovarian carcinoma: a gynecologic oncology group study.

BACKGROUND Topotecan, administeredintravenously at a dose of 1.5 mg/m2 per day for 5 days every 21 days, is an established regimen in the treatment of recurrent ovarian carcinoma. Alternate dosing strategies have sought to improve toxicity. The authors evaluated the tolerability and antitumor activity of a 3-day topotecan regimen. METHODS A multicenter Phase II study, which included patients with platinum-sensitive ovarian carcinoma, was conducted. Patients were to receive an intravenous dose of topotecan of 2.0 mg/m2 per day for 3 days every 21 days until disease progression or unacceptable toxicity occurred. Doses were modified in 0.25-mg/m2 increments based on tolerability. Granulocyte–colony-stimulating factor support was used as necessary. RESULTS From February to June 2000, 30 patients were enrolled. Their median age was 56 years (range, 41–81 years). Twenty-nine patients were evaluable for toxicity and efficacy. A median of 5 courses (range, 1–11 courses) of topotecan was administered. Eighteen of 30 (60%) patients experienced Grade 4 neutropenia. There was one report each of Grade 4 thrombocytopenia, anemia, and gastrointestinal toxicity (grading performed according to National Cancer Institute Common Toxicity Criteria). Ten patients developed Grade 3 leukopenia and 9 had Grade 3 neutropenia. Serious nonhematologic events were rare. There were 2 (7%) complete and 2 (7%) partial responses, for an overall response rate of 14%. Sixteen (55%) patients had stable disease and 9 (31%) experienced disease progression. CONCLUSIONS A 3-day regimen of topotecan at a dose of 2.0 mg/m2 per day was generally well tolerated, although the response rate was lower than that for the standard 5-day schedule. Cancer 2003. © 2003 American Cancer Society. DOI 10.1002/cncr.11690
Studies of low-lying levels of 33 S by the 30 Si (α,nγ) 33 S reaction.

Abstract The 30 Si (α, n γ) 33 S reaction was used to investigate 33S levels up to 4.3 MeV excitation energy. Each individual state was populated in turn with bombarding energies chosen to be sufficiently near threshold that neutrons of low-order angular momentum were emitted. Accurate excitation energies were determined. The angular distributions of γ-rays de-exciting these levels were analyzed according to standard angular-correlation theory. Experimental results include the spin limitations: J π (2969) = 7 2 + , J(4048) = 5 2 or 9 2 , J(4094) ≧ 3 2 , J(4142) = 3 2 or 5 2 . It is concluded that there exist two levels in 33S near 4.05 MeV excitation energy with a separation of 5±4 keV. The mixing-ratio determinations permit a critical comparison of recent shell-model calculations with the experimental data. The calculations are in reasonably good agreement with the experimental data.
Microbial Conversion of α-Ionone, α-Methylionone, and α-Isomethylionone

alpha-Ionone, alpha-methylionone, and alpha-isomethylionone were converted by Aspergillus niger JTS 191. The individual bioconversion products from alpha-ionone were isolated and identified by spectrometry and organic synthesis. The major products were cis-3-hydroxy-alpha-ionone, trans-3-hydroxy-alpha-ionone, and 3-oxo-alpha-ionone. 2,3-Dehydro-alpha-ionone, 3,4-dehydro-beta-ionone, and 1-(6,6-dimethyl-2-methylene-3-cyclohexenyl)-buten-3-one were also identified. Analogous bioconversion products from alpha-methylionone and alpha-isomethylionone were also identified. From results of gas-liquid chromatographic analysis during the fermentation, we propose a metabolic pathway for alpha-ionones and elucidation of stereochemical features of the bioconversion.
Bipartite structure of an early meiotic upstream activation sequence from Saccharomyces cerevisiae

Diploid a/alpha Saccharomyces cerevisiae cells cease mitotic growth and enter meiosis in response to starvation. Expression of meiotic genes depends on the IME1 gene product, which accumulates only in meiotic cells. We report here an analysis of the regulatory region of IME2, an IME1-dependent meiotic gene. Deletion and substitution studies identified a 48-bp IME1-dependent upstream activation sequence (UAS). Activity of the UAS also requires the RIM11, RIM15, and RIM16 gene products, which are required for expression of the chromosomal IME2 promoter and for meiosis. Through a selection for suppressors that permit UAS activity in an ime1 deletion mutant, we identified recessive mutations in three genes, SIN3 (also called RPD1, UME4, and SDI1), RPD3, and UME6 (also called CAR80), that were previously known as negative regulators of other early meiotic genes. Mutational analysis of the IME2 UAS reveals two critical sequence elements: a G+C-rich sequence (called URS1), previously identified at many meiotic genes, and a newly described element, the T4C site, that we found at a subset of meiotic genes. In agreement with prior studies, URS1 mutations lead to elevated IME2 UAS activity in the absence of IME1. However, the URS1 mutations prevent any further stimulation of UAS activity by IME1. Repression through URS1 has been shown to require the UME6 gene product. We find that activation of the IME2 UAS by IME1 also requires the UME6 gene product. Thus, UME6 and the URS1 site both have dual negative and positive roles at the IME2 UAS. We propose that IME1 modifies UME6 to convert it from a negulator to a positive Regulor.
Buckling, collapse and failure analysis of FRP sandwich panels ☆

Abstract Rectangular orthotropic fiber-reinforced plastic (FRP) sandwich panels were tested for buckling in uni-axial compression. The panels, with 0.32 cm (0.125 in.) face sheets and a 1.27 cm (0.5 in.) core of either balsa or linear poly(vinyl chloride) (PVC) foam, were tested in two sizes: 154×77 cm2 (72×36 in.2) and 102×77 cm2 (48×36 in.2). The sandwich panels were fabricated using the vacuum-assisted resin transfer molding process. The two short edges of the sandwich panels were clamped, while the two long edges were simply supported for testing. The clamped panel ends were potted into a steel frame. The experimental elastic buckling loads were then measured using strain gauges fixed to both sides of the panels. A total of 12 panels were tested under uni-axial compression. Bifurcation in the load versus engineering strain curve was noted in all cases. For all six sandwich panels tested using balsa core, the type of failure was easily identified as face sheet delamination followed by core shear failure. For all six PVC foam core sandwich panels tested, the type of failure consisted of core shear failure with little or no face sheet delamination. In the failed balsa core panels there was little or no evidence of balsa remaining on the FRP face sheet, however, in the PVC foam core panels there were ample amounts of foam left on the FRP face sheet. It was concluded that although the buckling loads for the foam core panels were not as high as those for the balsa core panels, PVC foam core bonding to the FRP face sheets was superior to balsa core bonding.
Septic Systems as a ‘Green’ Technology

ity. On-site treatment systems are now an integral part of our wastewater infrastructure and are collectively referred to as decentralized wastewater systems. Decentralized wastewater technology and management refers to wastewater treatment and dispersal systems from the individual on-site treatment system (septic systems) to small community collection and treatment systems (cluster systems) and includes the process involved in siting, installing, operating and maintaining the systems. These systems rely upon land application by surface or subsurface dispersal and proper treatment of the wastewater. They allow the treated wastewater to re-enter the hydrologic cycle close to where the potable water was removed. Often, as in the case of an individual system, this is less than a few hundred feet. They are considered to be non-point source discharges by federal and state standards. Often septic systems are portrayed in a negative light but they are now an integral part of our wastewater infrastructure. Photo by David Lindbo and courtesy of Soil Science @ NC State's Flickr photostream.
An orbital-overlap model for minimal work functions of cesiated metal surfaces

We introduce a model for the effect of cesium adsorbates on the work function of transition metal surfaces. The model builds on the classical point-dipole equation by adding exponential terms that characterize the degree of orbital overlap between the 6s states of neighboring cesium adsorbates and its effect on the strength and orientation of electric dipoles along the adsorbate–substrate interface. The new model improves upon earlier models in terms of agreement with the work function–coverage curves obtained via first-principles calculations based on density functional theory. All the cesiated metal surfaces have optimal coverages between 0.6 and 0.8 monolayers, in accordance with experimental data. Of all the cesiated metal surfaces that we have considered, tungsten has the lowest minimum work function, also in accordance with experiments.
Involvement of mitochondira in ischemic cell injury and in regulation of intracellular calcium

Abstract Ischemia causes a pathological drop in the cellular energy state due to inhibition of mitochondrial oxidative phosphorylation. The reversibility of this condition depends on the damage to mitochondrial membrane-linked activities during the period of ischemia or during reoxygenation of the tissue. It is likely that the ischemia-induced damage is due to a combination of factors including an increase in the cytosolic free Ca 2+ concentration, a triggering of phospholipase and protease activities, an increase in cellular free fatty acids, and a decrease in pH. Mitochondrial damage that occurs during reperfusion is probably a consequence of excessive mitochondrial Ca 2+ accumulation under adverse intracellular conditions. Mitochondria normally have an extremely high capacity for sequestering and buffering cytosolic Ca 2+ . However, during post-ischemic reperfusion these processes are inhibited due to existing conditions that potentiate Ca 2+ uptake-induced irreversible mitochondrial damage.
Recognition of common odors, pictures, and simple shapes.

Recognition of common odors and simple shapes decayed in a similar manner over the course of 4 months. Recognition of complex pictures was uniformly higher than recognition of the odors and simple figures, although the distractors for these stimuli were much less similar than for the odors or simple shapes. Recognition of these common odors was the same as recognition performance on single chemicals used in previous studies. These results suggest that simple chemicals and complex familiar odors are encoded or remembered in a similar fashion, and that visual stimuli exist which are encoded in a similar manner to odors, possibly as unitary images with few features.
Parametric Study of Ultrafiltration

The performance of cross flow hollow fiber ultrafiltration (UF) membrane with molecular weight cut off (MWCO) 100 kDaltons was studied in order to effectively remove suspended solids in wastewater. Experiments were carried out to investigate the influence of the several factors such as cross flow velocity, transmembrane pressure (TMP), water temperature, and concentration of suspended solids on the membrane performance. Several cleaning methods were applied to remove the fouling. The experimental results showed that increasing TMP, temperature and cross flow velocity all resulted in increasing permeate flux. It is observed that high TMP aggravated the fouling while high cross flow velocity alleviated the fouling. High concentrations of suspended solids led to the reduction of permeate flux. It is also found that both combination of chemical, back- and forward-washing as well as soaking cleaning methods effectively removed fouling and achieved high flux recovery. The suspended solids were effectively removed by our UF system, and the water quality is significantly improved after ultrafiltration.Copyright © 2009 by ASME
Customs Union and the Harris-Todaro Model with International Capital Mobility

Traditional customs union theory concludes that trade creation enhances welfare. Thus, Yu's (1982) conclusion that trade creation may decrease welfare in the presence of general unemployment is an important observation. Parai and Batra (1987) reestablish the traditional results in the Harris-Todaro model, where unemployment is sector-specific. We conclude that trade creation may decrease welfare in the Harris-Todaro model with international capital mobility when labor subsidies or capital taxes (subsidies) exist. Moreover, second-best labor subsidies or capital subsidies (taxes) recommended by some authors increase the chances of welfare decreasing trade creation.
Investigation of [67Ga]dimethylgallium(III) acetylacetonate as a potential radiopharmaceutical.

Abstract Carrier-added [ 67 Ga]dimethylgallium(III) acetylacetonate, a four coordinate Ga complex with two hydrolytically-stable GaC bonds, was prepared at a specific activity of 2.8 mCi/mmol. The biodistribution of this tracer was determined following intravenous injection into rats as a 5% ethanol: 19% propylene glycol solution in saline. Although the myocardial levels of 67 Ga were fairly constant over a 2 h time period (%ID/heart = 0.80 ± 0.19, 0.67 ± 0.04 and 0.62 ± 0.07 at 1, 30 and 120 min post-injection, respectively), somewhat slow clearance of activity from the blood would preclude the use of this organometallic gallium complex as a myocardial imaging agent.
Interaction of radical pairs through-bond and through-space: scope and limitations of the point-dipole approximation in electron paramagnetic resonance spectroscopy.

The validity of the popular point−dipole approximation for interpretation of the zero-field splitting (ZFS) parameter (D-value) in EPR spectroscopy is studied. This approximation is of central importance for the determination of distances by analysis of EPR data. In this work, a detailed experimental (EPR spectroscopy and X-ray crystallography) and theoretical study for a model system (2,2′,5,5′-tetra(tert-butyl)-4,4′-bis(ethoxy-carbonyl)-3,3′-bipyrrolyl-1,1′-dioxyl) was performed to understand the scope and limitations of the point−dipole model in EPR spectroscopy. For this diradical, the radical−radical distance derived with the point−dipole approximation deviates significantly (by ∼40%) from the results derived from the X-ray analysis. Explicit quantum chemical calculation of the D-value on the basis of B3LYP density functional calculations leads to excellent quantitative agreement with the measured D-value. The quantitative accuracy of the employed methodology was confirmed for two additional systems ...
Label-free measurement of DNA oligomer binding using a highly-sensitive photonic crystal biosensor

With a highly sensitive one dimensional photonic crystal biosensor, we have demonstrated quantitative real-time label-free detection of DNA oligomers, including binding to protein, concentration detection limits, and base-mismatched hybridization.
Genetic testing strategies in newly diagnosed endometrial cancer patients aimed at reducing morbidity or mortality from lynch syndrome in the index case or her relatives.

Endometrial cancer is the first malignancy in 50% of women with Lynch syndrome, an autosomal dominant cancer-prone syndrome caused by germline mutations in genes encoding components of the DNA mismatch repair (MMR) pathway. These women (2-4% of all those with endometrial cancer) are at risk of metachronous colorectal cancer and other Lynch syndromeassociated cancers, and their first-degree relatives are at 50% risk of Lynch syndrome. Testing all women newly diagnosed with endometrial cancer for Lynch syndrome may have clinical utility for the index case and her relatives by alerting them to the benefits of surveillance and preventive options, primarily for colorectal cancer. The strategy involves offering germline DNA mutation testing to those whose tumour shows loss-of-function of MMR protein(s) when analysed for microsatellite instability (MSI) and/or by immunohistochemisty (IHC). In endometrial tumours from unselected patients, MSI and IHC have a sensitivity of 80-100% and specificity of 60-80% for detecting a mutation in an MMR gene, though the number of suitable studies for determining clinical validity is small. The clinical validity of strategies to exclude those with false-positive tumour test results due to somatic hypermethylation of the MLH1 gene promoter has not been determined. Options include direct methylation testing, and excluding those over the age of 60 who have no concerning family history or clinical features. The clinical utility of Lynch syndrome testing for the index case depends on her age and the MMR gene mutated: the net benefit is lower for those diagnosed at older ages and with less-penetrant MSH6 mutations. To date, women with these features are the majority of those diagnosed through screening unselected endometrial cancer patients but the number of studies is small. Similarly, clinical utility to relatives of the index case is higher if the family’s mutation is in MLH1 or MSH2 than for MSH6 or PMS2. Gaps in current evidence include a need for large, prospective studies on unselected endometrial cancer patients, and for health-economic analysis based on appropriate assumptions. Funding Statement Alison Stewart is an employee of McKing Consulting Corporation. The author is currently a paid contractor working at the Office of Public Health Genomics, Centers for Disease Control and Prevention and this article was created during the course of that work.
Outcomes of open surgery versus nonoperative management of acute achilles tendon rupture.

This CJSM Journal Club contribution provides a commentary on the following article: Wilkins R, Bisson LJ. Operative versus nonoperative management of acute Achilles tendon ruptures: a quantitative systematic review of randomized controlled trials. Am J Sports Med. 2012;24:2154–2160.
Target-dependent structural changes accompanying long-term synaptic facilitation in Aplysia neurons

The mechanisms underlying structural changes that accompany learning and memory have been difficult to investigate in the intact nervous system. In order to make these changes more accessible for experimental analysis, dissociated cell culture and low-light-level video microscopy were used to examine Aplysia sensory neurons in the presence or absence of their target cells. Repeated applications of serotonin, a facilitating transmitter important in behavioral dishabituation and sensitization, produced growth of the sensory neurons that paralleled the long-term enhancement of synaptic strength. This growth required the presence of the postsynaptic motor neuron. Thus, both the structural changes and the synaptic facilitation of Aplysia sensorimotor synapses accompanying long-term behavioral sensitization can be produced in vitro by applying a single facilitating transmitter repeatedly. These structural changes depend on an interaction of the presynaptic neuron with an appropriate postsynaptic target.
Optical transmittance of fused silica at elevated temperatures during high energy electron bombardment

An experimental determination of the optical transmission of Corning 7940 UV and Suprasil I fused silica has been made. The LeRC dynamitron provided the equivalent ionizing radiation and high temperature that the transparent gas divider of an operating nuclear light bulb engine would experience. The irradiation induced absorption was measured at 2150 A, 2700 A, and 4500 A. The length of the irradiations were sufficient so that an equilibrium between radiation induced coloration and high temperature annealing was reached. The experimental results indicate a significant optical absorption, particularly at the shorter wavelength, which would make the use of fused silica in this concept questionable.
Arrested Kondo effect and hidden order in URu 2 Si 2

The so-called hidden-order state in URu2Si2 is further obscured by conflicting experimental observations. A first-principles calculation shows that an order parameter with real and imaginary parts can explain many of these conflicts.
Herbal medicinal products target defined biochemical and molecular mediators of inflammatory autoimmune arthritis

Rheumatoid arthritis (RA) is a chronic debilitating disease characterized by synovial inflammation, damage to cartilage and bone, and deformities of the joints. Several drugs possessing anti-inflammatory and immunomodulatory properties are being used in the conventional (allopathic) system of medicine to treat RA. However, the long-term use of these drugs is associated with harmful side effects. Therefore, newer drugs with low or no toxicity for the treatment of RA are actively being sought. Interestingly, several herbs demonstrate anti-inflammatory and anti-arthritic activity. In this review, we describe the role of the major biochemical and molecular mediators in the pathogenesis of RA, and highlight the sites of action of herbal medicinal products that have anti-arthritic activity. With the rapidly increasing use of CAM products by patients with RA and other inflammation-related disorders, our review presents timely information validating the scientific rationale for the use of natural therapeutic products.
CHF2OCHF2 (HFE-134): IR spectrum and kinetics and products of the chlorine-atom-initiated oxidation.

Smog chamber/FTIR techniques were used to measure k(Cl + CHF2OCHF2) = (5.7 ± 1.5) × 10−16 cm3 molecule−1 s−1 in 700 Torr of N2/O2 diluent at 296 ± 1 K. This result is 100 times lower than the previous literature value. The chlorine-atom-initiated atmospheric oxidation of CHF2OCHF2 gives COF2 in a molar yield of (185 ± 22) %. The IR spectrum was recorded, and a radiative efficiency of 0.44 W m−2 ppb−1 was determined. The results are discussed with respect to the atmospheric chemistry and environmental impact of CHF2OCHF2.
Moraic mismatches in Bantu

Research in moraic phonology has generally assumed that a single representation is sufficient to account for all phonological rules dependent on moraic structure (Hock 1984; Hyman 1984, 1985; McCarthy & Prince 1986; Zec 1988; Hayes 1989). Thus, if a CVC syllable has the moraic structure in (1), all phonological rules will treat it as bimoraic. I term this the MORAIC UNIQUENESS HYPOTHESIS: at any given stage of a derivation, there is only one moraic projection.
Palpable, Elevated, Pigmented Nodule in the Palate

\ 55-year-old black man under treatment for hypertension was re­ ferred to the dental service by his physician for evaluation of whitish areas distal to the mandibular molars. The buccal mucosa in these areas was partially covered by a filmy-white, thin, plaquelike material, which could be rubbed off, leaving a slightly red­ dened surface. The mucosa generally showed signs of inflammation and irri­ tation w ith generalized nicotine stomatitis of the palate, probably re­ lated to the patient’s moderately heavy smoking. A slightly elevated, palpa­ ble, bluish nodule measuring 0.3 cm in diameter was noticed in the posterior hard palate near the junction of the soft palate, just left of the midline (Fig 1). The clinical impression was of a lo­ calized reaction to irritation and pos­ sible overgrowth of Candida on the buccal mucosa; nicotine stomatitis, palate, and exogenous pigmentation; blue nevus; or thrombosed varix, pal­ ate. Radiographs of the palatal area showed no radiopaque material in as­ sociation with the bluish-black pig­ mented area.
Metabolic flux analysis of halogenated monoterpene biosynthesis in microplantlets of the macrophytic red alga Ochtodes secundiramea

Abstract The bioprocess engineering of marine macroalgae (i.e. seaweeds) for the production of secondary metabolites is an emerging area of marine biotechnology. One novel system is the biosynthesis of halogenated monoterpenes by “microplantlet” suspension cultures derived from the red alga Ochtodes secundiramea . This biosynthetic platform has three principal components: elaboration of myrcene from geranyl diphosphate (GPP); bromonium-ion promoted halogenation of myrcene to 10 E -bromomyrcene, 3-chloro-10 E -bromo-α-myrcene, and 3,10 E -dibromomyrcene; bromonium-ion promoted cyclization of myrcene to Apakaochtodene B. In this study, a metabolic flux analysis on halogenated monoterpene biosynthesis was performed. To facilitate this effort, a “bromine free” cell line of O. secundiramea microplantlets was developed where biohalogenation was temporarily disabled but myrcene biosynthesis was still enabled. This cell line was cultivated within an airlift photobioreactor under nutrient medium perfusion. Halogenated monoterpene biosynthesis was “turned on” by coordinated addition of bromide and vanadate (a co-factor for vanadium bromoperoxidase) to the perfusion medium. From these experiments, the effects of bromide and vanadate delivery on the metabolic flux of each metabolite were determined. Bromination of myrcene at its Δ 6–10 olefinic bond was the dominant branch of the bioreaction network, whereas chlorination steps in the pathway were “weakly rigid”. This study represents the first application of metabolic engineering principles to the analysis and manipulation of secondary metabolism in macrophytic marine organisms.
Estimating inhibition concentrations for different response scales using generalized linear models

Legal mandates exist for the protection of aquatic life and human health from the impacts of toxins released into receiving waters. To accomplish this objective, numeric environmental quality criteria are set. Data utilized commonly in the development of such criteria include no-observed-effect concentrations (NOECs), lowest-observed-effect concentrations (LOECs) and effective concentrations (ECs). The NOEC and LOEC are design-sensitive indices and are open to strong criticism. The EC indices are often estimated through the inversion of a fitted parametric regression model. One criticism leveled against the EC estimation routines has been that one model cannot be appropriate for the variety of different biological endpoints that are studied in aquatic toxicology. These biological endpoints include survival (dichotomous response), fecundity (counts), and biomass/growth (continuous response). In the present study, generalized linear models (GLiMs) are shown to provide a general model for data commonly encountered in aquatic toxicology. The proposed EC estimator, labeled a relative inhibition of RI estimator, is derived in this GLiM framework. This estimator represents the concentration, or more generally, the exposure level to some hazard, associated with a specified level of change in the response relative to the control response. Along with the construction of this estimator, standard errors and confidencemore » intervals are presented. This RI estimator is then applied to dichotomous, count, and continuous responses to illustrate its use.« less
The two-domain structure of 5'-adenylylsulfate (APS) reductase from Enteromorpha intestinalis is a requirement for efficient APS reductase activity.

5'-Adenylylsulfate (APS) reductase from Enteromorpha intestinalis (EiAPR) is composed of two domains that function together to reduce APS to sulfite. The carboxyl-terminal domain functions as a glutaredoxin that mediates the transfer of electrons from glutathione to the APS reduction site on the amino-terminal domain. To study the basis for the interdomain interaction, a heterologous system was constructed in which the C domain of EiAPR was fused to the carboxyl terminus of the APS reductase from Pseudomonas aeruginosa (PaAPR), an enzyme that normally uses thioredoxin as an electron donor and is incapable of using glutathione for this function. The hybrid enzyme, which retains the [4Fe-4S] cluster from PaAPR, was found to use both thioredoxin and glutathione as an electron donor for APS reduction. The ability to use glutathione was enhanced by the addition of Na 2 SO 4 to the reaction buffer, a property that the hybrid enzyme shares with EiAPR. When the C domain was added as a separate component, it was much less efficient in conferring PaAPR with the ability to use glutathione as an electron donor, despite the fact that the separately expressed C domain functioned in two activities that are typical for glutaredoxins, hydroxyethyl disulfide reduction and electron donation to ribonucleotide reductase. These results suggest that the physical connection of the reductase and C domain on a single polypeptide is critical for the electron-transfer reaction. Moreover, the effect of Na 2 SO 4 suggests that a water-ordering component of the reaction milieu is critical for the catalytic function of plant-type APS reductases by promoting the interdomain interaction.
A Formal [3 + 3] Cycloaddition Reaction. Improved Reactivity Using α,β-Unsaturated Iminium Salts and Evidence for Reversibility of 6π-Electron Electrocyclic Ring Closure of 1-Oxatrienes

A detailed account regarding a formal [3 + 3] cycloaddition method using 4-hydroxy-2-pyrones and 1,3-diketones is described here. This formal cycloaddition reaction or annulation reaction is synthetically useful for constructing 2H-pyranyl heterocycles. The usage of α,β-unsaturated iminium salts is significant in controlling competing reaction pathways to give exclusively 2H-pyrans. Most significantly, experimental evidence is provided to support the mechanism of this reaction that involves a sequential Knoevenagel condensation and a reversible 6π-electron electrocyclic ring-closure of 1-oxatrienes.
The second component of human complement: its isolation, fragmentation by C'1 esterase, and incorporation into C'3 convertase.

A method has been described for the purification and isolation of the second component of complement (C'2) from human serum. The protein is a β1-globulin with an approximate molecular weight of 117,000. Immunochemical analysis using a variety of specific antisera, including a monospecific antiserum to the isolated protein, indicate that the C'2 protein represents a heretofore unrecognized human serum constituent. Isolated C'2 contained 2 x 109 "effective molecules" per microgram and 1000 hemolytically active C'2 molecules were required to produce a single hemolytically effective C'2 site on erythrocytes undergoing immune cytolysis. C'1 esterase treatment of C'2 resulted in reduction of both its electrophoretic mobility and its molecular size, the latter observation indicating fragmentation of the molecule. Direct evidence was presented for the physical presence of C'2 as an integral part of the enzyme C'3 convertase.
Mean square values of Hecke L –series formed with r –th order characters

Let L be a number field containing the r–th roots of unity. Starting with the Rankin-Selberg convolution of a metaplectic Eisenstein series on the r–fold cover of GL(2) with itself, we construct a Dirichlet series defined over L whose coefficients involve the r–th order twists of a fixed Hecke L–function. We then observe that a group of functional equations can be naturally associated with this construction. Combining this with the convexity theorem for holomorphic functions of several complex variables, we show that this object, as a function of two complex variables, admits meromorphic continuation to ℂ2. As an application, we obtain asymptotic formulae for mean square values of the r–th order twists of an arbitrary Hecke L–function defined over L.
The Enthalpy of Insertion of Sulfur into the Metal−Hydrogen Bond. Synthetic, Structural, and Calorimetric Study of the Complexes HS−M(CO)3C5R5 [M = Cr, Mo, W; R = H, Me]

Synthetic and calorimetric studies of the sulfhydryl complexes HS−M(CO)3C5R5 (M = Cr, R = Me; M = Mo, W, R = H, Me) are reported. The Mo and W complexes can be obtained in high yield by reaction of the hydrido complexes H−M(CO)3C5R5 with Ph3SbS, which readily undergoes single S atom transfer to the metal−hydrogen bond yielding the metal−sulfhydryl complex. Direct reaction between the metal hydrides and a limited amount of sulfur also yields the sulfhydryl complexes as the dominant organometallic product. At sulfur atom/metal hydride ratios higher than 1/1, additional products formulated as HSn−M(CO)3C5R5 are detected. The enthalpies of insertion of sulfur from Ph3SbS and S8 into the metal−hydrogen bond have been determined by solution calorimetry. The HS−M(CO)3C5R5 complexes (M = Mo, W) are readily desulfurized by PCy3 for R = H, but not for R = Me. The M−SH bond strength estimates for the complexes HS−M(CO)3C5Me5 increases in the order Cr (46) < Mo (55) < W (63) (kcal/mol). The HS−Mo(CO)3C5Me5 group has ...
Low temperature tolerance of insects in relation to the influence of temperature on muscle apyrase activity

Abstract The influence of temperature on the rate of apyrase activity was examined in species that differ in chill-coma and habitat temperatures. Correlations were sought which might account for the ability of some insects to remain at temperatures causing inactivation or chill-coma in other species. Muscle apyrase determinations were made with the housefly, Musca domestica; the sarcophagid fly, Sarcophaga bullata; the waxmoth, Galleria mellonella; the giant death's head roach, Blaberus craniifer; warm-, cold-, and unadapted American cockroaches, Periplaneta americana; warm- and cold-adapted mealworms, Tenebrio molitor; the crayfish, Cambarus diogenes; and the horseshoe crab, Limulus polyphemus. At given low temperatures the rates and temperature coefficients of apyrase activity were generally higher in animals with the lower chill-coma temperatures. However, at temperatures 3–4°C above the respective chill-coma temperatures, the rates were nearly the same in each species (0·4±0·1 μg P/mg muscle/min). The relationship between chill-coma temperature and temperature coefficient was linear; in the insects, 1°C difference in coma temperature was equivalent to a difference of about 2400 cal in μ-value. Apyrase rate maxima occurred at lower temperatures in species having lower chill-coma temperatures, and the maxima were greater in species that might be regarded as normally most active. In an intraspecific comparison apyrase activity at given temperatures was greater in cold-adapted than in warm-adapted P. americana. However, intraspecific adaptation appeared to have little or no effect on the temperature coefficients of apyrase activity. It was concluded that (1) higher apyrase rates, (2) higher temperature coefficients in species with lower chill-coma temperatures, and (3) the occurrence of a common rate of apyrase activity at a temperature several degrees above the respective chill-coma temperatures might well constitute important mechanisms involved in the adaptive compensation permitting maintenance of activity at low temperatures. The data are consistent with the suggestion that perhaps a minimum rate of hydrolysis of ATP is necessary to permit muscular contraction.
Evidence for lipid packaging in the crystal structure of the GM2-activator complex with platelet activating factor

GM2-activator protein (GM2-AP) is a lipid transfer protein that has the ability to stimulate the enzymatic processing of gangliosides as well as T-cell activation through lipid presentation. Our previous X-ray crystallographic studies of GM2-AP have revealed a large lipid binding pocket as the central overall feature of the structure with non-protein electron density within this pocket suggesting bound lipid. To extend these studies, we present here the 2 A crystal structure of GM2-AP complexed with platelet activating factor (PAF). PAF is a potent phosphoacylglycerol whose toxic patho-physiological effects can be inhibited by GM2-AP. The structure shows an ordered arrangement of two bound lipids and a fatty acid molecule. One PAF molecule binds in an extended conformation within the hydrophobic channel that has an open and closed conformation, and was seen to contain bound phospholipid in the low pH apo structure. The second molecule is submerged inside the pocket in a U-shaped conformation with its head group near the single polar residue S141. It was refined as lyso-PAF as it lacks electron density for the sn-2 acetate group. The alkyl chains of PAF interact through van der Waals' contacts, while the head groups bind in different environments with their phosphocholine moieties in contact with aromatic rings (Y137, F80). The structure has revealed further insights into the lipid binding properties of GM2-AP, suggesting an unexpected unique mode of lipid packaging that may explain the efficiency of GM2-AP in inhibiting the detrimental biological effects of PAF.
Serving Multicultural Patients: Community Pharmacist Perceptions

ABSTRACT The purpose of this study was to examine perceptions of community pharmacists in New York City toward serving multicultural customers. The study also examined the effect of demographic factors on cultural sensitivity of pharmacists. A survey instrument was developed consisting of twenty-one attitude questions on a Likert scale. Factor Analysis revealed six dimensions underlying cultural sensitivity in pharmacy practice. A total of 257 pharmacists answered the survey instrument. The data was analyzed using SPSS 7.5 for Windows. In general, the pharmacists appeared to recognize the importance for practicing pharmacists to be sensitive to the needs of ethnic populations. The pharmacists felt that medication compliance, pharmacist-patient relationship, patient satisfaction, patient trust, and ability to understand OTC and prescription product directions would be greater if the pharmacist could speak the language and understand the culture of the customer population. Gender, ethnicity, and language sk...
Empirical evaluation of some features of instruction set processor architectures

This paper presents methods for empirical evaluation of features of Instruction Set Processors (ISPs). ISP features are evaluated in terms of the time used or saved by having or not having the feature. The methods are based on analysis of traces of program executions. The concept of a register life is introduced, and used to answer questions like: How many registers are used simultaneously? How many would be sufficient all of the time? Most of the time? What would the overhead be if the number of registers were reduced? What are registers used for during their lives? The paper also discusses the problem of detecting desirable but non-existing instructions. Other problems are briefly discussed. Experimental results are presented, obtained by analyzing 41 programs running on the DECsystem10 ISP.
UV-Visible Absorption Spectroscopy To Examine Shock-Induced Decomposition in Neat Nitromethane

Time-resolved UV−visible absorption spectroscopy was used to examine chemical decomposition in neat liquid nitromethane (NM) subjected to stepwise shock loading to 19 GPa. Up to a peak pressure (temperature) of 13.8 GPa (854 K), no sign of chemical reaction was observed in the nπ* absorption band centered at 270 nm. For shock compression resulting in peak temperatures above 940 K, extensive reaction was indicated by irreversible red-shifting of the absorption band edge that occurred after peak pressure was reached. This red-shift was followed by a loss of transmission through the sample, which was attributed to the formation of absorbing reaction products. Comparison of these reaction-induced spectral changes with previous absorption results for NM sensitized by ethylenediamine (EDA) suggests that the presence of the amine causes a change in the early stages of shock-induced decomposition. An induction time was observed between the attainment of peak pressure and the onset of reaction-induced spectral cha...
Morphology and properties of nanocomposites formed from ethylene/methacrylic acid copolymers and organoclays

Abstract Nanocomposites were prepared by melt mixing ethylene/methacrylic acid copolymers and organoclays, which were compared to equivalent composites prepared from low-density polyethylene (LDPE) and a sodium ionomer of poly(ethylene-co-methacrylic acid). The effects of matrix modification and organoclay structure on the morphology and properties of these nanocomposites were evaluated using stress–strain analysis, wide-angle X-ray scattering (WAXS), and transmission electron microscopy coupled with particle analysis. With all four polymers, the use of a two-tailed organoclay, M2(HT)2, led to the formation of more exfoliated nanocomposites than a one-tailed organoclay, M3(HT)1. Nanocomposites prepared from ethylene/methacrylic acid copolymers revealed better exfoliation compared to similar composites prepared from LDPE. It seems that the presence of relatively small quantities (1.3–3.1 mol%) of the polar methacrylic acid monomer aids in improving the organoclay exfoliation efficiency of these polymers. Nanocomposites prepared from the sodium ionomer of poly(ethylene-co-methacrylic acid) exhibited the highest levels of organoclay exfoliation compared to all other polymers examined in this study. However, from the observations made in this study, it was not possible to determine conclusively the relative interaction of carboxyl acid groups versus the salt form with the organoclay and, thus, their influence on exfoliation; additional studies will be needed to reach a conclusion on this important point.
A comparison of thromboelastogram and template bleeding time in the evaluation of platelet function after aspirin ingestion

Abstract Study Objective: To compare template bleeding time (TBT) with thromboelastography (TEG) in human subjects after aspirin ingestion. Design: Healthy volunteers were given a single 650 mg dose of aspirin or a dose of 650 mg of aspirin on three successive days. TBT and TEG studies were performed prior to aspirin ingestion and 4, 24, 72, and 168 hours after ingestion. Setting: Inpatient operating room support area at the UCLA Center for Health Sciences. Volunteers: Residents and nurses who were in good general health, had not taken aspirin for 2 weeks, had normal platelet counts, and had no evidence of bleeding or coagulation disorders. Intervention: TBT and TEG studies were performed prior to and after the ingestion of aspirin. Measurements and Main Results: TBT studies were significantly prolonged at 4, 24, and 72 hours compared with controls. Maximum bleeding time prolongation occurred 24 hours after aspirin ingestion. Bleeding time returned to control values by the end of 168 hours (1 week). No TEG parameter was significantly changed by aspirin ingestion. Conclusion: TEG results may not idenfity patients who have an increased bleeding time as a result of aspirin ingestion.
Controlling wound healing through debridement

The formation of slough (dead tissue) on a wound is widely accepted as an inhibitor to natural wound healing. In this article, a system of differential equations that models slough/wound interaction is developed. We prove a threshold theorem that provides conditions on the amount of slough to guarantee wound healing. As a state-dependent time scale, debridement (the periodic removal of slough) is used as a control. We show that closure of the wound can be reached in infinite time by debriding.
Comparison of artificial neural networks with logistic regression in prediction of in-hospital death after percutaneous transluminal coronary angioplasty.

Abstract Objectives Our objective was to compare artificial neural networks (ANNs) with logistic regression for prediction of in-hospital death after percutaneous transluminal coronary angioplasty and to assess the impact of guiding initial ANN variable selection with univariate analysis. Background ANNs can detect complex patterns within data. Criticisms include the unpredictability of variable selection. They have not previously been applied to outcomes modeling for percutaneous coronary interventions. Methods A database of consecutive (n = 3019) percutaneous transluminal coronary angioplasty procedures from an academic tertiary referral center between July 1994 and July 1997 was used. An ANN was developed for 38 variables (unguided model) (n = 1554). A second model was developed with predictors from an univariate analysis (guided model). Both were compared with a logistic regression model developed from the same database. Model validation was performed on independent data (n = 1465). Model predictive accuracy was assessed by the area under receiver operating characteristic curves. Goodness of fit was assessed with the Hosmer-Lemeshow statistic. Results Sixty unguided and guided ANNs were developed. Predictive accuracy and model calibration for all models were similar for training data but were significantly better for logistic regression for independent validation data. Overestimation of event rate in higher risk patients accounted for the majority of discrepancy in model calibration for the ANNs. This difference was partially amended by guiding variable selection. Conclusion ANNs were able to model in-hospital death after percutaneous transluminal coronary angioplasty when guiding variable selection. However, performance was not better than traditional modeling techniques. Further investigations are needed to understand the impact of this methodology on outcomes analysis. (Am Heart J 2000;140:511-20.)
Decay of Nuclear Hyperpolarization In Silicon Microparticles

We investigate the low-field relaxation of nuclear hyperpolarization in undoped and highly doped silicon microparticles at room temperature following removal from high field. For nominally undoped particles, two relaxation time scales are identified for ambient fields above 0.2 mT. The slower, ${T}_{1,\mathrm{s}}$, is roughly independent of ambient field; the faster, ${T}_{1,\mathrm{f}}$, decreases with increasing ambient field. A model in which nuclear spin relaxation occurs at the particle surface via a two-electron mechanism is shown to be in good agreement with the experimental data, particularly the field independence of ${T}_{1,\mathrm{s}}$. For boron-doped particles, a single relaxation time scale is observed. This suggests that for doped particles, mobile carriers and bulk ionized acceptor sites, rather than paramagnetic surface states, are the dominant relaxation mechanisms. Relaxation times for the undoped particles are not affected by tumbling in a liquid solution.