cssi/SciSciGPT-SciSciNet huggingface dataset:
HPLC-based monitoring of products formed from hydroethidine-based fluorogenic probes--the ultimate approach for intra- and extracellular superoxide detection.

Abstract Background Nearly ten years ago, we demonstrated that superoxide radical anion ( O 2 ⋅ ¯ ) reacts with the hydroethidine dye (HE, also known as dihydroethidium, DHE) to form a diagnostic marker product, 2-hydroxyethidium (2-OH-E + ). This particular product is not derived from reacting HE with other biologically relevant oxidants (hydrogen peroxide, hydroxyl radical, or peroxynitrite). This discovery negated the longstanding view that O 2 ⋅ ¯ reacts with HE to form the other oxidation product, ethidium (E + ). It became clear that due to the overlapping fluorescence spectra of E + and 2-OH-E + , fluorescence-based techniques using the “red fluorescence” are not suitable for detecting and measuring O 2 ⋅ ¯ in cells using HE or other structurally analogous fluorogenic probes (MitoSOX TM Red or hydropropidine). However, using HPLC-based assays, 2-OH-E + and analogous hydroxylated products can be easily detected and quickly separated from other oxidation products. Scope of review The principles discussed in this chapter are generally applicable in free radical biology and medicine, redox biology, and clinical and translational research. The assays developed here could be used to discover new and targeted inhibitors for various superoxide-producing enzymes, including NADPH oxidase (NOX) isoforms. Major conclusions HPLC-based approaches using site-specific HE-based fluorogenic probes are eminently suitable for monitoring O 2 ⋅ ¯ in intra- and extracellular compartments and in mitochondria. The use of fluorescence-microscopic methods should be avoided because of spectral overlapping characteristics of O 2 ⋅ ¯ -derived marker product and other, non-specific oxidized fluorescent products formed from these probes. General significance Methodologies and site-specific fluorescent probes described in this review can be suitably employed to delineate oxy radical dependent mechanisms in cells under physiological and pathological conditions. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.
A grand tour of multispectral components: A tutorial

The human interpreter is perhaps the best pattern-recognition engine currently available. Often, interpreting seismic data involves inspection and analysis of multiple seismic attributes. While interpreters are skilled at visualizing complex geologic features in 3D, they are less adept at visualizing a great many attributes at once. Recent software development provides interpreters with the means of corendering three attributes (using a red-green-blue color model) or four attributes (using a hue-lightness-saturation-opacity color model). While analysis of four or more attributes is simple from a mathematical point of view, it is overly taxing on the normal human interpreter who needs to relate these images to the underlying geologic processes.
The recombination of nitrogen atoms

Abstract Preliminary results of a study of nitrogen atom recombination in a static system are summarized. The third-order homogeneous recombination rate coefficient is found to be pressure dependent at low pressures. Real and apparent wall effects are evaluated quantitatively.
A software for the calculation of ion transport in solids

Abstract Based on the bipartition model of ion transport, a software, named PANDA-U, has been established for calculations of ion transport in solids. This software is designed running on the platform of WIN32. By PANDA-U, one can calculate reflection, range, radiation damage etc. for ion bombardments on multilayer targets. In PANDA-U, the distribution function of ions is stored in a module which could be accessed by user, thus one can develop more applications to calculate other concerned transport quantities. As an example of PANDA-U, we have calculated reflection energy spectrum at emission angle of 45° for 150 eV H bombardment on C. By comparing the results with Monte Carlo data and experimental data, the validity of our calculation has been tested.
Estrogen represses SOX9 during sex determination in the red-eared slider turtle Trachemys scripta

Production of male offspring in viviparous eutherian mammals requires a sex-determining mechanism resistant to maternal hormones. This constraint is relaxed in egg-laying species, which are sensitive to hormones during sex determination and often use an increase in aromatase, the estrogen-synthesizing enzyme, as a key feminizing signal. In the turtle Trachemys scripta, sex is normally determined by temperature, but estrogen treatment overrides this cue and leads exclusively to female development. We assessed whether the expression of SOX9, a central male sex-determining gene in mammals, or three other conserved transcription factors (WT1, GATA4, and LHX9) was regulated by estrogen signaling in the turtle. As in mice, all somatic cell types in the immature turtle gonad initially expressed WT1 and GATA4, whereas SOX9 was restricted to the Sertoli precursors and LHX9 to the coelomic epithelium and interstitium. After the bipotential period, SOX9 was abruptly down-regulated at the female temperature. Strikingly, embryos treated with β-estradiol at the male temperature lost SOX9 expression more than two stages earlier than controls, though WT1, GATA4, and LHX9 were unaffected. Conversely, inhibition of estrogen synthesis and signaling prevented or delayed SOX9 down-regulation at the female temperature. These results suggest that endogenous estrogen feminizes the medulla of the bipotential turtle gonad by inhibiting SOX9 expression. This mechanism may be involved in the male-to-female sex reversal in wild populations exposed to environmental estrogens, and is consistent with results showing that the estrogen receptor represses Sox9 to block transdifferentiation of granulosa cells into Sertoli-like cells in the adult mouse ovary.
Adrenal Trauma: Elvis Presley Memorial Trauma Center Experience

OBJECTIVES Adrenal gland injury is a potentially devastating event if unrecognized in the treatment course of a trauma patient. We reviewed our single-center experience and outcomes in patients with adrenal gland trauma. METHODS We performed a retrospective review of all patients presenting with trauma to the Regional Medical Center at Memphis who had adrenal gland injuries from January 1991 through March 2006. Each chart was reviewed with attention to the demographics, associated injuries, complications, and outcomes. Patients were stratified into two subgroups according to age (35 years or younger and older than 35 years) to allow for an age-based comparison between the two groups. RESULTS Of 58,000 patients presenting with trauma, 130 (0.22%) were identified with adrenal injuries, of which 8 (6.2%) were isolated and 122 (93.8%) were not. Of these 130 patients, 125 (96.2%) had their injury diagnosed by computed tomography and 5 (3.8%) had their injury diagnosed during exploratory laparotomy. Right-sided injuries predominated (78.5%), with six (4.6%) bilateral. Four patients (3.1%) underwent adrenalectomy. Seven patients (5.4%) with adrenal injuries died. One patient (0.77%) required chronic steroid therapy. Patients older than 35 years were more likely to have complications such as deep venous thrombosis, pneumonia, and urinary tract infections. Patient age of 35 years or younger was associated with a significantly increased incidence of liver lacerations. CONCLUSIONS Adrenal gland injury is uncommon, although mostly associated with greater injury severity. Although adding to morbidity, most are self-limited and do not require intervention.
Infrared radiometry using a dielectric-silver-coated hollow glass waveguide for polymer processing

We describe a novel on-line infrared method for remote sensing of the surface and the bulk temperatures of a polymer film during injection molding. The method may also be applied to other polymer forming processes such as extrusion and blow molding. The key feature of the new method is the use of a hollow waveguide that is incorporated into the injection mold to transmit the thermal radiation from the target to the sensor. The main characteristic of the hollow waveguide is that it exhibits low transmission loss of the thermal energy in the mid and far infrared, and no end reflection. This allows measurement of quite low temperatures, as low as near room temperature. Conventional optical fiber thermometers can neither measure such low temperature ranges nor measure the polymer surface temperature. In this article, we present the first on-line results of critical tests of the new device. A Husky injection molding press was used for the experiments. Good correlation was found between the radiometric results and those obtained with a thermal sensor inserted near the polymer mold interface, and with infrared imaging after the polymer part was ejected from the injection mold.
Cytotoxic antibody in Burkitt's tumor and normal human serum reactive with cultures of lymphoid cells.

SummaryHuman serum antibodies that react with a variety of human lymphoid cultures were detected by use of a complement-dependent cytotoxicity test. Cytotoxic antibody was detected in the sera of patients with Burkitt's lymphoma and also in sera from normal individuals. Positive reactions occurred with cell lines derived from the leukocytes of normal adults and with cell lines that lack detectable herpes-like virus. It seems likely, therefore, that this serum antibody is not tumor-specific or herpes virus-specific. The cell antigen is not associated with known leukocyte isoantigens and the available evidence indicates that this antibody reflects a separate antigenic identity in human cells.
Antibiotic sensitivity of the yeast and mycelial phases of Histoplasma capsulatum.

Cycloheximide and chloramphenicol in combination have a greater effect on yeast cells of Histoplasma capsulatum than on the mycelial phase of this fungus. In contrast, clotrimazole was found to be more effective against mycelia. Miconazole produced a pronounced effect against both phases whereas tolnaftate was only slightly active. Sulfadiazine and griseofulvin were completely inactive against both phases. The differential sensitivities of the 2 phases of H. capsulatum to various antibiotics can be useful in studying the transition of this dimorphic fungus from 1 phase to the other.
Cyclic phosphodiesterase activity and the action of papaverine.

Abstract Papaverine, a smooth muscle relaxant, inhibits phosphodiesterase activity in homogenates of rabbit aorta, rat uterus and rat diaphragm.This inhibitory effect of papaverine is about 15–30 times greater than that of theophylline. In rat diaphragm, papaverine increased glycogenolysis to the same extent as epinephrine and had a synergistic effect with epinephrine on glycogen breakdown. These results suggest that the relaxing effect of papaverine might be due to its action on phosphodiesterase and are in agreement with the postulation that cyclic 3′, 5′-AMP participates in the control of smooth muscle tone and contractility.
Spectral engineering of optical fiber preforms through active nanoparticle doping

Europium doped alkaline earth fluoride [Eu:AEF2 (AE = Ca, Sr, Ba)] nanoparticles were synthesized and systematically incorporated into the core of modified chemical vapor deposition (MCVD)-derived silica-based preforms by solution doping. The resulting preforms were examined to determine the impact of the nanoparticles chemistry on the spectroscopic behavior of the glass. The dominant existence of Eu3+ was demonstrated in all preforms, which is in contrast to conventional solution doped preforms employing dissolved europium salts where Eu2+ is primarily observed. Raman spectroscopy and fluorescence lifetime measurements indicated that the nanoparticles composition is effective in controlling, at a local chemical and structural level, the spectroscopic properties of active dopants in optical fiber glasses. Further, there is a systematic and marked increase in radiative lifetime, τ, of the Eu3+ emission that follows the cationic mass; τCa < τSr < τBa with the BaF2-derived sample yielding a 37% lengthening of the lifetime over the CaF2-derived one. Such nanoscale control of what otherwise is silica glass could be useful for realizing property-enhanced and tailored spectroscopic performance from otherwise “standard” materials, e.g., vapor-derived silica, in next generation optical fibers.
Chloride Labilization Resulting from Nucleophilic Addition to cis-Ru(tpy)(CO)2Cl+PF6-: Synthesis and Characterization of New CO2-Bridged and Formate Complexes of Ruthenium

Reaction of cis-Ru(tpy)(CO)2Cl+PF6- (1; tpy = 2,2‘:6‘,2‘‘-terpyridyl) with aqueous Na2CO3 in acetonitrile yields the CO2-bridged complex cis,cis-(CH3CN)(CO)(tpy)Ru(CO2)Ru(tpy)(CO)22+2PF6- (3). Reaction of 1 with aqueous NaOCHO yields the corresponding η1-formato complex 4; reaction of 4 with aqueous Na2CO3 also provides 3. Reaction of 3 with CO results in displacement of acetonitrile and formation of 5, cis,cis-(CO)2(tpy)Ru(CO2)Ru(tpy)(CO)22+2PF6-. Reaction paths leading to 3 and 4 from 1 are thought to occur by base-assisted trans labilization of chloride resulting from conversion of a π-acceptor ligand (CO) to a σ-donor (COOH). Support for proposed steps in the reaction paths leading to 3 and 4 was provided by a trapping experiment in which 1 reacts with cis-Ru(bpy)2(CO)COOH+PF6- in the presence of aqueous Na2CO3 to give cis,cis-(CO)(bpy)2Ru(CO2)Ru(tpy)(CO)22+2PF6- (7; bpy = 2,2‘-bipyridyl), which has been structurally characterized. Parallels between these reactions and the halide labilizations which o...
Cytokine mediated expansion of human umbilical cord blood CD34+ cells : comparison of the use of partially purified and pure CD34+ target cells

To determine the optimal cell population for cytokine mediated expansion, we compared the use of Magnetic Cell Sorting (MACS) system enriched CD34+ human umbilical cord blood (HUCB) cells with that of MACS enriched, flow purified CD34+ HUCB cells. Both MACS enriched CD34+ cells and MACS enriched, flow purified CD34+ cells (mean starting purity of CD34+ SC 51.27 ± 7.6% and 96.36 ± 1.34% respectively n = 6) were incubated for seven days with Interleukin-1 (IL-1)+IL-3+Stem Cell Factor (SCF) and showed a fold increase in the number of nucleated cells (10.02 ± 2.6 and 18.23 ± 4.73 respectively) and a reduction in the percentage of CD34+ cells (5.55 ± 1.23% and 12.21 ± 3.29% respectively). An increase in the absolute numbers of CD34+ cells (4.8 × 104 ± 2.3 × 104) was observed with MACS enriched CD34+ cells as compared to no change (1.3 × 105 ± 8.8 × 104) with MACS enriched, flow purified CD34+ cells. An increase in IL-3+GM-CSF+SCF responsive colony forming unit (CFU) (1.7 × 104 ± 9.4 × 103 and 1.6 × 105 ± 7.7 × 104 respectively) was also observed as compared with input values (1.5 × 104 ± 1 × 104 and 2.3 × 104 ± 8.9 × 103 respectively). We conclude that MACS enriched, flow sorted CD34+ HUCB cells have greater cytokine mediated expansion potential as measured by progenitor expansion, than MACS enriched CD34+ HUCB cells.
Nociception is enhanced by the intrathecal injection of 5-methoxy-N,N-dimethyltryptamine in the rat

Abstract The effect of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) at the spinal cord level on nociceptive reflexes was tested using the tail-flick assay in rats. 5-MeODMT was injected directly into the spinal subarachnoid space of conscious rats via a permanently indwelling intrathecal cannula. Administration of 100 μg/rat of 5-MeODMT into the thoracic region, using a 4 cm long cannula, reduced the average percent of control reaction time by 14%. The injection of the same dose of 5-MeODMT into the lumbosacral region, via an 8.6 cm long cannula, decreased the average percent of control reaction time by 25%. The ability of 5-MeODMT to mimic the facilitatory (hyperalgesic effect on nociception of similar doses of tryptamine, in contrast to the antinociceptive (analgesic) effect of serotonin, suggests an interaction of 5-MeODMT with tryptaminergic rather than serotonergic receptors in the spinal cord.
Conservation of sequence and function in fertilization of the cortical granule serine protease in echinoderms

Conservation of the cortical granule serine protease during fertilization in echinoderms was tested both functionally in sea stars, and computationally throughout the echinoderm phylum. We find that the inhibitor of serine protease (soybean trypsin inhibitor) effectively blocks proper transition of the sea star fertilization envelope into a protective sperm repellent, whereas inhibitors of the other main types of proteases had no effect. Scanning the transcriptomes of 15 different echinoderm ovaries revealed sequences of high conservation to the originally identified sea urchin cortical serine protease, CGSP1. These conserved sequences contained the catalytic triad necessary for enzymatic activity, and the tandemly repeated LDLr-like repeats. We conclude that the protease involved in the slow block to polyspermy is an essential and conserved element of fertilization in echinoderms, and may provide an important reagent for identification and testing of the cell surface proteins in eggs necessary for sperm binding.
A Surface Equation of State for a Partially Soluble Ionized Surfactant

The surface pressure and adsorption isotherm as functions of surfactant and salt concentration are determined for an ionized surfactant. This analysis differs from previous work in that the surfactant, while ionized in the bulk solution, is assumed to be nonionized at the surface. The analysis is applied to several soluble surfactants and provides a reasonable fit to experimental surface pressure data. With this analysis, the surface solution is found to be ideal for a number of surfactants, so one less parameter is required than is used by the regular solution theory model of Lucassen-Reynders (1).
Structural characterization of the ectodomain of a disintegrin and metalloproteinase-22 (ADAM22), a neural adhesion receptor instead of metalloproteinase: Insights on ADAM function

ADAMs (a disintegrin and metalloproteinases) are a family of multidomain transmembrane glycoproteins with diverse roles in physiology and diseases, with several members being drug targets for cancer and inflammation therapies. The spatial organization of the ADAM extracellular segment and its influence on the function of ADAMs have been unclear. Although most members of the ADAM family are active zinc metalloproteinases, 8 of 21 ADAMs lack functional metalloproteinase domains and are implicated in protein-protein interactions instead of membrane protein ectodomain shedding. One of such non-proteinase ADAMs, ADAM22, acts as a receptor on the surface of the postsynaptic neuron to regulate synaptic signal transmission. The crystal structure of the full ectodomain of mature human ADAM22 shows that it is a compact four-leaf clover with the metalloproteinase-like domain held in the concave face of a rigid module formed by the disintegrin, cysteine-rich, and epidermal growth factor-like domains. The loss of metalloproteinase activity is ensured by the absence of critical catalytic residues, the filling of the substrate groove, and the steric hindrance by the cysteine-rich domain. The structure, combined with calorimetric experiments, suggests distinct roles of three putative calcium ions bound to ADAM22, with one in the metalloproteinase-like domain being regulatory and two in the disintegrin domain being structural. The metalloproteinase-like domain contacts the rest of ADAM22 with discontinuous, hydrophilic, and poorly complemented interactions, suggesting the possibility of modular movement of ADAM22 and other ADAMs. The ADAM22 structure provides a framework for understanding how different ADAMs exert their adhesive function and shedding activities.
Marginal fractures of the medial tibial plateau: possible association with medial meniscal root tear.

We report two cases of marginal fractures of the medial tibial plateau associated with medial meniscal root tears. Both patients sustained knee dislocations, with complete tears of the posterior horn medial meniscal root. One sustained a “reverse Segond fracture”; the other sustained an “anteromedial impingement fracture” of the tibial plateau. The meniscal root tears were arthroscopically confirmed and repaired. In the first patient, the integrity of the meniscal root repair was confirmed at a 6-month follow-up arthroscopy for lysis of adhesions. In the second patient, follow-up MRI at 10 months demonstrated a healed meniscal root. The association of medial meniscal root tear with marginal fractures of the medial tibial plateau has not been previously reported.
Protection from Oxygen-Induced Seizures by Clonazepam and Propylene Glycol:

AbstractGeneral anesthetics, ganglionic blocking agents, anticonvulsants, and antioxidants have been shown to afford protection from seizures caused by exposure to hyperbaric oxygen. In the present study cats were exposed to 5 ATA oxygen in pairs in a hyperbaric chamber until both the control and pretreated cat convulsed or for a maximum 120 min exposure. Small amounts of four common antiepileptic agents and propylene glycol in amounts far less than previously reported (0.1 to 0.2 ml/kg) were initially tested for potential anticonvulsant activity. Two agents, clonazepam and propylene glycol, offered significant protection in delaying the onset of seizures whereas carbamazepine, valproic acid, and trimethadione appeared to hasten the onset of seizure activity. The time to seizures was increased nearly five times by clonazepam and over three times by very small amounts of propylene glycol.
Molecular diodes fabricated by a junction between mixed- and nonmixed-valent polymer films

A molecular junction between thin polymer films of occupied-state [${\mathrm{Fe}}^{\mathrm{II}}$(phen${)}_{3}$][Naf-${\mathrm{SO}}_{3}$${]}_{2}$ and half-occupied-state (mixed-valent) [${\mathrm{Fe}}^{\mathrm{I}\mathrm{I},\mathrm{I}\mathrm{I}\mathrm{I}}$(phen${)}_{3}$][Naf-${\mathrm{SO}}_{3}$${]}_{2.5}$ (where ``phen'' stands for 1,10-phenanthroline and ``Nafion'' is a perfluorosulfonate polymer) has been prepared. The junction exhibits current rectification and space-charge-limited current transients consistent with good hole injection into the occupied-state film from the mixed-valent film contact.
Electromigration studies using in situ TEM electrical resistance measurements

Abstract An in situ transmission electron microscopy (TEM) method has been devised for the measurement of electrical resistance as a function of temperature and/or time for thin film stripes. A custom TEM sample holder was fabricated through which up to eight leads may be passed. These leads provide currents to the heater and allow for the measurement of hot stage temperature and the electrical resistance of the sample. This configuration enables one to correlate changes in resistance of the stripe during electromigration experiments to the microstructural changes occurring at the same time. The time-dependent microstructural phenomena are recorded with a camcorder on video tape, a capability which greatly enhances the subsequent data analysis. Preliminary experiments have been performed using the Temperature-ramp Resistance Analysis to Characterize Electromigration (TRACE) method in order to determine the kinetic parameters for electromigration for pure aluminum films.
Influence of product species selection on thermochemical equilibrium calculations. Part I: Energetic materials

On a effectue des calculs d'equilibre chimique pour un certain nombre de composes explosifs contenant du carbone, de l'hydrogene, de l'azote et de l'oxygene. On a developpe une methodologie pour delimiter de maniere systematique le nombre de types de produits necessaires pour effectuer les calculs d'equilibre thermochimique. Les calculs ont ete compares a des valeurs de base obtenues en utilisant une vaste base de donnees composees de 900 types de produits gazeux et de 600 types de produits condenses. On a quantifie les erreurs dans les proprietes thermodynamiques principales (vitesse de detonation et pression) et dans la composition chimique des produits en terme de nombre d'especes considerees comme produits de reaction. Les proprietes de domaines le long de l'isotrope d'expansion sont egalement presentees.
A Point Mutation Associated with Leukocyte Adhesion Deficiency Type 1 of Moderate Severity

Abstract Leukocyte adhesion deficiency (LAD) is a genetic disease characterized clinically by severe bacterial infections, and biochemically by a deficiency in the surface expression of the CD 11/CD 18 leukocyte integrins. We studied a teenage girl with the moderate deficiency phenotype of LAD. B-lymphoblastoid cells from this patient displayed approximately 5% of normal levels of CD11/CD18 on the cell surface. Although a normal sized CD18 mRNA was detectable on Northern blotting, a small CD18 protein was present on Western blotting. Sequencing of the RNA revealed a single base pair substitution resulting in a glycine to serine amino acid substitution at amino acid 284. This amino acid substitution occurs within a highly conserved region of the extracellular domain of CD18 in which several other mutations have been identified in LAD.
Natural killer cells in rhesus monkeys: Properties of effector cells which lyse Raji targets

Abstract Spontaneously occurring natural killer cell activity of rhesus monkey peripheral blood mononuclear cells was assayed against five human cell lines, three of which were Epstein-Barr virus (EBV) positive, including the human B cell line Raji. The lytic activity to Raji cells was high, significantly higher than to any other cell line tested. Raji cells are normally insensitive to spontaneous lysis by human NK cells, and the contrasting vigor of the rhesus monkey cytolytic activity to Raji prompted us to investigate the properties of this effector cell. We found the effector cell-mediating lysis of Raji to be nonadherent and phagocytic with lytic activity slightly enhanced in the E-rosette-forming cell (ERFC + ) fraction and decreased in the ERFC − fraction. Further isolation of FcIgG receptor-positive and FcIgG receptor-negative subsets by rosetting resulted in significant enrichment of NK activity to Raji in the positive fraction and a loss of activity in the negative fraction. Depletion studies with various monoclonal antibodies (mAb's) confirmed that nearly all lytic activity was contained in the CD16 + (Leu 11b + ) population, while subsets of effector cells expressed CD2 (9.6) and CD8 (OKT8). Depletion of CD4 (OKT4)-, HLADR (OKIa)-, or LFA1 (MAC-1)-positive populations failed to reduce NK activity. We compared the phenotypic properties of alloimmune effector cells exhibiting specificity for allogeneic donor targets with those exhibiting lysis of Raji targets. Results indicated that allospecific cytotoxic T lymphocytes expressed a CD16 − , CD2 + phenotype, a pattern distinct from that of the effector cell population recognizing Raji targets. The presence of CD2 mAb's in the culture had no effect on NK lytic activity. In contrast, mAbs CD8 and Leu 11b were inhibitory. This would suggest a functional role for CD8 and FcIgG molecules in the lysis of Raji cells by rhesus effectors. In summary, these studies describe a distinct population of effector cells in the blood of rhesus monkeys which exhibit spontaneous lytic activity to Raji cells and exhibit the properties of NK cells.
Clinical and comparative utility of afatinib in non-small cell lung cancer

The first targeted agents approved for non-small cell lung cancer (NSCLC) treatment, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib, have an impressive activity in the presence of activating mutations of the EGFR gene. However, all patients develop acquired resistance principally through secondary mutations (T790M), HER2 amplification, MET amplification, and other molecular aberrations. An attempt to overcome EGFR TKI resistance has been through the development of irreversible blockers. Afatinib is an irreversible inhibitor of the tyrosine kinase activity of all members of the HER family. The pharmacologic properties of afatinib (formation of covalent bonds, inhibition of other family members, and in vitro and in vivo activity on T790M mutation positive tumors) made this drug particularly appealing to study in clinic. Therefore, an intense program of clinical research (LUX-Lung program) was started and clinical results have shown very encouraging activity profiles in patients harboring EGFR activating mutations and in those with acquired resistance to reversible TKIs.
Body Size and Fat Distribution as Predictors of Stroke among US Men

Evidence for an association between general obesity and risk of stroke is weak. However, abdominal obesity may be more closely related to stroke risk. The association of body mass index and abdominal obesity (waist/hip ratio) with stroke incidence was examined in 28,643 US male health professionals, aged 40-75 years in 1986, who had no history of cardiovascular disease or stroke. In 5 years of follow-up, there were 118 cases of stroke, of which 80 were ischemic. Compared with men in the lowest quintile of body mass index, men in the highest quintile had an age-adjusted relative risk of stroke of 1.29 (95% confidence interval 0.73-2.27). In contrast, the age-adjusted relative risk for extreme quintiles of waist/hip ratio was 2.33 (95% confidence interval 1.25-4.37). This relative risk was not substantially altered in a multivariate model including body mass index, height, and other potential risk factors. There was a weaker relation with waist circumference alone, with men in the highest quintile (> 40.2 inches) having a relative risk of 1.52 (95% confidence interval 0.82-2.82) compared with men in the lowest quintile (< or = 34.5 inches) (1 inch = 2.54 cm). The results suggest that abdominal obesity, but not elevated body mass index, predicts risk of stroke in men.
Digital replication of chest radiographs without altering diagnostic observer performance

A study to test the ability of a high-fidelity system to digitize chest radiographs, store the data in a computer, and reprint the film without altering diagnostic observer performance is reported. Two hundred and fifty-two (252) chest films with subtle image features indicative of interstitial disease, pulmonary nodule, or pneumothorax, along with 36 normal chest films were used in the study. Films were selected from a key word search on a computerized report archive and were graded by two experienced radiologists. Each film was digitized with 86 micron pixels and stored in 4000 X 5000 arrays using a research instrument. Replicates were printed using a commercial laser film printer (Eastman Kodak Company) having 80 micron pixels. Originals and replicates were observed separately by two different experienced radiologists. Each indicated a graded response for the three possible pathologies. The agreement of observers between responses for replicates and originals was described by the kappa statistic and compared to the agreement when rereading the original film. The final result of this study supports a hypothesis that the replicate is indistinguishable from the original.© (1991) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Specificity of Monoclonal Antibodies against Group B Streptococcus Type II and Inhibition of their Binding by Human Secretions

Mouse monoclonal antibodies against the type-specific polysaccharide antigen of type I1 group B Streptococcus may be divided into two general groups based on their antigen-binding properties. One group of antibodies binds to both intact and desialylated type I1 antigen and the binding can be inhibited by P-galactopy- ranosides. The second group of antibodies react only with intact type I1 polysaccharide and are not inhibited by 6- galactopyranosides. The binding of antibodies of the first group can also be inhibited by carbohydrate components of normal human secretions that share structural similari- ties with the type I1 polysaccharide. The binding of anti- bodies of one specificity precluded the binding of antibodies of the other specificity, apparently by competing for bind- ing sites within a combining area that includes both deter- minants (Pediatr Res 24: 68-72, 1988)
Scalable approximation of kernel fuzzy c-means

Virtually every sector of business and industry that use computing, including financial analysis, search engines, and electronic commerce, incorporate Big Data analysis into their business model. Sophisticated clustering algorithms are highly desired to deduce the nature of data by assigning labels to unlabeled data. We address two main challenges in Big Data. First, by definition, the volume of Big Data is too large to be loaded into a computer's memory (this volume changes based on the computer used or available). Second, in real-time applications, the velocity of new incoming data prevents historical data from being stored and future data from being accessed. Therefore, we propose our Streaming Kernel Fuzzy c-Means (stKFCM) algorithm, which reduces both computational complexity and space complexity significantly. The proposed stKFCM only requires O(n2) memory where n is the (predetermined) size of a data subset (or data chunk) at each time step, which makes this algorithm truly scalable (as n can be chosen based on the available memory). Furthermore, only 2n2 elements of the full N × N (where N >> n) kernel matrix need to be calculated at each time-step, thus reducing both the computation time in producing the kernel elements and the complexity of the FCM algorithm. Empirical results show that stKFCM, even with very small n, can provide clustering performance as accurately as kernel fuzzy c-means run on the entire data set while achieving a significant speedup.
Economics of Trolley Coach Power Supply

The total cost of power delivered to trolley coaches is influenced by system engineering as well as by prevailing power rates. In the case of a single-unit rectifier substation, the equipment cost per kilowatt decreases as substation rating increases. With increases in substation rating, however, proportionately more feeder copper is required to distribute the power from each station. Evaluation of these factors for various headways reveals substation ratings and spacings which result in minimum system investment. Cost of power delivered at the trolley coach is the sum of fixed charges and operating costs of the substations and overhead. Such factors as the number of points of power delivery, maintenance expense, and depreciation rates affect the over-all power cost. Their influence upon selection of substation rating is discussed. By careful investigation of all variables, the transit operator is able to minimize the cost of power delivered to his vehicles.
A hypothesized model of Korean women's responses to abuse.

Many abused married Korean women have a strong desire to leave their abusive husbands but remain in the abusive situations because of the strong influence of their sociocultural context. The article discusses Korean women’s responses to spousal abuse in the context of patriarchal, cultural, and social exchange theory. Age, education, and income as component elements share common effects on the emergent variable, sociostructural power. Gender role attitudes, traditional family ideology, individualism/collectivism, marital satisfaction, and marital conflict predict psychological-relational power as a latent variable. Sociostructural, patriarchal, cultural, and social exchange theories are reconceptualized to generate the model of Korean women’s responses to abuse.
Dietary Factors and Risk of Colon Cancer

The incidence rates of colon cancer are high in North America and northern Europe, lower in southern Europe, and much lower in Asia and Africa. It is widely believed that environmental factors, particularly dietary patterns, account for most of this marked variation in rates. Over the past decade, a large number of case-control and cohort studies have added a substantial body of evidence regarding our understanding of the causes of colon cancer. Although the data are not entirely consistent, several important risk factors have emerged. The epidemiological evidence that physical inactivity or excess energy intake relative to requirements increases risk of this malignancy is quite strong. Intake of red meat appears to increase risk, but protein-rich sources other than red meat probably do not elevate risk and may even reduce the occurrence of colon cancer. Dietary fat, at least that from sources other than red meat, does not appear to increase risk appreciably. High consumption of vegetables and fruits and the avoidance of highly refined sugar containing foods are likely to reduce risk of colon cancer, although the responsible constituents remain unclear. Alcohol intake may enhance risk of cancers of the distal colorectum, although the evidence is not entirely consistent. The influence of alcohol may be particularly strong when combined with a diet low in methionine and folate, suggesting that the effect of alcohol may be through antagonism of methyl-group metabolism. The combined effect of these dietary factors, as well as modifiable non-dietary factors such as cigarette smoking, suggest that the majority of cases of colon cancer are preventable.
The Use of MDL to Select among Computational Models of Cognition

How should we decide among competing explanations of a cognitive process given limited observations? The problem of model selection is at the heart of progress in cognitive science. In this paper, Minimum Description Length (MDL) is introduced as a method for selecting among computational models of cognition. We also show that differential geometry provides an intuitive understanding of what drives model selection in MDL. Finally, adequacy of MDL is demonstrated in two areas of cognitive modeling.
Injury to the suprascapular nerve during superior labrum anterior and posterior repair: is a rotator interval portal safer than an anterosuperior portal?

Purpose The purpose of this study was to compare the risk of injury to the suprascapular nerve during suture anchor placement in the glenoid when using an anterosuperior portal versus a rotator interval portal. Methods Ten bilateral fresh human cadaveric shoulders were randomized to anchor placement through the anterosuperior portal on one shoulder and the rotator interval portal on the contralateral shoulder. Standard 3 × 14 mm suture anchors were placed in the glenoid rim (1 o'clock, 11 o'clock, and 10 o'clock positions for the right shoulder). The suprascapular nerve was dissected. When glenoid perforation occurred, the distance from the anchor tip to the suprascapular nerve, the distance from the glenoid rim to the suprascapular nerve, and the drill-hole depth at each entry site were recorded. Results All far-posterior anchors perforated the glenoid rim when using the anterosuperior or rotator interval portal. The distance from the far-posterior anchor tip to the suprascapular nerve averaged 8 mm (range, 3.4 to 14 mm) for the anterosuperior portal and 2.1 mm (range, 0 to 5.5 mm) for the rotator interval portal ( P ≤ .001). Conclusions Using an anterosuperior or rotator interval portal results in consistent penetration of 1 o'clock and 2 o'clock posterior anchors and might place the suprascapular nerve at risk of iatrogenic injury. Based on closer proximity of the anchor tip to the suprascapular nerve, the risk of injury is significantly greater with a rotator interval portal. Clinical Relevance Using a rotator interval portal for suture anchor placement in the posterior aspect of the glenoid rim can lead to a higher likelihood of suprascapular nerve injury.
Role of aquaporin water channels in pleural fluid dynamics.

Continuous movement of fluid into and out of the pleural compartment occurs in normal chest physiology and in pathophysiological conditions associated with pleural effusions. RT-PCR screening and i...
Adjustment of the Marine Atmospheric Boundary Layer to a Coastal Cape

Abstract During summer, significant changes in marine atmospheric boundary layer (MABL) speed and depth occur over small spatial scales (<100 km) downstream from topographic features along the California coast. In June and July 1996, the Coastal Waves 96 project collected observations of such changes at capes with an instrumented aircraft. This paper presents observations from the 7 June flight, when the layer-averaged speed increased 9 m s−1 and depth decreased by 500 m over a 75-km downwind from Cape Mendocino, accompanied by enhanced surface fluxes and local cloud clearing. The acceleration and thinning are reproduced when the flow is modeled as a shallow transcritical layer of fluid impinging the bends of a coastal wall, leading to the interpretation that they are produced by an expansion fan. Model runs were produced with different coastlines and imposed pressure gradients, with the best match provided by a coastline in which the cape protruded into the flow and forced a response in the subcritical r...
Making sense of consensus: responses to Engelhardt, Hester, Kuczewski, Trotter, and Zoloth.

It has been a pleasure to read these papers and to contemplate their importance for what I believe to be a useful and provocative prism though which to view the field of bioethics: the nature of moral consensus. In my own most extended contribution to this literature, Deciding Together, I did not attempt to prescribe so much as to understand the role of moral consensus in the practice of bioethics. At the end of the book, I expressed the hope that it might help trigger an examination of bioethics and moral consensus. Though a few others shared my interest at that time (in particular Tris Engelhardt, for whose early encouragement I remain deeply grateful), with this set of stimulating papers the conversation has finally begun in earnest.
Estimating Gene Signals From Noisy Microarray Images

In oligonucleotide microarray experiments, noise is a challenging problem, as biologists now are studying their organisms not in isolation but in the context of a natural environment. In low photomultiplier tube (PMT) voltage images, weak gene signals and their interactions with the background fluorescence noise are most problematic. In addition, nonspecific sequences bind to array spots intermittently causing inaccurate measurements. Conventional techniques cannot precisely separate the foreground and the background signals. In this paper, we propose analytically based estimation technique. We assume a priori spot-shape information using a circular outer periphery with an elliptical center hole. We assume Gaussian statistics for modeling both the foreground and background signals. The mean of the foreground signal quantifies the weak gene signal corresponding to the spot, and the variance gives the measure of the undesired binding that causes fluctuation in the measurement. We propose a foreground-signal and shape-estimation algorithm using the Gibbs sampling method. We compare our developed algorithm with the existing Mann-Whitney (MW)- and expectation maximization (EM)/iterated conditional modes (ICM)-based methods. Our method outperforms the existing methods with considerably smaller mean-square error (MSE) for all signal-to-noise ratios (SNRs) in computer-generated images and gives better qualitative results in low-SNR real-data images. Our method is computationally relatively slow because of its inherent sampling operation and hence only applicable to very noisy-spot images. In a realistic example using our method, we show that the gene-signal fluctuations on the estimated foreground are better observed for the input noisy images with relatively higher undesired bindings.
Bringing the President Back In: The Collapse of Lehman Brothers and the Evolution of Retrospective Voting in the 2008 Presidential Election

Despite prevailing negative conditions, initial analyses of the 2008 presidential election, including this one, find significant but not particularly strong economic voting effects during the fall campaign. In this article, the authors pay special attention to how the economic information context changed during the campaign and how those changes affected the evolution of retrospective voting. The findings show that there were two distinct phases of the fall campaign, that retrospective voting was nonexistent prior to the collapse of Lehman Brothers but was strong following the collapse. In effect, the collapse of Lehman Brothers turned the election into a referendum election.
Chromobacteriosis in a Chinese Red Panda (Ailurus Fulgens Styani)

An adult Chinese red panda (Ailurus fulgens styani) transported by airplane from Florida to a North Dakota zoo died 1 week after arrival. Grossly, an interscapular abscess, subcutaneous inflammation, lymphadenitis, and pulmonary abscesses were observed. Microscopic findings included necrotizing inflammation in liver, lung, lymph node, and spleen. Chromobacterium violaceum was cultured from the interscapular abscess, liver, lung, and spleen and was injected into Swiss Webster mice. These mice died 18 hours postinoculation, and C. violaceum was cultured from liver, lung, and spleen. Chromobacterium violaceum is a sporadically reported but highly virulent pathogenic bacterium of both animals and humans typically found as a soil and water inhabitant of tropical and subtropical regions.
In-hospital mortality after resection of biliary tract cancer in the United States

Abstract Objective To assess perioperative mortality following resection of biliary tract cancer within the U.S. Background Resection remains the only curative treatment for biliary tract cancer. However, current data on operative mortality after surgical resections for biliary tract cancer are limited to small and single-center studies. Methods Using the Nationwide Inpatient Sample 1998–2006, a cohort of patient-discharges was assembled with a diagnosis of biliary tract cancer, including intrahepatic bile duct, extrahepatic bile duct, and gall bladder cancers. Patients undergoing resection, including hepatic resection, bile duct resection, pancreaticoduodenectomy, and cholecystectomy, were retained. The primary outcome measure was in-hospital mortality. Categorical variables were analyzed by chi-square. Multivariable logistic regression was performed to identify independent predictors of in-hospital mortality following resection. Results 31 870 patient-discharges occurred for the diagnosis of biliary tract cancer, including 36.2% intrahepatic ductal, 26.7% extrahepatic ductal, and 31.1% gall bladder. Of the total, 18.6% underwent resection: mean age was 69.3 years (median 70.0); 60.8% were female; 73.7% were white. Overall inpatient surgical mortality was 5.6%. Independently predictive factors of mortality included patient age ≥50 (vs. Conclusion Increased in-hospital mortality for patients undergoing biliary tract cancer resection corresponded to age, comorbidity, hospital volume, and emergent admission. Further study is warranted to utilize these observations in promoting early detection, diagnosis, and elective resection.
Ovid, Met. 6.640: a dialogue between mother and son

In telling the story of Tereus, Procne, and Philomela (Met. 6.401–674), Ovid transformed tragedy—the Tereus of Sophocles1—into epic. The result was a narrative that followed the tragic plot but with a very different presentation. For example, Ovid incorporated into his episode events from the play's prologue, such as the marriage of Procne and Tereus (426ff.), the birth of Itys (433ff), and the voyage of Tereus to Athens (444ff.). In addition, he brought offstage action into the limelight, including the violation of Philomela (549ff.), the slaughter of Itys (636ff.), and the metamorphoses of Tereus and the sisters (667ff). Finally, he explicated innermost thoughts, like the lust of Tereus (455ff.) and the rage of Procne (581ff.)— emotions whose external manifestations would have been clear in performance, but whose effects the reader perceives from the inside out. So sequential and immediate a treatment owes much to the shift from one genre to the other.