cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 3837: PI-3 kinase acts upstream of oncogenic Ras in hematopoietic cells through a cytokine-PLCγ-RasGRP pathway

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Introduction: KRAS is the most common gain-of-function mutation in human cancer and occur in some myeloid malignancies. Despite extensive data implicating aberrant responsiveness to cytokines in the pathogenesis of myeloid leukemias with hyperactive Ras, the underlying mechanisms are largely unknown. We investigated the biochemical basis of hypersensitivity to granulocyte macrophage colony stimulating factor (GM-CSF), IL-3, and stem cell factor (SCF) in primary cells from Mx1-Cre, KrasG12D mice. Methods: We utilized conventional biochemical techniques, phospho-specific flow cytometry, and small molecule inhibitors to interrogate signaling downstream of the activated GM-CSF and c-Kit receptors. Results: We found that endogenous KrasG12D expression deregulates multiple effectors in primary myeloid lineage cells. Although Ras-GTP levels are markedly elevated in bone marrow cells from KrasG12D mice, these cells only fully activate the Raf/MEK/ERK cascade upon cytokine stimulation. We used a “chemical genetic” strategy to explore the biochemical mechanism linking the activated GM-CSF receptor to oncogenic K-RasG12D and ERK. Surprisingly, inhibitors of type I PI3 kinases (PI-90, PI-103) as well as a p110 γ/α isoform inhibitor (AS605240) interfered with GM-CSF and SCF induced Ras/MAPK activation in wild-type and KrasG12D myeloid cells. These effects of PI3 kinase are mediated through activation of PLC-γ and the RasGRP guanine nucleotide exchange factors. Functional studies confirmed that inhibiting PI3 kinase or PLC-γ blocked KrasG12D-mediated myeloid progenitor colony growth. This PI3 kinase/PLC-γ module also functions downstream of the activated c-kit receptor in lineage- cKit+ Sca1+ (LSK) cells in SCF-induced ERK activation. Conclusions: PI3 kinase, PLC-γ, and RasGRPs function upstream of normal and oncogenic K-Ras to efficiently activate the Raf/MEK/ERK cascade in primary hematopoietic cells. These data infer that PI3 kinase is both an important upstream regulator as well as a major downstream effector of Ras-GTP. Significance: Targeting PI3 kinase in hematologic cancers characterized by hyperactive Ras may have unanticipated biochemical and functional consequences in malignant and normal hematopoietic cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3837.
Sequence of rubredoxin by x-ray diffraction.

Abstract A tentative amino acid sequence has been determined for rubredoxin from Clostridium pasteurianum by examining the shapes of the side chains in an electron density map at 2 A resolution. Superpositions of the appropiate portions of this map and “ball and stick” representations of the amino acids assigned are presented as evidence in support of our identifications. Discrepancies exist between the sequence shown here and that determined by chemical methods. The sequence deduced from the 2A resolution map, however, represents our best estimate in the absence of chemical data and before refinement of the structure. We emphasize the results at 2 A resolution because, until recently, the 2 A resolution map was usually the final result of an X-ray structure determination. It is instructive to show the level of reliability that can be expected at that stage and to illustrate the kinds of mistakes that are likely to occur when making identifications from electrondensity maps.
Synthesis and solution conformation studies of the modified nucleoside N4,2′-O-dimethylcytidine (m4Cm) and its analogues

The dimethylated ribosomal nucleoside m(4)Cm and its monomethylated analogues Cm and m(4)C were synthesized. The conformations (syn vs anti) of the three modified nucleosides and cytidine were determined by CD and 1D NOE difference spectroscopy. The ribose sugar puckers were determined by the use of proton coupling constants. The position of modification (e.g., O vs N methylation) was found to have an effect on the sugar pucker of cytidine.
Analysis of drug interactions with modified proteins by high-performance affinity chromatography: Binding of glibenclamide to normal and glycated human serum albumin

High-performance affinity chromatography (HPAC) was used to examine the changes in binding that occur for the sulfonylurea drug glibenclamide with human serum albumin (HSA) at various stages of glycation for HSA. Frontal analysis on columns containing normal HSA or glycated HSA indicated glibenclamide was interacting through both high affinity sites (association equilibrium constant, K(a), 1.4-1.9 × 10(6)M(-1) at pH 7.4 and 37 °C) and lower affinity sites (K(a), 4.4-7.2 × 10(4)M(-1)). Competition studies were used to examine the effect of glycation at specific binding sites of HSA. An increase in affinity of 1.7- to 1.9-fold was seen at Sudlow site I with moderate to high levels of glycation. An even larger increase of 4.3- to 6.0-fold in affinity was noted at Sudlow site II for all of the tested samples of glycated HSA. A slight decrease in affinity may have occurred at the digitoxin site, but this change was not significant for any individual glycated HSA sample. These results illustrate how HPAC can be used as tool for examining the interactions of relatively non-polar drugs like glibenclamide with modified proteins and should lead to a more complete understanding of how glycation can alter the binding of drugs in blood.
Focusing optics for a synchrotron x-radiation microprobe

Abstract We propose two constant deviation and energy-tunable fluorescent microprobe optical designs, which efficiently use X-rays available from bending magnets and insertion devices of synchrotron radiation sources. The simpler system consists of a cylindrically bent multilayer to focus the vertical opening angle by in-plane scattering, a fixed radius cylindrically curved multilayer which sagittally focuses the horizontal divergence and a pinhole to further reduce the beam to microprobe dimensions. A more versatile system has a pair of flat nondispersively arranged diffracting optics followed by crossed elliptical mirrors. These nondispersive combinations can produce a fixed-exit beam. We compare their relative intensity with other optical systems.
A custom-made two-photon microscope and deconvolution system.

We describe in detail a custom-built two-photon microscope based on a modified confocal scanhead (Olympus Fluoview) and mode-locked Ti:sapphire laser (Coherent Mira 900). This system has internal detectors as well as external whole-field detection and an electro-optical modulator for blanking the beam on flyback and effecting fast changes in excitation intensity. This microscope can be used in deep, scattering samples for quantitative measurements with a wide range of fluorophores (GFP, fura, calcium green, calcium orange, fluo-3, DiI, DiO, fluorescein, rhodamine), for fluorescent photobleaching recovery and for uncaging. Images obtained with this system can be deconvolved with the Estimation Maximization algorithm using the program XCOSM (freeware available at: http://www.ibc.wustl.edu/bcl/xcosm/).
Two new clinical/laboratory protocols for CAD/CAM implant restorations

ABSTRACT Background Conventional casting technology has some disadvantages for dental laboratory technicians and restorative dentists, including porosity of restorations, miscasting and inaccuracy. It also is labor-intensive. Computer-aided design/computer-aided manufacturing (CAD/CAM) technology was developed in the late 1980s for dentistry, and it significantly reduced and/or eliminated problems associated with dental castings. The purpose of this article is to give readers an overview of the use of CAD/CAM technology for dental implants and illustrate two clinical protocols for that use. Clinical Implications The CAD/CAM technology described in this article can reduce restorative dentists' chairside time associated with implant treatment in both edentulous and partially edentulous patients, can decrease costs without sacrificing accuracy or biocompatibility for both clinicians and dental laboratory technicians, and is available to dental laboratories without the capital expenses associated with purchasing new technology.
Oxygen isotope constraints on the petrogenesis of Aleutian arc magmas

The first measurement of 18 O/ 16 O ratios of plagioclase, clinopyroxene, orthopyroxene, and titanomagnetite phenocrysts from modern Aleutian island-arc lavas provides new insight and independent constraints on magma sources and intracrustal processes. Basalts are heterogeneous on the scale of the entire arc (δ 18 Oplag = 5.5‰-6.7‰) and individual volcanic centers (ranges of 0.3‰ to 0.8‰). Combined with Sr isotope and trace element data, δ 18 Oplag values suggest a variable magma source characterized by differences in the mantle wedge or the subducted sediment component along the volcanic front. Seven tholeiitic basalt to rhyodacite (50%-71% SiO 2 ) lavas from the Seguam volcanic center have nearly identical δ 18 Oplag values of 6.0‰ ±0.2‰, reflecting extensive closed-system plagioclase-dominated crystal fractionation. Oxygen isotope thermometry and pyroxene and oxide equilibria indicate that differentiation occurred between 1150 ±100 °C (basalt) and 950 ±100 °C (rhyodacite). In contrast, δ 18 Oplag values of 12 calc-alkalic basaltic andesites and andesites (53%-62% SiO 2 ) from the smaller Kanaga volcanic center span a broader range of 5.9‰-6.6‰, and consist of mostly higher values. Isotopic disequilibrium in the Kanaga system is manifest in two ways: two types of basaltic inclusions with contrasting δ 18 O values (6.0‰ and 6.5‰) occur in one andesite (δ 18 Oplag = 6.6‰), and in two other andesites plagioclase-titanomagnetite and clinopyroxene-titanomagnetite oxygen isotope temperatures are inconsistent. One andesite, however, yields concordant oxygen isotope temperatures of ∼850 ±100 °C, and a two-pyroxene temperature of 920 ±50 °C. Assimilation of isotopically heavy crustal wall rock and mixing off basaltic and andesitic magmas explains the variable and high δ 18 Oplag values and low eruptive temperature of the Kanaga andesites.
Development of the vacuum power flow channel for the Mini-G

The Mini-G explosive pulsed power system is a two-stage helical-coaxial FCG that is geometrically a half-scale version of LLNL's FFT device. The generator is capable of delivering 60 MA currents and 10 MJ of energy to suitable inductive loads. The Mini-G is presently used in high-energy-density physics experiments that require efficient current delivery through a vacuum power flow region to the load. As with the FFT device, the Mini-G system requires a compact, high-voltage gas-to-vacuum insulator and low-inductance vacuum power flow channel to achieve high performance and maximum energy delivery. In designing the Mini-G system, we followed the successful approach used in developing the FFT device. This included shaping the electrodes and insulators to manage electric field enhancements, applying coatings to cathode surfaces to suppress electron field emission, introducing baffles to the power flow channel to block UV, and applying coatings to electrode surfaces to absorb UV. This paper describes the design of the Mini-G vacuum interface and power flow region, and results of modeling and simulations that were done to evaluate and optimize performance. Appropriate codes were used to examine electric field enhancements, magnetic insulation, flashover inhibition and UV ray tracing in the channel. In this paper, we also present results of laboratory testing on`and shapes, UV induced insulator flashover, along with measurements of HV thresholds for electron emission. We also report on UV reflectance data for some of the coatings considered. To date, there have been eight experiments performed using the Mini-G system. For the first two tests, the power flow channel had an extremely low vacuum inductance of 0.9 nH. On the second Mini-G test it appeared that a partial shorting occurred in the power flow channel, limiting full energy delivery to the load. The design was modified to reduce electrical stress, improve UV attenuation, and incorporate additional diagnostics. This increased the inductance of the power flow channel to 1.5 nH. On the third Mini-G test the partial shorting reoccurred and the new diagnostics (inner Bdot probe) helped to identify the location at the vacuum insulator surface - about 10% of total current of 41 MA was diverted into the short. Further design modifications were incorporated to decrease electrical stress across the insulator and reduce UV illumination of the insulator surface. This increased the inductance of the power flow channel to 1.9 nH. On subsequent Mini-G experiments full current delivery to the load has been achieved with no occurrence of shorting.
Effect of solute segregation on the strength of nanocrystalline alloys : Inverse Hall-Petch relation

We have used a high-energy ball mill to prepare single-phased nanocrystalline Fe, Fe90Ni10, Fe85Al4Si11, Ni99Fe1 and Ni90Fe10 powders. We then increased their grain sizes by annealing. We found that a low-temperature anneal (T < 0.4 Tm) softens the elemental nanocrystalline Fe but hardens both the body-centered cubic iron- and face-centered cubic nickel-based solid solutions, leading in these alloys to an inverse Hall–Petch relationship. We explain this abnormal Hall–Petch effect in terms of solute segregation to the grain boundaries of the nanocrystalline alloys. Our analysis can also explain the inverse Hall–Petch relationship found in previous studies during the thermal anneal of ball-milled nanocrystalline Fe (containing ∼1.5 at.% impurities) and electrodeposited nanocrystalline Ni (containing ∼1.0 at.% impurities).
Implantable left ventricular assist devices: an evolving long-term cardiac replacement therapy.

Objective The authors' 8-year experience with both inpatient and outpatient left ventricular assist device (LVAD) support is presented to show the possibilities and limitations of long-term outpatient mechanical circulatory assistance. Background Data The limitation of suitable cardiac donors has led to the use of LVADs as a temporizing measure for patients awaiting cardiac transplantation. The success of such devices in the short and medium term as a bridge to transplantation has led to their evaluation as a long-term destination therapy for end-stage heart disease. Methods Between August 1990 and February 1997, 85 patients with end-stage heart disease underwent insertion of implantable LVADs. Fifty-two patients underwent pneumatic device insertion and 32 patients received a vented electric device. Results Patients were supported for a mean of 109 ± 13 days for an overall survival to transplant (54) or explant (3) of 73%. Nineteen patients were discharged from the hospital on a mean of postoperative day 41 ± 4 (range, 17-68) for an outpatient support time of 108 ± 30 days (range, 2-466). Of 12 patients supported after postcardiotomy cardiogenic shock, 10 (82%) survived to hospital discharge. Perioperative right ventricular failure was treated in most patients with inotropic agents and inhaled nitric oxide with only six patients requiring right ventricular assist device support. Thromboembolic rate was low (0.016 events/patient-month) despite minimal or no anticoagulation in all cases. Conclusions Left ventricular assist device support has evolved to become an outpatient therapy with excellent survival rates and an acceptable morbidity. Accordingly, wearable LVADs should be studied as permanent treatment options for patients who are not transplant candidates.
El pasado escindido: la enseñanza de la historia en las escuelas españolas, 1875-1900

During the Restoration the teaching of Spanish history at the primary and secondary level reflected the ideological and political conflicts of Spanish Society. Given the weakness of the liberal state and its inability to create and effectively transmit a vision of history, textbooks reflected the ideology and self-interest of History chair professors. Due to the state's relative inactivity, textbooks rarely gave students a coherent idea of Spain's and the Spaniards' past.
Effect of laser irradiation on gas sensing properties of sol–gel derived nanocrystalline Al-doped ZnO thin films

Abstract The effect of laser irradiation on the performance of gas sensor made with sol–gel derived Al-doped ZnO thin films was investigated. The films with desired thicknesses were deposited on the alkali-free glass substrates by a sol–gel process. A pulsed laser system with a wavelength of 532 nm, a pulsed duration of 8 ns, pulsed frequency of 5 kHz and the laser fluence in the range of 1.06–3.58 J/cm2 was used as the irradiation source. The microstructure, optical transmittance, surface morphology, electrical conductivity and gas sensor performance of the as-deposited and laser-irradiated Al-doped ZnO films were studied as a function of laser energy level. The X-ray diffraction results indicated that low laser energy significantly enhanced the crystallinity and promoted grain growth, whereas high laser energy irradiation resulted in deterioration of crystalline quality. It was also found that the laser irradiation affected the surface morphology and electrical conductivity of ZnO films. The gas sensor performance of Al-doped ZnO sensors was examined in terms of ZnO film thicknesses and H2 concentrations in the air at an operating temperature of 130 °C. It was found that the sensing response of Al-doped ZnO sensors varied depending on the film thickness as well as the laser energy level. An optimum laser energy level resulted in high and rapid response characteristics of gas sensors for the detection of H2. The results also suggested that the crystallinity was critical to achieve the optimum sensor performance.
Cloning of aquaporin-1 of the blue crab, Callinectes sapidus: its expression during the larval development in hyposalinity

Ontogenetic variation in salinity adaptation has been noted for the blue crab, Callinectes sapidus, which uses the export strategy for larval development: females migrate from the estuaries to the coast to spawn, larvae develop in the ocean, and postlarvae (megalopae) colonize estuarine areas. We hypothesized that C. sapidus larvae may be stenohaline and have limited osmoregulatory capacity which compromises their ability to survive in lower salinity waters. We tested this hypothesis using hatchery-raised larvae that were traceable to specific life stages. In addition, we aimed to understand the possible involvement of AQP-1 in salinity adaptation during larval development and during exposure to hyposalinity. A full-length cDNA sequence of aquaporin (GenBank JQ970426) was isolated from the hypodermis of the blue crab, C. sapidus, using PCR with degenerate primers and 5′ and 3′ RACE. The open reading frame of CasAQP-1 consists of 238 amino acids containing six helical structures and two NPA motifs for the water pore. The expression pattern of CasAQP-1 was ubiquitous in cDNAs from all tissues examined, although higher in the hepatopancreas, thoracic ganglia, abdominal muscle, and hypodermis and lower in the antennal gland, heart, hemocytes, ovary, eyestalk, brain, hindgut, Y-organs, and gill. Callinectes larvae differed in their capacity to molt in hyposalinity, as those at earlier stages from Zoea (Z) 1 to Z4 had lower molting rates than those from Z5 onwards, as compared to controls kept in 30 ppt water. No difference was found in the survival of larvae held at 15 and 30 ppt. CasAQP-1 expression differed with ontogeny during larval development, with significantly higher expression at Z1-2, compared to other larval stages. The exposure to 15 ppt affected larval-stage dependent CasAQP-1 expression which was significantly higher in Z2- 6 stages than the other larval stages. We report the ontogenetic variation in CasAQP-1 expression during the larval development of C. sapidus and the induction of its expression at early larval stages in the exposure of hyposalinity. However, it remains to be determined if the increase in CasAQP-1 expression at later larval stages may have a role in adaptation to hyposalinity.
New results at intermediate energies

Abstract Recent experimental results on light particle emission from intermediate energy nucleus-nucleus collisions are reviewed. Present, mostly single particle inclusive measurements are consistent with the concept of thermalization of a subset of nucleons. The measurement of thermally produced composite light particles is hoped to provide more specific information about the decay properties of hot nuclear matter and a possible liquid gas phase transition.
Unusual phosphorylation sequence in the gpIV (gI) component of the varicella-zoster virus gpI-gpIV glycoprotein complex (VZV gE-gI complex).

Abstract Varicella-zoster virus (VZV) glycoprotein gpIV, to be renamed VZV gI, forms a heterodimer with glycoprotein gpI (gE) which functions as an Fc receptor in virus-infected cells. Like VZV gpI (gE), this viral glycoprotein is phosphorylated in cell culture during biosynthesis. In this report, we investigated the nature and specificity of the phosphorylation event involving VZV gpIV (gI). Phosphoamino acid analysis indicated that gpIV (gI) was modified mainly on serine residues. To identify the precise location of the phosphorylation site on the 64-kDa protein, a step-by-step mutagenesis procedures was followed. Initially a tailless mutant was generated, and this truncated product was no longer phosphorylated. Thereafter, point mutations were made within the cytoplasmic tail of gpIV (gI) at potential phosphorylation sites. The phosphorylation site was localized to the following sequence: Ser-Pro-Pro (amino acids 343 to 345). Examination of the point mutants established that serine 343 in the cytoplasmic tail was the major phosphoacceptor. In addition, we found that the prolines located immediately to the C terminus of serine 343 were an integral part of the kinase recognition sequence. This site was located immediately N terminal to a predicted beta-turn secondary structure. By comparison with known substrate consensus sequences for various protein kinases, these data suggested that the phosphorylation of VZV gpIV (gI) was catalyzed by a proline-directed protein kinase. Computer homology analysis of other alphaherpesviruses demonstrated that a similar potential phosphorylation site was highly conserved in the cytoplasmic tails of herpes simplex virus type 1 gI, equine herpesvirus type 1 gI, and pseudorabies virus gp63.
Measuring leg muscle and fat mass in humans: comparison of CT and dual-energy X-ray absorptiometry

Dual-energy X-ray absorptiometry (DEXA) is reported to be inferior to computed tomography (CT) to measure changes in appendicular soft tissue composition. We compared CT- and DEXA-measured thigh mu...
Cold delay defect screening

Delay defects can escape detection during the normal production test flow; particularly if they do not affect any of the long paths included in the test flow. Some delay defects can have their delay increased, making them easier to detect, by carrying out the test with a very low supply voltage (VLV testing). However, VLV testing is not effective for delay defects caused by high resistance interconnects. This paper presents a screening technique for such defects. This technique, cold testing, relies on carrying out the test at low temperature. One particular type of defect, silicide open, is analyzed and experimental data are presented to demonstrate the effectiveness of cold testing.
Adverse Outcome Pathway Development II: Best Practices

Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including those derived through high-throughput in vitro, high content omics and imaging, and biomarker approaches, in risk-based decision making. The previously ad hoc process of AOP development is being formalized through development of internationally harmonized guidance and principles. The goal of this article was to outline the information content desired for formal AOP description and some rules of thumb and best practices intended to facilitate reuse and connectivity of elements of an AOP description in a knowledgebase and network context. For example, key events (KEs) are measurements of change in biological state that are indicative of progression of a perturbation toward a specified adverse outcome. Best practices for KE description suggest that each KE should be defined as an independent measurement made at a particular level of biological organization. The concept of “functional equivalence” can help guide both decisions about how many KEs to include in an AOP and the specificity with which they are defined. Likewise, in describing both KEs and evidence that supports a causal linkage or statistical association between them (ie, a key event relationship; KER), best practice is to build from and contribute to existing KE or KER descriptions in the AOP knowledgebase rather than creating redundant descriptions. The best practices proposed address many of the challenges and uncertainties related to AOP development and help promote a consistent and reliable, yet flexible approach.
A linear aperture radiating maximum power within prescribed angular constraints

For fixed aperture size, the aperture taper which maximizes the power radiated into a specified interval ( -\theta_{0},\theta_{0} ) is determined, and the properties of the corresponding pattern are compared to the ideal space pattern introduced by Taylor [1]. We consider the case of the linear aperture with no supergaining, although the results are directly applicable to the principal plane patterns of the two dimensional rectangular aperture. It is shown that for an aperture of width a , as ( \pi\alpha/\lambda ) sin \theta_{0} increases, one can not only maximize the power radiated into ( -\theta_{0},\theta_{0} ), but also constrain the sidelobe ratio outside ( -\theta_{0},\theta_{0} ) below a specified value.
Further Studies on Viability in Rhode Island Reds

Abstract NUMEROUS studies have indicated that viability is one of the most important problems in poultry breeding. In pedigreed flocks family mortality offers a very acceptable measure of viability. In the Rhode Island Red breed Hays (1948) showed that as fertility of females increased there was a decrease in viability within families as shown by increased mortality. This tendency was observed both before sexual maturity and during the first laying year. Hays (1949) later presented data indicating that lower viability from hatching to eight weeks and from eight weeks to sexual maturity was associated with higher first-year production in surviving females. Since it was shown (Hays, 1948) that high fertility in the females of a family was associated with low viability it is interesting and important to know whether highly fertile females are more likely to produce offspring with low viability compared with the offspring of females with lower fertility. Size . . .
Vitamin B12 as a Carrier for the Oral Delivery of Insulin

The noninvasive delivery of insulin continues to be a major goal for the treatment of diabetes mellitus. Oral-enteric administration would make insulin delivery easier and more effective, as higher patient compliance and improved glycemic control are likely; yet the oral-enteric pathway has been unfeasible owing to insulin's susceptibility to proteolytic degradation and inefficient enteric uptake. Herein we show that a noninvasive oral delivery route for insulin is possible through the vitamin B12 uptake pathway. In diabetic rat models, insulin-B12 conjugates can significantly lower blood glucose levels when administered orally.
Metabolic engineering of Serratia marcescens with the bacterial hemoglobin gene: alterations in fermentation pathways.

Serratia marcescens was transformed with plasmid vector pUC8 or pUC8 containing the bacterial (Vitreoscilla) hemoglobin gene (vgb) on either a 2.3-kb fragment (pUC8:15) or 1.4-kb fragment (pUC8:16) of Vitreoscilla DNA. The vgb-bearing strains were compared with the pUC8 transformant and untransformed S. marcescens with respect to growth in Luria-Bertani (LB) broth supplemented with glucose or casein acid hydrolysate. Growth (on a viable cell basis) was similar to that in unsupplemented LB. Total acid excretion (as estimated by medium pH) was similar for all strains in both LB plus 2% casein acid hydrolysate and LB without additions. Acid excretion in LB plus 2% glucose was somewhat greater at up to 10 h in culture for the two vgb-bearing strains; from 10 to 26 h in culture, the pHs of these cultures continued to decrease (to 4.1-4.2), whereas those of the non-vgb-bearing strains returned to near the starting pH (7.4-7.8). Concomitantly, after 26 h of culture in LB plus 2% glucose, the non-vgb-bearing strains had produced about 15 times as much acetoin and about three to four times as much 2,3-butanediol as the vgb-bearing strains. In general, for all strains, much more acetoin and 2,3-butanediol were produced in LB plus 2% glucose than in unsupplemented LB. The exception was acetoin production by the strain bearing vgb on plasmid pUC8:15; after 26 h of culture in LB without supplementation it was between three and four times that of the other strains, and about 50% higher than its level in LB plus 2% glucose. When grown with the 2% casein acid hydrolysate supplement, the strain bearing vgb on plasmid pUC8:15 produced much more acetoin and 2,3-butanediol than the other strains after 26 hours in culture. The results confirm that vgb can significantly alter carbon metabolism and suggest that the use of vgb technology for directed metabolic engineering may be a complicated process, depending in part on medium composition.
NEPHROLITHIASIS FROM INDINAVIR, A NEW HUMAN IMMUNODEFICIENCY VIRUS DRUG

A 37-year-old man with hemophilia and HIV who had been receiving 800 mg. indinavir sulfate 3 times daily for 4 months presented with gross hematuria, right flank pain and hydronephrosis. CD4+ count was 8 cells per mm.3. Excretory urography revealed a delayed nephrogram at 18 hours but no identifiable stone. The patient was treated with aggressive intravenous rehydration and meperidine. Two weeks later he passed a 3 mm. stone. Analysis revealed low birefringent crystals. Polarization microscopy with infrared spectroscopy demonstrated a compound identical to material passed in the urine of patients on indinavir. Indinavir treatment was discontinued and pain resolved with no further complications.
Exploiting the Prefetching Effect Provided by Executing Mispredicted Load Instructions

As the degree of instruction-level parallelism in superscalar architectures increases, the gap between processor and memory performance continues to grow requiring more aggressive techniques to increase the performance of the memory system. We propose a new technique, which is based on the wrong-path execution of loads far beyond instruction fetch-limiting conditional branches, to exploit more instruction-level parallelism by reducing the impact of memory delays. We examine the effects of the execution of loads down the wrong branch path on the performance of an aggressive issue processor. We find that, by continuing to execute the loads issued in the mispredicted path, even after the branch is resolved, we can actually reduce the cache misses observed on the correctly executed path. This wrong-path execution of loads can result in a speedup of up to 5% due to an indirect prefetching effect that brings data or instruction blocks into the cache for instructions subsequently issued on the correctly predicted path. However, it also can increase the amount of memory traffic and can pollute the cache. We propose the Wrong Path Cache (WPC) to eliminate the cache pollution caused by the execution of loads down mispredicted branch paths. For the configurations tested, fetching the results of wrong path loads into a fully associative 8-entry WPC can result in a 12% to 39% reduction in L1 data cache misses and in a speedup of up to 37%, with an average speedup of 9%, over the baseline processor.
Analysis of the effects of bearings-only sensors on the performance of the neural extended kalman filter tracking system

The neural extended Kalman filter (NEKF) has proven to be a quality maneuver target tracking system when the sensors provide a fully observable measurement, such as a radarpsilas range-bearing measurement or a position report. As with any state estimation technique, the NEKF requires observability in order to estimate the target track states. Observability is needed as well to train the weights of the neural network, since the neural network training paradigm is coupled to the target states. Passive sensor systems, such as electronic surveillance measures and passive sonar arrays, provide an angle-only measurement. Such bearings-only measurements make the tracking system an unobservable system. For a Kalman filter estimator, this will result in the eigenvalues of the error covariance matrix to grow without bound. For the NEKF, since both the target state and the weights of the neural network are affected by the lack of observability, the results could be more pronounced. In this paper, the application of the NEKF in bearings-only tracking problems is analyzed to determine the effects on performance. The analyzed cases look at a single sensor platform in four important scenarios: a stationary platform and straight-line target, a stationary platform and a maneuvering target, a maneuvering platform and a straight-line target, and a maneuvering platform and a maneuvering target.
PCMO Device With High Switching Stability

We studied the relationship between the resistive-switching properties of the Pr0.7Ca0.3MnO3 (PCMO) thin-film elements and their geometry dimensions below submicrometers. Our electrical test results of a series of PCMO-based resistive-switching devices with different sizes show that switching voltages of ±2.5 V were achieved by reducing the PCMO layer thickness to 30 nm. In addition, the reduction of the PCMO layer thickness does not incur a significant impact upon the device reliability, i.e., no significant degradation of the two resistance states was observed after 1.5 × 103 programming cycles.
Fibroma of the testicular tunics: an unusual extratesticular intrascrotal mass.

Fibromas are rare, benign intrascrotal tumors. There are only a handful of case reports that specifically discuss these masses. 1-5 Here we present a case of fibroma of the testicular tunics and its imaging characteristics. The radiologic appearance of these tumors is variable; our goal is to familiarize the radiologist with the imaging characteristics of this clinical entity.
Who Pays the Price: The Sociocultural Context of Environmental Crisis

Who Pays the Price: The Sociocultural Context of Environmental Crisis Edited by: Barbara Rose Johnston Publisher: Island Press for the Society for Applied Anthropology Date: 1994 ISBN: 1-55963-303-4
Integrins and Regulation of the Microcirculation: From Arterioles to Molecular Studies using Atomic Force Microscopy

Integrins are an important class of receptors for extracellular matrix proteins that can mediate both force transmission, by virtue of their connections with the cell matrix and cytoskeleton; and signal transduction, resulting from the assemblages of signaling proteins that associate with focal contacts. Consequently, integrins have been proposed to be the mechanosensor in vascular smooth muscle and endothelial cells and to play a central role in mechanotransduction. In this regard, mechanical force is an important stimulus for many vascular functions, including contractile and relaxation processes,proliferation, migration, attachment, and cell phenotype determination. Collectively, these functions define physiological properties of the vasculature such as control of blood flow, capillary pressure,permeability, and peripheral vascular resistance, and play a role in pathophysiological processes like hypertension, diabetes, and arteriosclerosis. Our knowledge concerning how integrins sense and transduce physical forces into cellular signals and which integrins are involved is incomplete. Compared to other cell surface receptors, integrins have a relatively low affinity for their binding sites on the extracellular matrix and their affinity can be regulated. These characteristics of integrin-ligand interaction may facilitate dynamic processes such as cell migration, cell remodeling, and contractile activation in response to external forces. Important questions remain concerning the nature and origin of integrin-mediated signaling in the vascular wall.
Selectivity of Face Aftereffects for Expressions and Anti-Expressions

Adapting to a facial expression can alter the perceived expression of subsequently viewed faces. However, it remains unclear whether this adaptation affects each expression independently or transfers from one expression to another, and whether this transfer impedes or enhances responses to a different expression. To test for these interactions, we probed the basic expressions of anger, fear, happiness, sadness, surprise, and disgust, adapting to one expression and then testing on all six. Each expression was varied in strength by morphing it with a common neutral facial expression. Observers determined the threshold level required to correctly identify each expression, before or after adapting to a face with a neutral or intense expression. The adaptation was strongly selective for the adapting category; responses to the adapting expression were reduced, while other categories showed little consistent evidence of either suppression or facilitation. In a second experiment we instead compared adaptation to each expression and its anti-expression. The latter are defined by the physically complementary facial configuration, yet appear much more ambiguous as expressions. In this case, for most expressions the opposing faces produced aftereffects of opposite sign in the perceived expression. These biases suggest that the adaptation acts in part by shifting the perceived neutral point for the facial configuration. This is consistent with the pattern of renormalization suggested for adaptation to other facial attributes, and thus may reflect a generic level of configural coding. However, for most categories aftereffects were stronger for expressions than anti-expressions, pointing to the possible influence of an additional component of the adaptation at sites that explicitly represent facial expressions. At either level our results are consistent with other recent work in suggesting that the six expressions are defined by dimensions that are largely independently normalize
A stimulating nerve cuff for chronic in vivo measurements of torque produced about the ankle in the mouse

Specific muscle training and chronic contractile measurements are difficult in rodents, especially in the mouse. The primary reason for this is the lack of a means for stimulating the motor nerve that does not damage the nerve and that permits reproducible measurements of contractility. In this paper, we describe procedures for the construction and implantation of a stimulating nerve cuff for use on the mouse common peroneal nerve. We demonstrate that nerve cuff implantation success rates can be high (i.e., 75-93%), as determined from measurements of maximal isometric torque produced by the anterior crural muscles. Isometric torque production is not adversely affected by the nerve cuff because the torque produced matches that observed in our established percutaneous stimulation model. We also demonstrate that use of the nerve cuff for stimulation is compatible with electromyographic measurements made on the tibialis anterior muscle, with no sign of stimulation artifact in the electromyographic signal.
Annealing stochastic approximation Monte Carlo algorithm for neural network training

We propose a general-purpose stochastic optimization algorithm, the so-called annealing stochastic approximation Monte Carlo (ASAMC) algorithm, for neural network training. ASAMC can be regarded as a space annealing version of the stochastic approximation Monte Carlo (SAMC) algorithm. Under mild conditions, we show that ASAMC can converge weakly at a rate of ? $(1/\sqrt{t})$ toward a neighboring set (in the space of energy) of the global minimizers. ASAMC is compared with simulated annealing, SAMC, and the BFGS algorithm for training MLPs on a number of examples. The numerical results indicate that ASAMC outperforms the other algorithms in both training and test errors. Like other stochastic algorithms, ASAMC requires longer training time than do the gradient-based algorithms. It provides, however, an efficient approach to train MLPs for which the energy landscape is rugged.
Magnetic Oxide Heterostructures

Complex transition metal oxides have played a central role in the study of magnetic materials, serving as model systems for explorations of fundamental exchange interactions and the relationships between structural, electronic, and magnetic responses. Enabled by advances in epitaxial synthesis techniques, abrupt heterointerfaces and superlattices have emerged as a powerful platform for engineering novel magnetic behavior in oxides. Following a brief introduction to the dominant exchange mechanisms in metal oxides, we review the general means by which interfacial magnetism can be tailored in ABO3 perovskites, including interfacial charge transfer, epitaxial strain and structural coupling, orbital polarizations and reconstructions, and tailoring exchange interactions via cation ordering. Recent examples are provided to illustrate how these strategies have been employed at isolated interfaces and in short-period superlattices. We conclude by briefly discussing underexplored and emerging research directions i...
Oncologists' Response to New Data Regarding the Use of Epidermal Growth Factor Receptor Inhibitors in Colorectal Cancer

The authors found that oncologists respond rapidly to new evidence and professional guidelines, and readily incorporate predictive biomarkers into clinical practice.
Refinement of approximate domain theories by knowledge-based neural networks

Standard algorithms for explanation-based learning require complete and correct knowledge bases. The KBANN system relaxes this constraint through the use of empirical learning methods to refine approximately correct knowledge. This knowledge is used to determine the structure of an artificial neural network and the weights on its links, thereby making the knowledge accessible for modification by neural learning. KBANN is evaluated by empirical tests in the domain of molecular biology. Networks created by KBANN are shown to be superior, in terms of their ability to correctly classify unseen examples, to randomly initialized neural networks, decision trees, "nearest neighbor" matching, and standard techniques reported in the biological literature. In addition, KBANN'S networks improve the initial knowledge in biologically interesting ways.
Artificial Life Models in Software. Andrew Adamatzky and Maciej Komosinski (Eds.). (2005, Springer-Verlag.) Hardcover, $69.95, 344 pages, 189 illustrations

Artificial Life Models in Software. Andrew Adamatzky and Maciej Komosinski (Eds.). (2005, SpringerVerlag.) Hardcover, $69.95, 344 pages, 189 illustrations. Artificial life models in software is a unique book that showcases a variety of freely available software for artificial life simulations. At first glance it may appear to be nothing new, but actually it is quite unprecedented. In these pages readers have a quick overview of what kind of simulation tools are available off the shelf on the Web today and what can be done by using them. It will be valuable for many related to artificial life, especially as an introductory reading for students who are about to plunge into this creative field of research. It will also be a nice informative reference for professional researchers and educators. Moreover, the software models introduced in this book should be quite appealing to nonscientific readers as well, potentially contributing to the outreach of artificial life research to a general audience. This book consists of thirteen chapters which are categorized into four parts as follows:
An update on estimating the cost of cryogenic refrigeration

This paper is an update of a report written in 19911 concerning cost estimating of refrigeration for superconducting magnets. This report updates cost data collected by Strobridge2,3,4 over 20 years ago and data collected by these authors. The actual costs have been inflated to 1997 dollars and are plotted. A correlation function between cost and refrigeration at 4.5 K and 1.8 K is given. An annual cost for refrigeration can also be estimated based on the refrigeration at 4.5 K or 1.8 K and the cost of electrical energy. A correlation function for estimating input power to the compressors to the refrigeration produced at 4.5 K and 1.8 K is also given.
A whole-path importance-sampling scheme for Feynman path integral calculations of absolute partition functions and free energies

Using Feynman path integrals, a molecular partition function can be written as a double integral with the inner integral involving all closed paths centered at a given molecular configuration, and the outer integral involving all possible molecular configurations. In previous work employing Monte Carlo methods to evaluate such partition functions, we presented schemes for importance sampling and stratification in the molecular configurations that constitute the path centroids, but we relied on free-particle paths for sampling the path integrals. At low temperatures, the path sampling is expensive because the paths can travel far from the centroid configuration. We now present a scheme for importance sampling of whole Feynman paths based on harmonic information from an instantaneous normal mode calculation at the centroid configuration, which we refer to as harmonically guided whole-path importance sampling (WPIS). We obtain paths conforming to our chosen importance function by rejection sampling from a distribution of free-particle paths. Sample calculations on CH4 demonstrate that at a temperature of 200 K, about 99.9% of the free-particle paths can be rejected without integration, and at 300 K, about 98% can be rejected. We also show that it is typically possible to reduce the overhead associated with the WPIS scheme by sampling the paths using a significantly lower-order path discretization than that which is needed to converge the partition function.
Selective exposure to podcast and political participation: the mediating role of emotions

Using an online national survey data collected during the 2012 South Korean Presidential campaign, this study examined whether and how partisan podcast consumption has an effect in activating the individuals' emotions towards candidates. This study also investigated whether citizens' such emotions consequently influenced political participation. The results showed that the more liberal a person was, the more they listened to a liberal podcast program, Naneun Ggomsuda. Such selective exposure to a liberal podcast program was positively associated with negative emotion and negatively related to positive emotion towards a conservative party presidential candidate. In contrast, the use of the liberal podcast was positively associated with positive emotion and negatively associated with negative emotion towards a liberal party presidential candidate. Both negative and positive emotions towards political candidates were significantly related with individuals' political participation. Most importantly, the results showed that the emotions mediated the relationship between partisan podcast use and political participation. Implications of the findings are discussed.