cssi/SciSciGPT-SciSciNet huggingface dataset:
Interference with Valine and Isoleucine Biosynthesis by Cyclic Hydroxamic Acids

Hogg, Robert W. (University of Illinois, Urbana), Chitra S. Biswas, and Harry P. Broquist. Interference with valine and isoleucine biosynthesis by cyclic hydroxamic acids. J. Bacteriol. 90:1265–1270. 1965.—The introduction of a hydroxyl group in a number of common barbiturates, a substitution which converts these compounds to cyclic hydroxamic acids, gives rise to compounds which inhibit growth of Escherichia coli. The toxicity of these hydroxybarbiturates appears to be associated, at least in part, with interference with valine and isoleucine biosynthesis, as a combination of these amino acids counteracts their toxicity. A subinhibitory level of 1-hydroxy-5-ethyl-5-isopropylbarbituric acid (hydroxyipral) was counteracted either by valine or by its early precursor, α-acetolactate, and led to a study of the effect of these cyclic hydroxamic acids on acetolactate synthesis in a cell-free enzyme system of E. coli. In this system, the parent barbiturates and their respective hydroxy derivatives were only moderately active in blocking acetolactate synthesis. Detailed kinetic studies of the most active compound, hydroxyipral showed no obvious relationship to the substrate or cofactors of the system. The inhibitory effects of hydroxyipral, either on growth of E. coli or in the acetolactate-forming system, could not be counteracted by Fe++, but the toxic effect of aspergillic acid and o-phenanthroline in these instances was reversed by Fe++, which implies an iron involvement in the acetolactate-forming system of E. coli.
Delicate coordination of TRIM21's dual activity in virus neutralization and signaling.

TRIM21 belongs to the tripartite motif (TRIM) family of ubiquitin E3 ligases. Approximately 100 TRIM proteins exist in humans, and they all share a common domain structure composed of a RING domain that confers the E3 ligase enzymatic activity, one or two B-boxes, and a coiled-coil domain (1). Many TRIM proteins play crucial roles in antiviral immune responses, often by targeting specific viral components. For example, TRIM5α inhibits the infection of many retroviruses, including HIV-1, by binding to incoming viral capsids, leading to capsid dissociation and inhibition of reverse transcription of the viral genome. TRIM19, also known as promyelocytic leukemia protein, is a key component of subnuclear structures that restrict a variety of RNA and DNA viruses. Furthermore, TRIM proteins modulate signal transduction pathways that lead to antiviral cytokine production, ultimately contributing to the establishment of an antiviral state in both the infected and uninfected cell (1). For example, TRIM25 activates the innate immune sensor RIG-I, potentiating the production of antiviral cytokines, such as type-I interferons (IFN-α/β) (2). Recent studies demonstrated that several TRIM proteins, including TRIM5α and TRIM19, play dual roles in antiviral immunity by acting both as “effectors” that neutralize viral infection, and as “sensors” that induce innate immune signaling. It has also been shown that the ability of TRIM proteins to catalyze different types of ubiquitination is important for their effector and sensor functions. However, the molecular details of how the dual activity of TRIM proteins is temporally and mechanistically coordinated are not well understood. In PNAS, Fletcher et al. uncover a mechanism of stepwise ubiquitination and deubiquitination in synchronizing the sensor and effector functions of TRIM21, providing molecular-level insights into the antiviral activity of TRIM proteins (3).
Carney complex and lentiginosis

Initially described as the 'complex of myxomas, spotty skin pigmentation and endocrine overactivity,' Carney complex (CNC) is known as an autosomal dominant multiple neoplasia syndrome involving skin and cardiac myxomas, pigmented skin lesions and endocrine tumors. Pigmented cutaneous manifestations in CNC are important diagnostically because they can be used for the early detection of the disease and, thus, the prevention of life-threatening complications of CNC related to heart myxomas and endocrine abnormalities. Specific for the disease skin lesions are present in more than half of the CNC patients. A major challenge is to distinguish pigmented skin lesions associated with CNC from other skin pathology, and thus accurately estimate the risk of cancer in affected patients; curiously, patients with CNC do not appear to have predisposition to skin cancers whereas this is not the case with other genetic syndromes associated with melanotic and other cutaneous lesions. In this paper, we review the current knowledge on cutaneous pathology associated with CNC and the most recent data on the molecular basis of the disease.
GH releasing peptides--structure and kinetics.

A new class of small synthetic peptides has been developed which specifically release GH. They consist of 6-7 amino acids and release GH in animals as well as humans. So far 3 of these peptides have been administered to humans, i.e., GHRP-6, GHRP-1 and GHRP-2. As in rats, these 3 peptides have been found to be increasingly more effective in releasing GH in humans. All 3 GHRPs release GH more efficaciously than GHRH 1-44 NH2 in humans. Particularly note-worthy is that GHRP-6, GHRP-1 AND GHRP-2 all release GH after oral administration. Near maximal amounts of GH can be released after GHRP-1 and GHRP-2 oral administration. In the present studies, the GH responses and serum irGHRP levels after i.v., s.c. and oral administration have been determined in normal younger men and/or women. By each route of administration GH was very effectively released. Additionally, GH release was induced by oral GHRP-6 in children with various degrees of GH deficiency. Noteworthy is the synergistic release of GH induced by the combined i.v. bolus administration of 1 microgram/kg of GHRP-1 + GHRH 1-44NH2. Thus, these results demonstrate GHRPs' potential importance at the theoretical as well as pharmaceutical level.
Color indices for the assessment of chlorophyll development and greening of fresh market potatoes

Abstract When displayed under supplemental lighting, potato (Solanum tuberosum L.) tubers develop chlorophyll, which leads to undesirable greening. Produce managers routinely cull potatoes that have greened; however, the process is subjective and variable, due to the absence of specific grading criteria and a lack of information on the time course and extent of greening under retail/fresh market conditions. The objectives of this study were to characterize the time course of greening/chlorophyll development for selected fresh market cultivars and to develop objectively-based scales of greening to subjectively sort tubers based on changes in visible color in retail markets. A survey of retail outlets showed that most potatoes are displayed at relatively low light intensities, ranging from 2 to 10 μmol quanta m−2 s−1 (400–700 nm). At 6.8 μmol quanta m−2 s−1, chlorophyll concentrations in cells underlying the periderm of cultivars White Rose (WR), Yukon Gold (YG), Dark Red Norland (DRN), Russet Norkotah (RN), and Reba (R) increased linearly over a 5–7 day greening interval. The increased chlorophyll content affected changes in the L-value (darkness) and hue angle (color) of the periderm, characterizing the off color development unique to each cultivar. A greening scale was developed for each cultivar by subjectively selecting tubers from a population that had greened for 0–7 days to achieve a visually perceivable sequence of greening that spanned 8–10 levels, depending on the cultivar. Chlorophyll content increased linearly over the greening scales for WR, YG, and DRN (R2 = 0.95–0.98, P ≤ 0.001), whereas the relationships were quadratic (R2 = 0.96–0.97, P ≤ 0.001) for R and RN. These data calibrated the scales for chlorophyll concentration and indicated that the visible color changes were directly linked to chlorophyll development. The discoloration resulting from greening and characterized by changes in hue angle was dictated by chlorophyll in conjunction with the periderm color unique to each cultivar.
Protein phosphorylation in a dopamine-sensitive homogenate of rat caudate. Effect of adenosine 3',5'-cyclic monophosphate and putative neurotransmitters.

Adenosine 3′,5′-cyclic monophosphate (cyclic AMP) and its 8-methylthio derivative stimulate the incorporation of 32P into proteins endogenous to a homogenate of rat caudate nucleus when 4 μM [γ−32P] ATP is usedas substrate. Higher concentrations of ATP reduced the effect of the cyclic nucleotide until at 400 μM no significant increase in protein phosphorylation was seen. Incubation of the homogenate with 400 μM ATP and 100 μM dopamine resulted in an approx. 2-fold increase in cyclic AMP but did not alter caudate protein phosphorylation suggesting that the catecholamine could not stimulate protein phosphorylation under the experimental conditions used in the present study.
Chromomycin SA analogs from a marine-derived Streptomyces sp.

Two chromomycin SA analogs, chromomycin SA3 and chromomycin SA2, along with deacetylchromomycin A3 and five previously reported chromomycin analogs were isolated from a marine-derived Streptomyces sp. The structures of the new compounds were determined by spectroscopic methods including 1D and 2D NMR techniques, HRMS and chemical methods. Chromomycin SA3 and chromomycin SA2 are the first naturally occuring chromomycin analogs with truncated side-chains. Biological evaluation of chromomycin analogs for cytotoxicity against two non-small cell lung cancer (NSCLC) cell-lines, A549 and HCC44, demonstrated a decrease in cytotoxicity for the truncated sides chain chromomycin analogs.
Reactivities of propane and propene with monopositive ions of fourth period elements produced in a spark

Abstract The fractional ion current of MCH3+ ions formed by the reaction of monopositive ions M+ of the elements of the fourth period with propane and propene in a spark source mass spectrometer is correlated inversely with the energy gap between a 4s1 ground state and the lowest excited state of a different configuration; or, if the element does not have a 4s1 ground state, directly with the energy gap between the ground state and the lowest 4s1 excited state, paying heed to the effect of more highly excited 4p states. This correlation is taken as further evidence for the intervention of excited states of metal ions in the chemistry of metals and organic molecules and supports the hypothesis that metal ions insert in carbon-carbon bonds via an s1 state.
CUTTING PROCESS DIAGNOSTICS UTILISING A SMART CUTTING TOOL

A new sensorised boring tool has been developed to enhance the flexibility and precision of line boring processes. A position sensor and tool tip actuator to control and its controller electronics were integrated into a cutting tool. To take further advantage of this highly sophisticated tool, a process diagnostic method based on cutting force measurement method was developed. An observer implemented in the tool controller estimates the disturbance to the actuator using the tool position sensing information. The estimated disturbance is the same as cutting force applied to the tool tip. The algorithm utilising the cutting force to detect cutting process faults, such as tool tip breakage and misalignment of workpiece has been designed and tested experimentally.
Restoring Banking Stability: Beyond Supervised Capital Requirements

Emerging economies have been particularly prone to financial sector crises, reflecting marked information asymmetries and political interference, as well as the substantial volatility in underlying economic conditions, and the vulnerability of banking and finance when structural economic changes create a new and uncharted operating environment. The standard regulatory paradigm relies mainly on supervised capital adequacy, but it may not be enough. Other measures to improve the incentive structure for bankers, regulators, and other market participants could effectively increase the number of concerned, skilled and watchful eyes. Intermittent application of supplementary "blunt instruments" could also be useful.
A TRPV Channel Modulates C. elegans Neurosecretion, Larval Starvation Survival, and Adult Lifespan

For most organisms, food is only intermittently available; therefore, molecular mechanisms that couple sensation of nutrient availability to growth and development are critical for survival. These mechanisms, however, remain poorly defined. In the absence of nutrients, newly hatched first larval (L1) stage Caenorhabditis elegans halt development and survive in this state for several weeks. We isolated mutations in unc-31, encoding a calcium-activated regulator of neural dense-core vesicle release, which conferred enhanced starvation survival. This extended survival was reminiscent of that seen in daf-2 insulin-signaling deficient mutants and was ultimately dependent on daf-16, which encodes a FOXO transcription factor whose activity is inhibited by insulin signaling. While insulin signaling modulates metabolism, adult lifespan, and dauer formation, insulin-independent mechanisms that also regulate these processes did not promote starvation survival, indicating that regulation of starvation survival is a distinct program. Cell-specific rescue experiments identified a small subset of primary sensory neurons where unc-31 reconstitution modulated starvation survival, suggesting that these neurons mediate perception of food availability. We found that OCR-2, a transient receptor potential vanilloid (TRPV) channel that localizes to the cilia of this subset of neurons, regulates peptide-hormone secretion and L1 starvation survival. Moreover, inactivation of ocr-2 caused a significant extension in adult lifespan. These findings indicate that TRPV channels, which mediate sensation of diverse noxious, thermal, osmotic, and mechanical stimuli, couple nutrient availability to larval starvation survival and adult lifespan through modulation of neural dense-core vesicle secretion.
The Biography of Furniture

Abstract The intimate relationship of the designer and the client has led me to a parallel practice of investigating the built form of biography. The notion of working with biography is a device for avoiding willful design. It provides a conceptual guidance to make decisions. The medium that has been used is “furniture,” which is a smaller and more direct vehicle for ideas than architectural space.
Reduced severity of HSV-1-induced corneal scarring in IL-12-deficient mice

Abstract Evidence suggests that in BALB/c mice infected with HSV-1, increased corneal scarring correlated with the presence of IL-12p40 mRNA in the cornea. To determine if this observed correlation reflected function, we have utilized mice with a homologous disruption of the gene encoding either the IL-12p35 subunit or the IL-12p40 subunit of IL-12. The severity of corneal scarring following ocular infection with HSV-1 was reduced significantly in naive IL-12p35- and IL-12p40-deficient mice compared with naive BALB/c mice, with the corneal scarring being low grade in the IL-12p35-deficient mice and completely absent in the IL-12p40-deficient mice. The reduction in the corneal scarring could not be attributed to a reduction in the HSV-1 titers in the eyes, which were not significantly different from the BALB/c mice, or to differences in the production of TH1 responses (IL-2 and IFN-γ production) by the infected mice. Taken together, these results suggest the importance of IL-12 in the induction of corneal scarring in HSV-1-infected mice.
A simple in vitro assay for vaccinia virus using tube cultures of human cells.

SummaryA satisfactory quantitative plaque assay of vaccinia virus may be obtained in tube cultures of established human cells using a simple method of fluid overlay. With this method stock cells may be employed with economy and the technical disadvantages of an agar overlay circumvented.
Performance of dynamic and isovolumetric trained skeletal muscle ventricles.

Background Dynamic training and maintaining muscle tension are important factors during skeletal muscle ventricle (SMV) conditioning that may improve SMV performance. This study sought to determine the effects of dynamic muscle training and progressive SMV resting pressure expansion on SMV pumping capability. Materials and methods SMVs were constructed in 14 goats using the left latissimus dorsi muscle. SMVs were conditioned with a 40 ml constant-volume isovolumetric implant (n = 5, IsoVol group) or a compliant, pneumatic system that allowed dynamic shortening and direct exposure to resting pressures. Dynamic SMV resting pressure was either progressively increased from 40 to 100 to 120 mmHg (n = 5, HiP group) or maintained at 40 mmHg (n = 4, LowP group) during conditioning. After 8 to 10 weeks of electrical stimulation conditioning, SMVs were connected to a counterpulsation mock circulation system and SMV pumping performance evaluated across a range of pressures and stimulation parameters. Results SMV pumping performance was similar in each group. Stroke works generally increased with pressure and reached a plateau in all groups above 80 mmHg (120 msec contraction ∼80 mJ/stroke; 480 msec contraction ∼180 mJ/stroke). Stroke volumes decreased with pressure except at high stimulation levels where loading effects were observed. Chronic changes in SMV volume significantly effected pumping performance. Conclusions These data suggest that acute pumping performance is not different between 8 to 10 weeks of dynamic or isovolumetric training if SMV volume is not constrained. A potentially improved SMV conditioning protocol is proposed that determines, positions, and maintains SMV volume near the initial volume for maximal isovolumetric pressure during conditioning.
Generalized optimum path search

The author gives a classification of the monotone path functions of a graph. It is shown that one possibility of performing an optimum path search for a generalized path function is to reduce the problem to a shortest path search through the state space. A general algorithm for the optimum path search is proposed and discussed. The proposed algorithm can be considered as a general method of performing a search in the state space for three classes of problems. Modifications of the algorithm for each of the three types of path functions are described. Under some conditions, behavior of the algorithm is close to linear. Finally, an analysis of the implementation of this algorithm for identifying an optimum path in the state space is given.
Hydrazide sol–gel synthesis of nanostructured titanium nitride: precursor chemistry and phase evolution

A hydrazide sol–gel (HSG) process has been developed for synthesizing nanostructured titanium nitride. The process consists of reacting titanium isopropoxide with anhydrous hydrazine in the presence of anhydrous acetonitrile to yield a solid titanium alkoxy hydrazide precursor. Gas chromatography supported by chemical analysis shows that ∼80% of the isopropoxy groups are replaced by hydrazine. The role of acetonitrile, used as a solvent in the formation of titanium alkoxy hydrazide, has been studied using thermogravimetric and mass spectrometry analyses combined with chemical analysis and Fourier transform infrared spectroscopy techniques. Crystalline TiN has been obtained after heat-treatment at temperatures above 800 °C in ultra high purity nitrogen (UHP-N2) and UHP-Ar atmospheres. Transmission electron microscopy and specific surface area analyses revealed that the TiN powder obtained after pyrolysis in UHP-N2 at 1200 °C consists of nanocrystalline (∼10–20 nm) particles exhibiting a high specific surface area (∼252 m2 g−1).
The nature of substrate-attached materials in human fibroblast cultures: Localization of cell and fetal calf serum components

Abstract Human fibroblasts have been used as an in vitro model to examine the morphology and origin of substrate-attached materials. In cultures of subconfluent cells, no ‘tracks’ or ‘pools’ of material could be detected on substrata by anodic oxide interferometry or electron microscopy. However, a continuous layer of densely staining material was present on Falcon plastic tissue culture dishes never exposed to cells or culture medium. Exposure of substrata to culture medium caused the adsorption of fetal calf serum (FCS) components onto the substratum within a few minutes. Although antigenic FCS components remained on the substrata for several days, they were seldom adsorbed to the cells. The hypothesis was formulated that adhesion was mediated by FCS components on the substrata, but not by cellular materials deposited extracellularly. Support for this hypothesis was obtained by studying serum-dependent differences in cell adhesion. Fibroblasts subcultured in the presence of FCS components were usually separated from the substratum by a distance of at least 30 A. In the absence of FCS components, the cells were more closely adherent, in the range at which the near van der Walls forces were effective. Fibroblasts subcultured in the absence of serum components could be removed readily from the substratum, leaving lsfootprints’ of cell surface material behind. Although this material has been prepared similarly to ‘microexudates’ from other types of cultured cells, its relationship to those microexudates has not been determined.
Cost of antibiotic beads is justified: a study of open fracture wounds and chronic osteomyelitis.

Background The purpose of this study was to track the cost of antibiotic-impregnated bead chains and the outcome of treatment over a 30-month period occurring before USP Chapter 797 went into effect. Our overall objective was to determine whether the costs of antibiotic beads were justified by reduced rates of active infections associated with open fracture wounds or chronic osteomyelitis. Methods We retrospectively reviewed 125 patients with open fracture wounds (Group 1) and 16 patients with chronic osteomyelitis (Group 2) treated over a 2.5-year period. We reviewed the medical records and performed cost calculations for the beads. The minimum time from treatment to the latest follow-up evaluation was six weeks (average, 30.7 weeks; range, 6-134 weeks) for Group 1 and six months (average, 61.8 weeks; range, 24-156 weeks) for Group 2. Results The overall infection rates were 3.2% (96.8% free of active infection) for Group 1 and 25.0% (75.0% free of active infection) for Group 2. The average cost of antibiotic bead treatment per patient was $419.36 for Group 1 and $484.54 for Group 2. Conclusions The costs of antibiotic beads to prevent active infection of open fracture wounds or to treat active infection associated with chronic osteomyelitis are justified based on the cost structure prior to the impact of new federal regulations (USP Chapter 797 regulations). We anticipate that the cost of antibiotic beads will increase dramatically with these new regulations.
Implications of Cost-Service Trade-offs on Industry Logistics Structures

The characteristics of the technology and markets within an industry will affect the range of logistics systems observed in that industry. In some industries the range is wide, while in others all firms make the same logistics choices. This paper explores these differences. We propose the concept of an efficient frontier of cost-service choices and show how firms align themselves along the frontier.
Relationships among monsoon-season circulation patterns, gulf surges, and rainfall within the Lower Colorado River Basin, USA.

The purpose of this study is to assess the connections between the monsoon anticyclone, gulf surges, and rainfall within the Lower Colorado River Basin (LCRB) during North American monsoon seasons from 1988-2006. The methods involved calculating rainfall characteristics and near-surface humidity for 500-hPa circulation patterns, creating circulation and near-surface humidity composites for rainfall days, and creating near-surface humidity composites for rainfall days occurring under each circulation pattern. The circulation was dominated by the monsoon anticyclone being over or to the immediate east of the basin. The anticyclone was shifted to the northwest (east) of its seasonal mean position on rainfall days in the central portion of the basin (far eastern portion of the basin). Rainfall influenced by gulf surges was most likely when the monsoon anticyclone was shifted westward, especially northwestward, of its typical position. The central portion of the basin received substantially more surge-influenced rainfall than did the far eastern portion of the basin.
Class in the Classroom: Engaging Hidden Identities

Using Marcuse's theory of the total mobilization of advanced technology society along the lines of what he calls “the performance principle,” I attempt to describe the complex composition of class oppression in the classroom. Students conceive of themselves as economic units, customers pursuing neutral interests in a morally neutral, socio-economic system of capitalist competition. The classic, unreflective conception of the classroom responds to this by implicitly endorsing individualism and ideals of humanist citizenship. While racism and cultural diversity have come to count as elements of liberal intelligence in most college curricula, attempts to theorize these aspects of social and individual identity and place them in a broader content of class appear radical and inconsistent with the humanistic notion that we all have control over who we are and what we achieve. But tags such as “radical” and “unrealistic” mark a society based on the performance principle. Marcuse allows us to recognize a single author behind elements of psychology, metaphysics, and capitalism. The fact that bell hooks hits upon a similar notion suggests that we might use Marcuse's theory of the truly liberatory potential of imagination to transform and reconceive our classrooms so that the insidious effects of class, racism, and individualistic apathy might be subverted. Specifically, I outline and place into this theoretical context three concrete pedagogical practices: (a) the use of the physical space of the classroom; (b) the performance of community through group readings and short full-class ceremonies, and (c) the symbolic modeling represented by interdisciplinary approaches to teaching. All three of these practices engage students in ways that co-curricularly subvert class (and, incidentally, race divisions) and allow students to imagine, and so engage in, political action for justice as they see it.
Visual Accommodation in the Green Turtle

Ophthalmological and anatomical studies indicate that the Atlantic green turtle is extremely myopic when its eyes are out of water. This finding bears on current theories of visual orientation and navigation in these animals.
Olivine/liquid distribution coefficients and a test for crystal-liquid equilibrium

We present major and trace element data for olivines and rapidly quenched groundmass material separated from eight samples of basaltic rock. From these data apparent olivine/liquid distribution coefficients (D) for the elements Mg, Mn, Ni, Co, Cr, Sc, Na, Sm, and Ca have been calculated. Petrographic and electron microprobe studies indicate that olivines in most of these samples are but slightly zoned and groundmass glasses are essentially uniform in composition; these data suggest that the co-existing olivine-groundmass pairs are in equilibrium. In addition, olivine crystallization temperatures were calculated using experimental calibrations of lnD vs.1/T for the elements Mg, Fe, Mn, Ni, and Co. A high degree of concordancy for the resulting temperatures, based on five different elements for most samples, also suggests that olivine-groundmass equilibrium was obtained. We conclude that the apparent olivine/liquidD's derived from this study are representative of equilibriumD's, but emphasize that variations in temperature, and possibly bulk composition, strongly affect suchD's in natural magmas.
Reduced symptoms and need for antisecretory therapy in veterans 3 years after Helicobacter pylori eradication with ranitidine bismuth citrate/amoxicillin/clarithromycin.

Abstract OBJECTIVE: The most effective combination therapy to eradicate Helicobacter pylori has not yet been found. The perfect combination would be effective, relatively free of side effects, and easy to comply with. We studied a 14-day course of three medications taken twice daily by H. pylori–infected patients who were enrolled in the outpatient Veterans Affairs (VA) clinics. The two major objectives were 1) to determine the effectiveness of the combination therapy and 2) to determine the compliance of patients in a VA population. METHODS: Fifty-two male patients were identified with H. pylori infection by positive CLO (Rapid Urease Test) test, positive Giemsa stain, or positive serology. Active infection was confirmed by a positive 13C urea breath test (UBT). Patients were treated for 14 days with open-label triple-combination therapy of ranitidine bismuth citrate (RBC; 400 mg b.i.d.), amoxicillin (1000 mg b.i.d.), and clarithromycin (500 mg b.i.d.). Successful eradication of H. pylori was confirmed by repeat UBT at 6–8 wk after the final dose of therapy. RESULTS: Of the 52 enrolled patients, 49 (94.2%) met the criteria for successful completion of the study (per protocol analysis based on compliance with at least 80% of medication and performance of both UBTs). Of the three patients who did not successfully complete, one was cured (after 6 days of treatment), and two remained infected (after 3 days and 9 days of treatment). Of the 49 completed patients, 45 (91.8%) were cured, and four remained infected. Overall, regardless of compliance (intent-to-treat analysis), 46 of the 52 (88.4%) patients had documented cure of H. pylori infection as determined by the posttreatment UBT. By 3 yr after H. pylori eradication, two of 15 (13.3%) patients who were not on baseline medications had developed the need for antisecretory therapy, but 18 of 31 (58.1%) who were on baseline medications were able to stop therapy. Thus, at 3 yr, successful H. pylori eradication decreased the need for antisecretory therapy from 67.4% of the H. pylori–infected population to 43% of the H. pylori–eradicated population. The effect of H. pylori eradication in improving symptoms at 3 yr was statistically significant in both the ulcer population and the nonulcer population. Adverse events were mild, and included diarrhea (26 patients), bad taste in mouth (24 patients), nausea/upset stomach (nine patients), and headache (two patients). The diarrhea was self-limiting in 25 of the 26 patients. Only two patients discontinued medication because of adverse events. CONCLUSION: The RBC/amoxicillin/clarithromycin combination was, in our VA population, an easily complied with, highly effective, and safe triple therapy with a 90% H. pylori eradication rate. Successful eradication of H. pylori leads to a dramatic decrease in upper-gut symptoms and decreased need for antisecretory therapy.
Focus Issue: Turning the Corner in Cancer Therapy?

This week’s issues of Science and Science ’s STKE are devoted to cancer research and to exploring how recent discoveries may impact our ability to diagnose and treat cancer. Science 9s STKE focuses on mechanisms by which growth factor–mediated stimulation of hypoxia-inducible factor signaling contributes to cancer progression and research that suggests a role as a tumor suppressor for a splicing variant of the c-H-ras oncogene.
Glycoprotein VI agonists have distinct dependences on the lipid raft environment.

Summary. Background: It has been reported that the association of glycoprotein VI (GPVI) with lipid rafts regulates GPVI signaling in platelets. Objective: Secreted adenosine 5′-diphosphate (ADP) potentiates GPVI-induced platelet aggregation at particular agonist concentrations. We have investigated whether the decrease in GPVI signaling, previously reported in platelets with disrupted rafts, is a result of the loss of agonist potentiation by ADP. Methods: We disrupted platelet lipid rafts with methyl-β-cyclodextrin and measured signaling events downstream of GPVI activation. Results: Lipid raft disruption decreases aggregation induced by low concentrations of convulxin, but this decrease is almost eliminated in the presence of ADP antagonists. Signaling indicators, such as protein phosphorylation and calcium mobilization, were not affected by raft disruption in collagen or convulxin stimulated platelets. Interestingly, however, raft disruption directly reduced GPVI signaling induced by collagen-related peptide. Conclusions: Lipid rafts do not directly contribute to signaling by the physiologic agonist collagen. The effects of disruption of lipid rafts in in vitro assays can be attributed to inhibition of ADP feedback that potentiates GPVI signaling.
Teaching applied ethics to the righteous mind

What does current empirically informed moral psychology imply about the goals that can be realistically achieved in college-level applied ethics courses? This paper takes up this question from the vantage point of Jonathan Haidt’s Social Intuitionist Model of human moral judgment. I summarize Haidt’s model, and then consider a variety of pedagogical goals. I begin with two of the loftiest goals of ethics education, and argue that neither is within realistic reach if Haidt’s model is correct. I then look at three goals that can be achieved if his model is correct; but each of these goals, I argue, lacks significant value. I end by identifying three goals that are of significant value and also realistically attainable on Haidt’s model. These should be the focus of applied ethics pedagogy if Haidt’s model is correct.
Myocardial tissue salvage by coronary thrombolysis with rt-PA: Absence of occlusion/reperfusion injury

The effect of recombinant tissue-type plasminogen activator (rt-PA) on myocardial infarct size was studied in a coronary thrombosis model in open-chested, anaesthetised beagle dogs. Myocardial ischaemia was produced by localised thrombosis via endothelial injury and instillation of thrombin and fresh blood into the left anterior descending coronary artery (LAD). Myocardial infarct size and the area at risk were determined histochemically after 24 h of reperfusion by ex vivo staining of the LAD bed with 1.5% triphenyltetrazolium chloride (TTC). In non-reperfused animals the persistance of a coronary thrombus resulted in 50.7 ± 5.0% of the area at risk developing an infarct. Intravenous administration of rt-PA at a rate of 12 500 IU/kg/min delivered for 60 min resulted in recanalisation of the thrombosed artery within 16.1 ± 4.1 min in animals in which the thrombus was in place for 75 min and within 19.0 ± 2.8 min after 165 min of stable thrombosis. Lysis of the coronary thrombus and subsequent reperfusion was not accompanied by reactive hyperaemia nor ventricular arrhythmias. Infarct size was reduced to 1.5 ± 1.2% and 6.3 ± 4.1% of the area at risk in the animals whose coronary thrombi were lysed with rt-PA after 1.5 and 3 h of ischaemia, respectively. In contrast, mechanical reperfusion after 1.5 h of ischaemia induced by ligation resulted in an infarct of 35.1 ± 4.5% of the area at risk. These results suggest that rt-PA has an additional cardioprotective effect independent of lysis of the thrombosed coronary artery.
Atomic basis of CRM1-cargo recognition, release and inhibition.

Abstract CRM1 or XPO1 is the major nuclear export receptor in the cell, which controls the nuclear-cytoplasmic localization of many proteins and RNAs. CRM1 is also a promising cancer drug target as the transport receptor is overexpressed in many cancers where some of its cargos are misregulated and mislocalized to the cytoplasm. Atomic level understanding of CRM1 function has greatly facilitated recent drug discovery and development of CRM1 inhibitors to target a variety of malignancies. Numerous atomic resolution CRM1 structures are now available, explaining how the exporter recognizes nuclear export signals in its cargos, how RanGTP and cargo bind with positive cooperativity, how RanBP1 causes release of export cargos in the cytoplasm and how diverse inhibitors such as Leptomycin B and the new KPT-SINE compounds block nuclear export. This review summarizes structure–function studies that explain CRM1-cargo recognition, release and inhibition.
The Azteca-Cecropia association: Are ants always necessary for their host plants?

We assessed the effects of Azteca alfari presence on herbivory and growth of saplings for two Amazonian Cecropia species. For both species, rates of herbivory were low and did not differ between ant-removed and ant-maintained plants. Plant growth, measured over six months, was also similar among treatments. This is the first experiment to show that in its native mainland habitat, Cecropia may suffer low incidence of attack by insect herbivores in the absence of associated ants.
The incorporation in vitro of labeled amino acids into the proteins of normal and regenerating rat liver.

Abstract The in vitro amino acid incorporation system obtained from regenerating rat liver differs from that obtained from normal rat liver mainly in two ways. First, the regenerating system incorporates [I- 14 C]leucine into its protein at a linear rate for twice the length of time that the normal system does, and second, the regenerating system has an increased tolerance over that of the normal system to changes in pH. The linear rates of amino acid incorporation in the two systems differ by no more than about 10% when the results are expressed in terms of equivalent amounts of microsomal-RNA.
MR Imaging Assessment of Arthritis of the Knee

The magnetic resonance (MR) imaging presentations of arthritis of the knee are important for radiologists to recognize because these disorders are often clinically unsuspected. When they are known or clinically suspected, knowledge of imaging features allows for the confirmation and characterization of the extent of disease. This article reviews the fundamental MR imaging manifestations of rheumatologic disorders of the knee and their presentation in specific arthropathies.
Effects of three feedback conditions employing videotape and audiotape on acquired speech skill

Students from a university Fundamentals of Speech course were randomly assigned to three groups for outside‐of‐class electronic feedback of within‐class speeches: (1) videotape replay, (2) audiotape replay, and (3) control. During the semester, all subjects received traditional feedback from their instructors and peers. Nine trained judges provided highly reliable ratings of videotape recordings of all subjects’ pretreatment and posttreatment speeches using the multi‐dimensional Price speech skill measurement instrument. Analyses indicated that all groups showed significant improvement during the course. However, in final speeches, videotape subjects demonstrated significantly greater speech skill than audiotape subjects; no differences were found between audiotape and control subjects.
The relationship of locus of control dimensions to reported hostility and aggression

The Fatalism and Social System Control dimensions of the Reid-Ware Three-Factor Locus of Control Scale were correlated with the two main factors of the Buss-Durkee Hostility-Aggression Inventory. For the total sample of 61 male and 96 female undergraduates, both locus of control dimensions correlated significantly with the Hostility factor. Externals on each dimension reported greater hostility than did internals. Only the Fatalism dimension correlated with the Aggression factor, with externals reporting more aggression than internals. For males, only the Fatalism dimension was significantly correlated with the Hostility factor. Both the Fatalism and Social System Control dimensions correlated with the Hostility factor among the females, but the correlation with the latter dimension was slightly stronger. Neither locus of control dimension was correlated significantly with the Aggression factor when data from males and females were analyzed separately.
Gender Differences in Sales Managers' Perceptions of Occupational Gender Stereotypes:

This study of gender stereotypes within a traditionally male occupation was based on the hypothesis that male managers would describe their female subordinates as more closely resembling occupational gender stereotypes than would female managers. A survey was conducted of 77 U.S. managers who supervised women in the traditionally male occupation of industrial sales. All the managers described their subordinate saleswomen (n = 202) on gender stereotypes relating to their “selling ability,” their “human relations ability,” and their “motivation.” The presence of some stereotypic thinking was evident. Male managers described the “selling ability” of their female subordinates more stereotypic ally than did 19 female managers. No significant gender differences were noted between male and female managers' perceptions of saleswomen's “human relationships” and “motivation.” The implications of these findings are discussed.
Vitamin B6 and Immune Competence

Animal and human studies suggest that vitamin B6 deficiency affects both humoral and cell-mediated immune responses. Lymphocyte differentiation and maturation are altered by deficiency, delayed-type hypersensitivity responses are reduced, and antibody production may be indirectly impaired. Although repletion of the vitamin restores these functions, megadoses do not produce benefits beyond those observed with moderate supplementation. Additional human studies indicate that vitamin B6 status may influence tumor growth and disease processes. Deficiency of the vitamin has been associated with immunological changes observed in the elderly, persons infected with human immunodeficiency virus (HIV), and those with uremia or rheumatoid arthritis. Future research efforts should focus on establishing the mechanism underlying the effects of vitamin B6 on immunity and should attempt to establish safe intake levels that optimize immune response.
The Discounted Economic Stock of Money with VAR Forecasting

We measure the economic capital stock of money implied by the Divisia monetary aggregate service flow, in a manner consistent with asset pricing theory. Based on Barnett’s (Monetary policy on the 75th anniversary of the Federal Reserve System, pp. 232–244, Kluwer, Boston, 1991) definition of the economic stock of money, we estimate the expected discounted flow of expenditure on the services of monetary assets, where expenditure on monetary services is evaluated at the user costs of the monetary components. We use forecasts based on martingale expectations, asymmetric vector autoregressive expectations, and the Bayesian vector autoregressive expectations. We find the resulting capital-stock index to be surprisingly robust to the modeling of expectations.
The prophylaxis of rat and mouse mammary gland tumorigenesis by suppression of prolactin secretion: A reappraisal

The purpose of this study was to evaluate the effect of early and temporal CB-154 induced suppression of prolactin secretion on the genesis of mammary tumors in female Sprague-Dawley rats treated i.g. with 3 doses of 7,12-dimethylbenzanthracene (DMBA); doses which yield a high (20 mg), moderate (5 mg) and low (1.25 mg) mammary carcinoma incidence. In addition, the effect of prolactin suppression on the genesis of mammary tumors in strains of rodents which, when treated with maximally tolerated doses of DMBA, develop a moderate (female Lewis rats) and a low (female Long-Evans rats and female Balb/c mice) mammary carcinoma incidence was also evaluated. Daily suppression of prolactin secretion during DMBA treatment (30 days before, during and 30 days after) (series 1) or commencing 30 days after DMBA treatment (for 60–81 days) (series 2) significantly (P<0.05) reduced the number of mammary carcinomas in Sprague-Dawley rats treated with 20 and 5 mg DMBA and in Lewis rats (series 2); treatment with CB-154 did not significantly lower mammary carcinoma incidence in Sprague-Dawley rats treated with 1.25 mg DMBA, nor in Lewis rats (series 1), Long-Evans rats and Balb/c mice. These results provide evidence that the effectiveness of prolactin suppression in the prophylaxis of chemical carcinogenesis of the rodent mammary gland is enhanced when a moderate or large dose of the carcinogen is used, or a strain of rodent is used which is moderately or highly susceptible to the mammary oncogenic effects of the carcinogen. Low doses of the carcinogen or use of a rodent strain relatively resistent to the carcinogen nullifies the chemopreventive activities of early prolactin suppression.
One-dimensional shock waves in uniformly distributed granular materials

Abstract Using a one-dimensional model for uniformly distributed granular solids, it is shown that the discontinuity in the porosity must be second order across a shock wave. This result implies that the Hugoniol properties of shock waves and their growth and decay behavior are qualitatively similar to those for homogeneous nonlinear elastic solids, but are quantitatively influenced by the initial porosity.
INTERPRETING CHILDREN'S PLAY

Abstract This paper discusses categories by which puzzling children can be identified by observing their play. Categories for interpreting children's play are outlined for cognitive play, social play, and play with language. Descriptors of normative behavior for each of these modes of play are provided. Recommendations for further assessment are made for each play mode.
Swelling-induced instabilities in microscale, surface-confined poly(N-isopropylacryamide) hydrogels

A hydrogel is a three-dimensional hyperelastic polymer network that swells to a specific volume upon exposure to a penetrating solvent. If mechanical constraints interfere with the swelling process, anisotropic compressive stresses are generated, which may manifest in local or global instabilities. Herein, we employ confocal microscopy for the in situ, three-dimensional study of micron-scale hydrogels that are pinned to a solid substrate. Depending on the initial geometry of the hydrogel, four general modes of swelling-induced deformation were found: lateral differential swelling, local sinusoidal edge buckling, bulk sinusoidal buckling, and surface creasing. The transition between local edge buckling and bulk buckling is consistent with linear elastic theory; however, linear theory cannot be used to predict many details of the swollen structures. Whereas global buckling has a well-defined wavelength that depends on height of the hydrogel structure, edge buckling appears to be independent of height and depends on sample history. Moreover, edge buckling can appear in globally buckled structures, suggesting two different mechanisms for the two instabilities.
LASER TRABECULOPLASTY AND ITS EFFECT ON TONOGRAPHY, CENTRAL VISUAL FIELDS, AND ANTERIOR CHAMBER DEPTH. A PRELIMINARY STUDY

A preliminary study of ten patients with glaucoma, each of whom has undergone laser trabeculoplasty to one or both eyes, is presented. Tonography-on-treatment was performed on each patient approximately four weeks prior to laser, and repeated approximately ten weeks afterwards. Central fields and anterior chamber depth measurements before and after laser trabeculoplasty are also presented. Intraocular pressures fell by a mean of 12.34 mm (SD +/- 8.5, range 3-23) in all 12 lasered eyes. Central fields improved in ten eyes, and the anterior chamber of treated eyes became shallower by an average of 0.27 mm, compared with untreated eyes (p less than 0.05). Po/C values improved in 11 treated eyes. Very little attempt was made to alter medical treatment during the period outlined above.