cssi/SciSciGPT-SciSciNet huggingface dataset:
Characteristics of thymidylate synthase purified from a human colon adenocarcinoma

Abstract Thymidylate synthase has been purified >4000-fold from a human colon adenocarcinoma maintained as a xenograft in immune-deprived mice. In this disease, the enzyme is an important target for the cytotoxic action of 5-fluorouracil, which is influenced by the reduced folate substrate CH 2 -H 4 PteGlu. Due to the importance of this interaction, and the existence in cells of folate species as polyglutamyl forms, the interaction of folylpolyglutamates with thymidylate synthase was examined. Polyglutamates of PteGlu were used as inhibitors, and the interaction of CH 2 -H 4 PteGlu polyglutamates as substrates or in an inhibitory ternary complex were also examined. Using PteGlu 1–7 , K i values were determined. A maximal 125-fold decrease in K i was observed between PteGlui and PteGlu 4 ; further addition of up to three glutamyl residues did not result in an additional decrease in K i . Despite the increased binding affinity of folylpolyglutamates for this enzyme, no change in the K m values for either dUMP (3.6 μ m ) or CH 2 -H 4 PteGlu (4.3 μ m ) were detected when polyglutamates of [6 R ]CH 2 -H 4 PteGlu were used as substrates. Product inhibition studies demonstrated competitive inhibition between dTMP and dUMP in the presence of CH 2 -H 4 PteGlu 5 . In addition, CH 2 H 4 PteGlu 4 stabilized an inhibitory ternary complex formed between FdUMP, thymidylate synthase, and CH 2 -H 4 PteGlu 4 . Thus the data do not support a change in the order of substrate binding and product release upon polyglutamylation of CH 2 -H 4 PteGlu reported for non-human mammalian enzyme. This is the first study to characterize kinetically thymidylate synthase from a human colon adenocarcinoma.
Gating demultiplexer integrated with MSM detector array in InGaAs/AlGaAs/GaAs for WDM

The authors demonstrate the integration of a grating demultiplexer with curved output waveguides and a MSM photodetector array in InGaAs/AlGaAs/GaAs operating in the 1- mu m wavelength region. The structure provides 38 channels with 1-nm channel spacing. The total loss, including scattering from the unmetallized grating, is about 17 dB. A channel crosstalk of -11 dB is obtained. The FWHM of the channel pass band is 0.5 nm. >
Experimental constraints on the origin of Martian meteorites and the composition of the Martian mantle

Abstract The major element compositions of partial melts of a chondritic (Homestead L5) model Mars mantle have been determined at 4.7–5.0 GPa in a multi-anvil device over a temperature interval that ranged from near solidus to near liquidus conditions. The purpose of these experiments is to determine if the major element abundances of Martian basalts (shergottite meteorites) or their parent magmas can be derived from a model Martian mantle composition at high pressure. Partial melting of our model composition at 4.7–5.0 GPa produces liquids with super-chondritic CaO/Al 2 O 3 similar to those of proposed Martian basalt parent magmas. The concentrations of CaO and Al 2 O 3 in the high-pressure experimental liquids are, however, lower than in Martian basalt parent magmas. We conclude that matches for both ratios and concentrations involving CaO and Al 2 O 3 between current model Mars compositions and proposed Martian basalt parent magmas would require at least two stages of magmatic differentiation. For example, partial melting at 5 GPa (425 km depth in Mars) produces a magma having super-chondritic CaO/Al 2 O 3 , but subsequent, lower pressure differentiation of olivine (±low-Ca pyroxene) is needed to increase the CaO and Al 2 O 3 concentrations to those of calculated Martian basalt parent magmas. This two-stage polybaric differentiation would be consistent with either a magma ocean or mantle plume-melting scenario. On the other hand, these multi-stage differentiation scenarios cannot reconcile the significant mismatch between the FeO content of our experimental liquids and Martian basalt parent magmas. A remedy for this apparent inconsistency might require a bulk Martian mantle or shergottite parent source region with a composition and Mg# closer to that of H-chondrites, but still much less magnesian than are terrestrial upper-mantle basalt source regions.
Inhibition of Mitochondrial Respiration A NOVEL STRATEGY TO ENHANCE DRUG-INDUCED APOPTOSIS IN HUMAN LEUKEMIA CELLS BY A REACTIVE OXYGEN SPECIES-MEDIATED MECHANISM

Cancer cells are under intrinsic increased oxidative stress and vulnerable to free radical-induced apoptosis. Here, we report a strategy to hinder mitochondrial electron transport and increase superoxide O2. radical generation in human leukemia cells as a novel mechanism to enhance apoptosis induced by anticancer agents. This strategy was first tested in a proof-of-principle study using rotenone, a specific inhibitor of mitochondrial electron transport complex I. Partial inhibition of mitochondrial respiration enhances electron leakage from the transport chain, leading to an increase in O2. generation and sensitization of the leukemia cells to anticancer agents whose action involve free radical generation. Using leukemia cells with genetic alterations in mitochondrial DNA and biochemical approaches, we further demonstrated that As2O3, a clinically active anti-leukemia agent, inhibits mitochondrial respiratory function, increases free radical generation, and enhances the activity of another O2.-generating agent against cultured leukemia cells and primary leukemia cells isolated from patients. Our study shows that interfering mitochondrial respiration is a novel mechanism by which As2O3 increases generation of free radicals. This novel mechanism of action provides a biochemical basis for developing new drug combination strategies using As2O3 to enhance the activity of anticancer agents by promoting generation of free radicals.
Characterizing hydrology and the importance of ground-water discharge in natural and constructed wetlands.

Although considered the most important component for the establishment and persistence of wetlands, hydrology has been hard to characterize and linkages between hydrology and other environmental conditions are often poorly understood. In this work, methods for characterizing a wetland’s hydrology from hydrographs were developed, and the importance of ground water to the physical and geochemical conditions in the root zone was investigated. Detailed sampling of nearly continuous hydrographs showed that sites with greater ground-water discharge had higher water tables and more stable hydrographs. Subsampling of the continuous hydrograph failed to characterize the sites correctly, even though the wetland complex is located in a strong regional ground-water-discharge area. By comparing soil-moisture-potential measurements to the water-table hydrograph at one site, we noted that the amount of root-zone saturation was not necessarily driven by the water-table hydrograph but can be a result of other soil parameters (i.e., soil texture and associated capillary fringe). Ground-water discharge was not a significant determinant of maximum or average temperatures in the root zone. High ground-water discharge was associated with earliest date of thaw and shortest period of time that the root zone was frozen, however. Finally, the direction and magnitude of shallow ground-water flow was found to affect the migration and importance of a geochemical species. Areas of higher ground-water discharge had less downward penetration of CO2 generated in the root zone. In contrast, biotically derived CO2 was able to penetrate the deeper ground-water system in areas of ground-water recharge. Although ground-water flows are difficult to characterize, understanding these components is critical to the success of wetland restoration and creation efforts.
Protein substrate specificity of a calmodulin-dependent protein kinase isolated from bovine heart

The protein substrate specificity of a calmodulin-dependent protein kinase activity from the cytosolic fraction of bovine heart was examined. Prior to the experiments, the kinase activity was purified more than 50-fold with a recovery of greater than 10% of the homogenate activity. Two endogenous protein substrates of molecular weight 57,000 and 73,000 were phosphorylated in these kinase preparations. The kinase preparation was also able to phosphorylate exogenous synapsin, phospholamban, glycogen synthase, MAP-2, myelin basic proteins and κ-casein, but not tubulin, pyruvate kinase, the regulatory subunit of cAMP protein kinase II, myosin light chain or phosphorylase b. High levels of calmodulin were required for activation of the kinase activity toward the 57,000 and 73,000 molecular weight endogenous substrates (K0.5 = 93 +/- 5 nM), glycogen synthase (K0.5 = 127 +/- 10 nM), and κ-casein (K0.5 = 321 +/- 107 nM). The kinase possessed a high affinity for glycogen synthase (half maximal activity at 0.9 +/- 0.4 μM) but a low affinity for κ-casein (21 +/- 2 μM). Sucrose density gradient centrifugation separated the calmodulin-dependent protein kinase activity into two fractions with apparent molecular weights of approximately 900,000 and 100,000. Both fractions phosphorylated the endogenous 57,000 molecular weight substrate and glycogen synthase similarly. These results indicate that cardiac calmodulin-dependent protein kinase previously observed to phosphorylate endogenous protein substrate possesses a wide range of substrate specificity.
TU‐EE‐A4‐02: Impact of Ultrasound‐Guided Patient Setup On OAR Dose in Conformal Radiation Therapy for Prostate Carcinoma

Purpose: To evaluate the impact of daily ultrasound‐guided patient repositioning on bladder and rectal dose in the treatment of prostate carcinoma with conformal radiation therapy.Method and Materials: Standard‐of‐care for the treatment of low and intermediate risk prostate carcinoma currently includes 3D conformal radiation therapy (3D‐CRT). During external beam therapy, ultrasound‐guided isocenter realignment can be performed daily to correct patient setup for prostate motion (up to 1 cm) relative to bony anatomical landmarks. In this study, five patients with substantial ultrasound‐documented inter‐fraction prostate motion during their treatment course were selected. Starting with the original treatment plan, two additional plans were retrospectively generated for each patient. In one set, using the ultrasound documented displacements, organ contours were moved for each fraction, thus simulating positioning with misalignment caused by organ motion if ultrasound guidance were not used. In a second set of plans, the isocenter was shifted, as were the organ contours, simulating realignment based on the ultrasoundimage. In all cases, the number of planned monitor units was set to those of the original plan. For a given patient, isodose distributions, DVHs and EUDs were calculated for the prostate, bladder, and rectum for each fraction and then combined for each shift condition. Results: In all reconstructed plans, there were no substantial changes in dose coverage of the prostate (<0.21 % change in EUD) compared to the original plan. However, in some cases with no realignment, higher dose maxima were predicted in the bladder and rectum, with the consequent EUD for each organ significantly greater compared to the original plan. Conclusion: Although fractional organ motions may have little effect on the overall dose delivery to the prostate, the effect on the dose to OARs (rectum and bladder) can be significant if no daily realignment is performed.
Manganese Stabilizing Protein of Photosystem II Is a Thermostable, Natively Unfolded Polypeptide†

The thermostability of manganese stabilizing protein of photosystem II was examined by biochemical and spectroscopic techniques. Samples of both native and recombinant spinach manganese stabilizing protein incubated at 90 °C and then cooled to 25 °C were capable of rebinding to, and of reactivating, the O2-evolution activity of photosystem II membranes from which the native protein had been removed. Far-UV circular dichroism and FT-IR spectroscopies were used to analyze the structural consequences of heating manganese stabilizing protein. The data obtained from these techniques show that heating causes a complete loss of the protein's secondary structure, and that this is a reversible, noncooperative phenomenon. Upon cooling, the secondary structures of the heat-treated proteins return to a state similar to, but not identical with, that of the native, unheated controls. Restoration of a near-native tertiary structure is confirmed both by size-exclusion chromatography and by near-UV circular dichroism. The...
An arterial grid of dirt roads

Between 2000 and 2030, cities in developing countries will double their population from 2 to 4 billion and at least triple their total built-up area. This essay assesses the state of preparedness for the projected urban expansion. The available anecdotal evidence suggests that areas needed for expansion are typically underestimated, that enforcement of land use regulations is relatively weak and cannot protect open space from development, and that essential arterial roads are commonly in short supply. The author proposes adopting a proactive strategy that does not overly rely on land use regulation, focusing instead on the layout and early acquisition of the right-of-way for an arterial road network, a 1-km-wide urban grid covering the entire area of expected expansion. This article reports on seven intermediate cities in Ecuador that are engaged in implementing this strategy, and examines the merits and pitfalls of pursuing it in Ecuador and elsewhere.
Aeroacoustics of supersonic jet flows from a contoured plug-nozzle

The results of an experimental study of the acoustic far-field, the shock-associated noise, and the nature of the repetitive shock structure of supersonic jet flows issuing from a plug-nozzle having an externally expanded contoured plug with a pointed termination, operated at a range of supercritical pressure ratios £ = 2.0 to 4.5, are reported. The supersonic jet flow from the contoured plug-nozzle (CPN) is shown to be shock free and virtually wakeless at pressure ratio £ = 3.60 (fully expanded jet flow Mach number M7 = 1.49). As compared with the noise characteristics of underexpanded jet flows from an "equivalent" convergent nozzle, substantial reductions in the overall sound pressure levels (OASPL's) are achieved at all observation angles in the entire range of the pressure ratios. The typical bucket-type behavior of the OASPL vs MJ9 characteristic of supersonic jet flows from the contoured convergent-divergent (CD) nozzle, is not observed for the CPN operated over a range of supercritical pressure ratios. At the off-design conditions, the noise reductions for the CPN are higher than for the equivalent contoured CD nozzle. Moreover, the noise intensity of the CPN nozzle jet flows scales to the second power of the shock-strength related parameter 0 = (M/ 1)' and not to the fourth power as observed for the underexpanded jet flows from a convergent round nozzle. Similarly, the OASPL's of the CPN scale to ft =MJ-Md and not to /3? as reported for the contoured CD nozzle where Md is the design Mach number of either the CPN or the contoured CD nozzle.
Reduced Ki67 Staining in the Postmortem State Calls Into Question Past Conclusions About the Lack of Turnover of Adult Human β-Cells

Some report that adult human β-cells do not replicate, but we postulate this assumption is erroneous due a postmortem decline in replication markers such as Ki67. Our earlier report showed that Ki67-marked β-cells were rarely found in human cadaveric pancreases but were in the range of 0.2–0.5% in human islets transplanted into mice. This study subjected 4-week-old mice to autopsy conditions that typically occur with humans. Mice were killed, left at room temperature for 3 h, and then placed at 4°C for 3, 9, or 21 h. There was a rapid marked fall in Ki67 staining of β-cells compared with those fixed immediately. Values at death were 6.9 ± 0.9% (n = 6) after a 24-h fast, 4.1 ± 0.9% (n = 6) at 3 h room temperature, 2.7 ± 0.7% (n = 5) at 6 h, 1.6 ± 0.6% (n = 5) at 12 h, and 2.9 ± 0.8% (n = 5) at 24 h. Similar postmortem conditions in newborn pigs resulted in very similar declines in Ki67 staining of their β-cells. These data support the hypothesis that conclusions on the lack of replication of adult human β-cells are incorrect and suggest that adult human β-cells replicate at a low but quantitatively meaningful rate.
Engaging Absent Fathers in the Treatment of Children

Absent fathers are often excluded from the treatment of their children for various reasons. They are often marginalized by mothers, and unintentionally excluded by clinicians. Absent fathers are also excluded from treatment in fear that their presence might undermine the competencies of single mothers, which social service agencies serve to empower. This article will discuss the potential benefits of including absent fathers in family therapy, and how to work with them once engaged in treatment.
Molecular epidemiology of Staphylococcus aureus in households of children with community-associated S aureus skin and soft tissue infections

Objectives Although colonization traditionally is considered a risk factor for Staphylococcus aureus infection, the relationship between contemporary S aureus colonization and infection is not well characterized. We aimed to relate the presence of colonizing and disease-causing strains of S aureus within individuals and households. Study design In a prospective study of 163 pediatric outpatients (cases) with community-associated S aureus skin and soft tissue infections in St Louis, infection isolates were obtained from cases and colonization cultures were obtained from cases and their household contacts (n = 562). Molecular typing by repetitive sequence-based polymerase chain reaction was used to compare infecting and colonizing isolates within each case. The infecting strain from each case was compared with S aureus strains colonizing household contacts. The colonization status of cases was followed for 12 months. Results A total of 27 distinct strain types were identified among the 1299 S aureus isolates evaluated. Between 1 and 6 distinct strain types were detected per household. A total of 110 cases (67%) were colonized at 1 or more body sites with the infecting strain. Of the 53 cases with an infecting strain that did not match a colonizing strain, 15 (28%) had 1 or more household contacts with a colonizing strain that matched the infecting strain. Intrafamilial strain-relatedness was observed in 105 families (64%). Conclusion One-third of cases were colonized with a different strain type than the strain causing the skin and soft tissue infection. Fewer than one-third of cases with discordant infecting and colonizing isolates could be linked to the strain from another household contact, suggesting acquisition from sources outside the household.
Effect of Abrupt Ration Changes on Milk and Blood Components

Abstract The effect of abrupt change between a normal and a fat-depressing ration on milk composition and several blood components was examined. An abrupt ration change was accomplished by simultaneously switching rumen contents and rations between two cows, one fed a ration having a grainto-roughage ratio of approximately 1:2 and the other a fat-depressing ration with a 3:1 ratio. Feed intake was not altered when the cows were abruptly switched from one ration to the other. Five to six days were necessary to affect complete transition in the level of milk fat following a ration change. This was interpreted to mean that the ration effect on milk fat content was eventually mediated through time-consuming metabolic adaptations by the host, rather than by immediate availability or supply of acetate, propionate, or butyrate from the rumen. Arterial levels of blood glucose, ketones, acetate, and triglycerides with the normal ration were 50.2, 2.13, 12.6, and 11.1 mg/100 ml, respectively. Corresponding values with the fat-depressing ration were 56.3, 2.44, 7.9, and 11.5 mg/100 ml. Values for blood glucose and acetate were significantly different (P
At the nexus between pattern formation and cell-type specification: the generation of individual neuroblast fates in the Drosophila embryonic central nervous system.

The specification of specific and often unique fates to individual cells as a function of their position within a developing organism is a fundamental process during the development of multicellular organisms. The development of the Drosophila embryonic central nervous system serves as an excellent model system in which to clarify the developmental mechanisms that link pattern formation to cell-type specification. The Drosophila embryonic central nervous system develops from a set of neural stem cells termed neuroblasts. Neuroblasts arise from the ectoderm in an invariant pattern, and each neuroblast acquires a unique fate based on its position within this pattern. Two groups of genes recently have been demonstrated to govern the individual fate specification of neuroblasts. One group, the segment polarity genes, enables neuroblasts that develop in different anteroposterior positions to acquire different fates. The second group, referred to as the columnar genes, ensures that neuroblasts that develop in different dorsoventral domains assume different fates. When integrated, the activities of the segment polarity and columnar genes create a Cartesian coordinate system that bestows unique fates to individual neuroblasts as a function of their position of formation within the ectoderm. BioEssays 1999;21:922-931.
Prior pregnancy ameliorates the course of intra-abdominal desmoid tumors in patients with familial adenomatous polyposis

PURPOSE: Intra-abdominal desmoid tumors occur in 12 percent of patients with familial adenomatous polyposis. A minority grow quickly and are lethal, most are relatively inert, and some cause problems by obstructing adjacent organs. Desmoid tumors may be estrogen-dependent, and estrogen-blocking drugs are part of the usual treatment of these tumors. This study was performed to examine the effect of pregnancy on the course of patients with familial adenomatous polyposis and intra-abdominal desmoids. METHODS: All females with familial adenomatous polyposis and an intra-abdominal desmoid treated or followed up at this institution were eligible. Stable, asymptomatic desmoids were followed up yearly with examination and CT scan. Growing or symptomatic desmoids were followed up at least every six months. Maximum tumor size was grouped as follows: 20 cm. A change in tumor size was defined as a change of ±50 percent or more of maximum diameter. Stable tumors showed no change in diameter during the study period; variable growth was defined as a significant change in either direction that was followed by a return to previous dimensions or a stabilization of growth. Rapid growth was a doubling of diameter within three months. Pregnant females were compared with nonpregnant females. Subgroups of females were matched for age at diagnosis of desmoid. RESULTS: Twenty-two females had never been pregnant, whereas 25 had been pregnant at least once. Eleven pairs were matched for age. There were no differences between groups in the incidence of extracolonic manifestations of familial adenomatous polyposis, family history of desmoids, number or type of surgeries done for familial adenomatous polyposis, length of follow-up, or time from surgery to desmoid diagnosis. Desmoids in pregnant females had a significantly more benign course: 18 were stable (vs. 6 nonpregnant females), 2 had variable growth (vs. 10), 1 had rapid growth (vs. 5), and 4 disappeared (vs. 1). There were also trends to smaller, less symptomatic tumors requiring treatment less often in pregnant females. CONCLUSIONS: Pregnancy seems to ameliorate the course of abdominal desmoid tumors significantly in females with familial adenomatous polyposis. This finding raises questions about the most appropriate hormonal treatment for these tumors. Perhaps progesterone or prolactin therapy should be tried, alone or in combination with estrogen. If further studies confirm these findings, females with a family history of desmoid tumors should not be advised against pregnancy.
Carborane-catalyzed graphitization in polyarylacetylene-derived carbon-carbon composites

Abstract Boron in the form of a carborane compound, C2B10H12, was used to catalytically graphitize a polyarylacetylene (PAA) resin, typically a nongraphitizing carbon, in bulk form and in a carbon-carbon (C-C) composite. In bulk form, significant graphitization was observed after heat treatment to 1800°C; complete graphitization was realized at 2400°C. Similar results were found for a PAA-derived carbon matrix in a unidirectional C-C composite. The effect of carborane addition on the mechanical properties of C-C unidirectional composites of PAA and T-50 carbon fibers was also examined. After heat treatment to 1100°C, the tensile strength of impregnated unidirectional fiber tows increased significantly with increasing concentration of carborane. The increase in tensile strength was accompanied by increased fiber pullout, suggesting that interface weakening decreases the tendency for matrix-dominated brittle fracture. After heat treatment to 1800°C and above, the carborane decreased the strength of the composites, but substantially increased the modulus. Catalytic graphitization of PAA offers a major potential advantage of obtaining graphitic matrices in C-C without the disadvantages of conventional pitch processing. In addition, the much lower temperatures required for catalytic graphitization would enable processing temperatures for C-C to be reduced significantly.
Dimensionless temperature at the wall of an infinite long cylindrical source with a constant heat flow rate

The differential diffusivity equation for an infinitely long cylindrical source with a constant heat flow rate in a homogeneous and isotropic medium has a solution in complex integral form. This integral cannot be expressed in terms of known functions. At present the temperature at the wall of the cylindrical source is determined by means of numerical integration techniques. However, in many cases the heat flow rate varies with time. In these cases the principle of superposition should be used, thus requiring an analytical solution for the constant heat flow rate case. In this paper we present a semi- analytical equation that can be used to approximate the transient dimensionless wall temperature. The accuracy of the equation proposed is also given.
Practical aspects in the implementation of symbolic substitution logic

A potential problem encountered in the implementation of symbolic substitution logic (SSL) is addressed in this paper. It is shown that in the case of intensity-coded data, the pattern recognizer in the architecture for the optical symbolic substitution processor does not recognize the presence of an overlapping pattern of interest. On the other hand, the architecture identifies the overlapping pattern in the case of polarization-coded SSL. However, the recognition of the overlapping search patterns can cause problem in certain applications when we try to make use of the parallelism in the spatial dimension. The above cases are illustrated by suitable examples.© (1989) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
The relationship between gut contents and supercooling capacity in hatchling painted turtles (Chrysemys picta).

Abstract Painted turtles ( Chrysemys picta ) typically spend their first winter of life in a shallow, subterranean hibernaculum (the natal nest) where they seemingly withstand exposure to ice and cold by resisting freezing and becoming supercooled. However, turtles ingest soil and fragments of eggshell as they are hatching from their eggs, and the ingestate usually contains efficient nucleating agents that cause water to freeze at high subzero temperatures. Consequently, neonatal painted turtles have only a modest ability to undergo supercooling in the period immediately after hatching. We studied the limit for supercooling (SCP) in hatchlings that were acclimating to different thermal regimes and then related SCPs of the turtles to the amount of particulate matter in their gastrointestinal (GI) tract. Turtles that were transferred directly from 26 °C (the incubation temperature) to 2 °C did not purge soil from their gut, and SCPs for these animals remained near − 4 °C for the 60 days of the study. Animals that were held at 26 °C for the duration of the experiment usually cleared soil from their GI tract within 24 days, but SCPs for these turtles were only slightly lower after 60 days than they were at the outset of the experiment. Hatchlings that were acclimating slowly to 2 °C cleared soil from their gut within 24 days and realized a modest reduction in their SCP. However, the limit of supercooling in the slowly acclimating animals continued to decline even after all particulate material had been removed from their GI tract, thereby indicating that factors intrinsic to the nucleating agents themselves also may have been involved in the acclimation of hatchlings to low temperature. The lowest SCPs for turtles that were acclimating slowly to 2 °C were similar to SCPs recorded in an earlier study of animals taken from natural nests in late autumn, so the current findings affirm the importance of seasonally declining temperatures in preparing animals in the field to withstand conditions that they will encounter during winter.
Combined Central and Peripheral Sympathetic Blockade: Absence of Additive Antihypertensive Effects

Two antihypertensive agents that inhibits sympathetic activity by differing pharmacologic mechanisms, the centrally-acting alpha-adrenergic agonist, clonidine, and the peripheral alpha-adrenergic antagonist, prazosin, were compared and also given in combination in 24 patients with essential hypertension. The patients were randomized into two groups; 11 received chlorthalidone (50 mg) daily throughout the protocol, whereas 13 received no diuretic. In the 13 patients not receiving the diuretic, supine mean blood pressure fell by 11.0 +/- 3.5 mmHg (p less than 0.01) with clonidine (0.3 mg daily), 5.5 +/- 2.9 mm Hg (p less than 0.05) with prazosin (15 mg daily), and 12.7 +/- 5.2 mmHg (p less than 0.02) with the combination. In the 11 patients concurrently receiving chlorthalidone, supine mean blood pressure fell by 9.5 +/- 2.0 mmHg (p less than 0.01) when clonidine was added, 2.3 +/- 1.9 mmHg (ns) when prazosin was added, and 7.9 +/- 2.1 mmHg (p less than 0.01) with the combination. In both the presence and absence of concurrent diuretic treatment, the blood pressure-lowering effects of clonidine were greater than those of prazosin, but were not different from the antihypertensive effects of the combination of clonidine and prazosin. Therefore, the simultaneous administration of clonidine and prazosin in the doses used in this study does not appear to be more effective than clonidine alone in the treatment of patients with hypertension.
Matter-field correlations and first Born photon statistics☆

Abstract It is shown that the final form of quantum statistics evolving via a first-Born approximation interaction depends critically on the dynamic inclusion of matter-field correlations. It is pointed out that these matter-field correlations are directly measured in photon statistic experiments.
Genetic analyses of putative conformation switching and cross-species inhibitory domains in Microviridae external scaffolding proteins

Putative conformational switching and inhibitory regions in the Microviridae external scaffolding protein were investigated. Substitutions for glycine 61, hypothesized to promote a postdimerization conformational switch, have dominant lethal phenotypes. In previous studies, chimeric alpha3/phiX174 proteins for structures alpha-helix 1 and loop 6/alpha-helix 7 inhibited phiX174 morphogenesis when expressed from high copy number plasmids. To determine if inhibition was due to overexpression, chimeric genes were constructed into the phiX174 genome. In coinfections with wild-type, protein ratios would be 1:1. The helix 1 chimera has a recessive lethal phenotype; thus, overexpression confers inhibition. In single infections, the mutant cannot form procapsids, suggesting that helix 1 mediates the initial recognition of structural proteins. The lethal chimeric helix 7 protein has a dominant phenotype. Alone, the mutant forms defective procapsids, suggesting a later morphogenetic defect. The results of second-site genetic analyses indicate that the capsid-external scaffolding protein interface is larger than revealed in the crystal structure.
Exploring multi‐country dynamic relations between trade and conflict

Most previous studies use a dyad as the unit of analysis and ignore the simultaneity of trade and conflict. The goal of this paper is to find out whether multi‐country trade and conflict relations are statistically significant and the nature of those relations. We employ a multi‐country, simultaneous framework, using the United States‐Soviet Union‐(West) Germany triangle as an example. The empirical analysis, from the first quarter of 1963 to the last quarter of 1991, demonstrates that trade and conflict are significantly interrelated, with positive reciprocity and inertia. Moreover, we find that dyadic flows strongly affect other dyads. The nature of these inter‐dyadic effects depends on particular dyads, but both inter‐ and intra‐dyad effects are statistically significant.
PETROLOGY OF EETA79006 AND IMPLICATIONS FOR THE FORMATION OF POLYMICT EUCRITES

A newly found polymict eucrite, EETA79006, is described. Lithic clasts are similar to those found in howardites and fall into four groups: fine-grained (aphanitic), coarse-grained, basaltic, and cataclastic. All have eucritic compositions and differ mainly in cooling and deformation histories. Some basaltic clasts cooled faster than others and may be impact melts. Analysis of pyroxene and feldspar in the matrix and in 20 lithic clasts indicates that the matrix was not derived from the observed lithic clast population. This meteorite and similar polymict eucrites may have formed by addition of younger more fractionated lithic clasts to the regolith of the parent body.
Physical symptoms/side effects during breast cancer treatment predict posttreatment distress.

Background: Studies suggest that the period following completion of treatment can be distressing for cancer patients. One potentially important predictor of distress is physical symptoms/side effects during treatment.Purpose: A longitudinal, observational design was used to examine whether the number of physical symptoms/side effects experienced during treatment was a correlate of cancer-related distress and general distress 4 months after treatment completion, as measured by the Impact of Events Scale and the Mental Health subscale of the Short Form-36, respectively.Methods: Participants were 151 women who had completed chemotherapy and/or radiotherapy for ductal carcinoma in situ or stage 1 or 2 breast cancer. Hierarchical multiple regression was conducted with relevant sociodemographic, clinical, and psychiatric variables entered as controls.Results: Greater physical symptoms/side effects predicted greater total cancer-related distress, intrusive thoughts, and general distress. Physical symptoms/side effects did not significantly predict avoidance. Follow-up analyses indicated that the relationship between physical symptoms/side effects and general distress was mediated by both total cancer-related distress and intrusive thoughts.Conclusions: These results suggest that patients who experience greater physical symptoms/side effects during treatment are at greater risk for later cancer-related distress and, in turn, general distress. Future research should evaluate whether early intervention with these patients is effective in preventing or reducing distress in the posttreatment period.
The mystery of the missing corpus

Until recently, two happy vices stole a good share of my time. Of those burglars, the first was the reading of science-fiction stories, a source of entertainment that I discovered at the age of eight, but kept manfully in check because I never stumbled upon a continuous supply. Of late, however, real life has mocked this branch of fiction so closely that I now miss in it the elements of fantasy and escape that used to delight. You might say that, being crowded out by the real thing, we armchair spacemen face technological obsolescence. My second time-stealer has been "Murder for Pleasure," as Howard Haycraft calls the detective story. Fortunately, I did not discover its existence until my twenties, so I had a little time for study before then. The great value of the detective story, quite apart from its educational aspects-after all, where else can one gather so much data about useful everyday questions such as tasteless poisons, homicidal law, and criminal psychology i s the fine training one gets in applied psychology and in the logic of everyday life. Sigmund Freud and Carl Gustav Jung can look to their laurels because, after even a short course, we mystery-story fans can twist the Slightest tongue-slip into a full confession, and impractical logic-choppers like Alfred North Whitehead and Bertrand Russell are pitifully pedestrian in their thinking, compared to the agile mental leaps we make--alongside Sherlock Holmes. We have to lump because Sherlock has a great reluctance to share his evidence with the reader. In fact, to put it bluntly, Sherlock cheated, but we excuse him because he performed before the rules were written. Now that we have rules of evidence for modern detective stories, all readers find it easy to search out the killer. (Anyway all readers I've ever met.) Indeed Robert Louis Stevenson commented upon this remarkable ability, "I t is the difficulty of the police romance that the reader is ahvays a person of such vastly greater ingenuity than the writer." And I personally have a sneaking suspicion that this is also one of the difficulties of Presidential Addresses. In best American style I wish to capitalize on my own deficiencies and take advantage of your ingenuity by pointing to a number of puzzles that seem to me to need more detective work in this Society--some minor like parking
The Suess effect in Fiji coral δ13C and its potential as a tracer of anthropogenic CO2 uptake

Abstract In the context of increasing anthropogenic CO2 emissions, determining the rate of oceanic CO2 uptake is of high interest. Centennial-scale changes in δ13C of the surface water dissolved inorganic carbon (DIC) reservoir have been shown to be influenced by the carbon isotopic composition of atmospheric CO2. However, the availability of direct oceanic δ13C measurements is limited and methods for reconstructing past δ13C variability of the oceanic DIC are needed. Geochemical reconstructions of DIC variability can help in understanding how the ocean has reacted to historical changes in the carbon cycle. This study explores the potential of using temporal variations in δ13C measured in five Fijian Porites corals for reconstructing oceanic δ13C variability. A centennial-scale decreasing δ13C trend is observed in these Fiji corals. Other studies have linked similar decreasing δ13C trends to anthropogenic changes in the atmospheric carbon reservoir (the “13C Suess effect”). We conclude that solar irradiance is the factor influencing the δ13C cycle on a seasonal scale, however it is not responsible for the centennial-scale decreasing δ13C trend. In addition, variations in skeletal extension rate are not found to account for centennial-scale δ13C variability in these corals. Rather, we found that water depth at which a Fijian Porites colony calcifies influences both δ13C and extension rate mean values. The water depth-δ13C relationship induces a dampening effect on the centennial-scale decreasing δ13C trend. We removed this “water depth effect” from the δ13C composite, resulting in a truer representation of δ13C variability of the Fiji surface water DIC (δ13CFiji-DIC). The centennial-scale trend in this Fiji coral composite δ13CFiji-DIC time-series shares similarities with atmospheric δ13CCO2, implicating the 13C Suess effect as the source of the this coral δ13C trend. Additionally, our study finds that the δ13C variability between the atmosphere and the ocean in this region is not synchronous; the coral δ13C response is delayed by ~ 10 years. This agrees with the previously established model of isotopic disequilibrium between atmospheric δ13CCO2 and oceanic surface water DIC.
Effects of atmospheric boundary layer moisture on friction velocity with implications for SAR imagery

Using computer simulations, it is shown that failure to consider water vapor effects may lead to anomalous friction velocity changes with static stability. When interpreting synthetic aperture radar (SAR) imagery showing sea surface features induced by marine boundary layer spanning eddies, consideration should be given to the effects of water vapor.
Learning from analogy‐enhanced science text

The present study examined the role that an elaborate analogy can play when middle school students learn a major concept from a science text. The elaborate analogy had both graphic and text components that integrated and mapped key features from an analog (a factory) to the target concept (an animal cell). The target features were the functions of the cell parts. In Experiment 1, eighth graders who studied an analogy-enhanced text had greater immediate and 2-week recall of cell-part functions than students who studied a control text. In Experiment 2, sixth graders who studied an analogy-enhanced text considered the target concept to be more understandable than students who studied a control text. The sixth graders who studied the analogy-enhanced text also had greater immediate and 2-week retention, as measured by both recall and recognition. In both experiments, the analogy was interpreted as acting as a mediator between the students' existing knowledge and the new knowledge in the text. The analogy mapped a familiar, concrete schema onto that of the target concept, making the target concept more understandable and memorable. Implications for the meaningful learning of science text are discussed. © 1998 John Wiley & Sons, Inc. J Res Sci Teach 35: 1129–1149, 1998.
Observations of Short-Period Seismic Energy from Earthquakes and Inferences about the Seismic Source

Summary In this paper we consider the short-period radiation from earthquakes as recorded at high quality seismic stations. We pay particular attention to the profile of energy release as a function of time. Mantle phases such as P are often unsuitable for this purpose because of lateral heterogeneity, but core reflected phases are frequently much simpler. By comparison with events of known character we are able to estimate duration of short-period energy radiation from earthquakes. Under certain assumptions, this gives us a maximum dimension D, over which there is significant short-period energy generated. mb 6 earthquakes with D, as small as 2 km and as large as 50 km are described. It seems possible with an array to examine the energy release pattern of extended earthquakes in some detail.
Ethanol suppression of peripheral blood mononuclear cell trafficking across brain endothelial cells in immunodeficiency virus infection.

Earlier studies suggested that the combination of alcohol use and immunodeficiency virus infection resulted in more severe neurologic disease than either condition individually. These deleterious interactions could be due to increased immune cell and virus trafficking or may result from interactions between ethanol and human immunodeficiency virus (HIV)-associated toxicity within the brain. To determine the extent to which increased trafficking played a role, we examined the effect of ethanol on the migration of different peripheral blood mononuclear cell (PBMCs) subsets across a brain endothelial cell monolayer. We utilized combinations of feline brain endothelial cells with astrocytes, and/or microglia with either acute exposure to 0.08 g/dL ethanol, a combination of ethanol and feline immunodeficiency virus (FIV), or FIV alone. Adherence of PBMCs to endothelium was increased in all combinations of cells with the addition of ethanol. Despite increased PBMC adhesion with ethanol treatment, transmigration of B cells, monocytes, CD4 T cells and CD8 T cells was not increased and was actually decreased in the presence of astrocytes. Expression of three common adhesion molecules, intercellular adhesion molecule-1 (ICAM1), ICAM2, and vascular cell adhesion molecule, was unchanged or slightly decreased by ethanol. This indicated that although adherence is increased by ethanol it is not due to an increased expression of adhesion molecules. RANTES, MIP1α, MIP1β, and MCP-1 mRNA expression was also studied in brain endothelial cells, astrocytes and microglia by reverse transcriptase-polymerase chain reaction. Ethanol treatment of astrocytes resulted in modest changes of message while FIV caused 7–92-fold increases. The combination of ethanol and FIV reversed the large increase in RANTES and MIP1α message in astrocytes but increased MIP1β and MCP to 20–38-fold over control cells. Thus, modest concentrations of alcohol do not directly influence immune cell trafficking at the endothelium but may exert more complex effects on chemokine expression from astrocytes when combined with FIV.
Low Concentrations of Methamphetamine Can Protect Dopaminergic Cells against a Larger Oxidative Stress Injury: Mechanistic Study

Mild stress can protect against a larger insult, a phenomenon termed preconditioning or tolerance. To determine if a low intensity stressor could also protect cells against intense oxidative stress in a model of dopamine deficiency associated with Parkinson disease, we used methamphetamine to provide a mild, preconditioning stress, 6-hydroxydopamine (6-OHDA) as a source of potentially toxic oxidative stress, and MN9D cells as a model of dopamine neurons. We observed that prior exposure to subtoxic concentrations of methamphetamine protected these cells against 6-OHDA toxicity, whereas higher concentrations of methamphetamine exacerbated it. The protection by methamphetamine was accompanied by decreased uptake of both [3H] dopamine and 6-OHDA into the cells, which may have accounted for some of the apparent protection. However, a number of other effects of methamphetamine exposure suggest that the drug also affected basic cellular survival mechanisms. First, although methamphetamine preconditioning decreased basal pERK1/2 and pAkt levels, it enhanced the 6-OHDA-induced increase in these phosphokinases. Second, the apparent increase in pERK1/2 activity was accompanied by increased pMEK1/2 levels and decreased activity of protein phosphatase 2. Third, methamphetamine upregulated the pro-survival protein Bcl-2. Our results suggest that exposure to low concentrations of methamphetamine cause a number of changes in dopamine cells, some of which result in a decrease in their vulnerability to subsequent oxidative stress. These observations may provide insights into the development of new therapies for prevention or treatment of PD.
Remote homology detection: a motif based approach.

Motivation: Remote homology detection is the problem of detecting homology in cases of low sequence similarity. It is a hard computational problem with no approach that works well in all cases. Results: We present a method for detecting remote homology that is based on the presence of discrete sequence motifs. The motif content of a pair of sequences is used to define a similarity that is used as a kernel for a Support Vector Machine (SVM) classifier. We test the method on two remote homology detection tasks: prediction of a previously unseen SCOP family and prediction of an enzyme class given other enzymes that have a similar function on other substrates. We find that it performs significantly better than an SVM method that uses BLAST or Smith-Waterman similarity scores as
Temporal responses of oxidative vs. glycolytic skeletal muscles to K+ deprivation: Na+ pumps and cell cations

When K+ output exceeds input, skeletal muscle releases intracellular fluid K+ to buffer the fall in extracellular fluid (ECF) K+. To investigate the mechanisms and muscle specificity of the K+ shif...