cssi/SciSciGPT-SciSciNet huggingface dataset:
Translation of pharmacogenetics to clinical practice: what will it take?

allele (which reduces the glucuronidation of irinotecan to the active metabolite SN-28) have a higher risk of irinotecan-induced neutropenia; genotypic-based (CYP2C9 and VKORC1) dosage recommendations are provided in the drug label for warfarin; and a warning concerning excessive metabolism of codeine to morphine in ultrafast metabolizers of CYP2D6. These examples demonstrate how genetic information related to drug metabolism influences therapeutics. Media attention has been given to the promise of individualized medicine/personalized health through the use of genomics, such as
The influence of gender and sex steroid hormones on the plasma binding of propranolol enantiomers.

Abstract 1. Plasma binding of tritium-labelled racemic propranolol (P) was measured by equilibrium dialysis. The unbound enantiomers were separated by h.p.l.c. after chiral derivatization. The binding of (-)-P was higher than that of (+)-P. 2. Contrary to previous suggestions, a sex difference in the plasma binding of the P enantiomers (9 young women, 12 young men) was not observed. The unbound percentage of (-)-P was 9.2 +/- 1.8 (mean +/- s.d.) in women vs 9.1 +/- 1.7 in men; for (+)-P it was 10.8 +/- 1.8 vs 10.8 +/- 2.1. 3. In the nine women, the binding did not change with fluctuating plasma oestradiol concentrations during the menstrual cycle. Testosterone cypionate doubled the circulating concentrations of testosterone in eight men but had no effect on P binding. 4. Ethinyl oestradiol (50 micrograms day-1) alone or together with norethindrone (OCD) in eight of the women produced an increase in the unbound percentage of both (-)-P (11.4 +/- 2.6 vs 9.5 +/- 1.6 for control; P < 0.001) and (+)-P (13.2 +/- 2.5 vs 11.2 +/- 1.5 for control; P < 0.001). This was due to a decrease in the plasma concentrations of alpha 1-acid glycoprotein from 0.54 +/- 0.11 mg ml-1 in control to 0.37 +/- 0.08 mg ml-1 (P < 0.001) during ethinyl oestradiol treatment. 5. Enantioselectivity in the unbound fraction of P increased with increasing total binding from a (-)/(+)-ratio of 0.93 at 84% binding to a (-)/(+)-ratio of 0.78 at 94% binding (P < 0.001).
Postgate's fixation

The Fundamentals of Nitrogen Fixation. By J.R. Postgate. Cambridge University Press: 1982. Pp.252. Hbk £20, $37.50; pbk £7.95, $12.95.
God's Triunity and Self‐Determination: A Conversation with Karl Barth, Bruce McCormack and Paul Molnar

: A recent disagreement between Bruce McCormack and Paul Molnar highlights some of the issues involved in discussing the relationship between God's triunity and determination to be God-with-us. Can we say that God's determination to be with us is the basis of God's triunity? Must we identify the Son's being as eternally toward-incarnation? How does God's freedom relate to God's eternal decision to be God-with-humanity? In this article I argue (contra McCormack) that God's triunity logically precedes God's determination to be with us, but (contra Molnar) that this logical precedence entails neither that the pre-incarnate Son is utterly unknown to us nor that God retains some freedom to be God-without-humanity.
Resistance to adriamycin in multicellular spheroids

Abstract Spheroids of EMT-6 mammary tumor cells were markedly more resistant to different exposure doses of Adriamycin (ADR) than monolayer cells in exponential or plateau growth phases. For example, after 1 hr exposures to 0.5 μ/ml, surviving fractions determined by colony formation assay were approximately 0.3 for cells from spheroids treated intact and 0.001 for single exponential phase cells. To evaluate whether this resistance was related to poor drug uptake the distribution of the natural fluorescence of ADR equivalents was determined fluorimetrically and by direct microscopic observations. A concentration gradient of fluorescence was observed from the outside to the centers of spheroids even after high concentrations (10 μ/ml) and long exposure times (2 hrs). Cells from dissociated spheroids took up more drug than intact spheroids further indicating the existence of a significant diffusion barrier. When the surviving fraction of cells was plotted versus absorbed ADR equivalents the cells in intact spheroids were still more resistant and both curves were bicomponent with the most resistant fraction comprising about 20% of the cells. By using a selective disaggregation technique after intact spheroids had been exposed to the drug it was possible to show directly that the inner spheroid cells were most resistant (D 0 = 0.25 μ/10 6 cells). This resistance was not due to differences in the cell cycle state of these inner cells since separate experiments showed that both exponential and plateau phase monolayer cells were about equally sensitive when the surviving fraction was plotted vs absorbed drug (D 0 , = 0.04 μ/10 6 cells). Thus, other factors related to the metabolic state of the cells, the microenvironment, or the formation of different drug products must account for the observed resistance. Pretreatment of spheroids with misonidazole before ADR effectively reduced this resistant population of cells.
Statistical regularities of art images and natural scenes: spectra, sparseness and nonlinearities.

Paintings are the product of a process that begins with ordinary vision in the natural world and ends with manipulation of pigments on canvas. Because artists must produce images that can be seen by a visual system that is thought to take advantage of statistical regularities in natural scenes, artists are likely to replicate many of these regularities in their painted art. We have tested this notion by computing basic statistical properties and modeled cell response properties for a large set of digitized paintings and natural scenes. We find that both representational and nonrepresentational (abstract) paintings from our sample (124 images) show basic similarities to a sample of natural scenes in terms of their spatial frequency amplitude spectra, but the paintings and natural scenes show significantly different mean amplitude spectrum slopes. We also find that the intensity distributions of paintings show a lower skewness and sparseness than natural scenes. We account for this by considering the range of luminances found in the environment compared to the range available in the medium of paint. A painting's range is limited by the reflective properties of its materials. We argue that artists do not simply scale the intensity range down but use a compressive nonlinearity. In our studies, modeled retinal and cortical filter responses to the images were less sparse for the paintings than for the natural scenes. But when a compressive nonlinearity was applied to the images, both the paintings' sparseness and the modeled responses to the paintings showed the same or greater sparseness compared to the natural scenes. This suggests that artists achieve some degree of nonlinear compression in their paintings. Because paintings have captivated humans for millennia, finding basic statistical regularities in paintings' spatial structure could grant insights into the range of spatial patterns that humans find compelling.
Corporate support mechanisms for families: An exploratory study and agenda for research and evaluation

Abstract Based on telephone interviews with representatives from 16 corporations in the Baltimore-Washington area, this article explores the awareness of corporate officers of the linkages between work and family systems, their perceived responsibility for implementing policies and services that lend support to the family circumstances of employees, and the types of actions they had initiated in their corporations to help employees better balance work and family demands. Study results demonstrate limited awareness among corporate officers toward the work and family interface, employer uncertainty about corporate responsibilities for the family situation and demands of employees, and limited corporate development of family-oriented policies and services. These results are discussed in the context of recent federal initiatives to encourage greater corporate response to the family circumstances of employees. Implications are suggested for further research and evaluation.
Carbon Diffusion in Steels: a Numerical Analysis Based on Direct Integration of the Flux

In the early 1970s, Professor Dayananda developed a technique for the direct integration of fluxes from the concentration profiles in vapor-solid diffusion couples to determine diffusion coefficients and atomic mobilities. As part of a project to control and optimize the industrial carburization process in mild- and low-alloyed steels, a modified integration analysis was applied to determine the mass transfer coefficient in the gas boundary layer and carbon diffusivity in austenite. Because carbon flux and surface carbon content vary with time during single-stage carburizing even with a fixed carbon potential in the atmosphere, a mass balance at the gas-solid interface must serve as a boundary condition. This article discusses the numerical modeling of gas carburizing, and focuses on calculating the mass transfer and carbon diffusivity parameters using the simulated concentration profiles. This approach validates the proposed method by comparing the calculated parameters with those used in simulation. The results were compared with previous determinations and predictions reported in the literature.
Thermal stresses in subducting lithosphere can explain double seismic zones

The discovery of double-planed zones of intermediate-depth seismicity associated with subducting oceanic lithosphere (refs 1–7 and L.S.H. and K.H.J., in preparation) has generated much interest in the origin and distribution of stresses in descending plates. Several mechanisms have been proposed to explain why double zones occur8. Here we investigate the role of thermal stresses for the state of stress in a descending plate and test whether they can account for the observed characteristics of double seismic zones. By modelling the descending slab as a thin elastic plate and using the temperatures in the slab estimated by Toksoz et al.9, we find that the polarities of thermally generated stresses agree with those obtained from the focal mechanisms of earthquakes in the two zones. Thermal stresses also can explain the separation between the two zones of seismicity at shallow depths and their gradual merging at greater depth.
On the formulation of invariant imbedding problems

The formulation of an invariant imbedding problem from a given linear, two-point boundary-value problem is not unique. In this paper, we illustrate how the formulation of the problem by partitioning the original vectory(z) into [u(z),v(z)], can affect the numerical accuracy. In fact, the partitioning, the choice of theR, O system orS, T system of equations in Scott's method, the location and number of switch points, and the switching procedure, all influence the numerical results and the ease of obtaining solutions. A new method of switching and the appropriate formulas are described, namely, the repeated switching from theR, Q system to theR, Q system of equations or from theS, T system to theS, T system of equations.
Estrogen prevention of lacrimal gland cell death and lymphocytic infiltration.

Abstract Previous studies have shown that ovariectomy causes necrosis of lacrimal acinar cells, apoptosis of plasma cells and gland lymphocytic infiltration. Both, lacrimal gland cell death and lymphocytic infiltration were prevented by androgen treatment. Since estrogens are removed by ovariectomy, and the synthetic estrogen diethylstilbestrol has been shown to affect some biochemical correlates of lacrimal secretion, the purpose of this study was to determine the effect of 17-β-estradiol treatment on ovariectomy-induced cell death and lymphocytic infiltration. Sexually mature female New Zealand white rabbits (4–4·5 kg) were ovariectomized and divided into two groups. One group was treated with 0·5 mg kg−1 per day 17-β-estradiol, and the other group with vehicle alone. A third group of sham operated rabbits was used as controls and they also were treated with vehicle alone. Six days after surgery, the animals were euthanized, the lacrimal glands removed and processed for analysis of apoptosis as assessed by DNA fragmentation, and for morphological examination. DNA fragmentation was determined using the TUNEL assay and agarose gel electrophoresis. Sections were also stained for rabbit thymic lymphocyte antigen (RTLA), and rabbit CD18. Labelled nuclei and stained areas were quantified by automated densitometry. Ovariectomized rabbits showed a significant increase in the values for degraded DNA as a percent of total nuclear area (2·90±0·40%) compared to sham operated rabbits (0·73±0·22%). 17-β-estradiol treatment in ovariectomized rabbits prevented the increase in DNA degradation. Examination of TUNEL assay at higher magnification (40×) confirmed previous studies showing that ovariectomy caused apoptosis of interstitial cells. Significant numbers of bulging cells of very pale appearance under light microscopy, also confirm previously identified necrotic cells in acinar regions. Treatment with 17-β-estradiol prevented this necrosis. Increased numbers of RTLA+ and CD18+ interstitial cells were also evident after ovariectomy. 17-β-estradiol treatment prevented the increase in the number of lymphoid cells. We confirmed previous observations that suggest that glandular atrophy observed after ovariectomy is likely to proceed by necrosis of acinar cells rather than apoptosis, and that ovariectomy triggers an inflammatory response in the gland. These results suggest that in addition to androgens, estrogens also seem to play a role to maintain lacrimal gland structure and function. A decrease in available estrogen levels could trigger both lacrimal gland apoptosis and necrosis, as well as lymphocytic infiltration. Although, the effect of estrogens in these experiments seems to be direct and not through androgens, the possibility of the role of an autocrine and/or paracrine factors, promoted by estrogen on lacrimal gland cells still needs to be investigated.
Stirling Powered Van Program Overview

The Stirling Powered Van Program (SPVP) is a multiyear, multiphase program to evaluate the automotive Stirling engine (ASE) in Air Force vans under realistic conditions. The objective of the SPVP is to transfer to manufacturer and end user(s) (i.e., on the path to commercialization) the second-generation Mod 2 ASE upon completion of the Automotive Stirling Engine Program in 1987. In order to meet this objective, the SPVP must establish Stirling performance, integrity, reliability, durability and maintainability. The ASE program background leading to the van program is reviewed and plans for evaluating the kinematic Stirling engine in Air Force vans examined. Also discussed are the NASA technology transfers to industry that have been accomplished and those which are currently being developed.
Motivation in marital communication: Comparison of distressed and nondistressed husbands and wives

Abstract Most research and training efforts concerned with marital communication have focused on the communication skills of spouses. Much less research has examined the communicative intentions of spouses. Some research suggests that wives may be “barometers” of the marital state, and in distressed marriages may have more negative intentions than their husbands. Thus, the current study hypothesized that wives in distressed marriages would make more negative ratings about the intents and impacts of communication than husbands in distressed marriages or husbands and wives in nondistressed marriages. Sixty marital dyads completed the Dyadic Adjustment Scale and participated in problem discussions while using the communication box. Ratings were made of message intent, predicted message impact, actual message impact, and perceived message intent. Intent ratings of distressed wives were significantly more negative than those provided by distressed husbands or by nondistressed wives. Distressed wives predicted ...
Deposition of Lignin Droplets Produced During Dilute Acid Pretreatment of Maize Stems Retards Enzymatic Hydrolysis of Cellulose

Electron microscopy of lignocellulosic biomass following high-temperature pretreatment revealed the presence of spherical formations on the surface of the residual biomass. The hypothesis that these droplet formations are composed of lignins and possible lignin carbohydrate complexes is being explored. Experiments were conducted to better understand the formation of these “lignin” droplets and the possible implications they might have on the enzymatic saccharification of pretreated biomass. It was demonstrated that these droplets are produced from corn stover during pretreatment under neutral and acidic pH at and above 130 °C, and that they can deposit back onto the surface of residual biomass. The deposition of droplets produced under certain pretreatment conditions (acidic pH; T > 150 °C) and captured onto pure cellulose was shown to have a negative effect (5–20%) on the enzymatic saccharification of this substrate. It was noted that droplet density (per unit area) was greater and droplet size more variable under conditions where the greatest impact on enzymatic cellulose conversion was observed. These results indicate that this phenomenon has the potential to adversely affect the efficiency of enzymatic conversion in a lignocellulosic biorefinery.
Efficacy of compressive sensing for dynamic spectrum access

Compressive sensing (CS) relies on the fact that CS sampled signals are much closer to their information rate rather than the signal bandwidth. This attribute helps to provide the much needed benefits of reduced storage or transmission bandwidth for the next-generation broadband wireless communications and to overcome the hardware limitations for wideband spectrum sensing in dynamic spectrum access. In order to opportunistically reuse holes in the spectrum, it is essential to have a spectral detection and estimation technique that is capable of sensing and identifying available frequency bands. Conventional methods of detection are saddled with the high sampling rate requirement of Nyquist rate, however timing requirements limits the number of samples that can be taken from the signals. In a situation whereby the signal spectrum in open-access networks is sparse in nature, this work develops a detection mechanism for identifying spectrum holes using compressive sensing based algorithm technique. Different compressive sensing reconstruction algorithms are investigated and FFT spectrogram with an edge detection algorithm is used to identify the holes in the spectrum. A quick wideband spectrum sensing can be achieved using the compressive sensing technique and a more refined sensing can be used by any of the other available methods such as energy detection. The proposed model is evaluated in different fading propagation environments, taking into account of both additive and multiplicative noise.
Finite-Element Modeling of Guardrail Timber Posts and the Post-Soil Interaction:

The performance of many guardrail terminal systems is dependent on the strength of timber guardrail posts and soil conditions. Accurately simulating the breakaway characteristits of guardrail posts mounted in soils is an important issue concerning researchers in the roadside safety community. Finite-element analysis is one method that can be used to evaluate roadside hardware designs, but good simulations are contingent on developing accurate models of the components. A description is provided of the development of a model of a breakaway timber post and soil system used in the breakaway cable terminal (BCT) and the modified eccentric loader terminal (MELT). The model is described and simulation results are compared with data from physical tests of BCT/MELT posts.
Use of iohexol to quantify hemodialysis delivered and residual renal function: Technical Note

Use of iohexol to quantify hemodialysis delivered and residual renal function . Background Classically, urea (molecular wt=60) is used to determine the urea reduction ratio (URR) or clearance, based on volume of distribution (Kt/V). These methods are subject to many errors. The purpose of this study was to determine whether iohexol (Io; molecular wt=821) could be used instead of urea and provide better information as well as middle molecule clearance data. Methods Ten hemodialysis (HD) patients were evaluated. All were dialyzed for three hours, and a single bolus of 100ml of Io was injected immediately post-HD. For direct dialysis quantification (DDQ), the spent dialysate was collected in a drum, and urea and iodine (I) determined immediately prior to, at the end of, and 30minutes post-HD. As routinely used, DDQ measures clearance directly rather than estimates the levels. Results Calculated Kt/V urea (1.21 ± 0.05) significantly overestimated DDQ Kt/V urea (0.78 ± 0.04, P P 30min 0.59 ± 0.02, P urea ), 247 ± 21ml/min, significantly overestimated DDQ C urea (157 ± 10ml/min P Io and DDQ C Io , however, were similar (109 ± 8 vs. 104 ± 7ml/min). Total body clearance (TBC) in six anuric subjects was 2.5 ± 0.3ml/min, and in four oliguric subjects was 5.2 ± 0.5ml/min. In 10 additional patients, direct urine measurements demonstrated a non-renal clearance (NRC) of 2.97 ± 0.18ml/min, which was 4.0 ± 0.3% of body wt. Use of this factor allowed an estimation of residual renal function (RRF) that accurately reflected measured RRF (1.32 ± 0.53 vs. 1.42 ± 0.55ml/min) Conclusion A single injection of Io can be used to determine Kt/V, RR, and RRF without rebound or the inconvenience of urine collection. It may also represent middle molecule clearance better than urea kinetics, and may serve as a superior method for determining HD delivered and dialysis adequacy.
Large-Scale Passive Earth Pressure Load-Displacement Tests and Numerical Simulation

Passive earth pressure is recorded in two different tests, using a 6.7-m long, 2.9-m wide soil container. In these tests, sand with 7% silt content is densely compacted behind a moveable test wall to a supported height of 1.68 m (5.5 ft). Lateral load is applied to the vertical reinforced concrete wall section, which displaces freely along with the adjacent backfill in the horizontal and vertical directions. The recorded passive resistance is found to increase until a peak is reached at a horizontal displacement of 2.7–3% of the supported backfill height, decreasing thereafter to a residual level. In this test configuration, a triangular failure wedge shape is observed, due to the low mobilized wall-soil friction. Backfill strength parameters are estimated based on this observed failure mechanism. From these estimates, along with triaxial and direct shear test data, theoretical predictions are compared with the measured passive resistance. Using the test data, a calibrated finite-element model is employed...
Functions of aggressive behavior and future functional impairment

Abstract The present study investigated relations between proactive and reactive functions of physical and relational aggression and functional impairment across early childhood. It was hypothesized that reactive functions of aggression would be associated with functional impairment. Hypotheses with regard to proactive functions of aggression were exploratory. Participants were 36 children (22 girls) from a longitudinal study. At Time 1 ( M = 50.31 months old, SD = 10.97), observations of aggressive behavior were collected during preschool free-play. At Time 2 ( M = 73.33 months old, SD = 10.88), parent-report of functional impairment was collected. Reactive physical aggression was a significant and unique predictor of future impairment when controlling for gender and all other types of aggression. Implications of these findings are discussed from a developmental perspective.
Occurrence of 13(S)-hydroxyoctadecadienoic acid in biological samples

The oxygenated metabolite of linoleic acid, 13(S)-hydroxyoctadecadienoic acid has recently been shown to play a role in cellular regulation. To detect this molecule in biological systems, we recently developed a specific polyclonal antibody. Using this antibody, we report the presence of 13(S)-hydroxyoctadecadienoic acid in human urine, cell culture media, and untreated goat serum for the first time by a specific, sensitive, and rapid enzyme immunoassay. Furthermore, the enzyme linked immunosorbent assay data are verified by gas chromatography/mass spectrometry analysis of the same samples.
Treatment of infant postrenal acute renal failure following obstruction due to upper urinary calculi

The surgical emergency treatments and curative effects of postrenal acute renal failure following obstruction due to upper urinary calculi in infants were evaluated. Of the 13 infants with postrenal acute renal failure following obstruction due to upper urinary calculi, 11 received retrograded catheterizations of the ureter with semi-rigid ureteroscopy (F 6.8), and two received open ureterolithotomy. The results showed that only one infant had anuresis and continuous reduction of hemoglobin 5 h after the open ureterolithotomy and received exploration via excision and peritoneal dialysis, and the remaining 12 patients well recovered in this group. The renal function of all the patients was restored without postoperative complications. It is concluded that the retrograded catheterization of the ureter with ureteroscopy is a minimally invasive, safe and effective therapy for postrenal acute renal failure following obstruction due to upper urinary calculi in infants. For those infants whose urethras are thin and small, the open ureterolithotomy is a suitable method. But patients with bleeding tendency need to be corrected prior to the open ureterotomy to remove obstructions.
Long-Path Interferometry through an Uncontrolled Atmosphere*

An investigation has been made of the degree to which the invariance of the relative dispersion of the atmosphere will permit an interferometric separation between geometric path differences and path differences due to atmospheric inhomogeneities. Humidity variations are the most serious. A difference in average humidity of 1% of saturation at 15°C would affect the comparison of two paths by approximately 2 parts in 108. The feasibility of photographing interference for long paths through an uncontrolled atmosphere has been investigated. Photographs of channel spectrum interference have been readily obtained for path lengths of 115 m near ground level.
Use of robust variance components models to analyse triglyceride data in families

Summary A robust approach for analysis of variance components models is presented which does not rely on the assumption of multivariate normality for its validity. This approach uses the multivariate normal distribution as a ‘working model’ but obtains standard errors for the final estimators which do not depend on this underlying distribution. By using the observed variance in the first derivatives of the multivariate normal ‘working model’ to modify the conventional score test, hypotheses regarding specific components can also be tested without relying directly on the assumption of multivariate normality. A special case is presented where both the modified score test and the likelihood ratio test are equally robust, and simulated data are used to illustrate this situation. Measurements of triglyceride levels in 391 individuals in 60 families randomly selected from the membership of a health maintenance organization are used to illustrate this robust approach to variance components.
Construction of large sets of pairwise disjoint transitive triple systems II

Abstract The maximum number of pairwise disjoint transitive triple systems (TTSs) of order n is 3( n − 2). Such a collection is called a large set of pairwise disjoint TTSs of order n . The main result in this paper is the proof of the following theorem: If n ≡ 1 or 5 (mod 6), and there exists a large set of pairwise disjoint TTSs of order 2 + ν , then there exists a large set of pairwise disjoint TTSs of order 2 + νn . Two consequences of this result are the existence of a large set of pairwise disjoint TTSs of every odd admissible order and the existence of a large set of pairwise disjoint TTSs of every admissible order ⩽1000, except possibly 130 and 258.
Taking Construction Site Waste Management to the Next Level

Abstract Building a single family home in the United States typically produces between three to five pounds of waste per square foot (SIH). Costs of disposing this waste are mounting throughout the country, and environmental aspects of this issue are receiving heightened scrutiny. Although research on this topic has shown that 80 percent of waste generated during the construction of a home can be recycled (Laquatra and Pierce 2004; SBIC 2007), less than 30 percent actually is (Martin 2007). This is likely to change as state and local government regulations of construction waste increase, with some mandating waste recycling. In addition, builders who participate in green building programs are learning that reducing the amount of waste generated during construction, and recycling waste that is produced, earns points toward certification. This paper describes elements of a successful waste management plan for home builders. Issues specific to each type of waste are examined, and ideas for improving recycling...
Focal adhesion kinase signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells

The intracellular signaling events controlling human mesenchymal stem cells (hMSC) differentiation into osteoblasts are not entirely understood. We recently demonstrated that contact with extracellular matrix (ECM) proteins is sufficient to induce osteogenic differentiation of hMSC through an ERK-dependent pathway. We hypothesized that FAK signaling pathways provide a link between activation of ERK1/2 by ECM, and stimulate subsequent phosphorylation of the Runx2/Cbfa-1 transcription factor that controls osteogenic gene expression. We plated hMSC on purified collagen I (COLL-I) and vitronectin (VN) in the presence or absence of FAK-specific siRNA, and assayed for phosphorylation of Runx2/Cbfa-1 as well as expression of established osteogenic differentiation markers (bone sialoprotein-2, osteocalcin, alkaline phosphatase, calcium deposition, and spectroscopically determined mineral:matrix ratio). We found that siRNA treatment reduced FAK mRNA levels by >40% and decreased ECM-mediated phosphorylation of FAK Y397 and ERK1/2. Serine phosphorylation of Runx2/Cbfa-1 was significantly reduced after 8 days in treated cells. Finally, FAK inhibition blocked osterix transcriptional activity and the osteogenic differentiation of hMSC, as assessed by lowered expression of osteogenic genes (RT-PCR), decreased alkaline phosphatase activity, greatly reduced calcium deposition, and a lower mineral:matrix ratio after 28 days in culture. These results suggest that FAK signaling plays an important role in regulating ECM-induced osteogenic differentiation of hMSC.
Pediatric cochlear implantation: Role of language, income, and ethnicity

Abstract Objective To compare post-cochlear implantation (CI) early speech perception (ESP) outcomes between a non-English speaking, ethnic minority study group and an English speaking, ethnic majority control group. Study design/methods We performed a retrospective case-control study at an academic tertiary care children's hospital. Records were reviewed of 49 children who underwent CI from February 2005 to September 2011. Children with abnormal cognitive function (n = 12), post-surgical complications (n = 1), or incomplete SP testing (n = 24) were excluded. The remaining 12 cases (mean implant age 4.3y) were reviewed for language, income, ethnicity, and ESP scores. Their scores were compared to a subset of patients (n = 18; mean implant age 2.2y) serving as control from the Childhood Development after Cochlear Implantation (CDaCI) study at 1 year follow up where standard ESP testing was performed. Briefly, CDaCI includes a demographically balanced and multicenter-based pediatric cohort from which publications are beginning to define normative post-CI SP outcomes. Results Of our 12 children, 7 were Hispanic, 2 Caucasian, 2 multi-ethnicity and 1 Russian. 4 were non-English speaking, 5 spoke English as a second language, and 7 were bilingual. Three received bilateral CI. Mean early speech perception (ESP) scores (reported on a scale of 1–4) collected at 6 and 12 months in the study group were 1.71 and 1.75, respectively; in the control group, 3.83 and 3.92. At both follow up intervals the study group performed significantly worse than the control group (6mo P = 0.048, 12mo P = 0.01). Conclusions This study suggests that among pediatric CI recipients, those from predominantly non-English speaking, socioeconomically disadvantaged backgrounds develop SP at slower than normal rates. Future interventions should be directed at overcoming these obstacles.
Avian seed dispersal of an invasive shrub

The incorporation of an animal-dispersed exotic plant species into the diet of native frugivores can be an important step to that species becoming invasive. We investigated bird dispersal of Lonicera maackii, an Asian shrub invasive in eastern North America. We (i) determined which species of birds disperse viable L. maackii seeds, (ii) tested the effect of gut passage on L. maackii seeds, and (iii) projected the seed shadow based on habitat use by a major disperser. We found that four native and one exotic bird species dispersed viable L. maackii seeds. Gut passage through American robins did not inhibit germination, but gut passage through cedar waxwings did. American robins moved mostly along woodlot edges and fencerows, leading us to project that most viable seeds would be defecated in such habitats, which are very suitable for L. maackii. We conclude that L. maackii has been successfully incorporated into the diets of native and exotic birds and that American robins preferentially disperse seeds to suitable habitat.
H3PW12O40-functionalized tip for scanning tunneling microscopy

Recent reports of C(60)-functionalized metal tips [Kelly, K. F., Sarkar, D., Hale, G. D., Oldenburg, S. J. & Halas, N. J. (1996) Science 273, 1371-1373] and carbon nanotube tips [Dai, H., Hafner, J. H., Rinzler, A. G., Colbert, D. T. & Smalley, R. E. (1996) Nature (London) 384, 147-151] demonstrate the potential of controlling the chemical identity and geometric structure of tip atoms in scanning tunneling microscopy (STM). This work reports the performance of a heteropolyacid (HPA)-functionalized Pt/Ir tip, which was formulated by contacting a mechanically formed tip with a solution of H(3)PW(12)O(40) molecules. Attachment of an H(3)PW(12)O(40) molecule on the metal tip was confirmed by observing the characteristic negative differential resistance (NDR) behavior of H(3)PW(12)O(40) in tunneling spectroscopy. Atomic resolution images of bare graphite as well as of H(6)P(2)W(18)O(62) HPA monolayers on graphite were successfully obtained with a Pt/Ir-HPA tip. In the H(3)PW(12)O(40) molecule on a metal tip, it is likely that a terminal oxygen of WO (an oxygen species projecting outward from the pseudospherical H(3)PW(12)O(40) molecule) serves as an atomically sharp and stable tip. Additionally, superimposed superperiodic structures commensurate with the underlying graphite lattice were regularly observed with the modified tips. This result suggests that tip functionalization with these metal oxide molecules may enhance resolution in a fashion analogous to functionalization with C(60).
High-resolution optical molecular imaging of changes in choline metabolism in oral neoplasia

This study was aimed at developing an optical molecular imaging approach to measure differences in uptake and intracellular retention of choline in clinically isolated tissue biopsies from head and neck cancer patients. An optically detectable analogue of choline (propargyl choline) was synthesized and evaluated in 2D and 3D models and clinically isolated paired biopsies (n = 22 biopsies). Fluorescence contrast between clinically abnormal and normal tissues based on uptake and intracellular retention of propargyl choline was measured and correlated with pathologic diagnosis. Results in 2D and 3D models demonstrated a rapid uptake of propargyl choline in cancer cells, uniform permeation in tissue models, and specific detection of intracellular entrapped propargyl choline using the click chemistry reaction with an azide-modified Alexa 488 dye. Fluorescence imaging measurements following topical delivery of propargyl choline in clinically isolated biopsies showed that the mean fluorescence intensity (MFI) of neoplastic tissues was four-fold to five-fold higher than the MFI of clinically and pathologically normal samples. This difference in fluorescence contrast was measured on the basis of comparison of paired biopsy sets isolated from individual patients as well as comparison of clinically abnormal and normal biopsies independent of anatomic locations in the head and neck cavity and across diverse patients. In conclusion, a novel imaging approach based on monoalkyne-modified choline was developed and validated using cell and tissue models. Results in clinically isolated tissue biopsies demonstrate a significant fluorescent contrast between neoplastic and normal tissues and illustrate high specificity of the optical imaging approach.
Postsynaptic Development of the Neuromuscular Junction in Mice Lacking the γ-Subunit of Muscle Nicotinic Acetylcholine Receptor

The mammalian muscle nicotinic acetylcholine receptor (AChR) is composed of five membrane-spanning subunits and its composition differs between embryonic and adult muscles. In embryonic muscles, it is composed of two α-, one β-, one δ-, and one γ-subunit; the γ-subunit is later replaced by the e-subunit during postnatal development. This unique temporal expression pattern of the γ-subunit suggests it may play specific roles in embryonic muscles. To address this issue, we examined the formation and function of the neuromuscular junction in mouse embryos deficient in the γ-subunit. At embryonic day 15.5, AChR clusters were absent and the spontaneous miniature endplate potentials were undetectable in the mutant muscles. However, electrical stimulation of the nerves triggered muscle contraction and elicited postsynaptic endplate potential (EPP) in the mutant muscles, although the magnitude of the muscle contraction and the amplitudes of the EPPs were smaller in the mutant compared to the wild-type muscles. Reintroducing a wild-type γ-subunit into the mutant myotubes restored the formation of AChR clusters in vitro. Together, these results have demonstrated that functional AChRs were present in the mutant muscle membrane, but at reduced levels. Thus, in the absence of the γ-subunit, a combination of α, β, and δ subunits may assemble into functional receptors in vivo. These results also suggest that the γ-subunit maybe involved in interacting with rapsyn, a cytoplasmic protein required for AChR clustering.
Lessons Learned: Use of Event Reporting by Nurses to Improve Patient Safety and Quality

The Magnet Recognition Program encourages nurse-initiated, data-driven quality projects. Using data gained from medical error event reporting has been cited as a strategy to improve safety and quality. This article describes a process by which nurses at the Children's Hospital Boston increased error reporting and used knowledge gained from event reports to provide education and implement practice changes. The medical and surgical units experienced a 35% increase in reported events and a decrease in the severity level of events over a 2-year period. Meaningful data from event reporting systems are critical in helping nurses develop interventions to prevent errors. The Magnet Model components are illustrated in the steps of this project.
The formation and dissolution of gels from collagen solutions: The effect of β-aminopropionitrile☆☆☆

Abstract Samples of extractable collagen from normal rats purified by different means were compared with similar samples from rats treated with β-aminopropionitrile (BAPN) with respect to gelling at 37 °C. and with respect to the extent to which the gels redissolve on cooling to 4 °C. The in vitro experiments confirm the in vivo findings of a defect in the intermolecular bonding of lathyritic collagen fibrils. The results are consistent with either an intrinsic defect in lathyritic collagen or the presence in normal connective tissue of a factor extrinsic to collagen which is absent in lathyritic connective tissue. The results are inconsistent with the presence of an inhibitor in lathyritic connective tissue preventing intermolecular bonding of collagen.
The ontogeny of isozyme patterns of lactate dehydrogenase in the mouse

Abstract The enzyme lactate dehydrogenase (LDH) was shown to exist as five electrophoretically distinct molecular varieties, or isozymes, within the tissues of the mouse. Nearly every tissue or organ of the adult mouse contains all five isozymes of LDH, but in proportions that are highly specific for the tissue. The pattern of isozyme distribution in embryonic tissues differs from the adult pattern. Most embryonic tissues initially contain principally LDH-5; as development proceeds LDH activity is gradually transposed toward the LDH-1 end of the spectrum. The LDH isozymes differ in kinetic properties, e.g., substrate concentration optima; these differences apparently enable the isozymes to fulfill distinct metabolic roles in cellular metabolism. LDH-5 is more abundant in tissues subject to relative anaerobiosis, and the isozymes at the other end of the spectrum are more abundant in highly oxygenated tissues. The isozyme patterns in the mouse are satisfactorily explained by the previously elaborated subunit hypothesis ( Markert, 1962 ), which pictures the LDH molecule as composed of four polypeptide subunits that may be separated into two distinct varieties, A and B, each presumably under the control of a separate gene. Assortment of these subunits in all possible combinations of four generates the five isozymes of LDH. The relative proportions of A and B synthesized by a cell would determine the tissue-specific patterns of LDH isozymes either in the adult or during the course of embryonic or neonatal development.
Image-guided tissue engineering

Replication of anatomic shape is a significant challenge in developing implants for regenerative medicine. This has lead to significant interest in using medical imaging techniques such as magnetic resonance imaging and computed tomography to design tissue engineered constructs. Implementation of medical imaging and computer aided design in combination with technologies for rapid prototyping of living implants enables the generation of highly reproducible constructs with spatial resolution up to 25 μm. In this paper, we review the medical imaging modalities available and a paradigm for choosing a particular imaging technique. We also present fabrication techniques and methodologies for producing cellular engineered constructs. Finally, we comment on future challenges involved with image guided tissue engineering and efforts to generate engineered constructs ready for implantation.
The sociology of adolescent drug and drinking behavior: A review of the state of the field: Part II

This is Part II of our general assessment of the state of sociological research on adolescent substance use. In Part I, presented in the previous issue of this journal, we analyzed the methodological issues in the field and summarized findings on extent and trends of use. Here, we summarize structural, interactional, and attitudinal correlates of teenage drinking and drug behavior. We characterize the field as being theoretically underdeveloped and argue that the place to look for theory to organize empirical generalizations and derive testable hypotheses is among the existing sociological theories of deviance, which have been given scant attention in the adolescent drug and drinking literature. The field of study is in need of primary data collected to test hypotheses from a single general theory that is capable of integrating structural, interactional, and attitudinal variables.
The TBA torsion pendulum: a technique for characterizing the cure and properties of thermosetting systems†

Generalizations on the cure and properties of thermosetting polymers, which have stemmed from the development and application of the torsional braid analysis (TBA) technique, have been formulated in terms of cure–property relationships. They are the isothermal time–temperature–transformation (TTT) cure diagram, the continuous heating time–temperature–transformation (CHT) cure diagram, the conversion–temperature–property (TgTP) diagram, and the glass transition temperature (Tg) versus conversion relationship. The relationships may be used to design time–temperature cure paths, that exploit gelation and vitrification, to optimize cure processes and glassy state properties. Glassy state properties studied have included modulus, density and microcracking versus conversion, and the dynamics of submolecular motions as represented by physical ageing and transitions. Rubber modification and water absorption have also been investigated. This review emphasizes results obtained by exploiting the ability of the TBA technique to examine amorphous specimens in which material changes from liquid (or rubber) to glass, and vice versa. ©1997 SCI
Effects of sociodemographic factors, stage of illness, and perceived stigma on the identification of a support person among women with HIV infection

Addressing the lack of research on the social distribution of social support and research on the social experience of women with HIV infection, this article examines how sociodemographic factors, stage of illness, and perceived stigma affected the identification of a supportive social relationship among HIV‐infected women. Data were collected from women with HIV disease living in the state of Georgia. Logistic regression analysis indicates that after taking account of other factors, marital status, rural‐urban residency, stage of illness, and stigmatization were significant predictors of whether the women identified a support person. Single status and rural residency had negative effects on the outcome. Those who were at the advanced stage of illness were less likely than those at the asymptomatic stage to identify a supportive relationship. Contrary to our expectation, stigmatization had positive effects on the outcome. Implications and limitations of the analysis are discussed, followed by directions fo...
Developing successful theories in marketing: insights from resource-advantage theory

All disciplines require both (1) the development of theories that explain and predict important phenomena and (2) empirical research that tests the theories. Purely conceptual/theoretical articles are central to theory development and are generally more influential than empirical articles. However, not all conceptual articles are equally successful. This article addresses the issue of why some theoretical articles are more successful than others. Using a highly successful theory in marketing, resource-advantage theory, as a case-example, this article develops five guides for authors seeking to develop successful theories: (1) focus theory development on important issues in macromarketing and/or micromarketing, (2) craft theories with high explanatory and predictive power, (3) respect other disciplines’ literatures, (4) publish the theory in nonmarketing journals, and (5) explore the normative implications of the theory.
Operating Systems: On overcoming high-priority paralysis in multiprogramming systems: a case history

High-priority paralysis is the degradation that can occur in multiprogramming systems when scheduling is based primarily on preassigned priorities. It can be alleviated by modifying the scheduling algorithm to maximize the number of programs active at one time. The case history given in this paper indicates two general methods by which simultaneity can be increased. Possible refinements in the scheduling algorithm for future improvements are considered briefly.