cssi/SciSciGPT-SciSciNet huggingface dataset:
Novel approaches to global mining of aberrantly methylated promoter sites in squamous head and neck cancer.

Abstract Objective Promoter hypermethylation is emerging as a promising molecular strategy for early detection of cancer. We examined promoter methylation status of 1143 cancer-associated genes to perform a global but unbiased inspection of methylated regions in head and neck squamous cell carcinoma (HNSCC). Study Design Laboratory-based study. Setting Integrated health care system. Subjects and Methods Five samples, two frozen primary HNSCC biopsies and three HNSCC cell lines, were examined. Whole genomic DNA was interrogated using a combination of DNA immunoprecipitation (IP) and Affymetrix whole-genome tiling arrays. Results Of the 1143 unique cancer genes on the array, 265 were recorded across five samples. Of the 265 genes, 55 were present in all five samples, and 36 were common to four of five samples, 46 to three of five, 56 to two of five, and 72 to one of five samples. Hypermethylated genes in the five samples were cross-examined against those in PubMeth, a cancer methylation database combining text mining and expert annotation ( http://www.pubmeth.org ). Of the 441 genes in PubMeth, only 33 are referenced to HNSCC. We matched 34 genes in our samples to the 441 genes in the PubMeth database. Of the 34 genes, eight are reported in PubMeth as HNSCC associated. Conclusion This pilot study examined the contribution of global DNA hypermethylation to the pathogenesis of HNSCC. The whole-genome methylation approach indicated 231 new genes with methylated promoter regions not yet reported in HNSCC. Examination of this comprehensive gene panel in a larger HNSCC cohort should advance selection of HNSCC-specific candidate genes for further validation as biomarkers in HNSCC.
Diffusion Limited Interface Kinetics in Multicomponent Systems

The stability of phases in materials can be related to reactions occurring at their interfaces, for example fiber/matrix reactions in composites. The reaction can be modelled in a simple way, even for multicomponent systems, when it is diffusion controlled and when no intermediate phases form. In the current work a model is proposed that assumes local equilibrium at the interface and small concentration differences in each phase. The physical properties required for the model are the “square root diffusivity” for each phase and the applicable phase diagram. The model is applied to predicting concentration profiles and interface velocities for the reaction of a B2 aluminide containing Ni-34at%Cr-12at%Al with various Ni-rich, gamma solid solutions containing Cr and Al. The example shows how varying the gamma composition can alter the aluminide stability with respect to dissolution or growth. In addition, a simplified form of the model is given for extrapolating experimental interface velocity data.
Crohn's disease: does race matter?

OBJECTIVE: The severity of Crohn’s disease (CD) has been reported to be greater in blacks than in whites. This possible disparity may be due, in part, to differences between these groups in health care utilization and accessibility. To explore these issues, we conducted a multicenter survey of patients with CD. METHODS: One-hundred and forty-five blacks with CD, recruited from four teaching hospitals and five private practices, and identified by medical record review or ICD-9 code, were enrolled and matched to 407 whites with CD (by age, gender, and practice type [teaching vs private practice setting]). Participants were interviewed regarding medical history, health status, personal health care practices during the preceding 5 yr, and beliefs regarding health care in the general population. RESULTS: Blacks and whites were similar with respect to age of CD onset, lag in time to diagnosis, and number of gastrointestinal (GI)-related hospitalizations and surgeries. Medication usage patterns were also similar in the two groups. Quality of life, measured by SF-36, was lower in all categories for blacks, compared with whites. Blacks were more likely to have had to stop work (p < 0.01) and have lost more work days (p < 0.01) than were whites. Whites were more likely to have health insurance and be able to identify a regular provider than were blacks. Blacks were more likely to report the following: receiving Medicaid; difficulty affording health care; delaying appointments due to financial concerns; difficulty traveling to their provider’s office; and experiencing unreasonable delays at their provider’s office. After adjusting for potential confounding variables, we found no differences between the groups, except for the number of days of work lost because of CD. CONCLUSIONS: These data suggest that black and white patients have similar reported disease presentations and course, and contrast with prior reports suggesting a more severe disease course among black patients. Although the disease itself appears similar, there were numerous reported differences between the races in health care utilization practices and in disease impact upon daily activities. We suggest that apparent disparities in CD according to race are actually due to social and economic factors, and not to the disease itself.
‘This inscrutable principle of an original organization’: epigenesis and ‘looseness of fit’ in Kant’s philosophy of science

Abstract Kant’s philosophy of science takes on sharp contour in terms of his interaction with the practicing life scientists of his day, particularly Johann Blumenbach and the latter’s student, Christoph Girtanner, who in 1796 attempted to synthesize the ideas of Kant and Blumenbach. Indeed, Kant’s engagement with the life sciences played a far more substantial role in his transcendental philosophy than has been recognized hitherto. The theory of epigenesis, especially in light of Kant’s famous analogy in the first Critique (B167), posed crucial questions regarding the ‘looseness of fit’ between the constitutive and the regulative in Kant’s theory of empirical law. A detailed examination of Kant’s struggle with epigenesis between 1784 and 1790 demonstrates his grave reservations about its hylozoist implications, leading to his even stronger insistence on the discrimination of constitutive from regulative uses of reason. The continuing relevance of these issues for Kant’s philosophy of science is clear from the work of Buchdahl and its contemporary reception.
Comparison of alpha1 Adrenoceptors in the Prostate Capsule of Men with Symptomatic and Asymptomatic Benign Prostatic Hyperplasia

The objective of this study was to compare the binding and functional properties of alpha 1 adrenoceptors in prostate capsules obtained from men with symptomatic and asymptomatic benign prostatic hyperplasia (BPH) undergoing simple retropubic prostatectomy and cystoprostatectomy respectively. Saturation experiments using 125I-Heat demonstrated that the density and binding affinity of alpha 1 adrenoceptors in the prostate capsules obtained from men with symptomatic and asymptomatic BPH were similar. Non-cumulative dose response experiments using phenylephrine demonstrated that the magnitude of the contractile response to phenylephrine was 4-fold greater in the prostate capsules from men with symptomatic BPH than from those with asymptomatic BPH. The EC50 of phenylephrine in the prostate capsules of men with symptomatic and asymptomatic BPH was similar. A correlation between alpha 1 adrenoceptor density and phenylephrine Emax was not observed, implying that either alpha 1 adrenoceptors are not localised exclusively to the prostate smooth muscle or that spare alpha 1 adrenoceptors exist. This study suggests that the neuropharmacological properties of the prostate capsule may play a significant role in the development of infravesical obstruction in the ageing male population.
Mean Power Estimation with a Recursive Filter

Power estimates from smoothed detector outputs of stationary signals are analyzed for linear, square law, and logarithmic receiverdetectors. Smoothing is accomplished with a first-order recursive digital filter. lnput amplitude is assumed to be Rayleigh distributed and detector output samples independent. Expansion of results to other distributions is indicated.
A model for central synaptic junctional complex formation based on the differential adhesive specificities of the cadherins

Cadherins control critical developmental events through well-documented homophilic interactions. In epithelia, they are hallmark constituents of junctions that mediate intercellular adhesion. Brain tissue expresses several cadherins, and we now show that two of these, neural (N)- and epithelial (E)-cadherin, are localized to synaptic complexes in mutually exclusive distributions. In cerebellum, N-cadherin is frequently found associated with synapses, some of which are perforated, and in hippocampus, N- and E-cadherin-containing synapses are found aligned along dendritic shafts within the stratum lucidum of CA3. We propose that the cadherins function as primary adhesive moieties between pre- and postsynaptic membranes in the synaptic complex. According to this model, once neurites have been guided to the vicinity of their cognate targets, it is the differential distribution of cadherins along the axonal and dendritic plasma membranes, and ultimately cadherin self-association, that "locks in" nascent synaptic connections.
Toxic mutations in the recA gene of E. coli prevent proper chromosome segregation.

The recA gene of Escherichia coli is the prototype of therecA/RAD51/DMC1/uvsX gene family of strand transferases involved in genetic recombination. In order to find mutations in the recA gene important in catalytic turnover, a genetic screen was conducted for dominant lethal mutants. Eight single amino acid substitution mutants were found to prevent proper chromosome segregation and to kill cells in the presence or absence of an inducible SOS system. All mutants catalyzed some level of recombination and constitutively stimulated LexA cleavage. The mutations occur at the monomer-monomer interface of the RecA polymer or at residues important in ATP hydrolysis, implicating these residues in catalytic turnover. Based on an analysis of the E96D mutant, a model is presented in which slow RecA-DNA dissociation prevents chromosome segregation, engendering lexA -independent, lethal filamentation of cells.
Quantum (nano-scale) limit in a parallel magnetic field in layered Q1D conductors

We show that electron wave functions in a quasi-one-dimensional (Q1D) layered conductor in a parallel magnetic field are always localized on conducting layers. Wave functions and electron spectrum in a quantum limit, where the “sizes” of quasi-classical electron orbits are of the order of nanoscale distances between the layers, are determined. Possible applications of our results to physical properties of Q1D materials in their superconducting and metallic phases are discussed.
Kinetics of vein graft hyperplasia: Association with tangential stress * **

Abstract Vein grafts become thicker as they adapt to arterial circulation, and in large measure this is the consequence of cellular hyperplasia. The kinetics of smooth muscle cell (SMC) and endothelial cell (EC) replication were evaluated in rabbit jugular vein segments transplanted into the carotid arterial circulation to define the role of cell proliferation in this process, and these data were correlated with dimensional changes in grafts from 1 hour to 24 weeks after implantation. At 1 hour most of the perianastomotic endothelium was denuded, as were occasional cells in the graft away from the anastomosis. EC replication (thymidine labeling index) in the center of the graft increased 400 times during the first week and produced an intact endothelial surface by 2 weeks. The EC thymidine index then fell progressively to quiescent pretransplant levels by the twelfth week. SMC replication was maximal at 1 week after grafting and returned to near quiescent levels at 12 and 24 weeks. Graft wall thickness and cross-sectional area reached a maximum at 12 weeks and then remained constant. Deoxyribonucleic acid content exhibited a thirty-five- fold increase in the first 4 weeks, then did not change. Likewise, SMC mass did not increase after 4 weeks. Further increase in cross-sectional wall area between 4 and 12 weeks was accounted for by accumulation of connective tissue. The final ratio of luminal radius to wall thickness decreased to a level equal to that of normal artery. Since blood pressure did not change over the period of the study, this observation supports a possible regulatory role for wall tangential stress in the modification of vein graft structure after transplantation into the arterial circulation. (J VASC SURG 1987;5:126-36.)
SU-FF-T-302: A Secure Web-Based, Real-Time System for Peer-Review, Quality Assurance and Clinical Outcome Studies in Radiation Therapy

Purpose: To develop a secure, integrated relational database and a system of web-based client applications for radiation therapy data submission, archiving, retrieval and data mining for performing peer-review, quality assurance and clinical outcome studies. Method and Materials: The Resource Center for Emerging Technologies (RCET) System was developed at our institution to support NCI sponsored advanced technology clinical trials. This system features multi-tiered distributed client-server architecture; content-based relational database for data storage (supports DICOM, DICOM-RT, RTOG and common electronic image formats), retrieval and data mining; web-based client applications for data submission and rapid review. The RCET System has the necessary tools for peer-review and quality assurance of radiation therapy planning data. Clinical outcome studies are currently conducted in our research office through a labor intensive process. Data are collected manually in code sheets and entered into a simple database. Clinical data are manually retrieved and analyzed for outcomes. We propose to automate this process by fully utilizing the RCET infrastructure. Customized web-based applications and protocol specific data forms are added. Patient and treatment records from hospital information system (HIS), facility management system (FMS) and treatment planning system (TPS) are extracted and automatically archived. Data mining, rapid review and reporting tools designed for outcome studies are added. Results: The RCET infrastructure has been developed and extensive field testing is underway. Electronic data entry forms have been developed with automatic upload into the RCET database. Data from HIS, FMS and TPS have been extracted. New tools are added for outcome studies. Conclusion: The RCET system has the necessary tools for peer-review and quality assurance of radiation therapy planning data. Extension of RCET to support clinical outcome studies is feasible and cost-effective. Proactive in addition to retrospective studies are possible. This work is supported by NCI Grants CA 81636 and CA 81647.
Warm temperatures activate TRPV4 in mouse 308 keratinocytes

Mammalian survival requires constant monitoring of environmental and body temperature. Recently, several members of the transient receptor potential vanilloid (TRPV) subfamily of ion channels have been identified that can be gated by increases in temperature into the warm (TRPV3 and TRPV4) or painfully hot (TRPV1 and TRPV2) range. In rodents, TRPV3 and TRPV4 proteins have not been detected in sensory neurons but are highly expressed in skin epidermal keratinocytes. Here, we show that in response to warm temperatures (>32 degrees C), the mouse 308 keratinocyte cell line exhibits nonselective transmembrane cationic currents and Ca2+ influx. Both TRPV3 and TRPV4 are expressed in 308 cells. However, the warmth-evoked responses we observe most closely resemble those mediated by recombinant TRPV4 on the basis of their electrophysiological properties and sensitivity to osmolarity and the phorbol ester, 4alpha-phorbol-12,13-didecanoate. Together, these data support the notion that keratinocytes are capable of detecting modest temperature elevations, strongly suggest that TRPV4 participates in these responses, and define a system for the cell biological analysis of warmth transduction.
Conformational effects of cations and pH on human growth hormone in solution.

Human GH (hGH) binding to membrane receptors is uniquely enhanced by 10 mM Ca++ and Mg++ or 150 tnM Na+ and K+. This study has used polarization of fluorescence (P) and circular dichroism (CD) to identify cation-dependent conformational alterations in hGH. CD indicated that the secondary structure of hGH consisted of 52% a-helix structure, 23% β-structure, and 25% disordered structure at pH 7.5. Increases in pH caused a small increase in a-helix structure to 55% at pH 10.5 with little change in β- structure. Decreases in pH from 7.5 resulted in decreases in ahelix and β-structure to 44% and 8%, respectively, at pH 4.1. Relatively large decreases in ordered structure occurred between pH 6 and 4. This corresponded to the pH optimum of hGH binding to membranes at pH 5.5. Cation-specific changes in structure were observed with increases in cation concentration generally associated with increases in ordered structure, i.e. α-helix and/or β-structure. The cation concentration range in which changes in structure...
A study of M center formation in additively colored KCl

Additively colored crystals of KCl were cooled rapidly from a high temperature and then exposed to light absorbed by the F band. The rate of growth of the M band was initially low and increased markedly during the first part of the irradiation giving rise to what is called a “delay period” in the M center formation. During this delay period it was observed that 1. the quantum efficiency of F center fluorescence decreases by a factor of 3 or 4, and 2. the ability to convert F centers to F′ centers is reduced by about a factor of 3. These effects are interpreted as arising because of an appreciable decrease in the average nearest neighbor F center separation during this period.
Growth of protein crystals suspended in a closed loop thermosyphon

Abstract The quality of protein crystals often suffers from their growth at a liquid or solid surface. A novel solution growth method was developed to alleviate this problem. A growing crystal is suspended in a specially configured upflow of supersaturated nutrient, which is provided by the effect of fluid buoyancy in a closed loop thermosyphon. The flow rate and supersaturation are controlled by the temperature distribution in the thermosyphon, while contact of the crystal with the wall during growth is practically eliminated. The method was applied to the growth of lysozyme single crystals, with surprising results. While the orthorhombic form of lysozyme grew readily to the suspension limit of this particular apparatus (1.5 mm), the tetragonal form grew only to a maximum size less than 0.1 mm. Seed crystals of tetragonal lysozyme introduced into stagnant batch controls did not experience the growth cessation that the suspended crystals did. A likely cause of this growth cessation is the fluid shear forces on the suspended crystals.
Making the web more inclusive with adaptive user interfaces

I build user interface that adapt their structure, appearance and behavior to the goals, abilities, preferences and cultural norms of their users. Prior work in adaptive user interface community has demonstrated that adaptive and adaptable interfaces can improve users' performance and satisfaction. These findings alone should make adaptation a core component of the user interface design practice. But I argue that adaptive interactive systems are even more fundamentally important: they help overcome implicit biases built into most interfaces and they are a scalable approach for democratizing access to digital resources. To convince you of it, I will first present several examples of situations in which the typical one-size-fits-all user interfaces can be a source of unintended, but systematic discrimination causing some groups to be less likely than others to take advantage of a digital resource in the first place, or causing them to have a less efficient or substantially different experience compared to their peers. I will then present examples of several adaptive user interfaces that successfully provided more equitable experiences to broader populations compared to traditional non-adaptive designs. I will conclude by reflecting on the major challenges that stand in the way of broad adoption of adaptive techniques in practice. In particular, I will highlight the mismatch between the abstractions needed to develop effective adaptive user interfaces and the current software engineering practice.
Positive child well-being: an index based on data for individual children.

Data from the 2007 National Survey of Children’s Health are used to develop an index of positive child well-being that has several innovative and important characteristics. It distinguishes child well-being from contexts of child development; it is built with rich micro-data (rather than population-level macro-data) to create unique measures of well-being for individual children; and it focuses on positive, rather than negative, aspects of development. These data can be aggregated to provide a perspective on the proportions of children in the population who are doing well on all, some, or no developmental domains. Based on child development theory and research, the index is constructed within a framework of four conceptually distinct developmental domains, each of which is comprised of three sub-domains. The index distinguishes among children in predicted directions, by poverty level and parental education. White children tend to do better than Hispanic or black children in all domains, though neither minority subgroup is consistently better or worse off than the other subgroup. Girls score slightly higher than boys on the index. About three in four children score positively on three or four domains. The index provides a composite, multidimensional view of positive child well-being that can be useful to researchers and policy analysts, and which addresses some weaknesses of other similar indices.
Resistance to HIV protease inhibitors

Resistance to the HIV-1 protease inhibitor indinavir involves the accumulation of multiple amino acid substitutions in the viral protease. A minimum of 11 amino acid positions have been identified as potential contributors to phenotypic resistance. Three or more amino acid substitutions in the protease are required before resistance becomes measurable (> or = four-fold). Further losses in susceptibility follow the stepwise accumulation of additional amino acid substitutions, indicating that antiviral activity (selective pressure) is maintained despite the appearance of multiple amino acid substitutions in the viral protease. Importantly, the sequential nature of these changes indicates that the effects of these substitutions are additive, and that the evolution of resistance is driven by viral replication. This result has significant implications for therapy. It predicts that viral variants resistant to indinavir are unlikely to pre-exist in protease inhibitor-naive patients, and further, that high-level resistance can only develop if the virus is allowed to replicate in the presence of the drug. The use of indinavir in combination with other antiretroviral agents has been demonstrated to dramatically reduce the incidence of resistance mutations, suggesting that with maximal suppression of viral replication, long-term control of HIV-1 infection may be achievable. Thus, the goal of therapy must be to never to allow the virus to replicate. This can be best accomplished by initiating therapy with a maximally suppressive regimen, to reduce viral replication as much as possible, and by imposing a high genetic barrier to resistance. Previous use of other protease inhibitors or inadequate adherence to therapy may compromise the long-term benefit of indinavir by allowing the virus to gain a foothold through the development of resistance. An understanding of these issues will be critical in realizing the full potential of this potent new drug for the control of HIV-1 infection.
Dynamics of fluid/particulate mixtures in tube flow

Magnetic resonance imaging (MRI) techniques have been utilized to experimentally measure the velocity profile of fluid/particulate mixtures as a function of flow rate, particle loading, and particle size. The experimental velocity profiles in tube flow were described by a power law model; the power law parameter decreased as flow rate, particle loading, and particle size increase. This work is relevant to aseptic processing of particulate foods.
A Mixed Finite Element Method for Elasticity in Three Dimensions

We describe a stable mixed finite element method for linear elasticity in three dimensions.
Trimodal spectroscopy as a tool for detecting cervical squamous intraepithelial lesions in vivo

Using intrinsic fluorescence, diffuse reflectance and light scattering spectroscopy we extracted quantitative biochemical and morphological information in vivo about the bulk tissue and the epithelial cell nuclei of ectocervical sites from 44 patients. Significant changes were observed in tissue morphology and biochemistry between normal, squamous metaplastic and squamous intraepithelial lesion (SIL) sites. The combined use of all three spectroscopic techniques (tri-modal spectroscopy) yielded superior results for detecting SILs than any one of the techniques alone.
EXPERIMENTAL TRANSMISSION OF CUTANEOUS CHYTRIDIOMYCOSIS IN DENDROBATID FROGS

In a series of three experiments during March–October, 1998, two species of captive-bred poison dart frogs (Dendrobates tinctorius and D. auratus) were exposed to Batrachochytrium dendrobatidis, a recently-described chytridiomycete fungus (chytrid) that was originally isolated from a blue poison dart frog (D. azureus). All frogs exposed to the chytrids developed a fatal skin disease, whereas none of the control frogs developed skin lesions. The most consistent clinical sign in chytrid-exposed frogs was excessive shedding of skin. Gross lesions were subtle, usually affected the legs and ventrum, and consisted of mild skin thickening and discoloration. Microscopic examination of shed skin pieces and/or skin imprints demonstrated the presence of chytrids and was used for ante mortem and post mortem confirmation of chytrid infection. Histologically, there was epidermal hyperkeratosis, hyperplasia, and hypertrophy associated with low to moderate numbers of chytrids in the keratinized layers. These experiments ...
Parathyroid venous sampling: a review of the technique and its utility in localizing parathyroid adenoma

Learning Objectives To discuss the technique of venous catheterization and sampling for localization of parathyroid adenoma. To determine the relevance of parathyroid venous sampling at our institution by performing a retrospective analysis of 29 patients over a 6 year period. Background Selective thyroid venous catheterization and detection of a venous PTH gradient allow for lateralization of parathyroid adenoma. Because of the rare instances that the inferior thyroid vein is not the major venous drainage route, our institution samples multiple other regional veins, to ensure that, if present, a PTH gradient is detected. Clinical Findings/Procedure Details Patients are referred by a single surgeon to a single interventional radiologist for parathyroid venous sampling. Venous samples for intact parathyroid hormone are obtained from multiple veins including: superior thyroid, internal jugular, innominate, inferior thyroid, thymic (if identified), left superior intercostal, SVC (above and below azygos vein), right hepatic, IVC, and bilateral iliac. Results from 29 patients, over a 6 year period, demonstrate that parathyroid venous sampling alone, or in conjunction with 4-D Neck CT, is effective for pre-surgical lateralization of parathyroid adenoma. Conclusion and/or Teaching Points Although an uncommon procedure, it is important to understand the technique and application of parathyroid venous sampling. The procedure is successful at localizing parathyroid adenomas pre-operatively, resulting in shorter operating room times and reduced patient morbidity.
The response of sweet corn to HF and SO2 under field conditions

Abstract “Marcorss” sweet corn plants grown in field plots were exposed continuously in open-top chambers for 32 days to ambient air, charcoal-filtered air or charcoal-filtered air containing HF ( ca. 0.5 μgF m −3 ), SO 2 ( ca. 235 μg m −3 ), or the two pollutants combined. Elliptical chlorotic leasions appeared after 23 days on leaves of plants exposed to SO 2 /HF, and shortly thereafter on plants exposed to all other treatments. At harvest, the number of plants with lesions was significantly greater in chambers supplied with SO 2 /HF than in chambers with SO 2 , HF, or filtered air. The different treatments had no effect on fresh or dry weights of leaves, husks, or tassels, height of plants, or number of kernels per ear. Exposure to SO 2 /HF reduced the fresh and dry weights of stalks. There were fewer mature ears in the SO 2 /HF and unfiltered air treatments than in the others. The reduction in yield from SO 2 /HF was about the same as that ascribed to ambient photochemical oxidants in the unfiltered air treatment. HF combined with SO 2 had no effect on accumulation of S as compared with SO 2 alone, but there was a striking reduction in accumulation of foliar F in plants exposed to SO 2 /HF as compared with HF alone.
Phospholipid-Stabilized Microbubble Foam for Injectable Oxygen Delivery

A detailed study is presented on the synthesis and characterization of purely oxygen-filled microbubbles (OMBs) stabilized by phospholipids. Microbubbles with a diameter of less than 10 μm were generated and concentrated to >50 vol % in saline. The lipid acyl chain length had little effect on the size distribution but profoundly affected the foam stability. For example, OMBs stabilized by dipalmitoyl phosphatidylcholine (DPPC) degraded over 3 weeks, but OMBs stabilized with distearoyl phosphatidylcholine (DSPC) retained over half of their initially encapsulated gas. Interestingly, the polydisperse size distribution remained nearly constant as the foam slowly broke down. Injection into an undersaturated solution led to the immediate release of the oxygen gas core. Injectable gas delivery by OMBs may find use in a variety of medical and industrial fields.
Phosphorylation of serine 916 of Ras-GRF1 contributes to the activation of exchange factor activity by muscarinic receptors.

The Ras-GRF1 exchange factor is strongly implicated in the control of neuronal Ras. The activity of Ras-GRF1 is regulated by increases in intracellular calcium and the release of Gβγ subunits from heterotrimeric G-proteins. Increases in Ras-GRF1 activity toward Ras that are stimulated by receptors coupled to G-proteins are associated with enhanced phosphorylation of Ras-GRF1 on one or more serine residues. Co-expression of Ras-GRF1 with subtype 1 human muscarinic receptors in COS-7 cells allowed mapping of a carbachol-stimulated phosphorylation site to a region composed of residues 916–976. Site-directed mutagenesis replaced each of the serine residues within this region with alanine and demonstrated that serine 916 is a major site of in vivo phosphorylation of Ras-GRF1 in both COS-7 cells and NIH-3T3 fibroblasts. Serine 916 was a substrate for protein kinase A both in vivo and in vitro, suggesting a novel link between the cAMP and Ras signaling systems. Carbachol-dependent phosphorylation of serine 916 occurred through a protein kinase A-independent pathway, however. Full-length Ras-GRF1 that contains an alanine 916 mutation was only partially activated by carbachol, suggesting that phosphorylation at residue 916 is necessary for full activation. Phosphorylation of serine 916 in response to forskolin treatment did not, however, increase the activity of Ras-GRF1, indicating that it is not sufficient for activation.
A method for the determination of thermal conductivity of sheet materials by differential scanning calorimetry (DSC)

Abstract The differential scanning calorimeter was adapted to perform the measurement of thermal conductivity of polymeric and other sheet materials. Conditions for maintaining stable and reproducible heat flow were developed, reproducible and recyclible sensor materials were fabricated, and the use of a thermal lubricant at the solid-solid interfaces tested. The technique was applied to poly(methylmethacrylate) and poly(tetrafluoroethylene) sheets of varied thicknesses over the temperature range 45–175 °C. Values for thermal conductivity were somewhat lower than those quoted in the literature. Further improvements and calibration methods are discussed.
Delivery rate accuracy of portable, bolus-capable infusion pumps used for patient-controlled continuous regional analgesia.

Background and Objectives Portable patient-controlled pumps used for perineural local anesthetic infusion appear to be gaining acceptance and are used for an increasing number of medically unsupervised ambulatory patients. The infusion rate accuracy and reliability of these pumps, which allow patient-controlled boluses of potentially toxic medication, has not been independently investigated. We performed this laboratory study to define the flow-rate accuracy, reliability, and profiles of various portable bolus-capable infusion pumps and varied several factors that may influence pump performance. Methods Using a computer/scale combination, 4 electronic pumps were tested with 1 and 2 sets of batteries over 100 hours. One elastomeric pump was tested with its flow-regulator at room temperature (20°C to 24°C), skin temperature (32°C), and increased temperature (36°C). The elastomeric pump was also tested by varying the height of the pump relative to the distal end of the catheter. Results Infusion rate accuracy differed significantly among the pumps, exhibiting flow rates within ±15% of their expected rate for 29% to 100% of their infusion duration. Changing the batteries after 50 hours affected the profile of 1 of the 4 electronic pumps. For the elastomeric pump, an increase in temperature significantly increased the infusion rate. An increase or decrease in pump-to-scale height significantly increased or decreased the infusion rate, respectively. Conclusions These results suggest that factors such as flow-rate accuracy and consistency, infusion profile, and temperature sensitivity should be taken into consideration when choosing a portable infusion pump for local anesthetic administration. Reg Anesth Pain Med 2003;28:17-23.
Stroke: sedation and anesthesia during endovascular stroke therapy.

A large, retrospective study indicates that in patients with acute ischemic stroke, endovascular interventions performed under conscious sedation carry a lower risk of poor neurological outcome and mortality than those performed under general anesthetic. Owing to a number of potential confounding factors, however, the results must be interpreted with caution.
On nontrivial solutions of a Dirichlet problem whose jumping nonlinearity crosses a multiple eigenvalue

Let Ω be a bounded domain in RN (N ⩾ 2) with smooth boundary ∂Ω. Let p(·)R → R be a continuous function such that p(0) = 0 and limt → ± ∞(p(t)t) = p± exist. We discuss the existence of nontrivial solutions of the Dirichlet problem, −Δu = p(u) in Ω, u = 0 on ∂Ω. Our hypotheses relate the position of the point (p−, p+) in the plane with the extended spectrum of −Δ. They seem to allow noticeably greater freedom for the numbers p± than is usually found in the literature in the sense that the interval with end points p± is here permitted to contain in its interior an eigenvalue of arbitrarily multiplicity of −Δ. It also appears that we significantly weaken some technical conditions on p(·) of another paper which treats the crossing of a simple eigenvalue.
The possibility of seiemic measurement of the rotation of the Earth's core

The calculations of Inglis show that the rate of transfer of angular momentum to the Earth's (liquid) core may be small enough to permit the axis of rotation of the core to lag about 2° behind that of the rock-mantle in the precessional motion of the Earth. The travel-time of P′ would be altered by about one-fifth of a second, which is too small to be detected by a single observation made with even the best instrument, but can be brought out statistically when we have accumulated about three thousand clear measurements, on sensitive vertical-component seismographs, of the P′-waves from accurately located earthquakes.
Musculoskeletal Disorder Risk Associated with Auto Rotation Angle during an Assembly Task

The purpose of this study was to quantify how musculoskeletal disorder exposure risk changes in an auto assembly task as a function of car body rotation. Twelve subjects participated in the study. There were three car body angles including 1) zero or standard, 2) forty-five degrees and 3) ninety degrees from horizontal. Musculoskeletal exposure included spine loads, spine posture, shoulder posture, neck posture and wrist posture, as well as normalized electromyography of the shoulder and neck. The results showed that musculoskeletal disorder exposure risk decreased as the car was rotated to forty-five degrees and further decreased as the car was rotated to ninety degrees. Thus, rotating the car body reduces musculoskeletal exposure which in turn may reduce the risk of musculoskeletal disorders. It should be noted that the results may vary with other assembly tasks.
Management of acute ureteral obstruction in pregnancy utilizing ultrasound-guided placement of ureteral stents

Of 6,275 pregnancies seen at our institution over a two-year period, 5 patients required operative intervention for acute urinary obstruction unresponsive to medical management. Ultrasonography was able to definitively diagnose the presence of an obstructing calculus in 4 of 5 patients. Using ultrasound guidance, 7 indwelling ureteral stents were successfully placed with local anesthesia supplemented by intravenous sedation. Complications consisted of distal stent migration in 1 patient. This method of management was successful for symptomatic nephrolithiasis in a pregnant renal transplant patient. Endoscopic placement of ureteral stents under ultrasound guidance is an effective, safe method of urinary decompression, with no radiation risks imparted to the mother or fetus. Definitive therapy then can be safely deferred to the post-partum period.
Changes in serum and bile bilirubin induced by acute hemolysis

The association between chronic hemolysis and pigment gallstones is well known but not adequately understood. To define the source and quantity of insoluble pigment resulting from hemolysis, hepatic bile in miniature swine was studied during the intravenous infusion of distilled water. Concentrations of both total bilirubin and insoluble unconjugated bilirubin rose rapidly during the first 2 hr to levels more than seven times above control values. In the third hour, unconjugated pigment continued to increase while total bilirubin plateaued, suggesting that glucuronidation or transport maxima had been reached. Elevations in unconjugated bilirubin could not be accounted for by the intrabiliary hydrolysis of conjugated bilirubin. It is concluded that hemolysis results in the secretion of large quantities of insoluble bilirubin directly into bile. This process may represent an important step in the development of pigment polymers or precipitates.
Sleeve gastrectomy in rats improves postprandial lipid clearance by reducing intestinal triglyceride secretion.

Background & Aims Postprandial hyperlipidemia is a risk factor for atherosclerotic heart disease and is associated with the consumption of high-fat diets and obesity. Bariatric surgeries result in superior and more durable weight loss than dieting. These surgeries are also associated with multiple metabolic improvements, including reduced plasma lipid levels. We investigated whether the beneficial effects of vertical sleeve gastrectomy (VSG) on plasma lipid levels are weight independent. Methods VSG was performed on Long-Evans rats with diet-induced obesity. Controls were sham-operated animals who were either pair-fed or ad libitum-fed. We measured fasting and postprandial levels of plasma lipid. To determine hepatic and intestinal triglyceride secretion, we injected the lipase inhibitor poloxamer 407 alone or before oral lipid gavage. 13 C-Triolein was used to estimate postprandial uptake of lipid in the intestine. Results Rats that received VSG and high-fat diets had markedly lower fasting levels of plasma triglyceride, cholesterol, and phospholipid than obese and lean (pair-fed) controls that were fed high-fat diets. Rats that received VSG had a marked, weight-independent reduction in secretion of intestinal triglycerides. VSG did not alter total intestinal triglyceride levels or size of the cholesterol storage pool nor did it affect the expression of genes in the intestine that control triglyceride metabolism and synthesis. VSG did not affect fasting secretion of triglyceride, liver weight, hepatic lipid storage, or transcription of genes that regulate hepatic lipid processing. Conclusions VSG reduced postprandial levels of plasma lipid, independently of body weight. This resulted from reduced intestinal secretion of triglycerides following ingestion of a lipid meal and indicates that VSG has important effects on metabolism.
On the evaluation of adhesion of coatings by automatic scratch testing

Automatic scratch testing is an expedient technique for comparatively evaluating the cohesive failure load and adhesion failure load of thin coatings on various substrates. In combination with SEM examination of the scratch track, this technique has been used herein to detect and evaluate various effects on coating strength and adhesion. For soft Triballoy T-800 and Stellite SF-6 cobalt-base coatings on 4340 low alloy steel, adhesion was found to be strong and failure was found to be cohesive in the coating. In the presence of a plated chromium interlayer, pre-existing cracks lowered substantially the cohesive failure load, which was also lowered by an increase in the coating deposition pressure. The spacing of transverse cracks within the coating was found in all cases to decrease with increasing applied normal load. In soft aluminum coatings on depleted uranium (DU)-0.75% Ti alloy specimens, alloying aluminum with magnesium or zinc enhanced the coating strength and adhesion. In (Al-Mg) coatings on this ...
"I Just Feel Safe With Him": Emotional Closeness in Male Youth Mentoring Relationships

This study provides an in-depth examination of close and enduring formal mentoring relationships between adolescent boys and adult men. Qualitative interviews conducted with 12 adolescent and adult pairs of participants (n 24) in a one-to-one communitybased youth mentoring program were analyzed thematically using a holistic-content approach. This yielded six major themes: (a) the importance of relationships with adult men in adolescence, (b) mentors’ desires to be involved and emotionally connected male role models, (c) the close and enduring nature of the emotional connections forged, (d) the ways these relationships provided safe places for emotional vulnerability and support, (e) how these relationships helped some boys manage feelings of anger more effectively, and (f) vacillations on the part of the mentors between more and less conventional forms of masculinity in relation to the emotional nature of these relationships. The findings of this study suggest that close and enduring male mentoring relationships have the potential to provide adolescent boys with models for less constricting and conventional forms of masculinity, particularly with regard to emotional disclosures and expressivity.
Gamma-hydroxybutyric Acid Tolerance and Withdrawal in a Rat Model

Long-term daily use of gamma-hydroxybutyrate (GHB) and related compounds has recently been associated with a withdrawal syndrome. To the best of the authors’ knowledge, there are currently no animal models of GHB withdrawal. Objectives: The authors studied and described the effect of chronic dosing of GHB (3–6 days) on tolerance and withdrawal in a rat model. Methods: Rats were administered GHB every three hours via intraperitoneal catheter. Groups of rats (2 per group) were dosed with GHB for either 3 (24 doses), 4 (32 doses), 5 (40 doses), or 6 (48 doses) days. The GHB dose was 0.25 g/kg for doses 1–8, 0.75 g/kg for doses 9–12, 1 g/kg for doses 13–16, 1.25 g/kg for doses 17–24, 1.5 g/kg for doses 25-32, 1.75 g/kg for doses 33– 40, and 2 g/kg for doses 41–48. Following the last dose of GHB, the rats were scored using a 16-point ethanol intoxication–withdrawal scale rating spontaneous behaviors, response to handling, grooming, and neurological signs. Lower scores indicate intoxication, while higher scores indicate withdrawal. Scores were recorded at hours 0, 1, 2, 3, 4, 5, 6, 9, 12, and 24. Results: Tolerance: Rats dosed with GHB for more days were less intoxicated one hour after their last GHB dose despite receiving higher doses. Withdrawal: The scores for all rats dosed with GHB increased at hours 4 (p ¼ 0.028), 5 (p ¼ 0.037), 6 (p ¼ 0.007), and 9 (p ¼ 0.024) after the last dose, indicating withdrawal. The scores demonstrated a linear increase dependent upon the number of days of GHB dosing at hours 3 (p \ 0.000), 4 (p ¼ 0.004), 5 (p ¼ 0.002), and 12 (p ¼ 0.039) as well as prior to the last dose at hour 0 (p ¼ 0.000). No rats developed seizures. Conclusions: Tolerance and mild withdrawal in rats can be induced by administering intraperitoneal GHB every three hours for 3-6 days. More prolonged dosing and higher doses of GHB may be necessary to induce severe withdrawal. Key words: gamma-hydroxybutyrate; GHB; tolerance; withdrawal; drug use. ACADEMIC EMERGENCY MEDICINE 2003; 10:697– 704.
Incorporation of a product of mevalonic acid metabolism into proteins of chinese hamster ovary cell nuclei

We have examined the nuclear localization of isoprenylated proteins in CHO-K1 cells labeled with [14C]mevalonate. Nuclear proteins of 68, 70, and 74 kD, posttranslationally modified by an isoprenoid, are also components of a nuclear matrix-intermediate filament preparation from CHO cells. Furthermore, the 68-, 70-, and 74-kD isoprenylated polypeptides are immunoprecipitated from cell extracts with two different anti-lamin antisera. Based on exact two-dimensional comigration with lamin B, both from rat liver lamin and CHO nuclear matrix-intermediate filament preparations, and its immunoprecipitation with anti-lamin antisera, we conclude that the 68-kD isoprenylated protein found in nuclei from [14C]mevalonate-labeled CHO cells is lamin B. The more basic 74-kD isoprenylated nuclear protein is similar in molecular mass and isoelectric pH variants to the lamin A precursor polypeptide reported by others. Starving cells for mevalonate results in a dramatic accumulation of a polypeptide that comigrates on two-dimensional, non-equilibrium pH gradient electrophoresis (NEPHGE) gels with the 74-kD isoprenylated protein. The 70-kD isoprenylated protein, which is resolved on NEPHGE gels as being higher in molecular mass and slightly more basic than lamin B, has not yet been identified.
POSSIBILITY AND CONSTRAINT: AFRICAN INDEPENDENCE IN HISTORICAL PERSPECTIVE

On the fiftieth anniversary of an ambiguous event – the referendum giving French Africans the choice of immediate independence or a new status within a ‘French Community’ – this article points to the alternative forms of political action which opened up at certain moments in African history and how, at other moments, some of those alternatives closed down. It assesses concepts, issues and arguments used in writing the history of Africa, now that the recent African past – spanning the last years of colonial rule and the years of independence – is becoming a focus of historical inquiry.
7.4: Extended Kerr Effect in a Polymer‐Stabilized Blue‐Phase Liquid Crystal Composite

As the electric field increases, the induced birefringence of a polymerstabilized bluephase liquid crystal gradually deviates from the conventional Kerr effect and finally saturates. A new convergence model, named extended Kerr effect, is proposed to explain this saturation phenomenon. This model will give a more accurate account on the electrooptic effect of the emerging blue phase LCDs.