cssi/SciSciGPT-SciSciNet huggingface dataset:
Role of lysosomotrophic reagents in glucocorticoid hormone action.

Abstract Administration of (10 mg/200 g) methylamine or chloroquine to adrenalectomized rats for 2 days followed by a single injection of either cortisol (2.5 mg/200 g) or dexamethasone (0.5 mg/200 g) resulted in a significant enhancement of the tyrosine aminotransferase enzymatic activity in rat liver versus rats given a single injection only of either steroid. Lysosomotrophic reagents were unable to induce tyrosine aminotransferase when administered alone. Cytosols from rat liver treated with lysosomotrophic reagents in vivo had approx. 20–30% more specific binding to [3H]dexamethasone as compared to the control, untreated rats. This enhanced binding was due to an increase in the concentration of the receptor rather than change in the affinity of the hormone for the receptor. Rat livers perfused with and homogenized in 10 mM Tris-HCl/0.25 M sucrose buffer (pH 7.5) containing about 5 mM lysosomotrophic reagents showed optimum stabilization of the steroid unbound glucocorticoid receptor in vitro at both 4°C and 25°C. These reagents had no effect on in vitro transformation of [3H]dexamethasone-receptor complex or on the binding of the thermally transformed receptor to the nuclei. It is concluded from these studies that lysosomotrophic reagents (a) enhance tyrosine aminotransferase induction by glucocorticoids and (b) stabilize unbound glucocorticoid receptor both in vivo and in vitro without any effect on in vitro transformation of the steroid-receptor complex.
Experienced clinical educators improve their clinical teaching effectiveness.

Objectives.—To determine if experienced clinical educators (CEs) can improve their teaching by incorporating 4 literature-based teaching methods into their instruction. Methods.—We trained 7 experienced CEs on the teaching methods during a monthly faculty development program. Each CE recorded use of these methods during 10 months on a personal digital assistant. We compared the CEs' teaching evaluations with those of nonparticipating faculty by analysis of variance at baseline, during the study period, and for 1 year after the study. Results.—Reported use of 2 teaching methods (priming and feedback) increased significantly over use at baseline; use of 2 other methods (teaching in the patient's presence and 1–2 focal teaching points) remained constant. Scores on the CEs' teaching evaluations were significantly higher during the study period on 1 item, whereas the comparison group showed no changes. The changes persisted during the follow-up period. CEs reported that the teaching methods focused the learner and teacher, making subsequent encounters more productive. They also found that the act of entering data daily prompted them to reflect on their teaching. Conclusions.—Experienced teachers can be persuaded to incorporate new methods into their daily teaching. Reflection on teaching is enhanced with group support and daily reminders. With these interventions, teaching effectiveness of these experienced educators improved.
Auditors' going‐concern judgments: rigid, adaptive, or both?

Purpose – The purpose of this paper is to examine when auditors' decision behavior is rigid and adaptive in the going‐concern judgment. Because rigid behavior has been found to produce inappropriate outcomes, understanding when decision behavior is rigid or adaptive can lead to improved decision making.Design/methodology/approach – An experiment is conducted using cases based on real companies to produce information search traces as dependent measures that are studied in the ill‐structured and structured parts of the going‐concern task.Findings – Auditors are adaptive in ill‐structured tasks and rigid in structured tasks as predicted by theory. Evidence of flawed decision making commonly found in studies of fixation and related concepts was not found.Research limitations/implications – The findings suggest the importance of explicitly accounting for task structure when studying decision behavior in situated contexts. Future research could assess whether task structure similarly impacts behavior in non‐aud...
Antitumor Agents XLVIII: Structure-Activity Relationships of Quassinoids as In Vitro Protein Synthesis Inhibitors of P-388 Lymphocytic Leukemia Tumor Cell Metabolism

A series of brusatol, bisbrusatol, and bruceantin esters were examined for their ability to inhibit protein synthesis in P-388 lymphocytic leukemia cells. Compounds which produced high T/C % values (170-272) resulted in ID50 of 5.4-15.5 microM for inhibition of whole cell protein synthesis, ID50 of 1.3-13 microM for inhibition of endogenous protein synthesis in cell homogenates, and ID50 of 1.9-6 microM for inhibition of polyuridine directed polyphenylalanine synthesis using "runoff" ribosomes and a "pH 5" enzyme preparation. The polyuridine directed polyphenylalanine synthesis requires neither initiation nor termination factors, suggesting that quassinoids are exclusively elongation inhibitors. Bruceantin, brusatol, and bisbrusatolyl malonate allowed a runoff of the polyribosomes to 80S free ribosomes. However, formation of the ternary complex and 80S initiation complex were not inhibited by the quassinoids. Thus, these agents do not affect the individual steps leading to the formation of a stable 80S initiation complex in P-388 cells. Brusatol, bruceantin, and bisbrusatolyl malonate inhibited the formation of the first peptide bond between puromycin and [3H]methionyl-transfer RNA bound to the initiation complex, indicating peptidyl transferase activity is inhibited by the quassinoids in P-388 cells. These studies also suggest that the free 80S ribosome is the site of binding by the quassinoid. Ribosomes actively conducting protein synthesis will continue protein synthesis and terminate before the quassinoids bind. This proves quassinoids are elongation inhibitors of tumor cells. A strong correlation was observed between potent antileukemic activity and the ability to inhibit protein synthesis in P-388 lymphocytic leukemia cells.
Why do people still die from brown-snake bites?

Brown snakes are the leading cause of snakebites and snakebite fatalities in Australia and the incidence may be rising. Most fatalities are the result of early events after the bite, often a general or cardiac collapse. Lack of appropriate first aid is a common finding. It is probable that an early thrombotic effect of venom procoagulants, prior to defibrination, is responsible for the cardiac collapse in most of these cases. CSL brown-snake antivenom, while not perfect, is usually effective if given in sufficient quantity, but cannot reverse established vital-organ damage. Increased public education about the danger of snakebite and correct first aid may reduce the death toll, and improved professional continuing education on snakebite is advisable but, ultimately, some brown-snake bite deaths are probably inevitable, despite optimum medical care.
The origin of some bone marrow fibroblasts

An attempt was mad to determine the origin of bone marrow fibroblasts which almost always appear when bone marrow aspirates and explants are grown on solid surfaces in tissue culture. Bone marrow aspirates from two individuals with chronic myelogenous leukemia demonstrating the Ph-1 chromosome and from an individual with acute leukemia demonstrating the trisomic C-group karyotype served as sources of the fibroblasts. These were analyzed for the presence of the marker chromosomes found in the leukemic cells of these patients. Over half of the dividing fibroblasts demonstrated the marker chromosomes. This positive finding indicates that at least some bone marrow fibroblasts are derived from hemopoietic stem cells. These cells should, therefore, prove useful in the study of cellular differentiation.
Analyses of In-Cage Singlet Radical-Pair Motions from Irradiations of 1-Naphthyl (R)-1-Phenylethyl Ether and 1-Naphthyl (R)-2-Phenylpropanoate in n-Alkanes

[reaction: see text] The regio- and stereochemistries of photo-Claisen reactions of 1-naphthyl (R)-1-phenylethyl ether ((R)-2), in combination with photo-Fries and photo-Claisen-type reactions of 1-naphthyl (R)-2-phenylpropanoate ((R)-1), have been investigated in n-alkanes of different viscosities and at several temperatures. Analyses of the results provide detailed information about the in-cage motions of the singlet prochiral 1-naphthoxy/1-phenylethyl radical pairs (radical-pair B) that are formed directly from (R)-2 and indirectly from (R)-1 via decarbonylation of singlet chiral 1-naphthoxy/2-phenylpropanoyl radical pairs (radical-pair A). In hexane at 23 degrees C, the photo-Claisen products from irradiations of (R)-2 retain up to 31% enantiomeric excess (ee), but the ees of the same photoproducts from (R)-1 are near 0%. This disparity is attributed to differences between the initial orientations of the constituent radicals of radical-pair B at the moment of their "birth". The regio- and stereoselectivities reach plateau values as the solvent viscosity increases, indicating that the relationships between the rates of radical-radical bond formation and either translational or tumbling motions within a solvent cage reach an asymptotic limit. Detailed analyses are presented of the various motions that are in competition within a solvent cage during the very short lifetimes of the radical pairs. The data, in toto, present interesting insights into how radical pairs move during short periods and over short distances when their solvent cages have walls of varying flexibility.
What is Heterodox Economics? Conversations with Historians of Economic Thought

Since its intellectual inception, the development of the economics discipline has been accompanied by divergence of thought. Through the years, particularly in the latter half of the twentieth century, a fissure has emerged within the discipline, sociologically dividing conventional, mainstream economics from the dissention of heterodox economics. The nature of that division, however, as well as the nature of heterodox thought is unclear. Historians of economic thought would seem to be uniquely suited to specify the nature of heterodox economics and the mechanism of its marginalization. Although anecdotal, personal interviews with historians of economic thought provide a breadth and depth of study not available through surveys with an immediacy not allowed by doctrinal examination. The purpose of this study and intent of this paper is to reveal the ways that orthodox and heterodox economics differ, whether heterodox economics has any clear research program other than criticizing the limits of the more orthodox view, and what aspects of heterodox economics remain underdeveloped, all through the lens of the historian of economic thought.
Roles of stromal cell RANKL, OPG, and M‐CSF expression in biphasic TGF‐β regulation of osteoclast differentiation

To better understand the complex roles of transforming growth factor-beta (TGF-beta) in bone metabolism, we examined the impact of a range of TGF-beta concentrations on osteoclast differentiation. In co-cultures of support cells and spleen or marrow osteoclast precursors, low TGF-beta concentrations stimulated while high concentrations inhibited differentiation. We investigated the influences of TGF-beta on macrophage colony stimulating factor (M-CSF), receptor activator of NF-kappaB ligand (RANKL), and osteoprotegerin (OPG) expression and found a dose dependent inhibition of M-CSF expression. RANKL expression was elevated at low TGF-beta concentrations with a less dramatic increase in OPG. Addition of OPG blocked differentiation at the stimulatory TGF-beta dose. Thus, low TGF-beta concentrations elevated the RANKL/OPG ratio while high concentrations did not, supporting that, at low TGF-beta concentrations, there is sufficient M-CSF and a high RANKL/OPG ratio to stimulate differentiation. At high TGF-beta concentrations, the RANKL/OPG ratio and M-CSF expression were both repressed and there was no differentiation. We examined whether TGF-beta-mediated repression of osteoclasts differentiation is due to these changes by adding M-CSF and/or RANKL and did not observe any impact on differentiation repression. We studied direct TGF-beta impacts on osteoclast precursors by culturing spleen or marrow cells with M-CSF and RANKL. TGF-beta treatment dose-dependently stimulated osteoclast differentiation. These data indicate that low TGF-beta levels stimulate osteoclast differentiation by impacting the RANKL/OPG ratio while high TGF-beta levels repress osteoclast differentiation by multiple avenues including mechanisms independent of the RANKL/OPG ratio or M-CSF expression regulation.
Snail Promotes Epithelial Mesenchymal Transition in Breast Cancer Cells in Part via Activation of Nuclear ERK2

Snail transcription factor is up-regulated in several cancers and associated with increased tumor migration and invasion via induction of epithelial-to-mesenchymal transition (EMT). MAPK (ERK1/2) signaling regulates cellular processes including cell motility, adhesion, and invasion. We investigated the regulation of ERK1/2 by Snail in breast cancer cells. ERK1/2 activity (p-ERK) was higher in breast cancer patient tissue as compared to normal tissue. Snail and p-ERK were increased in several breast cancer cell lines as compared to normal mammary epithelial cells. Snail knockdown in MDA-MB-231 and T47-D breast cancer cells decreased or re-localized p-ERK from the nuclear compartment to the cytoplasm. Snail overexpression in MCF-7 breast cancer cells induced EMT, increased cell migration, decreased cell adhesion and also increased tumorigenicity. Snail induced nuclear translocation of p-ERK, and the activation of its subcellular downstream effector, Elk-1. Inhibiting MAPK activity with UO126 or knockdown of ERK2 isoform with siRNA in MCF-7 Snail cells reverted EMT induced by Snail as shown by decreased Snail and vimentin expression, decreased cell migration and increased cell adhesion. Overall, our data suggest that ERK2 isoform activation by Snail in aggressive breast cancer cells leads to EMT associated with increased cell migration and decreased cell adhesion. This regulation is enhanced by positive feedback regulation of Snail by ERK2. Therefore, therapeutic targeting of ERK2 isoform may be beneficial for breast cancer.
Molecular and genetic ecotoxicologic approaches to aquatic environmental bioreporting.

Molecular and population genetic ecotoxicologic approaches are being developed for the utilization of arthropods as bioreporters of heavy metal mixtures in the environment. The explosion of knowled...
Measurement of retinal thickness by ocular coherence tomography in a case of scleral transparency in high myopia

Abstract Purpose Staphylomatous thinning of the sclera and retina are among the numerous changes associated with the elongated eye of high myopia. We report a case of scleral and retinal transparency in high myopia in which ocular coherence tomography was used to measure retinal and scleral thickness in vivo. Design Observational case report. Methods The clinical presentation and evaluation of a case of scleral transparency in high myopia are presented. Results This case demonstrates numerous anatomical changes to the sclera and retina known to occur in association with high myopia. Initial evaluation by optical coherence tomography demonstrated a retinal thickness of 74 μm and a scleral thickness of 80 μm. Conclusions Optical coherence tomography can be used to measure scleral and retinal thickness in vivo in a patient with high myopia. It is not known at this time what precautions are necessary in such a patient should intraocular surgery be required.
Regulation of signaling in B cells through the phosphorylation of Syk on linker region tyrosines. A mechanism for negative signaling by the Lyn tyrosine kinase.

The B cell antigen receptor (BCR) is coupled to the mobilization of Ca2+ by the protein-tyrosine kinase, Syk. Syk, recruited to the clustered BCR, becomes phosphorylated on three tyrosines (Tyr-317, Tyr-342, and Tyr-346) located within the linker region that separates the C-terminal catalytic domain from the N-terminal tandem Src homology 2 domains. Phosphorylation within the linker region can be either activating or inhibitory to Ca2+ mobilization depending on the sites that are modified. Syk that is not phosphorylated on linker region tyrosines couples the BCR to Ca2+ mobilization through a phosphoinositide 3-kinase-dependent pathway. The phosphorylation of Tyr-342 and -346 enhances the phosphorylation and activation of phospholipase C-γ and the early phase of Ca2+ mobilization via a phosphoinositide 3-kinase-independent pathway. The phosphorylation of Tyr-317 strongly dampens the Ca2+ signal. In cells that lack the Src family kinase, Lyn, the phosphorylation of the inhibitory Tyr-317 is suppressed leading to elevated production of inositol 1,4,5-trisphosphate and an amplified Ca2+ signal. This provides a novel mechanism by which Lyn functions as an inhibitor of BCR-stimulated signaling. Thus, Syk and Lyn combine to determine the pathway through which the BCR is coupled to Ca2+mobilization as well as the magnitude and duration of the Ca2+ flux.
Structure, Design and Process Control for Cu Bonded Interconnects in 3D Integrated Circuits

Three-dimensional integration (3DI) is a very promising fabrication methodology for extending the CMOS technology roadmap. As such, it is critical to evaluate the capability of this technique to provide reliable interconnection between stacked circuit layers. Since one of potential approaches for 3DI is through use of Cu bonded interconnects, the viability of this process is evaluated in this paper. More specifically, the integrity of bonded Cu interconnects has been investigated as a function of pattern geometry and density, as well as bonding process parameters. It is found that a pattern density around or more than 13 % coupled with the application of a small down-force (~1000 N) prior to temperature ramping and followed by large down-force (~10000 N) during bonding gives optimal yield and alignment accuracy, and provides excellent electrical connectivity and thermal reliability. This result is a key milestone in establishing the manufacturability of Cu-based interconnections for 3D integration technology
Effects of oxidized α-, γ- and δ-tocopherols on the oxidative stability of purified soybean oil

Oxidized α-, γ- and δ-tocopherols were prepared in methanol containing methylene blue for 30 h under light. The effects of 0, 100, 250, 500 and 1000 ppm of oxidized α-, γ- or δ-tocopherol on the oxidative stability of purified soybean oil in the dark at 55°C were studied by measuring the peroxide value and headspace oxygen of sample bottles. As the concentrations of oxidized tocopherols increased, the peroxide values increased and headspace oxygen decreased. Tukey's test showed that the oxidized α-, γ- and δ-tocopherols had prooxidant effects (P < 0.05) on the peroxide value and headspace oxygen of soybean oil. Although oxidized α-tocopherol had the greatest prooxidant effect, oxidized γ- and δ-tocopherols had similar but lesser effects.
Inter-Ring Interactions in [Fe(TalkylP)(Cl)] (alkyl = ethyl, n-propyl, n-hexyl) Complexes: Control by meso-Substituted Groups.

Syntheses, molecular structures and magnetic susceptibilities of three meso-substituted high-spin iron(III) porphyrinate complexes ([Fe(TEtP)(Cl)], [Fe(TPrP)(Cl)], and [Fe(THexP)(Cl)]) are described. It was determined that the inter-ring interactions within each dimeric unit change upon alteration of the alkyl groups at the meso-positions. Magnetic exchange couplings between iron centers of the dimers are in accord with the trends in structural inter-ring geometries. Crystal data for [Fe(TEtP)(Cl)]: a = 10.1710(5) A, b = 11.309(3) A, c = 12.170(3) A, α = 91.774(9) °, β = 113.170 (14) °, γ = 112.149(9) °, V = 1165.2(4) A 3 , triclinic, P1Z = 2, R1 = 0.0844 and ωR2 = 0.2073 for observed data. Crystal data for [Fe([Fe(TPrP)(Cl)])(Cl)]: a = 13.040(2) A, b = 15.221(2) A, c = 14.6681(9) A, β = 109.997(11) °, V = 2735.9(7) A 3 , monoclinic, P21/n, Z = 4, R1 = 0.0477 and ωR2 = 0.1176 for observed data. Crystal data for [Fe(THexP)(Cl)]: a = 10.246(7) A, b = 12.834(4) A, c = 17.420(15) A, α = 69.74(3) °, β = 87.52(4) °, γ, = 84.89(3) °, V = 2140(2) A 3 , triclinic, P1 Z = 2, R1 = 0.1024 and ωR2 = 0.2659 for observed data.
Tensile and compressive behavior of poly(p‐phenylene benzobisthiazole) fibers

Heat treated poly(p-phenylene benzobisthiazole) (PBZT) fibers tested in tension result in two types of failure modes. In failure mode I, the fiber exhibits a relatively sharp break; mode II is characterized by significant axial fiber splitting. Approximately 20% of the fibers failed in mode II when tested at 2.54, 7.62, and 12.7 cm gage lengths. At 1.25 cm gage length all the fibers failed in mode I. Tensile strength decreased from the 1.25 to 7.62 cm gage length, but tensile strength of the fibers tested at 7.62 and 12.7 cm gage lengths were similar. The two failure mode observation is supported by the Weibull statistical distribution. Fiber tensile properties were also measured at 150°C. Axial compressive strength of the PBZT fibers as determined from the recoil test is also reported and is found to be independent of fiber tensile modulus and fiber diameter. As-received heat-treated fibers were post heat treated between 700 and 775°C. Structural changes in the fiber were studied using infrared spectroscopy, small and wide angle x-ray scattering, and swelling studies. © 1995 John Wiley & Sons, Inc.
Information resources centers for community-based organizations : A field study of an AIDS-HIV service agency

Une enquete a ete menee pour comprendre comment les concepts des services et des gestions d'information peuvent etre appliques a l'etablissement de centre de ressources d'informations dans les organisations communautaires (community-based organizations). L'etude des besoins d'information a ete realisee a l'ASA (AIDS Services of Austin). Une interaction avec les bibliotheques est indispensable
Level of Living: Factors Influencing the Homemaker's Satisfaction1

This study was designed to determine factors that influenced the homemaker's satisfaction with the family's level of living. Multivariate regression analysis with successive elimination of independent variables was used with data from nuclear families in two samples. One sample was of 488 “typical” families and the other sample was of 191 “disadvantaged” families. The general hypothesis tested was that the homemaker's satisfaction with the family's level of living is influenced by similar factors for both types of families. In addition, it was hypothesized that the factors having the most influence on “typical” homemakers would tend to be more abstract and less concrete; it was also hypothesized that the reverse would be found in the “disadvantaged” sample. The results tended to support the general hypothesis and the specific hypothesis for the “typical” homemakers. They did not support the specific hypothesis for the “disad vantaged” homemakers. The final regression explained 40 and 39 percent of the variances in the homemaker's satisfaction with level of living for the “typical”a and “disadvantaged” samples, respectively. The adjusted coefficients of multiple determination for both samples were high for cross-section data, indicating that the method used should be given further consideration by other researchers.
Preparation and in vitro evaluation of polylactic acid-mitomycin C microcapsules

AbstractAn emulsion method was developed for the incorporation of water-soluble mitomycin C into polylactic acid biodegradable microcapsules. With an average particle size of about 95 μm, microcapsules with a desired loading of from 3.65 to 13.80 per cent were prepared. These microcapsules, which contained both crystalline and finely dispersed drug particles, showed a dose-dependent drug release pattern with microcapsules of higher drug loading having a faster release rate than those of lower drug loading. Effective sterilization of the microcapsules for parenteral use was achieved by 60Co γ-ray irradiation, which did not affect the microcapsule structure, release rate or drug stability. Mitomycin C showed dose-dependent antiproliferative activity against the growth of the K562 human erythroleukaemia cells. The microencapsulated dosage form of mitomycin C was found to enhance the drug's activity through sustained drug release. In experiments where drug concentrations in the cell medium were reduced accord...
Assured reconfiguration of fail-stop systems

Hardware dependability improvements have led to a situation in which it is sometimes unnecessary to employ extensive hardware replication to mask hardware faults. Expanding upon our previous work on assured reconfiguration for single processes and building upon the fail-stop model of processor behavior, we define a framework that provides assured reconfiguration for concurrent software. This framework can provide high dependability with lower space, power, and weight requirements than systems that replicate hardware to mask all anticipated faults. We base our assurance argument on a proof structure that extends the proofs for the single-application case and includes the fail-stop model of processor behavior. To assess the feasibility of instantiating our framework, we have implemented a hypothetical avionics system that is representative of what might be found on an unmanned aerial vehicle.
Phonon interactions at ultrasonic frequencies

The interaction of ultrasonic beams in solid media has only recently been explored experimentally. The techniques developed for this purpose are reviewed and the experimental results are related to the anharmonic properties of the solid. The origin of these anharmonic properties is discussed.
A Region of the Myosin Rod Important for Interaction With Paramyosin in Caenorhabditis elegans Striated Muscle

The precise arrangement of molecules within the thick filament, as well as the mechanisms by which this arrangement is specified, remains unclear. In this article, we have exploited a unique genetic interaction between one isoform of myosin heavy chain (MHC) and paramyosin in Caenorhabditis elegans to probe the molecular interaction between MHC and paramyosin in vivo. Using chimeric myosin constructs, we have defined a 322-residue region of the MHC A rod critical for suppression of the structural and motility defects associated with the unc-15(e73) allele. Chimeric constructs lacking this region of MHC A either fail to suppress, or act as dominant enhancers of, the e73 phenotype. Although the 322-residue region is required for suppression activity, our data suggest that sequences along the length of the rod also play a role in the isoform-specific interaction between MHC A and paramyosin. Our genetic and cell biological analyses of construct behavior suggest that the 322-residue region of MHC A is important for thick filament stability. We present a model in which this region mediates an avid interaction between MHC A and paramyosin in parallel arrangement in formation of the filament arms.
Sperm cell surface characteristics of Plumbago zeylanica L. in relation to transport in the embryo sac

Myosin associated with the male germ cells of angiosperms interacts with actin, promoting transport of the non-motile generative and later sperm cells in the pollen tube. Myosin localizing on the sperm cell plasma membrane seems negligible in Plumbago, as reflected by the absence of: (i) anti-myosin labeling using immunoelectron microscopy, (ii) sperm motility on actin matrices, and (iii) electrophoretic movement changes after addition of antibody. Sperm cells injected directly into actively streaming Nitella internodal cells, however, follow actin bundles and their movement is sensitive to ATP and Mg2+. This may be based on simple charge binding since negatively charged latex beads also migrate on actin, whereas neutral or positively-charged latex beads do not. Sperm cells are negatively charged according to capillary microelectrophoresis, whereas killed sperm cells, which are positively charged do not migrate. The sperm cell that normally fertilizes the egg has a higher calculated charge (8.277 × 103 esu/cm2) compared with the sperm cell that fuses with the central cell (6.120 × 103 esu/cm2).
Insulin Resistance, Apoptosis, and Colorectal Adenoma Risk

Compelling evidence from epidemiologic studies indicates that elevated circulating insulin-like growth factor (IGF)-I, insulin resistance, and associated complications, such as elevated fasting plasma insulin, glucose and free fatty acids, glucose intolerance, increased body mass index, and visceral adiposity, are linked with increased risk of colorectal cancer. However, the role of insulin and markers of glucose control in the development of adenomas, precursors to colorectal cancer, has not been fully explored. We evaluated the relationship between plasma insulin, glucose, IGF-I, IGF-II, IGF-binding protein-3 (IGFBP-3), apoptosis, and colorectal adenomas in a case-control study. Participants were drawn from consenting patients undergoing colonoscopy at the University of North Carolina hospitals (Chapel Hill, NC). Participants were classified as cases or controls based on whether they had one or more colorectal adenomatous polyps. Fasting plasma insulin, IGF-I, IGF-II, and IGFBP-3 levels were assessed by ELISA. Glucose was measured by glucose hexokinase assay. Apoptosis was assessed by morphology on HE 95% confidence interval, 1.1-4.2) and glucose (adjusted odds ratio, 1.8; 95% confidence interval, 0.9-3.6) were more likely to have an adenoma compared with the lowest quartile. Similarly, subjects in the highest two quartiles of insulin were more likely to be in the lowest two quartiles of apoptosis. Overall, there were no significant differences between mean circulating levels of glucose, IGF-I, IGF-II, and IGFBP-3 among cases and controls and no association between these variables and apoptosis. The results provide novel evidence that elevated insulin and glucose are associated with increased adenoma risk and decreased apoptosis in normal rectal mucosa. These findings suggest that insulin may act early in the adenoma-carcinoma sequence to promote the development of colorectal adenoma by decreasing apoptosis in the normal mucosa.
A Curriculum Development Simulation in a Graduate Program

Objective. To implement and evaluate a curriculum development seminar in which graduate students experienced circumstances that occur when faculty members develop and attempt to secure colleague approval for a curriculum. Design. Learning activities for the graduate seminar included classroom lectures, active learning, and a group project in which simulated faculty committees created new curriculums for the pharmacy practice department's 3 research areas. Assessment. Responses on pre- and post-seminar surveys indicated that graduate students’ self-confidence in their ability to conduct key curriculum development activities increased (p < 0.05). In a post-seminar focus group, graduate students stated that they valued participating in the faculty simulation, learning about curriculum development and research programs other than their own, and collaborating with their peers. Conclusion. A curriculum development faculty simulation was an effective tool for preparing graduate students for curriculum development responsibilities and generated valuable documents that the department could use in the revision of the 3 pharmacy practice graduate school curricula.
COMPARISON OF SHORT AND LONG FATIGUE CRACK GROWTH IN 7075‐T6 ALUMINUM

The fatigue crack growth rates of physically-short cracks (0.5 ≤a≤ 1.0 mm), intermediate cracks (1 < a≤ 2 mm) and long cracks (7 < a < 25 mm) were compared using SEN type tensile specimens in 7075-T6 aluminum alloy with load ratios, R, of 0.05, − 1 and 0.5 under constant amplitude testing at room temperature. It was found that the short cracks grew much faster than long cracks based on applied δK with da/dN≤ 10−7 m/cycle. Even the intermediate cracks grew faster than the long cracks below 10−7 m/cycle. The transition crack lengths where similitude with δK existed was between 1 and 2 mm. Mean stress effects were similar for R= 0.05 and − t, but R= 0.5 caused increased crack growth rates. The above differences are partially attributed to crack closure effects. Based upon plastic zone sizes, LEFM was justifiable with all the experiments.
Multiresolution Quadtree Beamformer

The delay-sum beamformer (DSBF) is a space-time domain beamforming,method that performs coherent summation of sensor data. However, the computational complexity of finding the steered response over all angles is O(N3). In this paper, an O(N2log 2 N) space-time domain beamforming algorithm it is proposed. This fast algorithm does not require uniform sensor spacing. It is called Quadtree Beamformer (QBF) because it is based on the iterative subband spectral decomposition method that has been used in the Quadtree BackProjection SAR imaging algorithm. The QBF is implemented by recursively performing a spectral decomposition process over the space-time domain sensor array data. It also provides intermediate stage data that can be used for multi-angle multiresolution beamforming.
SPO11 is required for sex-body formation, and Spo11 heterozygosity rescues the prophase arrest of Atm-/- spermatocytes

SPO11 introduces double-strand breaks (DSBs) that trigger the phosphorylation of H2AX during meiotic prophase. In mice, SPO11 is strictly required for initiation of meiotic recombination and synapsis, yet SPO11 is still considered to be dispensable for sex-body formation in mouse spermatocytes. We provide conclusive evidence showing that functional SPO11, and consequently recombination and synapsis, are required for phosphorylation of H2AX in the X-Y chromatin and for sex-body formation in mouse spermatocytes. We investigated the role in meiosis of the three kinases [ATM (ataxia telangiectasia mutated), ATR (ataxia-telangiectasia- and Rad-3-related) and DNA-PKcs (DNA-dependent-protein-kinase catalytic subunit)] known to phosphorylate H2AX in mitotic cells. We found that DNA-PKcs can be ruled out as an essential kinase in this process, whereas ATM is strictly required for the chromatin-wide phosphorylation of H2AX occurring in leptotene spermatocytes in response to DSBs. Remarkably, we discovered that Spo11 heterozygosity can rescue the prophase-I-arrest characteristic of ATM-deficient spermatocytes. Characterization of the rescued Atm -/- Spo11 +/- mutant indicates that ATM is dispensable for sex-body formation and phosphorylation of H2AX in this subnuclear domain. The co-localization of ATR, phosphorylated H2AX and the sex chromatin observed in the Atm -/- Spo11 +/- mutant, along with ATR transcription kinetics during the first wave of spermatogenesis, confirm and expand recent findings indicating that ATR is the kinase involved in H2AX phosphorylation in the sex body.
Frequent substructure-based approaches for classifying chemical compounds

Computational techniques that build models to correctly assign chemical compounds to various classes of interest have many applications in pharmaceutical research and are used extensively at various phases during the drug development process. These techniques are used to solve a number of classification problems such as predicting whether or not a chemical compound has the desired biological activity, is toxic or nontoxic, and filtering out drug-like compounds from large compound libraries. This paper presents a substructure-based classification algorithm that decouples the substructure discovery process from the classification model construction and uses frequent subgraph discovery algorithms to find all topological and geometric substructures present in the data set. The advantage of this approach is that during classification model construction, all relevant substructures are available allowing the classifier to intelligently select the most discriminating ones. The computational scalability is ensured by the use of highly efficient frequent subgraph discovery algorithms coupled with aggressive feature selection. Experimental evaluation on eight different classification problems shows that our approach is computationally scalable and, on average, outperforms existing schemes by 7 percent to 35 percent.
Donor spontaneous intracerebral hemorrhage is associated with systemic activation of matrix metalloproteinase-2 and matrix metalloproteinase-9 and subsequent development of coronary vasculopathy in the heart transplant recipient

Background— Matrix metalloproteinase (MMP)-2 and MMP-9 have been shown to play a role in the progression of hemorrhagic stroke. We hypothesized that donor intracerebral hemorrhage (ICH) is associated with activation of the metalloproteinases before transplantation that play a key role in the subsequent development of transplant vasculopathy. Methods and Results— We evaluated mRNA expressions of MMP-2 and MMP-9 in donor spleen lymphocytes (before transplantation) and in heart biopsies at 1 week after transplantation in 20 recipients from ICH donors and 20 recipients from trauma donors. Patients underwent serial coronary intravascular ultrasound, and interstitial myocardial fibrosis was quantified at 1 year. The baseline characteristics were similar except for increased donor age in the ICH group. Heart biopsies from the ICH group showed significant increased expression of MMP-2 (17-fold, P<0.0001) and MMP-9 (20-fold, P<0.0001) compared with the trauma group. Furthermore, the ICH group showed 1.8-fold (P=0....
An improved subband acoustic echo canceller for teleconferencing applications

In this paper a novel subband acoustic echo canceller (AEC) is proposed. The proposed scheme consists in 8 non-overlapping main subbands and 8 auxiliary subbands. The auxiliary subbands are introduced in order to provide frequency coverage in the non-overlapping region between the neighboring main subbands. Central to computational efficiency of the proposed scheme is the decimation of the auxiliary bands. Simulation results provided show that the proposed subband AEC has faster convergence speed for tracking acoustic echo path as well as better dB reduction in the echo level in comparison to overlapping subband schemes.
A Mechanical Oscillograph for Routine Tests of Rubber and Rubber-Like Materials

Abstract The oscillograph described has been developed primarily as a laboratory instrument to evaluate rubber and Neoprene compounds for mechanical applications. It is complete in itself as a means of measuring all of the quantities inherently involved in such service in units which are understandable to rubber technologists and mechanical engineers alike. It is hoped that it may serve its purpose by bringing into closer cooperation those who make and those who use rubber springs. The details of the test have been carefully developed, and it is expected that the machine and standard test-specimen described will not need essential modification for routine use. However, enough background has been given so that the machine may be modified in accordance with definite principles in order to gain greater load capacity if required. The test has been restricted thus far to compression. The author expects to adapt the machine to tests in shear, and by correlation between shear data and compression data to obtain ...
SmartArgos: Improving mobile surveillance systems with software defined networks

Mobile surveillance systems like vehicle mounted cameras (i.e. police dash cams) and body cameras play an important role in securing physical spaces. However, these systems can generate too much data that hampers timely analysis. Furthermore, existing infrastructure wireless networks may not have sufficient bandwidth to support real time streaming of videos to backend servers. This paper presents the design of SmartArgos, a control framework to regulate mobile surveillance systems. SmartArgos uses software defined networks and computer vision algorithms to manage multiple mobile surveillance streams. Our experiments indicate that SmartArgos makes video streaming efficient and saves bandwidth compared to traditional video uploading from multiple clients.
State Hospitals as "the most integrated setting according to their needs".

In its 1999 Olmstead v. L.C. decision, the U.S. Supreme Court ruled that states have an obligation to provide services to individuals with disabilities in “the most integrated setting appropriate to their needs,” as the unjustified institutionalization of people with disabilities is
The role of tyrosine phosphorylation in the regulation of insulin and insulin-like growth factor-I receptor kinase activities.

Insulin is a polypeptide hormone which plays a crucial role in regulating cellular metabolism and growth. Although both the acute and long-term effects of insulin in a variety of cell types have been widely examined and reported, the molecular mechanism or mechanisms mediating the actions of this hormone are still unknown. Due to the diverse effects of insulin on cellular functions, it is quite possible that a multitude of pathways may be involved in the signalling mechanism of this hormone. In spite of the possible existence of such an intricate network of signalling pathways, it is reasonable to expect that they may originate from the interaction of insulin with its cell approach to elucidate the molecular investigate events which may occur insulin to its receptor. surface receptor. Thus, a logical mechanism of insulin action is to immediately after the binding of insulin to its receptor.
Thomas Edison’s Science

Over a time of five-plus decades, Thomas Edison and his teams invented, developed, and manufactured a host of new products, first at Menlo Park then at West Orange, both in New Jersey. This chapter summarizes the methods and results of archaeological testing projects carried out at the sites of these “invention factories.” In addition, attention is called to the trove of Edison-era artifacts remaining at the Thomas Edison National Historical Park in West Orange, which have only been partially inventoried. The potential for learning about Edison’s strategies for creating recipes for new products is demonstrated by a study of the nickel-iron battery.
Renewable Epoxy Networks Derived from Lignin-Based Monomers: Effect of Cross-Linking Density

Three modification methods, which either improved molecular weight, orientation or the number of functional groups, were employed to increase the cross-linking density of biobased epoxy networks based on 2-methoxy-4-propylphenol (dihydroeugenol, DHE). The modifications were realized through o-demethylation and phenol–formaldehyde reactions. Structures of DHE-based monomers and cured networks were characterized by NMR and FTIR spectroscopy. Cross-linking densities of cured networks were calculated using rubber elasticity theory from dynamic mechanical analysis (DMA). Networks with higher cross-link density were found to exhibit greater mechanical and thermal performance as measured by DMA and thermogravimetric analysis. GEDHEO-NOVO, an epoxy monomer featuring all three modification processes, exhibited significant improvements in cross-linking density (0.39 to 9.77 mol/dm3), α-relaxation temperature (Tα, 40 to 139 °C) and statistic heat-resistant index temperature (Ts, 125 to 153 °C) compared to the unmodi...
Cleavage at Arg740 Appears Essential for Thrombin-Catalyzed Cleavage at Arg372 during the Activation of Factor VIII.

Factor VIIIa serves as an essential cofactor for the factor IXa-catalyzed activation of factor X during the propagation phase of coagulation. The factor VIII procofactor is converted to factor VIIIa by thrombin-catalyzed proteolysis of three P1 positions at Arg372 (A1–A2 junction), Arg740 (A2–B junction), and Arg1689 (a3–A3 junction). Cleavage at Arg372 exposes a cryptic functional factor IXa-interactive site, while cleavage at Arg1689 liberates factor VIII from von Willebrand factor and contributes to factor VIIIa specific activity, thus making both sites essential for procofactor activation. However, cleavage at Arg740, separating the A2–B domainal junction, has not been rigorously studied. To evaluate thrombin cleavage at Arg740, we prepared and stably expressed two recombinant factor VIII mutants, Arg740His and Arg740Gln. Results from a previous study examining proteolysis at Arg372 revealed substantially reduced cleavage rates following substitution of that P1 Arg with His, whereas replacing Arg with Gln at residue 372 yielded an uncleavable bond at that site (Nogami et al., Blood, 2005). Specific activity values for the factor VIII Arg740His and Arg740Gln variants as measured using a one-stage clotting assay were approximately 50% and 18%, respectively, that of the wild type protein. SDS-PAGE and western blotting following a reaction of factor VIII Arg740His with thrombin showed reduced rates of cleavage at His740 as well as at Arg372 relative to the wild type. Alternatively, factor VIII Arg740Gln was resistant to thrombin cleavage at Gln740 and showed little, if any, cleavage at Arg372 over an extended time course. The mutant proteins assayed in a purified system by factor Xa generation showed a slight increase in activity for the Arg740His variant compared with the Arg740Gln variant in both the absence and presence of thrombin, and the activities for both variants were reduced compared with wild type factor VIII. These results suggest that cleavage at residue 740 affects subsequent cleavage at Arg372 and generation of the active cofactor factor VIIIa. Preliminary results obtained evaluating proteolysis of these mutants by factor Xa, which cleaves the same sites in factor VIII as thrombin, also revealed slow proteolysis at the P1 His and no cleavage at the P1 Gln. However, subsequent cleavage at Arg372 exhibited less dependence on initial cleavage at residue 740. These observations may explain the higher than predicted specific activity values obtained for the two variants and suggest a different mechanism of action for the two activating proteinases. Overall, these results support a model whereby cleavage of factor VIII heavy chain by thrombin is an ordered pathway with initial cleavage at Arg740 required to facilitate cleavage at the critical Arg372 site to yield the active cofactor.
Crowdsourcing, Mixed Elastic Systems and Human-Enhanced Computing–A Survey

State-of-the-art practices have recognized the utility of leveraging human intervention as a crucial aspect of modern computing systems. The emerging crowdsourcing paradigm is based on harnessing human intelligence, effort and rational behaviors to augment computation and analysis. In addition to the crowdsourcing paradigm, new techniques have emerged that incorporate machine and human computational resources together forming a hybrid intelligence when addressing complex problems and tasks. This combined technique is particularly impactful if human and machine contributions can scale automatically in response to their respective efficiency and effectiveness when addressing subsets of a bigger problem – an approach that we have named mixed elastic systems . In this survey, we highlight state-of-the-art projects that investigate crowdsourcing, hybrid intelligence systems and mixed elastic systems. We also present a taxonomy and classification of the broader domain of human-enhanced computing systems as it assimilates crowdsourcing, hybrid intelligence, and mixed elastic systems.