cssi/SciSciGPT-SciSciNet huggingface dataset:
Molecular dynamics simulation of amorphous indomethacin–poly(vinylpyrrolidone) glasses: Solubility and hydrogen bonding interactions

Amorphous drug dispersions are frequently employed to enhance solubility and dissolution of poorly water-soluble drugs and thereby increase their oral bioavailability. Because these systems are metastable, phase separation of the amorphous components and subsequent drug crystallization may occur during storage. Computational methods to determine the likelihood of these events would be very valuable, if their reliability could be validated. This study investigates amorphous systems of indomethacin (IMC) in poly(vinylpyrrolidone) (PVP) and their molecular interactions by means of molecular dynamics (MD) simulations. IMC and PVP molecules were constructed using X-ray diffraction data, and force-field parameters were assigned by analogy with similar groups in Amber-ff03. Five assemblies varying in PVP and IMC composition were equilibrated in their molten states then cooled at a rate of 0.03 K/ps to generate amorphous glasses. Prolonged aging dynamic runs (100 ns) at 298 K and 1 bar were then carried out, from which solubility parameters, the Flory-Huggins interaction parameter, and associated hydrogen bonding properties were obtained. Calculated glass transition temperature (T(g)) values were higher than experimental results because of the faster cooling rates in MD simulations. Molecular mobility as characterized by atomic fluctuations was substantially reduced below the T(g) with IMC-PVP systems exhibiting lower mobilities than that found in amorphous IMC, consistent with the antiplasticizing effect of PVP. The number of IMC-IMC hydrogen bonds (HBs) formed per IMC molecule was substantially lower in IMC-PVP mixtures, particularly the fractions of IMC molecules involved in two or three HBs with other IMC molecules that may be potential precursors for crystal growth. The loss of HBs between IMC molecules in the presence of PVP was largely compensated for by the formation of IMC-PVP HBs. The difference (6.5 MPa(1/2)) between the solubility parameters in amorphous IMC (25.5 MPa(1/2)) and PVP (19.0 MPa(1/2)) suggests a small, positive free energy of mixing, although it is close to the criterion for miscibility (<7 MPa(1/2)). In contrast to the solubility-parameter method, the calculated Flory-Huggins interaction parameter (-0.61 ± 0.25), which takes into account the IMC-PVP interaction energy, predicts complete miscibility at all PVP compositions, in agreement with experimental observations. These results from MD simulations were combined with experimental values for the crystalline γ-polymorph of IMC and amorphous IMC to estimate the solubility of IMC in amorphous PVP dispersions and the theoretical enhancement in the aqueous solubility of IMC molecularly dispersed in PVP at various volume fractions.
Neuronal and Intestinal Protein Kinase D Isoforms Mediate Na+ (Salt Taste)–Induced Learning

Ubiquitously expressed protein kinase D (PKD) isoforms are poised to disseminate signals carried by diacylglycerol (DAG). However, the in vivo regulation and functions of PKDs are poorly understood. We show that the Caenorhabditis elegans gene, dkf-2 , encodes not just DKF-2A, but also a second previously unknown isoform, DKF-2B. Whereas DKF-2A is present mainly in intestine, we show that DKF-2B is found in neurons. Characterization of dkf-2 null mutants and transgenic animals expressing DKF-2B, DKF-2A, or both isoforms revealed that PKDs couple DAG signals to regulation of sodium ion (Na + )–induced learning. EGL-8 (a phospholipase Cβ4 homolog) and TPA-1 (a protein kinase Cδ homolog) are upstream regulators of DKF-2 isoforms in vivo. Thus, pathways containing EGL-8–TPA-1–DKF-2 enable learning and behavioral plasticity by receiving, transmitting, and cooperatively integrating environmental signals targeted to both neurons and intestine.
Laser beam characteristics using dc-induced second harmonic generation

Previous measurements of electric field induced second harmonic generation indicated that the confocal parameter for a laser beam as calculated from the second harmonic intensity profile was in disagreement with that calculated from the measured beam diameter. In this paper, we show that this discrepancy is caused by the departure of the beam from the pure TEM00 mode. We expand a distorted beam in terms of the component modes by using the experimental beamscan and calculate the second harmonic profile using this expansion. This calculational procedure is found to be consistent with experimental observations.
Investigation of in vivo tracer techniques in drug screening studies.

An in vivo tracer method for screening drugs which act by altering the normal body metabolism of certain elements is described. These studies involved the detection of natruretic or antinatruretic action of six compounds. Further extensions of the present work are also discussed.
The Role of PLCδ4 in the Activity of TRPM8 Expressing Sensory Neurons

Changes in environmental temperature are sensed by the peripheral endings of dorsal root ganglion (DRG) neurons. A subset of neurons expressing Transient Receptor Potential Melastatin 8 (TRPM8) channels function as major sensors of moderately cold temperatures. Previously it was demonstrated that Ca2+ influx through recombinant TRPM8 activates a Ca2+ sensitive phospholipase C (PLC) isoform, leading to depletion of phosphatidylinositol 4,5-bisphosphate with subsequent decrease of the TRPM8 currents (desensitization). We have found earlier that the most abundant highly Ca2+ sensitive PLC isoform in DRG neurons is PLCδ4. We performed patch-clamp experiments on TRPM8 expressing DRG neurons from PLCδ4-KO and WT animals, and identified 2 neuronal subpopulations based of their size. Small neurons had significantly larger TRPM8 current densities compared to the medium-large ones. PLCδ4-KO cells had larger currents upon menthol application and diminished desensitization. Current-clamp experiments further confirmed the differences in these subgroups. Both KO and WT small neurons had a more depolarized resting membrane potential than medium-large cells, and required smaller current injection to generate action potentials (AP) indicating their higher excitability. Positive current injection initially induced a train of AP during current pulses; increasing the current magnitude lead to a profound decline of the AP frequency in WT but KO neurons were able to generate AP at maximal frequency. AP shape and characteristics were also different for small and medium-large neurons. Negative current injection demonstrated characteristic voltage- and time- dependent rectification and rebound spike for both WT and KO small neurons. Menthol application induced transient generation of AP with frequency significantly higher in KO and larger depolarization compare to the WT neurons. Our present data support the role of PLCδ4 in the process of TRPM8 desensitization.
A numerical solution to calculate internal-external rotation at the glenohumeral joint.

Abstract Objective. To validate the approach of using angular velocity vectors to quantify internal–external rotation of the humerus. Design. An experimental approach was used to compare predictions of internal–external rotation of the humerus based on angular velocity vectors, and known measurements of internal–external rotation. Background. A primary concern associated with description of glenohumeral biomechanics is measurement of internal–external rotation of the humerus. Euler angles are often used, yet they do not address problems such as Codman's paradox and `gimbal lock'. Previous work has presented a technique that uses angular velocity vectors to quantify internal–external rotation instead of Euler angles. This approach is promising with regard to providing an independent measure of internal–external rotation of the humerus, and requires validation for subsequent use on humans. Methods. A gimbal with three axes of rotation that simulated the rotational d.o.f. of the humerus relative to the glenoid was developed and used to validate the use of angular velocity vectors to quantify internal–external rotation of the humeral shaft portion of the gimbal. Results. Correlations between calculated and measured rotation values revealed R2 values of 0.99, slopes at diagonal (1.0), and y-intercepts near zero (−0.6°). Conclusions. The expression developed here is a valid and useful method for measuring motion of the humerus relative to the glenoid. Relevance Angular velocity vectors can be used to accurately determine internal–external rotation of the humerus relative to the glenoid, and this may be useful for the development of arthrometers to characterize the glenohumeral joint.
The PtP(C6H11)3(C2H4)2 mediated activation of aldehyde CH bonds via chelate-assisted oxidative addition reactions

Abstract Hydrocarbon solutions of PtPCy 3 (C 2 H 4 ) 2 (Cy = cyclohexyl) react rapidly with 8-quinolinecarboxaldehyde (1 equiv.) to yield tricyclohexylphosphine quinolinecarboxyl platinum hydride ( 1 ) and CH 2 CH 2 (2 equiv.). Compound 1 reacts with CCl 4 in hydrocarbons to give PtPCy 3 (NC 9 H 6 CO)Cl ( 2 ) and CHCl 3 . The compound PtPCy 3 (C 2 H 4 ) 2 also reacts with Ph 2 P(C 6 H 4 - o -CHO) and Ph 2 As(C 6 H 4 - o -CHO) to give PCy 3 PtPh 2 P(C 6 H 4 - o -CO)(H) ( 3 ) and PCy 3 PtPh 2 As(C 6 H 4 - o -CO)(H) ( 4 ), respectively. Compounds 1, 2, 3, and 4 were characterized by infrared and 1 H NMR spectra, and the crystal structure of 3 was determined by X-ray diffraction. Crystals of 3 are monoclinic, with space group P 2 1 / n and Z = 4 with the unit cell dimensions a 9.7936(17), b 14.844(35), c 23.530(64) A, β 91.817 (18)°, and V 3419.09(1.36) A 3 . The structure is refined to final discrepancy factors of R = 0.055, and R w = 0.064. The molecular structure of 3 is that ligating atoms are in a plane containing Pt. The position of the hydride was not located crystallographically, but the 1 H NMR spectrum of 3 , supports the presence of a terminal hydride that is cis to the carbonyl. The IR band of 3 at 2023 cm −1 which is assigned to ν(PtH), and the hydride cleavage reaction of 1 with CCl 4 , provide evidence for the PtH bond.
Observation of Approval/Disapproval in Music: Perception Versus Actual Classroom Events

This study was designed to assess subjects' perceptions of teacher approval/disapproval given to elementary students compared to the actual responses of the teacher. Subjects were 109 graduate and undergraduate music therapy (n = 50) and music education (n = 59) majors enrolled in classes in behavioral techniques that constituted parts of teacher/therapist training programs. Subjects viewed a 23-min videotape of an ongoing kindergarten music class involving listening, movement, and rhythm instrument performance activities. Subjects were instructed to write as many succinct statements as possible while observing the tape concerning the setting, teacher behavior, teacher/student interactions, lesson organization, and students' musical and social behaviors. Following the viewing, subjects evaluated various aspects of the approval and disapproval, using seven-point semantic differential scales, and also estimated the percentages of teacher time spent giving approval, disapproval, and instruction. All subjects...
Modulation of the Behavioral and Neurochemical Effects of Psychostimulants by κ-Opioid Receptor Systems

The repeated, intermittent use of cocaine and other drugs of abuse produces profound and often long-lasting alterations in behavior and brain chemistry. It has been suggested that these consequences of drug use play a critical role in drug craving and relapse to addiction. This article reviews the effects of psychostimulant administration on dopaminergic and excitatory amino acid neurotransmission in brain regions comprising the brain's motive circuit and provides evidence that the activation of endogenous kappa-opioid receptor systems in these regions opposes the behavioral and neurochemical consequences of repeated drug use. The role of this opioid system in mediating alterations in mood and affect that occur during abstinence from repeated psychostimulant use are also discussed.
Inhibition of human immunodeficiency virus reverse transcriptase by synadenol triphosphate and its E-isomer.

Triphosphate 1c is a potent competitive inhibitor of wild-type HIV-1 reverse transcriptase with Ki close to ddATP. The E-isomer 2c is about 30-times weaker. Triphosphates 1c and 2c interact with the same active site of reverse transcriptase as ddATP. The extent of inhibition of two mutant forms of reverse transcriptase (RT), RTM184V and RTM184I, with triphosphate 1c was about 5 and 8 times lower than that of wild-type RTwt.
Unit tablet assay of 17α‐ethynylestradiol‐3‐methyl ether (mestranol) by a direct colorimetric and an automated fluorometric method

Unit tablet assays of 17 α -ethynylestradiol-3-methyl ether (mestranol) were obtained with optimum precision and accuracy by direct dissolution of sample tablets and standardized reference tablets in sulfuric acid-methanol (70:30) reagent. An automated method which utilized basic automatic analyzer (Auto Analyzer) components and a Turner fluorometer was more rapid but less precise than the direct method.
A simple, global, complementary variational principle

This brief note presents a simple, global, complementary variational principle for a broad class of general functions. That is, we show that a point ~ which minimizes a certain type of functional / over a set S also maximizes a computable functional /* over a set S* and satisfies/(~) =/*(*$); this fact can be used to provide error bounds for an approximate minimizer u of/. Complementary principles have been studied rather thoroughly for differential equations [5, 6, references therein~ and general operator extensions of the differential equation problem [7~, although primarily local principles from a somewhat different viewpoint are obtained. A global principle has been presented in [2, 91 for nonlinear boundary value problems of variational type in order to obtain variational error bounds; this present note extends those results to more general functionals.
Effects of electrical stimulation of the reticular formation and chlorpromazine on performance of trace conditioned avoidance response in the rat.

Abstract The effects of electrical stimulation to the mesencephalic reticular formation and chlorpromazine on the performance of a trace conditioned avoidance response by rats were studied. Either treatment alone impaired the performance; this impairment was a function of level of stimulation or dose of the drug, respectively. The performance deficit was not present when a high intensity of stimulation of the reticular formation was combined with a moderate dose of chlorpromazine. However, the combination of a high dose of the drug with a low stimulation intensity interfered with the avoidance responding more than any other condition tested. These effects appeared to be independent of neutral or negative reinforcement effects of the stimulation, as tested in an independent situation.
Application of the “probable future competition” doctrine to the commercial banking and savings and loan industries

This study identified two implicit assumptions inherent in the use of the probable future competition (PFC) doctrine by regulators in the commercial banking and savings and loan industries. One assumption was that an institution's merger request identified it as the most likely entrant (MLE). The other assumption was that the higher the likelihood that a merger requestor would enterde novo the more important it is to deny its merger request so as to maintain the over all probability of entry.
Predictors of Permanent Housing for Sheltered Homeless Families

The authors analyze 10 years of data on homelessness to determine the characteristics of homeless families most likely to find permanent housing after leaving a shelter environment. They studied 1,156 families from 1983 to 1992 to determine where these families go after leaving the shelter and whether the pattern changed over time. Logistic regression analysis found that the larger the family size and being African American were factors that predicted a decreased likelihood of finding permanent housing. Families with one child were 1.5 times more likely to find permanent housing than were families with three children, and whites were 1.9 times more likely to find permanent housing than were African Americans. Furthermore, homeless shelter residents were five times more likely to find permanent housing in 1983 than in 1992, regardless of demographic predictors. Practice and policy implications are discussed.
Bispectral index-guided administration of anaesthesia: comparison between remifentanil/propofol and remifentanil/isoflurane.

BACKGROUND AND OBJECTIVE: The bispectral index of the electroencephalogram is a measure of the hypnotic component of anaesthesia and can be used to guide the administration of anaesthesia. This study compares bispectral index-guided anaesthesia with remifentanil and either propofol or isoflurane. METHODS: Eighty consenting patients were randomly assigned to two groups. Following induction with propofol and remifentanil, anaesthesia was maintained with remifentanil/propofol or remifentanil/isoflurane. Remifentanil infusion rates were guided by haemodynamic responses--maintaining mean arterial pressure and heart rate within 20% of baseline. Propofol and isoflurane administration was guided using the bispectral index (45-60). Thirty minutes before the end of surgery, morphine was administered (0.15 mg kg(-1) intravenously). Fifteen minutes before end of surgery, propofol and isoflurane were reduced (bispectral index 60-75). At the end of surgery, the anaesthetic agents were discontinued. Groups were compared for recovery, remifentanil doses and signs of inadequate anaesthesia using the chi2-test and ANOVA (P< 0.05). RESULTS: The duration of surgery was longer in the propofol/remifentanil group (121 +/- 53 versus 94 +/- 40 min). Recovery data were not different between groups. The remifentanil infusion rate was significantly lower with additional isoflurane (0.18 +/- 0.06 microg kg(-1) min(-1)) than with additional propofol (0.31 +/- 0.20 microg kg(-1) min(-1)). The propofol infusion rate was 123 +/- 48 microg kg(-1) min(-1); isoflurane concentration was 0.66 +/- 0.13%. CONCLUSIONS: Bispectral index-guided anaesthesia with remifentanil plus propofol or isoflurane results in the absence of postoperative recall and a fast recovery with both drug combinations. In our patients, at comparable bispectral index-levels, haemodynamic control requires higher doses of remifentanil with propofol than with isoflurane.
EFFECTS OF HYPOPHYSEAL TRANSPLANTATION FOLLOWING TOTAL HYPOPHYSECTOMY IN THE CANINE

The experimental transplantation of fragments of ductless glands has in the past not met with striking success, possibly due to the fact that the principle emphasised by W. S. Halsted, that an existing “physiological deficit” is one of the essentials to a successful “take,” has been disregarded. Our experiences conform with those of others in showing that the transplanted glandular tissue—in this case the hypopyhsis—is prone to undergo necrosis and in the course of time to become replaced by fibrous tissue. It is nevertheless apparent, particularly in the cases of immediate auto-transplantation of the gland into the cortex cerebri, that the inevitable early consequence of a total hypophysectomy (cachexia hypophyseopriva) can be postponed; further, in the case of animals in whom a minute fragment only of anterior lobe remains, the transplant seems to have been the means of tiding them over a period in which, according to our previous experiences, death would certainly have occurred. These fragments we have subsequently found to show evidences of the condition which we regard as hypertrophy. The transplants themselves, both anterior and posterior lobe, show histological evidences of retained activity for periods of at least a month. It has been observed that marked polyuria follows the cortical transplantation of the entire gland; that it disappears after extirpation of the transplant; that it does not follow transplantation of the posterior lobe alone; and, further, that it does not occur in control animals with heterotransplants.
Endotoxin (LPS) stimulates 4E-BP1/PHAS-I phosphorylation in macrophages.

Abstract Introduction. Translational control of cytokine production in endotoxin (LPS)-stimulated macrophages is poorly characterized but likely important. An early step in protein translation is engagement of mRNA by eukaryotic initiation factor 4E (eIF-4E). Translation initiation can be prevented by small 4E-binding proteins (4E-BP1 or PHAS-I) which must be phosphorylated in order to disengage eIF-4E. We examined whether LPS alters 4E-BP1 phosphorylation in macrophages. Materials and methods. Elicited rat peritoneal macrophages and Raw 264.7 macrophages were treated with signal transduction inhibitors and then LPS. Cells were harvested and equal protein amounts were electrophoresed (SDS-PAGE). Western blots (WB) were developed with 4E-BP1 antibody. Alternatively cell lysates were exposed to 7-methyl GTP Sepharose beads in order to isolate the cap-binding protein eIF-4E. The relative amounts of 4E-BP1 associated with eIF-4E were then determined by WB. Results. Macrophage 4E-BP1 is phosphorylated upon stimulation by LPS as evidenced by the appearance of a more slowly migrating γ (hyperphosphorylated) band on gel electrophoresis. Inhibition of both the p42/p44 MAPK pathway (PD 98059) and the p38 MAPK pathway (SB 203580) failed to alter LPS-induced 4E-BP1 phosphorylation. Rapamycin (FRAP/mTOR inhibitor) blocked 4E-BP1 phosphorylation causing a predominance of the α (hypophosphorylated) band. This was confirmed further by 7-methyl-GTP Sepharose isolation of eIF-4E with which 4E-BP1 coprecipitates. Conclusion. LPS stimulates 4E-BP1 phosphorylation in macrophages through FRAP/mTOR signaling. This pathway may contribute to the translational control of cytokine gene expression in macrophages.
Increased Lipogenesis and Stearate Accelerate Vascular Calcification in Calcifying Vascular Cells

Vascular calcification is recognized as an independent predictor of cardiovascular mortality, particularly in subjects with chronic kidney disease. However, the pathways by which dysregulation of lipid and mineral metabolism simultaneously occur in this particular population remain unclear. We have shown that activation of the farnesoid X receptor (FXR) blocks mineralization of bovine calcifying vascular cells (CVCs) and in ApoE knock-out mice with 5/6 nephrectomy. In contrast to FXR, this study showed that liver X receptor (LXR) activation by LXR agonists and adenovirus-mediated LXR overexpression by VP16-LXRα and VP16-LXRβ accelerated mineralization of CVCs. Conversely, LXR inhibition by dominant negative (DN) forms of LXRα and LXRβ reduced calcium content in CVCs. The regulation of mineralization by FXR and LXR agonists was highly correlated with changes in lipid accumulation, fatty acid synthesis, and the expression of sterol regulatory element binding protein-1 (SREBP-1). The rate of lipogenesis in CVCs through the SREBP-1c dependent pathway was reduced by FXR activation, but increased by LXR activation. SREBP-1c overexpression augmented mineralization in CVCs, whereas SREBP-1c DN inhibited alkaline phosphatase activity and mineralization induced by LXR agonists. LXR and SREBP-1c activations increased, whereas FXR activation decreased, saturated and monounsaturated fatty acids derived from lipogenesis. In addition, we found that stearate markedly promoted mineralization of CVCs as compared with other fatty acids. Furthermore, inhibition of either acetyl-CoA carboxylase or acyl-CoA synthetase reduced mineralization of CVCs, whereas inhibition of stearoyl-CoA desaturase induced mineralization. Therefore, a stearate metabolite derived from lipogenesis might be a risk factor for the development of vascular calcification.
Equivalence Between Four-Fermion and Yukawa Coupling, and the Z 3 = 0 Condition for Composite Bosons

The principal objective of the present work is the derivation of conditions for equivalence (A) between a four-Fermi theory with pseudoscalar coupling and a Yukawa theory with pseudoscalar bosons, and (B) in the corresponding vector case. In general, two conditions are found to be both necessary and sufficient. The first is a condition for the existence of an appropriate boson bound state in the four-Fermi theory. The second condition is that the boson wave function renormalization constant ${Z}_{3}$ in the Yukawa theory be equal to zero. We first derive our results by consideration of fermion-fermion scattering in the chain approximation, and proceed afterwards to prove them valid to all orders in perturbation theory. We also discuss the degenerate vacuum theories of Nambu and Jona-Lasinio and of Bjorken in the chain approximation. In each of these four-Fermi theories, the existence of boson bound states (massless pseudoscalar and massive scalar bosons in the former case, massless vector bosons in the latter) follows automatically from self-consistency conditions. Hence to have equivalence to Yukawa theories in which the bosons are described by elementary fields, we need only impose the ${Z}_{3}=0$ conditions on the Yukawa theories. Finally, we comment on Birula's theory of quantum electrodynamics without electromagnetic field. It is to be stressed that we deal throughout with full-scale relativistic field theories of physical consequence.
A rapid chemical method for improving peel strength at Cu–epoxy interfaces

The effect of a chemical treatment of a Cu surface on the interfacial strength between a thermoset polymer and that Cu surface has been determined. Spray technology was used to apply fixed amounts of a silane surface modifier to the cleaned Cu surface using three different plain-orifice atomizer hand-pump sprayers. The amount of spray coverage was determined for each sprayer as a function of the number of sprays and the peel strength was found to increase with the spray coverage for each sprayer. Substantial improvements to 340% in peel strength were achieved compared to the as-received condition, indicating good chemical bonding between Cu and epoxy. These results compare favorably with the results from a more complicated cleaning and oxidizing treatment which produced nano-scale features which mechanically interlock with the epoxy.
Long-term retention and the spacing effect in free-recall and frequency judgments

In 2 experiments undergraduate students were presented with a long list of words in which items were repeated varying numbers of times according to either a massed presentation (MP) schedule or a distributed presentation (DP) schedule. Following list presentation, subjects were given either a frequency-judgment test (Experiment I) or a free-recall test (Experiment II). In both experiments, the retention test was given either immediately after or 24 hours after list presentation. As expected, on the immediate test MP items were judged to have occurred less frequently and they were recalled more poorly than DP items. On the delayed frequency judgment test, the spacing effect was slightly (though not significantly) smaller, and these results were considered to be consistent with the prevailing notion that MP items are more poorly registered in memory. The results of the delayed free-recall test, however, were less consistent with this explanation in that there was no difference in the recall of twice-presented MP and DP items. In a list presented for study, the successive occurrences of a repeated item may appear either in adjacent or nonadjacent list positions. Repeated items whose successive occurrences appear in adjacent positions are referred to as massed-presentation (MP) items, while those repeated in nonadjacent positions are referred to as distributed-presentation (DP) items. It has been consistently shown that, on tests of retention given immediately after presentation of the study list, MP items are more poorly recalled (e.g., Shaughnessy, Zimmerman, and Underwood, 1972) and are judged to have occurred less frequently (e.g., Underwood, 1969) than are DP items. Hintzman (1974) has provided a recent review of both the empirical findings and the proposed theoretical explanations related to this so-called spacing effect in free-recall and frequency judgments. Somewhat surprisingly, very little attention has been given to the study of the spacing effect in long-term tests of retention. Ciccone and Brels
Thyrotropin (TSH) Receptor Residue E251 in the Extracellular Leucine-Rich Repeat Domain Is Critical for Linking TSH Binding to Receptor Activation

The TSH receptor (TSHR) ectodomain comprises a tubular leucine-rich repeat domain (LRD) and a hinge [or signaling specificity domain (SSD)]. TSH binds to both the LRD and SSD, leading to signal transduction by the transmembrane domain. The SSD structure and spatial orientation to the other components are unknown. We exploited a fortuitous observation to obtain mechanistic insight into the relationship between TSH binding and signal transduction. A mouse TSHR cDNA generated by PCR was found to express a receptor with poor TSH-induced cAMP generation despite normal TSH binding. Progressive reversion to wild-type of six mutations revealed E251K in the LRD to be critical for reduced signal transduction in both mouse and human TSHR. An I286F substitution in the SSD had a much weaker effect and was additive with E251K. To our knowledge, there are no previous examples of specific amino acid mutations in the TSHR LRD that dissociate TSH binding from TSHR signal transduction. To prevent flailing of the TSHR LRD, its position vis-a-vis the SSD must be stabilized by multiple amino acid interactions. The present data suggest that TSHR residue E251 is one of these residues involved in stabilizing the LRD relative to the SSD, thereby enabling ligand binding to transduce a signal by the latter. That the E251K mutation can reduce signal transduction despite high-affinity TSH binding comparable with the wild-type TSHR provides mechanistic insight into the coupling between ligand binding and receptor activation.
Oleylamine as Both Reducing Agent and Stabilizer in a Facile Synthesis of Magnetite Nanoparticles

Monodisperse Fe3O4 nanoparticles are synthesized by a much simplified method of reductive decomposition of iron acetylacetonate in benzyl ether and oleylamine. The Fe3O4 nanoparticles are catalytically active for CVD growth of 1D boron nanowires.
The thermochemistry of phosphorus tetrahalide anions

The Br3P−Br- and I3P−I- bond strengths have been determined by measuring thresholds for collision-induced dissociation in a flowing afterglow-tandem mass spectrometer. The results are combined with previously determined values for the PF4- and PCl4- systems to determine the effect of the terminal atom on hypervalent bond strengths. The bond strengths correlate very well with the difference in the electronegativities of phosphorus and the halogen atoms. Computational results at the B3LYP/6-311+G(d) level indicate that PCl4- and PBr4- have seesaw geometries and are good examples of three-center, four-electron bonding. PF4- has a similar geometry, but the bonding is more ionic, whereas PI4- is tetrahedral, consistent with greater steric crowding.
Non-coordinate expression of collagen mRNAs during carbon monoxide-induced cardiac hypertrophy.

Collagen gene expression during volume overload-induced cardiac hypertrophy was investigated in adult male rats. Hypertrophy of the left ventricle (22%) and right ventricle (37%) occurred following 27 days continuous exposure to 700 ppm carbon monoxide; hematocrit increased nearly 47%. To examine potential cellular and molecular control of restructuring in the heart, we investigated the expression of two specific procollagen mRNAs for collagen types which have different structural-functional roles [Type I (alpha-1) & Type IV]. Type I (interstitial) mRNA levels increased at least 100% relative to controls within 3 days of initial exposure to 700ppm CO, then declined afterwards; type IV(basement membrane) mRNA levels increased more modestly at first, and increased further afterwards. The ratio of type I/type IV RNA's also increased initially, then later declined, with the greatest differences in the relative responses of type I and IV mRNAs seen in the right ventricle. These data suggest that types I and IV collagen mRNA expression is not coordinately expressed during this type of volume overload-induced hypertrophy in rat heart.
Evidence for diffusible, mating-type-specific trichogyne attractants inNeurospora crassa

Abstract A pheromone-like substance is secreted constitutively by the male cell (fertilizing element) of each mating type ( A, a ) which attracts specifically the tip cell of the receptive female filament (the trichogyne) of opposite mating type. The two trichogyne attractants have now been trapped on particles of activated charcoal. When such particles are placed near trichogynes of opposite mating type their tip cells grow toward and congregate around these particles. The trichogynes in the two combinations do not, however, respond with the same intensity; the A attractant → a trichogyne is a much stronger reaction than is its reciprocal. This asymmetry of the two combinations in N. crassa parallels the pattern found in two other heterothallic Euascomycetes, namely, Ascobolus stercorarius and Nectria haematococca .
Gold Nanowire Scattering and Absorption Measurements

Lithographically prepared gold nanodots and nanowires were placed onto a thermal sensor film to measure heat absorption. These identical wires are also subjected to dark field scattering measurements allowing for a comparison between absorption and scattering at the excitation wavelength. An increasing liner trend is found to exist between nanowires of increasing aspect ratio. The nanostructures also exhibit a decreasing temperature change with increasing wire length with a constant laser flux of 1.3 x 1010 W/m2.
Photodegradation of Carotenoids in a Vegetable Juice System

The kinetics of carotenoid photodegradation in a vegetable juice system were studied by exposing samples in glass vials to 230 ft-c of light at 4°C. Carotenoids were analyzed using HPLC at selected times during an 8-day period. Color changes were monitored using a Gardner colorimeter. Degradation reactions fit a first-order kinetic model. Lycopene degradation was about one-fifth that of α-carotene and β-carotene with rate constants of 0.061. 0.273 and 0.309 day−1. respectively. Colorimeter results showed a significant decrease in “yellowness” that correlated with the loss of α- and β-carotene (r2= 0.97).
Maternal Opioid Drug Use during Pregnancy and Its Impact on Perinatal Morbidity, Mortality, and the Costs of Medical Care in the United States

Objective. To identify factors associated with opioid use during pregnancy and to compare perinatal morbidity, mortality, and healthcare costs between opioid users and nonusers. Methods. We conducted a cross-sectional analysis of pregnancy-related discharges from 1998 to 2009 using the largest publicly available all-payer inpatient database in the United States. We scanned ICD-9-CM codes for opioid use and perinatal outcomes. Costs of care were estimated from hospital charges. Survey logistic regression was used to assess the association between maternal opioid use and each outcome; generalized linear modeling was used to compare hospitalization costs by opioid use status. Results. Women who used opioids during pregnancy experienced higher rates of depression, anxiety, and chronic medical conditions. After adjusting for confounders, opioid use was associated with increased odds of threatened preterm labor, early onset delivery, poor fetal growth, and stillbirth. Users were four times as likely to have a prolonged hospital stay and were almost four times more likely to die before discharge. The mean per-hospitalization cost of a woman who used opioids during pregnancy was $5,616 (95% CI: $5,166–$6,067), compared to $4,084 (95% CI: $4,002–$4,166) for nonusers. Conclusion. Opioid use during pregnancy is associated with adverse perinatal outcomes and increased healthcare costs.
Global stabilization of a chain of integrators with input saturation and disturbances: A new approach

In this article, we solve the problem of global stabilization for a chain of integrators in the presence of input saturation and disturbances. A novel and elegant approach to solve this problem, in the absence of disturbances, was proposed by Teel (1992) using saturation functions and coordinate transformation. With Teel's work as a foundation, many results have been proposed to improve the performance of controllers for a chain of integrators. Naturally, all such approaches also inherited the limitations of Teel's approach. Most importantly, in the presence of uncertainties and disturbances, the transformation introduced in Teel (1992) would considerably shrink the region where the controller is unsaturated and, severely limit the level of uncertainties and disturbances which can be tolerated. In order to overcome these difficulties, a conceptually different approach which does not rely on the coordinate transformation is presented in this work. Specifically, modified saturation functions are directly applied to the tracking error of actual states as opposed to transformed fictitious states to develop a globally stable controller. The proposed controller is less conservative in terms of the level of uncertainties and disturbances which can be handled. In addition, arbitrarily good disturbance rejection in the unsaturated region can be achieved theoretically. Comparative simulation studies performed on a third order integrator chain verified the effectiveness of the proposed scheme.
Characterization of a sodium deoxycholate-activatable proteinase activity associated with βA3/A1-crystallin of human lenses

Abstract A human lens proteinase was purified by a five-step procedure that included two consecutive size-exclusion agarose A 1.5 m chromatographies, a preparative non-denaturing gel-electrophoretic separation, HPLC on a size-exclusion column (TSK G-3000 PW XL ) followed by preparative isoelectric focusing. A 2300-fold purified enzyme showed a major band of 22 kDa during SDS-PAGE, a pH optimum of 7.8, p I between 4.5 and 5.0, a loss of activity above 45°C and a serine type nature. The partial N-terminal sequence of the enzyme, i.e. P-M-P-G-S-L-G-P-W, matched with the sequence of human lens βA3/A1-crystallin starting at residue No. 23. Based on the Western blot results of the enzyme with five different site-specific polyclonal antibodies raised against βA3/A1-crystallin, it was concluded that the 22 kDa crystallin enzyme had a cleaved N-terminus but an intact C-terminus. The βA3/A1-crystallin, isolated from human lenses, also exhibited proteinase activity following detergent activation and size-exclusion chromatography. The mouse recombinant βA3/A1-crystallin proteinase was purified by the above five-step procedure, from a homogenate of Sf-9 cells transfected with baculovirus containing the full length coding sequence of βA3/A1-crystallin. The mouse 22 kDa species also exhibited proteinase activity and immunoreactivity with anti-βA3/A1-C-terminal antibody. Together, the data suggest that a truncated species of βA3/A1-crystallin exhibits proteinase activity.
A PCR Marker for Growth Habit in Common Wheat Based on Allelic Variation at the VRN-A1 Gene

Growth habit varies among accessions of hexaploid wheat (Triticum aestivum L.). The winter habit genotype (homozygous recessive for vrn-A1, vrn-B1, vrn-D1) requires a cold treatment to induce flowering and is generally planted in the fall. Spring habit genotypes flower in the absence of a vernalization treatment. Spring habit is conferred by a dominant allele at any of the three VRN-1 loci, but varieties carrying the VRN-A1 locus are the most frequent and usually flower earlier. To facilitate selection in populations segregating at the VRN-A1 locus and to assist in genotyping wheat accessions of unknown VRN-1 composition, a PCR-based marker for growth habit would be useful. The VRN-A1 gene was recently cloned allowing for the development of markers for growth habit. In this report, we designed primer sets specific for the VRN-A1 locus, and used them to amplify an 810-bp segment of the VRN-A1 gene between intron 4 and exon 8 from 40 spring wheat lines and 37 winter wheat lines. Three diagnostic nucleotide changes were identified that differentiated the dominant Vrn-A1 and recessive vrn-A1 alleles in 75 out of the 77 genotypes analyzed in this study. One of these differences resulted in the presence of an additional AciI restriction site in the allele for spring growth habit. This difference was exploited to develop a cleavage amplification polymorphic sequence (CAPS) that can be used to determine the allelic state at VRN-A1 in germplasm collections, and as a marker in backcross breeding projects. An additional pair of dominant markers was developed from a different polymorphism.
The Impact of Changes in Advertising Agencies on Corporate Common Stock Prices

Abstract This research suggests that event study, a technique well established in financial and accounting research, can be used to analyze the effect of public announcements of advertising agency changes on the common stock prices of firms making such announcements. The research finds a positive impact on common stock prices for a period of approximately one month around the public announcement of an agency change.
Cultural congruence between investigators and participants masks the unknown unknowns: shame research as an example.

In addition to questions of the representativeness of Western, educated samples vis-a-vis the rest of humanity, the prevailing practice of studying individuals who are culturally similar to the investigator entails the problem that key features of the phenomena under investigation may often go unrecognized. This will occur when investigators implicitly rely on folk models that they share with their participants.
3D Cable-Based Cartesian Metrology System

A novel cable-based metrology system is presented wherein six cables are connected in parallel from ground-mounted string pots to the moving object or tool of interest. Cartesian pose can be determined for feedback control and other purposes by reading the lengths of the six cables via the string pots and using closed-form forward pose kinematics. This article focuses on a sculpting metrology tool, assisting a human artist in generating a piece from a computer model, but applications exist in manufacturing, rapid prototyping, robotics, and automated construction. We present experimental data to demonstrate the operation of our system, we study the absolute accuracy and also measurement resolution, and we discuss various error sources. The proposed real-time cable-based metrology system is less complex and more economical than existing commercial Cartesian metrology technologies. © 2004 Wiley Periodicals, Inc.
Residential electricity demand in Taiwan

This paper examines the residential demand for electricity in Taiwan as a function of household disposable income, population growth, the price of electricity and the degree of urbanization. Short- and long-term effects are separated through the use of an error correction model. In the long-run, the income elasticity is unit elastic. The own-price effect is negative and inelastic. In an error correction framework, the short-run income and price effects are small and less than the long-run effects. Cooling degree-day effects have a positive impact on short-run consumption. We have used a proxy variable, urbanization, to capture economic development characteristics and changes in electricity-using capital stocks not explained by income. The variable provides significant explanatory power to the model both in the short- and long-run. We interpret it as controlling for economic development factors not captured by the pure income effect and we think it holds promise for explaining residential electricity consumption in other developing countries.
Intervertebral foraminal ligaments of the lumbar spine: anatomy and biomechanics

The anatomical existence of the transforaminal ligaments has been studied extensively. However, there are very few studies examining how the transforaminal ligaments could be involved in the causation of nerve root compression and the low back pain syndrome. In this article, the authors review earlier studies in an attempt to find anatomical and biomechanical correspondence between the intervertebral foraminal ligaments of the lumbar spine and the low back pain syndrome.
Perioperative management of pediatric trauma patients

Pediatric trauma presents significant challenges to the anesthesia provider.This review describes the current trends in perioperative anesthetic management, including airway management, choice of anesthesia agents, and fluid administration.The review is based on the PubMed search of literature on perioperative care of severely injured children.
The Reproduction of Inequalities Through Emotional Capital: The Case of Socializing Low-Income Black Girls

The concept of emotional capital suggests that adults transfer emotion management skills to children in ways that are consequential for the social reproduction of inequalities. Using ethnographic data from a popular after-school program, this study analyzes the emotional capital transmitted to low-income black girls by staff. They passed on four aspects of emotional capital: stifling attitude, being emotionally accountable for peers, sympathizing with adult authority figures, and emotional distancing from cultural “dysfunction.” Staff intended to teach girls to manage their emotions as a way to counteract racism, but the socialization largely promoted emotional deference, thereby reinforcing racialized, classed, and gendered ideologies.
PARDIS: programmer-level abstractions for metacomputing

Abstract The potential offered by metacomputing is hard to realize due to the complexity of programming geographically distributed applications spanning different software systems. This paper describes PARDIS, a system designed to address this challenge, based on ideas underlying the Common Object Request Broker Architecture (CORBA), a successful industry standard. PARDIS is a distributed environment in which objects representing data-parallel computations, called Single Program Multiple Data (SPMD) objects, as well as non-parallel objects present in parallel programs, can interact with each other across platforms and software systems. Each of these objects represents a small encapsulated application and can be used as a building block in the construction of powerful distributed metaapplications. The objects interact through interfaces specified in the Interface Definition Language (IDL), which allows the programmer to integrate within one metaapplication component implemented using different software systems. Further, support for non-blocking interactions between objects allows PARDIS to build concurrent distributed scenarios.
Capital and Ownership Structures, and the Market for Corporate Control

The author analyzes optimal capital and ownership structures as resulting from anticipated future control contests. He focuses on leverage as a device that enables the incumbent management to extract the maximum value from the rival. He shows that firm value depends on both capital and ownership structures. The analysis leads to the following predictions: (1) more efficient managers use less debt, (2) firms facing better rivals for control issue more debt, and (3) firms with supermajority rules issue less debt. Several predictions are consistent with known empirical regularities. Article published by Oxford University Press on behalf of the Society for Financial Studies in its journal, The Review of Financial Studies.
Poster abstract: on the scaling laws of dense wireless sensor networks

We characterize the scaling laws of many-to-one dense wireless sensor networks and derive conditions governing the observability of random fields by such networks. We further extend our results to the multimodal case where the sensors observe multiple random processes simultaneously. Quite interestingly, our results show that an unbounded number of spatially bandlimited Gaussian processes can be observed simultaneously by a dense multimodal wireless sensor network.