cssi/SciSciGPT-SciSciNet huggingface dataset:
Assembly and Characterization of 3D, Vascularized Breast Cancer Tissue Mimics

Drug development platforms such as two-dimensional (2D) in vitro cell culture systems and in vivo animal studies do not accurately predict human in vivo effectiveness of candidate therapeutics [1]. Cell culture systems have limited similarities to primary human cells and tissues as only one cell type is employed and animal studies have a generally limited ability to recapitulate human drug response as different species have differences in metabolism, physiology, and behavior. Mike Leavitt, a former U.S. Secretary of Health and Human Services, has stated that “currently, nine out of ten experimental drugs fail in clinical studies because we cannot accurately predict how they will behave in people based on laboratory and animal studies” [2]. Therefore, this research project is focused on developing an in vitro platform to test candidate therapeutics for more efficacious predictions of human response. We have fabricated a three-dimensional (3D) breast cancer tissue volume containing a vascular network. This vascular network is necessary because current in vitro systems (e.g., rotating bioreactors, suspension of spheroids, and growth on a porous scaffold) are limited in size (1–2 mm) by their absence of micrometer-scale blood flow micro-channels that allow for oxygen and nutrient diffusion into the tissue [4]. The extracellular matrix scaffold has been developed to mimic the native extracellular matrix and includes relevant cell types (e.g., human breast cancer epithelial cells and human breast fibroblasts) along with the prefabricated vascular network (prevascularization). These systems are intended to support long-term growth, recapitulate physiological tissue function, and accurately model response to treatment. It is hypothesized that the development of reproducible tissue volumes will transform breast cancer drug development by providing reliable, cost-effective models that can more accurately predict therapeutic efficacy than current preclinical in vivo and in vitro models.Copyright © 2013 by ASME
Histochemical and cellular changes accompanying the appearance of lung fibrosis in an experimental mouse model for Hermansky Pudlak syndrome

Hermansky Pudlak syndrome (HPS) is a heterogeneous recessive genetic disease with a tendency to develop lung fibrosis with aging. A mouse strain with two mutant HPS genes affecting separate vesicle trafficking pathways, C57BL/6-Hps1 ( ep )-Ap3b1 ( pe ), exhibits severe lung abnormalities at young ages, including enlarged alveolar type II (ATII) cells with giant lamellar bodies and foamy alveolar macrophages (AMs), which are readily identified histologically. In this study, the appearance of lung fibrosis in older animals was studied using classical histological and biochemical methods. The HPS double mutant mice, but not Chediak Higashi syndrome (C57BL/6-Lyst ( bg-J )-J, CHS) or C57BL/6J black control (WT) mice, were found to develop lung fibrosis at about 17 months of age using Masson trichrome staining, which was confirmed by hydroxyproline analysis. TGF beta1 levels were elevated in bronchial alveolar lavage samples at all ages tested in the double mutant, but not WT or CHS mice, indicative of a prefibrotic condition in this experimental strain; and AMs were highly positive for this cytokine using immunohistochemistry staining. Prosurfactant protein C staining for ATII cells showed redistribution and dysmorphism of these cells with aging, but there was no evidence for epithelial-mesenchymal transition of ATII cells by dual staining for prosurfactant C protein and alpha-smooth muscle actin. This investigation showed that the HPS double mutant mouse strain develops interstitial pneumonia (HPSIP) past 1 year of age, which may be initiated by abnormal ATII cells and exacerbated by AM activation. With prominent prefibrotic abnormalities, this double mutant may serve as a model for interventive therapy in HPS.
Reversal of haloperidol induced deficits in self-stimulation by anti-Parkinsonian drugs

The effects of 0.1 mg/kg dose of haloperidol on self-stimulation were assessed in rats having 3 stable self-stimulation response rates of approximately 10, 50 and 100 responses per min generated by 3 levels of current intensity. Haloperidol reduced overall response rates at all current intensities and generated extinction-like response patterns. Concurrent anti-Parkinsonian (benztropine 4.0 mg/kg or diphenhydramine 4.0 mg/kg) eliminated the within session extinction performance pattern and at the highest current intensity benztropine restored self-stimulation to a non-drug performance level. These results suggested that haloperidol induced impairments in self-stimulation are secondary to a motoric rather than reinforcement dysfunction.
Missing data methods in longitudinal studies: a review

Incomplete data are quite common in biomedical and other types of research, especially in longitudinal studies. During the last three decades, a vast amount of work has been done in the area. This has led, on the one hand, to a rich taxonomy of missing-data concepts, issues, and methods and, on the other hand, to a variety of data-analytic tools. Elements of taxonomy include: missing data patterns, mechanisms, and modeling frameworks; inferential paradigms; and sensitivity analysis frameworks. These are described in detail. A variety of concrete modeling devices is presented. To make matters concrete, two case studies are considered. The first one concerns quality of life among breast cancer patients, while the second one examines data from the Muscatine children’s obesity study.
Nonparametric smoothing estimates of time-varying coefficient models with longitudinal data

This paper considers nonparametric estimation in a varying coefficient model with repeated measurements (Y ij , X ij , t ij ), for i = 1 n and j = 1 n i , where X ij = (X ij .,,X ijk ) T and (Y ij , X ij , t ij ) denote the jth outcome, covariate and time design points, respectively, of the ith subject. The model considered here is Y ij = X ij T β(t ij )+ e i (t ij ), where β(t)=(β 0 (t)., β k (t)) T , for k≥ 0, are smooth nonparametric functions of interest and e i (t) is a zero-mean stochastic process. The measurements are assumed to be independent for different subjects but can be correlated at different time points within each subject. Two nonparametric estimators of β(t), namely a smoothing spline and a locally weighted polynomial, are derived for such repeatedly measured data. A crossvalidation criterion is proposed for the selection of the corresponding smoothing parameters. Asymptotic properties, such as consistency, rates of convergence and asymptotic mean squared errors, are established for kernel estimators, a special case of the local polynomials. These asymptotic results give useful insights into the reliability of our general estimation methods. An example of predicting the growth of children born to HIV infected mothers based on gender, HIV status and maternal vitamin A levels shows that this model and the corresponding nonparametric estimators are useful in epidemiological studies.
Adaptive Optics for Single-Photon Fiber Coupling of Ions

We present a new adaptive-optics technique for the optimization of photon collection from a simulated ion. Our technique uses a genetic algorithm to correct wavefront aberrations via deformable mirror before coupling into a single-mode fiber.
Pseudocrystals of chrysotile

Abstract Short, uniform fibers of chrysotile asbestos exhibit strong interparticle forces parallel to the fiber axis. Wetting a matte of these fibers, and then allowing it to dry, results in the aggregation of the fibers into distinct geometrical shapes.
The Direction of Denominational Switching in Judaism

This research note examines patterns of denominational switching and the characteristics of switchers within Judaism in the United States. Viewing orthodox, conservative, and reform Judaism and a fourth “nonspecific” group as categories that range from the most traditional to the least traditional, respectively, we focus on the movement of individuals toward or away from a more traditional denomination in comparison with remaining in the same denomination in which they were raised. The data were drawn from the National Jewish Population Survey (NJPS) 2000–2001 (NJPS 2003). We found that 62 percent stay within the same group, 29 percent move away from tradition, and 9 percent move to a more traditional denomination. Multivariate logistic regression analyses show that a lower level of Jewish background, higher previous travel to Israel, a greater extent of organizational affiliation, and a higher level of spiritual feelings and beliefs are associated with moving to a more traditional denomination whereas a higher level of Jewish background, lower previous travel to Israel, and a lower level of spiritual feelings and beliefs are associated with moving to a less traditional denomination. In addition, a few sociodemographic factors (previously married, has a child at home, lives in a western state) are associated with movement toward tradition whereas others (older age, female, not living in the northeast or west) are associated with movement in the other direction.
Acoustic streaming in helium-II

Abstract The first quantitative measurements of acoustic streaming velocity in helium-II as a function of sound intensity and temperature are presented. Comparison with theoretical calculations to second order shows detailed agreement in the temperature range examined, 1.4 K ≤ T ≤ 2.0 K. The coefficient of second viscosity appears to be the dominant hydrodynamic parameter.
Requirement of translocated lysosomal V1 H+-ATPase for activation of membrane acid sphingomyelinase and raft clustering in coronary endothelial cells

Acid sphingomyelinase (ASM) mediates the formation of membrane raft (MR) redox signalosomes in a process that depends on a local acid microenvironment in coronary arterial endothelial cells (CAECs). However, it is not known how this local acid microenvironment is formed and maintained. The present study hypothesized that lysosomal V1 H+-ATPase provides a hospitable acid microenvironment for activation of ASM when lysosomes traffic and fuse into the cell membrane. Confocal microscopy showed that local pH change significantly affected MRs, with more fluorescent patches under low pH. Correspondingly, the ASM product, ceramide, increased locally in the cell membrane. Electron spin resonance assay showed that local pH increase significantly inhibited NADPH oxidase–mediated production of O2−. in CAECs. Direct confocal microscopy demonstrated that Fas ligand resulted in localized areas of decreased pH around CAEC membranes. The inhibitors of both lysosomal fusion and H+-ATPase apparently attenuated FasL-caused pH decrease. V1 H+-ATPase accumulation and activity on cell membranes were substantially suppressed by the inhibitors of lysosomal fusion or H+-ATPase. These results provide the first direct evidence that translocated lysosomal V1 H+-ATPase critically contributes to the formation of local acid microenvironment to facilitate activation of ASM and consequent MR aggregation, forming MR redox signalosomes and mediating redox signaling in CAECs.
Reproductive effects of low acute doses of cadmium chloride in adult male rats.

Abstract Adult male Sprague-Dawley rats were injected sc with cadmium (Cd, as cadmium chloride) in doses ranging from 1.6 to 152 μmol Cd/kg body weight (body wt). Fourteen days after dosing, animals were evaluated for reproductive damage. Evaluations for each animal included testes, seminal vesicles, and epididymides weights, vas deferens sperm concentration, and human chorionic gonadotropin (hCG) -stimulated serum testosterone concentration. Since 10 to 60% mortality occurred in the two highest dose groups (74 and 152 μmol/kg), no additional evaluations were conducted in these groups. The weights of the testes, seminal vesicles, and epididymides were reduced at least 40 to 50% in groups receiving 16 or 33 μmol Cd/kg while vas deferens sperm concentrations and hCG-stimulated serum testosterone concentrations were essentially zero. Significant depressions in the sperm concentrations and in the hCG-stimulated serum testosterone concentrations were found in animals receiving the two lowest doses (1.6 and 7.4 μmol Cd/kg) although no changes in tissue weights were observed in these animals. Curve-linear regression analyses for the dose responsiveness of these parameters demonstrated that serum testosterone concentration initially decreased at a rate of 19%/μmol Cd/kg, respectively, and was the most sensitive to Cd exposure. The initial rates of decrease for sperm concentrations and for seminal vesicles, testes, and epididymides weight were 6.45, 5.30, 4.19, and 2.45%/μmol Cd/kg, respectively, and were less responsive to Cd exposure than serum testosterone levels.
Occult Hepatitis C Virus Infection in Hemodialysis

Nosocomial transmission in dialysis units maintains a higher prevalence of hepatitis C virus (HCV) infection in patients on maintenance dialysis than in the general population.[1][1],[2][2] HCV infection has a detrimental effect on survival in patients on maintenance dialysis[3][3] and after renal
X‐ray diffraction studies of ABA propylene–ethylene block copolymers

ABA triblock copolymers of propylene and ethylene, where the central block is a random copolymer of ethylene and propylene and the A blocks are either isotactic polypropylene or polyethylene, are described. Structural changes induced by stretching at room and elevated temperatures are reported. WAXS was used to monitor these changes. The results indicate theat block copolymers were synthesized and that different combinations of mechanical properties may be obtained by varying the type and length of the A blocks and adjusting the monomer ratio in the random B block.
Solvent-dependent metabolite distribution, clustering, and protein extraction for serum profiling with mass spectrometry.

The aim of metabolite profiling is to monitor all metabolites within a biological sample for applications in basic biochemical research as well as pharmacokinetic studies and biomarker discovery. Here, novel data analysis software, XCMS, was used to monitor all metabolite features detected from an array of serum extraction methods, with application to metabolite profiling using electrospray liquid chromatography/mass spectrometry (ESI-LC/MS). The XCMS software enabled the comparison of methods with regard to reproducibility, the number and type of metabolite features detected, and the similarity of these features between different extraction methods. Extraction efficiency with regard to metabolite feature hydrophobicity was examined through the generation of unique feature density distribution plots, displaying feature distribution along chromatographic time. Hierarchical clustering was performed to highlight similarities in the metabolite features observed between the extraction methods. Protein extracti...
Pressure and field dependence of superconductivity in Rb3C60.

Direct measurements of the pressure dependence of the superconducting transition temperature {ital T}{sub {ital c}} for single-phase Rb{sub 3}C{sub 60} provide for the first time substantial evidence that {ital T}{sub {ital c}} in {ital A}{sub 3}C{sub 60} compounds may be a universal function of the lattice constant (inter-C{sub 60} spacing). Determination of the lower ({ital H}{sub {ital c}1}) and upper ({ital H}{sub {ital c}2}) critical fields, and consequently the superconducting penetration depth and coherence length, is also reported. Compared to K{sub 3}C{sub 60}, the measured quantities are consistent with a 15% larger electronic-state density in Rb{sub 3}C{sub 60} arising from a greater inter-C{sub 60} spacing in this compound.
Symplectic Integrator for General Near-Integrable Hamiltonian System

In this paper, following the idea of constructing the mixed symplectic integrator (MSI) for a separable Hamiltonian system, we give a low order mixed symplectic integrator for an inseparable, but nearly integrable, Hamiltonian system, Although the difference schemes of the integrators are implicit, they not only have a small truncation error but, due to near integrability, also a faster convergence rate of iterative solution than ordinary implicit integrators, Moreover, these second order integrators are time-reversible.
Treatment of isolated neuroendocrine liver metastases.

Data guiding the appropriate management of patients with hepatic metastases arising from NE primaries, including pancreatic NE tumors, are limited. Long-term survival seems to be enhanced in those patients undergoing resection when it is done with a curative intent and potentially when per-formed as a debulking procedure. Symptoms, includ-ing those arising from hormone production, and pain are effectively treated with locally aggressive treatments including resection, thermal ablation, and tumor embolization. Given the lack of effective chemotherapy, the limited duration of response with hormonal therapy, the often indolent oncologic nature of these diseases, and the increasingly safe profile of these local options, locally aggressive treat-ments remain an important component of care.
Detection of lateral CD shift with scatterometry on grating structures in production layout

In 32nm/22nm advanced technology node, double patterning lithography is considered for semiconductor manufacturing. It necessitates tightened requirement of overlay measurement, i.e. to measure the position of a pattern with respect to that of a pattern in the underlying layer. The measurement target design plays a fundamental role in overlay precision and accuracy. Typical alignment target, such as bar-in-bar or box-in-box (BIB), has precision, accuracy, and size restrictions. This prompts us to look into better alignment targets. Recently, scatterometry-based metrology and profile model capability have been extended to measure multi-level grating structures. In addition, scatterometry has been shown to be the best choice for integrated metrology to perform wafer-to-wafer control. Therefore, it makes sense to consider using scatterometry for overlay measurement. In this research, the modeling analysis is performed on the spectra taken directly from a real pattern area with grating-ongrating structure. The critical dimension (CD) at the grating on top and the lateral shift between the top and the bottom gratings can be detected simultaneously. The lateral shift between the layers can be verified with the traditional overlay box. Unlike the traditional BIB target that has micrometer CD size, the CD size of the scatterometry overlay (S_OVL) target is much closer to that on the real device. So, it can much better reflect the overlay (OVL) shift on real devices. We also studied the non-model-based S_OVL measurement using a 673-nm semiconductor laser with a 10μm x 20μm target size, wafer-to-wafer control of CD and lateral shifts on some critical layers with grating-on-grating structure, as well as the CD and OVL variations within layer and from layer to layer for double patterning.
Depth-discrimination thresholds as a function of binocular differences of retinal illuminance at scotopic and photopic levels.

The precision of depth discrimination has been measured in a two-rod test apparatus involving real-depth cues. The effects of two variables have been studied: (a) the level of equal retinal illuminance presented to the two eyes; and (b) the difference in the level of the retinal illuminance presented to the two eyes. It has been found that depth discrimination in this test varies as a function of the level of equal retinal illuminance presented to the two eyes in much the same way that acuity or intensity discrimination vary with luminance. Stereoscopic threshold angles vary more than 19:1 over some five log units of variation in illuminance.Unequal retinal illuminance presented to the two eyes at any given illuminance level has a comparatively small deleterious effect upon the precision of depth discrimination. This effect progressively increases as the inequality of retinal illuminance is increased.These results have significance for photochemical theories of vision and for the classical theory of binocular space discrimination.
Preparation of reactor-produced carrier-free 18F-fluoride as the potassium 18-crown-6 complex for synthesis of labelled organic compounds

Abstract An anion exchange and distillation procedure is described for preparing reactor-produced carrier-free 18F as K18F complexed with 18-crown-6 in acetonitrile for subsequent syntheses of labelled organic compounds. The reaction sequence 6Li(n, t)4He−16O(t. n)18F produced yields of approximately 250 mCi of 18F per hour per gram of 96% enriched 6Li, as 6LiOH·H2O target, in a reactor thermal neutron flux of 3 × 1013 n cm−2s−1. Yields of tritium-free carrier-free 18F dissolved in the crown ether solution typically reach 85 ± 5% within the 20–30 min required for the radiochemical procedure
Changes in 3′-nucleotidase during the germination of wheat embryos☆

Abstract When isolated wheat embryos were germinated on nutrient agar there was an 80-fold increase in the specific activity of 3′-nucleotidase, but little change in the activity of nonspecific phosphatase. This increase could not be attributed to the disappearance of an inhibitor, formation of an activator, or conversion of a proenzyme. Changes in 3′-nucleotidase were also measured in different parts of the whole wheat seed. While there was an increase in the total 3′-nucleotidase activity of germinating seeds and embryos, no evidence could be obtained for repression or derepression of the synthesis of this enzyme by its substrates or products. The effect of some growth regulators and the folic acid antagonist amethopterin on increases in 3′-nucleotidase were examined. The use of isolated embryos seems to offer certain advantages over intact seeds in the study of some of the enzyme changes which take place during germination.
Intracellular receptors use a common mechanism to interpret signaling information at response elements

The glucocorticoid receptor (GR) activates transcription in certain glucocorticoid response element (GRE) contexts, and represses or displays no activity in others. We isolated point mutations in one GRE, plfG, at which GR activated transcription under conditions in which the wild-type element was inactive or conferred repression, implying that GREs may carry signals that are interpreted by bound receptors. Consistent with this notion, we identified a mutant rat GR, K461A, which activated transcription in all GRE contexts tested, implying that this residue is important in interpretation of GRE signals. In a yeast screen of 60,000 GR mutants for strong activation from plfG, all 13 mutants isolated contained substitutions at K461. This lysine residue is highly conserved in the zinc-binding region (ZBR) of the intracellular receptor (IR) superfamily; when it was mutated in MR and RARP, the resulting receptors similarly activated transcription at response elements that their wild-type counterparts repressed or were inactive. We suggest that IR response elements serve in part as signaling components, and that a critical lysine residue serves as an allosteric "lock" that restricts IRs to inactive or repressing configurations except in response element contexts that signal their conversion to transcriptional activators. Therefore, mutation of this residue produces altered receptors that activate in many or all response element contexts.
Preparation of a Public Piano Performance: The Relation between Practice and Performance

This study investigated an expert pianist's nine-month preparation for a public music performance (recital) through the collection of practice diaries and MIDI recordings of the eight scheduled pieces. Recordings were made under the experimentally varied conditions of solitary performance and public performance. The practice diaries revealed that the expert (an advanced student performer) allocated practice time consistently across the entire preparation period and tended to use mornings to practice the pieces perceived as being more difficult. Total preparation time for each of the pieces could be predicted on the basis of the pianist's subjective ratings of complexity and independent ratings of complexity given by other experts. An analysis of the performance data showed that, near the time of the recital, variability in performance tempo was large between pieces but very small for multiple renditions of the same piece, even under the different experimental conditions. Thus, to attain a highly reproduci...
The Action Execution Process Implemented in Different Cognitive Architectures: A Review

An agent achieves its goals by interacting with its environment, cyclically choosing and executing suitable actions. An action execution process is a reasonable and critical part of an entire cognitive architecture, because the process of generating executable motor commands is not only driven by low-level environmental information, but is also initiated and affected by the agent’s high-level mental processes. This review focuses on cognitive models of action, or more specifically, of the action execution process, as implemented in a set of popular cognitive architectures. We examine the representations and procedures inside the action execution process, as well as the cooperation between action execution and other high-level cognitive modules. We finally conclude with some general observations regarding the nature of action execution.
PERCEPTIONS OF RACE AND REGION IN THE BLACK REVERSE MIGRATION TO THE SOUTH

This study examines how African Americans perceive and manage race and region as they migrate to the U.S. South—a region with a tenuous image of racial prejudice. The analysis is juxtaposed to literature that provides an inconsistent view of regional differences in prejudice. Some researchers argue that regional differences in levels of prejudice are now small, while other researchers argue that the South continues to be a place of much greater racial hostility. Guided by a spatial boundaries approach and using 127 narrative interviews with Black interregional migrants to Charlotte, North Carolina, results indicate that Black migrants focus less on levels of racial prejudice across regions and focus more on six dimensions of everyday racism they consider during migration. These dimensions include—the overtness0subtlety of prejudice, verbal and physical harassment, group economic opportunity, physical distance, racial symbols, and paternalism. Among these migrants, there is no consensus that the South is more or less racially hostile than other regions. They perceive most saliently that they are trading more subtle prejudice, higher levels of racial residential segregation, and greater constraints on Black economic opportunity in the North, for more overt prejudice, greater paternalism, and exposure to Confederate symbols in the South. Patterns also emerged in perceptions of regional boundaries based on class, motivation for moving, gender, and generation. Implications for theories of race and regionalism are discussed.
Trauma patients: you can get them in, but you can't get them out.

Abstract Background The majority of inpatient trauma care resources are consumed by a small proportion of severely injured patients. Methods Hospital lengths of stay (LOS), resource consumption, and postdischarge placement were abstracted from the institutional trauma registry. Results Patients (n = 4,070) were evaluated by the trauma service during the study period. The overall mean LOS was 4.4 days, and beds were occupied on 18,005 days. Two hundred forty-four (6%) patients remained in the hospital >14 days after injury and occupied beds on 8,560 (47%) days. These patients were older, more severely injured, and required proportionately more intensive care unit and operative care. Injuries to the head, abdomen, and extremities were independently associated with longer LOS. Most patients with longer LOS were placed in long-term acute care or received home nursing care after discharge. Conclusions Almost half of inpatient trauma bed-days are occupied by a small proportion of patients with long-term care needs.
Commodity trade between EU and Egypt and Orcutt’s hypothesis

Orcutt hypothesized that trade flows respond faster to a change in the nominal exchange rate as compared to a change in relative prices. Although he recommended testing his hypothesis at commodity level, due to lack of commodity prices previous studies used aggregate trade flows of one country with the rest of the world and did not support the hypothesis. In this paper, we test Orcutt’s hypothesis using trade flows of 59 industries that trade between European Union and Egypt. These are the industries that account for 100 % of the trade between the two regions and for which price data are available. We find support for the Orcutt’s hypothesis in 1/3rd of industries.
Restoration of Mitochondrial Gene Expression Using a Cloned Human Gene in Chinese Hamster Lung Cell Mutant.

Background: Gal-32 is a Chinese hamster lung cell nuclear mutant that is unable to grow in galactose due to a defect in mitochondrial protein synthesis. Since the product of the Gal-32 gene was unknown, it was imperative to use phenotypic complementation to clone a human gene that corrected the Gal-32 mutation. Results: Recessive Gal-32 cells were co-transformed with pSV2-neo plasmid DNA and recombinant DNA from a human genomic library containing the dominant human Gal+ gene and a chloramphenicol-resistance (camr) gene present in the pSV13 vector. Primary transformants were selected by growth in galactose and the neomycin analog G418. In order to rescue the human Gal+ gene, a genomic library was constructed with primary transformant DNA and the pCV108 cosmid vector. The camr gene was used to identify clones with the nearby human sequences. DNA from two camr, Alu-hybridizing clones was able to transform the recessive Gal-32 cells to the Gal+ phenotype and to restore mitochondrial protein synthesis. Conclusion: These data demonstrate the isolation of two pCV108-transformant recombinant clones containing a human gene that complements the Chinese hamster Gal-32 mutation and restores galactose metabolism.
Differential Effects of Direct and Indirect Dopamine Agonists on Prepulse Inhibition: A Study in D1 and D2 Receptor Knock-Out Mice

Stimulation of the dopamine (DA) system disrupts prepulse inhibition (PPI) of the acoustic startle response. On the basis of rat studies, it appeared that DA D2 receptors (D2Rs) rather than D1 receptors (D1Rs) regulate PPI, albeit possibly in synergism with D1Rs. To characterize the DA receptor modulation of PPI in another species, we tested DA D1R and D2R mutant mice with direct and indirect DA agonists and with the glutamate receptor antagonist, dizocilpine (MK-801). Neither the mixed D1/D2 agonist apomorphine (5 mg/kg) nor the more selective D1-like agonist SKF82958 (0.3 mg/kg) altered PPI in D1R knock-out mice, although both compounds disrupted PPI in D2R mutant and wild-type mice, suggesting that the D1R alone might modulate PPI in mice. However, amphetamine (10 mg/kg) significantly lowered PPI in each genotype of D1R mice, suggesting that the D1R is not necessary for the PPI-disruptive effect of the indirect agonist in mice. As reported previously, amphetamine (10 mg/kg) failed to disrupt PPI in D2R knock-out mice, supporting a unique role of the D2R in the modulation of PPI. Dizocilpine (0.3 mg/kg) induced similar PPI deficits in D1R and D2R mutant mice, confirming that the influences of the NMDA receptor on PPI are independent of D1Rs and D2Rs in rodents. Thus, both D1Rs and D2Rs modulate aspects of PPI in mice in a manner that differs from dopaminergic modulation in rats. These findings emphasize that further cross-species comparisons of the pharmacology of PPI are essential to understand the relevance of rodent PPI studies to the deficits in PPI observed in patients with schizophrenia.
Increased epidermal transglutaminase activity following 2,3,7,8-tetrachlorodibenzo-p-dioxin: in vivo and in vitro studies with mouse skin.

Abstract In previous studies it has been shown that topical treatment of hairless mice with 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD, dioxin) induces hyperproliferation and hyperkeratinization in the epidermis of hairless mice. The present investigation demonstrated that such TCDD-induced morphological changes in skin in vivo are accompanied by increased levels in activity of epidermal transglutaminase (ETG), the enzyme associated with terminal epidermal differentiation. Exposure of mouse epidermal cells in tissue culture to 10 −9 m TCDD also resulted in a significant increase in ETG activity, despite the fact that morphologically these cultures (grown at 0.07 m m ionic calcium concentrations) exhibited no signs of terminal differentiation. Thus one mechanism of action of TCDD in inducing cutaneous changes appears to relate to the stimulation of increased ETG levels.
Characterization of FGF23-Dependent Egr-1 Cistrome in the Mouse Renal Proximal Tubule

Fibroblast growth factor 23 (FGF23) is a potent regulator of phosphate (Pi) and vitamin D homeostasis. The transcription factor, early growth response 1 (egr-1), is a biomarker for FGF23-induced activation of the ERK1/2 signaling pathway. We have shown that ERK1/2 signaling blockade suppresses renal egr-1 gene expression and prevents FGF23-induced hypophosphatemia and 1,25-dihydroxyvitamin D (1,25(OH)2D) suppression in mice. To test whether egr-1 itself mediates these renal actions of FGF23, we administered FGF23 to egr-1-/- and wild-type (WT) mice. In WT mice, FGF23 induced hypophosphatemia and suppressed expression of the renal Na/Pi cotransporters, Npt2a and Npt2c. In FGF23-treated egr-1-/- mice, hypophosphatemic response was greatly blunted and Na/Pi cotransporter expression was not suppressed. In contrast, FGF23 induced equivalent suppression of serum 1,25(OH)2D concentrations by suppressing renal cyp27b1 and stimulating cyp24a1 mRNA expression in both groups of mice. Thus, downstream of receptor binding and ERK1/2 signaling, we can distinguish the effector pathway that mediates FGF23-dependent inhibition of Pi transport from the pathway that mediates inhibition of 1,25(OH)2D synthesis in the kidney. Furthermore, we demonstrate that the hypophosphatemic effect of FGF23 is significantly blunted in Hyp/egr-1-/- mice; specifically, serum Pi concentrations and renal Npt2a and Npt2c mRNA expression are significantly higher in Hyp/egr-1-/- mice than in Hyp mice. We then characterized the egr-1 cistrome in the kidney using ChIP-sequencing and demonstrate recruitment of egr-1 to regulatory DNA elements in proximity to several genes involved in Pi transport. Thus, our data demonstrate that the effect of FGF23 on Pi homeostasis is mediated, at least in part, by activation of egr-1.
A multi-variable parametric study on the performance of bolted busbar contacts

The reliability of bolted joints is a concern for high-powered devices as the generated heat and thermal expansion could loosen the connections over many actuation cycles. There currently appears to be relatively little information on what material combinations, surface finish, etc. would be beneficial. This work experimentally evaluates the reliability of bolted contacts over 100 cycles and develops theoretical models to predict the relative bolted contact performance. The experimental test arrangement includes eight busbar pairs connected in series, while a power supply cycles current so that the busbars reach a desired temperature rise. A variety of cases are tested that vary the busbar material and thickness, washers, torque, bolt property class, diameter, and head types, in 60 different combinations. Each combination is tested three times, and then the cases are compared to each other using statistical methods. As expected, the electrical and thermal cycling fatigues the bolts, and in some cases the limitations of the joint were exceeded.
Commentary: Attention to Eyes Is Present but in Decline in 2–6-Month-Old Infants Later Diagnosed with Autism

A recent Nature article provided preliminary evidence that infants age 2–6 months old, who were later diagnosed with Autism Spectrum Disorder (ASD), fixated more on the mouth than eyes and more at objects than people when viewing videos of typical childhood social scenes (1). While the sample was small, a reliable pattern of decline in eye fixation accurately predicted their level and classification of symptoms at age three suggesting that – for the first time – an infant could be assessed within the first 6 months of life for their potential of developing ASD (see Table ​Table11 for studies that used eye-tracking with infants 12 months and younger). These eye-tracking devices, which are currently in clinical trials, could provide access to an affordable and objective tool with the potential for extremely early intervention. Detecting ASD risk during the first 6 months of life presents unprecedented opportunities to intervene, providing children opportunities to build critical skills before autistic characteristics fully emerge. Because the eye-tracking device allows for a non-invasive, portable assessment, the device could also enable pediatricians to provide comparable screening services globally. With such promise, a near future where infants are placed into an eye-tracking device at routine pediatric visits is compelling, if not guaranteed.
Dissent: Political, Ethnic, and Religious

Dissent has a long and honorable tradition among the Russian intelligentsia. From the time of Alexander Radishchev in the eighteenth century to the present day, intellectuals have spoken out against the policies and practices of the regime. The tactics of dissident groups and the responses of the government, whether the tsarist regime or the Soviet, have also been remarkably consistent over the years. Radishchev, whose Journey from St. Petersburg to Moscow depicted the poverty of the serfs, was condemned to death, but Catherine the Great commuted the sentence to exile in Siberia. Like Radishchev, thousands of persons who have written or voiced their criticism of the Soviet regime have been imprisoned or exiled since the 1960s. Even the ghoulish practice of interning opponents in psychiatric hospitals has historical antecedents. The nineteenth-century philosopher, biologist, and leader of the Westernizers, Peter Chaadaev, was arrested, condemned as insane, and placed in an asylum. He emerged several years later to write his scathing Apology of a Madman. Neither are samizdat (self-published) tracts criticizing the regime a new development in the Soviet Union. In the mid-nineteenth century, Alexander Herzen, another Westernizer who had been forced to emigrate to the West, began publishing an underground newspaper, The Bell. Copies of The Bell were smuggled back into Russia and helped to arouse greater opposition to the tsarist regime. In 1896, Lenin was imprisoned and spent three years in exile in Siberia. Following his release, he fled to Zurich and founded the Social Democratic newspaper Iskra (The Spark). Trotsky also engaged in criticism from abroad. He was expelled from the Soviet Union in January 1929 and began publishing the Russian-language newspaper Bulletin of the Opposition from exile. The Bulletin, which was similar to today’s Chronicle of Current Events, focused on abuses of power by the party leadership.
Localized state distribution and its effect on recombination in organic solar cells

Transient photocurrent (TPC) and transient photovoltage (TPV) measurements are reported in bulk heterojunction organic solar cells. TPC is used to measure the band tail and deep trap density of states within the interface band gap and to identify the carrier species from the relative contribution of drift and diffusion. Steep exponential band tails are observed near the donor valence band edge, changing to a broader distribution of states at larger trap energies. The effect of the localized state distribution on the recombination is analyzed---particularly for geminate recombination, where it is shown that band tails can substantially enhance the probability that geminate pairs ionize to form free carriers. The TPV response is shown to have completely different characteristics from those of TPC, and the explanation is provided.
Altitude and Velocity Tracking Control for An Airbreathing Hypersonic Cruise Vehicle

This paper describes an adaptive linear quadratic (ALQ) altitude and velocity tracking control algorithm for the longitudinal model of a generic airbreathing hypersonic flight vehicle hypersonic flight vehicle. The vehicle design is inspired by a set of mission requirements broadly accepted for a hypersonic cruise vehicle intended for both space access and military applications. The vehicle, CSULA-GHV, has an integrated airframe-propulsion system configuration and resembles an actual test vehicle. The complete aerodynamic and scramjet engine data including the coupling between the two have been developed by both flow theoretic models and by using an integrated aero-propulsion CFD model in FLUENT. A set of nonlinear longitudinal equations of motion for the vehicle which include both an inverse square law, gravitational model and the centripetal acceleration as well as the CFD-generated aerodynamic, propulsion, and coupled aeropropulsion data are developed and used for control design. The certainty equivalence principle is used to combine the adaptive law with the control structure of the standard linear quadratic (LQ) problems. The aerodynamics of the AHFV is linearized at different trimmed conditions, and the traditional gain scheduling LQ design is also implemented. Simulation results demonstrate the effectiveness of ALQ control design in tracking altitude and velocity commands over LQ design with gain scheduling, in that it can discern aerodynamics changes and adapt the control laws accordingly. This also helps the system to achieve fault-tolerance to control surface damage.
Dynamic analysis of sanitation professional technicians in CDCs of Changchun during 2008-2012

Objective To analyze the composition of sanitation professional technicians of disease control and prevention institutions in Changchun from 2008 to 2012,and provide reference for superior departments tomake policy and planning of disease control and health manpower,optimize allocation of human resources and strengthen the construction of disease control and health workforce. Methods According to National Health Statistics and Direct Network Report system, the composition of health technical staff in the Disease control and prevention institution in Changchun area from 2008 to2012 was analyzed. Results From 2008 to 2012,the number of health technical staff in disease control and prevention institutions in Changchun area is reduced with the increase of the city's population. Their age composition tends to aging.The most of population of them has the educational background of junior college,technical secondary school or.The staff with primary professional title is the one with the largest proportions. Conclusion The number of health technical staff in the Disease control and prevention institution in Changchun area is growing. And the staff of them with older age,higher level of education and professional title accountfor an increasing proportion.But the situation has not met the requirements of the national level. It remains to be further adjusted and optimized.
More on Facing the Reality of Our Aging Population With Breast Cancer

For appropriate older women screening provides a benefit in this age group by identifying early-stage breast cancer.
FLUORESCENCE LIFETIME BIOSENSING: ENTERING THE MAINSTREAM

Publisher Summary This chapter emphasizes the salient features of florescence lifetime biosensing. When a fluorophore (fluorescent molecule or atom) is raised to an excited state by absorbance of a photon, it spends a very short time (typically a few nanoseconds) in that state before emitting a photon (or decaying by another process). For an individual fluorophore the time interval between absorption and emission varies randomly, but for an ensemble of fluorophores the average amount of time spent in the excited state is a characteristic of the fluorophore called the lifetime, т. The measurement of fluorescence lifetime biosensing can be done using a time-domain lifetime measurement approach or a frequency-domain lifetime measurement approach. This chapter also discusses the basic approaches for lifetime-based biosensing. While time- and frequency-domain instruments have been available commercially, they were not operable by scientists outside the field without significant training. However, the availability of essentially turnkey instrumentation has brought lifetime-based sensing much more into the mainstream. Finally, adaptation of the approach for use with the microscope and with optical fibers makes these sensors uniquely useful for biology and environmental monitoring; of particular importance is their utility for quantitative fluorescence resonance energy transfer (FRET)–based studies in live cells.
Religious Law and Religious Courts as a Challenge to the State (National Report for United States of America)

This book chapter outlines the changing landscape of religion and religious liberty protections within U.S. law. Written by invitation for the German Congress of the Society of Comparative Law, the chapter primarily functions as an introduction to the historical, constitutional, and statutory law of religious liberty in the United States. It also provides a glimpse into current controversies regarding religious liberty, including anti-Shari’a statutes, faith-based arbitration, conflicts between religious freedom and antidiscrimination norms, and religious rights for corporations.After first describing the sociological status of religious identity in the United States, the chapter focuses heavily upon the underpinnings of religious liberty in the United States. The chapter provides a crisp overview of the the current legal structures under which religious liberty claims are addressed. A historical framework guides the reader into constitutional and statutory protections for religious liberty at both the federal and state levels. The chapter then examines more carefully the role of religious groups and their rights, with a specific application of marriage and divorce law and anti-Shari’a statutes. Finally, the chapter looks broadly at some areas of jurisdictional overlap between religious groups and individuals, on the one hand, and those of the state and civil law, on the other. We conclude optimistically, believing that America’s history and commitment to religious liberty ultimately provide guidance and reason for hope even as religious liberty is under increasing pressure in the 21st century.