cssi/SciSciGPT-SciSciNet huggingface dataset:
On the possibility to investigate irradiated fuel pins non-destructively by digital neutron radiography with a neutron-sensitive microchannel plate detector with Timepix readout

Abstract Post irradiation examination (PIE) of nuclear fuels provides valuable information on their overall performance and is important for the assessment of safety and integrity of nuclear fuels. PIE is also very useful for the optimization of the spent fuel processing and for the development of future advanced fuels. Neutron radiography (NR) provides more comprehensive information about the internal condition of irradiated nuclear fuels than any other non-destructive PIE examination, and NR informs subsequent characterization by destructive techniques. At the present time most NR of irradiated fuel is conducted through image transfer methods using radiographic films or imaging plates. Digital neutron radiography of irradiated fuel poses significant challenges due to the extreme levels of radiation generated by the irradiated fuel itself. In this paper, we present the results of neutron imaging of irradiated fuel by a digital detector installed in a radial neutron beam with direct line of sight to the reactor core. The results of these experiments demonstrate the possibility to perform nearly real-time initial screening of the internal structure of an experimental transmutation fuel pin at the Neutron Radiography reactor at Idaho National Laboratory. The detector used in these experiments, based on neutron sensitive microchannel plates and Timepix readout. It sustained operation at high radiation environment with gamma dose rates of ∼ 5.5 Sv/hr from the sample itself and ∼ 2.0 Sv/hr in the neutron beam The influence of various experimental setup characteristics (beam collimation, gamma and neutron background fluxes, image integration time) on the quality of resulting neutron radiographic images was studied for the optimization of the future imaging experiments. These measurements also demonstrate the possibility to reduce the fraction of unwanted gamma events by lead filter installed between the detector and the irradiated fuel. At the optimal configuration the fraction of neuron counts was measured to exceed 90% of all registered events in the detector. The results indicate that non-destructive post irradiation examination of nuclear fuels can be extended beyond conventional neutron radiography to more advanced imaging techniques, which include tomographic, dark field, energy resolved neuron imaging and many others, enabling more detailed quantitative characterization beyond preliminary screening.
The human thymic microenvironment.

Publisher Summary Monoclonal reagents have made people able to phenotypically identify four major regions of the human thymus microenvironment: the thymic capsule, interlobular septae and stroma, the subcapsular cortex, the cortex, and the medulla. TE-4 + and TE-3 + thymic epithelium constitute HLA + , Ia + subsets of thymic epithelium that are candidates for cell types of the human thymic microenvironment that might participate in conferring major histocompatability complex (MHC) restriction to maturing T lymphocytes. TE-4, anti-p19, and BB TECS antibodies are thymic epithelial lineage markers; they all react with the basal layer of squamous epithelium of various organs. The concept that thymic epithelium is constantly differentiating in the developed thymus is suggested by the coexpression of TE-4, TE-8, TE-16, and TE-15 antigen by layers of squamous epithelial keratinocytes and by thymic epithelium. Three phases of thymic microenvironment development can be defined. The first phase is during early fetal development when mesodermal-derived fibrous tissue induces endodermal and ectodermal-derived thymic epithelium to proliferate and mature. The second phase occurs between 9 and 15 weeks of fetal development when the thymic primordia are colonized by blood-borne thymocyte precursors. Presumably during this stage, thymic epithelium promotes bone marrow cell colonization of thymus by producing chemoattractant molecules. The third phase of thymic microenvironment development consists of that period of time when the thymic microenvironment contributes to various stages of intrathymic T cell functional maturation. These functions involve participation in generation of the T cell repertoire, generation of MHC restriction, and the production of soluble thymotrophic factors—such as thymosinal, thymopoietin, and thymulin.
Build optimization of fiber-reinforced additively manufactured components

Additive manufacturing (AM) has enabled the fabrication of artifacts with unprecedented geometric and material complexity. The focus of this paper is on the build the optimization of short fiber reinforced polymers (SFRP) AM components. Specifically, we consider optimization of the build direction, topology, and fiber orientation of SFRP components. All three factors have a significant impact on the functional performance of the printed part. While significant progress has been made on optimizing these independently, the objective of this paper is to consider all three factors simultaneously and explore their interdependency, within the context of thermal applications. Towards this end, the underlying design parameters are identified, appropriate sensitivity equations are derived, and a formal optimization problem is posed as an extension to the popular Solid Isotropic Material with Penalization (SIMP). Results from several numerical experiments are presented, highlighting the impact of build direction, topology, and fiber orientation on the performance of SFRP components.
Effects of wavelength on transcranial laser stimulation: a Monte Carlo simulation study based on standard brain model (Conference Presentation)

Transcranial laser stimulation (TLS) is a neural type of photobiomodulation that has been shown beneficial effects on neurons. However, previous research in this field has used multiple wavelengths in the red to near-infrared range. It remains unclear which wavelength is optimal to stimulate the brain. In this study, Monte Carlo simulations are conducted to exposit the efficiencies of three representative wavelengths (660 nm, 810 nm and 1064 nm) in delivering photon energy into the brain. The results indicate that 1064 nm is the optimal, benefiting from its reduced tissue scattering.
College students' perceived knowledge of and perceived helpfulness of treatments for opioid use disorder at two American universities

Background The U.S. is experiencing an opioid overdose health crisis, largely driven by opioid use disorder (OUD). College students have relatively high rates of substance use disorders. Objectives To identify perceived knowledge of and perceived helpfulness of various OUD treatments, including medications for OUD (MOUD), among college students. Methods A convenience sample of students enrolled at two public universities during Fall 2018/Spring 2019 were recruited for an online cross-sectional survey. Questions examined reported knowledge of and perceived helpfulness of MOUD (i.e. methadone, buprenorphine, naltrexone) and non-MOUD treatments for OUD (e.g. peer support groups, individual counseling, group counseling, outpatient treatment). Logistic regression examined associations between knowledge, perceived helpfulness, and demographic variables. Results We received 1,439 responses and kept 1,280 (39% male; 61% female). Respondents were significantly more likely to report knowledge about non-MOUD treatments than MOUD treatments (48.7% of respondents reported being very knowledgeable about individual counseling, 4.4% about methadone, 3.8% about naltrexone, and 3.4% about buprenorphine). Among those reporting at least some MOUD knowledge, few perceived MOUD as helpful/very helpful (methadone 14%, naltrexone 14%, and buprenorphine 11%). Among those reporting at least some counseling knowledge, 71% felt counseling was helpful/very helpful. Perceived treatment knowledge was significantly and positively associated with perceived treatment helpfulness. Conclusions Students had more positive attitudes toward non-MOUD treatments than toward MOUD despite greater efficacy of the latter for OUD. Colleges could provide information about MOUD during orientation, in course work, through student extracurricular organizations, or through college health clinics.
De novo resveratrol production through modular engineering of an Escherichia coli – Saccharomyces cerevisiae co-culture

Resveratrol is a plant secondary metabolite with diverse, potential health-promoting benefits. Due to its nutraceutical merit, bioproduction of resveratrol via microbial engineering has gained increasing attention and provides an alternative to unsustainable chemical synthesis and straight extraction from plants. However, many studies on microbial resveratrol production were implemented with the addition of water-insoluble phenylalanine or tyrosine-based precursors to the medium, limiting in the sustainable development of bioproduction. Here we present a novel coculture platform where two distinct metabolic background species were modularly engineered for the combined total and de novo biosynthesis of resveratrol. In this scenario, the upstream Escherichia coli module is capable of excreting p-coumaric acid into the surrounding culture media through constitutive overexpression of codon-optimized tyrosine ammonia lyase from Trichosporon cutaneum (TAL), feedback-inhibition-resistant 3-deoxy-d-arabinoheptulosonate-7-phosphate synthase (aroGfbr) and chorismate mutase/prephenate dehydrogenase (tyrAfbr) in a transcriptional regulator tyrR knockout strain. Next, to enhance the precursor malonyl-CoA supply, an inactivation-resistant version of acetyl-CoA carboxylase (ACC1S659A,S1157A) was introduced into the downstream Saccharomyces cerevisiae module constitutively expressing codon-optimized 4-coumarate-CoA ligase from Arabidopsis thaliana (4CL) and resveratrol synthase from Vitis vinifera (STS), and thus further improve the conversion of p-coumaric acid-to-resveratrol. Upon optimization of the initial inoculation ratio of two populations, fermentation temperature, and culture time, this co-culture system yielded 28.5 mg/L resveratrol from glucose in flasks. In further optimization by increasing initial net cells density at a test tube scale, a final resveratrol titer of 36 mg/L was achieved. This is first study that demonstrates the use of a synthetic E. coli–S. cerevisiae consortium for de novo resveratrol biosynthesis, which highlights its potential for production of other p-coumaric-acid or resveratrol derived biochemicals.
Netarsudil for the Treatment of Open-Angle Glaucoma and Ocular Hypertension: A Literature Review.

Objective:To evaluate netarsudil’s role as first-line therapy for the treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT).Data Sources:A literature search utilizing MEDLINE and CIN...
The metastable Q 3 Δ 2 state of ThO: a new resource for the ACME electron EDM search

The best upper limit for the electron electric dipole moment was recently set by the ACME collaboration. This experiment measures an electron spin-precession in a cold beam of ThO molecules in their metastable H (3Δ1) state. Improvement in the statistical and systematic uncertainties is possible with more efficient use of molecules from the source and better magnetometry in the experiment, respectively. Here, we report measurements of several relevant properties of the long-lived Q (3Δ2) state of ThO, and show that this state is a very useful resource for both these purposes. The Q state lifetime is long enough that its decay during the time of flight in the ACME beam experiment is negligible. The large electric dipole moment measured for the Q state, giving rise to a large linear Stark shift, is ideal for an electrostatic lens that increases the fraction of molecules detected downstream. The measured magnetic moment of the Q state is also large enough to be used as a sensitive co-magnetometer in ACME. Finally, we show that the Q state has a large transition dipole moment to the C (1Π1) state, which allows for efficient population transfer between the ground state X (1Σ+) and the Q state via X-C-Q Stimulated Raman Adiabatic Passage (STIRAP). We demonstrate 90% STIRAP transfer efficiency. In the course of these measurements, we also determine the magnetic moment of C state, the X→C transition dipole moment, and branching ratios of decays from the C state.
Effect of Molecular Architecture on the Self-Assembly of Bottlebrush Copolymers

The characteristics of a new architecture of bottlebrush copolymers (BBCPs) self-assembly were studied using self-consistent field theory. In this molecule, a series of AB linear diblock side chains were connected at the diblock junction using a C backbone. The control over the linker length and its chemical nature created an additional constraint on the intrinsic AB diblock microphase separation. Increasing side-chain crowding by increasing the grafting density and total degree of polymerization induced improved phase separation. This was reflected in the overall reduction in the effective interaction parameter between the diblocks as well as the abrupt increase in phase density when crossing the order-disorder transition. Side-chain crowding resulted in an increase in the equilibrium domain spacing compared to a linear diblock. On the other hand, the localization of block C at the AB interface generated a diffuse domain boundary and reduction in side-chain stretching. The unique behavior of BBCPs was observed in 1D confined systems where the molecule showed the natural tendency to orient domains parallel to neutral confinement in contrast to the behavior of confined diblocks. Such behavior largely depended on the degree of incompatibility between the AB blocks and BBCP structure. A ternary phase diagram was constructed for different proportions of each block. Rich morphologies of core-shell domains and tiling patterns were observed including octagonal and pentagonal polygons. The unique architecture of this bottlebrush molecule and its improved nanoscale properties make it an attractive candidate for various applications of nanotechnology.
Viewpoint: Name Those Judges!

In reporting about decisions of the Court of Appeals, the news media seldom identify the judges who decided the appeal. The point of this opinion piece is that if the decision is noteworthy, the deciders should be noted.
Spontaneous Resolution of Diffuse Idiopathic Slit-Like "Syrinx" in a Pediatric Patient.

It is important to recognize that a prominent central canal of the spinal cord can be a normal variant and can spontaneously regress. A five-year-old male presented for evaluation of abnormal gait. Prior brain magnetic resonance imaging showed no hindbrain malformation, and the patient had no history of trauma. Full spine magnetic resonance imaging showed a vertical slit-like linear cavity within the center of the spinal cord, from C6-7 to the conus medullaris with a diameter ranging from 0.5 to 2 mm. This was initially reported as a syrinx. The patient's symptoms remained stable. Three years later, follow-up magnetic resonance imaging showed spontaneous resolution of the slit-like cavity. This case likely represented a prominent central canal (a normal variant) that underwent normal closure.
Modern confocal microscopy.

This unit re-examines confocal microscopy from a current perspective. It outlines many of the most modern applications of confocal microscopy and the issues surrounding them. The expanding applications of confocal microscopy demand both minor and major modifications of the technology to enhance imaging capabilities for a growing variety of samples. Techniques of interest such as FRET, FLIP, FRAP, and IFRAP are described. The unit includes a discussion on multispectral imaging, potentially the most exciting innovation in the field of biological imaging. The other area that is beginning to have considerable impact on biology, medicine, and pharmacology comprises high-content screening (HCS) and high-throughput screening (HTS). This unit also introduces programmable array microscopes (PAMs), which are based upon a technique in which spatial modulators are placed in the imaging plane of a microscope and used to generate patterns of illumination and/or detection. Keywords: confocal microscopy; multispectral imaging; programmable array microscope; FRET; FRAP
Sensor localization in an obstructed environment

Sensor localization can be divided into two categories: range-based approaches, and rang-free approaches. Although range-based approaches tend to be more accurate than range-free approaches, they are more sensitive to errors in distance measurement. Despite of the efforts on recovering sensors’ Euclidean coordinates from erroneous distance measurements, as will be illustrated in this paper, they are still prone to distance errors, particularly in an obstruction abundant environment. In this paper, we propose a new algorithm for sensor localization based on Multiscale Radio Transmission Power(MRTP). It gradually increases the scale level of transmission power, and the distance is determined by the minimal scale of received signals. Unlike the range-based approaches, which treat each measured distance as an approximation of the true one, in our new approach, the measured distance serves as a constraint that limits the feasible location of sensors. Our simulations have shown that the MRTP-based approach is able to provide accurate and robust estimation of location, especially in an area abundant in obstructions, where most current approaches fail to perform well.
Two Kinds of Stakes

I distinguish two different kinds of practical stakes associated with propositions. The W-stakes (world) track what is at stake with respect to whether the proposition is true or false. The A-stakes (attitude) track what is at stake with respect to whether an agent believes (or relies on) the proposition. This poses a dilemma for those who claim that whether a proposition is known can depend on the stakes associated with it. Only the W-stakes reading of this view preserves intuitions about knowledge-attributions, but only the A-stakes reading preserves the putative link between knowledge and practical reasoning that has motivated it.
Clinical color vision testing and correlation with visual function.

Purpose To determine if Hardy-Rand-Rittler (H-R-R) and Ishihara testing are accurate estimates of color vision in subjects with acquired visual dysfunction. Design Assessment of diagnostic tools. Methods Twenty-two subjects with optic neuropathy (aged 18–65) and 18 control subjects were recruited prospectively from an outpatient clinic. Individuals with visual acuity (VA) Results No relationship was found between H-R-R and D-15 scores ( P = .477). H-R-R score and contrast sensitivity were positively correlated ( P = .003). On multivariate analysis, contrast sensitivity (β = 8.61, P P = .022) both showed association with H-R-R scores. Similar to H-R-R, Ishihara score did not correlate with D-15 score ( P = .973), but on multivariate analysis was related to contrast sensitivity (β = 8.69, P P = .069). Conclusion Neither H-R-R nor Ishihara testing appears to assess color identification in patients with optic neuropathy. Both H-R-R and Ishihara testing are correlated with contrast sensitivity, and these tests may be useful clinical surrogates for contrast sensitivity testing.
Water Levels Accompanying Atlantic Coast Hurricanes

The water levels that occurred along the Atlantic coast during five recent hurricanes are described and compared. The forerunner, a rise in water level which may precede the passage of the storm by many hours, is found to depend upon the force and direction of the general wind field into which the storm advances. The surge that accompanies the violence of the storm depends in duration on the speed of progression of the storm center. Maximum water levels of 8 to 9 ft above the predicted tide developed at positions between 40 and 100 n mi to the right of the storm center; elevations in excess of 5 ft occurred from 50 n mi to the left to 150 n mi to the right of the center.
Chapter 1. Recent Approaches to Novel Antidepressant Therapy

Publisher Summary This chapter describes recent approaches to novel antidepressant therapy. Three basic improvements in antidepressant therapy; faster onset of action, improved efficacy in refractory patients, and an improved side-effect profile, remain the primary targets for new antidepressant research. Selective serotonin reuptake inhibitors (SSRIs) have been available since the 1980s for the treatment of depression. The most widely known SSRls are fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram. SSRIs possess a favorable side-effect profile relative to classical tricyclic antidepressants (TCAs). They are generally not more efficacious than the TCAs. In addition, they exhibit a marked delay in onset of antidepressant action, and are accompanied by their own particular set of side effects resulting from the non-selective stimulation of serotonergic receptor sites. The chapter highlights significant results in recent efforts to develop new pharmaceutical agents that could constitute a new generation of antidepressant therapy and discusses concepts related to monoamine reuptake inhibitors. A discussion on SSRIs is presented. Norepineohrine reuptake inhibitors are elaborated. Serotonin receptor ligands are discussed and other monoaminergic receptor ligands are described. Nonmonoaminergic receptor approaches are reviewed. Details of Hypericum and Mesembrine are also provided in the chapter.
Formation and evolution of self-interacting dark matter haloes

We have derived the first, fully cosmological, similarity solutions for cold dark matter (CDM) halo formation in the presence of non-gravitational collisionality (i.e. elastic scattering), which provides an analytical theory of the effect of the self-interacting dark matter (SIDM) hypothesis on halo density profiles. Collisions transport heat inward, which flattens the central cusp of the CDM density profile to produce a constant-density core, while continuous infall pumps energy into the halo to stabilize the core against gravothermal catastrophe. This is contrary to previous analyses based upon isolated haloes, which predict core collapse within a Hubble time. These solutions improve upon earlier attempts to model the formation and evolution of SIDM haloes, offer deeper insight than existing N-body experiments, and yield a more precise determination of the dependence of halo density profile on the value of the CDM self-interaction cross-section. Different solutions arise for different values of the dimensionless collisionality parameter Q ≡ σ ρ b r vir oc r vir /λ mfp , where σ is the scattering cross-section per unit mass, ρ b is the cosmic mean matter density, r vir is halo virial radius and λ mfp is the collision mean free path. The maximum flattening of central density occurs for an intermediate value of Q, Q th , at which the halo is maximally relaxed to isothermality. The density profiles with constant-density cores preferred by dwarf and low surface brightness (LSB) galaxy rotation curves are best fit by the maximally flattened (Q = Q th ) solution. If we assume that dwarfs and LSB galaxies formed at their typical collapse epoch in ACDM, then the value of a which makes Q = Q th is σ ≃ 200 cm 2 g -1 , much higher than previous estimates, σ ≃ [0.5-5] cm 2 g -1 , based on N-body experiments. If σ is independent of collision velocity, then the same value σ ≃ 200 cm 2 g -1 would make Q > Q th for clusters, which typically formed only recently, resulting in relatively less flattening of their central density profile and a smaller core.
Inhibition of DNA replication in HeLa S3 cells by macromomycin-I, an antitumor protein antibiotic.

Macromomycin-I, a chromophore-containing form of an antitumor protein antibiotic macromomycin, was found to be a potent inhibitor of [ 3 H]thymidine incorporation into DNA in intact nonsynchronous and G 1 /S-synchronized HeLa S 3 cells. This inhibitory effect depended on the drug dose and duration of treatment, but was essentially independent of the cell cycle position, within the G 1 through S phases. A parallel inhibition of DNA synthesis was observed in lysates and purified nuclei from drug-treated cells (as measured by incorporation of radioactive dTTP into DNA), indicating that the drug interferes with DNA biosynthesis after formation of deoxynucleoside triphosphates. The addition of a cytoplasmic fraction from untreated cells to purified nuclei from drug-treated cells failed to overcome the inhibition of DNA synthesis, while a cytoplasmic fraction from drug-treated cells was able to stimulate efficiently DNA synthesis in purified nuclei from untreated cells. Moreover, the inhibition of DNA synthesis in nuclei from drug-treated cells could be overcome by the addition of exogeneous DNA. These data demonstrate that macromomycin-I acts on DNA replication by interfering with the template and probably does not affect DNA polymerase or other factors involved in replication. In addition, macromomycin-I was found to enhance the incorporation of [ 3 H]thymidine into DNA in HeLa S 3 cells in the presence of hydroxyurea; thus, the drug seems to stimulate DNA repair. Both findings, inhibition of DNA replication and stimulation of repair synthesis, probably arise from the drug’s damage to DNA and support the assumption that this damage is a primary event in the cytotoxic action of macromomycin.
Variable time optimal control

Abstract : In problems of optimal control, the final time T may be fixed or it may be variable. For the variable time case, an additional necessary condition that the Hamiltonian be zero is added to the usual conditions used for the fixed time case. In this paper, it will be shown that this necessary condition may lead to a variable time local maximum as well as a local minimum. The paper first develops a computational algorithm using only the H=O condition, and then develops a sufficient condition for a variable time local minimum and a computational algorithm employing this condition. Numerical examples are given to illustrate all results. (Author)
Methylation of Herpesvirus saimiri DNA in lymphoid tumor cell lines

Several continuous lymphoid cell lines have been established from tumors induced by Herpesvirus saimiri. At least a portion of the viral DNA in the marmoset lymphoid cell line 1670, which does not produce detectable virus, is present as covalently closed circular episomal DNA. The use of restriction endonuclease digestion, transfer to nitrocellulose filters, and hybridization of the virus-specific DNA has produced strong evidence that viral DNA sequences present in total 1670 cell DNA and in isolated episomes are extensively methylated. The restriction endonuclease Hpa II has the same recognition sequence as Msp I but, unlike Msp I, fails to cleave when the C of the C-G dinucleotide is methylated. Viral DNA sequences of 1670 cells are refractory to cleavage by Hpa II but not Msp I; greater than 80% of the Hpa II cleavage sites appear to be methylated. Similarly, viral DNA sequences of 1670 cells are refractory to cleavage by Sma I (C-C-C-G-G-G) and Sac II (C-C-G-C-G-G) but not Sac I, Pvu II, or Pst I, which lack the dinucleotide C-G in their recognition sequences. Methylation of mammalian DNA has been previously found exclusively at C residues in the dinucleotide C-G. H. saimiri DNA sequences of another nonproducer cell line, 70N2, also appeared to be extensively methylated, but analysis of total cell DNA extracted from three virus-producing lymphoid lines revealed no evidence of methylation of viral DNA sequences. It remains to be seen if methylation of viral DNA plays a role in the lack of complete expression of H. saimiri genome information in nonproducing lymphoid cell lines.
Inositol 1,3,4,5-Tetrakisphosphate (IP 4 ) Receptor Modification during Hypoxia in Cerebral Cortical Neuronal Nuclei of the Term Guinea Pig Fetus

Inositol 1,3,4,5-Tetrakisphosphate (IP 4 ) Receptor Modification during Hypoxia in Cerebral Cortical Neuronal Nuclei of the Term Guinea Pig Fetus
Mapping technological capabilities into product markets and competitive advantage: the case of cholesterol drugs

While a lot of attention has been paid to those characteristics of capabilities that give firms a competitive advantage, a lot less attention has been given to supporting empirical evidence and to the deployment of these capabilities. This paper presents a model for mapping firm capabilities into customer value and competitive advantage in different markets. With empirical evidence from cholesterol drugs, I illustrate how the model can be used to estimate customer value and competitive advantage from technological capabilities. Copyright © 2002 John Wiley & Sons, Ltd.
Sexual revolutions in Cuba: passions, politics and memory

CARRIE HAMILTON, 2012, Chapel Hill, NC: University of North Carolina Press, 2012, 298 pp, ISBN 9780807835197, £56.93 (hardback) Cuban sexual politics have received an inordinate amount of attention...
Effects of cholecystokinin antagonists on the discriminative stimulus effects of cocaine in rats and monkeys

Abstract Cholecystokinin (CCK) has been implicated as a modulator of dopamine (DA) neurotransmission in the mesolimbic DA pathway, a primary pathway implicated in the effects of cocaine related to its abuse. The present experiment was designed to examine whether an antagonist that acts at either CCKA or CCKB receptors can modify the discriminative stimulus effects of cocaine in animals. Rats (N = 9) and rhesus monkeys (N = 3) were trained in two-lever drug discrimination paradigms to discriminate cocaine from saline. Lever pressing was maintained by food (all rats, two monkeys) or shock avoidance (one monkey). In rats, the CCKA antagonist MK-329 (1.0–32 mg/kg, i.p.) or the CCKB antagonist CI-988 (1.0–32 mg/kg, i.p.) were administered 30 min before determination of cocaine dose-response functions using a cumulative dosing method. In monkeys, CI-988 (8.0–32 mg/kg, i.m.) was administered 30, 60 or 120 min before the training dose of cocaine. In both species, cocaine produced dose-related increases in the percentage of responses emitted on the cocaine-appropriate lever. In rats, MK-329 shifted the cocaine dose-response function to the right in a dose-related manner. In contrast, CI-988 did not systematically alter the effects of cocaine in either rats or monkeys. Since drug discrimination serves as an animal model of the subjective effects of drugs in humans, these results suggest that CCKA antagonists may decrease the subjective effects of cocaine. It seems unlikely that CCKB antagonists will alter the subjective effects of cocaine.
Surprises from Drosophila: genetic mechanisms of synaptic development and plasticity

Drosophila are excellent models for the study of synaptic development and plasticity, thanks to the availability and applicability of a wide variety of powerful molecular, genetic, and cell-biology techniques. Three decades of study have led to an intimate understanding of the sequence of events leading to a functional and plastic synapse, yet many of the molecular mechanisms underlying these events are still poorly understood. Here, we provide a review of synaptogenesis at the Drosophila glutamatergic neuromuscular junction (NMJ). Next, we discuss the role of two proteins that forward genetic screens in Drosophila have revealed to play crucial-and completely unexpected-roles in NMJ development and plasticity: the origin of replication complex protein Latheo, and the enzyme glutamate decarboxylase. The requirement for these proteins at the NMJ highlights the fact that synaptic development and plasticity involves intense inter- and intracellular signaling about which we know almost nothing.
Cell affinity determining heterospecific graft intolerance in hydra.

Abstract Column segments taken from hydra of different species can be grafted together; they separate after a period ranging from hours to weeks, depending on the species pair. The healing and separation processes were studied in homografts and heterografts by light and electron microscopy, using seven species of the genera Hydra , Chlorohydra and Pelmatohydra . In homografts, the edge cells show pseudopodial activity and attach and adhere rapidly. Heterografts show some normal tissue healing activities, but the poorer heterotypic cell adhesions result in the tissues eventually separating. In combinations where the tissues heal poorly initially, the tissues fall apart soon after grafting. In other heterografts, cell attachments arise which resemble septate desmosomes, and there is sufficient healing to hold the tissues together for at least several days. Later a constriction develops at the graft site and progresses until the unlike tissues are pinched apart. This constriction appears to represent not immunological rejection, but rather a replacement of the heterotypic cell junctions by homospecific attachments, leading to a gradual separation of the tissues.
Electrically evoked locomotor activity in the turtle spinal cord hemi-enlargement preparation

We assessed the locomotor capacity of the left half of the spinal cord hindlimb enlargement in low-spinal turtles. Forward swimming was evoked in the left hindlimb by electrical stimulation of the right dorsolateral funiculus (DLF) at the anterior end of the third postcervical spinal segment (D3). Animals were held by a band-clamp in a water-filled tank so that hindlimb movements could be recorded from below with a digital video camera. Left hindlimb hip and knee movements were tracked while electromyograms (EMGs) were recorded from left hip and knee muscles. In turtles with intact spinal cords, electrical stimulation of the right D3 DLF evoked robust forward swimming movements of the left hindlimb, characterized by rhythmic alternation between hip flexor (HF) and hip extensor (HE) EMG discharge, with knee extensor (KE) bursts occurring during the latter part of each HE-off phase. After removing the right spinal hemi-enlargement (D8-S2), DLF stimulation still evoked rhythmic locomotor movements and EMG bursts in the left hindlimb that included HF-HE alternation and KE discharge. However, post-surgical movements and EMG bursts had longer cycle periods, and movements showed lower amplitudes compared to controls. These results show that (1) sufficient locomotor CPG circuitry resides within the turtle spinal hemi-enlargement to drive major components of the forward swim motor pattern, (2) contralateral circuitry contributes to the excitation of the locomotor CPG for a given limb, and (3) a sufficient portion of the descending DLF pathway crosses over to the contralateral cord anterior to the hindlimb enlargement to activate swimming.
Convergence analysis and preliminary experimental feasibility for MRI-localized region spectroscopy with NIR diffuse optical tomography

NIR tomography image reconstruction can be improved by incorporating spectral constraints and prior spatial information. The convergence of scattering power was studied based on the distribution of projection error with different parameters. The reason that scattering properties are harder to recover than chromophore concentrations was discussed. Using "hard prior" spectral reconstruction, the role of stopping criteria was found to be important. Multiple wavelength simulations were used to choose suitable stopping criteria. Preliminary tests using a wavelength tunable Ti-Sapphire laser shows promise for frequency domain measurements covering a wide range of wavelengths.
Monetary Calculation and the Unintended Extended Order: The Misesian Microfoundations of the Hayekian Great Society

In the last decade, a small group of Austrians has attempted to argue that there are crucial distinctions between the Misesian and Hayekian lines of influence, and that the former is the superior. This paper argues that the group has both misread Hayek and underplayed the similarities of Mises and Hayek. More specifically, it sees Mises's emphasis on monetary calculation and goal-driven human action as providing the microfoundations for Hayek's emphasis on spontaneous order and the epistemic properties of the price system. The paper also disputes the claim that Hayek held a “fully-informative,” neoclassical view of prices and explores the disequilibrium foundation for Hayek's understanding of the role of prices as knowledge surrogates. The relationship between monetary calculation and cooperation in anonymity is discussed in the final section.
EchoPAT: a system for real-time complex event pattern monitoring

Domain users are not only interested in the detection of predefined complex event patterns but also in their step by step execution and their usage statistics in order to make predictions or detect problems in defined patterns. However, existing Complex Event Processing engines are like a black box and are designed for a complete matching of a pattern and therefore do not consider the concept of partially fulfilled patterns. In this demo we present a pattern monitoring system based on the open source CEP engine Esper. The goal is to provide the current fulfillment degree of a pattern including a detailed pattern graph such that the domain user can see which part of the pattern is evaluated true and which not before taking any decisions.
Interpretation and review of health-related quality of life data in CKD patients receiving treatment for anemia

Recent evidence suggests that targeting higher hemoglobin values with erythropoiesis stimulating agents (ESAs) may lack mortality benefits and may even result in adverse cardiovascular complications when used in chronic kidney disease patients. However, ESAs are frequently reported to result in improvements in health-related quality of life (HRQOL). The purpose of this review is to evaluate the magnitude and nature of ESA-associated improvements in HRQOL, as well as to understand how to interpret the clinical significance of HRQOL data. HRQOL findings should be analyzed not by statistical significance but rather by using a minimal clinically important difference approach, or, alternatively, a distribution-based approach (such as Cohen's effect size). HRQOL domains that are most improved with ESAs relate to physical symptoms, vitality, energy, and performance; domains of social functioning and mental health show modest improvement, whereas the domains of emotional functioning and pain show very little improvement. Additional domains not measured by commonly used instruments (such as the SF-36) that have been shown to improve with ESAs include sleep, cognitive functioning, and sexual functioning. The maximal increase in HRQOL per incremental increase in hemoglobin appears to occur in the range of 10–12 g/dl. Beyond this range, additional normalization of hemoglobin (to 12–14 g/dl) results in continued (albeit blunted) improvements in HRQOL.
Bonding wood veneers with cellulose solvents.

Abstract Various solvent systems capable of dissolving cellulose have been reported in the literature. Cuene (cupriethylene diamine hydroxide) and FeTNa (ferric sodium tartrate) are well known examples. Preliminary experiments were conducted with Cuene and FeTNa to determine if the cellulose dissolving ability of these systems could be used to bond yellow birch veneers. The results indicate that relatively high dry shear strengths, and low wet shear strengths are obtained.
Determination of multicomponent protein structures in solution using global orientation and shape restraints.

Determining architectures of multicomponent proteins or protein complexes in solution is a challenging problem. Here we report a methodology that simultaneously uses residual dipolar couplings (RDC) and the small-angle X-ray scattering (SAXS) restraints to mutually orient subunits and define the global shape of multicomponent proteins and protein complexes. Our methodology is implemented in an efficient algorithm and demonstrated using five examples. First, we demonstrate the general approach with simulated data for the HIV-1 protease, a globular homodimeric protein. Second, we use experimental data to determine the structures of the two-domain proteins L11 and γD-Crystallin, in which the linkers between the domains are relatively rigid. Finally, complexes with Kd values in the high micro- to millimolar range (weakly associating proteins), such as a homodimeric GB1 variant, and with Kd values in the nanomolar range (tightly bound), such as the heterodimeric complex of the ILK ankyrin repeat domain (ARD) a...
Increased p21 and p53 levels are associated with S phase growth arrest in hyperoxia-treated human bronchial smooth muscle cells † 1968

Elevated levels of oxygen inhibit the growth of airway smooth muscle cells in vitro. The mechansim responsible for this effect is unknown. Since the proliferation of airway smooth muscle cells is regulated at the G1/S phase checkpoint by specific cyclin-dependent kinases, we tested the hypothesis that O2 would inhibit proliferation through p53-dependent regulation of p21, a cyclin-dependent kinase inhibitor. Methods: Human bronchial smooth muscle cells (BSMC) seeded 3000cells/cm2 were grown in smooth muscle growth media + 5% serum. After 24 hrs, cells were exposed to either 21, 40, or 95%O2 + 5%CO2 for 72 hrs. Every 24 hrs, culture plates were removed and analyzed for cell number, cell cycle distribution, p21 and p53 levels, and apoptosis (n=2-4/condition, time). Cell number was determined using a hemocytometer. Cell cycle distribution was assessed by propidium iodide staining and flow cytometry. p21 and p53 levels were determined by ELISA. Apoptosis was studied using a TdT-BrdU assay and flow cytometry. Trends were analyzed by ANOVA using Bonferroni comparison testing with α set at p≤0.05. Results: We found that hyperoxia inhibited BSMC growth in a time- and concentration-dependent manner (ANOVA, p<0.0001). Hyperoxia also increased%S phase cells over time (ANOVA, p<0.05) with differences found at 72 hrs (21%O2, 17.6±1.2 vs 95%O2, 31.4±1.5%; p<0.05). Both p21 and p53 levels were affected by O2 over time (ANOVA, p≤0.05) with increases occuring at 48 hrs(p21:21%O2, 0.52±.08 vs 95%O2, 1.10±.02 U/ml/104 cells; p53: 21%O2, 0.017±.004 vs 95%O2, 0.050±.002 ng/ml/104 cells; p<0.05). The% apoptotic cells was≤5% at all times and was unaffected by O2. Conclusions: We conclude that hyperoxia inhibits growth of BSMC through specific alterations in the cell cycle. Furthermore, exposure to 95%O2 leads to S phase arrest which is preceded by elevations of p21 and p53 levels. These results are consistent with p53-dependent regulation of proliferation occuring through alteration of the p21/PCNA complex necessary for the function of DBA polymerase δ.
High Agatston aortic valve calcium score predicts transcatheter paravalvular aortic regurgitation.

MATERIALS AND METHODS We reviewed the records of 303 patients who underwent transcatheter aortic valve replacement with the SAPIEN/SAPIEN XT valve (Edwards Lifesciences Corporation, Irvine, Calif) from November 2008 through August 2013. From this population, a study group was created of the 99 patients (32.9%) who underwent preopertive contrast-enhanced multidetector computed tomography with calculation of the Agatston aortic valve calcium score and aortic valve area. Categoric data are presented as counts with frequencies, and continuous data are presented as medians with interquartile ranges (IRQs). Transcatheter aortic valve oversize data are reported as percentages and were determined by the following formula: [(transcatheter aortic valve area/contrast-enhanced multidetector computed tomographically derived aortic valve area) 1]3 100. Logistic regression of dichotomous variables was done using the upper interquartile range Agatston score and lower interquartile range valve oversize calculation. Analysis was completed using JMP 10.0 software package (SAS Institute Inc, Cary, NC).
Performance study of a dual CDC Cyber 170/750 system

A performance study of a dual CDC Cyber 170/750 system is presented. The purpose of the study was twofold: to predict the maximum number of interactive users the system could satisfactorily support and to predict the effect of changes in workload and configuration. Two noteworthy aspects of the study are the use of a detailed event trace system to parameterize and validate the model and the use of a very-high-level simulation language. The results of the study, including the accuracy of predictions and the feasibility of the approach, are presented.
Bromocriptine, a dopamine D2 receptor agonist, inhibits adenylyl cyclase activity in rat olfactory epithelium.

Abstract The presence of large numbers of dopaminergic neurons in the olfactory bulb suggests that dopamine plays an important role in olfaction. Dopamine D2 receptors are produced in olfactory sensory neurons [Shipley et al . (1991) Chem. Senses 16 , 5] and found in relatively high concentrations in their terminals in the nerve and glomerular layers of the olfactory bulb [Nickell et al . (1991) NeuroReport 2 , 9–12]. In other systems D2 receptors are linked to adenylyl cyclase by an inhibitory G-protein, and activation of the receptors results in inhibition of the enzyme. We examined rat olfactory mucous membrane to determine whether the D2 receptors were linked functionally to adenylyl cyclase as they are in other tissues. Adenylyl cyclase is found in both the olfactory cilia of the sensory epithelium and olfactory nerve terminals in the bulb. Bromocriptine, a D2 receptor agonist, was added to olfactory epithelium membrane preparations from normal and unilaterally bulbectomized adult rats and the preparations were assayed for forskolin-stimulated adenylyl cyclase activity. In unoperated animals bromocriptine significantly inhibited adenylyl cyclase activity, and the inhibition was abolished following pertussis toxin treatment. In mucosa from unilaterally bulbectomized animals we saw significantly lower adenylyl cyclase activity on the operated side and a further decrease in response to bromocriptine. The data indicate that bromocriptine decreases adenylyl cyclase activity in olfactory tissue, specifically in the sensory neurons, and the reaction is dependent on a pertussis toxin-sensitive G-protein. Given the absence of dopaminergic input to the olfactory epithelium, we propose that dopamine D2 receptors are more probably functionally linked to the adenylyl cyclase that is being transported to the axon terminals than to the adenylyl cyclase in cilia. The results also suggest that receptors are coupled to G-proteins before they are transported to nerve terminals.
Wastewater Planning and Administration Concerns along Southeastern U.S. Coast

A survey of 166 southeastern U.S. coastal jurisdictions reveals numerous wastewater planning and administration problems in that region. Findings may not be unique to southeastern coastal systems. The survey finds that a very high percentage of the sanitary sewer systems in this region are in need of major improvement and yet do not apparently have resources available to perform improvements: Some jurisdictions must impose connection restrictions, moratoriums, or merge their systems with others; a quarter of the jurisdictions with sanitary sewer systems are adversely impacted by the sewer extension and expansion policies of nearby jurisdictions; package treatment plants cause many problems for jurisdictions that allow them; and that most jurisdictions without sanitary sewers plan to install them within three years to abate widespread failure of septic systems. Responding jurisdictions report some need for increased financial assistance to make required improvements to avoid incompliance with state and fed...