cssi/SciSciGPT-SciSciNet huggingface dataset:
Neurobiology of Relapse to Heroin and Cocaine Seeking: A Review

The objective of this article is to review data from studies that used a reinstatement model in rats to elucidate the neural mechanisms underlying relapse to heroin and cocaine seeking induced by exposure to the self-administered drug (drug priming), conditioned drug cues, and stressors. These factors were reported to contribute to relapse to drug use in humans following prolonged abstinence periods. In the reinstatement model, the ability of acute exposure to drug or nondrug stimuli to reinstate drug seeking is determined following training for drug self-administration and subsequent extinction of the drug-reinforced behavior. We will review studies in which pharmacological agents were injected systemically or intracranially to block (or mimic) reinstatement by drug priming, drug cues, and stressors. We also will review studies in which brain lesions, in vivo microdialysis and electrochemistry, and gene expression methods were used to map brain sites involved in relapse to drug seeking. Subsequently, we will discuss theoretical issues related to the processes underlying relapse to drugs and address methodological issues in studies on reinstatement of drug seeking. Finally, the implications of the findings from the studies reviewed for addiction theories and treatment will be discussed. The main conclusion of this review is that the neuronal mechanisms involved in relapse to heroin and cocaine seeking induced by drug priming, drug cues, and stressors are to a large degree dissociable. The data reviewed also suggest that the neuronal events mediating drug-induced reinstatement are to some degree dissociable from those mediating drug reinforcement.
A Simulation Model to Evaluate Decision Rules for Lock Operations on the Upper Mississippi River

We describe a discrete-event simulation model used to investigate the impact of alternative decision rules for operations in a congested section of the Upper Mississippi River navigation system. The model accommodates commercial vessels with different barge-tow configurations and recreational vessels. Activities vary by time of year, day of week and time of day. We reveal potential benefits of alternative priority dispatching rules and show their differential impact on vessels with different tow configurations
Mirrorless optical parametric oscillations in negative-index microstructures

The unique properties of resonant four-wave mixing of backward waves in negative-index materials are investigated. The possibility of realizing miniature mirrorless optical parametric oscillators is shown and their properties are numerically simulated.
Identifying Discourse Markers in Spoken Dialog

In this paper, we present a method for identifying discourse marker usage in spontaneous speech based on machine learning. Discourse markers are denoted by special POS tags, and thus the process of POS tagging can be used to identify discourse markers. By incorporating POS tagging into language modeling, discourse markers can be identified during speech recognition, in which the timeliness of the information can be used to help predict the following words. We contrast this approach with an alternative machine learning approach proposed by Litman (1996). This paper also argues that discourse markers can be used to help the hearer predict the role that the upcoming utterance plays in the dialog. Thus discourse markers should provide valuable evidence for automatic dialog act prediction.
The need for a nation‐wide program of observation‐wells

During the severe droughts of recent years almost the only water-supplies available throughout large areas of the United States have been those obtained from underground sources. Consequently, a great interest has developed in the ground-water resources of the country and there has been much concern lest the declining water-levels in wells and the diminished flow of springs may be warnings of the ultimate exhaustion of our ground-water supplies. As is well known, the United States Geological Survey has for half a century conducted investigations of the ground-water of the country and numerous investigations have been made by State geological surveys and other agencies. However, the time is now ripe for a coordinated, continuing program to obtain systematic records of water-levels in observation-wells and correlative records of natural discharge and artificial withdrawals of ground-water.
A NEW MODEL FOR THE SUCTION PRESSURE UNDER A CONTACT LENS

We present a new approach to compute the suction pressure under a soft contact lens. When a soft contact lens is placed on an eye, it is subjected to forces from the tear film in which it is immersed and from the blinking eyelid. In response, the lens bends and stretches. The equilibration of these forces generates a suction pressure that keeps the lens on the cornea. In this paper, we develop a mathematical model of the elastic equilibrium of a soft contact lens that allows us to predict the suction pressure distribution under such a lens. We explore the influence of the shape of the lens and its elastic properties on the suction pressure.
An outbreak of toxoplasmosis in farmed mink (Mustela vison S.).

A large Wisconsin mink (Mustela vison) farm experienced an outbreak of toxoplasmosis in the spring of 1999 following an outbreak of canine distemper during the previous fall. Major clinical signs f...
Low-intensity focused ultrasound pulsation device used during magnetic resonance imaging: evaluation of magnetic resonance imaging-related heating at 3 Tesla/128 MHz.

Author(s): Korb, Alexander S; Shellock, Frank G; Cohen, Mark S; Bystritsky, Alexander | Abstract: ObjectiveThe objective of this study was to determine magnetic resonance imaging (MRI)-related heating for a low-intensity focused ultrasound pulsation (LIFUP) device used during MRI performed at 3 T/128 MHz.Materials and methodsA special phantom was constructed to mimic the thermal properties of the human brain, and a piece of human temporal bone (skull) was embedded on top. Four fluoroptic thermometry probes, placed above and below the skull, were used to measure temperature changes during MRI (3 T/128 MHz; scanner-reported head average specific absorption rate 1.1-2 W/kg) with and without concurrent LIFUP sonication. LIFUP sonication was applied using a focused ultrasound device (BXPulsar 1001, Brainsonix, Inc., Los Angeles, CA, USA) at a derated spatial-peak temporal-average intensity of 3870 mW/cm(2) .ResultsMRI performed at relatively high specific absorption rate (SAR) caused a slight elevation in temperature (≤0.6°C). Concurrent use of MRI at a medium-strength SAR and LIFUP sonication resulted in maximum temperature rise of 3.1°C after 8 min of continuous use.ConclusionsUnder the specific conditions utilized for this investigation, LIFUP sonication does not appear to present significant heating risks when used concurrently with MRI. This information has important implications for the use of the LIFUP sonication in human subjects undergoing MRI at 3 T/128 MHz.
Simultaneous PCR Detection of the Two Major Bacterial Pathogens of Geranium

Xanthomonas campestris pv. pelargonii (Xcp) and Ralstonia solanacearum (Rs) are the two most important bacterial pathogens of commercially cultivated geraniums (Pelargonium spp.), both causing bacterial wilt and leaf spot. Asymptomatic infections are important reservoirs of infections in commercial growing facilities. Our objective was to design a multiplex PCR (Polymerase Chain Reaction) assay to detect infection by either or both of these pathogens. We used a previously characterized PCR primer pair for Xcp that amplifies a region of 200 bp. In addition, we designed a new primer pair specific for Rs that amplifies a region of 822 bp. With these two primer pairs, we could detect either or both pathogens. As geranium tissue extracts frequently contain inhibitors of the PCR process, a negative PCR could result from either an accurate indication that the plant was pathogen-free or from a false negative assay. We therefore designed 'amplification competence' primers, targeting a portion of the geranium 18 s rRNA gene, and generating a 494-bp amplification product that confirms amplification competence and validates a negative assay result. Thus, the triple primer pair multiplex PCR screens for the two most important bacterial pathogens of geraniums simultaneously confirms amplification competence for each geranium sample.
Editorial: Consulting, Research, and Consulting Research

Consulting and scholarly research often have very different objectives with respect to advancements in practice, theory, and observation e.g., data collections. For example, consulting often emphasizes immediate benefits, specialized applications, and a focus on only the key variables. Scholarly research often emphasizes replicability, generalizability, and introducing previously uninvestigated variables. However, these activities complement each other, and each activity is important for the advancement of the other. Benefiting from that complementarity requires the literature to bridge knowledge gained from each activity. It is unnecessary for every researcher to try to bridge theory and practice by working on the interface between academics and practice. However, it is critical that some researchers do so. This issue of Marketing Science examines several excellent applications of Marketing Science that provide detailed microexaminations of the fundamental marketing practices that we seek to understand and improve. Beyond demonstrating how to solve specific problems in practice, in my opinion, the articles and commentaries in this issue also illustrate at least the following ideas: Short-term tactics can produce significant short-term advantages. Existing models in the literature can be useful with proper implementation. State-of-the-art research is most useful for infrequent decisions. Finally, knowing the decision-making context is essential for determining which variables to include in the analysis.
Serotonin-Induced Contraction in Mesenteric Resistance Arteries Signaling and Changes in Deoxycorticosterone Acetate–Salt Hypertension

Large arteries from hypertensive subjects are hyperresponsiveness to 5-hydroxytryptamine (5-HT). We tested the hypothesis that small arteries (225 micro ID) have a profile similar to conduit arteries, including signal transduction mechanisms and the 5-HT receptor subtype(s) mediating arterial contraction in normal and high blood pressure. Aorta and mesenteric arteries from Sprague-Dawley (232+/-6 micro ID), sham (229+/-7 micro ID; systolic blood pressure, 120+/-2 mm Hg), or deoxycorticosterone acetate (DOCA)-salt rats (255+/-11 micro ID, 192+/-8 mm Hg) were mounted in a wire-based myograph. In resistance arteries from Sprague-Dawley rats, the 5-HT2A receptor mediated contraction; agonists of the 5-HT1B, 5-HT1D, 5-HT1F, and 5-HT2B receptor were inactive. The tyrosine kinase inhibitor genistein (5 micromol/L, 4.8-fold rightward shift), PD 098,059 (10 micromol/L, 3.2-fold shift), phospholipase C inhibitor NCDC (100 micromol/L), and nifedipine (50 nmol/L) reduced maximum 5-HT-induced contraction in small arteries (4.5% and 53% control, respectively). As in aorta, 5-HT had a decrease in threshold (100-fold lower), increase in potency (11.6-fold leftward shift), and increase in efficacy (140% sham response) in small arteries from DOCA-salt rats compared with sham. Unlike in aorta, 5-HT-induced contraction in DOCA-salt small arteries was shifted competitively by the 5-HT2A receptor antagonist ketanserin (-log K(B) [mol/L] for both sham and DOCA-salt, 9.25+/-0.1), and contraction to the 5-HT2B agonist BW723C86 was not observed. Thus, the 5-HT2A receptor remains the contractile receptor in hypertension in small arteries. Although similarities were observed for large and small arteries, differences under the condition of DOCA-salt hypertension exist that may determine serotonergic compounds effective in lowering blood pressure.
Dynamics of a Lactate Dehydrogenase Polymorphism in the Wood Louse PORCELLIO SCABER Latr.: Evidence for Partial Assortative Mating and Heterosis in Natural Populations

ABSTRACT Electrophoretic separation of lactate dehydrogenase (LDH) of Porcellio scaber from 14 natural populations in California, and one each in Oregon, Delaware and Massachusetts, indicates a biallelic polymorphism. Phenotypes are recovered from laboratory matings of virgin females in frequencies agreeing with simple Mendelian inheritance, and the frequency distributions of phenotypes in natural populations are typically in agreement with the appropriate Hardy-Weinberg distributions for these same populations. The same allele predominates in all natural populations examined. Temporal stability within populations suggests that the polymorphism is at, or near, equilibrium. The spatial distribution of allele frequencies, however, is apparently mosaic. Abrupt discontinuities in gene frequency over short distances (50 m to 1 km) suggest that interpopulation migration is insufficient to swamp local differences in gene frequency. Analysis of the transmission dynamics of the polymorphism in natural populations using mother-offspring genotype comparisons suggests that the allelic frequencies of transmitted male gametes are not independent of female genotype. Specifically, the observed mating scheme in natural populations appears to be partially assortative. Comparisons of progeny genotype distributions with yearling (or adult) genotype distributions from the same populations indicate a superior post-partum viability of heterozygous individuals relative to homozygotes. The distortion of progeny genotypic distributions created by assortment is thus apparently counteracted by subsequent heterosis.
Promoting the General Welfare: Political Economy for a Free Republic

This paper explores a political economy of liberty, in contrast to the customary pursuit of a political economy of control. Where a political economy of control theorizes in hierarchical fashion by postulating the state as a singular locus of control, a political economy of liberty theorizes in terms of polycentric processes of interaction. The origin of the American republic reflected a political economy of liberty, and this paper explores some of the cognitive and valuational issues that arise in exploring how political economy might be pursued in the service of liberty.
Migracja danych do zintegrowanego systemu bibliotecznego udostępnionego na licencji publicznej (open source). Dotychczasowe doświadczenia (przeł. Tomasz Olszewski).

The present article describes and discusses the aspects of structuring a library collection in an academic library. Direct and indirect actions aimed at improving the acquisitions policy at Docklands Library, one of the three libraries comprising the East London Library, are presented. The most important factors influencing acquisition at this, as well as other academic libraries, include: user’s needs, budget, research mission of the university, and envisaged tendencies in the development of academic disciplines. In conclusion, the author identifies the role of the library as a center whose mission is to maintain the highest possible substantive level of its book collection and provided services.
Oral word association norms for educable mentally retarded children in the public schools.

As word-association norms for non-institutionalized retardates do not exist, this study assessed the feasibility of collecting such norms, using a sample of 19 non-institutionalized retardates. Responses to 100 words from the Palermo-Jenkins study (1964) were obtained. Results indicated that individual testing of Ss is feasible. The verbal repertoire of the sample was mote heterogeneous than that of institutionalized retardates and smaller than that of normal Ss.
Synthesis and Properties of Uniform Polyisoprene Networks. I. Synthesis and Characterization of α,ω-Dihydroxy-Polyisoprene

Abstract The results of this study are the first to show that high-1,4 linear α,ω-dihydroxypolydienes can be synthesized with (a) predictable molecular weights, (b) narrow molecular weight distributions, and (c) high functionalities. Using the functionalized polyisoprenes prepared in this work, a series of networks was prepared with a purified triisocyanate as the chain linking agent. The soluble fraction in these networks ranged from 4.6 to 1.6 per cent. The characteristics and physical properties of these networks will be the subject of a forthcoming publication.
Evaluation of the conductive velocity of individual motor nerve fibre bundles. A neurophysiological study

Bei 10 gesunden Kontrollpersonen und 40 Patienten mit neurogenen und myogenen Schadigungen wurde der N. ulnaris percutan mit elektrischen Rechteckimpulsen gereizt und das Potential der Antwort des M. abductor digiti V. mittels Nadelelektroden registriert. Die Intensitat des Reizes wurde stufenweise von supramaximal bis zur Reizschwelle herabgesetzt. Das Verhaltnis zwischen Reizintensitat und Latenz der Muskelzuckung wurde ausgewertet. Sowohl bei Gesunden als auch bei Kranken wachsen die Latenzen der Muskelzuckung bei abnehmender Reizintensitat progressiv an. Dies zeigt, das bei abnehmender Reizintensitat sukzessiv immer langsamer leitende Nervenfasern des Muskelnerven erregt werden. Die Ergebnisse unserer Untersuchungen zeigen, das es typische Latenz-Intensitatskurven fur Gesunde und fur Kranke mit posttraumatischen Nervenlasionen, Polyneuritis, neuralen progressiven Atrophien (Charcot-Marie-Tooth), Morbus Friedreich und mit Myasthenia gravis pseudoparalytica gibt. Auf Grund der Analyse unserer Resultate schliesen wir, das das Verhaltnis zwischen Reizintensitat und Latenz der Muskelzuckung den aktuellen Zustand der einzelnen Fasergruppen eines peripheren Nerven bei verschiedenen pathologischen Prozessen anzeigt.
Spontaneous encephalitis in rabbits

In studying the brains of rabbits infected with the virus of herpes simplex, it was found that a large proportion of the animals with which we were working had chronic focal lesions within the brain and spinal cord and an exudate in the meninges consisting entirely of mononuclear cells. These lesions were attributed to a latent or pre-existing infectious disease. An apparently identical disease of the brain of rabbits has been described by Bull,1 Oliver,2 and more recently by Twort and Archer.3 Bull and Oliver found the lesions only in the central nervous system, while Twort connected the cerebral changes with similar foci in the kidneys, which he attributed to an identical etiologic agency. These observers failed to find organisms associated with the lesions,, and Twort, on the questionable ground that the cellular reaction consisted of cells of a mononuclear type only, assumed the etiologic agent to be a filtrable virus.
Research and Application on Seismic Image Enhancement Based on Wavelet Transformation

Digital image enhancement method is studied,and the theory of choosing hard-threshold and soft-threshold in wavelet transform is analyzed,and according to the trait of seismic data,the wavelet threshold is improved.Through the verification of the seismic images in Daqing oil field,the new threshold function can effectively remove Gaussian white noise and impulse noise,and the image enhancement effect is remarkable.
Quantitative Comparison of Linear and Non-linear Dimensionality Reduction Techniques for Solar Image Archives.

This work investigates the applicability of several dimensionality reduction techniques for large scale solar data analysis. Using the first solar domain-specific benchmark dataset that contains images of multiple types of phenomena, we investigate linear and nonlinear dimensionality reduction methods in order to reduce our storage costs and maintain an accurate representation of our data in a new vector space. We present a comparative analysis between several dimensionality reduction methods and different numbers of target dimensions by utilizing different classifiers in order to determine the percentage of dimensionality reduction that can be achieved on solar data with said methods, and to discover the method that is the most effective for solar images.
Facial reconstruction consideration in rheumatic diseases.

SUMMARY In conclusion, the management of facial involvement in JRA, Romberg disease, and scleroderma is dictated by the degree of severity of the disease, age of onset, and length of activity. Functional occlusal abnormalities are best addressed through a team approach consisting of initial orthodontics followed by orthognathic surgery if needed.57 In all types of scleroderma, surgical facial reconstruction is best delayed until the disease is quiescent for at least a year. The ideal option for facial skeletal and soft-tissue augmentation has not yet been realized. Careful surgical planning and choice of grafts, flaps, or implants are critical to obtain the desired result.
Pathology and Molecular Pathology of Melanoma

Melanoma is a neoplastic proliferation of melanocytes that most commonly arises in the skin. In more rare cases, melanoma may occur at mucosal sites and the uveal tract. Fortunately, most patients with melanoma have localized cutaneous tumor that is cured by surgical excision. However, for those patients with melanoma that leads to metastasis the prognosis is variable. Generally, patients diagnosed with widely metastatic melanoma survive less than a year. In order to provide a framework for understanding melanocytic neoplasia, this chapter describes many aspects of melanocytic pathophysiology. Beginning with the embryological development of the skin with an attention to melanocytic migration, normal cutaneous anatomy and histology, the text then moves on to melanocytic neoplasia, including benign nevi and malignant melanoma. Benign melanocytic proliferations, melanoma mimics and melanoma of the skin, eye, mucosa and metastatic sites are described in detail. Important pathological staging factors and therapy are touched upon. Finally, the use of immunohistochemical (IHC) and molecular techniques in melanocytic tumor diagnosis are described.
A numerical study of the local monotone polynomial edge detection for the hybrid WENO method

The weighted essentially non-oscillatory (WENO) method is a high order numerical method that can handle discontinuous problems efficiently. The hybrid WENO method adopts the WENO reconstruction in the region where the jump discontinuity exists, while other high order reconstruction is adopted in the smooth region. Thus for the hybrid WENO method, the jump location should be identified before the adoption. Various edge detection methods have been developed mostly focusing on finding edges as accurately as possible utilizing as many stencils as possible. However, if the reconstruction in the smooth area is obtained with the fixed finite number of cells, it would suffice to examine whether the considered stencils need to adopt the WENO reconstruction instead of finding edges in a global manner. In this note, we compare the multi-resolution analysis with the local monotone polynomial method for the 5th order hybrid WENO method. The monotone method uses the cell information within the given stencil only to decide whether to adopt the WENO reconstruction or not. In this sense, the local method is optimal. We provide a detailed numerical study and show that the monotone polynomial method is efficient and accurate.
Expert assessment of the resilience of drinking water and sanitation systems to climate-related hazards.

Abstract We conducted an expert assessment to obtain expert opinions on the relative global resilience of ten drinking water and five sanitation technologies to the following six climate-related hazards: drought, decreased inter-annual precipitation, flood, superstorm flood, wind damage, and saline intrusion. Resilience scores ranged from 1.7 to 9.9 out of a maximum resilience of 10, with high scores corresponding to high resilience. We find that for some climate-related hazards, such as drought, technologies demonstrated a large range in resilience, indicating that the choice of water and sanitation technologies is important for areas prone to drought. On the other hand, the range of resilience scores for superstorm flooding was much smaller, particularly for sanitation technologies, suggesting that the choice of technology is less of a determinant of functionality for superstorm flooding as compared to other climate-related hazards. For drinking water technologies, only treated piped utility-managed systems that use surface water had resilience scores > 6.0 for all hazards, while protected dug wells were found to be one of the least resilient technologies, consistently scoring
Application of protein A-modified capillary-channeled polymer polypropylene fibers to the quantitation of IgG in complex matrices

Abstract Polypropylene (PP) capillary-channeled polymer (C-CP) fibers loaded with recombinant Staphyloccocus aureus protein A (rSPA) were used as an affinity chromatography stationary phase for the quantitation of immunoglobulin G (IgG) in complex biological matrices. Optimization of the chromatographic method regarding mobile phase components and load/elution conditions was performed. The six-minute analysis, including a load step with 12 mM phosphate at pH 7.4, an elution step with 0.025% phosphoric acid and a re-equilibration step, was employed for quantitation of IgG1 from 0.075 to 3.00 mg mL−1 in an IgG-free CHO cell supernatant matrix. Quantification of IgG1 content in a different CHO cell line was accomplished using the external calibration curve as well as using a standard addition approach. The high level of agreement between the two approaches suggests that the protein A-modified C-CP fiber phase is immune from matrix effects due to concomitant species such as host cell proteins (HCPs), host cell DNA, media components and other leachables and extractables. The inter-day and intra-day precision of the method were 3.1 and 3.5%RSD respectively for a single column. Column-to-column variability was 1.31 and 6.62%RSD for elution time and peak area, respectively, across columns prepared in different batches. The method reported here is well-suited for IgG analysis in complex harvest cell culture media in both the development and production environments.
Ultra-deep bisulfite sequencing analysis of DNA methylation patterns in multiple gene promoters by massively parallel pyrosequencing

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 2863 Bisulfite genomic sequencing is currently considered the gold standard for DNA methylation analysis, but it is very low throughput, laborious and bias can occur during sub-cloning of bisulfite PCR products. Therefore, we investigated the use of massively parallel pyrosequencing technology for directly sequencing bisulfite PCR products. 122 (3 PCR amplification failures) bisulfite PCR amplicons were derived from 25 gene promoters in 5 groups of cells: 1. Normal lymphocytes; 2. ALL; 3. CLL; 4. FL; and 5. MCL. For each sample group, we pooled DNA samples isolated from 10 individuals with the same diagnosis and bisulfite-treated each pooled DNA sample. For each gene promoter, a group of specific 4 nucleotide tag was added to the 5’ end of each PCR primer pair so that the amplicons of the 5 groups could be computationally separated after sequencing. Individual amplicons were generated by PCR from each of the 5 groups for each of the 25 gene promoters. Each amplicon was purified, quantified and pooled together at equal molar ratios. The pooled 122 amplicons were sequenced on the GS20 sequencer from 454 Life Sciences. A total of 294,631 sequences were obtained in a single sequencing run, which included both forward and reverse strands. The average read length was 100bp (ranging from 35 bp to 300bp). We used a dynamic-programming alignment method to map each sequence to the in silico bisulfite-converted amplicon sequence. Among the total sequences, 288,358 were mapped to unique amplicons. Based on the quality of the alignment, 207,011 sequences with a sequence identity > 90% were used for computing methylation levels. The percentage of methylation at each CpG site within each amplicon was calculated based on the number of sequences containing a methylated CpG versus the total number of sequences obtained. Overall, the methylation of the 25 genes analyzed is consistent with our previous results obtained in the same group of samples by other independent methods. However, the new 454 sequencing result reveals great detail about the quantitative methylation at each single methyl-cytosine and the methylation patterns in each amplicon. Using the conventional bisulfite sequencing, only 6 to 8 clones are usually sequenced compared to hundreds and thousands of sequences obtained from the 454 sequencing for each sample. We observed significant differential methylation between normal and tumor samples. The percentage of analyzed CpG sites methylated at or above 20% is 10 times higher in the tumor samples compared to normal control lymphocyte samples (45.64% vs 4.25%). This new generation of methylome sequencing will revolutionize the current analytical methods of DNA methylation, provide digital profiles of aberrant DNA methylation for individual human cancers and offer a robust method for epigenetic classification of tumor subtypes.
Unimolecular reaction rate measurements for molecules with excited overtone vibrations

Unimolecular reaction rate constant measurements on systems with well known total energy contents permit detailed comparison with the predictions of statistical theories. Vibrational overtone excitation is a preparation technique that adds a precise energy increment to the reacting molecules and, when applied to a sample cooled in a free jet expansion, produces an ensemble with a known total energy content. Combining this preparation scheme with time resolved product detection yields the unimolecular reaction rate constant for a large molecule, tetramethyldioxetane. These free jet data serve to fix the parameters in an RRKM calculation, which is then averaged over a thermal distribution of initial vibrational energy for comparison to extensive room temperature measurements on the vibrational overtone initiated reaction. Applying this excitation scheme to a small molecule, hydrogen peroxide, in a free jet expansion permits the spectroscopic inference of its fast unimolecular reaction rate. Observation of the width of individual features in the well resolved vibrational overtone excitation spectrum establishes an upper limit to the unimolecular reaction rate constant for these molecules in their few lowest angular momentum states.
Residents’ educational attainment and preventive care utilization in China

Purpose China launched a comprehensive health reform in 2009 to improve healthcare quality. Because preventive care utilization in China has not been frequently discussed, the purpose of this paper is to focus on the association between education level and preventive care before and after the initiation of the reform. Education has been referred to as the best health outcome indicator and China's educational reform has been progressive, such as the health reform. Design/methodology/approach The authors analyzed data from four China Health and Nutrition Surveys (CHNS): 2004 ( n=9,617); 2006 ( n=9,527); 2009 ( n=9,873); and 2011 ( n=9,430). Variables were selected based on Andersen's healthcare utilization model (predisposing, enabling and need factors). Multivariable logistic regression models, odds ratios (ORs) and 95 percent confidence intervals (95 percent CI) were conducted and reported. Findings In the adjusted multivariable logistic regression models, the authors found that general education was associated ( p<0.05) with access to preventive care in 2004, 2009 and 2011, but not in 2006. Individuals with higher education had higher ORs for utilizing preventive care, compared with lower education (primary school education or none). Practical implications Policy implications include providing educational protocols regarding preventive care's significance to residents educated at lower level schools, especially younger individuals. Originality/value To the authors' knowledge, this is the first comparative assessment on education level and preventive care utilization before and after the implementation of the Chinese health reform.
Judicial Independence on Unelected State Supreme Courts

The state supreme court literature often overlooks the twelve states that use traditional appointment systems or fails to explore differences in their judicial designs. Eight states require justice...
Evolved Cas9 variants with broad PAM compatibility and high DNA specificity

A key limitation of the use of the CRISPR-Cas9 system for genome editing and other applications is the requirement that a protospacer adjacent motif (PAM) be present at the target site. For the most commonly used Cas9 from Streptococcus pyogenes (SpCas9), the required PAM sequence is NGG. No natural or engineered Cas9 variants that have been shown to function efficiently in mammalian cells offer a PAM less restrictive than NGG. Here we use phage-assisted continuous evolution to evolve an expanded PAM SpCas9 variant (xCas9) that can recognize a broad range of PAM sequences including NG, GAA and GAT. The PAM compatibility of xCas9 is the broadest reported, to our knowledge, among Cas9 proteins that are active in mammalian cells, and supports applications in human cells including targeted transcriptional activation, nuclease-mediated gene disruption, and cytidine and adenine base editing. Notably, despite its broadened PAM compatibility, xCas9 has much greater DNA specificity than SpCas9, with substantially lower genome-wide off-target activity at all NGG target sites tested, as well as minimal off-target activity when targeting genomic sites with non-NGG PAMs. These findings expand the DNA targeting scope of CRISPR systems and establish that there is no necessary trade-off between Cas9 editing efficiency, PAM compatibility and DNA specificity.
Modeling and rescue of defective blood–brain barrier function of induced brain microvascular endothelial cells from childhood cerebral adrenoleukodystrophy patients

X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene. 40% of X-ALD patients will convert to the deadly childhood cerebral form (ccALD) characterized by increased permeability of the brain endothelium that constitutes the blood–brain barrier (BBB). Mutation information and molecular markers investigated to date are not predictive of conversion. Prior reports have focused on toxic metabolic byproducts and reactive oxygen species as instigators of cerebral inflammation and subsequent immune cell invasion leading to BBB breakdown. This study focuses on the BBB itself and evaluates differences in brain endothelium integrity using cells from ccALD patients and wild-type (WT) controls. The blood–brain barrier of ccALD patients and WT controls was modeled using directed differentiation of induced pluripotent stem cells (iPSCs) into induced brain microvascular endothelial cells (iBMECs). Immunocytochemistry and PCR confirmed characteristic expression of brain microvascular endothelial cell (BMEC) markers. Barrier properties of iBMECs were measured via trans-endothelial electrical resistance (TEER), sodium fluorescein permeability, and frayed junction analysis. Electron microscopy and RNA-seq were used to further characterize disease-specific differences. Oil-Red-O staining was used to quantify differences in lipid accumulation. To evaluate whether treatment with block copolymers of poly(ethylene oxide) and poly(propylene oxide) (PEO–PPO) could mitigate defective properties, ccALD-iBMECs were treated with PEO–PPO block copolymers and their barrier properties and lipid accumulation levels were quantified. iBMECs from patients with ccALD had significantly decreased TEER (2592 ± 110 Ω cm2) compared to WT controls (5001 ± 172 Ω cm2). They also accumulated lipid droplets to a greater extent than WT-iBMECs. Upon treatment with a PEO–PPO diblock copolymer during the differentiation process, an increase in TEER and a reduction in lipid accumulation were observed for the polymer treated ccALD-iBMECs compared to untreated controls. The finding that BBB integrity is decreased in ccALD and can be rescued with block copolymers opens the door for the discovery of BBB-specific molecular markers that can indicate the onset of ccALD and has therapeutic implications for preventing the conversion to ccALD.
Antimicrobial actions of dual oxidases and lactoperoxidase

The NOX/DUOX family of NADPH oxidases are transmembrane proteins generating reactive oxygen species as their primary enzymatic products. NADPH oxidase (NOX) 1-5 and Dual oxidase (DUOX) 1 and 2 are members of this family. These enzymes have several biological functions including immune defense, hormone biosynthesis, fertilization, cell proliferation and differentiation, extracellular matrix formation and vascular regulation. They are found in a variety of tissues such as the airways, salivary glands, colon, thyroid gland and lymphoid organs. The discovery of NADPH oxidases has drastically transformed our view of the biology of reactive oxygen species and oxidative stress. Roles of several isoforms including DUOX1 and DUOX2 in host innate immune defense have been implicated and are still being uncovered. DUOX enzymes highly expressed in the respiratory and salivary gland epithelium have been proposed as the major sources of hydrogen peroxide supporting mucosal oxidative antimicrobial defenses. In this review, we shortly present data on DUOX discovery, structure and function, and provide a detailed, up-to-date summary of discoveries regarding antibacterial, antiviral, antifungal, and antiparasitic functions of DUOX enzymes. We also present all the literature describing the immune functions of lactoperoxidase, an enzyme working in partnership with DUOX to produce antimicrobial substances.
Phosphopeptide Mapping: A Basic Protocol

Publisher Summary Peptide mapping is a technique in which a radioactively labeled protein is digested with a sequence specific protease. The resulting peptides are separated in two dimensions on a thin-layer cellulose (TLC) plate by electrophoresis and chromatography. Proteins are usually separated from other contaminating proteins by SDS-PAGE and then subjected to phosphopeptide mapping or phosphoamino acid analysis. Line the gel up with the film using the markings on the paper backing and autorad, localize the protein of interest, and cut the protein band out of the gel with a clean, single edge razor or a surgical blade. Remove the paper backing from the gel slices by scraping gently with a razor blade. Phosphopeptide mixtures are usually separated by electrophoresis in the horizontal dimension and chromatography in the vertical dimension. The mixture is spotted 3 cm from the bottom of the plate and 5 cm from the left side for electrophoresis at pH 1.9 or pH 4.72 or in the center of the plate for electrophoresis at pH 8.9.
Glucagon for the management of hepatic emergencies

Studies performed in recent years have continued to clarify the role of glucagon in normal liver physiology and in several hepatic diseases. Several lines of evidence suggest that glucagon might be useful for the management of some hepatic disorders. However, glucagon has not received wide application for this purpose. In this paper, some of the acute liver conditions that might be managed with glucagon are reviewed.
Intracranial hemorrhage in the prematurely born infant. Timing of clots and evaluation of clinical signs and symptoms.

Intraventricular hemorrhage is a frequent postmortem finding in the preterm infant with severe perinatal problems, often with respiratory distress. It is a late event, most probably secondary to perinatal circulatory disturbances related to central cerebral infarction. The bleeding occurs generally during the second or third day of life. Except for characteristic seizures, individual clinical signs and symptoms are of limited value for the timing of the bleeding, although in most instances the general clinical picture may accurately indicate the diagnosis of intraventricular hemorrhage.
New Mechanisms, New Opportunities: Integrating Novel Antidepressants in the Treatment of Major Depressive Disorder

Listen to experts and view their slides from a panel session at the American Society of Clinical Psychopharmacology (ASCP) meeting, held on May 29, 2019, in Scottsdale, Arizona. Dr Murrough described the current understanding of depression etiology and new insights into antidepressant development. Dr Goldberg shared his expertise about whether antidepressant drugs with novel mechanisms of action can improve outcomes in patients with major depressive disorder. Dr Gaynes reviewed the link between major depressive disorder and elevated mortality risk and whether recovery from depression can reverse patients' mortality risk. Dr Citrome discussed current best practices and new medications for the treatment of depression. Finally, Dr Ketter provided his thoughts on his colleagues' presentations.
Effects of Proportional Hazard Assumption on Variable Selection Methods for Censored Data.

The Cox proportional hazard (PH) model is widely used to determine the effects of risk factors and treatments (covariates) on survival time of subjects that might be right censored. The selection o...
CHARACTERIZATION OF VIRAL, SINGLE-STRANDED DNA SEQUENCES IN ADENOVIRUS INFECTED CELLS

ABSTRACT. We show here that He La cells infected by two temperature-sensitive mutants of Adenovirus type 5, which are defective in viral DNA replication and complement one another, fail to synthesize “late” viral mRNA sequences at the non-permissive temperature. We also report the characterization of single-stranded viral DNA sequences, present in infected cells during viral replication, quantitation and the time course of synthesis of such sequences are described. A brief account is also given of experiments designed to follow changes in viral DNA sequences in ts-125 infected cells following a shift from permissive to non-permissive temperatures.
Structural insights into emergent signaling modes of G protein-coupled receptors.

G protein–coupled receptors (GPCRs) represent the largest family of cell membrane proteins, with >800 GPCRs in humans alone, and recognize highly diverse ligands, ranging from photons to large protein molecules. Very important to human medicine, GPCRs are targeted by about 35% of prescription drugs. GPCRs are characterized by a seven-transmembrane α-helical structure, transmitting extracellular signals into cells to regulate major physiological processes via heterotrimeric G proteins and β-arrestins. Initially viewed as receptors whose signaling via G proteins is delimited to the plasma membrane, it is now recognized that GPCRs signal also at various intracellular locations, and the mechanisms and (patho)physiological relevance of such signaling modes are actively investigated. The propensity of GPCRs to adopt different signaling modes is largely encoded in the structural plasticity of the receptors themselves and of their signaling complexes. Here, we review emerging modes of GPCR signaling via endosomal membranes and the physiological implications of such signaling modes. We further summarize recent structural insights into mechanisms of GPCR activation and signaling. We particularly emphasize the structural mechanisms governing the continued GPCR signaling from endosomes and the structural aspects of the GPCR resensitization mechanism and discuss the recently uncovered and important roles of lipids in these processes.
A redox-active organic cation for safer metallic lithium-based batteries

Abstract Safety concerns have severely impeded the practical application of high-energy-density lithium-based batteries. Dendrite growth and overcharging can lead to particularly catastrophic thermal failure. Here we report an organic cation, trisaminocyclopropenium (TAC), as a bi-functional electrolyte additive to suppress dendrite growth and offer reversible overcharge protection for metallic lithium-based batteries. During the Li plating process, TAC cations with aliphatic chains can form a positively charged electrostatic shield around Li protrusions, repelling the approaching Li+ and thereby attaining a more uniform plating. A two times longer cycle life of 300 h at 1 mA cm−2 is achieved in a Li|Li symmetric cell in comparison with the control. During the overcharging process, the redox-active TAC can repeatedly shuttle between two electrodes, maintaining the cell voltage within a safe value. A solid protection of 117 cycles (~1640 h) at 0.2 C with a 100% overcharge is achieved in a LiFePO4/Li4Ti5O12 cell. This study sheds fresh light on the ability of organic cations to build safer batteries.
LANSKAP MODERASI KEAGAMAAN SANTRI, REFLEKSI POLA PENDIDIKAN PESANTREN

Abstract. Positioning a pesantren in a series of continuum lines between liberals and conservatives, based on critical interpretations of religious texts as opposed to rigid and liberal understandings, is a misunderstanding of the landscape of religious moderation. This article elaborates on the complex process of Islamic boarding school understanding and practice in the midst of a religious shift towards a conservative direction. Through literature study based on a reading model based on maslahah on religious texts and the essence of religious texts based on the plurality of views of the schools of thought conducted by the Pondok Modern Darussalam Gontor. This article concludes that through preserving values through Pancajiwa and the motto of the pesantren, the integration between formal and informal curricula places Gontor's position as a moderate educational institution. Keywords: Islamic Moderation, Maslah, curriculum, PMDG, Indonesia. Abstrak. Memposisikan sebuah pesantren dalam rangkaian garis kontinum antara liberal dan konservatif, berdasarkan penafsiran kritis atas teks keagamaan sebagai lawan pemahaman kaku dan liberal, menjadi salah upaya memahami lanskap moderasi keagamaan. Artikel ini mengelaborasi proses kompleks pemahaman dan praktik keagamaan pesantren di tenggah pergeseran keagamaan ke arah konservatif . Melalui studi pustaka berdasarkan model pembacaan berdasarkan maslahah atas teks-teks keagamaan dan inti dari teks keagamaan berdasarkan pluralitas pandangan madzhab yang dilakukan oleh Pondok Modern Darussalam Gontor. Artikel ini menyimpulkan bahwa nilai-nilai dilestarikan melalui pancajiwa dan motto pesantren, intergrasi antara kurikulum formal dan informal menempatkan posisi Gontor sebagai lembaga pendidikan yang moderat. Kata Kunci: Moderasi Islam; Maslahah ; Kurikulum; PMDG; Indonesia.
מדע וערכים – הבסיס למדיניות סיכונים לאומית באיכות הסביבה ובבריאות הציבור Science and Values – the base for national risk policy in Environmental protection and Public health

תקציר בעברית: משבר הקורונה שנכנס לחיינו ומצריך החלטות מדיניות קשות "תוך כדי תנועה", מתרחש בקצב מסחרר שאינו מאפשר מבט תאורטי ודיון ציבורי סדור. כשייגמר המשבר, אפשר וצריך להסתמך גם על הניסיון בנושאי סביבה כדי לגבש מדיניות ניהול סיכונים לאומית בנושאי איכות הסביבה ובריאות הציבור שתסתמך על מדע וערכים. בצד המדעי יש צורך למפות את הסיכונים בתחומים אלה, להשלים פערי ידע בהם, ליצור בסיסי נתונים שיתמכו בקבלת ההחלטות וליצור מערכת של מודלים לאומיים מתעדכנים. בצד הערכי יש צורך לקיים דיון ציבורי דמוקרטי, משתף ומעמיק על מדיניות הסיכונים הלאומית, ולהחליט כמה בטוחים הדברים צריכים להיות כדי שיהיו בטוחים דיים. English Abstract: The Corona crisis that came into our lives requires rapid "on-the-go" policy decisions. When the crisis is over, it is possible and necessary to rely on experience in environmental issues in order to formulate a national risk management policy on environmental protection and public health that will rely on science and values. On the scientific side, it is necessary to map the risks in these areas, to bridge knowledge gaps, to create databases that will support decision-making and to create a system of updating national models. On the value side, there is a need for a democratic, participatory and in-depth public deliberation on national risk policy, and to decide how safe is safe enough.