cssi/SciSciGPT-SciSciNet huggingface dataset:
Moral Limits on State Action

Some moral philosophers argue that the moral limits on state action are different from and less stringent than those on the actions of private persons. Stanley Benn points out that the interests of the public are of greater magnitude than those of any individual or small group of individuals, that statesmen have a special duty as trustees of the national interests, and that they must act in a jungle world of threatening violence. Thomas Nagel argues that in the public morality consequences of action count more than restrictions on the means used, but in private morality the obligation to respect human rights of other persons outweighs the value of the outcome of action. However, these considerations do not eliminate the relevance of ordinary moral limits on the actions of public officials; they merely add other morally relevant considerations. One should distinguish between a supreme emergency as a threat so great as to be immeasurable against the moral limits on state responses and an almost supreme emergency where the threat so clearly outweighs those limits that there is no need to measure them against one another. The former might make moral limits on state action irrelevant because a necessary condition of morality is some level of security, but the latter would almost never justify any but a limited state response. Although in theory it might be possible for a nation state to be released from the moral obligations that limit measures of counterterrorism, this is highly improbable under any foreseeable conditions in the real world.
Improved Slip-Resistance on Oil from Surface Roughness of Footwear

Abstract This appears 10 be the first published investigation of friction measurements throughout the useful lives of footwear, and the changing patterns of slip-resistance found justify this approach. The polishing effect of walking on some surfaces needs further investigation, and there should now be an evaluation of friction relative to surface texture of soles and heels. It may be possible to engineer a permanent surface roughness by varying composition and size of spaces in a cellular structure. Although it is unlikely that any single material will prove to be satisfactory for all types of floor hazards, our experience with polyurethane is encouraging. If it proves impossible to find a single material giving adequate slip-resistance on wet or icy pavements, wet PVC tiles, ceramic tiles contaminated with grease and water, and factory floors contaminated with oil, then materials should be specified for each type of hazard.
Corporate Governance and Multinational Corporations

Introduction Analyses of liberal, coordinated, and most other varieties of capitalism focus on large national firms. In Latin America, such a purely domestic focus would miss major players; in most countries, MNCs constitute a third to a half of the largest firms. In terms of complementarities, MNCs often have patterns of interactions with other firms, workers, and governments that do not resemble patterns of domestic business groups. MNCs cannot be assumed to be “institution takers” that come to countries and blend into the corporate landscape (Pauly and Reich 1997). Debates continue about whether and how MNCs contribute to host country development, human capital, and technological progress. Although more radical views, for and against, persist, a more nuanced middle ground contends that the impact of MNCs depends on the context and that “the search for universal relationships is futile” (Lipsey and Sjoholm 2005, 40). The range of relevant contextual factors is wide, but generally, FDI is more likely to have positive effects in an economy characterized by more-developed financial markets (Alfaro et al. 2004), more technologically advanced local firms, more competitive markets (both locally and internationally), fewer restrictions on FDI flows, and higher stocks of human capital (Moran, Graham, and Blomstrom 2005). This range of contextual factors begins to shade into the core complementarities in the literature on varieties of capitalism, and this chapter thus takes the contextual analysis a step further to analyze how MNCs fit into hierarchical capitalism.
Optimal Initial Configuration of Treatment Solution for In Situ Remediation of Contaminated Groundwater using Engineered Injection and Extraction

Groundwater constitutes about 30 percent of the available freshwater on earth; however, it is often contaminated by industrial or agricultural sources. The efficiency of current groundwater remediation methods must be improved, especially given that global consumption of water and energy continues to rise. During in situ remediation, a treatment solution (often a chemical oxidant) is injected into the contaminated aquifer to degrade the groundwater contaminant. Simulations have shown that spreading of treatment solution through a series of engineered injection and extractions (EIE) of clean water at wells surrounding the contaminated region increases the contact area between the treatment solution and contaminant, thereby enhancing contaminant degradation reactions. Previous studies have evaluated the amount of reaction during EIE in simulations where the initial injection of treatment solution was modeled as a circular, filled plume. This study alters the initial configuration of treatment solution by injecting clean water at the center of the treatment solution plume to produce a donut-shaped plume; thereby reducing the total quantity of treatment solution that is used. An optimal initial radius of the interior clean water plume that minimizes the amount of treatment solution injected and maximizes the amount of contaminant degraded is determined. As conservation of materials is important to any engineering project, this study also evaluates the trade-off between the cost of treatment solution and the impact of less contaminant degradation, as the interior clean water plume increases.
Temporary Ahemeral Lighting for Increased Egg Size in Maturing Pullets

Abstract Temporary, 28-h, ahemeral lighting (TAL) cycles were compared with conventional, 24-h, hemeral lighting (CHL) cycles in an attempt to increase initial egg size from maturing pullets without reducing performance. The parameters measured were: 1) sexual maturity [age at first egg, age at 50% production, age when egg weight (EW) ≥56.7 g (large size)]; 2) EW; 3) productivity [hen-day egg production (HDP), eggs per hen, egg mass per hen-housed]; 4) efficiency (feed per hen per day, feed per egg, g of feed per g of egg); 5) egg-shell quality (specific gravity); and 6) mortality. During Trial 1,22-wk-old New Hampshire pullets were exposed to 12 h of light (L): 16 h of dark (D) for 12 wk and then changed to a 16L:8D ratio. During the 32-wk production period, the only significant (P≤.05) difference between TAL and CHL was EW (56.1 versus 54.3 g, respectively). The TAL treatment in Trial 2 exposed 17-wk-old Leghorn pullets to 11L:17D until EW reached 56.7 g at 26 wk, when the L:D ratio was changed to 13L:13D for 1 wk, then to 15L:9D from 28 to 70 weeks of age. The TAL caused the pullets to produce large eggs 2 wk (P In both trials, a reduction of HDP was observed during TAL; but long-term HDP was not significantly (P≤.05) affected. EW was permanently increased by TAL.
Electrodynamic Properties of Single-Crystal and Thin-Film Strontium Titanate, and Thin-Film Barium Strontium Titanate

We have used a coplanar waveguide structure to study broadband electrodynamic properties of single-crystal and thin-film strontium titanate (STO), and thin-film barium strontium titanate (BSTO). We have implemented low-frequency capacitance (100 Hz - 1 MHz), swept-frequency transmittance (45 MHz - 4 GHz), and time-domain transmittance (dc - several GHz) measurements to determine effective refractive index (or, dielectric constant), and dissipation factor (or, loss tangent) as a function of dc bias (up to 4×106 V/m) and temperature (20 - 300 K). The STO samples used superconducting electrodes and were designed to operate at cryogenic temperatures, whereas BSTO samples used normal conducting electrodes and exhibited optimal performance around room temperature. By using nearly identical electrode geometries for all devices, we were able to conduct a direct comparative study among them, and investigate not only single-crystal vs thin-film, but also cryogenic vs room-temperature applications.
Insights into surface runoff on early Mars from paleolake basin morphology and stratigraphy

We present observations on the morphology and stratigraphy of more than 400 paleolake basins on Mars. We show that there are two distinct classes of Martian paleolake basins: (1) paleolakes fed by regionally integrated valley networks (N = 251), and (2) paleolakes fed by isolated inlet valleys not integrated into broader regional drainage systems (N = 174). We conclude that valley network–fed paleolakes primarily formed prior to approximately the Noachian-Hesperian boundary, ca. 3.7 Ga, while isolated inlet valley paleolakes primarily formed later in Martian history. All 174 isolated inlet valley paleolakes are closed-basin lakes; however, there are surprisingly few (31) valley network–fed closed-basin lakes compared to a large number (220) of valley network–fed open-basin lakes. This observation is consistent with declining levels of fluvial activity over time on the Martian surface. Our results imply that during the era of valley network formation, ∼90% of topographic basins breached by an inlet valley had sufficiently high ratios of water influx to losses to fill, overtop, and form an outlet valley. This conclusion provides an important constraint on the balance between surface runoff production and water losses on early Mars that must be satisfied by any model of the early Martian climate and hydrologic cycle.
Suture materials and mechanical after care.

Summary Proper wound closure necessitates a familiarity with the various types of materials and the indications and contraindications of the many techniques available. Proper wound dressing and after-care instruction ensure optimal results and help minimize complications.
A specific hygiene hypothesis

Allergic diseases have reached epidemic proportions in Western populations in the last several decades. The hygiene hypothesis proposed more than twenty years ago has helped us to understand the epidemic and has been verified with numerous studies. However, translational measures deduced from these studies to prevent allergic diseases have not proven effective. Recent studies on immigrants' allergies and any potential association between oral infection and allergic diseases prompt me to propose a specific hygiene hypothesis to explain how oral hygiene practices might have contributed to the uprising of hay fever, the most common allergic disease. The historic oral hygiene level in US is closely associated with the emerging allergic epidemic. Future studies to test the hypothesis are needed and verification of the hypothesis can potentially yield highly effective measures to prevent allergic diseases.
Human Serum Modifies Aggregation Properties of Commonly Used Epidural Steroids

Background Case reports of catastrophic neurological sequelae during ESIs have questioned the safety of this procedure. A proposed mechanism is particulate steroid embolization resulting in neuralischemia. Previous reports have described steroid clumping in common epidural injection mixtures. We demonstrate that physiologic medium can also modify aggregation. Objective To inspect and compare aggregative properties of steroid preparations with and without human serum. Setting Academic tertiary care center. Hypothesis Particulate steroids display different aggregation characteristics in serum compared to non-physiologic solutions. Design Solutions were inspected under light microscopy: betamethasone sodium phosphate/betamethasone acetate, methylprednisolone, and dexamethasone were each mixed in lidocaine 1%, bupivacaine 0.5%, or sterile water in a 1:1 ratio. All preparations were inspected under light microscopy with 100x and 400x magnifications by a pathologist blinded to our expectations and hypothesis. Five random viewing fields were selected within each slide and the number of aggregates per field and the number of particles per aggregate was evaluated. Results The addition of serum had a significant effect on steroid particle aggregation and number of particles per aggregate. Limitations This study was limited by sample size as only 2 sets of human serum samples were tested with each preparation against one non-serum control. Additionally, as steroid preparations were evaluated under light microscopy, the ex vivo setting must be considered in the interpretation of results. Finally, mixing preparations with human serum as opposed to whole blood was necessary to allow for improved visibility on light microscopy despite the fact that whole blood may be necessary to more closely emulate in vivo coagulation setting. Conclusions Overall, the presence of serum resulted in fewer large steroid particle aggregates when compared to non-serum control samples. Amongst particulate steroids, betamethasone with bupivacaine 0.5% demonstrated the fewest and smallest particle aggregates, suggesting that preparation may reduce the risk of embolic infarction. Methylprednisolone formed significantly larger particles in bupivicaine 0.5% with serum compared to non-serum controls.
XLVII. Scientific standards vs. statistical associations and biologic logic in the analysis of causation

The word causation (or causality) refers to decisions about whether a particular cause has produced a particular effect. In clinical medicine, such decisions occur when causal efficacy is determined for the roles of etiologie agents in provoking a disease, or for therapeutic agents in either remedying a disease or preventing its adverse progress.
Microbial Quality of Fresh Potatoes: Effect of Minimal Processing.

Fresh-cut potatoes were treated with an antibrowning solution (l-cysteine-citric acid mixture) and chlorine solutions, and then packaged under a modified atmosphere. The effect of these treatments on the microbiology of the potatoes was evaluated. Dipping the potato strips in sodium hypochlorite solutions (100 and 300 ppm) resulted in higher microbial populations during the storage period, while potatoes treated with the antibrowning solution combined with modified-atmosphere packaging showed only a slight increase. Modified-atmosphere packaging had no significant-effect on the microbial population compared to nonpackaged samples. The predominant organisms were Pseudomonas fluorescens , along with other Pseudomonas species, and Vibrio fluvialis .
Anoxic marine environments

Absolute stagnation nowhere exists in the ocean, not even at its greatest depths. Dittmar 1884 Prior to about 1870, it was thought that the depths of the ocean were devoid of oxygen and devoid of life. In 1873, C. Wyville Thompson published The Depths of the S ea, an account of three expeditions in 1868–1870. He and his colleagues dredged and collected water samples for the first time to depths of about 2400 fathoms (more than 4400 m) and found life at all depths. Measurements of gases in water samples all showed the presence of oxygen. Then, during the great Challenger expedition, the major ocean basins were surveyed to considerable depths, and all the samples contained oxygen. The statement by Dittmar, above, is still true, because there is always some movement of the water, but there are important areas where oxygen is absent. Living things exist at all depths. Indeed (with the exception of the extremely hot water feeding the black smokers; see Chapter 13), there is no single liter of seawater anywhere in the ocean that is devoid of life, and all living things metabolize. If oxygen is present it will be used in respiration, and will eventually all be used, if it is not replaced. If all oxygen is gone, life continues, but the types of organisms present are different. Rates of oxygen consumption The first serious attempt to estimate the rate of oxygen consumption by evaluating the distributions of oxygen in the ocean relative to the physical motions of the water was presented by Gordon Riley in a classic paper published in 1951 (see Table 12.1). Another approach is to use the modern sediment-trap data and the equations fitted to these to calculate the oxygen consumption that must be associated with the observed decrease of particle flux as the depth in the water column increases (Figure 12.1). The agreement between the early estimate by Riley and this estimate from sediment-trap data is remarkable. It is, of course, possible or even likely (see the discussion in Chapter 11) that both estimates are too low, and in any case the fluxes are certainly quite variable spatially. Nevertheless, these estimates illustrate the point that, given enough time, there would be no oxygen in the deep sea unless it is somehow replaced.
Intel® Mash Maker

Publisher Summary This chapter explores the Intel Mash Maker, a browser extension for Firefox or Internet Explorer. Mash Maker was originally developed as a technology demonstration at Intel Research and is now being developed and maintained by a group in the Intel Software Solutions Group. Mash Maker combines several novel ideas into a complete system: an overlay mashup extends a Web page by adding new content that is visually distinguished but integrated into the page layout; suggestions allow users to find useful mashups as they browse. The collaborative wiki model for wrapper creation allows a mashup to keep working even when the wrapper it depends on breaks. The shared data tree allows a user to create a mashup by adding a set of widgets to each other and letting them work out how to help each other. The untrusted widget model allows users to apply a mashup to their page without having to trust it. And the copy-and-paste model allows users to combine Web sites together by simply choosing which Web sites have information that they like.
Author's Response: Response to Comments by Drs Schroeder and Jain.

We thank Dr Schroeder for his comments on our article. We agree with Dr Schroeder that some children may have bacteriuria even when they are asymptomatic. We disagree, however, on the prevalence and clinical implications of this finding. Schroeder states that 1.4% of children have asymptomatic bacteriuria, and because the prevalence of urinary tract infection (UTI) among those tested is low (∼5%), a large proportion of children with apparent UTIs actually may have asymptomatic bacteriuria and are therefore being misdiagnosed. However, closer reading of the original articles describing the asymptomatic bacteriuria (by using a method of urine collection less prone to contamination, such as suprapubic aspiration), show that the 1.4% number is the period prevalence of asymptomatic bacteriuria (cumulative over the 12-month follow-up period).1 At any 1 point in time after 1 month of age, only 0% to 0.4% (see Fig 3 in the article by Wettergren et … E-mail: shaikhnader{at}gmail.com
Reducing uncertainty in projections of terrestrial carbon uptake

Carbon uptake by the oceans and terrestrial biosphere regulates atmospheric carbon dioxide concentration and affects Earth's climate, yet global carbon cycle projections over the next century are highly uncertain. Here, we quantify and isolate the sources of projection uncertainty in cumulative ocean and terrestrial carbon uptake over 2006–2100 by performing an analysis of variance on output from an ensemble of 12 Earth System Models. Whereas uncertainty in projections of global ocean carbon accumulation by 2100 is 160 Pg C and driven primarily by model structure. To statistically reduce uncertainty in terrestrial carbon projections, we devise schemes to weight the models based on their ability to represent the observed change in carbon accumulation over 1959–2005. The weighting schemes incrementally reduce uncertainty to a minimum value of 125 Pg C in 2100, but this reduction requires an impractical observational constraint. We suggest that a focus on reducing multi-model spread may not make terrestrial carbon cycle projections more reliable, and instead advocate for accurate observations, improved process understanding, and a multitude of modeling approaches.
Automating Venous Thromboembolism Risk Calculation Using Electronic Health Record Data upon Hospital Admission: The Automated Padua Prediction Score.

Background Venous thromboembolism (VTE) risk scores assist providers in determining the relative benefit of prophylaxis for individual patients. While automated risk calculation using simpler electronic health record (EHR) data is feasible, it lacks clinical nuance and may be less predictive. Automated calculation of the Padua Prediction Score (PPS), requiring more complex input such as recent medical events and clinical status, may save providers time and increase risk score use. Objective We developed the Automated Padua Prediction Score (APPS) to auto-calculate a VTE risk score using EHR data drawn from prior encounters and the first 4 hours of admission. We compared APPS to standard practice of clinicians manually calculating the PPS to assess VTE risk. Design Cohort study of 30,726 hospitalized patients. APPS was compared to manual calculation of PPS by chart review from 300 randomly selected patients. Measurements Prediction of hospital-acquired VTE not present on admission. Results Compared to manual PPS calculation, no significant difference in average score was found (5.5 vs. 5.1, P = 0.073), and area under curve (AUC) was similar (0.79 vs. 0.76). Hospital- acquired VTE occurred in 260 (0.8%) of 30,726 patients. Those without VTE averaged APPS of 4.9 (standard deviation [SD], 2.6) and those with VTE averaged 7.7 (SD, 2.6). APPS had AUC = 0.81 (confidence interval [CI], 0.79-0.83) in patients receiving no pharmacologic prophylaxis and AUC = 0.78 (CI, 0.76- 0.82) in patients receiving pharmacologic prophylaxis. Conclusions Automated calculation of VTE risk had similar ability to predict hospital-acquired VTE as manual calculation despite differences in how often specific scoring criteria were considered present by the 2 methods. Journal of Hospital Medicine 2017;12: 231- 237.
Calcitriol-mediated reduction in IFN-γ output in T cell large granular lymphocytic leukemia requires vitamin D receptor upregulation

Constitutively activated STAT1 and elevated IFN-γ are both characteristic of T cell large granular lymphocytic leukemia (T-LGLL), a rare incurable leukemia with clonal expansion of cytotoxic T cells due to defective apoptosis. Interferon gamma (IFN-γ) is an inflammatory cytokine that correlates with worse progression and symptomology in multiple autoimmune diseases and cancers. In canonical IFN-γ-STAT1 signaling, IFN-γ activates STAT1, a transcription factor, via phosphorylation of tyrosine residue 701 (p-STAT1). p-STAT1 then promotes transcription of IFN-γ, creating a positive feedback loop. We previously found that calcitriol treatment of the TL-1 cell line, a model of T-LGLL, significantly decreased IFN-γ secretion and p-STAT1 while increasing the vitamin D receptor (VDR) protein. Here we further explore these observations. Using TL-1 cells, IFN-γ decreased starting at 4h following calcitriol treatment, with a reduction in the intracellular and secreted protein levels as well as the mRNA content. A similar reduction in IFN-γ transcript levels was observed in primary T-LGLL patient peripheral blood mononuclear cells (PBMCs). p-STAT1 inhibition followed a similar temporal pattern and VDR upregulation inversely correlated with IFN-γ levels. Using EB1089 and 25(OH)D3, which have high or low affinity for VDR, respectively, we found that the decrease in IFN-γ correlated with the ability of EB1089, but not 25(OH)D3, to upregulate VDR. However, both compounds inhibited p-STAT1; thus the reduction of p-STAT1 is not solely responsible for IFN-γ inhibition. Conversely, cells treated with VDR siRNA exhibited decreased basal IFN-γ production upon VDR knockdown in a dose-dependent manner. Calcitriol treatment upregulated VDR and decreased IFN-γ regardless of initial VDR knockdown efficiency, strengthening the connection between VDR upregulation and IFN-γ reduction. Our findings suggest multiple opportunities to further explore the clinical relevance of the vitamin D pathway and the potential role for vitamin D supplementation in T-LGLL.
Shame Disciplines in the Chinese Cultural Revolution: Lurid and Ludic

The Rhetorics of Power and The Power of Rhetoric: Reification, Hate And Desire: A Psychopolitical Analysis of Mass Atrocity and Genocide. This chapter demonstrates how the shame dynamics in traditional Chinese Confucian families influenced the modes of violence during the Chinese Cultural Revolution and Great Leap Forward. The Maoist inspired rejection of all cultural values and institutions associated with everything old or elderly represented an attempt to destroy Confucian family life and traditional disciplinary systems in favour of a collectivised communist society. This resulted in particular ideological formations and methods of staged public punishments. The presentation invokes a psycho-social analysis that suggests that Mao emerged as a totalitarian figure to displace traditional family shame mechanisms in particularly lurid and ludic ways.
Controversies in Traditional Oral and Maxillofacial Reconstruction.

Traditional reconstruction of the head and neck and significantly evolved over the last 20 to 30 years with advances in microvascular surgery, biologic materials such as bone morphogenic protein, and dental implant predictability. Earlier and more definitive reconstruction can now be achieved with combining therapies, allowing patients immediate restoration of function and improved cosmetics. Antiresorptive medications, such as Denosumab and bisphosphonates, have complicated bony reconstruction treatments with altered biology and less-predictable results. Virtual surgical planning is a major advancement for reconstruction pretreatment planning and designing of intraoperative tools to expedite the operation and achieve more predictable results.
Research Ethics: Research

Ethical and regulatory issues have raised questions requiring use of tools of social science, e.g., understanding how to respect children's privacy calls for use of empirical and methodological studies, developmental theory, and legal research. The topics of research on research ethics fall into five major categories: Theory, method and design considerations that precede research, including (a) values and epistemology of scientists, (b) validity of alternative methods, (c) equitable treatment of research subjects and populations, (d) risk and benefit of alternative approaches. Risk and benefit in specific research contexts, including (a) approaches to risk assessment and risk reduction, (b) understanding and maximizing benefit, (c) risk/benefit assessment to justify a given research procedure. Agreements and communication, including evaluation of approaches to (a) informed consent, (b) deception, (c) use of relationships as a source of data. Acquisition, presentation and use of data, including (a) privacy, (b) confidentiality, (c) data sharing and dissemination. External influences on research including (a) government regulations, (b) institutional review boards, (c) socially questionable, taboo or controversial topics of research, (d) scientific integrity and responsibility, (e) ethics and politics, (f) animal rights activism, (g) education in research ethics.
Microbial Community Analysis of Sauerkraut Fermentation Reveals a Stable and Rapidly Established Community

Despite recent interest in microbial communities of fermented foods, there has been little inquiry into the bacterial community dynamics of sauerkraut, one of the world’s oldest and most prevalent fermented foods. In this study, we utilize 16S rRNA amplicon sequencing to profile the microbial community of naturally fermented sauerkraut throughout the fermentation process while also analyzing the bacterial communities of the starting ingredients and the production environment. Our results indicate that the sauerkraut microbiome is rapidly established after fermentation begins and that the community is stable through fermentation and packaging for commercial sale. Our high-throughput analysis is in agreement with previous studies that utilized traditional microbiological assessments but expands the identified taxonomy. Additionally, we find that the microbial communities of the starting ingredients and the production facility environment exhibit low relative abundance of the lactic acid bacteria that dominate fermented sauerkraut.
The roles of gender and profession on gender role expectations of pain in health care professionals.

Introduction Gender-related stereotypes of pain may account for some assessment and treatment disparities among patients. Among health care providers, demographic factors including gender and profession may influence the use of gender cues in pain management decision-making. The Gender Role Expectations of Pain Questionnaire was developed to assess gender-related stereotypic attributions of pain regarding sensitivity, endurance, and willingness to report pain, and has not yet been used in a sample of health care providers. The purpose of this study was to examine the presence of gender role expectation of pain among health care providers. It was hypothesized that health care providers of both genders would endorse gender stereotypic views of pain and physicians would be more likely than dentists to endorse these views. Methods One-hundred and sixty-nine providers (89 dentists, 80 physicians; 40% women) were recruited as part of a larger study examining providers' use of demographic cues in making pain management decisions. Participants completed the Gender Role Expectations of Pain Questionnaire to assess the participant's views of gender differences in pain sensitivity, pain endurance, and willingness to report pain. Results Results of repeated measures analysis of variance revealed that health care providers of both genders endorsed stereotypic views of pain regarding willingness to report pain (F(1,165)=34.241, P<0.001; d=0.479). Furthermore, female dentists rated men as having less endurance than women (F(1,165)=4.654, P=0.032; d=0.333). Conclusion These findings affirm the presence of some gender-related stereotypic views among health care providers and suggest the presence of a view among health care providers that men are underreporting their pain in comparison to women. Future work can refine the effects of social learning history and other psychosocial factors that contribute to gender and provider differences in pain management decisions.
Tolerance and Sensitization to Cocaine: An Integrated View

Publisher Summary This chapter reviews basic research on the phenomena and mechanisms of changes in sensitivity to cocaine. Tolerance has long been felt to play a major role in drug abuse. It has been stated that sensitization is a consistent finding in animal studies of cocaine. The most comprehensive analysis of tolerance to cocaine is undertaken by Branch and his colleagues, investigating cocaine's effects on schedule-controlled behavior. The reinforcing effects of drugs are those effects that increase the probability of repeated drug self-administration. Reinforcing effects are essential for repeated drug administration that is necessary for tolerance to develop. If procedural and pharmacological factors are identical (species, age, drug, dose, experimental history, and injection regimen), and the only difference between groups is the novelty of the environment in which the drug is given, then any behavioral differences are likely to be attributed to associative learning. Conditioning and sensitization can be very persistent; it might be useful to explore the substrates of other well-investigated forms of long-term neuroplasticity. A great deal of research has been done to establish the mechanisms of memory in humans and nonhuman primates.
Teaching Compassion: Professional Education for Humane Care

It is one of the ideals in medicine to be known as a compassionate physician. Yet medical students often complain that they enter the study of medicine with a strong desire to be kind to others, and during their medical education find themselves losing this ideal. Apparently the rewards of medical education are gained largely by becoming a technically competent person, and not in becoming a kind person.
Population-scale study of eRNA transcription reveals bipartite functional enhancer architecture

Enhancer RNAs (eRNA) are non-coding RNAs transcribed bidirectionally from active regulatory sequences. Their expression levels correlate with the activating potentials of the enhancers, but due to their instability, eRNAs have proven difficult to quantify in large scale. To overcome this, we use capped-nascent-RNA sequencing to efficiently capture the bidirectional initiation of eRNAs. We apply this in large scale to the human lymphoblastoid cell lines from the Yoruban population, and detected nearly 75,000 eRNA transcription sites with high sensitivity and specificity. We identify genetic variants significantly associated with overall eRNA initiation levels, as well as the transcription directionality between the two divergent eRNA pairs, namely the transcription initiation and directional initiation quantitative trait loci (tiQTLs and diQTLs) respectively. High-resolution analyses of these two types of eRNA QTLs reveal distinct positions of enrichment not only at the central transcription factor (TF) binding regions but also at the flanking eRNA initiation regions, both of which are equivalently associated with mRNA expression QTLs. These two regions - the central TF binding footprint and the eRNA initiation cores - define the bipartite architecture and the function of enhancers, and may provide further insights into interpreting the significance of non-coding regulatory variants.
Autism in the broader context of cognitive sex differences

Autism spectrum disorder (ASD) is characterized by difficulties with reciprocal social interactions, understanding and using (e.g., making eye contact) social cues, repetitive behaviors, and narrow interests (1). About 1% of individuals will meet current diagnostic criteria for ASD (2), with about a 4:1 ratio of males to females (3). Diagnostic criteria are categorical but the associated behaviors and cognitions fall along a continuum. Baron-Cohen et al. (4) proposed that ASD is at the extreme of the distributions of what they argued are two core human sex differences, and this is the focus of a recent study in PNAS by Greenberg et al. (5). These sex differences are called empathizing, which favors girls and women, and systemizing, which favors boys and men. The former represents sensitivity to the thoughts and feelings of others; the latter, a focus on identifying the rules that underlie how natural (e.g., weather) and mechanical (e.g., machines) systems work. From this perspective, ASD results from a combination of high systemizing and low empathizing, which is proposed to represent an extreme male brain (EMB). The EMB hypothesis integrates sex differences in brain and cognition with the core features of ASD and provides a parsimonious explanation of the overrepresentation of males with this disorder. The sex differences in empathizing and systemizing, in turn, are hypothesized to represent ancestral sex differences in the division of labor, specifically the greater parental care of women, and hunting and tool making in men (6). The study of sex differences in brain and cognition has a long and fraught history, but a consensus has emerged for many cognitive sex differences (discussed below), and brain imaging studies are converging on the functional and structural brain systems underlying the cognitive differences (7, 8). Debates now center on the magnitude of the sex differences … [↵][1]1Email: gearyd{at}missouri.edu. [1]: #xref-corresp-1-1
Weak Interactions in Alkaline Earth Metal Dimers by Pair-Density Functional Theory

Alkaline earth dimers have small bond energies (less than 5 kcal/mol) that provide a difficult challenge for electronic structure calculations. They are especially challenging for Kohn-Sham density functional theory (KS-DFT) using generalized gradient approximations (GGAs) as the exchange-correlation density functional because GGAs often do not provide accurate results for weak interactions. Here we treat alkaline earth dimers from six different rows of the periodic table. We show that the dominant correlating configurations are the same in all six dimers. We also show that multiconfiguration pair-density functional theory (MC-PDFT) using a fully translated GGA as the on-top density functional not only performs much better than KS-DFT with GGAs in predicting equilibrium distances and dissociation energies but also performs better than the more computationally demanding complete active space second-order perturbation theory (CASPT2) with large basis sets and performs even better than CASPT2 with smaller basis sets.
Gas separation properties of polybenzimidazole/thermally-rearranged polymer blends

Abstract Polybenzimidazole (PBI) is highly selective for H2 removal from mixtures with CO2, but it exhibits low gas permeabilities. Celazole® PBI was blended with more permeable HAB-6FDA-CI, an ortho-functional thermally rearrangeable polyimide, to improve its gas permeabilities while attempting to maintain high selectivity. A compatibilizer, 1-methylimidazole, enhanced phase dispersion when added to the casting solutions. Films containing 20–40 wt% polyimide exhibited a matrix-droplet morphology as observed by scanning and transmission electron microscopy. Heat treatment at 400 °C under inert atmosphere thermally rearranged the polyimide in the blends. After heat treatment, H2/CO2 selectivities at 35 °C doubled for Celazole® and 20–33 wt% polyimide compatibilized blends, exceeding the 2008 upper bound. Simultaneous increases in both H2 permeability and H2/CO2 selectivity were observed after heat treatment for the 33/67 wt% HAB-6FDA-CI/Celazole® compatibilized blend, which exhibited over twice the H2 permeability of Celazole® and similar selectivity. Heat treatment reduced free volume and induced para-crystallinity in the PBI phase of the blends as evidenced by x-ray scattering. Thermally treated blend films were mechanically flexible and exhibited elastic moduli and tensile strengths similar to Celazole®, despite having low elongation at break.
A systematic survey of bar-built estuaries along the California coast

Abstract Of California's 577 coastal confluences, 278 of these are characterized as bar-built estuaries or coastal river mouth lagoons. Development during the 20th century has led to varying and often extreme levels of alteration to these estuarine systems. Changes to the natural timing and magnitude of riverine flows and modification of the mouth have affected the frequency and depth of marsh plain flooding, as well as the timing of breaching events. This project used standard assessment techniques to document and quantify the current environmental condition of 32 bar-built estuaries of various sizes, distributed throughout California. Estuary lagoon filling/flushing patterns (documented using pressure/temperature loggers) were found to fluctuate most in spring (due to bar closure with continued fluvial discharge) and late fall (due to high wave overtopping events). These spring and fall water level increases led to marsh plain flooding. Marshes were flooded for periods ranging from 9 to 65 days. Sites that supported long summer ponding periods increased hydraulic connectivity with side channels and back water environments and were characterized as having optimal habitat condition using the California Rapid Assessment Method. Bar-built estuaries with lower condition were found to have higher abundance of agriculture and impervious surface within their watersheds. The lowest condition sites had more than 65% impervious surface within the 2 km radius around the bar-built estuary. Also, bar-built estuary systems where bar management occurred (periodic or permanent) were found to have a lower habitat condition and support fewer native plant species. Summer salinity exceeded 25 within portions of thirteen of the 32 estuaries and all but three systems had water within portions of the main channel with salinity below 5. Our findings suggest that water elevations, dissolved oxygen concentrations, salinity and temperature vary widely within bar-built estuaries and thus, management decisions should account for this variability to ensure support for a diversity of endemic species.
Multimodal quantitative imaging of brain cancer in cultured cells

Fluorescence emission, polarization and subcellular localization of methylene blue (MB) were studied in four cancerous and two normal human brain cell lines. Fluorescence emission and polarization images were acquired and analyzed. The co-localization of MB with mitochondria, lysosomes and nuclei of the cells was evaluated. Glioblastoma cells exhibited significantly higher MB fluorescence polarization compared to normal astrocytes. Preferential accumulation of MB in mitochondria of glioblastoma cells may explain higher fluorescence polarization values in cancer cells as compared to normal. These findings may lead to the development of a quantitative method for the detection of brain cancer in single cells.
Integrated Approach for Data Acquisition, Visualization and Processing of Analog Polarographic Systems for Bioenergetics Studies

Bioenergetic function is characterized with assays obtained by polarographic systems. Analog systems without data acquisition, visualization, and processing tools are used but require cumbersome operations to derive respiration rate and ADP to oxygen stoichiometry of oxidative phosphorylation (ADP/O ratio). The analog signal of a polarograhic system (YSI-5300) was digitized and a graphical user interface (GUI) was developed in MATLAB to integrate visualization, recording, calibration and processing of bioenergetic data. With the GUI, the signal is continuously visualized during the experiment and respiratory rates and ADP/O ratios can be determined. The integrated system was tested to evaluate bioenergetic function of subpopulations of mitochondria isolated from rat skeletal muscle (n = 10). Signal processing was applied to denoise data recorded at the sampling rate of 1000Hz, and maximize data decimation for computational applications. The error in calculating the bioenergetic outputs using decimated data is negligible when data are denoised. The estimate of respiration rate, ADP/O ratio and RCR obtained with denoised data at sampling rate as low as 5Hz was similar to that obtained with raw data recorded at sampling rate of 1000Hz. In summary, the integrated tools of the GUI overcome the limitations of data processing, accuracy, and utilization of analog polarographic systems.
Finding an Academic Residency Program

The preceding chapters in this book presented knowledge and insight into the field of academic medicine, and why diversity and inclusion are vital to medical education. This chapter provides information on how medical students can select an appropriate residency with the goal of preparing them for a career in academic medicine.
Stable compensation voltages in differential mobility spectra by separating neutral vapors from ions in sample flow

In small planar differential mobility spectrometers with ambient pressure ion sources, both ions and neutral vapors of sample commonly flow from the ion source directly into and through the analyzer region. Although simple and convenient both for fabrication and operation, product ions derived from sample in this design may form clusters with neutral unreacted sample or matrix constituents particularly at vapor levels of 50 ppm or greater. Uncontrolled and changing levels of such neutrals cause concentration dependent formation of ion clusters with variations in compensation voltages of DMS spectra. Stable compensation voltages were achieved for product ions by extracting ions into a counter flow of purified gas excluding neutral vapors from ppm to percent levels. An interface with electric fields and purified air was placed between ion source and analyzer region and operated with both on-axis and orthogonal extraction of ions. Effectiveness of removal of neutrals was determined using variations in peak position for protonated monomers and proton bound dimers of dimethylmethylphosphate, significantly avoiding complications of ionization chemistry with high vapor concentrations of methylene chloride, iso-propanol, water, and methanol. In-silico modeling using COMSOL and SIMION clarified the flow of ions and gases in two modes of operation. Findings anticipate the development of multiple stages of DMS analyzers where vapors may be intentionally added as modifiers in one stage and removed before entering a subsequent stage.
The PI3K pathway impacts stem gene expression in a set of glioblastoma cell lines

The PI3K pathway controls diverse cellular processes including growth, survival, metabolism, and apoptosis. Nuclear FOXO factors were observed in cancers that harbor constitutively active PI3K pathway output and stem signatures. FOXO1 and FOXO3 were previously published to induce stem genes such as OCT4 in embryonic stem cells. Here, we investigated FOXO-driven stem gene expression in U87MG glioblastoma cells. PI3K-activated cancer cell lines were investigated for changes in gene expression, signal transduction, and clonogenicity under conditions with FOXO3 disruption or exogenous expression. The impact of PI3K pathway inhibition on stem gene expression was examined in a set of glioblastoma cell lines. We found that CRISPR-Cas9-mediated FOXO3 disruption in U87MG cells caused decreased OCT4 and SOX2 gene expression, STAT3 phosphorylation on tyrosine 705 and clonogenicity. FOXO3 over expression led to increased OCT4 in numerous glioblastoma cancer cell lines. Strikingly, treatment of glioblastoma cells with NVP-BEZ235 (a dual inhibitor of PI3K and mTOR), which activates FOXO factors, led to robust increases OCT4 gene expression. Direct FOXO factor recruitment to the OCT4 promoter was detected by chromatin immunoprecipitation analyses using U87MG extracts. We show for the first time that FOXO transcription factors promote stem gene expression glioblastoma cells. Treatment with PI3K inhibitor NVP-BEZ235 led to dramatic increases in stem genes in a set of glioblastoma cell lines. Given that, PI3K inhibitors are actively investigated as targeted cancer therapies, the FOXO-mediated induction of stem genes observed in this study highlights a potential hazard to PI3K inhibition. Understanding the molecular underpinnings of stem signatures in cancer will allow refinements to therapeutic strategies. Targeting FOXO factors to reduce stem cell characteristics in concert with PI3K inhibition may prove therapeutically efficacious.
Self-organization, human resilience and psychotherapy

This chapter applies self-organization theory to human resilience and psychotherapy. Three broad classes of modeling are described: network modeling, topological approaches, and time-series analysis. Unique aspects and common features of each model is discussed, and empirical literature is reviewed, with a focus on how these various models contributes to a common theory of biopsychosocial resilience.
Where's the gas?

The recent finding of hot interstellar hydrogen gas in elliptical galaxies is discussed. The belief held until recently that elliptics had no such gas and thus were past their star-forming stage is contradicted by new evidence obtained primarily with the X-ray images from the Einstein satellite. The hot gas is present in far greater amounts than could be accounted for by an outflowing galactic wind. The gas exists in isolated elliptics as well as in cluster members and thus is not part of the intracluster medium. It is concluded that the gas must be forming new small stars, since few massive hot stars are visible in elliptical galaxies.