cssi/SciSciGPT-SciSciNet huggingface dataset:
Presence of activation-related m-RNA for EBV and CMV in the bone marrow of patients with myelodysplastic syndromes

Abstract The bone marrow (BM) in myelodysplastic syndromes (MDS) undergoes pathobiological changes that mimic an inflammatory process, and hence, an infectious etiology was suspected in these disorders. In the present report, we examined the bone marrow mononuclear cells (BMMNC) of 19 MDS patients and seven normal donors for the expression of one latency-related (Latency membrane protein 1 (LMP-1) and immediate early protein (IEP)) and one activation-related (BZLF and DNA-Pol) m-RNA each for two herpes viruses, Epstein–Barr virus (EBV) and cytomegalovirus (CMV), respectively. Reverse transcriptase polymerase chain reaction was used for this purpose. The latency-related transcripts (EBV-LMP-1 and CMV-IEP) were present in all the MDS and normal specimens. Intriguingly, 10/19 MDS specimens (∼53%) and 2/7 normal donors (∼28%) were positive for active EBV-BZLF ( P =0.0067), while 2/19 MDS specimens (∼11%) with 1/7 normal (∼14%) showed active CMV-DNA-Pol ( P =0.1588). Later, from another set of MDS patients ( n =7) and normal donors ( n =4), BM stromal cultures were established, which, at a 75% confluency, were overlaid with cord blood mononuclear cells (CBMNC). IEP was detectable in the CBMNC before and after co-incubation with MDS, as well as normal stroma. So, it was also present both in MDS and normal stromal cells. The other three were absent both in MDS and normal stromal layers. In CBMNC though, active EBV-BZLF and CMV-DNA-Pol m-RNA were detectable in one of seven MDS co-cultures each, albeit from different patients. None of the normal co-cultures showed active virus, either in stroma or CBMNC. Thus, the present report demonstrates, for the first time, the presence of active herpes viruses in the BMMNC of MDS patients and reveals the ability of the MDS stroma to support the viral activation.
Psychological Profile of Male and Female Animal Abusers

This study had three purposes: to explore psychological characteristics of animal abusers (criminal thinking styles, empathy, and personality traits), to replicate previously reported results (past illegal actions, bullying behavior), and to examine potential gender differences. The self-reported animal abuser group was 29 college students who reported two or more incidents of animal abuse; controls were 29 college students matched on age and gender. Participants completed self-report measures of criminal thinking, illegal behaviors, bullying, empathy, and the five-factor personality traits. Results indicated animal abusers had more previous criminal behaviors, were more likely to bully, and had the highest scores on the power orientation criminal thinking scale. Abuser by gender interactions were detected; female animal abusers scored significantly higher on several measures of criminal thinking, were found to be more likely to bully, and exhibited lower scores on measures of perspective taking and empathy compared to female controls.
(R)-2-Phenylpyrrolidine Substituted Imidazopyridazines: A New Class of Potent and Selective Pan-TRK Inhibitors

Deregulated kinase activities of tropomyosin receptor kinase (TRK) family members have been shown to be associated with tumorigenesis and poor prognosis in a variety of cancer types. In particular, several chromosomal rearrangements involving TRKA have been reported in colorectal, papillary thyroid, glioblastoma, melanoma, and lung tissue that are believed to be the key oncogenic driver in these tumors. By screening the Novartis compound collection, a novel imidazopyridazine TRK inhibitor was identified that served as a launching point for drug optimization. Structure guided drug design led to the identification of (R)-2-phenylpyrrolidine substituted imidazopyridazines as a series of potent, selective, orally bioavailable pan-TRK inhibitors achieving tumor regression in rats bearing KM12 xenografts. From this work the (R)-2-phenylpyrrolidine has emerged as an ideal moiety to incorporate in bicyclic TRK inhibitors by virtue of its shape complementarity to the hydrophobic pocket of TRKs.
cDNA cloning and mRNA expression of the six mouse insulin-like growth factor binding proteins

The insulin-like growth factor binding proteins (IGFBPs) comprise a family of six distinct proteins which modulate insulin-like growth factor action. We have isolated cDNAs encoding the six mouse IGFBPs (mIGFBPs). In addition, we studied the mRNA expression of the six mIGFBPs during development and in various adult tissues. Our results show that each of the six mIGFBPs is highly homologous to their human and rat counterparts, whereas only the N and C terminal ends are conserved between the six mIGFBPs. Northern blotting revealed that mIGFBP-2, -3, -4 and -5 genes are already expressed at gestational day 11.5, suggesting a role for these mIGFBPs in embryonal development. In liver, a peak of mIGFBP-1 mRNA expression was found around birth, suggesting a function for mIGFBP-1 in the newborn mouse. Finally, tissue-specific expression of the six mouse IGFBP genes was observed in adult tissues suggesting different roles or modes of actions in adult life.
Repeatable behavioural type and stable dominance rank in the bluefin killifish

While the prevalence of animal personalities has become apparent in recent years, the importance of animal personalities in determining the outcome of sexual selection remains imperfectly understood. In particular, there are few data on whether repeatable personality differences among males are associated with repeatable outcomes of male–male interactions within the mating context. Using the bluefin killifish, Lucania goodei, we examined the repeatability of individual differences in mating behaviours and the stability of dominance rank, which partially determines mating success in this species. The expression of male behaviours in competition between males and female courtship was significantly repeatable over a 5-week period; the number of aggressive behaviours to males and females, and the number of courtship bouts had significant repeatabilities of 0.71, 0.72 and 0.65, respectively. A male's personality or behavioural type within the mating context, as measured by a composite measure of the overall level of mating behaviour activity, was significantly repeatable at 0.75. Males showed repeatable, linear dominance hierarchies, and a male's rank in the hierarchy was highly correlated with his behavioural type. Neither behavioural type nor dominance rank was associated with body size or body condition. The repeatability of behavioural types and stability in the outcomes of aggressive interactions suggest that these behavioural phenotypes are inherent characteristics of individuals rather than short-term responses to recent social experience or daily levels of food or stress, and may potentially have an early environmental and/or genetic basis.
Adult Barriers To Higher Education: A Comparison Of Gender, Age, And Ethnicity In Faith-Based Colleges

The study compares the responses of students in nontraditional undergraduate and graduate degree programs from three faith-based institutions and multiple campuses to determine what barriers exist for adult students. Nontraditional, in this case, refers to degree programs offered within the context of night classes and accelerated programs of study that cater primarily to working adults.
Discriminatory Power of Heterogeneity Statistics with Respect to Error of Precipitation Quantile Estimation

AbstractAt low sample size, sampling error may be reduced by pooling multiple gauge records. This creates an error component due to heterogeneity, the degree to which the pooled regional data’s quantile estimates are different from the true at-site quantiles. Heterogeneity statistics attempt to quantify the degree to which error is added due to regional heterogeneity. They are justified through elucidation of a so-called reasonable proxy relationship with error caused by heterogeneity and through the ability of heterogeneity thresholds to detect heterogeneous regions. In this paper, previous findings regarding three heterogeneity statistics H1–H3 are revisited; a previous finding that H1 is superior to H2 and H3 is amended based on simulation experiments and upon enumeration of all possible regionalizations of a small gauge dataset across time scales from daily to monthly. Thresholds defined based on H1 are shown to be 4× too high for application to H2 and new thresholds are derived for H2. Two nonparamet...
Designing zeolite catalysts for shape-selective reactions: Chemical modification of surfaces for improved selectivity to dimethylamine in synthesis from methanol and ammonia

The relative contributions of external and intracrystalline acidic sites of small pore H-RHO zeolite for the selective synthesis of methylamines from methanol and ammonia have been studied. Nonselective surface reactions which produce predominantly trimethylamine can be eliminated by “capping” the external acidic sites with trimethylphosphite (TMP) and other reagents, thus improving the selectivity toward the formation of dimethylamine. For small pore zeolites, neither the zeolite pore size nor the internal acidic sites is significantly affected by this treatment. In situ infrared and MAS-NMR studies show that TMP reacts irreversibly with the zeolite acidic sites via a modified Arbusov rearrangement to form surface-bound dimethylmethylphosphonate.
Creative approaches to development of marketing information systems

The measurement and meaning of creativity are discussed and creativity techniques that can be used in marketing information management are described. Two exploratory studies are reported that applied creativity techniques to questions surrounding the design and development of a marketing information system. The results of the experiments indicate that certain creativity techniques may be quite useful in eliciting more enlightened views of what marketing information should be gathered by an organization. >
Certificate program in teaching for pharmacy residents.

The Notes section welcomes the following types of contributions: (I) practical innovations or solutions to everyday practice problems, (2) substantial updates or elaborations on work previously published by the same authors, (3) important confirmations of research findings previously published by others, and (4) short research reports, including practice surveys, of modest scope or interest.
Wound healing of mouse skin incised with a plasma scalpel.

Abstract Healing characteristics of mouse skin wounds induced with a plasma scalpel are examined and compared with the healing of similar steel scalpel wounds. The tissue response to the plasma scalpel incision corresponds to local heat injury, and results in necrosis of the epithelium approximately 3.0 mm on either side of the lesion. The residual scars from plasma scalpel wounds are three times larger than corresponding steel scalpel scars. Epithelial migration is successful in isolating necrotic from living tissue in both types of wounds. The onset and completion of epithelial migration in plasma scalpel wounds are delayed by approximately 36 hr and 4–8 days, respectively, in comparison to steel scalpel wounds. The initial inflammatory response is well removed from the plasma scalpel wound margin, but occurs directly at the margin of steel scalpel wounds. This difference results from the existence of vascular damage near the plasma scalpel incision. The inflammatory response in plasma scalpel wounds is initially less intense than the response in steel scalpel wounds. However, the overall inflammatory response in plasma scalpel wounds is, in time, more intense due to the larger amount of necrotic tissue. The significant result in this study is that a wound induced by the plasma scalpel in mouse skin does heal without undue complications.
Microbial Degradation Products Influence Colon Cancer Risk: the Butyrate Controversy

All dietary fiber, by definition, escapes digestion in the small intestine and thus arrives relatively intact in the large intestine. Its fate in the large intestine depends upon the type of fiber and the colonic microflora. Highly fermentable fibers result in short chain fatty acids including butyrate, which is thought by some to be protective against colon cancer. However, not all studies support a chemopreventive effect for butyrate and the lack of agreement (particularly between in vivo and in vitro studies) on butyrate and colon cancer has been termed the "butyrate paradox." There are a number of reasons for this discrepant effect including differences between the in vitro and in vivo environments, the timing of butyrate administration, the amount of butyrate administered, the source of butyrate (usually dietary fiber) as a potential confounder, and an interaction with dietary fat. Collectively, the studies suggest that the chemopreventive benefits of butyrate depend in part on amount, time of exposure with respect to the tumorigenic process, and the type of fat in the diet.
Naproxen Metabolites Interfere With Certain Bilirubin Assays Elimination of Interference by Using a Roche Bilirubin Assay on the Hitachi 917 Analyzer

A recent report indicated significant interference of naproxen with total bilirubin measurement when using the Jendrassik and Grof method. We explored the possibility of avoiding this interference by using a different method. We observed that naproxen has no effect on total bilirubin measurement by any method, but O-desmethylnaproxen (the naproxen metabolite) interfered significantly with total bilirubin assays using the Jendrassik and Grof method (Beckman Coulter [Brea, CA] and Siemens [Tarrytown, NY] bilirubin method). The Roche (Indianapolis, IN) bilirubin assay based on a different method was not affected. When serum samples of 9 patients receiving naproxen were analyzed for total bilirubin level, we observed good correlation in total bilirubin values measured by all 3 methods in 7 of 9 patients with therapeutic naproxen concentrations. In contrast, in 2 patients with elevated naproxen levels, the total bilirubin values observed by using the Beckman and Siemens methods were significantly higher than the value obtained by the Roche assay. The naproxen metabolite interferes with assays based on the Jendrassik and Grof method but not with the Roche bilirubin assay.
Toward empirically-based software visualization languages

Underlying any single-user software visualization (SV) system is a visualization language onto which its users must map the computations they would like to visualize with the system. We hypothesize that the usability of such systems turns on their ability to provide an underlying visualization language that accords with the ways in which their users conceptualize the computations to be visualized. To explore the question of how to design visualization languages grounded in human conceptualization, we present an empirical study that made use of a research method called visualization storyboarding to investigate the human conceptualization of the bubblesort algorithm. Using an analytical framework based on entities, attributes, and transformations, we derive a semantic-level visualization language for bubblesort, in terms of which all visualizations observed in our study can be expressed. Our empirically-based visualization language provides a means for predicting the usability of the visualization language defined by Lens (Mukherjea and Stasko, 1994), a prototypical single-user SV system. We draw from a follow-up usability study of Lens to substantiate our predictions.
Vitamin D analogues for secondary hyperparathyroidism

Secondary hyperparathyroidism (2HPT), a common disorder in patients with chronic renal failure, develops in response to phosphate retention and low serum 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3), calcitriol). Replacement therapy with calcitriol or its precursor 1alpha-hydroxyvitamin D(3) (1alphaOHD(3), alfacalcidol) often produces hypercalcaemia, especially when combined with calcium-based phosphate binders. In addition, these vitamin D compounds can aggravate the hyperphosphataemia in these patients. Several vitamin D analogues have been developed that retain the direct suppressive action of 1,25(OH)(2)D(3) on the parathyroid glands but have less calcaemic activity, thereby offering a safer and more effective means of controlling 2HPT. 1,25-Dihydroxy-19-norvitamin D(2) (19-norD(2)) and 1alpha-hydroxyvitamin D(2) (1alphaOHD(2)) are available in the US and 1,25-dihydroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) and 1,25-dihydroxy-26,26,26,27,27,27-hexafluorovitamin D(3) (1,25(OH)(2)26,27F6 D(3), falecalcitriol) have been approved for use in Japan. Animal studies have demonstrated that OCT and 19-norD(2) have a wider therapeutic window for suppression of parathyroid hormone (PTH) because of their lower calcaemic and phosphataemic activities. The low calcaemic activity of OCT has been attributed to its rapid clearance, which prevents sustained effects on intestinal calcium absorption and bone resorption, but still allows a prolonged suppression of PTH gene expression and parathyroid cell growth. The calcaemic activity of 19-norD(2) diminishes with the duration of treatment by as yet unknown mechanisms. The lower toxicity of 1alphaOHD(2), compared with 1alphaOHD(3), has also been noted with chronic, but not acute administration, perhaps due to differential metabolism. The unique actions of falecalcitriol may also result from an altered metabolism. A clear understanding of the molecular basis for the selectivity of vitamin D analogues on parathyroid function may allow the design of even more effective analogues.
COMPARISONS AMONG DESIGNS FOR EQUATING CONSTRUCTED‐RESPONSE TESTS

This study examined variations of a nonequivalent groups equating design used with constructed-response (CR) tests to determine which design was most effective in producing equivalent scores across the two tests to be equated. Using data from a large-scale exam, the study investigated the use of anchor CR item rescoring in the context of classical equating methods. Four linking designs were examined: (a) an anchor set containing common CR items, (b) an anchor set incorporating common CR items rescored, (c) an external multiple-choice (MC) anchor test, and (d) an equivalent groups design incorporating CR items rescored (no anchor test). The use of CR items without rescoring or the use of an external MC anchor resulted in much larger bias than the other two designs. The use of a rescored CR anchor and the equivalent groups design led to similar levels of equating error.
The effects of quantitative skills training on college outcomes and peers

Abstract This paper estimates the causal effect of taking a course in quantitative reasoning on students’ academic performance and classroom peer-group composition at a liberal arts college. To identify effects, the paper compares the outcomes of otherwise similar students who barely passed a baseline quantitative skills assessment (not taking the course) with students who barely failed (taking the course). The regression-discontinuity estimates show little impact on academic outcomes for student close to the passing cutoff, including grades on subsequent courses with quantitative content, but we are unable to distinguish small from zero effects. Exogenous course assignment does affect the composition of students’ classroom peer groups in subsequent years. The effects can only be generalized to students in the vicinity of the passing threshold (but not students with much worse quantitative skills at the baseline). We discuss implications for research and policy on remediation.
Advances in Photovoltaics at NREL

This paper discusses the critical strategic research and development issues in the development of next-generation photovoltaic technologies, emphasizing thin-film technologies that are believed to ultimately lead to lower production costs. The critical research and development issues for each technology are identified. An attempt is made to identify the strengths and weaknesses of the different technologies, and to identify opportunities for fundamental research activities suited to advance the introduction of improved photovoltaic modules.
Structure of the ovipositor of Hylotrupes bajulus (Coleoptera: Cerambycidae)

The female of Hylotrupes bajulus (L.) has an elongated ovipositor comprising modified abdominal segments 8 and 9, intersegmental membrane 8/9, and a pair of distal gonostyli. When not in use, the ovipositor is retracted within abdominal segment 7. An internal apodeme attached to the base of the 8th sternite allows for extension and retraction of the ovipositor. Intersegmental membrane 8/9 makes up half the length of the ovipositor. The 9th sternum is split along the midline to form a pair of hemisternites. The gonostyli comprise basal coxites and apical styli. Segment 8 has long tactile hairs and short trichoid sensilla; intersegmental membrane 8/9 has no visible sensory receptors; segment 9 has campaniform sensilla and short trichoid sensilla. Gonostyli have several types of sensory receptors, including long tactile hairs, medium trichoid sensilla, short trichoid sensilla, and basiconic sensilla. Long tactile hairs and campaniform sensilla are innervated by a single dendrite, thus functioning as mechanoreceptors. Medium trichoid sensilla are innervated by three dendrites, two of which extend into the lumen of the receptor. Short trichoid sensilla are innervated by five sensory neurons. Basiconic sensilla are innervated by 1–3 dendrites, depending on type and location of the receptor. All three types of sensilla function as contact chemoreceptors, and may provide information on suitability of the oviposition substrate.
Ultra Low-Energy Relaxation Oscillator With 230 fJ/cycle Efficiency

An ultra low-energy oscillator circuit is presented for use in picowatt level systems. The core oscillator uses an 18 transistor 3 stage architecture designed to minimize short circuit current. In addition, a transistor threshold is used to set the trip point as opposed to a voltage reference and comparator scheme, leading to overall energy savings. While operating across a wide range of low frequencies from 18 to 1000 Hz, the oscillator core consumes 110 fJ/cycle at 0.6 V. The circuit is demonstrated alongside an integrated current source to set the reference frequency. The combined system consumes a total power of 4.2 pW at 18 Hz, resulting in 230 fJ/cycle at 0.6 V.
Presence of acetylsalicylic acid in plasma following oral ingestion of aspirin.

SummaryThe absorption and hydrolysis of aspirin has been examined under various experimental conditions. Aspirin appears to be absorbed intact from the gastrointestinal tract. High concentrations of acetylsalicylate in the plasma can be demonstrated following oral ingestion of soluble but not insoluble aspirin preparations. This is correlated with the increased rate of absorption of the soluble products. There appears to be a rapid hydrolysis of acetylsalicylate in vivo and it is suggested that the principal site of this hydrolysis is the tissues. Direct evidence for hydrolysis of acetylsalicylate to salicylate by the liver of the dog has been demonstrated.
Effect of a converting enzyme inhibitor (SQ 20,881) on angiotensin-induced drinking.

SummaryThe effects of an ACE inhibitor, SQ 20,881, on the dipsogenic response to centrally administered angiotensins I and II were investigated. Central pretreatment with the inhibitor antagonized drinking behavior induced by angiotensin I, but not by angiotensin II. Peripheral treatment with 20,881 did not affect drinking responses to either angiotensin I or II. SQ 20,881 most likely inhibits brain ACE after central but not peripheral administration.
Rationale for intergroup trial E-3695 comparing concurrent biochemotherapy with cisplatin, vinblastine, and DTIC alone in patients with metastatic melanoma.

Purpose The modest activity of chemotherapy and biologic agents in the treatment of advanced metastatic melanoma has prompted investigators to consider combinations of chemotherapy and biologic agents (i.e., biochemotherapy) as a way of improving response rates and survival. Although biochemotherapy has generated a great deal of interest over the last several years, and these regimens have produced high response rates in single-institution phase II trials, they have yet to demonstrate a significant survival benefit in randomized trials compared with either chemotherapy or biotherapy alone. Methods The available literature regarding the clinical experience with single- and multiagent chemotherapy, immunotherapy, and biochemotherapy was reviewed. Results Treatment of metastatic melanoma with either single-agent or combination chemotherapy regimens is clearly suboptimal; the majority of responses are partial and of short duration. In contrast, interleukin (IL)-2 produces long-term durable complete remission in a subset of patients. Over 1,000 patients have been treated with IL-2-based biochemotherapy regimens in single-institution phase II trials, and response rates have ranged from 40% to 60%. Most encouraging have been the durable responses observed in 10% to 20% of patients in most of these trials. Large databases, including two meta-analyses, have confirmed the substantial improvement in response rate associated with biochemotherapy regimens that include both IL-2 and interferon alfa (IFN-alpha) compared with chemotherapy or biotherapy alone. Biochemotherapy is currently being evaluated in randomized controlled trials to determine if this treatment strategy can provide a survival benefit compared with current standard treatments. A pilot study at Beth Israel Deaconess Medical Center has demonstrated the feasibility of administering a modification of a concurrent biochemotherapy regimen, initially described by Legha et al, consisting of cisplatin, vinblastine, and dacarbazine (CVD) plus IL-2 and IFN-alpha in the cooperative group setting. Conclusion These studies provided the rationale for intergroup trial E-3695, which is currently randomizing patients to concurrent biochemotherapy with CVD plus IL-2 and IFN-alpha versus CVD alone.
Coma in the elderly: evaluation and treatment.

Accurate and expeditious differential diagnosis and treatment, starting with basic emergency measures, should reduce both morbidity and mortality.
Development and initial results of a mandatory department of surgery faculty mentoring pilot program.

Abstract Background Mentoring of junior faculty by senior faculty is an important part of promotion and/or tenure and enhanced job satisfaction. This study reports the development and results to date of a faculty mentorship program in surgery. Methods We implemented a departmental faculty mentoring program in July 2014 that consisted of both structured and informal meetings between junior faculty mentees and assigned senior faculty mentors. All senior faculty mentors attended a brief mentor training session. We then developed an evidence-based mentorship instrument that featured standardized metrics of academic success. This instrument was completed by each mentee, and then reviewed at the junior faculty's annual career conference with their division chief. A survey was distributed in July 2015 to assess junior faculty satisfaction with the new mentorship program. Results Junior or senior faculty consisted of six of three women and 16 of 11 men, respectively. Junior faculty members were aged 40 ± 3 y and had been an attending for 4 ± 2 y. Mentorship meetings occurred approximately three times during the year (range = 0-10). Total meeting time with senior mentors per meeting was a mean of 40 min (range = 0-300 min). Over 75% of junior faculty members were very or somewhat satisfied with the mentorship program and would like to continue in the program. The best aspect of the program was the opportunity to meet with an accomplished surgeon outside their division. Opportunities to improve the program included better matching of mentor to mentee by disease or research focus. Interestingly, almost the entire junior faculty members tended to have at least two other mentors besides the mentor assigned to them in this program. In terms of program outcomes, junior faculty members agreed that the mentorship program improved their overall career plans and enhanced their involvement in professional organizations but has not yet helped with academic productivity, home and/or work balance, and overall job satisfaction. Conclusions A mandatory, structured mentorship program with senior surgeons benefits most junior faculty members in terms of academic career planning and becoming more involved with surgical organizations. More research is required to understand the best method to pair mentors and mentees and more objective measurements of academic surgery success.
International Courts: A Theoretical Assessment

Scholars have long been fascinated by the role of international courts in the enforcement of international rule of law. They start with a foundational question: Can international courts affect how international law is implemented? In this review, we lay out four of the most common theoretical arguments for why international courts matter. We then interrogate these accounts. In particular, we examine their views on how much influence courts have and what the likely welfare consequences are for the signatories of an agreement. In so doing, we identify critical conditions that must obtain for court influence under each of the arguments. We then bring more recent scholarship to bear on the plausibility of these conditions. In particular, we examine what research on the structure of law, the preferences of judges, and institutional design implies about the efficacy of international courts based on the four foundational arguments. We conclude with suggestions for future research.
Selenium enriched dietary supplement rapid screening method using XRF and DART-HRAM-MS for label verification

Selenium is a biologically relevant trace element that is a common ingredient of commercially available dietary supplements. Label verification of dietary supplements enriched with selenium has been performed using liquid chromatography with inductively coupled plasma mass spectrometry (LC/ICP-MS) in research applications. While this method represents the gold standard, performing LC/ICP-MS analysis on dietary supplements can be cumbersome and comes with the cost of time, ultimately limiting the throughput of this technique. A rapid screening method would improve throughput and reduce the number of samples requiring the complete LC/ICP-MS characterization of selenium for dietary supplement label verification. A rapid screening method for the determination of total selenium using energy dispersive X-ray fluorescence (XRF) (limit of detection 4 μg g−1, limit of quantitation 30 μg g−1) and unbound “selenoamino acids” using direct analysis in real time high resolution accurate mass–mass spectrometry (DART-HRAM-MS) was successfully applied to 13 dietary supplements previously characterized by LC/ICP-MS. Overall, determining total and speciated selenium in enriched dietary supplements using the combined XRF/DART-HRAM-MS approach reduces the analysis time from several hours to less than 40 minutes per sample.
Polymorphic Architectures of Graphene Quantum Dots

A systematic strategy for designing structured nanomaterials is demonstrated through self-assembly of graphene quantum dots. The approach reveals that graphene derivatives at the nanoscale assemble into various architectures of nanocrystals in a binary solution system. The shapes of the nanocrystals continue to evolve in terms of the intimate association of organic molecules with the dispersion medium, obtaining a high index faceted superlattice. This facile synthetic process provides a versatile strategy for designing particles to new structured materials systems, exploiting the crystallization of layered graphitic carbon structures within single crystals.
Moral Transformation and Duties of Beneficence

Some ideas are at the heart of the world’s great ethical and religious traditions, yet they play little or no role within certain debates in modern philosophical ethics. One such idea is that most of us have unreliable moral intuitions and we must transform ourselves into better people before we can reliably judge how to behave. This paper explores that idea by focusing on a transformative experience that I will call the moral experience. In the paper’s initial sections, I describe the moral experience and explain why it constitutes a genuine transformation in ethical outlook. I then argue that the moral experience could thereby affect our views on certain contemporary ethical debates, illustrating those points with a discussion of the debate about global poverty.
Attitudes Toward Dating Violence: How Does Sexual Identity Influence Perceptions Among College Students?

ABSTRACTIn the current study, we explore how sexual identity affects attitudes toward dating violence by utilizing a survey of 1,645 college students. We examine attitudes toward justification for relationship violence and perceptions of unhealthy relationships. It is important to explore how sexual identity influences perceptions of intimate partner violence because recent research suggests that rates of IPV among LGBT individuals are equal to or higher than IPV rates among heterosexuals (Walters, Chen, & Breiding, 2013). Additionally, non-heterosexual individuals often face different difficulties than their heterosexual counterparts when they attempt to report IPV and seek help. Considering prior research has often failed to examine how these differences influence attitudes toward relationship violence, the current study attempts to fill this void in the literature. Findings from the current study indicate that gender, more than sexuality, appears to be influencing attitudes towards IPV. Implications fo...
Molecular Imaging of Stem Cells and Exosomes for Myocardial Regeneration

Stem cell therapy is studied for the treatment of ischemic heart disease. Despite high expectations, investigation has yielded mixed results. For further advancement of this field, it is essential to understand the fate of the transplanted stem cells in living subjects. A myriad of tools has been developed to allow for the immediate and longitudinal monitoring of stem cells in vivo. In this review, we outline the most reliable techniques and their implications for cardiac regenerative medicine. Direct (e.g., PET/SPECT, MRI) and indirect labeling (e.g., reporter gene) techniques have existed for decades prior to their use in stem cell imaging. In this review, we describe some of the key developments in the context of stem cell therapy for cardiac ischemia, including new contrast agents (MRI, SPECT) and novel reporter genes (e.g., near-infrared fluorescent protein). Furthermore, we discuss innovative techniques that integrate direct and indirect labeling, such as PET reporter gene systems. Finally, we examine the potential of exosomes, a component of the stem cell secretome, which has recently garnered much attention for its potential in myocardial regeneration, and how they may be imaged in vivo. This review outlines the most reliable techniques for stem cell imaging in cardiac injury animal models, new and notable advancements in the field, and possible directions for cardiac regenerative medicine.
Whitman & Dickinson: A Colloquy, edited by Éric Athenot and Cristanne Miller: U of Iowa P, 2018.

The eleven essays collected in Whitman & Dickinson: A Colloquy began as conference presentations delivered at the Universite Paris-Est Creteil in March 2015, at a gathering of European and North Am...
A Data Architecture for Library Collections

ABSTRACTThe current ad-hoc, organically grown system of digital library inventory management is inefficient, ineffective, and costly, both in dollar terms and in the time and effort of librarians a...
Clinical use of Prostate Specific Antigen in Patients with Prostate Cancer

AbstractThe clinical use of prostate specific antigen as a screening test for prostate cancer, as a preoperative determinant for staging of prostate cancer and to monitor response to therapy in prostatic cancer patients was evaluated in 168 men with benign prostatic hyperplasia and 231 men with prostate cancer. Only 3% of the men with benign prostatic hyperplasia had prostate specific antigen levels greater than 10ng. per ml. compared to 44% of the men with proved prostate cancer. Preoperative prostate specific antigen levels increased with higher clinical stages of prostate cancer but there was substantial overlap among stages. Among patients with stage Al prostate cancer who were followed expectantly none had an elevated prostate specific antigen value or metastatic disease during a followup of 15 to 120 months. After radical prostatectomy serum prostate specific antigen values decreased to undetectable levels (less than 0.6ng. per ml.) in 89% of the patients with organconfined disease, in 87% of those ...
Mechanistic Insight through Irreversible Inhibition: DNA Polymerase θ Uses a Common Active Site for Polymerase and Lyase Activities.

DNA polymerase θ (Pol θ) is a multifunctional enzyme. It is nonessential in normal cells, but its upregulation in cancer cells correlates with cellular resistance to oxidative damage and poor prognosis. Pol θ possesses polymerase activity and poorly characterized lyase activity. We examined the Pol θ lyase activity on various abasic sites and determined that the enzyme is inactivated upon attempted removal of the oxidized abasic site commonly associated with C4′-oxidation (pC4-AP). Covalent modification of Pol θ by the DNA lesion enabled determination of the primary nucleophile (Lys2383) responsible for Schiff base formation in the lyase reaction. Unlike some other base excision repair polymerases, Pol θ uses a single active site for polymerase and lyase activity. Mutation of Lys2383 significantly reduces both enzyme activities but not DNA binding. Demonstration that Lys2383 is required for polymerase and lyase activities indicates that this residue is an Achilles heel for Pol θ and suggests a path forwar...
Mechanism of human platelet activation by endotoxic glycolipid-bearing mutant Re595 of Salmonella minnesota

The mechanism through which human blood platelets interact with gram-negative bacteria with well-defined structural variations in endotoxic lipopolysaccharide was studied. Secretion of 14C-serotonin and aggregation of platelets separated from plasma proteins were observed on challenge with rough mutant Re595 of Salmonella minnesota possessing a glycolipid outer layer composed of Lipid A and 2-keto-3-deoxyoctonate (KDO) but lacking heptose phosphate in the core and O-polysaccharide in its outer portion. Both 14C-serotonin secretion and platelet aggregation were concentration-dependent, with a half-maximum response at the ratio of one bacterial colony-forming unit (CFU) to two platelets. The aggregation of human platelets induced by mutant Re595 was divalent cation-dependent and required secretion of ADP and fibrinogen from platelet storage granules because it was inhibited by chelators, by the ADP-splitting enzyme apyrase, and by monospecific antifibrinogen Fab fragments. The synthetic peptide analog of the platelet receptor recognition site on the gamma chain of fibrinogen, gamma 400-411, inhibited platelet aggregation induced by mutant Re595 (IC50 160 mumol/L), whereas serotonin secretion was unaffected. Tetrapeptide, RGDS, analogous to human fibrinogen alpha chain (alpha 572-575) and to the cell adhesion site of fibronectin, also inhibited aggregation induced by mutant Re595 (IC50 60 mumol/L). Secretion of 14C-serotonin was preceded by a very rapid phosphorylation of a platelet protein of mol wt 47,000, which is associated with protein kinase C activation. Myosin light chain (mol wt 20,000) was also phosphorylated. Both phosphoproteins were dephosphorylated while secretion was reaching maximum. Furthermore, release of 3H-arachidonic acid from platelet phospholipids and generation of thromboxane B2 via the cyclooxygenase pathway were observed. Inhibition of this pathway with acetylsalicylic acid (10(-4) mol/L) or indomethacin (5 X 10(-4) mol/L) reduced 14C-serotonin secretion and platelet aggregation. The role of Lipid A in the interaction of mutant Re595 with human platelets was deduced from the inhibitory effect of the Lipid A-binding protein present in Limulus amebocyte lysate. Likewise, polymyxin B, known to complex with Lipid A, was inhibitory. The reactivity of mutant Re595 toward platelets was attenuated by mild acid hydrolysis, during which KDO was dissociated from the glycolipid, and by alkaline hydrolysis, which breaks ester-linked fatty acids in Lipid A. In contrast to mutant Re595, strain S218 of S minnesota bearing "complete" endotoxic lipopolysaccharide did not induce secretion and aggregation of human platelets.(ABSTRACT TRUNCATED AT 400 WORDS)
Performing Static Inferences with Attributes

When an editor-designer creates an editor, a substantial part of the specification consists of attribute declarations and attribute equations. This chapter illustrates some of the considerations that influence the way an editor specification’s attribution schemes are written.
The Developing Use of Inorganic Membranes: A Historical Perspective

To most users, inorganic membranes are a relatively new product. But in fact, their development started in the 1940s and can be schematically divided into three periods: 1. The development and mass production of membranes for the separation of uranium isotopes by the process of gaseous diffusion applied to UF6. 2. Starting from this basis, the development and industrial use of a new generation of membranes adapted to the ultrafiltration and microfiltration of process hquid streams. 3. The more recent research work on a much broader range of membrane types aiming at separations using a variety of basic processes, including the coupling of catalytic reactions and membrane separation.
Immunological Reactivity of Human Recipients of Syngeneic and Allogeneic Marrow Grafts

This report describes preliminary observations of immunological function on 7 patients with bone marrow grafts. Three patients with aplastic anemia were prepared for grafting with cyclophosphamide (CY) and received marrow from HL-A-matched siblings [7, 10]. Four patients with hematological malignancy were prepared for grafting with whole body irradiation; 2 of these patients received marrow from an identical twin [6], and 2 patients received marrow from an HL-A-matched sibling [8, 9]. Table 1 summarizes the clinical and hematological data in these patients. None of these patients had significant graft-versus-host (GVH) disease and none has, as yet, shown recurrence of disease. Thus, immunologic parameters could be studied in the absence of these 2 important variables.
General Expressions for Carr-Purcell-Meiboom-Gill Relaxation Dispersion for N-Site Chemical Exchange

The Carr–Purcell–Meiboom–Gill (CPMG) nuclear magnetic resonance experiment is widely used to characterize chemical exchange phenomena in biological macromolecules. Theoretical expressions for the nuclear spin relaxation rate constant for two-site chemical exchange during CPMG pulse trains valid for all time scales are well-known as are descriptions of N-site exchange in the fast limit. We have obtained theoretical expressions for N-site exchange outside of the fast limit by using approximations to an average Liouvillian describing the decay of magnetization during a CPMG pulse train. We obtain general expressions for CPMG experiments for any N-site scheme and all experimentally accessible time scales. For sufficiently slow chemical exchange, we obtain closed-form expressions for the relaxation rate constant and a general characteristic polynomial for arbitrary kinetic schemes. Furthermore, we highlight features that qualitatively characterize CPMG curves obtained for various N-site kinetic topologies, qua...
Gq-Coupled Muscarinic Receptor Enhancement of KCNQ2/3 Channels and Activation of TRPC Channels in Multimodal Control of Excitability in Dentate Gyrus Granule Cells

KCNQ (Kv7, “M-type”) K+ channels and TRPC (transient receptor potential, “canonical”) cation channels are coupled to neuronal discharge properties and are regulated via Gq/11-protein-mediated signals. Stimulation of Gq/11-coupled receptors both consumes phosphatidylinositol 4,5-bisphosphate (PIP2) via phosphalipase Cβ hydrolysis and stimulates PIP2 synthesis via rises in Ca2+i and other signals. Using brain-slice electrophysiology and Ca2+ imaging from male and female mice, we characterized threshold K+ currents in dentate gyrus granule cells (DGGCs) and CA1 pyramidal cells, the effects of Gq/11-coupled muscarinic M1 acetylcholine (M1R) stimulation on M current and on neuronal discharge properties, and elucidated the intracellular signaling mechanisms involved. We observed disparate signaling cascades between DGGCs and CA1 neurons. DGGCs displayed M1R enhancement of M-current, rather than suppression, due to stimulation of PIP2 synthesis, which was paralleled by increased PIP2-gated G-protein coupled inwardly rectifying K+ currents as well. Deficiency of KCNQ2-containing M-channels ablated the M1R-induced enhancement of M-current in DGGCs. Simultaneously, M1R stimulation in DGGCs induced robust increases in [Ca2+]i, mostly due to TRPC currents, consistent with, and contributing to, neuronal depolarization and hyperexcitability. CA1 neurons did not display such multimodal signaling, but rather M current was suppressed by M1R stimulation in these cells, similar to the previously described actions of M1R stimulation on M-current in peripheral ganglia that mostly involves PIP2 depletion. Therefore, these results point to a pleiotropic network of cholinergic signals that direct cell-type-specific, precise control of hippocampal function with strong implications for hyperexcitability and epilepsy. SIGNIFICANCE STATEMENT At the neuronal membrane, protein signaling cascades consisting of ion channels and metabotropic receptors govern the electrical properties and neurotransmission of neuronal networks. Muscarinic acetylcholine receptors are G-protein-coupled metabotropic receptors that control the excitability of neurons through regulating ion channels, intracellular Ca2+ signals, and other second-messenger cascades. We have illuminated previously unknown actions of muscarinic stimulation on the excitability of hippocampal principal neurons that include M channels, TRPC (transient receptor potential, “canonical”) cation channels, and powerful regulation of lipid metabolism. Our results show that these signaling pathways, and mechanisms of excitability, are starkly distinct between peripheral ganglia and brain, and even between different principal neurons in the hippocampus.
Needed: Early-term adjustments for Lake Erie phosphorus target loads to address western basin cyanobacterial blooms

Abstract For Lake Erie, it is already time to revise the phosphorus target loads set to address the problem of cyanobacterial blooms in the Western Basin. Current targets were proposed by the Annex 4 task group in 2015, adopted by U.S. and Canadian governments in 2016, and set as objectives of domestic action plans in 2017. These targets, applicable to all spring discharges below the 90th percentile, set a maximum load for both total phosphorus (TP) and dissolved reactive phosphorus (DRP) equivalent to 60% of their 2008 spring loads. This essentially mandates 40% reductions in both particulate phosphorus (PP) and DRP loading relative to 2008 loads. These targets do not explicitly incorporate the difference in bioavailability between DRP (~100% bioavailable) and PP (~25% bioavailable). From 2008 to 2017, DRP comprised 24% of the spring TP load and over half (~56%) of the total bioavailable phosphorus (TBAP) load, while PP comprised 76% of the TP load but only ~44% of the TBAP load. Subsequent deposition of PP in the estuarine and nearshore zones further reduces its significance in bloom development. By ignoring differences in bioavailability, the current targets provide no guidance for choosing among practices based on their relative effectiveness in reducing DRP or PP and their combined reductions in TBAP loading. Current targets place more emphasis on PP than needed to efficiently reach targeted cyanobacterial bloom reductions. To clarify appropriate management approaches and lead to greater success in reducing cyanobacterial blooms, target loads should be based on TBAP.