cssi/SciSciGPT-SciSciNet huggingface dataset:
Comparative Genotoxicity of TEMPO and 3 of Its Derivatives in Mouse Lymphoma Cells

TEMPO (2, 2, 6, 6-tetramethylphiperidine-1-oxyl) and its derivatives are stable free radical nitroxides widely used in the field of chemistry, biology, and pharmacology. TEMPO was previously found to be mutagenic and to induce micronuclei in mammalian cells. In this study, we investigated and quantified the genotoxicity of 4 structurally similar nitroxides, TEMPO and 3 of its derivatives (4-hydroxy-TEMPO, 4-oxo-TEMPO, and 4-methoxy-TEMPO), using the mouse lymphoma assay (MLA) and Comet assay in L5178Y Tk+/- cells. The results showed that all tested nitroxides were cytotoxic and mutagenic in the MLA, both in the presence and absence of S9, with metabolic activation significantly enhancing the cytotoxicity and/or mutagenicity. In addition, the 4 nitroxides caused DNA-strand breakage. The mutagenicity and DNA damaging dose-responses of the test articles were compared using the PROAST benchmark dose software package. The potency ranking of the 4 nitroxides for mutagenicity was different from the ranking of the DNA damaging effects. The mode of action analysis by a multi-endpoint DNA damage pathway assay classified all 4 nitroxides as clastogens. In addition, the majority of the induced Tk mutants showed loss of heterozygosity at the Tk and D11Mit42 loci (ie, chromosome damage <31 Mbp). These results suggest that TEMPO and its 3 derivatives are cytotoxic and mutagenic in mouse lymphoma cells through a mechanism that involves strand breakage and large alterations to DNA. The potency rankings indicate that the different TEMPO derivatives vary in their mutagenic and DNA damaging potential.
Talimogene laherparepvec: First in class oncolytic virotherapy

Oncolytic viruses represent a novel drug class in which native or modified viruses mediate tumor regression through selective replication within and lysis of tumor cells as well as induction of systemic antitumor immunity capable of eradicating tumor at distant, uninjected sites. Talimogene laherparepvec (TVEC) is a type I herpes simplex virus genetically modified to preferentially replicate in tumor cells, enhance antigen loading of MHC class I molecules and express granulocyte-macrophage colony-stimulating factor to increase tumor-antigen presentation by dendritic cells. It is presently the only oncolytic virus approved by the FDA with an indication for advanced melanoma based upon improved durable response rate in a randomized, phase III trial. Clinical trials are underway in melanoma investigating TVEC as neoadjuvant monotherapy and in combination with checkpoint inhibitors for unresectable disease as well as in an array of other malignancies. It is appropriate to review TVEC's biology mechanism of action, clinical indication and future directions as a prototype of the burgeoning class of oncolytic viruses.
Relative contributions of ruminal bacteria and protozoa to the degradation of protein in vitro.

Mixed ruminal microorganisms from a cow fed timothy hay and concentrate supplement (50:50) were incubated with various protein sources for 15 h (no carbohydrates or growth), and deamination was studied under enzyme-limiting substrate-excess conditions (n = 3). Addition of amphotericin (10 micrograms/ml) killed protozoa and decreased (P less than .05) ammonia production from killed bacteria but it had no effect (P greater than .05) on casein deamination. Monensin (5 micrograms/ml) also killed protozoa; however, it decreased (P less than .05) casein deamination to a much greater extent than amphotericin. Antibacterial antibiotics (penicillin G, polymixin B, cephalosporin C and streptomycin) greatly reduced (P less than .05) ammonia formation from casein. Isolated bacteria always produced more ammonia than isolated protozoa, but the difference was less with heat-treated, particulate proteins. Heated soybean protein was as soluble as heated casein but it was deaminated (P less than .05) at a faster rate by bacteria. Nonammonia-nonprotein N accumulation was greater (P less than .05) with the protozoa than bacteria. When incubations containing bacteria or protozoa were compared with combinations of protozoa and bacteria, the combinations always caused a synergistic increase in ammonia and decrease (P less than .05) in nonammonia-nonprotein N. These results suggest: soluble proteins were primarily degraded by bacteria; protozoa could contribute to the degradation of insoluble, particulate proteins; protozoa were limited in their ability to assimilate peptides (or amino acids); low molecular weight products could be fermented more readily by bacteria and monensin was toxic to protozoa, but decreases in ammonia were primarily due to action of monensin on bacteria.
Open Problems in the Theory of Ultrafilters

The purpose of this paper is to present a list of open questions in the theory of ultrafilters. Most of them seem almost impenetrable by the usual methods of set-theory. Needless to say, the list of such questions is infinite, and the topics chosen for this paper reflect the personal tastes and prejudices of the author. Our notation and terminology follows that of the most recent set-theoretic literature; for example |x|denotes the cardinality of the set x, small Greek letters α,β,γ,… denote ordinals, cardinals are initial ordinals, the set y x or x y denotes the set of all functions y → x etc. For more, we refer the reader to Mathias [20]. By an ultrafilter over a set x we mean here a maximal filter in the field of subsets of x; that is: 1. Definition: D is an ultrafilter over a set x if D is a collection of subsets of x so that (a) D is a filter: $$z \in D,y \supseteq z \to y \in D$$ $${x_1} \ldots {x_n} \in D \to {x_1} \cap \ldots \cap {x_n} \in $$ $$z \in D \to z \ne 0$$ (b) D is maximal: $$z \subseteq x \to z \in Dorx - z \in D$$ D is non-principal if in addition (c) $$y \in x \to \left\{ y \right\} \notin D.$$
What Is a Confidence Interval Anyway

Forty people are selected at random and given a test to identify their dominant eye. The person holds a piece of paper about 81/2“ by 11” with a 1“ by 1” square cut in the middle at arm’s length with both hands. The person looks through the square at a relatively small object across the room. The person then closes one eye. If he or she can still see the object, the open eye is the dominant eye. If not, the closed eye is the dominant eye.
Toward A New Framework for Presence Evaluation: A Representational Design Perspective

Although researchers suggest that presence is a multi-dimensional concept, little research is available to explain the underlying relationships among the dimensions and variables. Presence is regarded as illdefined because of this measurement issue. This article proposes to look at presence as a representational issue and to inspect presence using a systematic approach. A new framework with four components for presence evaluation is introduced. It argues that investigating how media content affects presence is the solution to achieving a more complete understanding of presence and to taking individual characteristics and contexts as important factors in presence study. The article also presents a plan of empirical study designed to test narrative contrasted to expository text in an instructional design to evaluate presence.
Neural Signatures of Advice Utilization During Human–Machine Agent Interactions: Functional Magnetic Resonance Imaging and Effective Connectivity Evidence

Abstract Understanding how individuals utilize advice from humans and machines has become progressively more pertinent as technological advances have pervaded our society. However, how individuals respond to such advice and the neural signatures involved need to be better understood. We examined the impact of misses and false alarms during advice utilization from human and machine agents by combining an X-ray luggage-screening task with functional magnetic resonance imaging. Participants were asked to accept or reject good or bad advice from a human or a machine agent with manipulated reliability (study 1, high false alarm rate; study 2, high miss rate). For each study, we demonstrated unique behavioral responses and brain activation patterns associated with each error type, ultimately serving to optimize our understanding of how individuals choose to utilize or discount advice from different agents. Our findings have significant implications for society because of progressions in technology and increased interactions of humans with machines.
FDA Analysis of Outcomes in Older Adults with Relapsed or Refractory Multiple Myeloma

Background: Multiple myeloma (MM) is a disease of older adults with a median age of onset of 70 years. Approximately 20% of the incident cases are diagnosed in patients 85 years and older. There is significant heterogeneity among older adults with regards to the tolerability of myeloma directed therapy. In newly diagnosed transplant ineligible patients with MM, available evidence indicates that age greater than 80 is an independent risk factor for adverse clinical outcomes ("frail"). However, there are limited data on outcomes in adults 80 years and older in the relapsed or refractory disease setting. Over the past few years, the therapy armamentarium for patients with relapsed or refractory MM has expanded considerably with approval of at least 5 new drugs including two monoclonal antibodies, an HDAC inhibitor, and an oral proteasome inhibitor. The impact of these recent drug approvals on clinical outcomes in adults 80 years and older with relapsed or refractory MM is also unknown. This pooled analysis attempts to evaluate outcomes by age in patients with relapsed or refractory multiple myeloma Methods: Data from 10 clinical trials submitted to support approval of drugs for patients with relapsed or refractory multiple myeloma from 2011-2018 were pooled for this analysis. Participants were grouped according to three age strata: 80 years. Clinical outcomes including response rates (ORR, CR, and PR) in the different age groups were analyzed. Preliminary results of response rates by age are presented. Results: We identified 4766 patients enrolled in 10 clinical trials of relapsed or refractory multiple myeloma. The median age of the patient population was 64.5 (range 30.0-91.0). Eighty-five percent of the patients were less than 75 years of age, 11% were between 75-80 years of age, and only 4% were older than 80 years of age. Seventy percent of the population was classified as ISS Stage I or II and 24% was ISS Stage III. Overall response rate (ORR) in the pooled studies was 69% (67.6, 70.2) with less than 15% of the responses being complete responses (CR). ORR was 63.3 % (55.6, 70.6) in those 80 years and older; 70.6 % (66.6, 74.5) in the 75-80 years age group; and 68.9 % (67.5, 70.4) in patients younger than 75 years of age. CR rates were 8.3% in both the 75-80 age group and those older than 80 years, and 14.0% in those younger than 75 years. Conclusion: In this large database of recent approvals for the treatment of RRMM, preliminary results show no significant differences in ORR between patients over 80 years and those 80 years and younger (difference -5.4%; 95% CI (-13.1%, 2.3%)) suggesting response to treatment is independent of age. However, our results need to be interpreted with caution considering differences in patient populations particularly with respect to different treatment regimens and therapies. Analysis of survival outcomes is ongoing. Disclosures No relevant conflicts of interest to declare.
Mortality in open abdominal aortic surgery in patients with morbid obesity

Abstract Background Open abdominal aortic surgery is among procedures with high morbidity and mortality. Adverse postoperative complications may be more common in morbidly obese patients. Objectives This study compared the outcomes of open abdominal aortic surgeries in patients with and without morbid obesity. Setting A retrospective analysis of 2007–2014 Healthcare Cost and Utilization Project-Nationwide Inpatient Sample. Methods We included patients who underwent open abdominal aortic aneurysm (AAA) repair or open aorta-iliac-femoral (AIF) bypass. Demographic factors, morbid obesity, co-morbidities, and emergent versus elective surgery were considered for univariate and multivariate analyses. Results A total of 29,340 patients (13,443 AAA repair and 15,897 AIF bypass) were included (age 66.3 ± 10.8 years, 65.7% male). The mortality was 9.1% in 536 patients with morbid obesity compared with 7.1% in patients without morbid obesity. Based on multivariate analysis, age, existing co-morbidities, emergent versus elective setting, and morbid obesity were found to be independent predictors of mortality. Patients with morbid obesity had an odds ratio of 3.61 (95% CI, 1.50–8.68; P = .004) for mortality, longer mean length of stay (11.2 versus 9.3 days, P Conclusions Morbid obesity is an independent risk factor of mortality in patients undergoing open AAA repair and AIF bypass. Weight loss strategies should be considered for morbidly obese patients with an anticipation of open abdominal aortic procedures.
Dialysis Dependence Is Associated With Significantly Increased Odds of Perioperative Adverse Events After Geriatric Hip Fracture Surgery Even After Controlling for Demographic Factors and Comorbidities.

Previous studies evaluating the risk of perioperative adverse events after hip fracture surgery for dialysis-dependent patients are either institutional cohort studies or limited by patient numbers. The current study uses the National Surgical Quality Improvement Program database's large national patient population and 30-day follow-up window to address these weaknesses. Methods National Surgical Quality Improvement Program databases (2006 to 2016) were queried for patients aged 60 years or older who underwent hip fracture surgery. Differences in 30-day outcomes based on preoperative dialysis dependence were compared using risk-adjusted logistic regression and coarsened exact matching for adverse events, need for revision surgery, readmission, and mortality. The proportion of adverse events that occurred before versus after discharge was also assessed. Results A total of 288 dialysis-dependent and 16,392 non-dialysis-dependent patients met the inclusion criteria. Matched populations controlling for demographic factors (ie, age, sex, body mass index, and functional status) and overall health (American Society of Anesthesiologists class) found dialysis-dependent patients to be associated with significantly greater odds of any adverse event (odds ratio [OR] = 1.90), major adverse event (OR = 1.77), and unplanned readmission (OR = 2.48). Increased odds of minor adverse event (OR = 1.05), return to the operating room (OR = 1.66), and death (OR = 1.42) within 30 postoperative days were also found but were not statistically significant. Discussion Even after controlling for demographics and health status, geriatric dialysis patients undergoing surgery for hip fracture are at significantly greater odds of adverse outcomes. Because of increased risks for geriatric dialysis patients undergoing surgery for hip fracture, surgical caution, patient counseling, and heightened surveillance must be observed throughout the perioperative period for this fragile population. Furthermore, hospitals and physicians must take the increased risks associated with dialysis into account when considering bundled payment reimbursement strategies and resource allocation for hip fracture care.
Testing the sediment fingerprinting technique using the SIAR model with artificial sediment mixtures

The accurate identification of primary sediment sources in a watershed is necessary to implement targeted management practices that will reduce erosion and restore water quality. Sediment fingerprinting is a commonly used tool to accomplish this task. However, the accuracy and precision of different procedures to select tracers for un-mixing sediment sources are still a largely uninvestigated area in relation to sediment fingerprinting. The goal of this research was to validate a sediment fingerprinting methodology by applying it to the Oostanaula Creek watershed in southeast Tennessee, USA. We assessed three method protocols (soil digestion procedure, objective source grouping, and tracer selection) that are utilized for assessing the performance of fingerprinting in terms of apportionment outputs. The major and trace elemental composition of sediment source and suspended sediment were determined by total dissolution and nitric acid extraction followed by analysis with inductively coupled plasma-optical emission spectrometry (ICP-OES). The Kruskal-Wallis (KW) test as well as stepwise discriminant function analysis (DFA) was utilized during tracer selection. The source un-mixing model utilized was a Bayesian mathematical model within Stable Isotope Analysis in R (SIAR). Sediment fingerprinting in the Oostanaula watershed proved to be difficult due to the chemical and mineralogical similarities of the potentially erodible source material. Upon analysis, it was found that the sediment tracers identified as those with low misclassification during cluster analysis would not guarantee a high degree of accuracy during source apportionment. However, there are certain outputs with low errors as compared with the real proportional contributions in artificial mixtures, for example, findings showed that bank erosion is a primary source of suspended sediment in the Oostanaula Creek. Source apportionment from sediment fingerprinting was sensitive to the digestion procedure, objective source groupings, and the tracer selection. Our research provides a quantitative approach for assessing the validity of the sediment fingerprinting technique.
Nest site selection by Loggerhead Shrike (Lanius ludovicianus) in a fragmented landscape

Understanding which factors influence nest site selection can lead to more effective species conservation. The Loggerhead Shrike (Lanius ludovicianus) has experienced severe declines since the 1940s and could potentially benefit from fine-scale management for nesting habitat, especially where fragmentation impedes conservation at the landscape scale. We examined how habitat characteristics at the nest tree and territory core scales influenced nest site selection by Loggerhead Shrikes in the coastal plain of South Carolina. We found 41 Loggerhead Shrike nests and measured habitat characteristics at the nest site and at available sites to model selection factors at the tree and territory core scales. Loggerhead Shrikes selected for low heterogeneity of vegetation density, high heterogeneity of vegetation height, and lower shrub and tree densities at the territory core scale. Loggerhead Shrikes also preferred nest trees with larger diameters at breast height. Overall, Loggerhead Shrikes appeared to select for nest site characteristics that enhanced foraging ease and success, and limited predation risk. We suggest that landowners in the southeastern coastal plain increase grassy habitat on their property and retain large trees in suitable nesting locations to increase optimal nesting habitat for Loggerhead Shrikes.
Data integration in high dimension with multiple quantiles

This article deals with the analysis of high dimensional data that come from multiple sources (experiments) and thus have different possibly correlated responses, but share the same set of predictors. The measurements of the predictors may be different across experiments. We introduce a new regression approach with multiple quantiles to select those predictors that affect any of the responses at any quantile level and estimate the nonzero parameters. Our estimator is a minimizer of a penalized objective function, which aggregates the data from the different experiments. We establish model selection consistency and asymptotic normality of the estimator. In addition we present an information criterion, which can also be used for consistent model selection. Simulations and two data applications illustrate the advantages of our method, which takes the group structure induced by the predictors across experiments and quantile levels into account.
Bariatric surgery works through a novel bile acid.

Bariatric surgery causes high rates of remission of type 2 diabetes; however, the mechanisms remain unresolved. A new study identifies cholic-acid-7-sulfate as a novel contributor to the metabolic benefits of bariatric surgery and an attractive target for treatment of type 2 diabetes.
25. WHAT'S THE EVIDENCE? EVALUATING THE IMPACT OF A RESIDENT EVIDENCE-BASED MEDICINE CURRICULUM

Background The ability to incorporate evidence-based medicine (EBM) into clinical practice is an ACGME competency, yet many pediatric residents have limited knowledge, comfort, and skill in this area. In addition, there is a lack of data regarding how residents apply EBM curricula to clinical practice. Objective: Describe the effect of an EBM curriculum on resident attitudes and clinical use of EBM. Methods We implemented a twice-weekly EBM curriculum to review key literature and guidelines. In this IRB-exempt mixed methods study, we surveyed residents, fellows, and faculty about use of EBM at baseline and 6 months later. Results were compared using Mann-Whitney U tests. We surveyed faculty twice weekly about residents’ EBM use on rounds. Residents participated in focus groups, which were audio-recorded, transcribed and coded using conventional content analysis to develop themes. Results Residents (N=61 pre- and 41 post-curriculum) reported increased: satisfaction with conferences (p=0.0037), importance of EBM (p = 0.0041), comfort generating a search question (p= 0.0001), and citation of evidence on rounds (p Conclusion As a result of this EBM curriculum, trainees described increased use of EBM in clinical practice and better understanding of research methodology. Additionally, resident use of EBM reinforced plans, taught faculty, and at times, changed management. Ongoing work is needed to create a culture that promotes EBM.
Perspective on Kramers symmetry breaking and restoration in relativistic electronic structure methods for open-shell systems

Without rigorous symmetry constraints, solutions to approximate electronic structure methods may artificially break symmetry. In the case of the relativistic electronic structure, if time-reversal symmetry is not enforced in calculations of molecules not subject to a magnetic field, it is possible to artificially break Kramers degeneracy in open shell systems. This leads to a description of excited states that may be qualitatively incorrect. Despite this, different electronic structure methods to incorporate correlation and excited states can partially restore Kramers degeneracy from a broken symmetry solution. For single-reference techniques, the inclusion of double and possibly triple excitations in the ground state provides much of the needed correction. Formally, however, this imbalanced treatment of the Kramers-paired spaces is a multi-reference problem, and so methods such as complete-active-space methods perform much better at recovering much of the correct symmetry by state averaging. Using multi-reference configuration interaction, any additional corrections can be obtained as the solution approaches the full configuration interaction limit. A recently proposed "Kramers contamination" value is also used to assess the magnitude of symmetry breaking.
Ambient daily pollen levels in association with asthma exacerbation among children in Philadelphia, Pennsylvania

Abstract Pollen from trees, grasses, and weeds can trigger asthma exacerbation in sensitized individuals. However, there are gaps in knowledge about the effects, such as the relative risks from different plant taxa and threshold levels of effect. We aimed to describe the local association between pollen and asthma exacerbation among children in the City of Philadelphia, and to evaluate whether effects are modified by children’s characteristics and clinical factors (e.g., child’s age, race/ethnicity, comorbidities). We conducted a time-stratified case-crossover study of pediatric (age
The impact of badminton lessons on health and wellness of young adults with intellectual disabilities: a pilot study

Background: Physical activity has been proposed as a context to foster the healthy development of individuals and reduce the risk of many chronic problems. This study evaluates the impact of badmin...
Cascade of interactions between candidate genes reveals convergent mechanisms in keratoconus disease pathogenesis.

Keratoconus is a progressive thinning, steepening and distortion of the cornea which can lead to loss of vision if left untreated. Keratoconus has a complex multifactorial etiology, with genetic an...
Comparing the fate of pristine and wastewater-aged gold nanoparticles in freshwater

The surface coatings applied to engineered nanomaterials (ENMs) during their manufacture have been shown to affect their aggregation behavior in aquatic media. This phenomenon has important implications on the environmental fate of ENMs and is often examined using ENMs in their ‘pristine’ form. However, the physiochemical properties of ENMs will be altered during their life cycle. Engineered systems, such as sewers and wastewater treatment plants, represent one pathway wherein ENMs can be transformed prior to their release. The focus of the current study was to compare the aggregation behavior of ‘pristine’ and ‘wastewater-aged’ ENMs in freshwater to provide insights into the impact of wastewater aging on ENM environmental fate. Gold nanoparticles (AuNPs) coated with polyethylene glycol (PEG), lipoic acid (COOH) and branched polyethylenimine (bPEI) were selected as model ENMs. The AuNPs were aged in filtered primary wastewater using a previously reported technique. The aged and pristine AuNPs were dosed into separate samples of raw and filtered freshwater and the loss of AuNPs from suspension by aggregation and sedimentation quantified using inductively coupled plasma mass spectrometry. Regardless of the initial surface coating, the AuNPs homoaggregated and acquired an organic matter corona while aging in the wastewater media. Following dispersion in the raw and filtered river water, the aged AuNPs were consistently lost from suspension. Greater loss was observed in the raw river water compared to the filtered river water, demonstrating that the aged AuNPs undergo heteroaggregation in addition to the homoaggregation that occurred during the aging process. This contrasts with the behavior of the pristine AuNPs, which were generally resistant to aggregation. These results indicate that while the physiochemical properties of the pristine AuNPs largely prevent their aggregation and subsequent sedimentation in the river water, the stabilizing effects of the engineered surface coatings examined in this study are lost after aging in wastewater. This demonstrates the importance of explicitly accounting for ENM transformations when designing experiments and selecting materials intended to elucidate the factors impacting ENM environmental fate.
Factors predictive of hospice care in patients with Ischemic stroke (P1.077)

OBJECTIVE: Hospice is an option in providing terminally ill ischemic stroke patients with good quality of life and end of life care. We sought to examine factors associated with likelihood of discharge to hospice when faced with such circumstances. DESIGN/METHODS: This was a retrospective chart review utilizing de-identified data from our Get With The Guidelines database. Data from patients admitted at the University of Kentucky Medical Center with the diagnosis of ischemic stroke that died during the period starting from July 1, 2012 to June 30, 2014 was reviewed. RESULTS: 149 patients (68 male, 81 female) with ischemic stroke died during the study period. 81 (54[percnt]) of these and/or their families chose hospice. 60[percnt] (50/83) of women were transferred to hospice compared to 47[percnt] (31/66) of men. Based on age, 18[percnt] (2/11) of patients aged less than 50 years, 39[percnt] (15/38) of patients between ages 50 to 70 years, and 64[percnt] (64/100) older than 70 years chose hospice. 88[percnt] (8/9) of patients with mild stroke (NIHSS 20) went to hospice. Only 37[percnt] (12/32) patients who received IV t-PA and none of the patients who underwent mechanical thrombectomy went to hospice. Of patients transferred to hospice, 70[percnt] of patients had prior strokes, 66[percnt] had atrial fibrillation, 60[percnt] had hypertension, 58[percnt] had coronary disease, 55[percnt] had diabetes and 60[percnt] had underlying hyperlipidemia. 65[percnt] of patients were on anti-platelets prior to hospice discharge, while 61[percnt] were on anticoagulation, and 62[percnt] on statins. CONCLUSIONS: In our patient population, factors associated with hospice discharge were female gender, age > 70 years, prior stroke and not receiving thrombolysis and/ or intervention. Severity of deficits (NIHSS) was not a reliable marker. Study Supported by: Disclosure: Dr. Sultan has nothing to disclose. Dr. Lee has nothing to disclose.
Fundamentals of Neutron Diffraction

The purpose of this article is to describe the differences between neutron diffraction and X-ray diffraction, and to give specific examples of how these differences have been exploited in the study of biological structures. Those who wish a comprehensive treatment of this topic can turn to a number of reviews and symposium volumes that deal with the application of neutron scattering to biological problems (Schoenborn and Nunes, 1972; Engelman and Moore, 1975; Jacrot, 1976; Kneale et al., 1977; Moore, 1982; Schoenborn, 1984).
Randomized controlled trials are needed to determine appropriate blood transfusion strategies in patients with acute coronary syndromes

Setting and Patients: 24,112 patients from three large international trials of patients with acute coronary syndromes (the GUSTO IIb, PURSUIT, and PARAGON B trials). Patients were grouped according to whether they received a blood transfusion during the hospitalization. The association between transfusion and outcome was assessed using Cox proportional hazards modeling that incorporated transfusion as a time-dependent covariate and the propensity to receive blood, and a landmark analysis. Outcomes: The primary outcome was 30-day all-cause mortality, with a secondary composite endpoint of 30-day mortality or myocardial infarction (MI).
Modeling the user in natural language systems

For intelligent interactive systems to communicate with humans in a natural manner, they must have knowledge about the system users. This paper explores the role of user modeling in such systems. It begins with a characterization of what a user model is and how it can be used. The types of information that a user model may be required to keep about a user are then identified and discussed. User models themselves can vary greatly depending on the requirements of the situation and the implementation, so several dimensions along which they can be classified are presented. Since acquiring the knowledge for a user model is a fundamental problem in user modeling, a section is devoted to this topic. Next, the benefits and costs of implementing a user modeling component for a system are weighed in light of several aspects of the interaction requirements that may be imposed by the system. Finally, the current state of research in user modeling is summarized, and future research topics that must be addressed in order to achieve powerful, general user modeling systems are assessed.
Configuration-space continuum calculations

While considerable progress has been made in the numerical methods for the configuration-space scattering problem, there remains a considerable amount of work to do before the calculations have the accuracy which has been achieved for the bound-state calculations. However, several groups are actively working on this problem, and realistic numerical calculations should become more available in the next few years.
Terror Management and Civic Engagement

Stories of death flood the media, making mortality a salient theme in American news. Research shows that subconscious reminders of death influence a range of behaviors associated with charitable giving and a bolstered sense of patriotism (Burke, Martens, & Faucher, 2010, Personality & Social Psychology Review, 14, 155–195). Terror management theory (TMT) explains this relationship by positing that subconscious mortality salience motivates individuals to embrace their cultural worldviews (e.g., engaging in volunteerism or politically oriented activities). Moreover, collectivistic, relative to individualistic, self-construals motivate individuals to serve others and meet group needs. In a first-known attempt to understand the relationship between TMT, self-construals, and civic engagement, a 2 (mortality salience: high or low) × 2 (self-construal: individualistic or collectivistic) experiment (N = 124) revealed that counter to common findings, increased mortality salience was negatively related to civic eng...
Use of DSOM before/after metaclass for enabling object access control

We review the IBM's System Object Model (SOM) and Distributed SOM (DSOM). Then, we introduce DSOM's approach to object access control and contrast it with traditional procedural systems. Subsequently, we elaborate on the problem addressed in this paper that seeks to enable the process of object access control within DSOM kernel transparently from application developers. We discuss different approaches to solving the problem and present the adopted method. We provide implementation details of the solution and conclude with remarks on future improvement.
The Mechanism of Precipitation Formation in Northeastern Colorado Cumulus I. Observations of the Precipitation Itself

Abstract The structure of ice precipitation in northeastern Colorado, collected within summer cumulus clouds and at the ground beneath thunderstorms, shows that the dominant precipitation formation mechanism is the riming of small ice particles, not liquid coalescence. While direct evidence of a stage involving the vapor growth of ice crystals is rare, such a stage is probably present in most cases.
Neonatal dexamethasone treatment leads to alterations in cell signaling cascades controlling hepatic and cardiac function in adulthood

Increasing evidence indicates that early-life glucocorticoid exposure, either involving stress or the therapy of preterm labor, contributes to metabolic and cardiovascular disorders in adulthood. We investigated cellular mechanisms underlying these effects by administering dexamethasone (DEX) to neonatal rats on postnatal (PN) days 1-3 or 7-9, using doses spanning the threshold for somatic growth impairment: 0.05, 0.2 and 0.8 mg/kg. In adulthood, we assessed the effects on hepatic and cardiac cell function mediated through the adenylyl cyclase (AC) signaling cascade, which controls neuronal and hormonal inputs that regulate hepatic glucose metabolism and cardiac contractility. Treatment on PN1-3 produced heterologous sensitization of hepatic signaling, with upregulation of AC itself leading to parallel increases in the responses to beta-adrenergic or glucagon receptor stimulation, or to activation of G-proteins by fluoride. The effects were seen at the lowest dose but increasing DEX past the point of somatic growth impairment led to loss of the effect in females. Nonmonotonic effects were also present in the heart, where males showed AC sensitization at the lowest dose, with decreasing effects as the dose was raised; females showed progressive deficits of cardiac AC activity. Shifting the exposure to PN7-9 still elicited AC sensitization but with a greater offsetting contribution at the higher doses. Our findings show that, in contrast to growth restriction, the glucocorticoids associated with stress or the therapy of preterm labor are more sensitive and more important contributors to the cellular abnormalities underlying subsequent metabolic and cardiovascular dysfunction.
Collagen attachment to the substrate controls cell clustering through migration

Cell clustering and scattering play important roles in cancer progression and tissue engineering. While the extracellular matrix (ECM) is known to control cell clustering, much of the quantitative work has focused on the analysis of clustering between cells with strong cell–cell junctions. Much less is known about how the ECM regulates cells with weak cell–cell contact. Clustering characteristics were quantified in rat adenocarcinoma cells, which form clusters on physically adsorbed collagen substrates, but not on covalently attached collagen substrates. Covalently attaching collagen inhibited desorption of collagen from the surface. While changes in proliferation rate could not explain differences seen in the clustering, changes in cell motility could. Cells plated under conditions that resulted in more clustering had a lower persistence time and slower migration rate than those under conditions that resulted in less clustering. Understanding how the ECM regulates clustering will not only impact the fundamental understanding of cancer progression, but also will guide the design of tissue engineered constructs that allow for the clustering or dissemination of cells throughout the construct.
A new heterocyclic system: Imidazo[2,1‐d][1,5]benzothiazepine. Its synthesis from 4‐amino‐2,3‐dihydro‐1,5‐benzothiazepine

The synthesis of 4-amino-2,3-dihydro-1,5-benzothiazepine and its transformation to the new heterocycle Imidazo[2,1-d][1,5]benzothiazepine is described.
The Experience of Experience

This article describes the process of implementing a museum experience into the course content of a literacy methods course. A museum workshop was designed to help graduate students better understand the concept of literacy as a language-based learning process that builds on and extends each child's understanding of the world. Framed by relevant readings, instruction and assignments, the experience appears to support participants' ability to articulate, implement, and advocate for early childhood practice that is both developmentally and linguistically appropriate and culturally relevant.
Effects of chronic administration of nicotine on drug-induced hypnosis in mice.

Chronic administration of nicotine in mice for six weeks did not affect the duration of hypnosis induced by pentobarbital, hexobarbital, barbital or zoxazolamine. The onset of barbital hypnosis remained unaffected. These results suggest that chronic administration of nicotine did not affect the drug metabolizing activity of hepatic microsomes. While psychotropic drugs significantly potentiated the hypnosis due to pentobarbital and hexobarbital, the degree of potentiation was the same in both chronically nicotine pretreated mice and controls. Nicotine pre-treatment significantly increased the duration of sleeping time caused by ethanol alone. However, when treatment of nicotine continued for a longer period of time, the duration of hypnosis induced by ethanol returned to control level.
Effect of the inhomogeneity of ice crystals on retrieving ice cloud optical thickness and effective particle size

Spherical or spheroidal air bubbles are generally trapped in the formation of rapidly growing ice crystals. In this study the single-scattering properties of inhomogeneous ice crystals containing air bubbles are investigated. Specifically, a computational model based on an improved geometric-optics method (IGOM) has been developed to simulate the scattering of light by randomly oriented hexagonal ice crystals containing spherical or spheroidal air bubbles. A combination of the ray-tracing technique and the Monte Carlo method is used. The effect of the air bubbles within ice crystals is to smooth the phase functions, diminish the 22deg and 46deg halo peaks, and substantially reduce the backscatter relative to bubble-free particles. These features vary with the number, sizes, locations and shapes of the air bubbles within ice crystals. Moreover, the asymmetry factors of inhomogeneous ice crystals decrease as the volume of air bubbles increases. Cloud reflectance lookup tables were generated at wavelengths 0.65 m and 2.13 m with different air-bubble conditions to examine the impact of the bubbles on retrieving ice cloud optical thickness and effective particle size. The reflectances simulated for inhomogeneous ice crystals are slightly larger than those computed for homogenous ice crystals at a wavelength of 0.65 microns. Thus, the retrieved cloud optical thicknesses are reduced by employing inhomogeneous ice cloud models. At a wavelength of 2.13 microns, including air bubbles in ice cloud models may also increase the reflectance. This effect implies that the retrieved effective particle sizes for inhomogeneous ice crystals are larger than those retrieved for homogeneous ice crystals, particularly, in the case of large air bubbles.
Experiences of Pioneer Nurse Practitioners in Establishing Advanced Practice Roles

Purpose: To describe pioneers' experience of establishing the nurse practitioner (NP) role, and their experiences in maintaining and building the NP role in the contemporary practice environment. Design: The study sample included 50 middle-aged women currently practicing in Washington State as licensed advanced practice nurses, who began the NP role during 1965–1979. Methods: This descriptive study included interviews and focus groups to gather data about the nurses' early experiences. Interpretative methods of grounded theory were used in data collection and analysis. Findings: The central organizing theme, Advancing Autonomy to Make a Difference, was manifested through six broad themes: Breaking Free, Molding the Clay, Encountering Obstacles, Surviving the Proving Ground, Staying Committed, and Building the Eldership. Conclusions: Autonomy was requisite to practice to one's full potential and maintain commitment over time. The data findings show the evolution of advanced nursing practice in the United States and provide guidance for nurses who are working to establish advanced practice nursing in other countries.
Quantitative analysis of the probability of intracellular ice formation during freezing of isolated protoplasts.

Abstract 1. (i) A quantitative prediction of the temperature and cooling-rate dependence of IIF requires information on the probability distribution for IIF temperature; the supercooling tolerance; and membrane permeability, initial cell size, Boyle-van't Hoff relation, and other parameters associated with the thermodynamic description of cell volumetric behavior. 2. (ii) A probabilistic analysis of IIF was developed on the basis that IIF occurs if the underlying potential IIF temperature T ∗ falls within the range of temperatures over which the cell is supercooled beyond its tolerance ΔT ∗ . The “location” of the transition range of cooling rates, in which the Pr{IIF} increases from 0 to 1, depends on the mean of T ∗ and ΔT ∗ . The breadth of the transition range increases strongly with variability in T ∗ . 3. (iii) Cryomicroscopic studies of IIF in rye protoplasts isolated from cold acclimated and nonacclimated leaves showed that the range of IIF temperatures and the incidence of IIF are strongly dependent on the solute used to manipulate osmolality in the suspending medium. The ionic solutes used in this study (NaCl + CaCl 2 , KCl + CaCl 2 , KNO 3 + CaCl 2 ) generally yielded median IIF temperatures lower than those of the nonionic solutes (sucrose, sorbitol, proline). Cold acclimation reduced the median IIF temperature for all suspending media and reduced the incidence of IIF for KCl + CaCl 2 , sorbitol, and proline. A Weibull distribution was found to describe adequately the distribution of IIF temperatures at the highest cooling rate. 4. (iv) Estimates of the supercooling tolerance were generally from 1.0 to 1.5 °C based on the location of the transition range of cooling rates and on the estimates of L p and ΔE from (6). The breadth of the transition range of cooling rates could mostly be attributed to random variability in the underlying potential IIF temperature. The rise in median IIF temperature with higher cooling rates was correctly predicted by the model when the supercooling tolerance was also assumed to be random. For rye protoplasts, both the model and the data showed that cooling-rate dependence in median IIF temperatures occurs within the transition range of cooling rates.
Anselm on praising a necessarily perfect being

Pour Anselme de Canterbury, Dieu est necessairement parfait et totalement bon. Il refuse la conception qui voudrait que la bonte de Dieu consiste a satisfaire des devoirs moraux et que la liberte de Dieu consiste a choisir entre differentes options. Dieu est par consequent le plus louable des etres. Le probleme pose est celui de nombreux philosophes qui voient un paradoxe dans le fait de glorifier un etre necessairement et parfaitement bon
Fast neutron irradiation damage on room temperature PbS detectors

The effects of high-energy neutron irradiation on the photoconductive properties of chemically-deposited PbS infrared detectors have been investigated in the I011 n/cm2 to 1014 n/cm2 fluence range. Long term degradation in signal response has been observed subsequent to room temperature irradiation of 2×1012 n/cm2 or greater fluetices. Seventy-five percent of the degradation can be attributed to a reduction in majority carrier lifetime, and the most likely source for the additional 25% reduction in the photoconductivity is the quantum efficiency. However, the degradation is not permanent. The recovery proceeds logarithmically with time. The dark resistance was unaffected by the irradiation. Additionally, if the detector views a visible light source simultaneously with the neutron irradiation, a significant increase in signal degradation rate is found.
Modeling of Tritium Retention in TFTR

The Tokamak Fusion Test Reactor (TFTR) tritium retention experience is reviewed and the data related to models of plasma surface interactions. Over 3.5 years of TFTR deuterium-tritium operations, approximately 51% of the tritium injected into TFTR was retained in the torus. Most of this was subsequently recovered by glow discharges and air ventilation. Co-deposition rates for representative conditions in tritium operation were modeled with the BBQ code. The calculations indicate that known erosion mechanisms and subsequent co-deposition are sufficient to account for the order of magnitude of retention.
You're going to need a bigger (glass bottom) boat.

Signaling molecules of the transforming growth factor (TGF)–β family are generated from proprotein precursors containing prodomain sequences that are typically removed to allow signaling by the mature ligands. A form of a TGF-β family ligand that remains covalently attached to its prodomain but retains signaling activity has been identified. Glass bottom boat (Gbb), a Drosophila homolog of the bone morphogenetic protein 5/6/7/8 subfamily, is active as a carboxyl-terminal fragment of the proprotein (Gbb15) that is generated by a conventional processing event common to TGF-β ligands. Unexpectedly, a larger form (Gbb38) produced by processing at a newly identified furin site in the prodomain is also secreted and active. Contrary to the present paradigm in which TGF-β ligands require dissociation of the entire prodomain for activity, Gbb38 is active in cell culture and in vivo without additional processing at conventional sites. The large form can restore the viability of gbb mutant animals but has distinct signaling properties compared with the conventional form. Production of multiple functional ligands from one proprotein is a potential mechanism to fine-tune TGF-β signaling outputs. Mutations in TGF-β family members have been linked to human diseases, several of which affect potential furin cleavage sites in prodomains. However, given the diversity of potential furin processing sites and prodomain functions, direct experimentation will be required to determine whether production of active jumbo ligands is a general feature of TGF-β superfamily members.