cssi/SciSciGPT-SciSciNet huggingface dataset:
On the execution of the young giraffe, Marius, by the Copenhagen Zoo: Conquergood’s “Lethal Theatre” and posthumanism

ABSTRACTThe author uses the work of Dwight Conquergood and posthumanist analysis to frame the killing of the young giraffe, Marius, by the Copenhagen Zoo as an execution. In doing so, he deploys the work of Irus Braverman to demonstrate the imbrication of humans, animal others, and technology in discourses of management of biopower and breeding value to pose the queer observation that it is none of our obligation to breed in captivity.
Evidence that a mitochondrial death spiral underlies antagonistic pleiotropy

The antagonistic pleiotropy (AP) theory posits that aging occurs because alleles that are detrimental in older organisms are beneficial to growth early in life and thus are maintained in populations. Although genes of the insulin signaling pathway likely participate in AP, the insulin-regulated cellular correlates of AP have not been identified. The mitochondrial quality control process called mitochondrial autophagy (mitophagy), which is inhibited by insulin signaling, might represent a cellular correlate of AP. In this view, rapidly growing cells are limited by ATP production; these cells thus actively inhibit mitophagy to maximize mitochondrial ATP production and compete successfully for scarce nutrients. This process maximizes early growth and reproduction, but by permitting the persistence of damaged mitochondria with mitochondrial DNA mutations, becomes detrimental in the longer term. I suggest that as mitochondrial ATP output drops, cells respond by further inhibiting mitophagy, leading to a further decrease in ATP output in a classic death spiral. I suggest that this increasing ATP deficit is communicated by progressive increases in mitochondrial ROS generation, which signals inhibition of mitophagy via ROS-dependent activation of insulin signaling. This hypothesis clarifies a role for ROS in aging, explains why insulin signaling inhibits autophagy, and why cells become progressively more oxidized during aging with increased levels of insulin signaling and decreased levels of autophagy. I suggest that the mitochondrial death spiral is not an error in cell physiology but rather a rational approach to the problem of enabling successful growth and reproduction in a competitive world of scarce nutrients.
Freezing for control of stored-product psocids

Abstract A series of studies was conducted by exposing young and old eggs, nymphs, and adults of the psocids Liposcelis bostrychophila (Badonnel), L. paeta (Pearman), L. decolor (Pearman), and L. entomophila (Enderlein) to −18 °C for various time intervals. Survival was assessed as initial and final, at different times depending on the life stage. Young eggs of L. bostrychophila were the most tolerant life stage of any of the species, with scattered survival out to 120 h of exposure to −18 °C. Eggs were the most tolerant life stage for each species, requiring 24, 12, and 2 h of exposure for complete kill of L. paeta, L. decolor, and L. entomophila, respectively. Nymphs and adults of all species were far more susceptible than eggs, with no final survival after two hours of exposure. Results show the extreme variation between different psocid life stages and species to cold temperatures, and provide guidelines for using cold as a control strategy for psocids. Our results show that 24 h at −18 °C is sufficient to kill all life stages of the psocid species tested, except for young L. bostrychophila eggs which will require at least 128 h of exposure at −18 °C for complete mortality.
Amygdala functional connectivity is associated with locus of control in the context of cognitive aging.

Abstract Locus of control (LOC) measures the extent to which individuals perceive control over their lives. Those with a more “internal” LOC feel self-sufficient and able to determine important aspects of their own future, while those with a more “external” LOC feel that their lives are governed by events beyond their control. Reduced internal LOC and increased external LOC have been found in cognitive disorders, but the neural substrates of these control perceptions are yet unknown. In the present study, we explored the relationship between amygdala functional connectivity and LOC in 18 amnestic mild cognitive impairment (MCI) and age-, sex-, and education-matched, 22 cognitively healthy controls (HC). Participants completed cognitive challenge tasks (Stroop Word Color task and Dual 1-back) for 20 min, and underwent resting-state functional magnetic resonance imaging immediately before and after the tasks. We found significantly lower internal LOC and higher external LOC in the MCI group than the HC group. Compared to HC, MCI group showed significantly stronger positive associations between internal LOC and baseline right amygdala connections (including right middle frontal gyrus and anterior cingulate cortex), and stronger negative associations between internal LOC and change of these right amygdala connections. Across all participants, external LOC explained the relationships between associations of another set of right amygdala connections (including middle cingulate cortex and right superior frontal gyrus), both at baseline and for change, and performance in the cognitive challenge tasks. Our findings indicate that the right amygdala networks might be critical in understanding the neural mechanisms underlying LOC's role in cognitive aging.
Linguistic Diversity and Education

It is almost unthinkable for new students of language and education that barely half a century ago, the official wisdom, based on then cutting-edge research, considered multilingualism bad for individuals and society. Today, the far-reaching benefits of linguistic diversity has become so well established in scholarly circles that language planning stakeholders have, gradually but assuredly, shifted from research to policy advocacy and grassroots multilingual education (MLE) programming.
Effects of short- and long-course antibiotics on the lower intestinal microbiome as they relate to traveller's diarrhea.

Background Antibiotics have profound and lasting effects on the lower intestinal (gut) microbiome that can both promote resistance and increase susceptibility to colonization and infection; knowledge of these changes is important to the prevention and treatment of traveler's diarrhea. Methods Recent data from epidemiologic and modern metagenomics studies were reviewed in regard to how such findings could inform the prevention and treatment of traveler's diarrhea. Results Although it is well recognized that antibiotics increase the risk for Clostridium difficile infection, it is less recognized how they predispose patients to typically foodborne pathogens such as Salmonella or Camplyobacter spp. While these pathogens account for only a fraction of traveler's diarrhea, such predisposition reflects how antibiotic exposure that precedes or occurs during travel may increase the risk for infection with other more common pathogens, even possibly enterotoxigenic Eschericia coli, especially in the setting of acquired resistance. Even short antibiotic exposures disrupt the gut microbiome up to a year or more and repeated exposures appear to attenuate recovery from ever occurring. One bacterial phylum that commonly increases in the gut following antibiotics are the proteobacteria including Enterobacteriacea; these are pro-inflammatory and often carry antibiotic resistance genes, the number and diversity of these genes (i.e. the resistome) commonly expands following antibiotics. The gut resistome among healthy community-dwelling adults reflects geographic variability in antibiotic use practices in both humans and food-producing animals as well as possibly the transmission of antibiotic resistance genes through the food supply. Conclusions Because antibiotic use among travelers will influence the resistome and thereby promote geographic spread of resistance, it is important that antibiotic use recommendations for travelers be guided by resistance surveillance data as well as a careful assessment of the risks and benefits to both the individual and society.
Clinical Mimics: An Emergency Medicine-Focused Review of Streptococcal Pharyngitis Mimics.

Abstract Background Pharyngitis is a common disease in the emergency department (ED). Despite a relatively low incidence of complications, there are many dangerous conditions that can mimic this disease and are essential for the emergency physician to consider. Objective This article provides a review of the evaluation and management of group A β-hemolytic Streptococcal (GABHS) pharyngitis, as well as important medical conditions that can mimic this disease. Discussion GABHS pharyngitis often presents with fever, sore throat, tonsillar exudates, and anterior cervical lymphadenopathy. History and physical examination are insufficient for the diagnosis. The Centor criteria or McIsaac score can help risk stratify patients for subsequent testing or treatment. Antibiotics may reduce symptom duration and suppurative complications, but the effect is small. Rheumatic fever is uncommon in developed countries, and shared decision making is recommended if antibiotics are used for this indication. Oral analgesics and topical anesthetics are important for symptom management. Physicians should consider alternate diagnoses that may mimic GABHS pharyngitis, which can include epiglottitis, infectious mononucleosis, Kawasaki disease, acute retroviral syndrome, Lemierre's syndrome, Ludwig's angina, peritonsillar abscess, retropharyngeal abscess, and viral pharyngitis. A focused history and physical examination can help differentiate these conditions. Conclusions GABHS may present similarly to other benign and potentially deadly diseases. Diagnosis and treatment of pharyngitis should be based on clinical evaluation. Consideration of pharyngitis mimics is important in the evaluation and management of ED patients.
Organization of Cholinergic Perikarya in the Caudate Nucleus of the Cat with Respect to Heterogeneities in Enkephalin and Substance P Staining

We present here a series of studies examining the organization of cholinergic perikarya in the caudate nucleus of the cat and their relationship to heterogeneities observed in enkephalin and substance P staining. Cholinergic interneurons comprise only a small proportion of the total number of striatal cells (Phelps et al., 1985). Most studies have not reported any obvious organization in the distribution of these cells in single sections (Fibiger, 1982) although some authors have commented that they did not appear to be evenly distributed but were organized into poorly defined clusters (Everitt et al., 1988; Mesulam et al., 1984). In addition, no consistent relationship has been demonstrated between the cholinergic perikarya and the striosomal compartment as delineated by acetylcholinesterase. While cholinergic neuropil and the high affinity choline uptake system are distributed primarily within the matrix (Graybiel et al., 1986; Rhodes et al., 1987), cholinergic cell bodies have been reported to occur both within patch and matrix in equal densities (Brand, 1980) or to be slightly increased in density within the matrix compartment (Graybiel et al., 1983, 1986).
Structure-Function Studies on PEDF

Pigment epithelium-derived factor (PEDF) is a neurotrophic factor. In vitro it induces neuronal differentiation of retinoblastoma cells and promotes survival of cerebellar granule cell neurons. By virtue of amino acid sequence homology PEDF is a unique serpin member.
Inflammatory fibroid polyp (hemangiopericytoma) of the stomach; report of a case.

A case of an unusual type of gastric polyp has been reported to help illuminate the problem of pathogenesis of these lesions. The reasons for believing they are inflammatory rather than neoplastic in nature has been discussed.
Behavioral Emergencies for the Emergency Physician

Emergency physicians, in all practice settings, care for patients with both undifferentiated psycho-behavioral presentations and established psychiatric illness. This reference-based text goes beyond diagnostics, providing practical input from physicians experienced with adult emergency psychiatric patients. Physicians will increase their understanding and gain confidence working with these patients, even when specialized psychiatric back-up is lacking. Behavioral Emergencies for the Emergency Physician is comprehensive, covering the pre-hospital setting and advising on evidence-based practice; from collaborating with psychiatric colleagues to establishing a psychiatric service in your ED. Sedation, restraint and seclusion are outlined. Potential dilemmas when treating pregnant, geriatric or homeless patients with mental illness are discussed in detail, along with the more challenging behavioral diagnoses such as malingering, factitious and personality disorders. This go-to, comprehensive volume is invaluable for trainee and experienced emergency physicians, as well as psychiatrists, psychologists, psychiatric and emergency department nurses and other mental health workers.
Effects of perturbing a reference atmosphere on sonic boom propagation and metrics

There is substantial interest in the accurate noise prediction that ranges from sonic boom noise from conventional supersonic aircraft to low-boom noise (a sonic thump sound) from future aircraft designed for quiet flight. A carefully designed reference atmosphere was developed for comparing multiple sonic boom propagation programs. In the current work, that reference atmosphere was perturbed in a number of ways to assess the importance of each perturbation. The code PCBoom was used for this study, and the perturbations were for the temperature, humidity, and wind profiles. One result is that in the absence of winds, perturbing the temperature profile does not substantially affect the metrics on the ground, but perturbing the humidity profile does. [Work supported by the U.S. Federal Aviation Administration Office of Environment and Energy through ASCENT, the FAA Center of Excellence for Alternative Jet Fuels and the Environment, Project 41 through FAA Award No. 13-C-AJFE-PSU under the supervision of Sandy Liu. Any opinions, findings, conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the FAA.]
Conserving novel ecosystems and layered landscapes along the inter-German border

For forty years, Germany was cut in two, its internal border a legacy of the Second World War and ground zero of the Cold War. But the border region, shaped for decades by demographic and economic decline, became an ecological refuge for many of Germany’s endangered plant and animal species. When the wall fell in 1989, conservationists launched an effort to protect the former borderlands and convert them into an ecological corridor called the Green Belt. This paper explores the novel ecosystems along the Green Belt: one a restoration and rewilding project, the other aimed at maintaining the imprint of the Cold War landscape. It shows how conservation of novel ecosystems in Germany and beyond requires a long-range approach that emphasizes opportunism, multifunctionality, experimentation, a flexible interpretation of historical fidelity, and respect for both emergent ecosystems and the deep layers of human history and memory.
Implications of Early Decline in eGFR due to Intensive BP Control for Cardiovascular Outcomes in SPRINT.

BACKGROUND The Systolic BP Intervention Trial (SPRINT) found that intensive versus standard systolic BP control (targeting <120 or <140 mm Hg, respectively) reduced the risks of death and major cardiovascular events in persons with elevated cardiovascular disease risk. However, the intensive intervention was associated with an early decline in eGFR, and the clinical implications of this early decline are unclear. METHODS In a post hoc analysis of SPRINT, we defined change in eGFR as the percentage change in eGFR at 6 months compared with baseline. We performed causal mediation analyses to separate the overall effects of the randomized systolic BP intervention on the SPRINT primary cardiovascular composite and all-cause mortality into indirect effects (mediated by percentage change in eGFR) and direct effects (mediated through pathways other than percentage change in eGFR). RESULTS About 10.3% of the 4270 participants in the intensive group had a ≥20% eGFR decline versus 4.4% of the 4256 participants in the standard arm (P<0.001). After the 6-month visit, there were 591 cardiovascular composite events during 27,849 person-years of follow-up. The hazard ratios for total effect, direct effect, and indirect effect of the intervention on the cardiovascular composite were 0.67 (95% confidence interval [95% CI], 0.56 to 0.78), 0.68 (95% CI, 0.57 to 0.79), and 0.99 (95% CI, 0.95 to 1.03), respectively. All-cause mortality results were similar. CONCLUSIONS Although intensive systolic BP lowering resulted in greater early decline in eGFR, there was no evidence that the reduction in eGFR owing to intensive systolic BP lowering attenuated the beneficial effects of this intervention on cardiovascular events or all-cause mortality.
Autoimmune hepatitis in patients with human immunodeficiency virus infection: A systematic review of the published literature.

AbstractBackground:Liver disease in patients with HIV is common and typically has complex and multifactorial presentations that represent a major cause of morbidity and mortality. Autoimmune hepatitis (AIH) is rarely reported in patient with HIV and the disease course and clinical outcomes for treat
Effects of velocity second slip model and induced magnetic field on peristaltic transport of non-Newtonian fluid in the presence of double-diffusivity convection in nanofluids

The significance of velocity second slip model of non-Newtonian fluid on peristaltic pumping in existence of double-diffusivity convection in nanofluids and induced magnetic field is deliberated. Mathematical modelling of current problem is defined in fixed frame of reference and then abridges under well- known conjecture of long wavelength and low but finite Reynolds number approximation. Precise results of coupled nonlinear partial differential equations are presented. Graphical results exhibit the performance of various supportive parameters. The phenomenon of stream functions with different wave forms is also discussed in detail. The effects of thermal energy, solute concentration, and nanoparticle fraction are also described using graphical representation.
Cardiac Biomarkers and Subsequent Risk of Hospitalization With Bleeding in the Community: Atherosclerosis Risk in Communities Study

Background hs‐cTnT (high‐sensitivity cardiac troponin T), but not NT‐proBNP (N‐terminal pro–B natriuretic peptide), has been shown to predict bleeding in patients with atrial fibrillation. Whether ...
Resistance to sliding of orthodontic archwires under increasing applied moments

Background:Orthodontic treatment with fixed appliances involves sliding of brackets along archwires. These movements involve friction, which causes resistance to sliding. In addition, moments cause...
Charting Sequential Person Transfers Between Devices, Agents, and Robots

In the not-so-distant future, people in service experiences are likely to interact with more than a single intelligent system, often sequentially, including different robots and devices. However, there has been sparse work exploring the characteristics of transferring people from one intelligent system to another. This paper aims to create a context-independent taxonomy to differentiate and categorize the transfer of users across robots, devices, and human staff in service interactions. We conducted two sets of design workshops where participants generated scenarios of human-multi-robot interactions and existing person transfers. Using the outcomes of both workshops, we analyzed scenarios and constructed a taxonomy for person transfers with 4-dimensions: Rationale, Type, Design, and Information Shared. We showcase different ways to utilize the taxonomy, and, through it, we discuss the trade-offs and design considerations in the implementation of person transfers.
The Learning Experience of Becoming a FPV Drone Pilot

An immersive drone-flying modality known as First-Person View (FPV) flying is increasing in popularity. Nonetheless, due to its recency, there is a lack of research focusing on FPV drones. Specifically, the journey FPV pilots go through when learning how to fly was not studied yet. Understanding their learning experience allows the development of FPV drones with a gentle learning curve for the pilots. We conducted an online survey with 515 FPV pilots to evaluate how they learned to fly, and how they recommend beginners to learn. We found that most pilots learned using a stabilized flight mode, but the majority of them later switched to an acrobatic (non-stabilized) flight mode. Although only half of the surveyed pilots used flight simulators to learn, 90% of all pilots recommend beginners to use simulators. Our results allow further understanding of the emerging FPV pilot's culture and composition of research questions for future studies.
A new kinematic criterion for vortex ring pinch-off

This study lays out a methodology whereby conditions necessary for a vortex ring to separate from the shear flow can be identified by a relationship between characteristic velocities of the jet and the vortex ring along the axis of symmetry. This criterion identifies pinch-off to take place when the velocity induced at the origin of the forming vortex ring surpasses the maximum feeding velocity along the centerline, defined to be twice the piston velocity. A strategy for determining these characteristic velocities purely from the jet driving programs (i.e., without direct knowledge of the state of the leading vortex ring) is presented. A variety of jet driving conditions, including different nozzle geometries (converging radial velocity) and different jet velocity programs, are examined to validate the relationship between pinch-off and the characteristic velocities. These parameters are examined and adjusted independently of each other so that the effect of each jetting parameter can be observed independently. Nozzles which induce a converging radial velocity decrease the jet formation number to approximately two (for nearly constant velocity programs), due to the large increase in vorticity flux without increasing volume flux. Accelerating the jet velocity to compensate for the growing vortex ring substantially increases the formation number of both parallel and converging jet flows. The new centerline velocity criterion coincided very closely with vortex ring pinch-off for all cases tested, validating this criterion as a predictive tool.
Tenacity is Instinctual

This chapter sets the foundation of seven instincts, which is that our genes play a significant role in shaping who we are and who we become. The process of developing into adulthood is dependent not only on our genes, but also on our environment, experiences, and opportunities to acquire knowledge and enact it. The longer it takes for our young to progress into adulthood, then the more important experience becomes in shaping how our genes express themselves. In genetics, this concept is multi-finality—similar genes may lead to different outcomes based upon an organism’s experiences. Instincts are genetically endowed and shape our developmental path from childhood into adulthood. The seven instincts of Tenacity are: Intuitive Optimism, >Intrinsic Motivation, Compassionate Empathy, Simultaneous Intelligence, Genuine Altruism, Virtuous Responsibility, and Measured Fairness. Parents who gain an understanding of these genetically driven instincts and the ways in which they can reinforce these instincts will help their children acquire self-discipline and resilient mindsets to persist in the face of adversity and failure. While the path to adulthood is shaped by numerous factors including a child’s temperament, family values, educational and social experiences, and broader cultural values, the power of understanding the seven instincts is that they are universal.
Kdm6b confers Tfdp1 with the competence to activate p53 signalling in regulating palatogenesis

Epigenetic regulation plays extensive roles in diseases and development. Disruption of epigenetic regulation not only increases the risk of cancer, but can also cause various developmental defects. However, it is still unclear how epigenetic regulators coordinate with tissue-specific regulatory factors during morphogenesis of specific organs. Using palatogenesis as a model, we reveal the functional significance of Kdm6b, a H3K27me3 demethylase, in regulating embryonic development. Our study shows that Kdm6b plays an essential role in neural crest development, and loss of Kdm6b disturbs p53 pathway-mediated activity, leading to complete cleft palate along with cell proliferation and differentiation defects. Furthermore, activity of H3K27me3 on the promoter of p53 is precisely controlled by Kdm6b, and Ezh2 in regulating p53 expression in cranial neural crest cells. More importantly, Kdm6b renders chromatin accessible to the transcription factor Tfdp1, which binds to the promoter of p53 along with Kdm6b to specifically activate p53 expression during palatogenesis. Collectively our results highlight the important role of the epigenetic regulator Kdm6b and how it cooperates with Tfdp1 to achieve its functional specificity in regulating p53 expression, and further provide mechanistic insights into the epigenetic regulatory network during organogenesis.
The Fragility of Significance in the Hip Arthroscopy Literature: A Systematic Review.

The purpose of the present study was to perform the first examination of the utility of p values and the degree of statistical fragility in the hip arthroscopy literature by applying both the Fragility Index (FI) and the Fragility Quotient (FQ) to dichotomous comparative trials. We hypothesized that dichotomous comparative trials evaluating categorical outcomes in the hip arthroscopy literature are statistically fragile. Methods The PubMed and MEDLINE databases were queried from 2008-2018 for comparative studies evaluating dichotomous data in the hip arthroscopy literature. The present analysis included both randomized controlled trials (RCTs) and non-RCTs in which dichotomous data and associated p values were reported. Fragility analysis was performed with use of the Fisher exact test until an alteration of significance was determined. Results Of the 5,836 studies screened, 4,156 met the search criteria, with 52 comparative studies included for analysis. One hundred and fifty total outcome events with 33 significant (p < 0.05) outcomes and 117 nonsignificant (p ≥ 0.05) outcomes were identified. The final FI incorporating all 150 outcome events from 52 comparative studies was only 3.5 (interquartile range, 2 to 6), with an associated FQ of 0.032 (interquartile range, 0.017 to 0.063). Twenty-two studies (42.3%) either failed to report loss to follow-up (LTF) data or reported LTF greater than the overall FI of 3.5. Conclusions The peer-reviewed hip arthroscopy literature may not be as stable as previously thought, as the sole reliance on a threshold p value has proven misleading. We therefore recommend reporting of the FI and FQ, in conjunction with p values, to aid in the evaluation and interpretation of statistical robustness and quantitative significance in future comparative hip arthroscopy studies.
Cardiac Effects of Peptidoleukotrienes

The leukotrienes are a group of newly identified eicosanoids of the lipoxygenase pathway of arachidonic acid metabolism (Samuelsson, 1981). The peptide-con-taining leukotrienes (LT) (i. e., LTC4, LTD4, and LTE4) are known to possess potent biological properties including bronchoconstriction (Holroyde et al., 1981), enhancement of vascular permeability (Peck et al., 1981), and vasoconstriction (Yokochi et al., 1982). In this regard, it is well documented that leukotrienes C4and D4 are potent coronary constrictors in a number of animal species (Woodman and Dusting, 1983; Terashita et al., 1981). Previous work in our laboratory has shown that the leukotrienes are potent constrictors of isolated perfused cat coronary arteries (Roth and Lefer, 1984). Leukotrienes have also been claimed to exert direct negative inotropic effects on the myocardium (Burke et al., 1982). The purpose of this investigation was to examine the inotropic effects of the leukotrienes in relation to their potent coronary constricting activity and to clarify the relationship between coronary vasoactivity and inotropicity in cardiac preparations isolated from three commonly used mammalian species.
Parenting Teens in These Digital Times

Parents and other primary caregivers are vital to young people’s understanding of sexuality, intimacy, and gender. They are the people who held, touched, kissed, and cuddled the young ones, providing them with the earliest understanding of human intimacy and relationship.
Trauma Junkie: Taking Charge of My Survival

1. Nurses face the threat of violence daily. 2. Awareness of your individual responses to violent behavior may help you survive a critical incident. 3. Deliberately enrich and balance your personal, work, and spiritual life to enhance both your quality of life and your ability to resist the negative effects of stress. Language: en
Assessment of Aerodynamic Challenges of a Variable-Speed Power Turbine for Large Civil Tilt-Rotor Application

The main rotors of the NASA Large Civil Tilt-Rotor notional vehicle operate over a wide speed-range (100% at take-off to 54% at cruise). The variable-speed power turbine, when coupled to a fixed-gear-ratio transmission, offers one approach to accomplish this speed variation. The key aero-challenges of the variable-speed power turbine are related to high work factors at cruise, where the power turbine operates at 54% of take-off speed, wide incidence variations into the vane, blade, and exit-guide-vane rows associated with the power-turbine speed change, and the impact of low aft-stage Reynolds number (transitional flow) at 28 kft cruise. Meanline and 2-D Reynolds-Averaged Navier- Stokes analyses are used to characterize the variable-speed power-turbine aerodynamic challenges and to outline a conceptual design approach that accounts for multi-point operation. Identified technical challenges associated with the aerodynamics of high work factor, incidence-tolerant blading, and low Reynolds numbers pose research needs outlined in the paper
Chapter 7 Variable Selection QSAR Modeling, Model Validation, and Virtual Screening

Publisher Summary This chapter discusses and illustrates variable selection that rigorously validate quantitative structure–activity relationship (QSAR) models with statistically significant external predictive power ultimately afford their application as reliable virtual screening tools for database mining or chemical library design. Several criteria of model robustness have been presented in the chapter, particularly emphasizing on the external predictive power of the model. The traditional LOO q 2 is insufficient statistical characteristic of model predictive power. Thus, although low values of q 2 almost certainly indicate that the model is not expected to be predictive externally, high values of this parameter alone also provide no guarantee that the underlying models can be used for the reliable external prediction. The application of these principles to the development of the predictive QSAR models of anticonvulsant agents followed by the use of these models for database mining is shown to afford the discovery of novel anticonvulsant agents. The robustness and external predictive power and applicability domain as the most important parameters of QSAR models shall increase their practical use as reliable virtual screening tools for pharmaceutical lead identification.
Dietary factors affecting the urinary mutagenicity assay system: I. Detection of mutagenic activity in human urine following a fried beef meal

Abstract Studies have been conducted to determine whether the mutagens in fried beef ingested by human subjects are excreted in urine. Urine samples were collected from individuals on liquid or regular diets before and after a fried beef meal. The mutagenic activity of the samples was tested in the Ames Salmonella/microsome assay system. The results showed that in individuals on liquid diets, most of the urinary mutagenic activity is recovered within 2–6 h after consuming a fried beef meal. In one individual tested, mutagenic activity was found in urine samples obtained 6–15 h after the fried beef meal. No mutagenic activity was detected in any of the urine samples obtained 15–24 h following the meal. In individuals on a regular diet, however, mutagenic activity was frequently observed in urine samples obtained 16–24 h following the fried beef meal, although the mutagenic activity was not as great as that in the preceding 16 h. It appears that the mutagenic agents generated by the frying of beef are ingested, absorbed, and excreted by the human body in biologically detectable quantities. These results suggest that subjects should abstain from fried beef at least one day prior to and during urine mutagenicity screening.
EpoDB: An Erythropoiesis Gene Expression Database in Progress

EpoDB is a database intended for the study of gene expression during differentiation and development of vertebrate erythropoietic lineages. It currently contains 1442 Genbank entries (663 are globin and 779 non-globin) which have been augmented manually and computationally. Each entry was analyzed by an expert system that corrects errors in GenBank features and generates a uniformly annotated set of features. Gene names and gene, family names were manually added. Beyond the standard database queries, the functionality of EpoDB includes the ability to extract features and subsequences (e.g. retrieve −500 to +20 region relative to the start of transcription for all β-globins), display graphically transcription unit features and sequences using Java applets, and direct export of sequences to TESS, a transcription element search program. Information on gene regulatory sites and gene expression levels is being added.
Thermal stability of correlated defects introduced by heavy ion irradiation in YBa 2 Cu 3 O 7-δ

We study the thermal stability of columnar defects in ${\mathrm{YBa}}_{2}{\mathrm{Cu}}_{3}{\mathrm{O}}_{7\ensuremath{-}\ensuremath{\delta}}$ single crystals introduced by irradiation with 3.9 GeV ${\mathrm{Au}}^{29+}.$ The dependence of the critical current density on the annealing temperatures is correlated with changes in the microstructure of the defects, as seen from transmission electron microscopy measurements. We find that the defects induced by irradiation are stable upon thermal annealing up to temperatures of 600 \ifmmode^\circ\else\textdegree\fi{}C and that the critical current density at temperatures $Tg~45\mathrm{K}$ can actually increase with thermal annealing.
A Grateful Recollecting: A Qualitative Study of the Long-Term Impact of Service-Learning on Graduates.

Service-learning practitioners design community engagement activities to affect students in powerful and even transformative ways. This qualitative study explores the long-term impacts (3-16 years after graduation) of participation in a senior-level service-learning course. Through interviews with 20 randomly selected participants, the researchers explored whether and in what ways graduates continued to experience impacts from the course, including those that have become interwoven with other life experiences or have catalyzed altered perspectives and/or actions. Graduates were first asked to identify their most significant learning experiences in college in order to gauge the relative importance, if any, of the service-learning course in their college education. Then graduates were asked to recall their experiences in the course and to share what impacts those experiences had at the time and in the intervening years. Findings are discussed through the lens of transformational learning processes and outcomes.
Effect of Increasing Atmospheric CO2 on Photosynthesis

Two principle reasons for world wide interest in rising atmospheric CO2 are potential climate changes from the greenhouse effect and increase photosynthesis for plant growth. Past steady state level of atmospheric CO2 is estimated to have been 250 to 270 ppm before the industrial revolution. It was measured at 290 ppm in 1890 to 1910. Atmospheric CO2 is now being monitored atop Mona Loa volcano in Hawaii, and it has increased from 315 in 1958 to 340 ppm by 1982, an 8% increase. The rate of increase has doubled from 0.7 ppm per year to 1.5 ppm per year (Kellog, 1978). Extrapolation predicts a CO2 level of over 600 ppm within a few decades. Greenhouse experiments indicate that the rate of photosynthesis by most C3 plants increased proportionally, and additional experiments are in progress on photosynthesis and plant growth at 600 and 1000 ppm CO2 (Lemon 1983). The data on CO2 increase is well established and the world must adapt to the consequences of higher atmospheric CO2. The effect that 600 ppm CO2 will have on the climate is less certain, but the general consensus is for a 2 to 3°C rise in global temperature and a 7 to 9°C rise in the polar regions (NAS 1977).
Pathogenesis of immune complex glomerulonephritis of New Zealand mice.

Observations based on elution of IgG from nephritic kidneys of NZ mice and absorption of the eluted IgG with selected antigens indicate that their immune complex nephritis involves at least two kinds of antigen-antibody complexes. Antibodies reactive with nuclear antigens account for nearly half of the IgG eluted from the kidneys while antibodies reactive with Gross viral antigens make up a significant but lesser amount. Superimposed chronic viral infections affect the nephritis of NZ mice in different ways. LCM and polyoma infections hasten and intensify the antinuclear antibody responses and glomerulonephritis of these mice while LDV infection appears to protect against both antinuclear antibody formation and development of nephritis.
The Irvine-Minnesota inventory to measure built environments: development.

Background: Researchers and policymakers increasingly identify active living-including walking and bicycling for travel and recreation-as a potential strategy to increase rates of physical activity in the United States. Understanding the impact of the built environment on physical activity levels requires reliable methods to measure potentially relevant built environment features. This paper presents an audit tool-the Irvine Minnesota Inventory-that was designed to measure a wide range of built environment features that are potentially linked to active living, especially walking. Methods: The inventory was created through a literature review, focus group interviews, a panel of experts, and field testing in 27 settings. The inventory was developed in 2003-2004. Results: The Irvine Minnesota Inventory includes 162 items, organized into four domains: accessibility (62 items), pleasurability (56 items), perceived safety from traffic (31 items), and perceived safety from crime (15 items). (Some items are in multiple domains.) The inventory includes both a paper version and a version in Microsoft Access, to allow data to be input directly into the computer. Conclusions: Limitations of methods used to develop the inventory are discussed. Strategies are offered for using the Irvine Minnesota Inventory to systematically and reliably measure characteristics of the built environment that are potentially linked to active living.
Rhetorical sensitivity and social interaction

Contemporary attitudes toward communication can be viewed as two‐dimensional—expressive and instrumental. The argument of this article is that the instrumental, or as we would label it, the rhetorical approach, best promises to facilitate human understanding and to effect social cohesion. Five characteristics of rhetorical sensitivity are described. These are features which, if incorporated and operationalized in discourse, can help men make the most of social interactions. The rhetorically sensitive person (a) tries to accept role‐taking as part of the human condition, (b) attempts to avoid stylized verbal behavior, (c) is characteristically willing to undergo the strain of adaptation, (d) seeks to distinguish between all information and that information acceptable for communication, and (e) tries to understand that an idea can be rendered in multi‐form ways.
Anaerobic biodegradation of para-cresol under three reducing conditions.

The anaerobic degradation ofp-cresol was studied with one sediment source under three reducing conditions-denitrifying, sulfidogenic, and methanogenic. Loss ofp-cresol (1 mM) in all the anaerobic systems took initially 3 to 4 weeks. In acclimated culturesp-cresol was degraded in less than a week.p-Cresol was completely metabolized under denitrifying, sulfidogenic, and methanogenic conditions, with formation of nitrogen gas, loss of sulfate, and formation of methane and carbon dioxide, respectively.p-Cresol metabolism proceeded throughp-hydroxybenzal-dehyde andp-hydroxybenzoate under denitrifying and methanogenic conditions. These compounds were rapidly degraded in cultures acclimated top-cresol under all three reducing conditions. These results suggest that the initial pathway ofp-cresol degradation is the same under denitryfying, sulfidogenic, and methanogenic conditions and proceeds via oxidation of the methyl substituent top-hydroxybenzaldehyde andp-hydroxybenzoate. The initial rate ofp-hydroxybenzaldehyde degradation was high in both the unacclimated cultures and in the cultures acclimated top-cresol, suggesting that this step is nonspecific. Benzoate was additionally detected as a metabolite followingp-hydroxybenzoate in the methanogenic cultures, but not in the denitrifying or sulfidogenic cultures. The degradation pathway therefore may diverge afterp-hydroxybenzoate formation depending on which electron acceptor is available.
The effects of hypothalamic and reticular stimulation on evoked responses in the visual system of the cat.

Abstract The purpose of this experiment was to compare the changes induced by reticular stimulation in the magnitude of evoked responses of the visual system of the cat with the changes occurring during stimulation of two areas in the hypothalamus, each of which directed the cat's attention to specific visual stimuli. The responses of the lateral geniculate body, optic radiation, superior colliculus, and visual cortex evoked by a shock to the optic tract and the response of the visual cortex evoked by an optic radiation shock were recorded in the absence of any other electrical stimulation of the brain and when preceded by 100 msec trains of either reticular stimulation, stimulation of the lateral hypothalamus, or stimulation of the medial hypothalamus. In some subjects large bilateral reticular lesions were made so that the effects of loss of reticular function on the changes in evoked potential amplitude induced by hypothalamic stimulation could be assessed. It was found that: 1. 1. Hypothalamic and reticular stimulation significantly increased the amplitude of evoked responses recorded from the lateral geniculate body, optic radiation, and superior colliculus. 2. 2. The cortical response evoked by stimulating the optic radiation was depressed by hypothalamic stimulation and facilitated by reticular stimulation. 3. 3. The cortical response evoked by stimulating the optic tract was facilitated by low intensities and depressed by high intensities of hypothalamic stimulation. Reticular stimulation facilitated the cortical evoked response at all intensities. 4. 4. Lesions of the reticular formation did not alter either the facilitatory effect of hypothalamic stimulation at the subcortical level or its depressive effect at the cortex. 5. 5. Stimulation of the lateral hypothalamus which elicited quiet attack directed at a rat and stimulation of the medial hypothalamus which elicited affective attack directed at the experimenter or at the rat had the same effects on visual evoked potentials.
Locally controlled inhibitory mechanisms are involved in eukaryotic GPCR-mediated chemosensing

Gprotein–coupled receptor (GPCR) signaling mediates a balance of excitatory and inhibitory activities that regulate Dictyostelium chemosensing to cAMP. The molecular nature and kinetics of these inhibitors are unknown. We report that transient cAMP stimulations induce PIP3 responses without a refractory period, suggesting that GPCR-mediated inhibition accumulates and decays slowly. Moreover, exposure to cAMP gradients leads to asymmetric distribution of the inhibitory components. The gradients induce a stable accumulation of the PIP3 reporter PHCrac-GFP in the front of cells near the cAMP source. Rapid withdrawal of the gradient led to the reassociation of G protein subunits, and the return of the PIP3 phosphatase PTEN and PHCrac-GFP to their pre-stimulus distribution. Reapplication of cAMP stimulation produces a clear PHCrac-GFP translocation to the back but not to the front, indicating that a stronger inhibition is maintained in the front of a polarized cell. Our study demonstrates a novel spatiotemporal feature of currently unknown inhibitory mechanisms acting locally on the PI3K activation pathway.
Administrative Turnover in State Government A Research Note

The frequency with which lop administrative officials in state government retain (or leave) their positions as agency heads is documented and discussions in this preliminary descriptive analysis of administrative turnover/tenure in state government. Two-year turnover rates during a 24-year period (1959-1983) are analyzed for 72 different types of administrative agencies in all 50 stales. Several findings ape prominent. (1) turnover rates have increased over time; (2) recently, about 50% of all state agency heads remain in the same position over each two-year period; (3) turnover is higher-among newly created agencies; and (4) turnover is higher among the directors of redistributive " agencies a1(d lower-among the heads of "distributive" agencies.
Graphene synthesis via droplet CVD AND its photonic applications

The process of “droplet CVD” for the synthesis of graphene sheets and its photonic applications have been demonstrated. Metal (Cu or Ni) droplets are naturally transformed from thin films under high temperature and used as the catalysts to grow graphene via the chemical vapor deposition (CVD) process. This work has achieved several advancements: (1) first demonstration of “droplet CVD” for graphene synthesis; (2) constructions of continuous graphene sheets with discontinuous metal droplets - readily available for graphene sensing applications; and (3) preliminary proof-of-concept demonstration of a photonic sensor based on the droplet CVD graphene. As such, this new class of fabrication process could open up various graphene-based device/system applications, including photonic sensors.
Study of the reliability of the semiclassical instanton contribution to the inclusive cross section

Abstract The reliability of the semiclassical instanton calculation of the inclusive cross section is studied. This is done in the two-dimensional linear sigma model, where the contribution of constrained instantons to the semiclassical cross section is compared with an exact unitarity bound. The conclusion is that, at energies in which the semiclassically calculated cross section becomes unsuppressed (at least in some range of parameters), the instanton calculation cannot be trusted.