cssi/SciSciGPT-SciSciNet huggingface dataset:
Variation theory: A theory of learning and a useful theoretical framework for chemical education research

Instructors are constantly baffled by the fact that two students who are sitting in the same class, who have access to the same materials, can come to understand a particular chemistry concept differently. Variation theory offers a theoretical framework from which to explore possible variations in experience and the resulting differences in learning and understanding. According to variation theory, there are a limited number of features of a given phenomenon to which we can pay attention at any given time. Our experience of that phenomenon depends on the specific features to which we direct our attention. Two individuals who experience the same phenomenon may focus on different features and, thus, come to understand the phenomenon differently. The purpose of this article is to present variation theory as (1) a useful way for instructors to think about student learning and (2) a potentially powerful theoretical framework from which to conduct chemical education research.
Presentation of the Distinguished Public Service Medal of the Mineralogical Society of America for 2009

Madame President, Members of the Society, and honored guests: It’s a great pleasure to introduce Robert M. Hazen, the recipient of the 2009 Distinguished Public Service Medal of the MSA. Trained as a crystallographer/mineralogist and former MSA Award winner, councilor, distinguished lecturer, and President of the Society, Bob has had and continues to have an extraordinary career in the mineral sciences. Here we honor him for his remarkable Public Service as a communicator of science and for advancing public knowledge and appreciation of science. Along with being a Senior Staff scientist at the Geophysical Laboratory, Bob is a Clarence J. Robinson Professor at George Mason University, where he has designed innovative undergraduate and graduate courses to engage broad audiences in the scientific process. Bob …
R&D policy, agency costs and innovation in personalized medicine.

The Orphan Drug Act (ODA) was designed to spur the development of drugs for rare diseases. In principle, its design also incentivizes pharmaceutical firms to develop drugs for “rare” subdivisions of more prevalent diseases. I find that in response to this incentive, firms develop drugs for ODA-qualifying subdivisions of non-rare diseases. The impact in these tailored drug markets represents half of the total R&D response to the ODA. I also find that 10-percent of the innovation in subdivided disease drugs induced by the ODA would have been conducted without the policy. While modest in size, this inefficiency suggests that agency problems should be considered when designing innovation policy.
Detection, tracking and classification of moving objects for unstable video surveillance applications

Detecting, tracking, and classifying moving objects using a single fixed camera is quickly becoming commonplace in many applications ranging from advanced traffic monitoring systems to security applications including border monitoring. In this paper, we present a framework for the detection, tracking, and classification of moving objects in an unstable video taken of a traffic intersection in India. Combinations of methods have been implemented in an attempt to successfully perform the aforementioned tasks automatically. An initial evaluation of these methods is discussed and compared to preliminary results from a manually segmented video.
A new program for optimizing periodic boundary models of solvated biomolecules (PBCAID).

Simulations of solvated macromolecules often use periodic lattices to account for long-range electrostatics and to approximate the surface effects of bulk solvent. The large percentage of solvent molecules in such models (compared to macromolecular atoms) makes these procedures computationally expensive. The cost can be reduced by using periodic cells containing an optimized number of solvent molecules (subject to a minimal distance between the solute and the periodic images). We introduce an easy-to-use program “PBCAID” to initialize and optimize a periodic lattice specified as one of several known space-filling polyhedra. PBCAID reduces the volume of the periodic cell by finding the solute rotation that yields the smallest periodic cell dimensions. The algorithm examines rotations by using only a subset of surface atoms to measure solute/image distances, and by optimizing the distance between the solute and the periodic cell surface. Once the cell dimension is optimized, PBCAID incorporates a procedure for solvating the domain with water by filling the cell with a water lattice derived from an ice structure scaled to the bulk density of water. Results show that PBCAID can optimize system volumes by 20 to 70% and lead to computational savings in the nonbonded computations from reduced solvent sizes. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1843–1850, 2001
Methods for calculating the absolute entropy and free energy of biological systems based on ideas from polymer physics.

The commonly used simulation techniques, Metropolis Monte Carlo (MC) and molecular dynamics (MD) are of a dynamical type which enables one to sample system configurations i correctly with the Boltzmann probability, P, while the value of P is not provided directly; therefore, it is difficult to obtain the absolute entropy, S ∼ −ln P, and the Helmholtz free energy, F. With a different simulation approach developed in polymer physics, a chain is grown step-by-step with transition probabilities (TPs), and thus their product is the value of the construction probability; therefore, the entropy is known. Because all exact simulation methods are equivalent, i.e. they lead to the same averages and fluctuations of physical properties, one can treat an MC or MD sample as if its members have rather been generated step-by-step. Thus, each configuration i of the sample can be reconstructed (from nothing) by calculating the TPs with which it could have been constructed. This idea applies also to bulk systems such as fluids or magnets. This approach has led earlier to the “local states” (LS) and the “hypothetical scanning” (HS) methods, which are approximate in nature. A recent development is the hypothetical scanning Monte Carlo (HSMC) (or molecular dynamics, HSMD) method which is based on stochastic TPs where all interactions are taken into account. In this respect, HSMC(D) can be viewed as exact and the only approximation involved is due to insufficient MC(MD) sampling for calculating the TPs. The validity of HSMC has been established by applying it first to liquid argon, TIP3P water, self-avoiding walks (SAW), and polyglycine models, where the results for F were found to agree with those obtained by other methods. Subsequently, HSMD was applied to mobile loops of the enzymes porcine pancreatic α-amylase and acetylcholineesterase in explicit water, where the difference in F between the bound and free states of the loop was calculated. Currently, HSMD is being extended for calculating the absolute and relative free energies of ligand–enzyme binding. We describe the whole approach and discuss future directions. Copyright © 2009 John Wiley & Sons, Ltd.
Functional Interplay between Histone Demethylase and Deacetylase Enzymes

Histone deacetylase (HDAC) inhibitors are a promising class of anticancer agents for the treatment of solid and hematological malignancies. The precise mechanism by which HDAC inhibitors mediate their effects on tumor cell growth, differentiation, and/or apoptosis is the subject of intense research. Previously we described a family of multiprotein complexes that contain histone deacetylase 1/2 (HDAC1/2) and the histone demethylase BHC110 (LSD1). Here we show that HDAC inhibitors diminish histone H3 lysine 4 (H3K4) demethylation by BHC110 in vitro. In vivo analysis revealed an increased H3K4 methylation concomitant with inhibition of nucleosomal deacetylation by HDAC inhibitors. Reconstitution of recombinant complexes revealed a functional connection between HDAC1 and BHC110 only when nucleosomal substrates were used. Importantly, while the enzymatic activity of BHC110 is required to achieve optimal deacetylation in vitro, in vivo analysis following ectopic expression of an enzymatically dead mutant of BHC110 (K661A) confirmed the functional cross talk between the demethylase and deacetylase enzymes. Our studies not only reveal an intimate link between the histone demethylase and deacetylase enzymes but also identify histone demethylation as a secondary target of HDAC inhibitors.
How important is treatment? One‐year outcomes of treated and untreated alcohol‐dependent individuals

Aims To compare representative treatment and untreated samples of alcohol-dependent individuals in rates of abstinence and non-problematic use at 1-year follow-up. Participants and design A total of 482 alcohol-dependent adults in a northern California county identified through a probability survey of problem drinkers in the general population (n = 111) or a survey of consecutive admissions to public and private substance abuse programs (n = 371) were interviewed in person at baseline and by telephone at 1 year. Measurements Logistic regression models were used to predict 30-day abstinence and 12-month non-problematic alcohol use. Results At follow-up, alcohol-dependent individuals in the treatment sample had higher abstinence rates and non-problematic use outcomes than those in the untreated general population sample. In logistic regression models of the merged samples, being in the treatment sample was related strongly and positively to abstinence and non-problematic use. Having more drug users and heavy drinkers in one's social network, higher psychiatric comorbidity, and more social consequences were inversely related to abstinence and non-problematic use in the treatment sample. The number of drug users and heavy drinkers in one's social network was also inversely related to abstinence in both the treatment and untreated general population samples. Results predicting non-problematic use were similar. Conclusions These results are consistent with other studies that examine treatment effectiveness in the absence of a controlled trial. Although natural recovery also occurs, alcohol-dependent individuals benefit from treatment. Co-occurring psychiatric problems continue to be major barriers to treatment effectiveness. An emphasis on changing social networks to be conducive to recovery could heighten both clinical effectiveness and prevention efforts within communities.
The pediatric research initiative in the United States : Implications for global pediatric research

Recognition of cultural and ethnic differences in target populations for drugs, an increase in multi-country new drug application submissions, harmonization of international regulatory requirements and research guidelines, and the availability of multinational contract research organizations (CROs) will facilitate the current trend toward increased multinational clinical research trials. Currently, approximately 20% of research by United States-based companies is already conducted outside the United States. Since new drug applications submitted to the United States Food & Drug Administration (FDA) will require pediatric studies for any drugs with potential use in the pediatric population, it is likely that they will be done by any drug sponsor planning to enter its product in the United States market at some point in the product’s life cycle regardless of the country of origin. Although the current United States domestic market for pediatric drugs is considered small, nearly 20% of all drug sales in developed countries worldwide are for patients under 18 years of age. The pediatric drug market in developing countries may be just as important. It has been estimated that by the year 2000, developing countries, where more than half of the population are children, will comprise 36% of the world market for pharmaceuticals. Establishment of international standards for pediatric drug development, currently in process by the International Conference on Harmonization (ICH), should eventually result in availability of consistent formulations of needed therapeutic drugs for all children worldwide.
Sensor-based distributed control scheme for mobile robots

We present a sensor-based distributed control scheme for mobile robots. This scheme combines centralized and decentralized control strategies. A server-client model is used to implement this scheme where the server is a process that caries out the commands to be executed, and each client is a process with a certain task. The clients are running in parallel issuing commands to the server which selects the command to be executed based on a predefined priority scheme. In this scheme, a collision avoidance client is running all the time with the highest priority. This improves the performance of the other clients since it removes the burden of avoiding obstacles and allows each client to concentrate on performing its task. The logical sensor approach is used to model the sensory system which provides different levels of data representation with tolerance measures and analysis. The simulation results of this model are presented with a brief discussion and conclusion on these results.
Behavior of Tied Multiple-Lane Portland Cement Concrete Pavement: Effects of Environmental Loading and Dowel Bar Use

Tie bars are used at longitudinal construction joints (LCJs) in portland cement concrete (PCC) pavement primarily to keep lanes from separating. As more lanes are tied together because of ever-increasing traffic volume, concerns about the potential for longitudinal cracking have led to the use of dowel bars at LCJs. However, a survey of a number of state highway agencies (SHAs) revealed that few of them have guidelines and design standards for the use of dowel bars at LCJs and that no in-depth studies conducted in this area have been identified. The effects of multiple lane ties and dowel bar placements in PCC pavements are analyzed in this paper to provide basic information on whether dowel bars are really needed, and if they are, where they should be placed and what their advantages and disadvantages are. Field testing verified that the longitudinal cracking potential is greater as slab thickness and lane width increase. The effects of multiple lane ties and dowel bar placements at LCJs are evaluated wi...
How Large are the Coinsurance Benefits of Mergers

Using a structural model, I estimate the value gain from coinsurance when two firms merge. For most mergers, the estimated gains from coinsurance are small, smaller than the counterfactual gains if firms were to merge randomly, suggesting that coinsurance is not the primary motivation for most mergers. Diversifying mergers produce no higher coinsurance than related mergers. Target leverage and relative size predict coinsurance better than cash flow correlation. The cumulative abnormal return around merger announcement increases 0.89% for every 1% estimated value gain from coinsurance, suggesting that stockholders benefit from coinsurance, contrary to a common claim in textbooks.
Scientists as Prophets: A Rhetorical Genealogy

Scientists as Prophets: A Rhetorical Genealogy is a welcome contribution to the rhetoric of science literature. Lynda Walsh argues that a better understanding of the historical evolution of prophet...
849 SERUM 25-HYDROXYVITAMIN D (250HD) LEVELS IN INFANTS OF DIABETIC MOTHERS

Thirty-five mothers with previously documented diabetes and their infants born at term were studied. Thirty infants remained normocalcemic (serum ionized calcium > 3.0mg/dl) and 5 infants became hypocalcemic during the first 4 days of life. Serum levels of 250HD from these diabetic mothers and their infants were compared to values obtained from 30 normal term pregnancies. Serum levels of 250HD in ng/ml are expressed as mean ± 1SD: Serum 250HD values from normal term mothers and their neonates were greater (p<0.001)than values from diabetic mothers and their infants. Serum levels of 250HD in diabetic mothers and their infants who became hypocalcemic were significantly lower (p<0.01) than values from diabetic mothers and their infants who remained normocalcemic. Serum 250HD level increased (p<0.05) in both groups of infants of diabetic mothers from day 1 to day 14 of life with levels in the normocalcemic group remaining greater than the hypocalcemic group (p<0.05). These data indicate that pregnancy in diabetics is associated with a low serum level of 250HD and suggest that infants born to diabetics with the lowest concentrations of 250HD are at considerable risk to develop early neonatal hypocalcemia.
Generalized Mantel-Haenszel estimators for K 2 x J tables.

Mickey and Elashoff (1985, Biometrics 41, 623-635) gave an extension of Mantel-Haenszel estimation to log-linear models for 2 x J x K tables. Their extension yields two generalizations of the Mantel-Haenszel odds ratio estimator to K 2 x J tables. This paper provides variance and covariance estimators for these generalized Mantel-Haenszel estimators that are dually consistent (i.e., consistent in both large strata and sparse data), and presents comparisons of the efficiency of the generalized Mantel-Haenszel estimators.
Harmonic Oscillation Theory: Competitive and Cooperative Entrainment as a View of the Firm

Scholars have long sought to explain how organizational forms tend to change and perform over time, but until recently, frequently glossed over the nuances of time itself. Entrainment theory, vacil...
Social Framework of Pediatric Heart Recipients Who Have Survived More Than 15 Post Transplant Years: A Single Center Experience

s S111 ReL were younger, had a lower ejection fraction (EF), and more cardiac events but both groups had similar years since primary transplant (table 1). There was no difference in survival at time of diagnosis of CAV for ReL and NReL (p= 0.399)(figure 1). Survival remained equivalent excluding patients who had cardiac dysfunction (EF< 50%) and/or a cardiac event (p= 0.308). Conclusion: Re-listing does not appear to provide a long-term survival in patients with CAV even after excluding high-risk patients for mortality. Further studies are needed to define appropriate selective use of this therapy. Patient Characteristics CAV re-listed (387) CAV not re-listed (777) p-value Age at transplant 6.73±6.08 9±6.56 < 0.001 Years to CAV dx 6.9±4.2 7.1±4.7 0.808 EF (most recent) 53±14 58±13 < 0.001 Cardiac events 38% (148) 16% (122) < 0.001
Ritual Process and the Family in the Chicano Novel

In an autobiographical article entitled "Going Home Again: The American Scholarship Boy," Richard Rodriguez made a provocative observation about the Chicano novel. He speculated that "the novel ... is not a form capable . . . of being true to the basic sense of communal life that typifies Chicano culture." Rodriguez argues that the novel is best capable of depicting a solitary existence against a large social background. Thus, he argues, "Chicano novelists nearly always fail to capture the breathtakingly rich family life of most Chicanos and instead often describe only the individual Chicano in transit between Mexican and American cultures."' This speculative opinion would probably be negligible were it not for the fact that it appeared in The American Scholar and an anthology of rhetoric.2 Thus, like his recent media-acclaimed autobiography, it is more accessible to the American literary and academic mainstream than more informed opinions, which often appear in less widely circulated publications. While this opinion, first published in 1974, may be accurate in describing some Chicano novels, most notably Jose Antonio Villareal's Pocho, it seems to have been written with no acknowledgement of the fact that Tomas Rivera's Y no se lo trago la tierra and Rudolfo Anaya's Bless Me, Ultima had been in circulation since 1971. Both of these novels show the
Significance of size, temperature and call attributes to sexual selection in Bufo woodhousei australis.

Advertisement calls of a population of Bufo woodhousei australis were recorded in the field to determine possible effects of size and temperature on call attributes. Analysis of dom- inant frequency, pulse rate and duration of advertisement calls revealed that only frequency was correlated (negatively) with size. Observations of the same individuals on successive nights showed there was substantial variation in call attributes independent of temperature. Only pulse rate was correlated (positively) with body temperature; frequency and call duration were independent of body temperature over a 5?C range. It is concluded that females might distinguish males of different sizes on the basis of frequency, but temperature has no effect on this possible size indicator. These results are discussed in relation to the work of Fairchild (1981) on Bufo woodhousei fowleri.
Land Use Efficiency and Governmental Behavior Orientation from Perspective of Public Administration

It is difficult to solve the problem of land supply in the process of accelerating industrialization and urbanization in China and the only way out is to improve the efficiency of land use.Since land is a special factor of production,the efficiency of land use should be understood integratedly from the perspective of public administration,i.e.,such characteristics must be considered as externality of land use,functional diversity,sustainability and constitutive property of the system.To this end,it is necessary to establish appropriate mechanisms on the levels of both central and local governments to improve the overall efficiency of land use.
The Application of Self-adaptive Threshold Method Based on OTSU in Pre-magnetic Drawings

A self-adaptive threshold method based on OTSU was researched in this paper.This method can fix on the window size parameter self-adaptively through making the best of image pixel points information and the contiguous correlative information based on OTSU,the influence of interfering factors such as noise,grid and so on can not only be avoided,but also the computation can be optimized.Experiments shows this method has a high veracity and better extending applicaton value.
Some Notes (with Badiou and Žižek) on Event/Truth/Subject/Militant Community in Jean-Paul Sartre's Political Thought

The main object of this paper is to examine the new philosophical frame proposed by Alain Badiou and Slavoj Žižek and to show that it implies some traces of Sartre's philosophical and political heritage. According the project of Alain Badiou and Slavoj Žižek one should no longer accept today's constellation of freedom, particularistic truth and democracy, but to (re)inscribe the issues of freedom and universal truth into a political project that attempts to re-activate a thinking of revolution. Their thinking consists in the wager that it is still possible to provide a philosophical frame for this leftist emancipatory position that claims the dimension of the universal against the vicious circle of capitalist globalization-cum-particularization and, by following Marx's claim that there are formal affinities between the ambitions of emancipatory politics and the working mode of capitalism, takes up the struggle of universalism against globalization (capital). It is only through this struggle for the universal that the intertwined processes of a constant expansion of the automatism of capital and "a process of fragmentation into closed identities," accompanied by "the culturalist and relativist ideology" (Badiou) can be suspended. It is precisely this constellation of revolutionary act, universal truth, subject, and militant community, that reveal some similarities with Sartre's concepts of the subject, the revolutionary action, the militant community a.o.
Activity-based protein profiling for mapping and pharmacologically interrogating proteome-wide ligandable hotspots

Despite the completion of human genome sequencing efforts nearly 15 years ago that brought with it the promise of genome-based discoveries that would cure human diseases, most protein targets that control human diseases have remained largely untranslated, in-part because they represent difficult protein targets to drug. In addition, many of these protein targets lack screening assays or accessible binding pockets, making the development of small-molecule modulators very challenging. Here, we discuss modern methods for activity-based protein profiling-based chemoproteomic strategies to map 'ligandable' hotspots in proteomes using activity and reactivity-based chemical probes to allow for pharmacological interrogation of these previously difficult targets. We will showcase several recent examples of how these technologies have been used to develop highly selective small-molecule inhibitors against disease-related protein targets.
Local Value Chain Development in Vietnam: Motorcycles, Technical Learning and Rents Management

ABSTRACTThis article analyses how foreign direct investment drives technological upgrading in the motorcycle industry in Vietnam. Using the analytical framework of rent management, the article evaluates the rent management mechanisms that provided the incentives and pressures for domestic firms to develop a local value chain by participating in the foreign supply network. This article offers a case study analysis of two periods: 1995–2000 and 2000–05. Two case studies examine the exchanges between lead firms and their suppliers; between multinational corporations and local firms; and among the state, private and foreign firms in the context of the value chain for motorcycle production. The analyses suggest that industrial upgrading has been predominantly driven by foreign direct investment starting in the early 2000s. In addition, market competition among Japanese and Chinese lead firms led to significant technical learning for domestic firms through collaboration with foreign firms despite the government...
The “Retrofitting” Approach to Adapting Evidence-Based Interventions: A Case Study of Pediatric Asthma Care Coordination, United States, 2010–2014

Adaptation of evidence-based interventions upon implementation into new practice settings is universal, yet poorly understood. During a cross-site evaluation of the implementation of a proven intervention for pediatric asthma care coordination into 4 resource-challenged settings, we conducted in-depth interviews with site representatives, who reported how and why they modified intervention components. Interview notes were coded for themes. We focused on a single theme from a respondent who described the adaptation process as "backing" the intervention into ongoing services; we found evidence of a similar process at other sites. We labeled this process "retrofitting" to signify adaptation that consists of altering existing services to align with intervention components, rather than modifying the intervention to fit a new setting. Advantages of retrofitting may include allowing organizations to keep what works, capitalizing on existing support for program activities, elevating the role of local knowledge, and potentially promoting the sustainability of effective innovations.
Efficient Eradication of Mature Pseudomonas aeruginosa Biofilm via Controlled Delivery of Nitric Oxide Combined with Antimicrobial Peptide and Antibiotics.

Fast eradication of mature biofilms is the ‘holy grail’ in the clinical management of device-related infections. Endogenous nitric oxide (NO) produced by macrophages plays an important role in host defense against intracellular pathogens, and NO is a promising agent in preventing biofilms formation in vitro. However, the rate of delivery of NO by various NO donors (e.g., diazeniumdiolates, S-nitrosothiols, etc.) is difficult to control, which hinders fundamental studies aimed at understanding the role of NO in biofilm control. In this study, by using a novel precisely controlled electrochemical NO releasing catheter device, we examine the effect of physiological levels of NO on eradicating mature Pseudomonas aeruginosa biofilm (7 d), as well as the potential application of the combination of NO with antimicrobial agents. It is shown that physiological levels of NO exhibit mixed effects of killing bacteria and dispersing ambient biofilm. The overall biofilm-eradicating effect of NO is quite efficient in a dose-dependent manner over a 3 h period of NO treatment. Moreover, NO also greatly enhances the efficacy of antimicrobial agents, including human beta-defensin 2 (BD-2) and several antibiotics, in eradicating biofilm and its detached cells, which otherwise exhibited high recalcitrance to these antimicrobial agents. The electrochemical NO release technology offers a powerful tool in evaluating the role of NO in biofilm control as well as a promising approach when combined with antimicrobial agents to treat biofilm-associated infections in hospital settings, especially infections resulting from intravascular catheters.
A Behavioral Process Model of Familism

Familismo, or familism, an important Latino cultural construct associated with youth adjustment, describes the importance of family regarding support, comfort, and services. Increased research on familism among Latino families in the past decade has called for a theoretical process model of familism that can guide research on familism, family processes, and youth development. In this article, we propose the behavioral process model of familism (BPMF), which identifies proximal mechanisms through which familism is expected to promote youth psychological adjustment. Specifically, we propose that parenting behaviors (e.g., monitoring, discipline strategies) are a mechanism by which parent familism relates to youth familism and psychological adjustment both directly and via their familism-consistent behaviors. We hypothesize direct and mediated pathways in the BPMF and consider how sociodemographic variables modify the described processes.
Density, biomass, and diversity of grasshoppers (Orthoptera: Acrididae) in a California native grassland

A native California perennial grassland was sampled for grasshopper populations. The grassland is managed for the preservation of the native perennial bunchgrass, Nassella pulchra Hitch. Grasshopper density, biomass, diversity, and richness were measured from July 1993 to October 1994. Average density of all grasshoppers was 2.30 hoppers/m 2 (0.66 s ) for 1994 (June through August). Overall forage consumed for 1994 was 140 kg/ha, suggesting that grasshopper populations exist at economically damaging levels. Grasshoppers do not appear in the grasslands until late spring, after annual grasses have set seed. Biomass of grasshoppers peaks in July when adults are predominant. Both grasshopper density and biomass were higher in 1993 than in 1994, and a total of 5 species were found throughout the study. Melanoplus sanguinipes Fabricus dominated the acridid communities and accounted for more than 95% of the individuals.
Open and Closed States of the NaVAb Activation Gate

The bacterial voltage-gated sodium channel NavAb is a structural model for eukaryotic voltage-gated sodium channels, and it has been crystallized in both the pre-open and inactivated states (Payanadeh et al 2011, 2012). These structures revealed the general architecture of bacterial voltage-gated sodium channels and provided insight into mechanisms of voltage-sensing, electromechanical coupling, and the selective conductance of sodium ions. Comparison with structures of other bacterial sodium channels (Zhang et al 2012, Bagneris et al 2013) has also informed hypotheses of activation gating, an opening transition now thought to involve twisting movements of the S6 helix that ultimately result in an iris-like dilation of the intracellular ends of the four S6 segments. We sought to capture closed and open states in the same channel protein through x-ray crystallography and electrophysiological studies of mutations in the S6 of NavAb. Our studies show that paired mutations of hydrophobic residues in the S6 helix can uncouple voltage-sensor movement from pore opening and thereby lock the channel in a permanently closed state in which the intracellular ends of the four S6 helices interact tightly with each other. On the other hand, truncation of the intracellular extensions of the S6 segments results in an open conformation of the activation gate. These analyses allow for comparison of the closed, open, and inactivated states of NavAB's activation gate, a first for a voltage-gated sodium channel. Our results help confirm and sharpen the previously hypotheses for the pore-opening transition of sodium channels and reveal key conformational changes that connect the closed, open, and inactivated states of NavAb.
How Can I Change My Patients' Treatment Decision Making by Becoming a Nurse Scientist? .

"What would you do?" I have heard this question numerous times throughout my nursing career by patients and families affected by cancer. As a pediatric blood and marrow transplantation nurse, I have often seen patients and their families wrestle with difficult treatment decisions. I have witnessed parents struggle between beginning end-of-life care for their child, or pursuing a risky but potentially life-saving clinical trial. With science driving advances in cancer treatments and patients playing more active roles in their care, uncertainty around cancer treatment decisions will only become more complicated. For me, being a good nurse meant helping these patients navigate this uncertainty. I was compelled to pursue research to understand the process patients experience as they make treatment decisions, who they choose to involve in decision making, and what role the unique nurse- patient relationship could play in facilitating patient-centered decisions. .
A CO2 utilization approach towards the synthesis of terephthalic acid via a catalytic double carboxylation

Abstract A catalytic double carboxylation of a bisboronate ester benzene was disclosed to synthesize terephthalic acid under a CO2 utilization approach. The double carboxylation was accomplished with several other bisboronate ester arenes to provide support for this being a general transformation. The double carboxylation was conducted on a gram scale to provide terephthalic acid in 90% yield.
Martingales: The Next Steps

Discrete-time martingales live under a star of grace. They offer inferences of power, purpose, and surprise, yet they impose little in the way of technical nuisance. In continuous time, martingale theory requires more attention to technical foundations — at a minimum, we need to build up some of the basic machinery of probability spaces and to sharpen our view of conditional expectations. Nevertheless, by focusing on martingales with continuous sample paths, we can keep technicalities to a minimum, and, once we have a stopping time theorem, our continuous-time tools will be on a par with those we used in discrete time. We can then examine three classic martingales of Brownian motion that parallel the classic martingales of simple random walk. These martingales quickly capture the most fundamental information about hitting times and hitting probabilities for Brownian motion.
Change Point Detection Based on Empirical Quantiles

The paper studies the problem of testing the null hypothesis that the observations X 1,…, X n have the same distribution or follow the same stochastic model versus the alternative that the distribution or the model change at some point in the sample. Using L 1, L 2 and max type statistics based on empirical quantiles, the validity of the subsampling method for independent observations and GARCH processes is verified. A simulation study assesses the performance of the tests in finite samples.
The Antifibrogenic Potential of PPARγ Ligands in Pulmonary Fibrosis

Pulmonary fibrosis is characterized by the accumulation of fibroblasts, myofibroblasts, collagen, and other extracellular matrix proteins in the interstitium of the lung, with subsequent scarring and destruction of the alveolar capillary interface. In some cases, pulmonary fibrosis is preceded by lung inflammation and can be treated with anti-inflammatory therapies. However, idiopathic pulmonary fibrosis is characterized by a relative paucity of underlying inflammation and currently has no effective treatment. There is increasing evidence that the transcription factor peroxisome proliferator-activated receptor (PPAR) gamma plays an important role in controlling cell differentiation and that PPARgamma ligands can modify inflammatory and fibrotic responses. Peroxisome proliferator-activated receptor gamma ligands, including the thiazolidinedione class of antidiabetic drugs and novel triterpenoid compounds derived from oleanic acid, inhibit TGF-beta-stimulated profibrotic differentiation of lung fibroblasts in vitro and reduce lung scarring in animal models of fibrosis. The mechanism of action of the PPARgamma ligands is under investigation but seems to involve both PPARgamma-dependent and PPARgamma-independent pathways. These in vitro and in vivo data highlight the potentially exciting role of PPARgamma ligands as novel therapies for fibrosis of the lung and other organ systems prone to scarring. Many of the synthetic PPARgamma ligands are orally active, and several are currently available and Food Drug Administration approved for use in therapy of type 2 diabetes. Further research is urgently required to more clearly elucidate the mechanism of action of these drugs and to develop more potent antifibrotic agents for patients with scarring diseases for whom there are currently few effective therapies.
Tuberculosis: A Reemerging Disease at the Interface of Domestic Animals and Wildlife

Complex interactions involving humans, domestic animals, and wildlife create environments favorable to the emergence of new diseases. Today, reservoirs of Mycobacterium bovis, the causative agent of tuberculosis in animals and a serious zoonosis, exist in wildlife. The presence of these wildlife reservoirs is the direct result of spillover from domestic livestock in combination with anthropogenic factors such as translocation of wildlife, supplemental feeding of wildlife and wildlife populations reaching densities beyond normal habitat carrying capacities. As many countries attempt to eradicate M. bovis from domestic livestock, efforts are impeded by spillback from wildlife reservoirs. It will not be possible to eradicate M. bovis from livestock until transmission between wildlife and domestic animals is halted. Such an endeavor will require a collaborative effort between agricultural, wildlife, environmental and political interests.
Slowing less than 1 Hz is decreased near the seizure onset zone

Focal slowing (<4 Hz) of brain waves is often associated with focal cerebral dysfunction and is assumed to be increased closest to the location of dysfunction. Prior work suggests that slowing may be comprised of at least two distinct neural mechanisms: slow oscillation activity (<1 Hz) may reflect primarily inhibitory cortical mechanisms while power in the delta frequency (1–4 Hz) may correlate with local synaptic strength. In focal epilepsy patients, we examined slow wave activity near and far from the seizure onset zone (SOZ) during wake, sleep, and postictal states using intracranial electroencephalography. We found that slow oscillation (0.3–1 Hz) activity was decreased near the SOZ, while delta activity (2–4 Hz) activity was increased. This finding was most prominent during sleep, and accompanied by a loss of long-range intra-hemispheric synchrony. In contrast to sleep, postictal slowing was characterized by a broadband increase of spectral power, and showed a reduced modulatory effect of slow oscillations on higher frequencies. These results suggest slow oscillation focal slowing is reduced near the seizure onset zone, perhaps reflecting reduced inhibitory activity. Dissociation between slow oscillation and delta slowing could help localize the seizure onset zone from interictal intracranial recordings.
Partial-Hessian Strategies for Fast Learning of Nonlinear Embeddings

Stochastic neighbor embedding (SNE) and related nonlinear manifold learning algorithms achieve high-quality low-dimensional representations of similarity data, but are notoriously slow to train. We propose a generic formulation of embedding algorithms that includes SNE and other existing algorithms, and study their relation with spectral methods and graph Laplacians. This allows us to define several partial-Hessian optimization strategies, characterize their global and local convergence, and evaluate them empirically. We achieve up to two orders of magnitude speedup over existing training methods with a strategy (which we call the spectral direction) that adds nearly no overhead to the gradient and yet is simple, scalable and applicable to several existing and future embedding algorithms.
Choice-selective sequences dominate in cortical relative to thalamic inputs to nucleus accumbens, providing a potential substrate for credit assignment

How are actions linked with subsequent outcomes to guide choices? The nucleus accumbens (NAc), which is implicated in this process, receives glutamatergic inputs from the prelimbic cortex (PL) and midline regions of the thalamus (mTH). However, little is known about what is represented in PL or mTH neurons that project to NAc (PL-NAc and mTH-NAc). By comparing these inputs during a reinforcement learning task in mice, we discovered that i) PL-NAc preferentially represents actions and choices, ii) mTH-NAc preferentially represents cues, iii) choice-selective activity in PL-NAc is organized in sequences that persist beyond the outcome. Through computational modeling, we demonstrate that these sequences can support the neural implementation of temporal difference learning, a powerful algorithm to connect actions and outcomes across time. Finally, we test and confirm predictions of our circuit model by direct manipulation of PL-NAc neurons. Thus, we integrate experiment and modeling to suggest a neural solution for credit assignment.
Torso injuries after fall from standing-empiric abdominal or thoracic CT imaging is not indicated.

Abstract Purpose Falls from standing (FFS) have become the most common mechanism of injury at many trauma centers. Liberal imaging of low energy trauma has questionable value. We hypothesize that torso trauma intervention is rare in the FFS population, and physical examination sufficiently screens for torso injuries needing intervention. Methods We queried our ACS-verified Level 1 trauma center registry for falls from standing from 1/1/14 to 12/31/16. Exclusion criteria were: falls from height, falls associated with penetrating trauma, lack of an abdominal or chest CT, a Glasgow Coma Scale Score (GCS) less than 15, and surgical intervention at another facility prior to arrival at our center. Demographics, historical details, hemodynamics, injuries, injury severity, procedures, initial vital signs, and outcome were recorded. Results 1,654 patients had a FFS during our study period. 728 had an abdominal or chest CT and a GCS of 15 and comprised the evaluable population. Mean age was 56.5 years. 55.8% were female. The mortality rate was 8%. There were 179 chest injuries in 121 patients, and 54 abdominal injuries in 43 patients. 379 patients had a GCS of 15 and underwent thoracic CT, yet only 11 (3%) underwent intervention. The negative predictive value for physical exam was 100% for chest intervention. 349 patients had a GCS of 15 and abdominal CT, yet only 13 (3.7%) underwent procedural intervention. Abdominal physical exam had a negative predictive value of 99.7% for intervention, but when combined with vital signs, the value was 100%. Conclusion Torso injuries in FFS are rare. Of our study population, 13 abdominal injuries underwent intervention, and 11 chest injuries underwent intervention. Screening patients by physical examination and vital signs is sufficient and safely allows for the use of selective abdominal and chest CT.
Explicit Time Stepping of PDEs with Local Refinement in Space-Time

Traditional numerical time stepping allows variable node densities in space, but not also in time. Having the ability to utilize nodes that are placed irregularly in the space-time domain leads to many advantages when solving time dependent problems. In this paper we introduce a new method utilizing the radial basis function generated finite difference approach in order to accomplish this goal. Benefits include improved stability conditions and the option to use small time steps only in select spatial regions.
An Aging-focused Heuristic Evaluation of Home Automation Controls:

Smart home technology can help older adults maintain independent lifestyles. Recent technological advancements have made smart home technology less expensive and more attainable for the average con...
Non-financial performance measures, CEO compensation, and firms’ future value

Abstract This study examines whether non-financial performance measures (NFPMs) included in CEO bonus contracts are complementary to equity-based compensation, and whether they jointly explain future firm value. We predict that in a performance evaluation system, NFPMs integrated into CEO bonus contracts complement the use of equity-based compensation, and that they are jointly and positively associated with firms’ long-term value. Consistent with our predictions, we find that the inclusion of NFPMs in bonus contracts is positively associated with the relative importance of equity-based compensation (especially in the form of restricted stocks), indicating a complementary relationship between NFPMs and equity-based compensation. We also show that equity-based compensation is marginally associated with higher future firm value when the firm uses NFPMs in its CEOs’ bonus contracts. Overall, our findings suggest that equity-based compensation is more effective in aligning managerial efforts and actions with firms’ long-term value when firms include NFPMs in CEO bonus contracts.
Too Much of a Good Thing: Hyperoxia and Pediatric Respiratory Illnesses

The advent of pulse oximetry as a widely adopted technology has transformed the overall clinical assessment of children with acute respiratory illness. One result of this transformation is a stronger clinical focus on treating hypoxemia in young children hospitalized with common respiratory illnesses, such as bronchiolitis, asthma, and pneumonia. For example, in acute viral bronchiolitis, international guidelines provide lower-limit oxygen saturation thresholds despite a weak evidence base and lack of consensus on the specific values. Nonetheless, advice to keep oxygen saturations above a precise threshold can be found in almost every bronchiolitis order set or hospital pathway. On the other hand, there has not been much debate about the opposite end of the spectrum: an upper saturation boundary once supplemental oxygen is administered for these common pediatric conditions. Pulse oximetry readings of 100% are not generally treated as abnormal, but they can represent a wide variety of Pao2 values and tissue oxygen delivery; thus, some readings of 100% while on supplemental oxygen will likely constitute tissue hyperoxia. Furthermore, nebulized therapies given in the hospital setting are typically driven by the flow of 100% oxygen from centralized supply lines, thus providing another source of exposure, which can be substantial for patients on continuously nebulized treatments. Nevertheless, there is a dearth of pediatric research on the scope of the exposure and the potential for harm from excess oxygen … Address correspondence to Shawn L. Ralston, MD, MS, Division of Quality and Safety, Johns Hopkins Children’s Center, 1800 N Orleans St, Baltimore, MD 21287. E-mail: sralsto3{at}jhmi.edu