cssi/SciSciGPT-SciSciNet huggingface dataset:
Photochemical CVD of Ru on functionalized self-assembled monolayers from organometallic precursors

Chemical vapor deposition (CVD) is an attractive technique for the metallization of organic thin films because it is selective and the thickness of the deposited film can easily be controlled. However, thermal CVD processes often require high temperatures which are generally incompatible with organic films. In this paper, we perform proof-of-concept studies of photochemical CVD to metallize organic thin films. In this method, a precursor undergoes photolytic decomposition to generate thermally labile intermediates prior to adsorption on the sample. Three readily available Ru precursors, CpRu(CO)2Me, (η3-allyl)Ru(CO)3Br, and (COT)Ru(CO)3, were employed to investigate the role of precursor quantum yield, ligand chemistry, and the Ru oxidation state on the deposition. To investigate the role of the substrate chemistry on deposition, carboxylic acid-, hydroxyl-, and methyl-terminated self-assembled monolayers were used. The data indicate that moderate quantum yields for ligand loss (φ ≥ 0.4) are required for ruthenium deposition, and the deposition is wavelength dependent. Second, anionic polyhapto ligands such as cyclopentadienyl and allyl are more difficult to remove than carbonyls, halides, and alkyls. Third, in contrast to the atomic layer deposition, acid-base reactions between the precursor and the substrate are more effective for deposition than nucleophilic reactions. Finally, the data suggest that selective deposition can be achieved on organic thin films by judicious choice of precursor and functional groups present on the substrate. These studies thus provide guidelines for the rational design of new precursors specifically for selective photochemical CVD on organic substrates.
Measuring aspects of player experience : A systematic review of human-computer interaction journals

The present paper introduces the results of a review of the methods measuring player experience proposed in articles published in human-computer interaction journals. The present review focused more specifically on the cases of combination of two or more methods. The results showed that 11 articles, all published in the last decade, proposed mixed methods to measure player experience. All these articles proposed at least a subjective measure method, always questionnaire, in combination with an objective one, mainly physiological measures. Player's emotions were the aspects of player experience that were the most studied in the case of mixed methods. A synthesis of these results was proposed and may be discussed at the workshop.
Eliminating inertia in a stochastic model of a micro-swimmer with constant speed

We are concerned with the dynamical description of the motion of a stochastic micro-swimmer with constant speed and fluctuating orientation in the long time limit by adiabatic elimination of the orientational variable. Starting with the corresponding full set of Langevin equations, we eliminate the memory in the stochastic orientation and obtain a stochastic equation for the position alone in the overdamped limit. An equivalent procedure based on the Fokker-Planck equation is presented as well.
Eosinophilic meningoencephalitis associated with rat lungworm (Angiostrongylus cantonensis) migration in two nine-banded armadillos (Dasypus novemcinctus) and an opossum (Didelphis virginiana) in the southeastern United States.

Angiostrongylus cantonensis, the rat lungworm, was the cause of neural larval migrans in two nine-banded armadillos (Dasypus novemcinctus) and one Virginia opossum (Didelphis virginiana) from the southeastern United States. Histologic findings in all three cases included eosinophilic meningoencephalitis with variable numbers of nematode larvae in the meninges or the neuroparenchyma. In two of the three cases, nematodes were extracted from brain tissue via a "squash prep" method. Identification of the nematodes was confirmed by amplification and sequence analysis of the partial cytochrome c oxidase subunit I gene from all three cases. Sequences (704bp) from the two cases from Louisiana were identical and 99.7% similar to nematodes detected in the armadillo from Florida. As A. cantonensis is now considered endemic in the southern United States, it should be considered as an important differential for any wild or domestic animal or human patient with neurological signs and eosinophilic meningitis. Many wildlife species frequently consume snails and slugs and could serve as sentinels for the detection of this parasite in regions where the presence of this parasite has not been confirmed. To the authors' knowledge, this is the first report of neural larval migrans due to A. cantonensis in an armadillo and provides additional documentation that this nematode can cause disease in wildlife species in the southeastern United States.
Knowledge of the 911 Good Samaritan Law and 911-calling behavior of overdose witnesses.

Background: Overdose deaths tripled between 1999 and 2014. Most fatal overdoses are witnessed, offering an opportunity for bystanders to call 911. However, fear of arrest may prevent them from call...
Obesity counseling: Beyond 'eat less, move more'.

Not all cancers are treated the same, and not all patients with diabetes are treated the same. The same should go for patients with obesity.
The prognostic role of perioperative allogeneic blood transfusions in gastric cancer patients undergoing curative resection: A systematic review and meta-analysis of non-randomized, adjusted studies.

Abstract The impact of allogeneic perioperative blood transfusions (APTs) on the prognosis of gastric cancer patients undergoing curative-intent gastrectomy is still a highly debated topic. Two meta-analyses were published in 2015, and new studies report conflicting results. A literature review was conducted using PubMed, Scopus, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews, updated to March 1, 2016. Thirty-eight non-randomized studies reporting data on overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS) and postoperative complications (PCs) were included. An inverse variance random-effects meta-analysis was conducted. APTs showed an association with worse OS, DFS, DSS and an increased number of PCs. The hazard ratio (HR) for OS was 1.49, with a 95% confidence interval (95% CI) of 1.32–1.69 (p This meta-analysis showed a significant association between transfusions and OS, DFS, DSS and PCs. The quality of the evidence was low. Aggregation, selection and selective reporting bias were detected. The biases shifted the results towards significance. Further studies using accurate adjustment methods are needed. Until such additional studies are performed, caution in administering transfusions and optimization of cancer patient blood management are warranted.
8. DECREASING CARDIOVASCULAR RISK IN PERSONS WITH SCHIZOPHRENIA: INTERVENTIONS AND FUTURE DIRECTIONS

Abstract Overall Abstract: Persons with schizophrenia experience two to three times higher mortality than the overall population. This premature death is due in large part to cardiovascular disease and is potentially preventable. All cardiovascular risk factors are elevated in persons with schizophrenia. This presentation will describe the evidence for interventions to reduce cardiovascular risk factors in this vulnerable population, including obesity and tobacco smoking, and will describe models of integrated physical and mental health care. Ongoing research on interventions to decrease cardiovascular risk in schizophrenia will be presented, and future research needs will be discussed including implementation strategies to scale-up interventions to reduce cardiovascular disease risk in community settings.
Adaptation Without Boundaries: Population Genomics in Marine Systems

From the surface, the world’s oceans appear vast and boundless. Ocean currents, which can transport marine organisms thousands of kilometers, coupled with species that spend some or all of their life in the pelagic zone, the open sea, highlight the potential for well-mixed, panmictic marine populations. Yet these ocean habitats do harbor boundaries. In this largely three-dimensional marine environment, gradients form boundaries. These gradients include temperature, salinity, and oxygen gradients. Ocean currents also form boundaries between neighboring water masses even as they can break through barriers by transporting organisms huge distances. With the advent of next-generation sequencing approaches, which allow us to easily generate a large number of genomic markers, we are in an unprecedented position to study the effects of these potential oceanic boundaries and can ask how often and when do locally adapted marine populations evolve. This knowledge will inform our understanding of how marine organisms respond to climate change and affect how we protect marine diversity. In this chapter I first discuss the major boundaries present in the marine environment and the implications they have for marine organisms. Next, I discuss the how genomic approaches are impacting our understanding of genetic connectivity, ocean fisheries, and local adaptation, including the potential for epigenetic adaptation. I conclude with considerations for marine conservation and management and future prospects.
Laser/Materials Interactions: CW DF Laser Ablation of Carbon

DF chemical laser interactions with isotropic (graphNOL) and anisotropic (pyrolytic graphite, diamond) carbons have been studied in order to analyze the intrinsic ablation performance of these materials and to measure their responses and properties under well-characterized laser irradiation conditions. Several hundred experiments were performed over a broad range of intensities in order to determine burnthrough times, reflectances at DF wavelengths, and front and back surface temperatures during irradiation. Burnthrough data were analyzed to provide Q⋆ values (energies of ablation per gram of material) as a function of laser intensity and to understand energy and mass balances associated with laser-induced ablation. In addition, a laser probe absorption spectrometer was used to observe quantitative time-resolved spectra of carbon vapor species in laser-ablated plumes. All of the experiments are used to examine the physical and chemical processes that produce the phenomenology and effects characteristic of pure thermochemical ablation of materials by cw infrared lasers.
Frame semantics and the domain of functioning, disability and health.

We explore the use of FrameNet (FN) frames and their frame elements to represent content from the International Classification of Functioning, Disability and Health (ICF) Self-Care chapter. Terms were extracted from the ICF and mapped to FN frames later validated by an expert. FN provided relevant and nearly complete coverage of ICF terms, suggesting FN may be an important resource to leverage for semantic language processing and knowledge representation in this domain.
Fracture of the Costal Cartilage: Presentation, Diagnosis, and Management

A 52-year-old woman sustained a fracture of the left 7th costal cartilage after a ski injury. She presented complaining of painful clicking over the area. Initial imaging studies were negative for fracture; however, 3-dimensional reconstruction of a chest computed tomography scan, formatted to costal cartilage, revealed the fracture. She was offered and underwent surgical fixation of the fracture with a plate and 4 screws using a biaxial, convergent construct. Postoperatively, her symptoms resolved. In this case report, we review the rationale for fixation of costal cartilage, including a summary of previous literature pertaining to this relatively rare thoracic injury.
Genome-scale metabolic modeling identifies novel targets of redox metabolism in radiation-resistant tumors

Ionizing radiation results in the generation of reactive oxygen species, causing DNA damage and a depletion of the antioxidative capacities of cancer cells. Tumors that are resistant to radiation therapy rely on the production of reducing equivalents and maintenance of redox homeostasis to overcome the damaging effects of ionizing radiation. To identify components of redox metabolism that can be targeted to improve radiation sensitivity in individual patient tumors, we have developed personalized genome-scale metabolic models of 716 radiation-sensitive and 199 radiation-resistant tumors using genomic and transcriptomic data from The Cancer Genome Atlas. Through incorporation of multi-omic, kinetic, and thermodynamic information, these computational models can quantitatively predict maximum metabolite production and steady-state reaction fluxes within individual tumors. Metabolic models predict that radiation-resistant tumors show increased reduction of NAD+ to NADH (p = 4.5e-4) and NADP+ to NADPH (p = 8.5e-3), as well as increased reduction of glutathione (p = 4.5e-6). Enhanced NADPH production allows radiation-resistant tumors to produce greater levels of deoxyribonucleotides (p = 1.3e-10), which are needed for DNA damage repair after ionizing radiation. The increase in reduction of NADP+ to NADPH in radiation-resistant tumors is eliminated when simulating hypoxic conditions, demonstrating the importance of oxygen availability in radiation therapy response. By performing a simulated knockout screen of 3,268 genes throughout the human metabolic network, we identified 47 knockouts that caused a significantly greater decrease in NADP+ reduction in radiation-resistant tumors compared to radiation-sensitive tumors (adjusted p
PAH and Pregnancy: Physiologic Changes, Challenges, and Outcomes

For most expectant mothers, pregnancy is a happy time. It is a time of scheduled obstetrical appointments, prenatal vitamins, prenatal classes, and baby showers, with the greatest concern being sho...
Erdős-Ginzburg-Ziv Constants by Avoiding Three-Term Arithmetic Progressions

For a finite abelian group $G$, The Erdős-Ginzburg-Ziv constant $\mathfrak{s}(G)$ is the smallest $s$ such that every sequence of $s$ (not necessarily distinct) elements of $G$ has a zero-sum subsequence of length $\operatorname{exp}(G)$. For a prime $p$, let $r(\mathbb{F}_p^n)$ denote the size of the largest subset of $\mathbb{F}_p^n$ without a three-term arithmetic progression. Although similar methods have been used to study $\mathfrak{s}(G)$ and $r(\mathbb{F}_p^n)$, no direct connection between these quantities has previously been established. We give an upper bound for $\mathfrak{s}(G)$ in terms of $r(\mathbb{F}_p^n)$ for the prime divisors $p$ of $\operatorname{exp}(G)$. For the special case $G=\mathbb{F}_p^n$, we prove $\mathfrak{s}(\mathbb{F}_p^n)\leq 2p\cdot r(\mathbb{F}_p^n)$. Using the upper bounds for $r(\mathbb{F}_p^n)$ of Ellenberg and Gijswijt, this result improves the previously best known upper bounds for $\mathfrak{s}(\mathbb{F}_p^n)$ given by Naslund.
Integrating functional connectivity and MVPA through a multiple constraint network analysis

Traditional general linear model-based brain mapping efforts using functional neuroimaging are complemented by more recent multivariate pattern analyses (MVPA) that apply machine learning techniques to identify the cognitive states associated with regional BOLD activation patterns, and by connectivity analyses that identify networks of interacting regions that support particular cognitive processes. We introduce a novel analysis representing the union of these approaches, and explore the insights gained when MVPA and functional connectivity analyses are allowed to mutually constrain each other within a single model. We explored multisensory semantic representations of concrete object concepts using a self-paced multisensory imagery task. Multilayer neural networks learned the real-world categories associated with macro-scale cortical BOLD activity patterns from the task, with some models additionally encoding regional functional connectivity. Models trained to encode functional connections demonstrated superior classification accuracy and more pronounced lesion-site appropriate category-specific impairments. We replicated these results in a data set from the openneuro.org open fMRI data repository. We conclude that mutually constrained network analyses encourage parsimonious models that may benefit from improved biological plausibility and facilitate discovery.
Genomic and Fitness Consequences of Genetic Rescue in Wild Populations

Gene flow is an enigmatic evolutionary force because it can limit adaptation but may also rescue small populations from inbreeding depression [1-3]. Several iconic examples of genetic rescue-increased population growth caused by gene flow [4, 5]-have reversed population declines [6, 7]. However, concerns about outbreeding depression and maladaptive gene flow limit the use of human-mediated gene flow in conservation [8, 9]. Rescue effects of immigration through demographic and/or genetic mechanisms have received theoretical and empirical support, but studies that monitor initial and long-term effects of gene flow on individuals and populations in the wild are lacking. Here, we used individual-based mark-recapture, multigenerational pedigrees, and genomics to test the demographic and evolutionary consequences of manipulating gene flow in two isolated, wild Trinidadian guppy populations. Recipient and source populations originated from environments with different predation, flow, and resource regimes [10]. We documented 10-fold increases in population size following gene flow and found that, on average, hybrids lived longer and reproduced more than residents and immigrants. Despite overall genomic homogenization, alleles potentially associated with local adaptation were not entirely swamped by gene flow. Our results suggest that genetic rescue was caused not just by increasing individual genetic diversity, rather new genomic variation from immigrants combined with alleles from the recipient population resulted in highly fit hybrids and subsequent increases in population size. Contrary to the classic view of maladaptive gene flow, our study reveals conditions under which immigration can produce long-term fitness benefits in small populations without entirely swamping adaptive variation.
Effect of particle size distribution on the packing of powder beds: A critical discussion relevant to additive manufacturing

Abstract Several additive manufacturing (AM) methods use powder feed materials. Selective laser sintering is an example of a versatile AM method, using feed material in powder form, capable of producing polymer and metallic parts. In the variations of this technique, a laser spot or an electron beam is used to locally sinter or melt a packed powder bed. After the completion of sintering on each layer, further powder is added on top of the existing bed so that the next layer may be joined. A major challenge in this method is controlling the porosity of the powder bed so that the final part has uniform and maximum density. Uniformity in the packing of bed from one layer to the other is important for optimizing the processing parameters. This review is focused on considering the packing characteristics of polydisperse hard particle beds and the determination of the expected density achievable for a given particle size and shape distribution. Models are presented for discrete mixtures as well as continuous distributions. The effect of the initial configuration of a particle bed on its ability to form a highly dense packing is also discussed. Blending of different particle sizes and shapes can be used to substantially increase the packing density, but can also lead to separation or segregation of the bed. Through appropriate control of the particle shape and use of wide distributions, packing densities close to 100 % can theoretically be achieved, but practicality and various effects that appear at small size scales prevent from achieving such high packing densities. Recent advancements have reduced the dependence of AM part quality on the density of the packed particle bed but the packing is still important for considerations such as thermal conductivity of the bed and absorption of laser power in the bed. Improved knowledge of packed bed characteristics can be helpful in developing AM methods for novel material systems.
Genomic sequencing of Gracilibacillus dipsosauri reveals key properties of a salt-tolerant α-amylase.

Gracilibacillus dipsosauri is a moderately-halophilic Gram-positive bacterium which forms an extracellular α-amylase that is induced by starch, repressed by d-glucose, and active in 2.0 M KCl. Previous studies showed that while enzyme activity could be measured with the synthetic substrate 2-chloro-4-nitrophenyl-α-d-maltotrioside (CNPG3), other assays were inconsistent and the protein showed aberrant mobility during nondenaturing gel electrophoresis. To clarify the properties of this enzyme, the genome of G. dipsosauri was sequenced and was found to be 4.19 Mb in size with an overall G+C content of 36.9%. A gene encoding an α-amylase composed of 691 amino acids was identified. The protein was a member of the glycosyl hydrolase 13 family, which had a molecular mass of 77,396 daltons and a pI of 4.39 due to an unusually large number of aspartate and glutamate residues (95/691 or 13.7%). BLAST analysis of the amino acid sequence revealed significant matches to other proteins with cyclodextrin glycosyltransferase activity. Partial purification of the protein from G. dipsosauri showed that fractions catalyzing the hydrolysis of CNPG3 and p-nitrophenyl-d-maltoheptoside also catalyzed the formation of β-cyclodextrin but not α-cyclodextrin or γ-cyclodextrin. Formation of β-cyclodextrin was not stimulated by high salt concentrations but did occur with rice, potato, wheat, and corn starches and amylopectin. These studies explain the unusual features of the α-amylase from G. dipsosauri and indicate it should be classified as EC 2.4.1.19. The availability of the complete genomic sequence of G. dipsosauri will provide the basis for studies on other enzymes from this halophile which may be useful for biotechnology.
Liquid biopsy is a valuable tool in the diagnosis and management of lung cancer

Liquid biopsy refers to the use of various body fluids to test for circulating biological elements derived from the tumor. Liquid biopsy has taken on an increasingly important role in lung cancer diagnosis, molecular characterization, surveillance, monitoring, and determining mechanisms of resistance. These assays can utilize various sources of cell-free DNA (cfDNA) including blood, pleural fluid, urine, and others to detect tumor associated alterations. With the increasing power of next-generation sequencing technologies and the development of assays such as digital droplet PCR, rare tumor alleles can be detected in cfDNA to determine key characteristics of the tumor. Current assays, while effective, are still challenged by limited sensitivity and capacity to single genes or small panels of genes, though this is rapidly expanding. Nevertheless, testing of cfDNA has been shown to be valuable in detecting resistance to targeted inhibitors, particularly for detection of T790M in EGFR and monitoring response to therapy. With the continued development of more powerful and sensitive assays, these techniques will empower clinicians to better characterize early stage disease and can be used in the screening of high-risk patients, which may eliminate the requirement for tissue diagnosis in some settings. That said, since the majority of these alterations are not specific to lung cancer, there will continue to be a need for tissue in at least the initial diagnosis. Used in conjugation with tissue sampling, these assays will assist the treating clinician and the pathologist to better characterize individual tumors, even in the setting of limited tissue.
Expectations of Students Participating in Voluntary Peer Academic Coaching

Peer mentoring and associated programs have gained prominence due to demonstrated positive effects on student retention and matriculation, but scant research exists on voluntary peer academic coach...
Prenatal stress induced chromatin remodeling and risk of psychopathology in adulthood

New insights into the pathophysiology of psychiatric disorders suggest the existence of a complex interplay between genetics and environment. This notion is supported by evidence suggesting that exposure to stress during pregnancy exerts profound effects on the neurodevelopment and behavior of the offspring and predisposes them to psychiatric disorders later in life. Accumulated evidence suggests that vulnerability to psychiatric disorders may result from permanent negative effects of long-term changes in synaptic plasticity due to altered epigenetic mechanisms (histone modifications and DNA methylation) that lead to condensed chromatin architecture, thereby decreasing the expression of candidate genes during early brain development. In this chapter, we have summarized the literature of clinical studies on psychiatric disorders induced by maternal stress during pregnancy. We also discussed the epigenetic alterations of gene regulations induced by prenatal stress. Because the clinical manifestations of psychiatric disorders are complex, it is obvious that the biological progression of these diseases cannot be studied only in postmortem brains of patients and the use of animal models is required. Therefore, in this chapter, we have introduced a well-established mouse model of prenatal stress (PRS) generated in restrained pregnant dams. The behavioral phenotypes of the offspring (PRS mice) born to the stressed dam and underlying epigenetic changes in key molecules related to synaptic activity were described and highlighted. PRS mice may serve as a useful model for investigating the pathogenesis of psychiatric disorders and may be a useful tool for screening for the potential compounds that may normalize aberrant epigenetic mechanisms induced by prenatal stress.
Quasi-Judicial Oversight of Legislative and Executive Branches at the Local Level

Oversight is a function commonly associated with the legislative branch of government at the federal and state level. To a lesser extent, the concept is extended to the judicial branch in the form of court cases clarifying the powers between the legislative-executive-judicial branches. However, at the local level, the judicial branch may not be limited to oversight of co-equal branches through court cases alone. In the state of California, there exists county-level civil grand juries which are housed in the judicial branch. Civil grand juries, which have endured since the state’s founding constitution of 1850, have complete discretion to investigate the operations of local government officials, departments, and agencies. These civil grand juries represent quasi-judicial oversight of local legislative and executive branches of government. How responsive are local legislative and executive branches of governments to such oversight?
THERMAL AND TRANSPORT PROPERTIES OF A NONRELATIVISTIC QUANTUM GAS INTERACTING THROUGH A DELTA-SHELL POTENTIAL

This work extends the seminal work of Gottfried on the two-body quantum physics of particles interacting through a delta-shell potential to many-body physics by studying a system of nonrelativistic particles when the thermal De-Broglie wavelength of a particle is larger than the range of the potential and the density is such that average distance between particles is larger than the above range. The ability of the delta-shell potential to reproduce some basic properties of the deuteron are examined. Relations for moments of bound-states are derived. The virial expansion is used to calculate the first quantum correction to the ideal gas pressure in the form of the second virial coefficient. Additionally, all thermodynamical functions are calculated up to the first-order quantum corrections. For small departures from equilibrium, the net flows of mass, energy and momentum, characterized by the coefficients of diffusion, thermal conductivity and shear viscosity, respectively, are calculated. Properties of th...
I’m Here for the Hard Re-Set: Post Pandemic Pedagogy to Preserve Our Culture

The challenge of the COVID-19 pandemic exposed many of the nation’s vulnerabilities—health care, economic, climate, and educational disparities—and put us all on alert. While many are scrambling fo...
Development and genetics of red coloration in the zebrafish relative Danio albolineatus

Abstract Animal pigment patterns play important roles in behavior and, in many species, red coloration serves as an honest signal of individual quality in mate choice. Among Danio fishes, some species develop erythrophores, pigment cells that contain red ketocarotenoids, whereas other species, like zebrafish (D. rerio) only have yellow xanthophores. Here, we use pearl danio (D. albolineatus) to assess the developmental origin of erythrophores and their mechanisms of differentiation. We show that erythrophores in the fin of D. albolineatus share a common progenitor with xanthophores and maintain plasticity in cell fate even after differentiation. We further identify the predominant ketocarotenoids that confer red coloration to erythrophores and use reverse genetics to pinpoint genes required for the differentiation and maintenance of these cells. Our analyses are a first step towards defining the mechanisms underlying the development of erythrophore-mediated red coloration in Danio and reveal striking parallels with the mechanism of red coloration in birds.
Clinical rebirth of flavopiridol in chronic lymphocytic leukemia (CLL): Utilizing in vitro and in vivo pharmacodynamic measurements to improve efficacy and interrogate relevant mechanism(s) of action

Proc Amer Assoc Cancer Res, Volume 46, 2005 1672 Flavopiridol is a broad cyclin dependent kinase (CDK) inhibitor that exhibited promising pre-clinical activity in CLL and other cancers. In vitro , flavopiridol has been noted to promote a rapid decrease in Mcl-1 and XIAP expression in CLL cells. This was presumed to be secondary to inhibition of CDK9 and CDK7 and subsequent global transcription inhibition by preventing RNA Polymerase II (RPII) phosphorylation. Despite potent pre-clinical activity of flavopiridol, previous clinical trials in CLL and other diseases using a one-, 24-, and 72-hour schedule of administration demonstrated either marginal or no activity. Significant plasma protein binding of flavopiridol in human serum relative to fetal bovine serum prompted our group to perform pharmacokinetic modeling, which suggested an optimal dosing schedule of 30-minute IV bolus followed by four-hour continuous infusion. A mature phase I dose escalation study of single agent flavopiridol, utilizing this schedule included 23 relapsed and refractory, genetically high risk CLL patients, demonstrated a 43% response rate and a dose limiting toxicity of acute tumor lysis syndrome. In conjunction with this study, we sought to explore the in vitro modulation of select flavopiridol targets in human serum and the relevance of these to in vivo observations. In vitro, we demonstrated that Mcl-1 protein level dramatically decreased after four hours, while XIAP, Bcl-2, and Bax levels did not change. Diminishment of Mcl-1 mRNA was noted as early as 30 minutes post-treatment with flavopiridol. Of interest, no change in RPII phosphorylation was detected at concentrations where Mcl-1 protein and mRNA were decreased. We next sought to determine if similar modulation of Mcl-1 occurred in vivo following treatment. In two of three responding patients, significant diminishment of Mcl-1 protein, but not XIAP, Bcl-2, Bax, RPII, or RPII phosphorylation, was noted. In five non-responding patients, there was either no change or an increase in Mcl-1 protein. Our preliminary in vitro and in vivo data suggest that flavopiridol is influencing an alternative transcription factor responsible for Mcl-1 expression in CLL, and not global transcription via inhibition of RPII. Additionally, we demonstrate the value of translational in vitro and in vivo studies in CLL for both interrogating the mechanism of action of new therapeutic agents and optimizing the schedule of administration in human phase I studies.
A “Smart” Biosensor-Enabled Intravascular Catheter and Platform for Dynamic Delivery of Propofol to “Close the Loop” for Total Intravenous Anesthesia

Background Target-controlled infusion anesthesia is used worldwide to provide user-defined, stable, blood concentrations of propofol for sedation and anesthesia. The drug infusion is controlled by a microprocessor that uses population-based pharmacokinetic data and patient biometrics to estimate the required infusion rate to replace losses from the blood compartment due to drug distribution and metabolism. The objective of the research was to develop and validate a method to detect and quantify propofol levels in the blood, to improve the safety of propofol use, and to demonstrate a pathway for regulatory approval for its use in the USA. Methods We conceptualized and prototyped a novel "smart" biosensor-enabled intravenous catheter capable of quantifying propofol at physiologic levels in the blood, in real time. The clinical embodiment of the platform is comprised of a "smart" biosensor-enabled catheter prototype, a signal generation/detection readout display, and a driving electronics software. The biosensor was validated in vitro using a variety of electrochemical methods in both static and flow systems with biofluids, including blood. Results We present data demonstrating the experimental detection and quantification of propofol at sub-micromolar concentrations using this biosensor and method. Detection of the drug is rapid and stable with negligible biofouling due to the sensor coating. It shows a linear correlation with mass spectroscopy methods. An intuitive graphical user interface was developed to: (1) detect and quantify the propofol sensor signal, (2) determine the difference between targeted and actual propofol concentration, (3) communicate the variance in real time, and (4) use the output of the controller to drive drug delivery from an in-line syringe pump. The automated delivery and maintenance of propofol levels was demonstrated in a modeled benchtop "patient" applying the known pharmacokinetics of the drug using published algorithms. Conclusions We present a proof-of-concept and in vitro validation of accurate electrochemical quantification of propofol directly from the blood and the design and prototyping of a "smart," indwelling, biosensor-enabled catheter and demonstrate feedback hardware and software architecture permitting accurate measurement of propofol in blood in real time. The controller platform is shown to permit autonomous, "closed-loop" delivery of the drug and maintenance of user-defined propofol levels in a dynamic flow model.
Pragmatic derivations

In this paper I have tried to give the SAS some descriptive content with respect to English. I have suggested that correlations of form, function and fit play a central role in accounting for understanding literal and direct communication, and I have tried to take some initial steps towards constructing a plausible theory of such communication incorporating these notions.
Narrow Therapeutic Index drugs: clinical pharmacology perspective

OBJECTIVES Historically, the identification of drugs with the Narrow Therapeutic Index (NTI) has been empirically based on the clinical practice. In general terms, NTI drugs can be defined based on the steepness of the dose-response relationship and the degree of overlap between the effective and the toxic concentrations. KEY FINDINGS The current definition in the Code of Federal Regulations is based on animal data and as such lacks direct clinical relevance. By basing these criteria on those factors that affect the degree of separation of the concentrations that elicit the therapeutic and the adverse effects, it was attempted to avoid the vagaries inherent in preparing a list of individual drugs themselves. SUMMARY The overall conclusions are: (1) The issue of NTI drugs is still highly controversial, (2) The lists of NTI drugs are arbitrary and (3) Variability may contribute to the safety and efficacy. The objectives are to (1) To facilitate consensus on the definition of a NTI, (2) To identify characteristics of NTI and (3) To develop criteria for identifying NTI. The FDA should consider not only the pharmacokinetics (PK) studies, but also comparative efficacy and safety studies, for the NTI drugs to further to try 'convince or educate' the prescribers.
Birth and delineation of the intestinal stem cell niche

Abstract Wnt and Rspondin (RSPO) signaling triggers proliferation, and bone morphogenetic protein inhibitors (BMPi) impede differentiation, of intestinal stem cells (ISCs). Here we report that the functional ISC niche is a complex, multi-layered mesenchymal structure that includes distinct smooth muscle populations and describe how that niche organizes early in mouse life. Diverse sub-cryptal cells provide redundant supportive factors, with distinct BMPi and the most potent Wnt agonist, RSPO2, restricted to single cell types. Two functionally opposing elements arise in tandem during a critical period of crypt morphogenesis: a prominent shelf of BMP+ sub-epithelial myofibroblasts that promote epithelial differentiation and the muscularis mucosae, a specialized muscle layer generated de novo to supplement other RSPO and BMPi sources. In vivo ablation of smooth muscle, while preserving trophocytes, raises crypt BMP activity and potently limits crypt expansion. Thus, distinct and progressively refined mesenchymal components together create the milieu necessary to propagate crypts during rapid organ growth and to sustain ISCs in the adult niche.
Stress Distributions and Notch Stress Intensity Factors in Multimaterial V-notches Under Antiplane Shear and Torsion

This study investigates how the insertion of multimaterial circular regions embracing the tip of a finite V-notch can be used to reduce the Notch Stress Intensity Factors (NSIFs) in structures subjected to antiplane shear or torsion. Towards this goal, this work presents a novel theoretical framework to calculate stress distributions and NSIFs in closed-form. Thanks to the new solution, it is shown that by tuning multimaterial region radii and elastic properties it is possible to significantly reduce the NSIFs and stress concentrations at the material interfaces. To investigate whether the proposed multimaterial system translates into increased structural capacity even in the presence of significant nonlinear deformations, computational simulations were conducted using nonlinear hyperelastic-damage and elasto-plastic-damage models. The preliminary results show increases of structural capacity up to 46% and of nominal strain at failure of up to 86% at the expenses of only a 8% reduction in structural stiffness. It is expected that a similar approach can be extended to other loading conditions (e.g. mode I and mode II, and fatigue) and that even larger gains can be obtained by performing thorough optimization studies.
Clinical Aspects in Vascular Malformations

Since the turn of the last century, relentless efforts were made on the congenital vascular malformation (CVM) for better understanding. But, the CVM still remains as an enigma in modern medicine with such wide range of clinical presentation, unpredictable clinical course, and erratic response to the treatment with high recurrence: the most difficult and confusing diagnostic as well as therapeutic challenge among various vascular disorders [1–3].
Use of human minor salivary glands in basic and applied secretion research.

Previous findings from studies utilizing human labial and palatine minor salivary glands are reviewed. These studies took histopathological, biochemical, and ultrastructural approaches, and focused on control and diseased glands. Disease-oriented summarizations are used, and control results are discussed in the context of disease-related findings. Findings are reviewed separately for electrolytes, macromolecules, and ultrastructure. In control subjects, minor gland salivary electrolyte concentrations are dependent on flow rate, and this dependence may be altered by diseases such as cystic fibrosis as-well as by inflammatory situations such as graft-versus-host disease. There is also evidence that salivary electrolyte secretion processes are not similar in labial and palatine minor glands. Studies of salivary macromolecular composition are reviewed for control subjects and for patients with graft-versus-host disease and Sjogren's syndrome. The findings indicate that the macromolecular contents of labial an...
A microfluidic 2/spl times/2 optical switch

A novel 2/spl times/2 microfluidic-based optical switch is demonstrated. The device is made of an optically clear elastomer, using soft lithography, and having insertion loss smaller than 1 dB, extinction ratio of 20 dB and switching speed less than 20 milliseconds.
Optimal Information Transfer and Real-Vector-Space Quantum Theory

Consider a photon that has just emerged from a linear polarizing filter. If the photon is then subjected to an orthogonal polarization measurement—e.g., horizontal vs vertical—the photon’s preparation cannot be fully expressed in the outcome: a binary outcome cannot reveal the value of a continuous variable. However, a stream of identically prepared photons can do much better. To quantify this effect, one can compute the mutual information between the angle of polarization and the observed frequencies of occurrence of “horizontal” and “vertical.” Remarkably, one finds that the quantum-mechanical rule for computing probabilities—Born’s rule—maximizes this mutual information relative to other conceivable probability rules. However, the maximization is achieved only because linear polarization can be modeled with a real state space; the argument fails when one considers the full set of complex states. This result generalizes to higher dimensional Hilbert spaces: in every case, one finds that information is transferred optimally from preparation to measurement in the real-vector-space theory but not in the complex theory. Attempts to modify the statement of the problem so as to see a similar optimization in the standard complex theory are not successful (with one limited exception). So it seems that this optimization should be regarded as a special feature of real-vector-space quantum theory.
Title VII in the Hands of a Principal: A Strategy for Change

Abstract Title VII programs offered the promise of change to many Hispanics who saw their children receiving an inferior education in the public schools they attended. A principal of an elementary school in the Los Angeles, California area attempted to make good on the promise when he was offered the program for his school. Against the backdrop of a typology of change strategies used in the schools, the principal’s development of a Title VII program and the kinds of changes that took place during the program’s ten year history are examined. It was possible to see how different strategies were utilized within an overall framework of renewal. Some of the strategies were successful, others were not. So far, the challenge has been met; the children continue to achieve at a high level, more parents are active at the school than ever before and the reputation goes on.
New rare earth-alkaline earth oxide compounds: Predicted compound formation and new families found

Abstract The study of crystal chemical relationships between sesquioxides of certain rare earth ions [La, Gd, (Y), Ho, Yb] and the alkaline earth oxides shows that compound formation at two compositions is extensive. The molar ratios of these compositions, alkaline earth oxide to rare earth oxide, are 1:1 and 1:2. There appear to be three different structures at the 1:1 composition. From the similarities of X-ray diffraction patterns obtained, the prepared compounds are grouped as follows: (I) CaY 2 O 4 and CaHo 2 O 4 (II) CaYb 2 O 4 , SrGd 2 O 4 , SrY 2 O 4 , SrHo 2 O 4 , and SrYb 2 O 4 (III) BaGd 2 O 4 , BaY 2 O 4 , BaHo 2 O 4 , and BaYb 2 O 4 Even within one of these structural families, it is probable that there are minor distortions which affect exact space group correspondence. The 1:2 compounds have X-ray diffraction patterns which are even more similar. The compounds CaGd 4 O 7 , CaY 4 O 7 , CaHo 4 O 7 , CaYb 4 O 7 , and SrGd 4 O 7 were prepared. Application of simple field strength calculations in these systems predicts compound formation only between BaO and rare earth oxides possessing trivalent rare earth ions of the smallest radii.
Application of AAPM TG 119 to volumetric arc therapy (VMAT).

The purpose of this study was to create AAPM TG 119 benchmark plans for volumetric arc therapy (VMAT) and to compare VMAT plans with IMRT plan data. AAPM TG 119 proposes a set of test clinical cases for testing the accuracy of IMRT planning and delivery system. For these test cases, we generated two treatment plans, the first plan using 7–9 static dMLC IMRT fields and a second plan utilizing one- or two-arc VMAT technique. Dose optimization and calculations performed using 6MV photons and Eclipse treatment planning system. Dose prescription and planning objectives were set according to the TG 119 goals. Plans were scored based on TG 119 planning objectives. Treatment plans were compared using conformity index (CI) for reference dose and homogeneity index (HI) (for D5–D95). For test cases prostate, head-and-neck, C-shape and multitarget prescription dose are 75.6Gy, 50.4 Gy, 50 Gy and 50 Gy, respectively. VMAT dose distributions were comparable to dMLC IMRT plans. Our planning results matched TG 119 planning results. For treatment plans studied, conformity indices ranged from 1.05–1.23 (IMRT) and 1.04–1.23 (VMAT). Homogeneity indices ranged from 4.6%–11.0% (IMRT) and 4.6%–10.5% (VMAT). The ratio of total monitor units necessary for dMLC IMRT to that of VMAT was in the range of 1.1–2.0. AAPM TG 119 test cases are useful to generate VMAT benchmark plans. At preclinical implementation stage, plan comparison of VMAT and IMRT plans of AAPM TG 119 test case allowed us to understand basic capabilities of VMAT technique.
Learning in the museum

Learning in the Museum examines major issues and shows how research in visitor studies and the philosophy of education can be applied to facilitate a meaningful educational experience in museums. Hein combines a brief history of education in public museums, with a rigorous examination of how the educational theories of Dewey, Piaget, Vygotsky and subsequent theorists relate to learning in the museum. Surveying a wide range of research methods employed in visitor studies is illustrated with examples taken from museums around the world, Hein explores how visitors can best learn from exhibitions which are physically, socially, and intellectually accessible to every single visitor. He shows how museums can adapt to create this kind of environment, to provide what he calls the 'constructivist museum'. Providing essential theoretical analysis for students, this volume also serves as a practical guide for all museum professionals on how to adapt their museums to maximize the educational experience of every visitor.