cssi/SciSciGPT-SciSciNet huggingface dataset:
Suppression of nonpremixed flames by fluorinated ethanes and propanes

Abstract Suppression of methane/air and propane/air nonpremixed counterflow flames, and n-heptane and methanol cup burner flames by fluorinated hydrocarbons was investigated. Four fluorinated ethanes, 10 fluorinated propanes, four bromine- or iodine-containing halons, and the inert agents CF 4 , SF 6 , and N 2 were tested in some or all of the flames. Laser Doppler velocimetry (LDV) determinations of peak velocity gradients in the oxidizer flow of the counterflow flames were found to be linearly correlated with the expression for global strain rate derived for plug flow boundary conditions. This correlation was used to estimate strain rate values at extinction. The bromine- or iodine-containing agents are more effective on a molar basis than the fluorinated propanes, followed by the fluorinated ethanes, and finally SF 6 , CF 4 , and N 2 . Agent effectiveness increases with the number of CF 3 groups present in the agent molecular structure. Numerical investigations of the flame speed reduction of methane/air mixtures doped with either CHF 2 CHF 2 or CF 3 CH 2 F predict that the latter is the better agent, in accord with experimental observations. Chemical contributions to suppression account for less than 35% of the total suppression offered by fluorinated hydrocarbons not containing bromine or iodine. At strain rates below 100 s −1 , suppression effectiveness rankings in methane and propane counterflow flames are similar to those obtained in n-heptane and methanol cup burner flames. Methanol flames are more difficult to extinguish than the alkane flames investigated, particularly with the chemical agent CF 3 Br.
Optimum Design of a Reinforced Cylindrical Pressure Vessel

The distribution of fibers in a cylindrically reinforced pressure vessel of given size and constituent properties is optimized using the criterion of minimum strain energy. A stress function approach, in conjunction with the modified Rayleigh-Ritz technique, is employed to obtain an approximate solution to the non-linear optimization problem. Constraint conditions in clude specification of the global volume fraction of fibers and satisfaction of stress boundary conditions. Numerical results are presented for reinforced cylinders having various radii, modulus ratios, and global volume fractions. Included is the case of a reinforced concrete cylinder, in which the concrete is assumed to be ineffective in tension. In most cases examined, use of the op timum fiber distribution, rather than a uniform distribution, results in a substantial reduction in the maximum radial displacement and an increase in the failure pressure load.
Computational experiments on the migration of internal energy in macromolecular systems

Abstract The mechanistic details of internal energy flow in models of polyethylene containing up to 300 000 atoms (with explicit treatment of hydrogens) is discussed. The intra- and intermolecular dynamics of the macromolecular systems is studied as a function of CH-stretch excitation, temperature, pressure, crystal structure, and phase (solid, melt, or gas) by employing the quasiclassifical trajectory method coupled with computational neural networks. The rate of energy flow local and normal CH stretching modes is found to be very rapid and irreversible, occuring on a time scale of less than 1.0 picosecond at low temperatures and increases with rising temperature. The flow of energy follows a pathway that traces out multiple stages, with an initial rapid flow due to the decay of the excitation followed by a slower flow related to redistribution throughout the system. The mechanism for the facile energy flow is shown to involve strong nonlinear couplings dominated by a CH-stretch/HCH bend Fermi (1:2) resonance. This strong dynamical interaction facilitates the overall process of energy flow away from CH stretching sites in all of the various macromolecular systems that were examined. A second type of energy relaxation process is observed in the long-time dynamics which demonstrates two primary components: the time required to redistribute the initial energy intramolecularly (within a chain) and the time associated for complete redistribution among all of the available vibrational modes (intermolecularly, chain to chain). Intramolecular redistribution occurs on a 2 picosecond time scale while the intermolecular process requires up to 270 ps (two orders of magnitude longer). However, both processes are coupled, even on a picosecond time scale, thereby leading to intermolecularly assisted intramolecular energy transfer. Overall, the results demonstrate that there are invariant pathways for energy redistribution in polyethylene (marked by strong nonlinear coupling such as Fermi resonances). However, due to the differences in the intermolecular interactions for the various environments (different phases), the processes occur over a range of time scales. A thermal conductivity of 0.253 J/ (K m s) and a rate for heat diffusion of 1.6 Km/s were determined for a highly crystalline model of polyethylene based on the simulations. The thermal conductivity tends to decrease substantially as the model is allowed to have more amorphous content and approaches a value near 0.15 J/ (K m s).
Biomolecular Path Sampling Enabled by Processing in Network Storage

Computationally complex and data intensive atomic scale biomolecular simulation is enabled via processing in network storage (PINS): a novel distributed system framework to overcome bandwidth, compute, storage, and security challenges inherent to the wide area computation and storage grid. High throughput data generation requirements for our scientific target are overcome through novel aggregate bandwidth capabilities. Biomolecular simulation methods are correlated with the client tools, hybrid database/file server (GEMS), computation engine (Condor), virtual file system adapter (Parrot), and local file servers (Chirp). PINS performance is reported for the path sampling of a solvated protein domain requiring over 1000 simulations with total output data generation on the order of 1TB.
Enabling technologies and architectures for 5G wireless

The proliferation of smart devices and the resulting exponential growth in data traffic has increased the need for higher capacity wireless networks. The cellular systems industry is envisioning an increase in network capacity by a factor of 1000 over the next decade to meet this traffic demand. In addition, with the emergence of Internet of Things (IoT), billions of devices will be connected and managed by wireless networks. Future networks must satisfy the above mentioned requirements with high energy efficiency and at low cost. Hence, the industry attention is now shifting towards the next set of innovations in architecture and technologies that will address capacity and service demands envisioned for 2020, which cannot be met only with the evolution of 4G systems. These innovations are expected to form the so called fifth generation wireless communications systems, or 5G. Candidate 5G solutions include i) higher densification of heterogeneous networks with massive deployment of small base stations supporting various Radio Access Technologies (RATs), ii) use of very large Multiple Input Multiple Output (MIMO) arrays, iii) use of millimeter Wave spectrum where larger wider frequency bands are available, iv) direct device to device (D2D) communication, and v) simultaneous transmission and reception, among others. In this paper, we present the main 5G technologies. We also discuss the network and device evolution towards 5G.
Phylogenetic analysis of 5'-noncoding regions from the ABA-responsive rab16/17 gene family of sorghum, maize and rice provides insight into the composition, organization and function of cis-regulatory modules.

Phylogenetic analysis of sequences from gene families and homologous genes from species of varying divergence can be used to identify conserved noncoding regulatory elements. In this study, phylogenetic analysis of 5′-noncoding sequences was optimized using rab17, a well-characterized ABA-responsive gene from maize, and five additional rab16/17 homologs from sorghum and rice. Conserved 5′-noncoding sequences among the maize, sorghum, and rice rab16/17 homologs were identified with the aid of the software program FootPrinter and by screening for known transcription-factor-binding sites. Searches for 7 of 8 (7/8)bp sequence matches within aligned 5′-noncoding segments of the rab genes identified many of the cis-elements previously characterized by biochemical analysis in maize rab17 plus several additional putative regulatory elements. Differences in the composition of conserved noncoding sequences among rab16/17 genes were related to variation in rab gene mRNA levels in different tissues and to response to ABA treatment using qRT-PCR. Absence of a GRA-like element in the promoter of sorghum dhn2 relative to maize rab17 was correlated with an ∼85-fold reduction of dhn2 RNA in sorghum shoots. Overall, we conclude that phylogenetic analysis of gene families among rice, sorghum, and maize will help identify regulatory sequences in the noncoding regions of genes and contribute to our understanding of grass gene regulatory networks.
On Failing to Resolve Theism-Versus-Atheism Empirically

At least since Hume's Dialogues Concerning Natural Religion , theism has been under indictment; indeed it has been on trial for its life. In part, this indictment is that the enormous quantity, variety, and distribution of evils evident in the natural world disconfirm the core beliefs of theism. Those core beliefs, I think, are the following pair: there exists a being at once omnipotent, omniscient, perfectly good, the worshipful creator of the universe (henceforth G); and G stands in a relation to the natural world which might be called one of moral responsibility (henceforth M). Obviously, theism says a lot more than the above, rather abrupt, conjunction; nevertheless, that conjunction constitutes its core.
Religion and Scientific Literacy in the United States

Objective This study examines how commitment to sectarian Protestant religious groups and fundamentalist beliefs in the inerrancy of the Bible influence basic scientific literacy. Methods I analyze data from the 2006 General Social Survey (N = 1,780), which included a 13-point examination of scientific facts and reasoning. Ordinary least squares regression models are estimated to determine the impact of religious affiliations and beliefs net of other control variables such as race, gender, education, income, region, and rural residence. Results Analyses show that sectarian Protestants, Catholics, and people with fundamentalist beliefs in the inerrancy of the Bible have significantly lower levels of scientific literacy when compared with secular Americans. Religious differences are identifiable in multivariate analyses controlling for other demographic factors. Conclusions Religion plays a sizeable role in the low levels of scientific literacy found in the United States, and the negative impact of religious factors is more substantial than gender, race, or income.
Heuristic risk assessment using cost factors

The author describes an expert system tool that can be used to analyze patterns of software cost driver ratings submitted for a Cocomo cost estimate. These results help users determine and rank associated sources of software project risk.
5,5,5′,5′‐Tetramethyl‐2,2′‐bi‐1,3,2‐dioxaborinane

[201733-56-4] C10H20B2O4 (MW 225.89) InChI = 1S/C10H20B2O4/c1-9(2)5-13-11(14-6-9)12-15-7-10(3,4)8-16-12/h5-8H2,1-4H3 InChIKey = MDNDJMCSXOXBFZ-UHFFFAOYSA-N (reagent to prepare boronic acid esters) Alternate Name: bis(neopentyl glycolato)diboron. Physical Data: mp 180.5–184.5 °C (dec). Solubility: sol in common organic solvents. Form Supplied in: white solid, commercially available. Preparative Method: by reaction of tetrakis(dialkylamino)diboron with alcohols with removal of dialkylamine by-product in gaseous form (eq 1).1 (1) Handling, Storage, and Precautions: avoid breathing dust, vapor, mist, or gas. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation. Use with adequate ventilation. Wash clothing before reuse. Store in a tightly closed container. Store in a dry area. Keep refrigerated (store below 4 °C/39 °F).
Intrinsic Myofilament Alterations Underlying the Decreased Contractility of Stunned Myocardium: A Consequence of Ca2+-Dependent Proteolysis?

Abstract We investigated the mechanism of the decreased myofilament Ca2+ responsiveness in stunned myocardium. The steady state force-[Ca2+] relationship was measured before and after skinning in t...
Childhood trauma, the neurobiology of adaptation, and "use-dependent" development of the brain: How "states" become "traits."

Childhood trauma has profound impact on the emotional, behavioral, cognitive, social, and physical functioning of children. Developmental experiences determine the organizational and functional status of the mature brain. The impact of rruumufic experiences on the development and function of the brain are discussed in context of basic principles of neurodevelopment. There are various adaptive mental and physical responses to trauma, including physiological hyperarousal and dissociation. Because the developing brain organizes and internalizes new information in a use-dependent fashion, the more a child is in a state of hyperarousal or dissociation, the more likely they are to have neuropsychiatric symptoms following trauma. The acute adaptive states, when they persist, can become maladaptive traits. The clinical implications of this new neurodevelopmental conceptualization of childhood trauma are discussed.
Determination of Basic Drugs in Post Mortem Tissues: A Microextraction Technique Utilizing GLC/NPD of Effluents

A method is described for the estimation of basic drugs and metabolites in post mortem tissues and fluids. The method is based upon the selective extraction of these substances, differential weak acid cleanup, and the final preparation of a microextract that is compatible with the rubidium source found in most nitrogen-phosphorous detectors (NPD). Application of this extract to gas chromatography/NPD allows for the measurement of common basic drugs at subtherapeutic, therapeutic, and toxic concentrations in a variety of tissue matrices (liver, brain, lung, heart, and kidney) using a minimum of sample (less than one gram). Internal standards are used to allow for the quantitative as well as qualitative aspects of the assay. Examples of tissue extract chromatograms containing commonly encountered basic drugs are presented along with precision data.
Small cell undifferentiated bronchogenic carcinoma: Current status with emphasis upon the role of chemotherapy

Current opinions concerning tumor biology and clinical characteristics of small cell undifferentiated bronchogenic carcinoma are reviewed. Special emphasis is placed upon chemotherapy for this lung cancer subtype and presently achievable response rates and survival times are presented. A series of 16 patients with small cell undifferentiated bronchogenic carcinoma is also presented. All patients were given cyclophosphamide, methotrexate, vincristine, and procarbazine as treatment for this neoplasm. Sixty-eight percent of patients responded and the survival time in partial responders was 33.4+ weeks as compared to 13.7 weeks with nonresponders. These data correlate well with the previous data of Alberto et al [Alberto P, Brunner KW, Martz G, Obrect JP: Cancer 38:2208--2216, 1976], who investigated the same agents for this tumor, but at higher dosages.
Floorplan-aware automated synthesis of bus-based communication architectures

As system-on-chip (SoC) designs become more complex, it is becoming harder to design communication architectures to handle the ever increasing volumes of inter-component communication. Manual traversal of the vast communication design space to synthesize a communication architecture that meets performance requirements becomes infeasible. In this paper, we address this problem by proposing an automated approach for synthesizing cost-effective, bus-based communication architectures that satisfy the performance constraints in a design. Our synthesis flow also incorporates a high-level floorplanning and wire delay estimation engine to evaluate the feasibility of the synthesized bus architecture and detect timing violations early in the design flow. We present case studies of network communication SoC subsystems for which we synthesized bus architectures, detected timing violations and generated core placements in a matter of hours instead of several days it took for a manual effort.
Emotion Regulation of Goals in Bipolar Disorder and Major Depression: A Comparison of Rumination and Mindfulness

Progress towards goals is intertwined with emotional responding, yet little is known about how emotions are regulated during this process. This is especially pertinent in disorders characterized by emotional and goal dysregulation, such as bipolar disorder (BD) and major depressive disorder (MDD). The current study experimentally examined the influence of two emotion regulation strategies—rumination and mindfulness—on emotional responding to goal striving among individuals with BD, MDD, and a healthy control group. Participants visualized a future unattained goal and then engaged in a maladaptive (rumination) or adaptive (mindfulness) induction while experiential and autonomic responses were measured. Across participants, ruminating on a future goal was associated with increased negative and positive emotion and elevated cardiovascular arousal. Compared with ruminating, mindfulness was associated with increased positive emotion and parasympathetic responding. Ruminating on goals appears to exacerbate emotional reactivity while being mindful of one’s goals is beneficial in healthy and clinical samples.
Response to ‘Remarkable prevalence of celiac disease in patients with irritable bowel syndrome plus fibromyalgia in comparison with those with isolated irritable bowel syndrome: a case-finding study’

In a recent issue of Arthritis Research & Therapy, I read with interest the report by Rodrigo and colleagues [1] documenting a fairly high rate of celiac disease in patients with irritable bowel syndrome and fibromyalgia. It is noteworthy that their patients improved on a gluten-free diet. However, that article references the report by Taubman and colleagues [2] and implies that our patient improved on a gluten-free diet whereas she actually, as reported, had an exacerbation of her symptoms on a gluten-free diet. Although the majority of such patients may improve when their celiac disease is treated, I do not want your readers to have the impression that such improvement is a uniform phenomenon. Both conditions are relatively common and therefore it is to be expected that some individuals will be unfortunate enough to have both conditions, unrelated to each other.
Hemodynamics of revascularization for iliofemoral venous occlusion: a short-term canine model.

Abstract A short-term canine model of lower extremity venous hypertension was created to study the hemodynamics of crossfemoral venous bypass grafts (CFB). Specifically, the hemodynamic effects of bypass conduit diameter and adjunctive arteriovenous fistulas (AVFs) were investigated. Unilateral hind limb venous hypertension was produced by iliofemoral venous ligation in six groups of five greyhounds each. Group I had venous ligation alone. CFBs were constructed in the remaining five groups: group II, 3 mm bypass conduit alone; group III, 3 mm bypass plus sequential AVF; group IV, 3 mm bypass plus caudad AVF; group V, 3 mm bypass plus cephalad AVF; group VI, 6 mm bypass conduit alone. Venous hypertension was significantly reduced by CFB (group II, p p p p p p p
Nickel hypersensitivity: a clinical review and call to action

Nickel sensitivity is common and increasing in prevalence. This review discusses nickel sensitivity and its association with body piercing and other environmental factors, occupational relevance, and potential implications for implantable metal medical devices. In addition, current European legislation that limits the release of nickel from jewelry is highlighted and an argument for similar legislation elsewhere is presented.
S-MATRIX INTERPRETATION OF QUANTUM THEORY.

The usual interpretation of quantum theory is clouded by the following points. (1) Invalid classical concepts are ascribed fundamental status. (2) The process of measurement is not describable within the framework of the theory. (3) The subject-object distinction is blurred. (4) The observed system is required to be isolated in order to be defined, yet interacting in order to be observed. These problems are resolved in a straightforward way by the unequivocal acceptance of a thoroughly pragmatic $S$-matrix viewpoint. This interpretation is described, and it is explained how and why the full physical content of quantum theory resides in the $S$ matrix.
Responses of the Codominant Grassland Species Andropogon gerardii and Sorghastrum nutans to Long-term Manipulations of Nitrogen and Water

Abstract The availability and distribution of essential resources such as water and nitrogen are changing on a global scale and it is important to determine the effects of such alterations on dominant and subdominant species in ecosystems. We examined the effects of long-term additions of water and nitrogen on leaf-level ecophysiological characteristics of the tallgrass prairie codominants Andropogon gerardii (big bluestem) and Sorghastrum nutans (Indian grass). Both species responded to irrigation with increased water potentials and to fertilization with decreased water potentials. Only in S. nutans, however, were net photosynthesis and stomatal conductance greater in response to both water and nitrogen addition. In contrast, A. gerardii, which currently is more abundant than S. nutans, was relatively unresponsive to resource manipulations. If net photosynthesis is positively related to plant productivity, as has been shown for tallgrass prairie species, the differential photosynthetic responses of these...
Addressing Ethics And Technology In Business: Preparing Today's Students For The Ethical Challenges Presented By Technology In The Workplace

The ethical development of information systems is but one of those sensitive scenarios associated with computer technology that has a tremendous impact on individuals and social life. The significance of these issues of concern cannot be overstated. However, since computer ethics is meant to be everybody’s responsibility, the result can often be interpreted as nobody’s responsibility. Therefore, an effective while still practical moral framework needs to be recognized in order to put computer ethics on a sound foundation for further exploration.
Vallejo y Picasso: "en humanidad su arte, en arte su guerra"

At the Second International Congress of Antifascist Writers Cesar Vallejo viewed Guernica , Pablo Picasso’s masterpiece that influenced Vallejo’s magnificent collection of poems Spain, Take This Cup from Me. Both works and their numerous manuscripts and sketches reveal the dialog between Picasso and Vallejo within a rupture that they create in order to build a new humanity. Both artists erase the concept of enemy and focus on the victims instead, raise the notion of politics from mere ideology to a natural human preoccupation and strive to rebuild the humanity with the people's art as its fabric since it is humanity, not politics, that nourishes their art, and it is the people's art that sustains the humanity.
Transnational Chinese Immigrant Smuggling to the United States via Mexico and Cuba, 1882-1916

During the late nineteenth and early twentieth century's, Chinese immigrants circumvented the American exclusionary policy through the use of Mexico as a surreptitious gateway into the United States.1 The following is a case in point. On July 1 or July 2, 1911, Chinese immigrants Hom Hing, Ah Fong, Lee Lock, Sam Seu, and Leu Lin, accompanied by their Chinese-Mexican compatriot Joaquin Mon, drove by wagon from Ensenada to Carise, Lower California. Hom, Ah, Lee, Sam, and Leu were received at the vicinity of the border by two Mexicans, Francisco Rios and Antonio Solis, who were contracted to take them safely across into the United States.
Understanding abuse of women with physical disabilities: an overview of the abuse pathways model.

The purpose of this article is to provide an overview of an empirically based theoretical model of abuse of women with physical disabilities. The Abuse Pathways model was developed from a critical disability life history research study conducted with 37 women who had simultaneously experienced abuse and physical disability. The model begins to address the complexity of abuse of women with physical disabilities by identifying the interactive components of the phenomenon. These components include (1) the social context of disability; (2) women's abuse trajectories; and (3) vulnerability factors for abuse. The article concludes by discussing potential applications and limitations of the model. Language: en
Improved meteorology from an updated WRF/CMAQ modeling system with MODIS vegetation and albedo

Realistic vegetation characteristics and phenology from the Moderate Resolution Imaging Spectroradiometer (MODIS) products improve the simulation for the meteorology and air quality modeling system WRF/CMAQ (Weather Research and Forecasting model and Community Multiscale Air Quality model) that employs the Pleim-Xiu land surface model (PX LSM). Recently, PX LSM WRF/CMAQ has been updated in vegetation, soil, and boundary layer processes resulting in improved 2 m temperature (T) and mixing ratio (Q), 10 m wind speed, and surface ozone simulations across the domain compared to the previous version for a period around August 2006. Yearlong meteorology simulations with the updated system demonstrate that MODIS input helps reduce bias of the 2 m Q estimation during the growing season from April to September. Improvements follow the green-up in the southeast from April and move toward the west and north through August. From October to March, MODIS input does not have much influence on the system because vegetation is not as active. The greatest effects of MODIS input include more accurate phenology, better representation of leaf area index (LAI) for various forest ecosystems and agricultural areas, and realistically sparse vegetation coverage in the western drylands. Despite the improved meteorology, MODIS input causes higher bias for the surface O3 simulation in April, August, and October in areas where MODIS LAI is much less than the base LAI. Thus, improvements may be needed in the CMAQ dry deposition model for low LAI areas where deposition on the soil surface becomes important.
The Politics of Elementary and Secondary Education Act Waivers

Executive leadership of the U.S. Department of Education (USDOE) initiated a flexibility offering from No Child Left Behind. Our work explores specific design decisions made in these state-specific accountability systems as associated with state political environments, resources, and demographic characteristics. Our analysis, focused on 42 states with approved flexibility waivers, provides some evidence that design decisions are associated with prior education policies, political leanings, and financial resources within each state. Policymakers should also take note, as these results suggest that state political factors may influence how state policymakers will react in future negotiations with the USDOE.
Genetic markers in thyroid tumors.

Tissue from nine patients with malignant tumors and two with benign tumors was cultured briefly before cytogenetic analysis. The tumors included one goiter and one Hurthle cell adenoma, one lymphoma, one medullary carcinoma, two Hurthle cell cancers, and five papillary cancers, varying widely in clinical staging and histologic differentiation. When assessed, DNA content was aneuploid in two of six malignant tumors. Various culture conditions (oxygen levels, dissociation methods, and media) were evaluated; the end points were growth, cell differentiation, and time to first harvest. Clonal aberrations were detected in one of four successfully harvested papillary cancers: they consisted of trisomy 7 and a rearrangement of chromosome 10. The rea (10) seen in 22 of 27 cells involved bands q11-21. Two other papillary tumors and a medullary cancer (a family member with multiple endocrine neoplasia type IIA) showed tetraploidy and nonclonal numerically aberrant cells. A lymphoma and two benign lesions showed no cytogenetic abnormality. The tumor with rea (10) is of special interest because abnormalities of 10q have been reported repeatedly in thyroid tumors, including two cases of papillary thyroid tumors with a structural aberration similar to that of the presented case. This rearrangement could affect the ret-proto-oncogene, localized to 10q11.2 which is activated in some papillary thyroid carcinomas.
National Technology Planning: Digital Divide in Emerging Economies (Case: Costa Rica)

The methodology selected for conducting this study is the analytic hierarchy process, and the model is based on the United Nations Development Program report titled “Creating a Development Dynamic: Final Report of the Digital Opportunity,” concepts from the literature and expert judgments. A four-level hierarchical decision model has been developed using weights provided by an expert panel. The model computes the contribution to the reduction of the internal DD, due to the reduction of the DD in different key sectors, ICT applications, and ICTs. The model was developed for short and longer terms. The judgmental values were tested for consistency and sensitivity, and verified by the expert panel. The study found that a reduction of the DD in the education sector would have the largest impact followed by the reduction of the DD in the economic, government, and health sectors. Education and government applications have the largest impact on reducing the internal digital divide, due to their focus on innovation and creativity, enhancing the education process through ICT use as well as improving the efficiency of public administration.
Regulation of synthesis and degradation of rat adrenal phenylethanolamine N-methyltransferase. IV. Synergistic stabilization of the enzyme against thermal and tryptic degradation by S-adenosylmethionine and biogenic amine substrates.

The effect of several biogenic amines that are substrates for adrenal phenylethanolamine N-methyltransferase (PNMT) on thermal and tryptic stability of the enzyme is described. While all substrates tested were somewhat effective in stabilizing the enzyme against tryptic degradation, only phenylethanolamine, phenylethylamine and octopamine were effective in stabilizing PNMT against thermal denaturation. Stabilization of PNMT was maximal when the m and p positions of the phenylethylamine nucleus were unsubstituted. Thus phenylethylamine was the most effective stabilizing compound studied, while norepinephrine was least effective. Epinephrine was completely ineffective in stabilizing the enzyme against proteolytic or thermal breakdown. The interaction of S-adenosylmethionine and substrate in protecting PNMT against thermal and tryptic degradation was also tested. While both substrate and S-adenosylmethionine protect the enzyme against tryptic proteolysis when present singly, the combination of the two compounds affords a degree of stabilization that is substantially greater than that seen by either compound alone. Moreover, the presence of substrate increases the affinity of the enzyme for S-adenosylmethionine, thus reducing the concentration of S-adenosylmethionine required for maximal stabilization of the enzyme. S-adenosylmethionine does not increase the affinity of PNMT for norepinephrine, nor does it augment the stabilization afforded by substrate. These results suggest that in vivo PNMT proteolysis is controlled by the constituents of the PNMT reaction, particularly S-adenosylmethionine. We postulate that interaction of the transferase with its substrate and with S-adenosylmethionine alters the spatial conformation of the protein in such a way that proteolytically vulnerable sites on the molecule are protected.
Abstract 3727: Small molecule Mcl-1 inhibitors induce apoptosis and death in multiple cancer subtypesin vitro

Mcl-1 is a member of the Bcl-2 family of proteins that play a major role in conferring resistance to apoptosis in cancer cells. Inhibiting Mcl-1 using peptides or RNAi has been shown to induce apoptosis in a broad array of cancer cell lines in numerous studies, making Mcl-1 a compelling target for anticancer therapy. We have discovered potent and selective small molecule Mcl-1 inhibitors that bind to the BH3 binding site of Mcl-1 with sub nanomolar affinities. These agents rapidly induced apoptosis in the Mcl-1 dependent NCI-H929 myeloma cell line, as demonstrated by mitochondrial membrane depolarization, caspase activation, and decreased viability. We measured the anti-proliferative activity of our compounds in cell lines from several cancer subtypes and found a broad spectrum of sensitivity to Mcl-1 inhibition. In cell lines that were resistant to Mcl-1 antagonists, combination with the dual Bcl-2/Bcl-xL inhibitor ABT-263 (navitoclax) greatly enhanced the activity of both compounds. These findings demonstrate that pharmacologic inhibition of Mcl-1 as a single agent or in combination with other cancer therapeutic agents is an effective way to modulate the intrinsic apoptotic pathway and promote cell death in cancer cells. Citation Format: John L. Sensintaffar, Allison Arnold, Craig Goodwin, Leah Hogdal, Subrata Shaw, James C. Tarr, Taekyu Lee, Edward Olejniczak, Stephen W. Fesik. Small molecule Mcl-1 inhibitors induce apoptosis and death in multiple cancer subtypes in vitro. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3727.
Failing Heart and Starving Brain: Ketone Bodies to the Rescue.

One of my favorite quotes in literature comes from the biochemist-turned-writer Isaac Asimov (1920–1992), who wrote, “The saddest aspect of life right now is that science gathers knowledge faster than society gathers wisdom.”1 Two recent articles2,3 published back to back in Circulation seem to challenge this notion by exposing results of strategic value. Both studies analyzed and sorted vast amounts of metabolites, proteins, and gene transcripts in failing human heart muscle,2,3 and both came independently to the same conclusions: Of all of the energy-providing substrates for the heart, the enzymes regulating ketone body metabolism are upregulated while those regulating glucose and fatty acid metabolism are downregulated. In other words, a strong signal emerged from a mountain of data. What does this mean? Here are my thoughts. When I am in congenial company, and especially over a glass of wine, I like to reflect on the story of metabolism, which is actually the story of people. It has been said that I am the only practicing cardiologist with a living connection to the Krebs cycle. Krebs often referred to metabolism as “biochemistry with a purpose”. More specifically, contraction and metabolism in the heart are inextricably linked and obey the First Law of Thermodynamics (energy in=energy …
Abstract IA05: Targeting MYC-mediated cancer metabolism

Myc, as a transcription factor capable of amplifying gene expression, frequently activates genes involved in cell metabolism to support cell growth and proliferation. Because many metabolic genes are ambiently expressed, it is not surprising in retrospect, that many metabolic genes are targets for Myc-mediated gene expression amplification. Collectively, Myc drives the expression of genes that are involved in glucose uptake, glycolysis, amino acid uptake - particularly glutamine- and catabolism, supporting increased protein synthesis required for a growing cell. In this regard, Myc stimulates many genes involved in nucleotide synthesis, ribosome biogenesis and translation. Furthermore, Myc can stimulate mitochondrial biogenesis and lipogenesis. When Myc is ectopically expressed in oncogenic settings where checkpoints are lost, MYC-transformed cells are constitutively driven to undergo ribosome biogenesis and growth, rendering them addicted to nutrients such as glucose or glutamine. Hence, targeting enzymes that are involved in glycolysis and/or glutaminolysis provides a strategy to treat MYC-driven cancers. We provide proof-of-concept that targeting glutaminolysis in GEMM or xenograft models is feasible and therefore provide a foundation for further studies. Citation Format: Chi Van Dang. Targeting MYC-mediated cancer metabolism. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr IA05.
FST and kinship for arbitrary population structures II: Method of moments estimators

F ST and kinship are key parameters often estimated in modern population genetics studies. Kinship matrices have also become a fundamental quantity used in genome-wide association studies and heritability estimation. The most frequently used estimators of F ST and kinship are method of moments estimators whose accuracies depend strongly on the existence of simple underlying forms of structure, such as the island model of non-overlapping, independently evolving subpopulations. However, modern data sets have revealed that these simple models of structure do not likely hold in many populations, including humans. In this work, we provide new results on the behavior of these estimators in the presence of arbitrarily complex population structures. After establishing a framework for assessing bias and consistency of genome-wide estimators, we calculate the accuracy of F ST and kinship estimators under arbitrary population structures, characterizing biases and estimation challenges unobserved under their originally assumed models of structure. We illustrate our results using simulated genotypes from an admixture model, constructing a one-dimensional geographic scenario that departs nontrivially from the island model. Using 1000 Genomes Project data, we verify that population-level pairwise F ST estimates underestimate differentiation measured by an individual-level pairwise F ST estimator introduced here. We show that the calculated biases are due to unknown quantities that cannot be estimated under the established frameworks, highlighting the need for innovative estimation approaches in complex populations. We provide initial results that point towards a future estimation framework for generalized F ST and kinship.
Motivation, strategy, and English as a foreign language vocabulary learning: A structural equation modelling study.

Background In spite of considerable advancements in our understanding of the different factors involved in achieving vocabulary-learning success, the overall pattern and interrelationships of critical factors involved in L2 vocabulary learning – particularly, the mechanisms through which learners regulate their motivation and learning strategies – remain unclear. Aims This study examined L2 vocabulary learning, focusing on the joint influence of different motivational factors and learning strategies on the vocabulary breadth of adolescent learners of English as a foreign language (EFL) in China. Sample The participants were 107 tenth graders (68 females, 39 males) in China. Methods The data were collected via two questionnaires, one assessing students' motivation towards English-vocabulary learning and the other their English vocabulary-learning strategies, along with a test measuring vocabulary breadth. Results Structural equation modelling (SEM) indicated that learning strategy partially mediated the relationship between motivation (i.e., a composite score of intrinsic and extrinsic motivation) and vocabulary learning. Separate SEM analyses for intrinsic (IM) and extrinsic motivation (EM) revealed that there were significant and positive direct and indirect effects of IM on vocabulary knowledge; and while EM's direct effect over and above that of learning strategies did not achieve significance, its indirect effect was significant and positive. Conclusions The findings suggest that vocabulary-learning strategies mediate the relationship between motivation and vocabulary knowledge. In addition, IM may have a greater influence on vocabulary learning in foreign-language contexts.
Oxidation of Cyclohexene Catalyzed by Nanoporous Au(Ag) in Liquid Phase

Nanoporous gold with minor silver content has been identified as a new type of gold based catalyst for selective oxidation of cyclohexene with molecular oxygen in liquid. By oxidation of the leached nanoporous gold foils in ozone, the minor silver content was oxidized to form silver oxide nanoclusters on the surface of nanoporous gold. With further treatment in methanol, the surface silver oxide was reduced and surface alloy was formed on gold ligaments. Both nanoporous gold treated with ozone only and the one with ozone and then methanol are very active for selective oxidation of cyclohexene with molecular oxygen in liquid of cyclohexene with a turn-over-frequency (TOF) of 0.55–0.99 molecules per surface Au atom per second under a solvent-free and initiator- free condition. The total selectivity for production of 2-cyclohexene-1-one, 2-cyclohexene-1-ol, and cyclohexene oxide was increased from 57.5 % to 80.8 % by an additional treatment of nanoporous gold in methanol after activation in zone. The correlation of catalytic selectivity for the production of the three products and corresponding surface chemistry of ligament suggests that (1) the formed Au–Ag alloy surface is favorable for the formation of 2-cyclohexen-1-one, 2-cyclohexene-1-ol, and cyclohexene oxide and (2) the surface silver oxide is favorable for the production of cyclohexenyl hydroperoxide.
Abstract 1032: The acetylcholine signaling pathway: A novel molecular target for lung cancers

Cigarette smoking is a major risk factor for all types of lung cancers. Nicotine, the addictive component of cigarettes, accelerates the growth and angiogenesis of human lung cancers. The biological activity of nicotine is mediated by nicotinic acetylcholine receptors (nAChRs). The endogenous ligand of nAChRs is acetylcholine (ACh). We show that both human SCLCs and NSCLCs contain all proteins of the acetylcholine signaling pathway, namely nAChRs, choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), choline transporter (ChT1) and acetylcholinesterase (AChE). ACh functions as an autocrine growth factor for human lung cancer cells. Lung adenocarcinoma (LAC), squamous cell carcinoma (SCC-L) and invasive mucinous adenocarcinoma (IMA) express a diverse array of nAChRs. In addition, normal human lung cells also express nAChRs and other ACh signaling proteins. Nicotine amplifies the ACh signaling loop in human lung cancer cells. It increases the levels of alpha7-nAChR subunit in human SCC-Ls. The alpha7-nAChR is responsible for the proliferative and pro-angiogenic activity of nicotine in lung cancer. The level of alpha7-nAChR was analyzed in human SCC-L samples isolated from patients. It was found that the level of alpha7-nAChR in SCC-L patients (who are heavy smokers) was much higher than that of moderate smoker suffering from SCC-Ls. Nicotine was also found to elevate the levels of ChAT and VAChT in human lung cancers. The acetylcholine signaling pathway may be a useful molecular target for the diagnosis and therapy of human lung cancers in smokers. Our results are also relevant to lung cancer patients who are exposed to nicotine via secondhand smoke, nicotine patches, gums or electronic cigarettes. Citation Format: Kathleen C. Brown, Jamie K. Lau, Haley E. Perry, Brent A. Thornhill, Cathryn D. Stevenson, William D. Rollyson, Cody A. Stover, Dennie V. Jones, Joseph F. Pulliam, Piyali Dasgupta. The acetylcholine signaling pathway: A novel molecular target for lung cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1032. doi:10.1158/1538-7445.AM2015-1032
Making a Difference: A Study of Cognitive Stimulation Therapy for Persons with Dementia

Affecting nearly 5.4 million older adults in the United States and 35.6 million individuals worldwide, dementia is one of the greatest public health crises of our time. As a result, helping profess...
LABORATORY-SCALE REACTION INJECTION MOLDING OF POLY(CAPROLACTONE) ELASTOMERS FOR RAPID PROTOTYPING OF STIMULI-RESPONSIVE THERMOSETS

ABSTRACT Semicrystalline polymer networks offer valuable shape-memory and shape-shifting properties; however, material processing and scale-up remain major challenges. A laboratory-scale reaction injection molding (RIM) apparatus and methodology are described to mold and cure urethane linked poly(caprolactone) networks from commercially available polyols and polyisocyanate. The highly customized RIM system is capable of making small shot sizes (∼39 g) at precise stoichiometric ratios and forming elastomers with low run-to-run variation of mechanical properties. Experiments conducted with a dye in one feed stream enable evaluation of mixing efficacy, and component mixing is substantially improved by recirculating reagents at higher pressures. Networks prepared with excess isocyanate exhibited higher modulus, which is most likely due to the formation of allophanates.
Variational Principle for EM-Fields

We show how dimensional considerations, along with study of properties of invariants of electromagnetic fields, lead to the covariant format of dynamical Maxwell field equations with sources. We complement these four differential equations with another four covariant equations that allow us to relate fields to potentials once a gauge is chosen. We describe the Lorentz covariant gauge condition and obtain a covariant 4-vector format for the electromagnetic (EM) potential. We explore the causal solutions of Maxwell equations for moving charged particles. The explicit form of energy-momentum locked in the fields is derived. We note that the Lorentz force is incomplete as it misses the particle dynamics associated with the magnetic dipole moment that any charged or neutral particle can carry. This clarifies that the empirical form of EM force is not yet fully known.
Attitudes and behaviors related to distracted driving in college students: a need for interventions in adolescence

Objective One of the biggest contributors to distracted driving among young people in the United States is technology. The objective of this study was to describe distracted driving behaviors among college students, with a specific focus on attitudes towards and use of social media. Methods With written permission, a survey was adapted from the Distracted Driving Public Opinion Poll distributed by the National Safety Council. The survey comprised 43 questions assessing attitudes and behaviors. A total of 411 students enrolled in a personal health course were invited to complete the survey. In total 324 surveys were completed, resulting in a response rate of 79%. Results Among students with a driver's license, 95.2% reported engaging in distracted driving behaviors. The use of social media while driving was common, with 30.7% reporting that they glance at, read, or post to social media while driving, most commonly on Snapchat or Instagram. It was common for students to make or answer phone calls (72.0%), review or send text messages (54.6%), or glance at or read automatic notifications (43.3%). Almost all students (91.5%) reported that they believed a hands-free solution is safer than holding the phone while driving, but only 67.9% reported that they usually used a hands-free device. Students in a health major and students who drive in urban areas were more likely to engage in distracted driving behaviors. Conclusions These findings suggest a need for interventions, particularly those which target adolescents in an attempt to deter these behaviors as they transition into adulthood.