cssi/SciSciGPT-SciSciNet huggingface dataset:
Methionine kinetics in adult men: effects of dietary betaine on L-(2H3-methyl-1-13C)methionine

The effects of a daily 3-g supplement of betaine on kinetic aspects of L-[2H3-methyl-1-13C]methionine (MET) metabolism in healthy young adult men were explored. Four groups of four subjects each were given a control diet, based on an L-amino acid mixture supplying 29.5 and 21.9 mg.kg-1.d-1 of L-methionine and L-cystine for 4 d before the tracer study, conducted on day 5 during the fed state. Two groups received the control diet and two groups received the betaine supplement. Tracer was given intravenously (iv) or orally. The transmethylation rate of MET (TM), homocysteine remethylation (RM), and oxidation of methionine were estimated from plasma methionine labeling and 13C enrichment of expired air. RM tended to increase (P = 0.14) but the TM and methionine oxidation were significantly (P less than 0.05) higher after betaine supplementation when estimated with the oral tracer. No differences were detected with the intravenous tracer. Methionine concentration in plasma obtained from blood taken from subjects in the fed state was higher (P less than 0.01) with betaine supplementation. These results suggest that excess methyl-group intake may increase the dietary requirement for methionine.
A Human REV7 Homolog That Interacts with the Polymerase ζ Catalytic Subunit hREV3 and the Spindle Assembly Checkpoint Protein hMAD2

Widespread alteration of the genomic DNA is a hallmark of tumors, and alteration of genes involved in DNA maintenance have been shown to contribute to the tumorigenic process. The DNA polymerase zeta of Saccharomyces cerevisiae is required for error-prone repair following DNA damage and consists of a complex between three proteins, scRev1, scRev3, and scRev7. Here we describe a candidate human homolog of S. cerevisiae Rev7 (hREV7), which was identified in a yeast two-hybrid screen using the human homolog of S. cerevisiae Rev3 (hREV3). The hREV7 gene product displays 23% identity and 53% similarity with scREV7, as well as 23% identity and 54% similarity with the human mitotic checkpoint protein hMAD2. hREV7 is located on human chromosome 1p36 in a region of high loss of heterozygosity in human tumors, although no alterations of hREV3 or hREV7 were found in primary human tumors or human tumor cell lines. The interaction domain between hREV3 and hREV7 was determined and suggests that hREV7 probably functions with hREV3 in the human DNA polymerase zeta complex. In addition, we have identified an interaction between hREV7 and hMAD2 but not hMAD1. While overexpression of hREV7 does not lead to cell cycle arrest, we entertain the possibility that it may act as an adapter between DNA repair and the spindle assembly checkpoint.
Flexible and disposable immunosensors based on layer-bylayer self-assembled carbon nanotubes and biomolecules

A low-cost, flexible, and disposable immunosensor is presented in this paper. The single-walled carbon nanotubes (SWNT) and biomolecules are self-assembled on micro patterned electrodes. The immuno-chip acts as the platform of a horseradish peroxidase (HRP) labeled sandwiched Enzyme-Linked Immunosorbent Assay (ELISA). The pH change induced by the biochemical reactions influences the electrical conductance of SWNT. The detection resolution of 0.4 ng/ml (2.5 pM) for normal rabbit immunoglobulin G (IgG) is demonstrated. The new fabrication technique and the HRP labeled detection protocol can be extended to the recognition of other antigens for critical applications to clinical diagnosis, food toxin detection, and environment monitoring, etc.
The Context of Proving

Discussions of mathematical problem-solving and heuristic reasoning have typically examined how proofs that are already known might be found. This approach has at least three problems: first, prove...
Clinical Pharmacology of the Fluoroquinolones: Studies in Human Dynamic/Kinetic Models

Traditional antibiotic dosage adjustments, compensate only for disease-induced changes in the serum concentration profile. Dosage adjustments tend to be effective when a well-defined range of concentration is associated with efficacy. However, the bacterial target of antibiotic action-minimum inhibitory concentration (MIC) is variable, because even susceptible bacteria may differ greatly in their antibiotic susceptibility. Newly developed computerized methods for the quantitation of susceptibility allow for testing of integrated kinetic-susceptibility models in patients. Our attention has focused on fluoroquinolones, since they are relatively nontoxic and provide the necessary dosage range needed to elucidate correlations between concentration and response. Studies of patients with nosocomial gram-negative pneumonia reveal that the best correlation parameters of favorable outcome are approximately 80% of time over MIC and 24-h area under the time-concentration curve (AUC)-to-MIC values >125.
Single mode photonic crystal heterostructure cavity lasers

We demonstrate the single mode lasing characteristics of a photonic crystal heterostructure cavity formed from an inner kagome lattice surrounded by a hexagonal lattice. Finite element domain decomposition analysis is used to justify the observed modal selectivity.
An "effective" capacitance based delay metric for RC interconnect

Efficient, yet accurate delay estimation for RC interconnect is required for the optimization loop of timing-driven physical design tools. For many applications, the Elmore delay metric [4] has been widely used due to its efficiency and ease of use. However, it is well known that the Elmore metric can have significant error since it ignores the resistive shielding of down-stream capacitance. We present a new interconnect metric called ECM that accounts for this resistive shielding by computing an effective capacitance to model the downstream capacitance. ECM can also be computed with the same complexity as the Elmore delay and does not require the computation of moments. Experiments show that ECM is significantly more accurate than Elmore delay and is competitive with other metrics that use multiple moments.
Fluorinated free radicals

All aspects of the structure, reactivity and chemistry of fluorine-containing, carbon-based free radicals in solution are presented. The influence of fluorine substituents on the structure, the stability and the electronegativity of free radicals is discussed. The methods of generation of fluorinated radicals are summarized. A critical analysis of the reactivities of perfluoro-n-alkyl, branched chain perfluoroalkyl and partially-fluorinated free radicals towards alkene addition, H-atom abstraction, and towards intramolecular rearrangement reactions is presented. Lastly, a summary of the synthetically-useful chemistry of fluorinated radicals is presented.
Implications of Historical Trends in the Electrical Efficiency of Computing

The electrical efficiency of computation has doubled roughly every year and a half for more than six decades, a pace of change comparable to that for computer performance and electrical efficiency in the microprocessor era. These efficiency improvements enabled the creation of laptops, smart phones, wireless sensors, and other mobile computing devices, with many more such innovations yet to come. The Web Extra appendix outlines the data and methods used in this study.
Monitoring access to stateful resources in grid environments

Currently, grid technologies are widely used in large-scale scientific applications. Grids support stateful interactions with explicit exposure of state information across the boundaries of a service. In this paper, we present a stateful Web service architecture that provides efficient sharing of a service instance between heterogeneous service requesters with monitoring of the interactions. We describe how we compose the state information based on the formalized sequence of the interactions. We also describe how the shared service instance is managed, and interacted with, through standard Web services interfaces. We analyze the performance of our approach in a large-scale scientific grid application.
PLASMA PROTEIN METABOLISM-NORMAL AND ASSOCIATED WITH SHOCK : OBSERVATIONS USING PROTEIN LABELED BY HEAVY NITROGEN IN LYSINE

Labeled plasma proteins are produced by administering to dogs the amino acid lysine synthesized with heavy nitrogen. Such labeled proteins are apparently indistinguishable biologically from proteins of normal isotope concentration. Labeled plasma proteins, as plasma, injected into normal dogs pass out of the blood stream at an initially rapid but constantly decreasing non-logarithmic rate. This outflow is balanced by a simultaneous inflow of plasma proteins from the tissues. Fifty per cent of the labeled protein is out of the blood stream in about 24 hours; 75 per cent in about 6 days. Shock due to trauma of intestine or leg shows a dilution curve of labeled plasma protein not unlike that of the normal dog. If anything, dilution appears a little less rapid in shock. Since the usual shrinkage of plasma volume and plasma protein mass is present in these shocked dogs, these data are compatible with a decreased inflow of protein into the plasma during shock. Methods are described which are suitable for the use of heavy nitrogen incorporated in the epsilon group of lysine and its subsequent analysis in body fluids. These data may indicate that the plasma proteins are normally in constant and rapid exchange with a mobile pool of body protein.
Perspectives on Evidence-Based Research in Education—What Works? Issues in Synthesizing Educational Program Evaluations:

Syntheses of research on educational programs have taken on increasing policy importance. Procedures for performing such syntheses must therefore produce reliable, unbiased, and meaningful information on the strength of evidence behind each program. Because evaluations of any given program are few in number, syntheses of program evaluations must focus on minimizing bias in reviews of each study. This article discusses key issues in the conduct of program evaluation syntheses: requirements for research design, sample size, adjustments for pretest differences, duration, and use of unbiased outcome measures. It also discusses the need to balance factors such as research designs, effect sizes, and numbers of studies in rating the overall strength of evidence supporting each program.
Discussion of “The Value-Relevance of Changes in Financial Leverage Beyond Growth in Assets and GAAP Earnings”

Dimitrov and Jain examine whether changes in leverage are associated with firm performance after controlling for growth in assets and accounting earnings. They find that firms with increases (decreases) in leverage have negative (positive) current and future stock returns and negative (positive) accounting performance in future periods. By providing new evidence on the relation between debt financing and firm performance, the study extends prior research on the economic implications of firms' financing choices.I examine potential measurement problems associated with the authors' empirical construct for changes in leverage. These problems stem from the use of accounting book values of assets and liabilities in the measurement of leverage and the endogeneity of firms' decisions to change leverage levels. I comment on the unusual characteristics of firms with extreme changes in leverage and their possible effect on the authors' results and inferences. I also discuss issues involved in interpreting the author...
Mechanical Behavior and Microstructure of Nanoporous Gold Films

Nanoporous gold (NPG) thin films offer an opportunity to investigate the effects of nanoscale geometric confinement on the mechanical properties of metals. In the present study, NPG films supported by substrates were fabricated by dealloying Au-Ag films on Kapton and silicon. The microstructural evolution of NPG at various stages of dealloying was observed and analyzed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Cracking occurred at grain boundaries during dealloying and may be exacerbated by pre-existing tensile stress in the film. Stress evolution of NPG films on silicon substrates during dealloying was measured with the wafer curvature technique and revealed an overall shift toward compressive stress.
Experimental results and performance analysis of a 500 m/sec linear induction launcher (LIL)

A computer model, previously validated, was used to study the performance of an experimental three-phase launcher energized by a capacitor bank and designed to impart to a 137 gram projectile a muzzle velocity of 500 m/s: (1) the build-up of the traveling wave was examined; (2) the connection of the drive coils was changed; (3) the resistances of the drive circuits were calculated and measured; and (4) the effect of the conductivity of the cylindrical tube (sleeve) constituting the projectile was assessed. Experimentally, a doubling of the muzzle velocity was achieved, from an earlier-obtained 250 m/s, to its present 476 m/s. This was done by strengthening the thin-walled aluminum sleeve by heat treatment (aging) to prevent it from being crushed when the input energy was raised to its design value. >
Role of Peers in Cultural Innovation and Cultural Transmission: Evidence from the Play of Dolphin Calves

Observations of the spontaneous play behaviors of a group of captive bottlenose dolphins ( Tursiops truncatus ) revealed that each individual calf's play became more complex with increasing age, sug- gesting that dolphin play may facilitate the ontogeny and maintenance of flexible problem solving skills. If this is so, play may have evolved to help young dolphins learn to adapt to novel situations. Novel play behaviors were more likely to be produced by dolphin calves than by adults, demonstrat- ing that calves were the main source of innovative play behaviors in the group. Calves were also more likely to imitate novel play behaviors first produced by another dolphin, suggesting that calves contribute significantly to the spread of novel behaviors within a group. All in all, these data suggest that peers may be important catalysts for both cultural innovation and cultural transmission, and that the opportunity to interact with peers may enhance the effect play has on the emergence of flexible problem solving skills.
RNA-mediated displacement of an inhibitory snRNP complex activates transcription elongation

The transition from transcription initiation to elongation at the HIV-1 promoter is controlled by Tat, which recruits P-TEFb to TAR RNA to phosphorylate RNA polymerase II. It has long been unclear why the HIV-1 promoter is incompetent for elongation. We report that P-TEFb is recruited to the promoter in a catalytically inactive state bound to the inhibitory 7SK small nuclear ribonucleoprotein (snRNP), thereby preventing elongation. It also has long been believed that TAR functions to recruit Tat to the promoter, but we find that Tat is recruited to the DNA template before TAR is synthesized. We propose that TAR binds Tat and P-TEFb as it emerges on the nascent transcript, competitively displacing the inhibitory 7SK snRNP and activating the P-TEFb kinase. Recruitment of an inhibitory snRNP complex at an early stage in the transcription cycle provides a new paradigm for controlling gene expression with a noncoding RNA.
The Grasshopper Neuroblast Short-Term Assay for Evaluating the Effects of Environmental Chemicals on Chromosomes and Cell Kinetics

The grasshopper neuroblast (GHNb) is a newcomer to the library of tests available for evaluating the mutagenicity of environmental chemicals. Most of the current tests have been in use since the beginning of the present era of active research on the identification of environmental mutagens and carcinogens, which began to attain international momentum in the late 1960s.(28,56) Why, then, did we recently develop another assay? First, the neuroblast (Nb) of the grasshopper Chortophaga viridifasciata (De Geer) has been shown to be very sensitive to X rays (the effects of doses as low as 1 rad on chromosome breakage and on mitotic rate can be detected(42,43)), so we reasoned that it might also be very sensitive to chemical mutagens. Second, the fact that the spontaneous chromosome aberration frequency in the GHNb is zero means that significant data on mutagens can be obtained with a minimum number of cells. Third, the GHNb has a short cell cycle(44) with a number of well-defined phases, and thus, much information about the effects of agents on cell progression can be obtained. This aspect of environmental mutagen action has received relatively little attention and is of considerable relevance to teratogenesis.(36) The short cell cycle (Chortophaga, 4 hr; Melanoplus sanguinipes, 2 hr, 38°C) is also advantageous for testing chemicals with short half-lives.
Fuzzy Set Theory: Past Present Future

In this volume twenty four previously unpublished papers have been selected to provide a reference work in the important area of fuzzy set theory and its applications. These contributions provide significant extensions of fuzzy set and possibility theories, as well as some novel applications of their concepts.
Production of Antihormones by Prolonged Administration of Pituitary Extract. Effect on Anterior Hypophysis

A cytological study has been made of the hypophyses of 2 dogs and 2 sheep which had received prolonged injections of extracts of sheep-pituitary glands,∗ and of 2 dogs that had been injected with antihormone-serum. The striking physical changes in one of the dogs, namely, an atrophy of the thyroid, adrenals and gonads, a cessation of growth, and the development of obesity, have been reported elsewhere.1The 2 dogs which were injected subcutaneously with the sheep-pituitary extract for 4 and 7 months respectively, developed anti-hormones which inactivated not only the injected pituitary extract, but also several of the hormones of their own hypophyses.The 2 dogs which were injected daily with 10 cc of canine antihormone-serum showed signs of moderate inactivation of the gonads, thyroids and adrenals.Twin ewes were injected with sheep-pituitary extract† daily for 6 months. Their genitalia and mammary glands continually showed signs of activation, and at autopsy their gonads and uteri were found to be stimula...
A Substrate for Uniform Production of Perithecia In Gibberella Zeae

Fresh carnation leaf tissue treated with ethanol offers a satisfactory substrate for the study of sexual reproduction in Gibberella zeae. Carnation leaf tissue disks were soaked in 70% aqueous etha...
REGIONAL DIFFERENCES IN PEDIATRIC CARDIAC GRAFT UTILIZATION AND TRENDS OVER TIME

Pediatric cardiac transplant waitlist mortality remains high with significant regional variability. Differences in graft utilization may contribute to disparities in outcomes. This study aims to assess regional differences in graft utilization and trends over time. Organ Procurement and
Liver sinusoidal endothelial cells undergo apoptosis during sepsis, leading to organ dysfunction. (54.13)

Sepsis is the leading cause of death in critically ill patients, and treatment options are limited. Our laboratory studies polymicrobial sepsis in murine models, and uses the liver as a model organ to investigate the disease’s pathophysiology. The liver, characterized as an immune tolerant organ, is susceptible to septic induced inflammation. We have previously reported that there is a twofold increase in the number of liver CD8+ T cells, 24 hours following cecal ligation and puncture (CLP—a surgical procedure that generates sepsis in mice). Since activated T lymphocytes must transverse the endothelium to reach the site of infection, it is possible that they directly interact with LSECs, and mediate liver injury through Fas-mediated apoptosis. This led us to hypothesize that as CD8+ T cells directly interact with LSECs, endothelial cell dysfunction occurs. Our preliminary results indicate that septic liver CD8+ T cells have cytotoxic effects on endothelial monolayer integrity, and release pro-inflammatory cytokines when directly co-cultured with CRL-2167, a murine endothelial cell line. We have also observed through flow cytometry that LSECs (CD146+/CD45- and CD31+/CD45- populations) have an increased expression of CD54 (ICAM-1), Fas, and Annexin V staining in vivo. These data suggest that CD8+ T cells directly interact with LSECs, alter the tolerance capacity of LSECs, and potentially kill LSECs through the Fas-FasL system, ultimately leading to liver organ injury in sepsis.
Dynamic adaptation of user migration policies in distributed virtual environments

A distributed virtual environment (DVE) consists of multiple network nodes (servers), each of which can host many users that consume CPU resources on that node and communicate with users on other nodes. Users can be dynamically migrated between the nodes, and the ultimate goal for the migration policy is to minimize the average system response time perceived by the users. In order to achieve this, the user migration policy should minimize network communication while balancing the load among the nodes so that CPU resources of the individual nodes are not overloaded. This paper considers a multi-player online game as an example of a DVE and presents an adaptive distributed user migration policy, which uses Reinforcement Learning to tune itself so as to minimize the average system response time perceived by the users. Performance of the self-tuning policy was compared on a simulator with the standard benchmark non-adaptive migration policy and with the optimal static user allocation policy in a variety of scenarios, and the self-tuning policy was shown to greatly outperform both benchmark policies, with performance difference increasing as the network became more overloaded.
Jewish Comedy and the Contradictions of Culture

In a fantastical and funny story by Philip Roth entitled “On the Air,”2 Milton Lippman, a talent scout, writes to Albert Einstein to ask if Einstein would agree to star on a radio program that Lippman hopes to negotiate with the networks, “The Jewish Answer Man.” It will demonstrate to the world that “the Greatest Genius of all Time is a Jew.” When his first approach to Einstein goes unanswered, Lippman bravely writes again: Dear Mr. Einstein: I can understand how busy you must be thinking, and appreciate that you did not answer my letter suggesting that I try to get you on a radio program that would make “The Answer Man” look like the joke it is. Will you reconsider, if the silence means no? I realize that one of the reasons you don’t wear a tie or even bother to comb your hair is because you are as busy as you are, thinking new things. Well, don’t think that you would have to change your ways once you become a radio personality. Your hair is a great gimmick, and I wouldn’t change it for a second. It’s a great trademark. Without disrespect, it sticks in your mind the way Harpo Marx’s does. Which is excellent. (Now I wonder if you even have the time to know who The Marx Brothers are? They are four zany Jewish brothers, and you happen to look a little like one of them. You might get a kick out of catching one of their movies. Probably they don’t even show movies in Princeton, but maybe you could get somebody to drive you out of town. You can get the entire plot in about a minute, but the resemblance between you and Harpo and his hair and yours, might reassure you that you are a fine personality in terms of show business just as you are.)
Stem cell-derived interneuron transplants as a treatment for schizophrenia: preclinical validation in a rodent model

An increasing literature suggests that schizophrenia is associated with a reduction in hippocampal interneuron function. Thus, we posit that stem cell-derived interneuron transplants may be an effective therapeutic strategy to reduce hippocampal hyperactivity and attenuate behavioral deficits in schizophrenia. Here we used a dual-reporter embryonic stem cell line to generate enriched populations of parvalbumin (PV)- or somatostatin (SST)-positive interneurons, which were transplanted into the ventral hippocampus of the methylazoxymethanol rodent model of schizophrenia. These interneuron transplants integrate within the existing circuitry, reduce hippocampal hyperactivity and normalize aberrant dopamine neuron activity. Further, interneuron transplants alleviate behaviors that model negative and cognitive symptoms, including deficits in social interaction and cognitive inflexibility. Interestingly, PV- and SST-enriched transplants produced differential effects on behavior, with PV-enriched populations effectively normalizing all the behaviors examined. These data suggest that the stem cell-derived interneuron transplants may represent a novel therapeutic strategy for schizophrenia.
The Radical Conceptualization of Perceptual Experience

Perceptual experience does not consist in a mere passive reception of sensations which come ready-marked with their identities and interrelationships. A child sees an animal, where we see a camel, and a biologist might see a dromedary. I see a Picasso, you see the work of someone obsessed with blue; I hear noise, you hear a composition by John Cage. Thus, the content of our perceptual experience is, surely to some extent, structured by the conceptual resources which we possess. But to what extent? In this chapter I will defend the view, which I will call the ‘conceptualist’ view, that the possession of concepts is a necessary condition of all perceptual experience.
The impact of technology exposure on student perceptions of a 1:1 program

Many school districts across the United States have enacted one-to-one (1:1) programs to boost students’ “21st Century Skills”. These programs provide a laptop or other personal digital device to every student, with the expectation that teachers will employ modern instructional processes and students will benefit from greater access to knowledge, tools, and both collaborative and individualized instruction. The transformative potential of 1:1, along with the varied contextual variables, makes program implementation difficult. This paper discusses the partial results of a year-long 1:1 laptop program evaluation in one Pennsylvania district. The study employs multiple methods to obtain an initial view of the programs’ impact on students. The study found that, overall, students did not have positive perceptions of the 1:1 program or its impacts, and a significant decline was found for many indicators between semesters. Regression analysis of the collected data suggests that greater use of the 1:1 laptops, along with a robust IT infrastructure, significantly predicts the perceived level of impact a 1:1 program has on students. The information obtained from this case study provides further insight into how attitudes, behavior, and perceptions of students are impacted by these programs.
Sequence Determinants of the Conformational Properties of an Intrinsically Disordered Protein Prior to and upon Multisite Phosphorylation

Many cell signaling events are coordinated by intrinsically disordered protein regions (IDRs) that undergo multisite Serine/Threonine phosphorylation. The conformational properties of these IDRs prior to and following multisite phosphorylation are directly relevant to understanding their functions. Here, we present results from biophysical studies and molecular simulations that quantify the conformational properties of an 81-residue IDR from the S. cerevisiae transcription factor Ash1. We show that the unphosphorylated Ash1 IDR adopts coil-like conformations that are expanded and well-solvated. This result contradicts inferences regarding global compaction that are derived from heuristics based on amino acid compositions for IDRs with low proline contents. Upon phosphorylation at ten distinct sites, the global conformational properties of pAsh1 are indistinguishable from those of unphosphorylated Ash1. This insensitivity derives from compensatory changes to the pattern of local and long-range intrachain c...
The roles of testosterone and cortisol in friendship formation

Abstract Although research has investigated the neuroendocrine correlates of romantic relationships, the neuroendocrine correlates of friendship formation are largely unexplored. In two conditions, participants’ salivary testosterone and cortisol were measured before and after a high versus low closeness activity with another same-sex participant. In the high closeness task, participants took turns answering questions that fostered increases in self-disclosure. The low closeness task fostered low levels of self-disclosure. Dyadic multilevel models indicated that lower basal testosterone and decreases in testosterone were associated with increased closeness between recently acquainted strangers. Our results suggest that people high in testosterone felt less close to others and desired less closeness. Further, lower basal cortisol and dynamic cortisol decreases were associated with greater closeness and desired closeness in the high closeness condition. Finally, we found that the partners of those who had lower cortisol desired more closeness. These findings suggest that lower testosterone and cortisol are linked to the facilitation of initial social bonds and that these social bonds may, in turn, be associated with changes in these hormones.
Elastic Stability of Cosserat Rods and Parallel Continuum Robots

Classic theories in nonlinear elasticity have increasingly been used to obtain accurate and efficient models for continuum robots and other elastic structures. Numerically computed solutions of these models typically satisfy the first-order conditions necessary for equilibrium, but do not provide any information about the elastic stability of the solution. The inability to detect or avoid physically unstable model solutions poses a major hindrance to reliable model-based simulation, planning, design, and control. In this paper, we adapt results from optimal control to determine the stability of Kirchhoff rods and Cosserat rods subject to general end constraints, including coupled multirod models which describe parallel continuum robots. We formulate a sufficient condition for the stability of a solution, a numerical test for evaluating this condition, and a heuristic stability metric. We verify that our numerical stability test agrees with the classical results for the buckling of single columns with various end constraints and for multicolumn frames. We then validate our approach experimentally on a six degree-of-freedom parallel continuum robot.
Genomics in Clinical Trials

The evolution of technology and bioinformatics in genomic research over the last 10 years has enabled the investigator to include complex molecular analyses in clinical trial design to explore the biological mechanisms behind the observations seen with clinical intervention. Whether you incorporate whole genome expression studies, genome-wide screening for polymorphisms, or pharmacogenomics, these methods are now not only feasible, but provide a very powerful translational strategy. Genomic analyses might be the primary focus of a trial, but they also fit well modularly as a secondary line of investigation supporting a primary clinical protocol. Newer technologies like next generation sequencing and genetic engineering offer the promise of rapid throughput, more cost effective, real-time clinical applicability. Using these methods to guide patient diagnosis, staging, and treatment in a personalized medicine approach will greatly and positively impact clinical outcomes. Collaboration between clinical scientists, molecular biologists, and bioinformatics experts provides synergy that drives the success of a comprehensive multidisciplinary genomic medicine program.
Future (of) Synchrotrons for Particle Therapy

The field of particle therapy is quickly growing and yet it's more widespread adoption is limited by size, cost and adaptation to the more conformal treatment techniques. In order to realize the benefits of this modality the equipment used to generate and deliver the beam is evolving. The accelerator is one of the key components and its future is dictated by the ability to accommodate the clinical requirements. This lecture is intended to provide an introduction to these requirements and identify how synchrotrons are designed to deliver the desired beams as well as what limitations exist and expectations for the future of synchrotrons.
CORONALS AND THE PHONOTACTICS OF NONADJACENT CONSONANTS IN ENGLISH

Publisher Summary This chapter discusses coronals and the phonotactics of nonadjacent consonants in English and presents a distinction between morpheme structure constraints (MSCs) and syllable structure constraints (SSCs). Hooper argued against the existence of MSCs altogether. Hooper contended that all MSCs are expressible as, and so reducible to, syllable structure constraints. Hooper's argument for replacing MSCs with SSCs comes largely from Spanish data. A way of determining whether a constraint is an MSC rather than an SSC is by examining polysyllabic monomorphemic words. For example, if a constraint is posited between two segments based on monosyllabic monomorphemic words and that constraint is also relevant for the same segments in polysyllabic monomorphemic words, then that constraint is an MSC rather than an SSC.
Clinical Relation Extraction Toward Drug Safety Surveillance Using Electronic Health Record Narratives: Classical Learning Versus Deep Learning

Background: Medication and adverse drug event (ADE) information extracted from electronic health record (EHR) notes can be a rich resource for drug safety surveillance. Existing observational studies have mainly relied on structured EHR data to obtain ADE information; however, ADEs are often buried in the EHR narratives and not recorded in structured data. Objective: To unlock ADE-related information from EHR narratives, there is a need to extract relevant entities and identify relations among them. In this study, we focus on relation identification. This study aimed to evaluate natural language processing and machine learning approaches using the expert-annotated medical entities and relations in the context of drug safety surveillance, and investigate how different learning approaches perform under different configurations. Methods: We have manually annotated 791 EHR notes with 9 named entities (eg, medication, indication, severity, and ADEs) and 7 different types of relations (eg, medication-dosage, medication-ADE, and severity-ADE). Then, we explored 3 supervised machine learning systems for relation identification: (1) a support vector machines (SVM) system, (2) an end-to-end deep neural network system, and (3) a supervised descriptive rule induction baseline system. For the neural network system, we exploited the state-of-the-art recurrent neural network (RNN) and attention models. We report the performance by macro-averaged precision, recall, and F1-score across the relation types. Results: Our results show that the SVM model achieved the best average F1-score of 89.1% on test data, outperforming the long short-term memory (LSTM) model with attention (F1-score of 65.72%) as well as the rule induction baseline system (F1-score of 7.47%) by a large margin. The bidirectional LSTM model with attention achieved the best performance among different RNN models. With the inclusion of additional features in the LSTM model, its performance can be boosted to an average F1-score of 77.35%. Conclusions: It shows that classical learning models (SVM) remains advantageous over deep learning models (RNN variants) for clinical relation identification, especially for long-distance intersentential relations. However, RNNs demonstrate a great potential of significant improvement if more training data become available. Our work is an important step toward mining EHRs to improve the efficacy of drug safety surveillance. Most importantly, the annotated data used in this study will be made publicly available, which will further promote drug safety research in the community. [JMIR Public Health Surveill 2018;4(2):e29]
MORAS: An energy-scalable system using adaptive voltage scaling

This paper presents an energy-scalable computing platform for flexible and smart WSN edge applications. The platform comprises a 32-bit OpenRISC processor and two 4KB instruction and data caches on a chip, which can be operated in a wide supply voltage range. Adaptive voltage scaling makes this processor search its minimal operating voltage given a performance prerequisite. Different from many embedded MCU platforms, DRAM is supported here to expend flexibility of programing and data logging. This system on a chip (SoC) was implemented using TSMC 0.18 μm CMOS process, the operating range is from 0.6V, 2.5MHz to 1.2V, 40MHz. Measurements show the SoC achieves 170μW/MHz at 0.6V, offering a cost- and energy-efficient edge design solution.
Labor Standards and Human Rights Abuses: A Look at Some Neglected Rights Issues

Various groups have been demanding that discussions of labor standards be included in all future trade negotiations. The press is full of stories of alleged exploitation of child labor and other employment abuses in developing countries and human rights groups have demanded that something be done about it. However, the press and the academic literature have neglected various property, contract and association rights issues relating to labor standards in lesser developed countries. This paper attempts to remedy that deficiency and to start a discussion of some issues that have been overlooked or inadequately discussed. The tools of analysis will include both utilitarian ethics and rights-based ethics.
Comparative Analysis of Local Search Strategies for Transmission Network Expansion Planning

The demands for electricity and the electrical power generation in various areas may change significantly with time. These changes require additional transmission corridors to be installed in the existing electrical power network. The problem of electrical grid expansion can be formulated as a nonlinear mixed integer programming problem. The local search algorithms, which employ constructive heuristics for defining a neighborhood, could be used iteratively to find approximate solutions for this problem. In this study, we compare a number of local search strategies using statistical analysis techniques.
ISO 26262 konforme Software Entwicklung mit Model‐Based Design

Der modellbasierte Ansatz (Model‐Based Design) zur Entwicklung von Software in der Automobil Industrie ist weit verbreitet und gehort in vielen Anwendungen zur Standard Vorgehensweise. Die Charakteristika des modellbasierten Ansatzes sind komplexe Funktionalitaten durch Modelle zu beschreiben, diese Modelle dann mittels Simulation fruh zu testen und abzusichern. Model‐Based Design findet auch Einzug in Anwendungen wie Spurassistent oder elektromechanische Lenkunterstutzung. Diese sicherheitsrelevanten Systeme mussen Anforderungen der Norm zur funktionalen Sicherheit im Automobil ISO 26262 erfullen.
Preeclampsia: Short-term and Long-term Implications

Preeclampsia is a hypertensive disorder that affects 4% of pregnancies and has a high risk of maternal, fetal, and neonatal morbidity and mortality, as well as long-term cardiovascular risk. Recent updates in the definition, diagnosis, and management guidelines for preeclampsia warrant review by general obstetrician-gynecologists. Screening and prevention algorithms for preeclampsia are available, but ultimately the cure remains delivery of the fetus and placenta. Close monitoring for the development and worsening of preeclampsia during pregnancy is essential to optimize both maternal and fetal/neonatal outcomes.
Inter- and intraspecific competition and shade avoidance in the carnivorous pale pitcher plant in a nutrient-poor savanna.

Premise of the study Ecologists generally agree that weak interspecific competition for light contributes to high plant species diversity in ecosystems with nutrient-poor soils. However, the role of competition for light in such ecosystems that are also maintained by fire is poorly understood. I quantified intra- and interspecific competition for light in a fire-maintained nutrient-poor pine savanna by contrasting the effects of conspecific and heterospecific neighbors of the pale pitcher plant, Sarracenia alata. Methods Accounting for initial neighbor abundance/aboveground production and initial transplant size, I measured growth and survival of small and large pitcher plant ramets of Sarracenia alata transplanted to the vicinity of natural, undisturbed mixtures of large pitcher plants and their heterospecific neighbors in the field. I tested competition for light and nutrients by clipping conspecific neighbors and by excluding prey from unclipped neighbors of transplants. I tested interspecific competition by uprooting heterospecific neighbors. Key results Plant survivorship increased when conspecific neighbors were clipped and/or starved but not when heterospecific neighbors were uprooted. Small pitcher plants benefited from clipping large conspecific neighbors, suggesting that competition for light was important. Large pitcher plants benefited from excluding prey from their neighbors, with no additional benefit of clipping, suggesting that competition for prey limited their survival. Transplants produced new pitchers that were taller with narrower openings (i.e., shade avoidance) when heterospecific neighbors were left intact but not when conspecifics were unclipped. Conclusions Results demonstrate size-dependent intraspecific competition for light and nutrients and interspecific shade avoidance in Sarracenia alata, which could be important to understanding species coexistence in fire-maintained nutrient-poor ecosystems.
Investigation of the relative abundances of single-core and multicore compounds in asphaltenes by using high-resolution in-source collision-activated dissociation and medium-energy collision-activated dissociation mass spectrometry with statistical considerations

Abstract Asphaltenes cause multiple problems in the petroleum industry, such as clogging crude oil transportation pipelines and fouling catalysts. Characterization of the structures of the compounds in asphaltenes is essential for addressing these problems. Two main categories of asphaltene molecular structures, single-core (island) and multicore (archipelago), have been agreed upon. However, their relative abundances in asphaltenes have been debated for decades. This may be partially due to the fact that many mass spectrometry studies carried out in both academia and industry make conclusions for the entire asphaltene sample based on information derived from a group of ionized asphaltenes with m/z values ranging from one up to ten. This approach makes the unvalidated assumption that the relative abundances of single- and multicore compounds are uniform within the entire sample. In this study, medium-energy collision-activated dissociation (MCAD) in a linear quadrupole ion trap/orbitrap high-resolution mass spectrometer was employed to explore the structures of asphaltene molecular ions with m/z values in the ranges of 350 ± 10, 450 ± 10, 550 ± 10 and 650 ± 10. The ions studied displayed different extents of decrease in their weighted average ring and double bond equivalence (RDBE) values when undergoing dissociation, suggesting that the abundances of single-core and multicore compounds are not uniform within the entire asphaltene samples. Therefore, traditional mass spectrometry approaches used to determine the relative abundances of single- and multicore asphaltene compounds may suffer from a sampling bias. However, in-source collision-activated dissociation (IS-CAD) is not susceptible to sampling bias because no ion selection is involved.
Microaggression Experiences of Fathers With Children With Autism Spectrum Disorder

Using interpretive phenomenological analysis, we interviewed six fathers to learn about their experiences in acclimating others to their children’s autism spectrum diagnoses. Results indicate a nee...
Machine Learning Based Adaptive Gait Phase Estimation Using Inertial Measurement Sensors

This paper presents a portable inertial measurement unit (IMU)-based motion sensing system and proposed an adaptive gait phase detection approach for non-steady state walking and multiple activities (walking, running, stair ascent, stair descent, squat) monitoring. The algorithm aims to overcome the limitation of existing gait detection methods that are time-domain thresholding based for steady-state motion and are not versatile to detect gait during different activities or different gait patterns of the same activity. The portable sensing suit is composed of three IMU sensors (wearable sensors for gait phase detection) and two footswitches (ground truth measurement and not needed for gait detection of the proposed algorithm). The acceleration, angular velocity, Euler angle, resultant acceleration, and resultant angular velocity from three IMUs are used as the input training data and the data of two footswitches used as the training label data (single support, double support, swing phase). Three methods 1) Logistic Regression (LR), 2) Random Forest Classifier (RF), and 3) Artificial Neural Network (NN) are used to build the gait phase detection models. The result shows our proposed gait phase detection with Random Forest Classifier can achieve 98.94% accuracy in walking, 98.45% in running, 99.15% in stair-ascent, 99.00% in stair-descent, and 99.63% in squatting. It demonstrates that our sensing suit can not only detect the gait status in any transient state but also generalize to multiple activities. Therefore, it can be implemented in real-time monitoring of human gait and control of assistive devices.
Cognitive Behavior Therapy for Postpartum Depression.

In women with postpartum depression, the addition of CBT reduces depressive symptoms more effectively than usual care alone (medication and other therapies), with a medium effect size at the end of the intervention and a residual small effect size six months later.
Abstract 183: Phosphodiesterase 9 Inhibition Improves Cardiometabolic Profile in Female Mice Independent of Estrogen Status

Approximately 6.5 million Americans are living with heart failure (HF) currently and the number of persons is projected to increase 46% by 2030. One particularly notable syndrome associated with in...
Surgical Management of the Lumbar Spine in Rheumatoid Arthritis

Study Design:Narrative review.Objective:To provide an overview on the diagnosis and surgical management of rheumatoid involvement of the lumbar spine. Rheumatoid arthritis (RA) is a chronic inflamm...