cssi/SciSciGPT-SciSciNet huggingface dataset:
Analysis of intracellular drug (ouabain) sequestration as a mechanism of detoxification.

The cardiac glycoside ouabain, bound in a brief pulse to growing HeLa cells, is released over a period of days in a nonexponential manner that indicates heterogeneity of the dissociation processes. On release, the drug is chromatographically indistinguishable from authentic ouabain. We describe a model for release as the sum of three first-order processes: (a) simple dissociation from its membrane binding site [(Na++K+)-ATPase] into the medium; (b) sequestration or internalization of the drug, possibly together with its binding site, as part of membrane turnover; and (c) externalization of the internalized drug. Processes (a) and (b) lead to physiological recovery, and together occur substantially more rapidly than the sum of processes (a) and (c), which lead to release of drug from the cell. A program devised by Chandler et al. [(1972) Comp. Biomed. Res., 5, 515-534] is used to compute from drug release data the optimum least-squares fit as well as the compartment sizes and rate constants for the three processes. The analyses, based on data from intact cells, yield results that closely resemble those from data obtained from more disruptive cell fractionation procedures. These results show that ouabain is neither degraded nor stored in the cell. It can be found free in the cytoplasmic fraction, but it is not cytotoxic in that location. It is eventually released intact. Thus ouabain is not converted to an innocuous form by the cell, but rather is translocated to an innocuous location within the cell, with concomitant physiological recovery of normal functions at the cell surface prior to drug release.
Normal Mode Energetics of the General Circulation during the FGGE Year

Abstract Three-dimensional normal mode functions are applied to the analysis of the energetics of the general circulation during the FGGE year. The GFDL FGGE data are used for the computation of both the normal mode energetics and the standard spectral energetics. The normal mode energetics of the global circulation are presented in a barotropic and baroclinic decomposition for the zonal mean and eddy energies for the stationary and transient components of the flow. The energy generated in the zonal mean baroclinic component is first transformed to the eddy baroclinic component through the process of atmospheric baroclinic instability. It is then further transformed to eddy and zonal mean barotropic components by the nonlinear up-scale cascade of kinetic energy. The zonal mean kinetic energy thus maintains its barotropic structure by the activities of baroclinic waves. The time series of energy variables during the FGGE Northern Hemisphere winter clearly indicates a sequence of energy transformations from...
A non-quadratic gradient algorithm

Based on a non-quadratic cost function, a gradient-type algorithm is developed for estimating parameters of a linear model, resulting in a bounded normalized estimation error which converges to zero asymptotically with time and belongs to L/sup 1+/spl alpha// for 0 >
DISCOURSE INTONATION IN L2: FROM THEORY AND RESEARCH TO PRACTICE

DISCOURSE INTONATION IN L2: FROM THEORY AND RESEARCH TO PRACTICE. Dorothy M. Chun. Amsterdam: Benjamins, 2002. Pp. xvii + 285. CD-ROM. $52.95 paper.The objectives of this book are to emphasize the importance of intonation within the discourse domain and to draw upon research to suggest ways of teaching discourse-based intonation to second language (L2) learners. This book is organized in three parts. The first provides an overview of linguistic theories on prosodic elements. In this part, the author discusses four major categories of intonation according to function: grammatical (e.g., using intonation to mark prominence or stress), affective (e.g., to express attitudes or emotions), sociolinguistic (e.g., to signal politeness), and, importantly in this book, discourse (e.g., to contribute to cohesion in speech). Part 2 takes a look back at L2 research on pronunciation and intonation and the early teaching focus on individual sounds. This leads to the discussion of the current and future direction for teaching that emphasizes the discourse level of speech with an eye toward developing interactional competence at the macro level of communication. Studies have shown that improvement in the functional use of prosody contributes to higher production ratings for L2 speakers (Wennerstrom, 1998).
A glabrous Microsporum canis in Greater London

A variant of Microsporum canis, which produces glabrous colonies on primary culture, has been frequently isolated from cases of scalp and body ringworm by this department. The records of this laboratory, which undertakes a diagnostic service covering most of the Greater London Area, show that the prevalence of M. canis among scalp infections has increased during the past ten years, and this species is presently responsible for the majority of cases diagnosed by culture. The glabrous form now represents one third of the scalp isolates of M. canis and it has been found most commonly in the West and South of Greater London.
Effect of low body temperature on associative interference in conditioned taste aversion.

Summary When two novel conditioned stimuli precede an unconditioned stimulus (US), the interval between the two conditioned stimuli (CS1 and CS2) influences the magnitude of the CS-US associability of each CS. As the interval between CS1 and CS2 increases, the associability of CS1 with the US decreases due to interference by CS2 and the associability of CS2 increases, given its temporal proximity to the US. Because hypothermia has been reported to increase the interval at which conditioned taste aversions can be formed, its influence was examined on the above relationship, i.e., how interference from CS2 affects the associability of CS1 with the US. Rats received a conditioned taste aversion procedure where CS1 and CS2 were presented either one after the other or separated by an 80-min. delay. For all subjects, the US or pseudo-US was presented immediately after CS2. When hypothermia was interpolated between the two flavor stimuli that were spaced 80 min. apart, CS2-interference with the CS1-US associatio...
Pattern analysis of the genetic code

The genetic code is examined in a new and systematic fashion: we consider the code as mapping of one finite set (the 64 codons) to another (the 20 amino acids). Given a class of mappings simpler than the actual code, we ask which mappings best approximate it. This leads to an analysis of the effects of ambiguities (codon degeneracy) in one or two positions. With the 0-1 metric (counting the amino acids as equal or not equal), the codon third base degeneracy is apparent, but the first and second positions are indistinguishable; with the integrated amino acid ''distance'' metric compiled by Sneath (J. Theoret. Biol. 12 (1966), 157-195), the analysis ranks the information content of the three codon positions as follows: 2nd > 1st > 3rd. We discuss possible further applications of this approach to patterns in the genetic code and other codes.
Spin Torque Induced Magnetization Switching Variations

Spin torque induced magnetization switching variations are studied using experimental measurement and theoretical modeling. The study covers a wide time range, from the short time dynamic switching (10 ns) to the long time thermal switching (0.1 s). The modeling results agree well with the measurement data on switching mean and variation. Both data and model show different scaling behaviors of switching current variation and switching time variation as time scales down from the second to the nanosecond region. This study not only provides understanding of the physics involved, but also tools for making design tradeoffs between current switching magnitude, switching variation, switching speed, and thermal stability.
Evidence for a structural relationship between sarcoplasmic reticulum and Z lines in dog papillary muscle.

Electron micrographs of dog papillary muscle fibers show the sarco-plasmic reticulum (SR) as an extensive three-dimensional network of diverging and converging tubules that is continuous throughout each sarcomere and in successive sarcomeres. The network surrounds each myofibril and is continuous across the fiber. Tubules of the SR network are oriented transversely and longitudinally. Interconnections of transversely and longitudinally oriented SR tubules form circular pathways in the network. A structural relationship appears to exist between the Z line and longitudinally and transversely oriented tubules of the SR network at their points of apposition with the Z line. A rather constant space approximately 100 A wide is seen between SR tubules apposed at the Z line in cross-sections and in favorable longitudinal sections of fibrils. This space is traversed by electron-opaque strands which appear to be connections between SR tubules and the Z line. Other lines of evidence support the view that Z lines and SR tubules are connected. One of these is the change of position of Z line SR tubules in relation to the change of position of Z lines in adjacent fibrils. Another line of evidence is the continuity of SR apposed at the Z line and SR connected to the sarcolemma.
Trends in pathology graduate medical education.

Comprehensive data show trends in graduate medical education in pathology with regard to the numbers of accredited programs, persons certified from those programs, and demographics of the population of first year-trainees in pathology. Experience with US seniors and foreign-trained physicians in the PGY match process for pathology from 1991 through 2000 is presented, along with data on the types of medical schools generating pathology trainees for the PGY-1 year and the top medical schools of origin of US medical graduates who completed the program and became certified in pathology between 1995 and 1999. The impact of reimbursement of the credentialing year is also addressed through data collected from the PRODS Survey 2000, and those results are reviewed. Finally, turnover rates among pathology program directors of combined AP/CP programs and subspecialty programs since 1994 are presented. An analysis of these trends is provided, along with suggestions to improve both the perception of careers in pathology and the actual choice of a career in pathology.
Less Is More: Making Shareholder Activism A Valued Mechanism Of Corporate Governance

Institutional investors have increasingly engaged in corporate governance activities, introducing proxy proposals and negotiating with management, with a goal of improving corporate performance. As shareholder activism has increased, financial economists have sought to measure its effect on performance. This paper reviews the corporate finance literature on institutional investors' activities in corporate governance and also empirically investigates the effect of confidential voting proposals on voting outcomes. It then uses the findings of the empirical literature to inform normative recommendations for the proxy process. In brief, there is an apparent paradox: Notwithstanding the development of shareholder activism and commentators' generally positive assessments of it, the empirical research indicates that such activism has little or no effect on targeted firms' performance. This implies that activist institutions ought to reassess their agenda, in order to use their resources more effectively. The paper takes a two-pronged approach to furthering this aim. First, it suggests a mechanism of internal control, whereby funds would engage in periodic review of their shareholder-activism programs to identify the most fruitful governance objectives. Second, it seeks to provide incentives to undertake such internal revaluations by advocating elimination or significant reduction of the subsidy of proposal sponsorship under the SEC rules unless a proposal achieves substantial voting support, or permitting firms' shareholders to choose what level of subsidy they wish to provide proposal sponsors. The estimated savings from eliminating the subsidy for proposals that fail to receive at least 40% of the votes ranges from $293 million to $1.9 billion.
Skart: a skewness-and autoregression-adjusted batch-means procedure for simulation analysis

We discuss Skart, an automated batch-means procedure for constructing a skewness- and autoregression-adjusted confidence interval for the steady-state mean of a simulation output process. Skart is a sequential procedure designed to deliver a confidence interval that satisfies user-specified requirements concerning not only coverage probability but also the absolute or relative precision provided by the half-length. Skart exploits separate adjustments to the half-length of the classical batch-means confidence interval so as to account for the effects on the distribution of the underlying Student?s t -statistic that arise from nonnormality and autocorrelation of the batch means. Skart also delivers a point estimator for the steady-state mean that is approximately free of initialization bias. In an experimental performance evaluation involving a wide range of test processes, Skart compared favorably with other simulation analysis methods-namely, its predecessors ASAP3, WASSP, and SBatch as well as ABATCH, LBATCH, the Heidelberger-Welch procedure, and the Law-Carson procedure.
Boxing Training for Patients With Parkinson Disease: A Case Series

Background and Purpose A nontraditional form of exercise recently applied for patients with Parkinson disease (PD) is boxing training. The primary purpose of this case series is to describe the effects of disease severity and duration of boxing training (short term and long term) on changes in balance, mobility, and quality of life for patients with mild or moderate to severe PD. The feasibility and safety of the boxing training program also were assessed. Case Descriptions Six patients with idiopathic PD attended 24 to 36 boxing training sessions for 12 weeks, with the option of continuing the training for an additional 24 weeks (a seventh patient attended sessions for only 4 weeks). The 90-minute sessions included boxing drills and traditional stretching, strengthening, and endurance exercises. Outcomes were tested at the baseline and after 12, 24, and 36 weeks of boxing sessions (12-, 24-, and 36-week tests). The outcome measures were the Functional Reach Test, Berg Balance Scale, Activities-specific Balance Confidence Scale, Timed “Up & Go” Test, Six-Minute Walk Test, gait speed, cadence, stride length, step width, activities of daily living and motor examination subscales of the Unified Parkinson Disease Rating Scale, and Parkinson Disease Quality of Life Scale. Outcomes Six patients completed all phases of the case series, showed improvements on at least 5 of the 12 outcome measures over the baseline at the 12-week test, and showed continued improvements at the 24- and 36-week tests. Patients with mild PD typically showed improvements earlier than those with moderate to severe PD. Discussion Despite the progressive nature of PD, the patients in this case series showed short-term and long-term improvements in balance, gait, activities of daily living, and quality of life after the boxing training program. A longer duration of training was necessary for patients with moderate to severe PD to show maximal training outcomes. The boxing training program was feasible and safe for these patients with PD.
Regulation of Ca(2+)-activated K+ channels by protein kinase A and phosphatase inhibitors

Many proteins including ion channels are regulated by phosphorylation. We tested the effect of 10 U/ml catalytic subunit protein kinase A on 260-pS Ca(2+)-activated K+ channels in excised inside-out membrane patches from freshly dispersed smooth muscle cells of the canine proximal colon. At +50 mV with 10(-7) M Ca2+ and -50 mV with 10(-6) M Ca2+, open probability of the channels was increased to 270 +/- 48% of control (n = 12). This increase was due to a shift in voltage-dependent activation by 13.9 +/- 3.2 mV (n = 3) to more negative potentials. Protein kinase A in the absence of ATP had no effect on channel activity (n = 3). Regulation by phosphorylation must be accompanied by dephosphorylation. We tested the effect of two potent inhibitors of protein phosphatases, calyculin A and okadaic acid. Application of 10(-9) to 10(-6) M of each inhibitor in the presence of protein kinase A further increased open probability by up to 250%. Calyculin A appeared to be less effective in increasing open probability than okadaic acid, suggesting that the phosphatase involved is neither type 1, 2A, nor 2B. Calyculin A in the absence of protein kinase A was ineffective. These data suggest that endogenous phosphatases are found in excised membrane patches and that a balance between phosphorylation and dephosphorylation may provide an important control of colonic motility.
Waste products as chrysomelid defenses

The phrase ‘chrysomelid defense’ evokes images of the remarkable glandular products that protect many leaf beetles. Yet several chrysomelids employ more mundane materials to defend themselves. Specifically, many leaf beetles recycle waste products, such as feces and exuviae, as protective devices.
A 14-Year-Old Boy with Vomiting

A 14-year-old boy was transferred from an outside hospital for evaluation of vomiting. He had been well until he traveled to India 3 weeks earlier. Upon return, he developed abdominal pain and recurrent episodes of nonbilious, nonbloody emesis. The day of admission, he ate a slice of pizza and then experienced numerous episodes of vomiting every 15 to 30 minutes. There had been minimal diarrhea at the beginning of the illness, but none over the following 3 weeks. Review of systems was otherwise unremarkable. The patient’s medical history was remarkable for poor weight gain and linear growth without any evaluation. He is in an eighth-grade classroom, but functions at a first-grade level. His parents are aware that his IQ is low, but they can’t describe the extent of his cognitive impairment. All we know of his developmental/intellectual history is that he walked at 2 years of age and spoke his first words at 3 years. The family follows a traditional Jain vegetarian diet (in this case, essentially vegan). They had given him Ensure in the past because of his poor weight gain. The family history is unremarkable. He has one healthy brother of normal stature. There is no known history of consanguinity. Birth history was unremarkable. On exam, the patient was a small, thin, malnourished boy. He was afebrile, pulse 82, respiratory rate 20, and blood pressure 112/70. His height was
A multivariate study of the relationship between dispersal and demography in populations of Microtus ochrogaster in eastern Kansas.

Stepwise multiple regression analysis was used to determine which demographic variables explained the most variation in numbers of dispersers and rates of dispersal in prairie vole (Microtus ochrogaster) populations. Dispersal was estimated by the removal of all voles appearing on two treatment grids that were live-trapped biweekly. Population density was important in explaining variation in numbers of dispersers of all age classes. Season was important for adult males and females. It was concluded that dispersal was density-independent, in that a constant proportion of the population emigrated at all densities. Different demographic variables were important in explaining the rates of dispersal of each age class. A principal components analysis reduced the original set of demographic variables to four components. The first principal component had high positive loadings for population density variables; PC-II had high negative loadings for survival; PC-III was a reflection of seasonality, with a high positive loading for autumn; PC-IV had a high negative loading for male reproductive activity. There were statistically significant positive correlations between the factor scores of PC-II and rates of dispersal of adult males and females, and a significant negative correlation between PC-II and the rate of dispersal of juvenile males. There were significant positive correlations between PC-IV and rates of dispersal of adult males, adult females and subadult females. Except for juvenile females, number of dispersers of all age classes was correlated positively with the factor scores of PC-I. PCII was correlated positively with the number of dispersers of both subadult males and females, and number of subadult male dispersers was correlated positively with PC-III.
Thin Beds: Seismic Analysis workflows to see what is barely resolved

Poor definition of thin beds when approaching the limits of seismic resolution is one problem we are often confronted with when interpreting reflectivity data, particularly when trying to distinguish the stratigraphic relationships between sedimentary packages being imaged. The loss of higher frequencies due to the filtering effect of the earth (attenuation), and the impossibility to fully recover those frequencies during the processing stages severely affect our ability to vertically separate events in our seismic sections as continuous individual reflectors below the tuning frequency. Seismic resolution is paramount for looking at stratigraphic features that indicate internal bedding geometries, pinch outs and reflector terminations all that often fall close to or below the limit of seismic resolution. In this paper we illustrate several techniques such as Frequency Analysis, Wavelet Geometry Analysis and Spectral Enhancement, which help identify thin beds and aid the interpretation of their extents in poorly resolved data.
Alleviating Poverty Through Housing Policy Reform

The purpose of this paper is to describe proposals for reform of low-income housing assistance that will alleviate poverty without increasing public spending. Low-income housing assistance is fertile ground for such reforms. The majority of current recipients are served by programs whose cost is enormously excessive for the housing provided. Phasing out these programs in favor of the system’s most cost-effective program would ultimately free up the resources to provide housing assistance to millions of additional people (Olsen 2014). Furthermore, the current system of low-income housing assistance provides enormous subsidies to some households while offering none to others who are equally poor, and it provides subsidies to many people who are not poor while offering none to many of the poorest. Avoiding these excessive subsidies and focusing assistance on the poorest families will contribute further to poverty alleviation. Well-designed reforms of the current system of low-income housing assistance would produce substantial poverty alleviation without greater public spending.
Detecting unprotected SIP-based voice over IP traffic

The use of Voice over IP (VoIP) applications has dramatically increased in recent years. Large, medium, and small organizations, as well as individuals, are reducing the cost of their phone calls using their data infrastructure or a broadband Internet service to transmit phone calls over IP networks. Like data networks, VoIP networks are also vulnerable to security threats such as Denial-of-Service (DoS) attacks, interception of private communications, registration hijacking, spam, and message tampering. Security mechanisms, such as encryption and authentication, may be used to reduce the potential impact of some of these security threats. However, in reality, VoIP providers may not supply adequate security, or otherwise they are adopting and implementing these countermeasures at very slow rates without informing users whether their phone calls are protected. Given the fact that the interception of private communications is one of the most commonly seen attacks in VoIP, we present a solution to detect unprotected SIP-based VoIP packets. Upon positive detection, alerts may be sent to users informing them about the unprotected VoIP calls, thus potentially preventing identity theft and improving security awareness. Our testing results show that our solution provides accurate detection with zero false detection rate of unprotected SIP-based VoIP traffic.
Reflections on Narrative in Pastoral Theology

This essay recounts the story of a pastoral interaction with a man who tried to rob a local church on a Sunday morning. The individual had recently been released from prison and found himself in a position where he could not find employment. Lacking basic supplies and frustrated by his inability to take care of his family, he almost fell back into familiar patterns of criminal activity. Turning to a variety of sources, this essay reflects on the ministry of listening, the human need for emotional connection with others, and the eschatological hope found in the Christian tradition. In providing room for the narratives of those we serve, pastoral theologians provide a gracious space wherein the Spirit moves upon the teller of the tale as well as the listener. Together, we are transformed as we follow the path of God’s plot that unfolds chapter by chapter.
Socialism: Globalization as the Fulfilment of History

This chapter examines how different meanings are bestowed on the concept of globalization depending on the variation in interpretations of the concepts located in its proximity within the three main socialist currents of Marxism, democratic socialism and social democracy. The fact that the respective concepts of globalization are diverse and in some respects incompatible serves as a pungent reminder that the analysis of the ideological readings of globalization requires attention not just to differences between broad ideological families but also to conceptual shifts within the ambit of any family as having a potentially significant bearing upon the resultant understandings of globalization.
Universal Conductance Fluctuations and Quantum Interference Effects in Microstructures

The low-temperature conducting properties of microstructures are observed to vary in a random manner as a function of magnetic field or carrier density. These fluctuations are sample-specific, but time-independent and reproducible within a given sample. It is now understood that these fluctuations result from random quantum interference of diffusing electrons. We review the recently-developed theory of these novel fluctuation phenomena, which predicts that the order of magnitude of the absolute fluctuations in the conductance of any metallic system is e 2 /h,as long as the conductor is probed on length scales of the order of the inelastic diffusion length. Differences between the behavior of the fluctuations measured in a two-probe as compared to a multi-probe geometry are discussed, and some recent results relevant to the multi-probe case are presented. A recent hypothesis relating these time-independent fluctuation effects to low-frequency noise in dirty metals is reviewed, and a decisive experiment for testing the theory is proposed.
A Primer on Diabetes Mellitus: Foundations for the Incoming First-Year Resident.

Abstract Introduction Given the increasing prevalence of diabetes mellitus, trainees should have a strong foundation in the management of diabetes. Published literature on the knowledge base and co...
Why Do Some Firms Expand by Acquisitions and Others by Creating Alliances

This study investigates the choice between mergers and acquisitions (M&As) and strategic alliances, and the wealth implications associated with these alternatives of expansion. The findings reported here yield little support for managerial self-interest or hubris as relevant determinants of the decision to acquire or to ally. The results suggest that firms establish alliances because valuation uncertainty and costly access to external capital limit their access to the market for M&As. M&As are more prevalent than alliances, and they are associated with superior increases in shareholder’s wealth in periods other than during the aftermath of industry shocks. Ownership-sharing in alliances, however, appears as a valuable mechanism to ameliorate the consequences of market failures caused by informational asymmetries. The analysis also suggest that a significant proportion of the gains associated with alliances stems from a positive reassessment of the value of partner firms.
Effects of Defects on the Performance of Hierarchical Honeycomb Metamaterials Realized Through Additive Manufacturing

Cellular metamaterials are of immense interest for many current engineering applications. Tailoring the structural organization of cellular structures leads to new metamaterials with superior properties leading to low weight and very strong/stiff materials. Incorporation of hierarchy to regular cellular structures enhances the properties and introduces novel tailorable metamaterials.For many complex cellular metamaterials, the only realistic manufacturing process is additive manufacturing (AM). The use of AM to manufacture large structures may lead to several types of defects during the manufacturing process, such as missing/broken cell walls, irregular thickness, flawed joints, missing (partial) layers, and irregular elastic plastic behavior due to toolpath. For large structures, it would be beneficial to understand the effect of defects on the overall performance of the structure to determine if the manufacturing defect(s) are significant enough to abort and restart or whether the material can still be used.Honeycomb structures are used for the high strength to weight ratio applications. These metamaterials have been studied and several models have been developed based on idealized cell structures to explain their elastic plastic behavior. However, these models do not capture real-world manufacturing defects resulting from AM. The variation of elastic plastic behavior of regular honeycomb structures with defects has been studied, but the performance of hierarchical honeycomb structures with defects is still unknown. In this study, the effects of missing cell walls are investigated to understand the elastic behavior of hierarchical honeycomb structures through simulations using finite element analysis. Regular (zero order), first order and second order hierarchical honeycombs have been investigated in this study. The first level of hierarchy has been implemented by changing each three edge vertex of a regular hexagonal honeycomb lattice by adding another smaller hexagon. The second level of hierarchy is created by adding another smaller hexagon at each three edge vertex of the hexagons added for the first order hierarchy. For the hierarchical cases, the overall density of the honeycomb is held constant to the parent structure (zero order or regular) by reducing the thickness of the cell wall in the first and second order structures. ANSYS® was used to develop finite element models to analyze the performance of both perfect and defected regular, first order and second order hierarchical honeycombs. Defects were added to the model by randomly removing cell walls. Hierarchical honeycombs demonstrated more sensitivity to missing cell walls than regular honeycombs. On average, the elastic modulus decreased by 45% with 5.5% missing cell walls for regular honeycombs, 60% with 4% missing cell walls for first order hierarchical honeycomb and 95% with 4% missing cell walls for second order hierarchical honeycombs.Copyright © 2016 by ASME
Detecting signals of chronic shedding to explain pathogen persistence: Leptospira interrogans in California sea lions.

Identifying mechanisms driving pathogen persistence is a vital component of wildlife disease ecology and control. Asymptomatic, chronically infected individuals are an oft-cited potential reservoir of infection, but demonstrations of the importance of chronic shedding to pathogen persistence at the population-level remain scarce. Studying chronic shedding using commonly collected disease data is hampered by numerous challenges, including short-term surveillance that focuses on single epidemics and acutely ill individuals, the subtle dynamical influence of chronic shedding relative to more obvious epidemic drivers, and poor ability to differentiate between the effects of population prevalence of chronic shedding vs. intensity and duration of chronic shedding in individuals. We use chronic shedding of Leptospira interrogans serovar Pomona in California sea lions (Zalophus californianus) as a case study to illustrate how these challenges can be addressed. Using leptospirosis-induced strands as a measure of disease incidence, we fit models with and without chronic shedding, and with different seasonal drivers, to determine the time-scale over which chronic shedding is detectable and the interactions between chronic shedding and seasonal drivers needed to explain persistence and outbreak patterns. Chronic shedding can enable persistence of L. interrogans within the sea lion population. However, the importance of chronic shedding was only apparent when surveillance data included at least two outbreaks and the intervening inter-epidemic trough during which fadeout of transmission was most likely. Seasonal transmission, as opposed to seasonal recruitment of susceptibles, was the dominant driver of seasonality in this system, and both seasonal factors had limited impact on long-term pathogen persistence. We show that the temporal extent of surveillance data can have a dramatic impact on inferences about population processes, where the failure to identify both short- and long-term ecological drivers can have cascading impacts on understanding higher order ecological phenomena, such as pathogen persistence.
Extended X-Ray Absorption Fine Structure Studies of Actinide Ions in Aqueous Solution

Extended x-ray absorption fine structure (EXAFS) spectroscopy can be used to probe the local atomic environment around actinide atoms in a variety of systems. Uranium LIII-edge spectra were obtaine...
A Catalog of Security Architecture Weaknesses

Secure by design is an approach to developing secure software systems from the ground up. In such approach, the alternate security tactics are first thought, among them, the best are selected and enforced by the architecture design, and then used as guiding principles for developers. Thus, design flaws in the architecture of a software system mean that successful attacks could result in enormous consequences. Therefore, secure by design shifts the main focus of software assurance from finding security bugs to identifying architectural flaws in the design. Current research in software security has been neglecting vulnerabilities which are caused by flaws in a software architecture design and/or deteriorations of the implementation of the architectural decisions. In this paper, we present the concept of Common Architectural Weakness Enumeration (CAWE), a catalog which enumerates common types of vulnerabilities rooted in the architecture of a software and provides mitigation techniques to address them. The CAWE catalog organizes the architectural flaws according to known security tactics. We developed an interactive web-based solution which helps designers and developers explore this catalog based on architectural choices made in their project. CAWE catalog contains 224 weaknesses related to security architecture. Through this catalog, we aim to promote the awareness of security architectural flaws and stimulate the security design thinking of developers, software engineers, and architects.
Mammalian Glutamyl Aminopeptidase Genes (ENPEP) and Proteins: Comparative Studies of a Major Contributor to Arterial Hypertension

Glutamyl aminopeptidase (ENPEP) is a member of the M1 family of endopeptidases which are mammalian type II integral membrane zinc-containing endopeptidases. ENPEP is involved in the catabolic pathway of the reninangiotensin system forming angiotensin III, which participates in blood pressure regulation and blood vessel formation. Comparative ENPEP amino acid sequences and structures and ENPEP gene locations were examined using data from several mammalian genome projects. Mammalian ENPEP sequences shared 71-98% identities. Five N-glycosylation sites were conserved for all mammalian ENPEP proteins examined although 9-18 sites were observed, in each case. Sequence alignments, key amino acid residues and predicted secondary and tertiary structures were also studied, including transmembrane and cytoplasmic sequences and active site residues. Highest levels of human ENPEP expression were observed in the terminal ileum of the small intestine and in the kidney cortex. Mammalian ENPEP genes contained 20 coding exons. The human ENPEP gene promoter and first coding exon contained a CpG island (CpG27) and at least 6 transcription factor binding sites, whereas the 3’-UTR region contained 7 miRNA target sites, which may contribute to the regulation of ENPEP gene expression in tissues of the body. Phylogenetic analyses examined the relationships of mammalian ENPEP genes and proteins, including primate, other eutherian, marsupial and monotreme sources, using chicken ENPEP as a primordial sequence for comparative purposes.
A hybrid approach to improving program security

The security of computer programs and systems is a very critical issue. With the number of attacks launched on computer networks and software, businesses and IT professionals are taking steps to ensure that their information systems are as secure as possible. However, many programmers do not think about adding security to their programs until their projects are near completion. This is a major mistake because a system is as secure as its weakest link. If security is viewed as an afterthought, it is highly likely that the resulting system will have a large number of vulnerabilities, which could be exploited by attackers. One of the reasons programmers overlook adding security to their code is because it is viewed as a complicated or time-consuming process. This paper presents a tool that will help programmers think more about security and add security tactics to their code with ease. We created a model that learns from existing open source projects and documentation using machine learning and text mining techniques. Our tool contains a module that runs in the background to analyze code as the programmer types and offers suggestions of where security could be included. In addition, our tool fetches existing open source implementations of cryptographic algorithms and sample code from repositories to aid programmers in adding security easily to their projects.
Domestic Political Incentives, Congressional Support, and U.S. Mediation

Powerful states have numerous resources that can be mobilized in mediation processes. However, evidence suggests that such states are not more likely to be successful than other mediators. This article examines U.S. mediations through the lens of foreign policy decision making and argues that leaders make foreign policy decisions primarily with their domestic consequences in mind. Further, it contends that presidential administrations seek to build a record of success in order to improve their domestic political fortunes based on the policy options available to them. The study tests two explanations of foreign policy substitution based on domestic conditions and institutional configurations, the “party cover” and “policy availability” arguments, for U.S. mediations from 1945–1999. Results for the party cover argument are more robust, suggesting that domestic conditions play an important role in the decision to engage in mediation and imply that successful mediation is secondary to domestic politics.
Assessment using peer evaluations, random pair assignment, and collaborative programing in CS1

In this paper we describe a technique for student assessment that uses peer evaluation and random pair assignment in collaborative programming assignments in CS1. A common concern of professors implementing collaborative (pair) programming is the potential for a student to not actively participate in the programming process. In this case, a student's skills and abilities may not be developed or evaluated. In addition to traditional grading of an assignment, a survey was given to each student following every assignment in order to assess the individual contribution and comprehension of the assignment requirements. The survey asked each student to briefly evaluate his or her teammate's cooperation as well as to project the teammate's ability to re-write the code. The results of this assessment method indicate that the assignment quality greatly increased and exam scores were comparable compared to previous course offerings when assignments were completed individually.
Mathematical Modeling of Bacteria-Enabled Drug Delivery System Penetration into Multicellular Tumor Spheroids

Bacteria-based cancer treatment is a promising approach to address the need for targeted tumor therapies in an effort to avoid the systemic toxicity inherent in conventional chemotherapy. A number of bacterial strains have been shown to preferentially colonize tumors and impart therapeutic benefits. However, the physical underpinnings of bacteria intratumoral transport remain poorly studied. It is hypothesized that cell Iysis in hypoxic and necrotic regions of tumors creates a niche in which some bacteria thrive. To understand if preferential growth plausibly explains the experimentally observed bacterial colonization profiles, we have developed a mathematical model incorporating transport and growth dependent on tumor cell Iysate. We fit model parameters to experimental data, showing that our formulation captures experimentally observed trends. Moreover, we find that bacteria have a higher effective diffusivity than nanoparticles alone, demonstrating transport advantages to designing bacteria-based cancer therapy. This model serves as a first step towards building computational tools for designing optimized bacteria- based chemotherapeutic delivery systems.
Synthesis and surface spectroscopy of α-pinene isotopologues and their corresponding secondary organic material

Atmospheric aerosol-cloud interactions remain among the least understood processes within the climate system, leaving large uncertainties in the prediction of future climates. In particular, the nature of the surfaces of aerosol particles formed from biogenic terpenes, such as α-pinene, is poorly understood despite the importance of surface phenomena in their formation, growth, radiative properties, and ultimate fate. Herein we report the coupling of a site-specific deuterium labeling strategy with vibrational sum frequency generation (SFG) spectroscopy to probe the surface C-H oscillators in α-pinene-derived secondary organic aerosol material (SOM) generated in an atmospheric flow tube reactor. Three α-pinene isotopologues with methylene bridge, bridgehead methine, allylic, and vinyl deuteration were synthesized and their vapor phase SFG spectra were compared to that of unlabeled α-pinene. Subsequent analysis of the SFG spectra of their corresponding SOM revealed that deuteration of the bridge methylene C-H oscillators present on the cyclobutane ring in α-pinene leads to a considerable signal intensity decrease (ca. 30-40%), meriting speculation that the cyclobutane moiety remains largely intact within the surface bound species present in the SOM formed upon α-pinene oxidation. These insights provide further clues as to the complexity of aerosol particle surfaces, and establish a framework for future investigations of the heterogeneous interactions between precursor terpenes and particle surfaces that lead to aerosol particle growth under dynamically changing conditions in the atmosphere.
Impact of a diet and activity health promotion intervention on regional patterns of DNA methylation

Studies demonstrate the impact of diet and physical activity on epigenetic biomarkers, specifically DNA methylation. However, no intervention studies have examined the combined impact of dietary and activity changes on the blood epigenome. The objective of this study was to examine the impact of the Make Better Choices 2 (MBC2) healthy diet and activity intervention on patterns of epigenome-wide DNA methylation. The MBC2 study was a 9-month randomized controlled trial among adults aged 18–65 with non-optimal levels of health behaviors. The study compared three 12-week interventions to (1) simultaneously increase exercise and fruit/vegetable intake, while decreasing sedentary leisure screen time; (2) sequentially increase fruit/vegetable intake and decrease leisure screen time first, then increase exercise; (3) increase sleep and decrease stress (control). We collected blood samples at baseline, 3 and 9 months, and measured DNA methylation using the Illumina EPIC (850 k) BeadChip. We examined region-based differential methylation patterns using linear regression models with the false discovery rate of 0.05. We also conducted pathway analysis using gene ontology (GO), KEGG, and IPA canonical pathway databases. We found no differences between the MBC2 population (n = 340) and the subsample with DNA methylation measured (n = 68) on baseline characteristics or the impact of the intervention on behavior change. We identified no differentially methylated regions at baseline between the control versus intervention groups. At 3 versus 9 months, we identified 154 and 298 differentially methylated regions, respectively, between controls compared to pooled samples from sequential and simultaneous groups. In the GO database, we identified two gene ontology terms related to hemophilic cell adhesion and cell-cell adhesion. In IPA analysis, we found pathways related to carcinogenesis including PI3K/AKT, Wnt/β-catenin, sonic hedgehog, and p53 signaling. We observed an overlap between 3 and 9 months, including the GDP-l-fucose biosynthesis I, methylmalonyl metabolism, and estrogen-mediated cell cycle regulation pathways. The results demonstrate that the MBC2 diet and physical activity intervention impacts patterns of DNA methylation in gene regions related to cell cycle regulation and carcinogenesis. Future studies will examine DNA methylation as a biomarker to identify populations that may particularly benefit from incorporating health behavior change into plans for precision prevention.
Narrow-linewidth VCSELs based on multi-mirror cavities (Conference Presentation)

We report on the design and characterization of multi-mirror vertical-cavity surface-emitting lasers (VCSELs) that achieve linewidths less than 2 MHz. We have fabricated all-semiconductor multi-mirror VCSELs at 850 nm that operate in a single mode and are suitable for high-resolution spectroscopy. Cold-cavity linewidth measurements confirm increased quality factors relative to standard VCSEL resonators. Frequency noise power spectral density measurements exhibit 1/f noise and white-noise floors consistent with Lorentzian linewidths less than 2 MHz.