cssi/SciSciGPT-SciSciNet huggingface dataset:
Complex Hydroindoles by an Intramolecular Nitrile-Intercepted Allylic Alkylation Cascade Reaction.

Bisnucleophilic reagents derived from malononitrile, ketones, benzaldehydes, and nitromethane can react with bisallylic electrophiles via a nitrile-intercepted allylic alkylation cascade reaction to yield complex hydroindole architectures. Also noteworthy is that the only stoichiometric byproducts from the preparation and reaction of the bisnucleophile and biselectrophile are water, acetic acid, and bicarbonate, making it a potentially “green” platform for multistep complex molecule synthesis. These scaffolds can be converted into hydrooxindoles by a unique olefin isomerization followed by Witkop–Winterfeldt-like oxidation.
Developing and assessing electronic checklists for safety mindfulness, workload, and performance.

Abstract Purpose The aim of this study is to propose a set of innovative principles for the effective design of electronic checklists to enhance safety mindfulness (a specific safety mindful mindset that offers the opportunity to operate more preemptively during routine quality assurance tasks) and discuss some of our preliminary results from testing our proposed electronic checklist with dosimetrists and physicists. Methods and materials A multidisciplinary team designed, developed, and evaluated the utility of the electronic checklist (vs paper-based checklist) to promote safety mindfulness. Subjective workload was measured at the end of each assessment/scenario. Performance was quantified on the basis of discovery of purposefully embedded errors, time to complete the scenario, and additional concerns that were documented by the participants. Results Use of the electronic checklist was associated with decreases in time to scenario completion (P Conclusions Our proposed principles for the design of electronic checklists may improve the efficiency of quality assurance procedures while enhancing users' safety mindfulness. Future research is needed to better understand the utility of our proposed design principles on patient safety from a long-term use perspective.
Interprofessional education through a telehealth team based learning exercise focused on pharmacogenomics.

Abstract Background Traditional interprofessional educational (IPE) exercises are those where learning exists “about, from, and with” trainees in two or more professions in order to prepare health sciences professionals to work on interprofessional teams. One emerging difficulty with IPE is the paucity of health profession students at single institutions, and the geographic and financial constraints of multi-institutional collaboration. Interprofessional education activity To circumvent these barriers, we developed a multi-institution telehealth team-based learning (TBL) event between medical and pharmacy students on the topic of pharmacogenomics (PGx). Using a validated pre-post survey design, student attitudes and perceptions were measured before and after an educational intervention designed to simulate interprofessional telehealth collaboration. The survey results showed significant improvement across all areas of student attitudes toward interprofessional collaboration. Also, medical student PGx confidence increased substantially during the exercise even though the only PGx instruction they received was from pharmacy students. Discussion These data demonstrate that learning exists “about, from, and with” trainees in other professions, even if they do not physically train in the same location. Free tools are available to create virtual interactions between students on different campuses, and telehealth exercises using these tools are a valid way to conduct IPE across different campuses. The instructional experience does not need to be identical for all participants in the IPE event; rather, tailoring the educational experience to each group of students provides opportunities for inter-student teaching.
Left-Right Asymmetry and Cardiac Looping

Publisher Summary This chapter focuses on the progress that has been made in the past in the identification of genes that may play roles in the specification of left-right (L-R) asymmetry and cardiac looping in early vertebrate embryos. The morphological changes are summarized that occur during early heart development, genes that have been identified to be asymmetrically expressed before and during heart looping, embryonic manipulations that can affect looping, and mutations that randomize or reverse the direction of looping. It is found that Looping of the heart is the first morpological indication of L-R asymmetry in vertebrates. Several proteins, including TGF-β-related signaling molecules, bHLH transcription factors, zinc finger transcription factors, and ECM components are asymmetrically expressed both prior to and during the looping of the heart. The chapter also proposes a novel molecular model for the initial determination of the L-R asymmetry. Since heart looping represents the first morphological manifestation of L-R asymmetry in vertebrates, an intriguing goal for research on cardiac embryogenesis is to elucidate the specific signals that are used to translate molecular L-R asymmetry into architectural L-R asymmetry.
Phoneme classification over the reconstructed phase space using principal component analysis.

Although isolated phoneme classification using features from time-domain phase space reconstruction has been investigated recently, the best representation of feature vectors for the discriminability over phoneme classes is still an open question. This paper applies Principal Component Analysis (PCA) to feature vectors from the reconstructed phase space. By using PCA projection, the basis of the feature space is orthogonalized. A Bayes classifier uses the transformed feature vectors to classify phoneme exemplars. The results show that the classification accuracy with PCA method surpasses the accuracy using only original features in most cases. PCA projection was implemented in three ways over the reconstructed phase space on both speaker-dependent and speaker-independent data. Models are trained and tested using data drawn from the TIMIT database.
Reading as Culturally Mediated, Mediating, and Meaningful Action

In discussions of readers and texts, it is common to refer to the importance of the text’s meaning to the reader. Yet the idea that texts should be meaningful is rarely defined. Rather, it is assumed to be not only a property of a worthwhile reading experience, but a concept that all reading theorists and practitioners understand in more or less the same way.
Next Partition of an n -Set (NEXEQU)

This chapter discusses an algorithm for generating next partition of an n -set. It describes a partition of S is defined. No significance attaches to the names of the classes within a partition. Yet, on output, the computer is forced to name these classes for reference purposes. The algorithm does this naming in such a way that the smallest element of class j is the first integer, which does not belong to any earlier class 1, 2, …, j −1. The chapter discusses subroutine specifications for the subprogram NEXTEQU. It presents the sample output of the subprogram. NEXEQU was called repeatedly with N = 5, until termination. The chapter presents 52 output vectors Q (1), Q (2), …, Q (5).
Variable costs of eavesdropping a green leaf volatile on two plant species in a common garden experiment

Herbivore-induced plant volatiles (HIPVs) from one plant may cue eavesdropping neighboring plants to prepare, or 9prime9, defenses prior to experiencing herbivory. HIPV-mediated defense priming is now a well-documented, inducible phenomenon that should, like any inducible phenomenon, incur fitness costs. Yet, ecological costs associated with exposure to volatile cues alone are not clear. For the first time under field conditions, we tested the hypothesis that exposure to a single HIPV would decrease herbivore damage at the cost of reduced plant growth and reproduction. In a common garden experiment, we exposed lima bean (Phaseolus lunatus) and pepper (Capsicum annuum) plants to a persistent, low-dose (~10ng/hour) of the green leaf volatile cis-3-hexenyl acetate (z3HAC), which is a HIPV that alone can prime plant defense. z3HAC-treated pepper plants were shorter, had less aboveground and belowground biomass, and produced fewer flowers and fruits relative to controls. In contrast, z3HAC-treated lima bean plants were taller and produced more leaves and flowers than did controls. Additionally, we observed species-specific differences in herbivore damage: herbivory was reduced only in z3HAC-exposed lima bean plants but not pepper plants. Synthesis: Differential responses to an identical priming cue in a shared common field have important implications for ecological costs and benefits of volatile-mediated inter-plant communication.
Redshift inference from the combination of galaxy colours and clustering in a hierarchical Bayesian model

Powerful current and future cosmological constraints using high precision measurements of the large-scale structure of galaxies and its weak gravitational lensing effects rely on accurate characterization of the redshift distributions of the galaxy samples using only broadband imaging. We present a framework for constraining both the redshift probability distributions of galaxy populations and the redshifts of their individual members. We use a hierarchical Bayesian model (HBM) which provides full posterior distributions on those redshift probability distributions, and, for the first time, we show how to combine survey photometry of single galaxies and the information contained in the galaxy clustering against a well-characterized tracer population in a robust way. One critical approximation turns the HBM into a system amenable to efficient Gibbs sampling. We show that in the absence of photometric information, this method reduces to commonly used clustering redshift estimators. Using a simple model system, we show how the incorporation of clustering information with photo-$z$'s tightens redshift posteriors, and can overcome biases or gaps in the coverage of a spectroscopic prior. The method enables the full propagation of redshift uncertainties into cosmological analyses, and uses all the information at hand to reduce those uncertainties and associated potential biases.
An Exploratory Study of Speech-Language Pathologists Using the Echo Show™ to Deliver Visual Supports

With the burgeoning array of voice-activated, intelligent personal assistants (IPA), repurposing these products for individuals with autism spectrum disorder (ASD) has become increasingly possible. This study aims to determine the feasibility of speech-language pathologists (SLP) delivering hands-free, just-in-time (JIT) visual content via the Echo Show™, a voice-activated IPA with a 7-in. touchscreen that displays graphic content (e.g., photographs, videos, text). The following questions were explored: (1) Can SLPs use a carrier phrase consistently to retrieve visual content on the Echo Show™?, (2) Is the Echo Show™ able to accurately retrieve personalized visual content?, and (3) Do SLPs respond positively to using the Echo Show™ as a potential clinical tool?. Outcomes provide preliminary evidence for the feasibility of SLPs using the Echo Show™ as a potential clinical tool to retrieve personalized visual content. Results will be discussed in terms of clinical implications and use of the Echo Show™ with individuals with ASD.
Parathyroid hormone(1–34) and its analogs differentially modulate osteoblastic Rankl expression via PKA/SIK2/SIK3 and PP1/PP2A–CRTC3 signaling

Osteoporosis can result from the loss of sex hormones and/or aging. Abaloparatide (ABL), an analog of parathyroid hormone–related protein (PTHrP(1–36)), is the second osteoanabolic therapy approved by the United States Food and Drug Administration after teriparatide (PTH(1–34)). All three peptides bind PTH/PTHrP receptor type 1 (PTHR1), but the effects of PTHrP(1–36) or ABL in the osteoblast remain unclear. We show that, in primary calvarial osteoblasts, PTH(1–34) promotes a more robust cAMP response than PTHrP(1–36) and ABL and causes a greater activation of protein kinase A (PKA) and cAMP response element–binding protein (CREB). All three peptides similarly inhibited sclerostin (Sost). Interestingly, the three peptides differentially modulated two other PKA target genes, c-Fos and receptor activator of NF-κB ligand (Rankl), and the latter both in vitro and in vivo. Knockdown of salt-inducible kinases (SIKs) 2 and 3 and CREB-regulated transcription coactivator 3 (CRTC3), indicated that all three are part of the pathway that regulates osteoblastic Rankl expression. We also show that the peptides differentially regulate the nuclear localization of CRTC2 and CRTC3, and that this correlates with PKA activation. Moreover, inhibition of protein phosphatases 1 and 2A (PP1/PP2A) activity revealed that they play a major role in both PTH-induced Rankl expression and the effects of PTH(1–34) on CRTC3 localization. In summary, in the osteoblast, the effects of PTH(1–34), PTHrP(1–36), and ABL on Rankl are mediated by differential stimulation of cAMP/PKA signaling and by their downstream effects on SIK2 and -3, PP1/PP2A, and CRTC3.
Complementary parametric probit regression and nonparametric classification tree modeling approaches to analyze factors affecting severity of work zone weather-related crashes

Identifying risk factors for road traffic injuries can be considered one of the main priorities of transportation agencies. More than 12,000 fatal work zone crashes were reported between 2000 and 2013. Despite recent efforts to improve work zone safety, the frequency and severity of work zone crashes are still a big concern for transportation agencies. Although many studies have been conducted on different work zone safety-related issues, there is a lack of studies that investigate the effect of adverse weather conditions on work zone crash severity. This paper utilizes probit–classification tree, a relatively recent and promising combination of machine learning technique and conventional parametric model, to identify factors affecting work zone crash severity in adverse weather conditions using 8 years of work zone weather-related crashes (2006–2013) in Washington State. The key strength of this technique lies in its capability to alleviate the shortcomings of both parametric and nonparametric models. The results showed that both presence of traffic control device and lighting conditions are significant interacting variables in the developed complementary crash severity model for work zone weather-related crashes. Therefore, transportation agencies and contractors need to invest more in lighting equipment and better traffic control strategies at work zones, specifically during adverse weather conditions.
Control of Whispering Gallery Modes and PT-Symmetry Breaking in Colloidal Quantum Dot Microdisk Lasers with Engineered Notches

Whispering gallery mode resonators have been demonstrated to be a great way to achieve superior optical cavities with high quality factor and small mode volume. However, due to the high sensitivity of these modes to the properties of the resonator boundary, they are susceptible to parasitic splitting of clockwise and counterclockwise modes. In this work, we investigate the effect of implantation of an engineered notch into the boundary of a circular microdisk resonator fabricated from colloidal quantum dots, which are particularly sensitive to boundary defects. We observed a strong reduction of parasitic mode splitting with introduction of a large engineered notch, as well as enhanced directionality of laser emission. We further investigate the performance of these resonators in evanescently coupled pairs, where the modal interaction allows modulation of laser behavior through variation of the gain and loss induced by the optical pump. We show that two distinct cases of modal interaction can be achieved by adjusting the size of the engineered notch, providing a bridge between intra- and interdisk modal interactions for laser spectral control.
The synthesis, characterization, and X-ray crystal structure of trans-bis(1,3-diamino-2-propanolato-N, N', O)-cobalt(III) perchlorate trihydrate

The crystal structure of [Co(C3H9N2O)2]ClO4⋅3H2O was established by single-crystal X-ray diffraction techniques. The compound crystallized in the monoclinic space group P21 with unit cell dimensions a = 6.715(2) A, b = 12.097(3) A, c = 9.904(3) A, β = 100.80(3)○, and z = 2. The final R value for 1359 reflections was 0.039. The 1,3-diamino-2-propanolato ligands are tridentately coordinated to cobalt atoms that have slightly distorted octahedral coordination. The five-membered chelate rings exhibit conformations between pure twist and pure envelope, while the six-membered ring adopts a boat confirmation.
The complete mitogenome of the invasive Japanese mud snail Batillaria attramentaria (Gastropoda: Batillariidae) from Elkhorn Slough, California, USA.

Genomic analysis of the invasive marine snail Batillaria attramentaria from Elkhorn Slough, Moss Landing, California, USA using 150 bp paired-end Illumina sequences resulted in the assembly of its ...
Data analytics for network intrusion detection

A network intrusion can be any unauthorized activity on a network and network intrusion detection is a significant topic in cybersecurity. Data analytics is conducted on the database ‘spambase’ as ...
The role of activation of IL-6/STAT3 signaling in Th17/Tr imbalance of Kawasaki disease

Objective To investigate the role of IL-6/STAT3 signaling in Th17/Tr imbalance of Kawasaki disease(KD). Methods Forty-eight children with KD and eighteen age-matched healthy children were consented to participate in this study. Protein concentration of IL-6 in plasma was measured by ELISA. Transcriptional levels of IL-17A, IL-17F, RORγt, Foxp3, SOCS1 and SOCS3 were assessed by real-time PCR. The proportion of CD4+CD25+Foxp3+ regulatory T(Tr) cells and mean fluorescence intensity(MFI) for phosphorylated-STAT3(pSTAT3) protein in CD4+ T cells was analyzed by flow cytometry. A quantitative methylation specific PCR based on SYBR Green was used to evaluate methylation status of CpG islands in SOCS1 exon2, three potential bind sites for STAT3 in 5'-untraslated region(5'-UTR) of SOCS3 in CD4+ T cells. Results (1)Compared with healthy volunteers, plasma IL-6 concentration and MFI for pSTAT3 in CD4+ T cells were elevated significantly during acute phase of KD[IL-6:(54.02±20.58) pg/ml vs (8.72±2.06) pg/ml, P 0.05). ConclusionAberrant activation of IL-6/STAT3 signaling caused by hypomethylation of SOCS1 and SOCS3 might be one contributing factor to unbalance of Th17/Tr in KD. Key words: SOCS1; SOCS3; Mucocutaneous lymph node syndrome; Th17; Regulatory T cells
Is It Just Water Under the Bridge? An Eight-Day-Old With Late-Onset Group B Streptococcal Infection After Water Birth.

Group B Streptococcus (Streptococcus agalactiae or GBS) infections are known as a leading cause of morbidity and mortality in the neonatal population. The role of water birth in colonizing and transmitting GBS between mother and infant is unclear. We present a case of an exclusively breastfed full-term infant, born via water birth, to a GBS-negative woman who developed GBS mastitis. The infant presented with severe, late-onset GBS meningitis/septic shock and subsequently developed fatal necrotizing enterocolitis. Literature regarding the potential role of water birth in GBS transmission is reviewed.
Genetic reduction of cilium length by targeting intraflagellar transport 88 protein impedes kidney and liver cyst formation in mouse models of autosomal polycystic kidney disease

Polycystin-1 (PC1) and -2 (PC2), products of the PKD1 and PKD2 genes, are mutated in autosomal dominant polycystic kidney disease (ADPKD). They localize to the primary cilia; however, their ciliary function is in dispute. Loss of either the primary cilia or PC1 or PC2 causes cyst formation. However, loss of both cilia and PC1 or PC2 inhibits cyst growth via an unknown pathway. To help define a pathway, we studied cilium length in human and mouse kidneys. We found cilia are elongated in kidneys from patients with ADPKD and from both Pkd1 and Pkd2 knockout mice. Cilia elongate following polycystin inactivation. The role of intraflagellar transport proteins in Pkd1-deficient mice is also unknown. We found that inactivation of Ift88 (a gene expressing a core component of intraflagellar transport) in Pkd1 knockout mice, as well as in a new Pkd2 knockout mouse, shortened the elongated cilia, impeded kidney and liver cystogenesis, and reduced cell proliferation. Multi-stage in vivo analysis of signaling pathways revealed β-catenin activation as a prominent, early, and sustained event in disease onset and progression in Pkd2 single knockout but not in Pkd2.Ift88 double knockout mouse kidneys. Additionally, AMPK, mTOR and ERK pathways were altered in Pkd2 single knockout mice but only AMPK and mTOR pathway alteration were rescued in Pkd2.Ift88 double knockout mice. Thus, our findings advocate an essential role of polycystins in the structure and function of the primary cilia and implicate β-catenin as a key inducer of cystogenesis downstream of the primary cilia. Our data suggest that modulating cilium length and/or its associated signaling events may offer novel therapeutic approaches for ADPKD.
Modeling the dynamic kinetics of microbial disinfection with dissipating chemical agents—a theoretical investigation

The most notable microbial survival models of disinfection kinetics are the original and modified versions of the static Chick-Watson-Hom’s (CWH) initially developed for water chlorination. They can all be viewed as special cases of the Weibull survival model, where the observed static curve is the cumulative form (CDF) of the times at which the individual targeted microbes succumb to the treatment. The CWH model time’s exponent is the distribution’s shape factor, and its concentration-dependent rate parameter represents the distribution’s scale factor’s reciprocal. Theoretically, the concentration- dependence of the Weibull model’s rate parameter need not to be always in a form of a power-law relationship as the CWH model requires, and two possible alternatives are presented. Apart from being chemically reactive, most chemical disinfectants are also volatile, and their effective concentration rarely remains constant. However, the published dynamic versions of the original CWH model are mathematically incongruent with their static versions. The issue is nonexistent in the dynamic version of the Weibull or other distribution-based models, provided that the momentary inactivation rate is expressed as the static rate at the momentary concentration, at the time that corresponds to the momentary survival ratio. The resulting model is an ordinary differential equation (ODE) whose numerical solution can describe survival curves under realistic regular and irregular disinfectant dissipation patterns, as well as during the disinfectant dispersion and/or its replenishment. • The Chick-Watson-Home models are treated as special cases of the Weibull distribution. • Dynamic microbial survival curve described as ordinary differential equation solution. • Survival rate models of disinfectant dissipation and replenishment patterns presented.
Use of features and geometry in leopard geckos (Eublepharis macularius)

All animals must move efficiently throughout their world. However, the mechanisms through which they accomplish this potentially vary among species. Previous work exploring the use of feature information and geometric information in movement through space has indicated that geometric information is commonly used and that some species sometimes also use feature information. Here, I investigated if a cold-blooded species, leopard geckos (Eublepharis macularius), would use geometric and/or feature information. In training, geckos learned to move to a correct corner within the box with a distinctive feature. In test when only geometric information was available, geckos chose either their assigned corner or its geometric opposite. In another test when feature information conflicted with geometric information, geckos did not use feature information and instead made choices consistent with using geometric information. This suggests geckos used geometric information preferentially to feature information in this experiment after both had been available throughout training when they were placed in conflict.
Wound care quality of life in aging patients undergoing electrodessication and curettage on the back.

Patient satisfaction is an important consideration when determining the optimal treatment for non-melanoma skin cancer (NMSC). One critical aspect of patient satisfaction is post-procedural wound care quality of life (QOL), especially as the elderly population grows. This study aimed to evaluate post-procedural wound care QOL in elderly patients undergoing electrodessication and curettage (ED&C) for NMSC in difficult-to-reach areas, namely the posterior shoulder and back. To do so, patient demographics, functionality, co-morbidities, and post-procedural wound care QOL were assessed in twenty elderly patients (age > 65) who underwent ED&C for NMSC at a single academic dermatologic surgery clinic. Independent t-tests were used to evaluate how QOL related to patient age, gender, living situation, relationship status, co-morbidities, and functionality. Patients who lived alone had better-wound care QOL compared to patients who did not live alone (p = 0.04). Patients reported concerns about knocking the wound and did not feel they could care for the wound independently. Patients who were married, female, or had a lower comorbidity score reported poorer QOL, although this finding was not statistically significant. This study indicates that patients’ QOL can be negatively affected by post-procedural wounds located in difficult-to-reach areas. As dermatologists strive to improve patient satisfaction, wound care quality of life should be considered when choosing treatment for NMSC.
PSELLOS’ HAGIOGRAPHICAL WRITINGS: RESOURCES AND NEW DIRECTIONS

Resources available for Byzantine scholarship in general and for studying Psellos in particular have improved greatly in recent years. Electronic databases assist editors of texts in isolating an author’s stylistic habits and in identifying parallel and source texts, while increasingly sensitive search engines provide wide access to scholarly articles, online manuscript catalogues, online publications of texts and translations and great potential for further expansion. Teubner has published Psellos’ extensive writings in genre-defined volumes such as poetry, philosophy, forensic orations and hagiographic orations that represent modern categories of literature but do not capture Byzantine conceptualizations. Two examples illustrate this observation. (1) Although the oration on the Miracle at Blachernae is among Psellos’ hagiographic writings, it contains a brief ecphrasis of a “living icon” prominent in art-historical discussions; however, the oration chiefly focuses upon the Byzantine court system and Psellos’ suggestion for designating a miracle to resolve a vexed legal case. (2) Psellos’ Encomion on Symeon Metaphrastes resembles a saint’s vita and his hymn/canon for Metaphrastes represents a step towards honoring a “new” Byzantine saint. This process continued for 400 years. The 14th-century Hesychast movement used Metaphrastes’ writings to validate their own views and expedited his inclusion in the Synaxarion of Constantinople in the 15th Century.
The methodologies of the marketing literature: mechanics, uses and craft

Of the three scholastic modes with which to develop ideas and create knowledge in research: logic, empirics, and the literature, the latter is perhaps one of the least understood and studied. This paper is a first-of-its-kind delve into what the literature is, how it is used, and its impact as a foundation for theory and conceptual work in the discipline of marketing. We create a novel approach that provides a framework to understand the way literature functions in the research process and expose the hidden mechanics of how it creates and ties together various forms of meaning through what we call, citation-based reasoning. It is through this lens that we conclude with insights for how a deeper understanding of the literature can stoke continued impact in the marketing discipline, especially for theory building and conceptual development.
Filopodia and Lamellipodia

Filopodia and lamellipodia are dynamic membrane protrusions of the cell edge. Their activity is largely responsible for the forward progression of the anterior edge of migrating cells. Pushing force driving protrusion of lamellipodia and filopodia is generated by coordinated polymerization of a cohort of actin filaments, which are organized into branched (dendritic) networks in lamellipodia and parallel bundles in filopodia. Molecular machineries controlling actin polymerization within lamellipodia and filopodia comprise distinct, but overlapping, sets of accessory proteins.
Context-Sensitive Linking: It's a Small World After All

Abstract Linking services that provide seamless access to a library's e-journal collections are becoming increasingly prominent. This article outlines some of the hurdles to seamless linking and discusses the technologies that make linking services possible. These include the Digital Object Identifier, the CrossRef initiative, the development of emerging standards like the OpenURL, resolution servers, and an examination of how these are incorporated into a linking service. The authors interviewed representatives from four companies providing linking services—Ex Libris, Sirsi, Endeavor, and Openly Informatics—and describes features of their systems. Serials Review 2002; 28:267–282.
Epidemiology and Culture: Anthropological Contributions to the Study of Cholera

Those with power were expected to take action against cholera. Those without power were the likely victims. Each had a choice of action, quarantine, cleansing, medical provision, prayer or just doing nothing on the one hand, and flight, anger, alarm, obedience to regulations, or just doing nothing on the other. Values emerged in choices between life and property, between work and safety, between charitable action and government agencies. (Morris 1976:18–19, on the 1832 cholera epidemic in Britain) Outbreak investigations are a classic method in epidemiology; they have determined the causes of new epidemics such as Legionnaires' disease, Hanta virus, Ebola virus, SARS, and E. coli O157:H7. An outbreak investigation is designed primarily to identify the sources of unusual diseases or unusual numbers of cases of disease, as well as to prevent additional cases (Reingold 1998). The steps in an epidemiological outbreak investigation include finding cases, verifying diagnoses, and comparing rates with background expectations; interviewing both cases and controls about onset and exposure; establishing causes; and developing measures of control. Disease outbreaks are almost always newsworthy and a topic of great public concern. The public reads many sensational tales of disease and heroism, real and imagined, with titles like The Coming Plague, The Hot Zone, Outbreak, The Demon in the Freezer, The Andromeda Strain , and Plague Time . But there are other, somewhat less thrilling, stories to be told about new pathogens.
On the Necessity of Recalibrating Heavy Flavor Decays and its Impact on Apparent Puzzles in High Energy Physics

It is demonstrated that charm is systematically undercounted in various experiments. Via a process of elimination, $B(D^0 \rightarrow K^- \pi^+ )$ is identified as the culprit. It calibrates essentially all charmed meson production and decay properties, and thus is central to the physics of heavy flavors. We predict it to decrease significantly below currently accepted values. We suggest several novel methods for precise measurements of $B(D^0 \rightarrow K^- \pi^+ )$. The $B(\Lambda_c \rightarrow pK^-\pi^+)$, on the other hand, calibrates heavy-flavored baryons. Its world average relies heavily on a model of baryon production in $B$ decays, which would be invalidated if $\overline B\rightarrow D^{(*)} \stackrel{(-)}{N} X$ processes were found to be significant. A Dalitz-plot analysis explains naturally the soft inclusive $\Lambda_c$ momentum spectrum in $\overline B$ decays, and predicts sizable $\overline B\rightarrow D^{(*)}\stackrel{(-)}{N} X$ processes. Consistently carrying through these modifications to charmed meson and baryon yields has the potential to resolve the heavy-flavor puzzles at $Z^0$-factories [$R_c,\; R_b$], the number of charm per $B$-decay puzzle, and the semi-leptonic $B$ decay puzzles. We emphasize that state of the art theoretical calculations are consistent with precise experimental measurements regarding $B(\overline B\rightarrow X\ell\bar\nu )$. Recent CLEO measurements are interpreted as newly available cross-checks that any inclusive theoretical investigation must satisfy. Another topic of this report concerns the $b\rightarrow c + \overline D^{(*)}\overline K$ transitions, which were predicted to be sizable and subsequently confirmed by CLEO. This report discusses the underlying dynamics of those processes and quantifies the necessary modifications in existing
The tragic vision of politics: Running red lights and ruling the world

Ancient Hubris breeds, again and again, Another Hubris, young and stout. Aeschylus I now turn to contemporary international relations and social science, and exploit my analysis of classical realism to offer a critique of both. I begin with post-Cold War American policy, and examine some of the striking similarities – and important differences – between the United States and Athens. Like mid-fifth-century Athens, Washington gives evidence of breaking free from the traditional constraints which served its broader interests so well in the past. For the United States, these constraints arise from international law, institutional obligations, norms of consultation and policy by consensus among close allies and more general norms associated with the country's frequently proclaimed commitment to a democratic and peaceful world order. For classical realists, this is well-trodden path, down which ancient tyrants, Xerxes' Persia, Periclean Athens, numerous tragic heroes, and many subsequent empires have trod. Success and power breed hubris and now raise the disturbing possibility of America becoming a tragedy. Current realist theories are blind to this possibility because they are focused on power and external threats. In addition, they tend to equate material capabilities with power and power with influence, ignoring the extent to which the latter is a psychological relationship. Classical realists recognize that the most efficient way to wield influence is through consent, not coercion, and that consent is greatly facilitated by hegemonia and convincing others of the benefits of following one's lead.
Making Sense of Ambiguity through Dialogue and Collaborative Action

This paper outlines the importance of ambiguity in organizations that manage hazardous operations in a rapidly changing environment. Three kinds of ambiguity are described: fundamental ambiguity in categories and labels for understanding what is happening; causal ambiguity for understanding cause–effect relationships that enable explanation, prediction, and intervention; and role ambiguity of agreeing on responsibilities. Examples of successful and unsuccessful ways that organizations deal with ambiguity are drawn from several industries. Although the most typical response is to avoid ambiguity or to seek a false clarity from confident leaders, more successful strategies engage diverse participants from inside and outside the organization to provide multiple perspectives and innovative suggestions that contribute to learning-by-doing.
Accuray CyberKnife® image-guided radiosurgical system

Radiosurgery is the application of radiation therapy in an extremely precise manner. These techniques apply large bioequivalent doses of radiation to a small area in order to destroy tumor cells, while sparing surrounding normal tissues. Radiosurgery has been available for intracranial abnormalities since the 1950s but it has only recently become available to treat tumors outside of the brain and skull base. This article outlines the authors experience with CyberKnife® in the treatment of spinal and spine-associated abnormalities.
Role of feedback inhibition in stabilizing the classical operon

Abstract The Goodwin equations for a repressible operon (Goodwin, 1965) are modified (1) to describe a time lag between genetic regulation and appearance of functional enzyme, (2) to describe consumption of endproduct in protein synthesis, and (3) to describe feedback inhibition of enzyme activity. The stability of the modified equations is determined by a method outlined in the appendix which treats a class of negative feedback systems with time delays. With parameters estimated from experimental data on the tryptophan operon of Escherichia coli, we conclude that the operon becomes unstable as normal feedback inhibition is lost. Numerical solution of the modified equations shows that an example with a partial loss of feedback inhibition can have a period of oscillation less than the cell generation time, and the numerical solutions are shown to be in qualitative agreement with experiments showing oscillations in tryptophan operon expression.
The Combination of Energy-Dependent Internal Adaptation Mechanisms and External Factors Enables Listeria monocytogenes to Express a Strong Starvation Survival Response During Multiple-Nutrient Starvation

Abstract The goal of this study was to characterize the starvation survival response (SSR) of a wild-type Listeria monocytogenes 10403S and an isogenic ΔsigB mutant strain during multiple-nutrient starvation conditions over 28 days. This study examined the effects of inhibitors of protein synthesis, the proton motive force, substrate level phosphorylation, and oxidative phosphorylation on the SSR of L. monocytogenes 10403S and a ΔsigB mutant during multiple-nutrient starvation. The effects of starvation buffer changes on viability were also examined. During multiple-nutrient starvation, both strains expressed a strong SSR, suggesting that L. monocytogenes possesses SigB-independent mechanism(s) for survival during multiple-nutrient starvation. Neither strain was able to express an SSR following starvation buffer changes, indicating that the nutrients/factors present in the starvation buffer could be a source of energy for cell maintenance and survival. Neither the wild-type nor the ΔsigB mutant strain was...
Further characterization of sleep-active neuronal nitric oxide synthase neurons in the mouse brain.

We recently demonstrated that Fos is induced in a subpopulation of cortical neuronal nitric oxide synthase (nNOS)-immunoreactive neurons in three rodent species both during spontaneous sleep (SS) and recovery sleep (RS) after a period of sleep deprivation (SD); the proportion of cortical Fos+/nNOS neurons was significantly correlated with non-REM (NREM) sleep delta energy. The present study was undertaken to evaluate the specificity of this state-dependent activation of cortical nNOS cells. The percentage of nNOS neurons that expressed Fos during SD and RS was determined in nine subcortical brain regions and the cortex of the mouse brain; a significantly greater proportion of Fos+/nNOS neurons was observed during RS only in the cortex and in none of the nine subcortical regions. The proportion of calretinin-, calbindin- and parvalbumin-immunoreactive cortical interneurons that expressed Fos during SD and RS was also determined. In contrast to cortical nNOS neurons, a higher percentage of Fos+/calbindin neurons was found during SD than RS; there were no differences in the proportions of Fos-expressing parvalbumin or calretinin neurons between these conditions. Since the nNOS and calretinin cortical interneuron populations overlap extensively in the mouse brain, triple-labeling with these two phenotypic markers and Fos was undertaken in mice from the RS group to determine which combination of markers could best identify the rare “sleep-active” cortical interneuron population. The proportions of both Fos+/nNOS neurons and Fos+/nNOS/calretinin neurons far exceeded the proportion of Fos+/calretinin neurons during RS, but the proportions of these two cell types were not significantly different during RS. Thus, functional activation of nNOS neurons during sleep appears to be restricted to the cerebral cortex and cortical nNOS cells and nNOS/calretinin cells collectively define a cortical interneuron population that is activated during sleep.
Effects of interactive voice response self-monitoring on natural resolution of drinking problems: utilization and behavioral economic factors.

Objective:Most problem drinkers do not seek help, and many recover on their own. A randomized controlled trial evaluated whether supportive interactive voice response (IVR) self-monitoring facilitated such “natural” resolutions. Based on behavioral economics, effects on drinking outcomes were hypothesized to vary with drinkers’ baseline “time horizons,” reflecting preferences among commodities of different value available over different delays and with their IVR utilization.Method:Recently resolved untreated problem drinkers were randomized to a 24-week IVR self-monitoring program (n = 87) or an assessment-only control condition (n = 98). Baseline interviews assessed outcome predictors including behavioral economic measures of reward preferences (delay discounting, pre-resolution monetary allocation to alcohol vs. savings). Six-month outcomes were categorized as resolved abstinent, resolved nonabstinent, unresolved, or missing. Complier average causal effect (CACE) models examined IVR self-monitoring effe...
Dietary baked milk accelerates the resolution of cow’s milk allergy in children

Background The majority (approximately 75%) of children with cow's milk allergy tolerate extensively heated (baked) milk products. Long-term effects of inclusion of dietary baked milk have not been reported. Objective We report on the outcomes of children who incorporated baked milk products into their diets. Methods Children evaluated for tolerance to baked milk (muffin) underwent sequential food challenges to baked cheese (pizza) followed by unheated milk. Immunologic parameters were measured at challenge visits. The comparison group was matched to active subjects (by using age, sex, and baseline milk-specific IgE levels) to evaluate the natural history of development of tolerance. Results Over a median of 37 months (range, 8-75 months), 88 children underwent challenges at varying intervals (range, 6-54 months). Among 65 subjects initially tolerant to baked milk, 39 (60%) now tolerate unheated milk, 18 (28%) tolerate baked milk/baked cheese, and 8 (12%) chose to avoid milk strictly. Among the baked milk–reactive subgroup (n = 23), 2 (9%) tolerate unheated milk, and 3 (13%) tolerate baked milk/baked cheese, whereas the majority (78%) avoid milk strictly. Subjects who were initially tolerant to baked milk were 28 times more likely to become unheated milk tolerant compared with baked milk–reactive subjects ( P P 4 levels in the baked milk–tolerant group increased significantly ( P Conclusions Tolerance of baked milk is a marker of transient IgE-mediated cow's milk allergy, whereas reactivity to baked milk portends a more persistent phenotype. The addition of baked milk to the diet of children tolerating such foods appears to accelerate the development of unheated milk tolerance compared with strict avoidance.
Ex vivo live imaging of single cell divisions in mouse neuroepithelium.

We developed a system that integrates live imaging of fluorescent markers and culturing slices of embryonic mouse neuroepithelium. We took advantage of existing mouse lines for genetic cell lineage tracing: a tamoxifen-inducible Cre line and a Cre reporter line expressing dsRed upon Cre-mediated recombination. By using a relatively low level of tamoxifen, we were able to induce recombination in a small number of cells, permitting us to follow individual cell divisions. Additionally, we observed the transcriptional response to Sonic Hedgehog (Shh) signaling using an Olig2-eGFP transgenic line 1-3 and we monitored formation of cilia by infecting the cultured slice with virus expressing the cilia marker, Sstr3-GFP 4. In order to image the neuroepithelium, we harvested embryos at E8.5, isolated the neural tube, mounted the neural slice in proper culturing conditions into the imaging chamber and performed time-lapse confocal imaging. Our ex vivo live imaging method enables us to trace single cell divisions to assess the relative timing of primary cilia formation and Shh response in a physiologically relevant manner. This method can be easily adapted using distinct fluorescent markers and provides the field the tools with which to monitor cell behavior in situ and in real time.
Hypotheses Of ‘No Interaction’ In Multi-dimensional Contingency Tables

The statistical analysis of multi-dimensional contingency tables is discussed from the point of view of the associated underlying model. Different formulations of hypotheses of ‘no interaction’ are considered. The corresponding test statistics are based on a general and computationally simple criterion originally due to Wald [1943]. The suggested methods are illustrated with several numerical examples.
Gene-expression profiling in Parkinson's disease: discovery of valid biomarkers, molecular targets and biochemical pathways

In the past decade, several gene mutations have been described in families with a Mendelian inheritance pattern of Parkinson’s disease (PD), using linkage mapping. These cases represent only a small percentage (<5%) of the patients who develop PD. The current understanding of the mechanisms that underlie aspects of the neurodegenerative process of PD is based mainly on research of functional pathways related to these genes. However, even with knowledge of these pathways, the number of relevant genes may still be very large. In the post-genomic era, seven high-throughput gene array studies have attempted to identify candidate genes and biochemical pathways in PD. In this review, results from these studies and different factors influencing optimal target and biomarker discovery with gene-expression profiling are discussed.
Eligibility policies for the state AIDS drug assistance programs.

Drug treatments for HIV infection and related opportunistic infections have had dramatic impacts on the morbidity and mortality associated with HIV disease. HIV drug therapies are essential to the survival and to improved quality of life for individuals with HIV. However, not all people with HIV disease are receiving these medications. The state AIDS drug assistance programs (ADAPs) can provide access to drug therapies for many people with HIV disease who lack adequate drug coverage. This research presents the results of a national survey that identified eligibility-related policies implemented by .48 state ADAPs during 1998 and 1999. The survey assessed the number of people receiving ADAP coverage, the percentage of ADAP beneficiaries who are women, financial and medical eligibility requirements, characteristics of the application process, any implementation of waiting lists, and any coordination of the ADAPs with other public programs.
Pest-resistance in SiC/BN/SiC composites

Abstract State-of-the-art non-oxide ceramic-matrix composites (consisting of SiC fibers, cvi -BN interphase coating, and mi -SiC matrix) exhibit excellent mechanical properties at room temperature, as well as above ∼1000 °C (where oxidation easily seals flaws with silica); but they are prone to pest degradation at intermediate temperatures in an oxidizing environment, and especially so in the fast, moist flame of a jet engine. Two modes of pest may be distinguished in these composites. The more severe type of pest is promoted by extraneous factors, like a layer of elemental carbon underlying the BN interphase and undermining its intrinsic oxidation resistance. It is shown that, when care is taken to exclude such a carbon layer, SiC/BN/SiC composite can easily survive a 100-h exposure in a burner rig without noticeable loss of strength or strain to fracture.