cssi/SciSciGPT-SciSciNet huggingface dataset:
The role of E-liquid vegetable glycerin and exhaled aerosol on cue reactivity to tank-based electronic nicotine delivery systems (ENDS)

Electronic nicotine delivery systems (ENDS or e-cigarettes) share salient features of combustible smoking, such as inhalation and exhalation behaviors, and evidence indicates that first- and second-generation ENDS generalize as smoking cues. The present study examined whether newer, tank-based third-generation ENDS (“mods”) also evoke smoking urges, and whether enhancing the visibility of exhaled aerosol clouds—by increasing the e-liquid vegetable glycerin (VG) content—strengthens the cue salience of ENDS. The objective was to assess the role of exhaled aerosol clouds on ENDS cue potency using a standardized laboratory paradigm designed to mimic real-world exposures. Using a mixed design, young adult smokers (n = 50; mean age 26.5 years; ≥ 5 cigarettes/day) observed a study confederate drinking bottled water (control cue) and vaping an ENDS mod containing e-liquid with either high (73%) or low (0%) VG. Participants completed the Brief Questionnaire on Smoking Urges (BQSU) and visual analog scales (VAS) assessing cigarette and e-cigarette desire pre- and post-cue exposure. Increasing the e-liquid content of VG enhanced the size and visibility of the exhaled aerosol clouds and evoked a greater increase in smoking desire and a more sustained increase in e-cigarette desire relative to the low VG cue. Both cues elicited increases in smoking urges. These results remained after controlling for sex, prior ENDS experience, recent smoking behavior, and menthol preference. Observation of tank-based ENDS use generalizes as a smoking cue and its cue salience is strengthened by increasing the e-liquid content of VG to enhance the visibility of the exhaled aerosol cloud.
Quantitative Reasoning and Its Role in Interdisciplinarity

The Real Science, Technology, Engineering Mathematics (STEM) Project was conducted in middle schools and high schools in Georgia, USA. The project supported the development of interdisciplinary STEM modules and courses in over 20 schools. A project focus was development of five 21st century STEM reasoning abilities. In this chapter, I provide classroom activities from the Real STEM project that exemplify each form of reasoning: complex systems; model-based; computational; engineering design-based; and quantitative reasoning. Quantitative reasoning plays a critical role in authentic real-world interdisciplinary STEM problems, providing the tools to construct data informed arguments specific to the problem context, which can be debated, verified or refuted, modelled mathematically and tested against reality. Yet quantitative reasoning is often misrepresented, underdeveloped, and ignored in STEM classrooms. The chapter finishes with a discussion of the impact of Real STEM.
Assessment of Automated Identification of Phases in Videos of Cataract Surgery Using Machine Learning and Deep Learning Techniques.

Importance Competence in cataract surgery is a public health necessity, and videos of cataract surgery are routinely available to educators and trainees but currently are of limited use in training. Machine learning and deep learning techniques can yield tools that efficiently segment videos of cataract surgery into constituent phases for subsequent automated skill assessment and feedback. Objective To evaluate machine learning and deep learning algorithms for automated phase classification of manually presegmented phases in videos of cataract surgery. Design, Setting, and Participants This was a cross-sectional study using a data set of videos from a convenience sample of 100 cataract procedures performed by faculty and trainee surgeons in an ophthalmology residency program from July 2011 to December 2017. Demographic characteristics for surgeons and patients were not captured. Ten standard labels in the procedure and 14 instruments used during surgery were manually annotated, which served as the ground truth. Exposures Five algorithms with different input data: (1) a support vector machine input with cross-sectional instrument label data; (2) a recurrent neural network (RNN) input with a time series of instrument labels; (3) a convolutional neural network (CNN) input with cross-sectional image data; (4) a CNN-RNN input with a time series of images; and (5) a CNN-RNN input with time series of images and instrument labels. Each algorithm was evaluated with 5-fold cross-validation. Main Outcomes and Measures Accuracy, area under the receiver operating characteristic curve, sensitivity, specificity, and precision. Results Unweighted accuracy for the 5 algorithms ranged between 0.915 and 0.959. Area under the receiver operating characteristic curve for the 5 algorithms ranged between 0.712 and 0.773, with small differences among them. The area under the receiver operating characteristic curve for the image-only CNN-RNN (0.752) was significantly greater than that of the CNN with cross-sectional image data (0.712) (difference, −0.040; 95% CI, −0.049 to −0.033) and the CNN-RNN with images and instrument labels (0.737) (difference, 0.016; 95% CI, 0.014 to 0.018). While specificity was uniformly high for all phases with all 5 algorithms (range, 0.877 to 0.999), sensitivity ranged between 0.005 (95% CI, 0.000 to 0.015) for the support vector machine for wound closure (corneal hydration) and 0.974 (95% CI, 0.957 to 0.991) for the RNN for main incision. Precision ranged between 0.283 and 0.963. Conclusions and Relevance Time series modeling of instrument labels and video images using deep learning techniques may yield potentially useful tools for the automated detection of phases in cataract surgery procedures.
The polarization field in Al-rich AlGaN multiple quantum wells

This paper investigates the quantum confined Stark effect in AlGaN multiple quantum well structures with a high Al content grown on single-crystalline AlN substrates. The quantitative relationship between the quantum well structure parameters, photogenerated carrier density, built-in electric field and ground-level emission is discussed. It is found that the electric field strength increases from 0.5 MV cm−1 to almost 3 MV cm−1 when the Al content in the quantum well barriers is increased from 65% to 100%, which is consistent with the theory of spontaneous and piezoelectric polarization in III-nitrides. In addition, the built-in electric field increases significantly with increasing barrier thickness. Based on these results, the electric field in an Al0.55Ga0.45N single quantum well with AlN cladding is predicted to be around 5 MV cm−1.
Pilot of primary care physician discussion and resource allocation after screening for unintentional injuries and social determinants of health.

Standardized screening tools used by pediatric providers can help determine a child’s injury and social risks. This study determined if an office-based quality improvement program could increase targeted anticipatory guidance and community resource distribution to families. Practices recruited from the Ohio Chapter, American Academy of Pediatrics’ database self-selected to participate in a quality improvement project. Two age-appropriate screening tools, corresponding talking points and local resources for birth–1 year and 1–5 year aged children were developed for unintentional injury and social health determinant topics. After a one-day learning session, practice teams implemented the tools into well-child care visits for children < 5 years of age. Two months of retrospective baseline data was collected for each participating clinician. During the 6-month collaborative, physicians randomly reviewed 5 screening tools monthly for each age category to identify injury and social risk discussions and to determine if resources were provided. Frequencies of counseling and resource distribution were calculated. Participating providers received Maintenance of Certification IV credit. Ten practices (18 providers) participated and 667 tools (n = 313, birth-1 year, n = 354, 1–5 year) were collected. For birth–1 year, the most common risky behaviors were related to unintentional injuries: no CPR training 164(52%), car seat not checked 149(48%) and home furniture not secured 117 (37%). For 1–5 year screens, unintentional injuries were also most common: no CPR training 222(63%), car seat not checked 203(57%) and access to choking hazards 198(56%). Families practiced riskier behaviors for unintentional injuries compared to social risks for both age groups (birth – 1 year, social 189/4801 (4%) vs. unintentional injury questions 999/6260 (16%) and 1–5 years, social 271/5451 (5%) vs unintentional injury questions 1140/6372 (18%). From baseline, discussions increased from 31% to 83% for birth – 1 year and 24% to 86% for 1–5 year families. Resource distribution increased by 63% for birth-1 year and 69% for 1–5 year families by pilot conclusion. Using standardized screening tools in an office setting shows that families often practice unintentional injury risks more than having social concerns. After screening, appropriate resources can be provided to families to encourage behavior change.
Open Data: A Twenty-First-Century Asset for Small and Medium-Sized Enterprises

The purpose of this paper is to better understand how open and shared data impacts the economy. Focusing on small and medium-sized enterprises (SMEs) and start-ups, we consider 354 case studies of companies currently using open data, so that we can better understand how open data can be used and how it can contribute to economic growth, new jobs, greater innovation, and other improvements in our social and economic lives. Grounding our analysis in empirical studies allows us to identify the most important issues confronting any SME considering an open data strategy. It provides lessons and principles that have proven, real-world applicability.
Abstract 2173: Developing a high-throughput, high content screening technology to identify new anticancer drug treatments

The high attrition rate of new chemotherapeutic drugs represents the single most important challenge in anticancer drug development. With only one drug out of 10, 000 test compounds gaining FDA-approval, attrition is often attributed to failure of in vitro drug efficacy to translate to clinical success. The overall drug discovery and development pipeline can be dramatically improved with new, innovative assays of high pharmacological relevance that can shorten the discovery/preclinical phase and ensure rapid translation to clinic. We report the development of a three-dimensional phenotypic drug screening platform based on spheroidsMARY-X. The tight, compact spheroidsMARY-X form spontaneously due to innate molecular determinants with proliferative cells on the outer periphery and a dormant tumor cell core. These features mimic the intratumoral biological complexities of tumor tissue and thus provide a relevant in vitro model for drug discovery with a high degree of predictive value. Significantly, this model allows analysis of drug targeting of dormant tumor cells, the difficult to treat resistant or highly refractory cell population. Drug response can be reliably assessed using brightfield microscopy and can be quantified by measuring spheroid circularity (i.e., dissolution index). Evaluation of soluble factor concentration is performed using molecular rotors through restricted intramolecular rotation upon protein binding with a subsequent quantum yield. Overall, we present a 3-dimensional anticancer assay that provides a rapid, efficient, relevant platform for the evaluation of drug response and allows identification of small molecule hits in both proliferative and more importantly, dormant tumor cells, the major cause of relapse and recurrent metastatic disease. Citation Format: Andrew T. Milcarek, Kevin Daus, Mary L. Alpaugh. Developing a high-throughput, high content screening technology to identify new anticancer drug treatments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2173.
Ultrawideband Flush-Mountable Dual-Polarized Vivaldi Antenna

A dual-polarized, flush-mounted, Vivaldi antenna directly integrated with all-metal cavity is introduced as an alternative to coax-fed quad-ridge (QR) horns. Eigen-mode analysis is used to demonstrate that the entire structure may resonate with degraded impact on its far-field when not properly integrated with the cavity. An approach based on shaping the side walls of the cavity is used to eliminate the occurrence of these resonances. The proposed dual-polarized resonant-free antenna has two orthogonal $2 \times 1$ arrays with two elements in the E-plane and one element in the H-plane and is fed using two 2-way power dividers that can be easily designed to maintain low amplitude and phase imbalances. The antenna is fabricated in a single piece and experimentally shows monotonic gain increase with low cross-polarization over 4:1 bandwidth. Symmetric far-field performance between orthogonal polarizations with gain better than 8 dBi and sidelobe levels lower than −20 dB from 2 to 8 GHz is demonstrated. VSWR < 2, and port to port isolation greater than 35 dB is also measured over the same bandwidth.
Implantation of BIV ICD with Near Zero Contrast Use in Patients with Advanced Renal Insufficiency Using Three Dimensional Electro-anatomical Mapping.

Background Biventricular (BIV) ICD implantations are traditionally performed using contrast and fluoroscopic guidance. Contrast use in patient with advanced renal disease can cause deterioration of renal function and even lead to dialysis. Objective To evaluate the feasibility of utilizing 3 D mapping technique in reducing or eliminating contrast use in patient with advanced renal disease. Methods and Results The study consisted of 30 consecutive adult patients, in which BIV implantation was accomplished in advanced renal disease (stage III and IV GFR 15 to 59) by electroanatomical 3D mapping (EAM).Acute procedural success was 96% and only one patient LV lead implantation was unsuccessful due to unsuitable anatomy.47 % of patients had BIV ICD implantation with zero contrast. Average contrast exposure for the group was 4.3 ml only. Average ratio of contrast use to GFR (glomerular filtration rate) was only 0.1. Improved mean GFR was observed from 42 to 50 post procedure (P value<0.01), and continued to improve to 48 at 3 and 6 month (P value<0.01) and improvement decreased to 45 and 44 beyond 6 month and 1 year (P value NS). There was no single case of contrast induced acute renal insufficiency (CI-ARI) due to minimal use of contrast.69 % of the patients experienced an improvement in their functional class. A decrease in QRS duration was seen from 159 to 136 milliseconds (86% of patients had improved QRS duration); P value = <0.001. The average pre procedure ejection fraction (EF) for the group was 23%. The average EF post procedure for the group was 35%; P values = <0.001 (72% of patient had EF improvement).93% of patient had either EF and/or GFR improvement suggesting substantial clinical benefit from the procedure.There was no minor or major complications. Conclusions Implantation of BiV ICD using EAM with near zero contrast is feasible, safe and effective in patients with moderate to severe renal insufficiency. There is an added renal protection and benefit from procedure in this group of patients.
Strategic Placement of Distributed Generators Against Extreme Events

An extreme event can cause power outages in power grids due to damaged lines and/or substations. Line outages may also result in voltage instabilities which may finally lead to partial or complete blackout in the grid. This paper is concerned about the placement of distributed generators (DG) in order to strengthen the power grid against such extreme events. The proposed approach places a minimum number of distributed generators to secure the system against expected contingencies also ensuring voltage stability of the grid.
Understanding Patient Anxieties in the Social Media Era: Qualitative Analysis and Natural Language Processing of an Online Male Infertility Community.

Background: Couples struggling with infertility are increasingly turning to the internet for infertility-related content and to connect with others. Most of the published data on infertility and the internet only address the experiences of women, with limited studies focusing exclusively on internet discussions on male factor infertility. Objective: The aim of this study was to understand the concerns and experiences of discussants on an online male infertility community and to provide insight into their perceptions of interactions with health care professionals. Methods: Using the large-scale data analytics tool BigQuery, we extracted all posts in the r/MaleInfertility community (877 members) of the social media website and discussion board Reddit from November 2017 to October 2018. We performed a qualitative thematic analysis and quantitative semantic analysis using Language Inquiry and Word Count 2015 of the extracted posts to identify dominant themes and subthemes of discussions. Descriptive statistics and semantic analytic Z-scores were computed. Results: From the analysis of 97 posts, notable themes and subthemes emerged: 70 (72%) posts shared personal experiences, including feeling emasculated or isolated or describing a negative (28/97, 29%), positive (13/97, 13%), or neutral (56/97, 58%) experience with a health care professional; 19% (18/97) of the posts posed questions about personal semen analysis results. On the basis of semantic analysis, posts by men had higher authenticity scores (Z=3.44; PP<.001), suggesting a more tentative or anxious style of writing, compared with posts by women. Conclusions: To our knowledge, this study represents the first evaluation of a social media community focused exclusively on male infertility using mixed methodology. These results suggest a role for physicians on social media to engage with patients and connect them to accurate resources, in addition to opportunities to improve in-office patient education.
Early Post-Operative Atrial Fibrillation after Lung Transplantation

Purpose Atrial fibrillation (AF) is a common complication after lung transplantation that is associated with adverse outcomes. While some evidence-based protocols exist for prophylaxis and treatment of AF after general thoracic surgery, there lacks necessary evidence-based recommendations in the lung transplant population to standardize care delivery. This paucity of literature contributes to limited evidence-based guidelines for treatment and prophylaxis of AF in this specialty population. The purpose of this descriptive study was to identify the evidence-based practices for prophylaxis and treatment of AF at lung transplant centers across the United States and Canada after lung transplantation. Methods A ten-item questionnaire was sent with the use of Qualtrics to lung transplant centers across the United States and Canada over a six-week period via email and list serve distribution. This study was reviewed and exempt by the Social and Behavioral Sciences Institutional Review Board. Results The reported incidence rates of AF varied per institution from less than ten percent to the highest rate at seventy percent. Of the twelve centers that completed the survey, four (26.7%) of the institutions reported the use of a standardized treatment protocol whereas eight (53.5%) did not. Regarding the use of a standardized prophylaxis protocol, three (20%) reported the implementation of specific protocols while; nine (60%) did not. An individualized protocol for post-operative AF was addressed in three (20%) cases. Conclusion This study analyzed current practices for prophylaxis and treatment guidelines for the occurrences of AF, and found similarities to the transplant literature. Despite the implementation of prophylaxis and treatment protocols within various institutions, the reported rates of AF remain constant. Guidelines may decrease incidence, improve early recognition, decrease adverse outcomes, prevent potential complications, and standardize care delivery. Further research is needed to establish standards of practice for AF prevention and treatment in post-operative lung transplant patients.
Land and ethnographic practices—(re)making toward healing

While ‘place-making’ is a productive concept for many scholars, I consider land relations and research through Indigenous (re)making by narrating embodied and experiential ethnographic approaches. ...
Please Help Us (or Don’t): External Interventions and Negotiated Settlements in Civil Conflicts:

How do different types of external intervention affect the likelihood of a negotiated settlement in civil conflicts? Drawing on the negotiation literature, which shows that the nature of the partie...
The role of impulsivity on health behavior related to cardiovascular disease among young adults.

Background: There is a large body of research indicating that trauma increases risk for cardiovascular disease, but mechanisms that explain this relationship are not well understood. One potential explanation may be that trauma has been found to be associated with both impulsivity and dysfunctional health behaviors, which in turn lead to cardiovascular disease. The purpose of this article was to determine the pathway from trauma to impulsivity to health behaviors related to cardiovascular disease. Method: Data from the National Longitudinal Study of Adolescent to Adult Health, a large, longitudinal survey of adolescents starting in Grades 7-12, was analyzed. Structural equation modeling was used to determine pathways from adverse childhood events to 2 types of impulsivity (choice and risk-taking) to health behaviors related to cardiovascular disease. Results: Adverse childhood events is a predictor of both types of impulsivity and health behaviors. Findings have further indicated that both types of impulsivity also lead to more dysfunctional health behaviors related to cardiovascular disease. Conclusions: Impulsivity related to decision-making (tendency to favor smaller, short-term rewards over long-term, longer rewards) and to risk-taking (thrill and novelty seeking) are both affected by traumatic events, and both influence health behaviors. Clinicians should consider the range of strategies offered through behavioral economics to improve health in at-risk populations exposed to trauma. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Semi-Automatically Mining Students’ Common Scratch Programming Behaviors

In this paper, we introduce a semi-automatic approach to enable scalable data collection and analysis of students’ programming processes in Scratch. We describe a logging tool that records students’ interactions with the Scratch environment as they code. We analyze these programming interaction logs using a combination of automated and manual techniques to uncover patterns that provide insights into common programming behaviors among users during the coding process. We demonstrate this semi-automatic logging and mining approach with a case study, in which students performed the same open-ended coding task in two college courses introducing programming (37 Education and Human Development majors taking an Ed Tech course and 44 non-CS majors taking a general introductory CS course). Our findings demonstrate that we can uncover patterns that help identify which constructs students commonly used for a given task, various types of tinkering behavior within a given task, and some indications of students’ levels of understanding of the blocks. This kind of information is a valuable starting point for where and how to direct teaching efforts.
Periorbital Soft Tissue Trauma

Eyelid trauma occurs across a broad spectrum of pathology, ranging from simple periorbital lacerations to severe, vision-threatening injuries requiring expert oculoplastic consultation. Any injury, no matter how benign, is also inherently cosmetically sensitive, further adding to the reconstructive challenge. In this review, we discuss the anatomy of the eyelid and develop an understanding of evaluating for signs of more serious, potentially occult, trauma. A framework is developed for approaching the patient with periorbital trauma to assess for injury and triage necessary treatments. Damage to the lacrimal drainage system, which can be particularly difficult to detect and repair, is specifically emphasized and explored.
A Randomized Algorithm for Sparse Recovery

This paper considers the problem of sparse signal recovery where there is a structure in the signal. Efficient recovery schemes can be designed to leverage the signal structure. Following the model-based compressive sensing framework, we have developed an efficient algorithm for both head and tail approximations for the model-projection problem. The problem is modeled as a constrained graph optimization problem, which is an NP-hard optimization problem. Solving the NP-hard optimization program is then transformed to solving a linear program and finding a randomized algorithm to find an integral solution. The integral solution is optimal-in-expectation. The algorithm is proved to have the same geometric convergence as previous work. The algorithm has been tested on various compressing matrices. The proposed algorithm demonstrated improved recoverability and used fewer number of iterations to recover the signal.
Pediatric cerebral cysts: comparison of early complications following fenestration versus shunting procedures.

Objective: Characterize practice patterns and acute (30-day) surgical complications following fenestration and shunt procedures for the treatment of cerebral cysts in pediatric patients.Methods: This study utilized the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Pediatric database. Patients were identified by International Classification of Disease codes for cerebral cysts and Current Procedural Terminology codes for shunting or fenestration. Demographic data, preoperative comorbidities, and postoperative complications were compared between the two procedures.Results: 741 patients were included in the data analysis, with a majority aged 4 years or younger (55.9%) and a male predominance (62.6%). Fenestration was performed in 590 (79.6%) patients. Primary shunting was performed in 151 (20.4%) patients. Patients who received shunts were more commonly aged 0-4 years and had proportionately worse preoperative health status. No statistically significant differences in postoperative complications were detected. Reoperation rate was 7.9% and 8.6% in the shunt and fenestration groups, respectively. Common reasons for reoperation were shunt revision or replacement and shunt placement after fenestration. Patients requiring shunting after a failed fenestration tended to be younger with higher American Society of Anesthesiologists (ASA) classification.Discussion: Fenestrations are performed more often than shunting. Generally, children who receive shunts are younger than those who undergo fenestration. Acute surgical risk appears to be similar for both operations.
Selective activation of language specific structural representations: Evidence from extended picture-word interference

Abstract How do bilingual speakers represent and use information that guides the assembly of the words into phrases and sentences (i.e., sentence structures) for languages that have different word orders? Cross-language syntactic priming effects provide mixed evidence on whether bilinguals access sentence structures from both languages even when speaking just one. Here, we compared English monolinguals, Korean-immersed Korean-English bilinguals, and English-immersed Korean-English bilinguals while they produced noun phrases (“the lemon below the lobster”), which have different word orders in English and Korean (the Korean translation word order is [lobster][below][lemon]). We examined when speakers plan each noun using an extended picture-word interference paradigm, by measuring articulation times for each word in the phrase with either the distractor word “apple” (which slows the planning of “lemon”) or “crab” (which slows the planning of “lobster”). Results suggest that for phrases that are different in linear word order across languages, bilinguals only access the sentence structure of the one language they are actively speaking at the time, even when switching languages between trials.
Psychiatric Comorbidity Burden in Chronic Migraine and Medication Overuse Headache in Pregnancy (593)

Objective: Identify the diagnosis of anxiety, depression, perceived stress in pregnant patients with headache referred to the tertiary headache clinic at the University of Washington. Background: Typically, women with migraine improve during pregnancy. However, this trend is less certain for patients with chronic migraine. We wanted to identify if women whose migraine headaches worsened during pregnancy were more likely to have psychiatric comorbidity. Design/Methods: All new patients referred to our headache clinic complete a detailed patient intake questionnaire prior to their first visit. Our database has questions regarding current pregnancy, headache characteristics, depression and anxiety symptoms and perceived stress. All patient data are analyzed by headache providers, who collected information about previous diagnoses and treatments, and diagnose headache disorders using the ICHD-3 criteria. Results: Of the patients who were seen at the headache clinic, 38 were pregnant and 37 patients had migraine. Of those, 29 had chronic migraine, and 22 were identified with medication overuse headache. 20 patients (52%) had comorbid anxiety or depression, 17 (44%) had anxiety and 14 (36%) patients had depression, 4 patients had post-traumatic stress disorder and 2 had bipolar disorder. In 31(81%), the patients’ headache had a major impact on their work. Conclusions: Our results show high incidence of psychiatric comorbidities in pregnant women presenting to the headache clinic. Migraine is common in women of reproductive age, and hormonal fluctuations in connection with pregnancy can influence attack frequency. Previous studies, including analyses of patient data at our headache clinic, suggest that psychiatric comorbidities are more common in chronic migraine. These mechanisms may explain the high prevalence of chronic migraine as well as psychiatric comorbidity in this group. These patients warrant a greater degree of attention in headache clinic, as they may have more severe health issues while having limited treatment options due to pregnancy. Disclosure: Dr. Krashin has nothing to disclose. Dr. Cuneo has nothing to disclose. Dr. Schorn has nothing to disclose. Dr. Chan-Goh has nothing to disclose. Dr. Budica has nothing to disclose. Dr. Murinova has nothing to disclose.
Correcting for Hidden Population Structure in Single Marker Association Testing and Estimation

Chapter 2 discussed both relatedness of study participants and hidden population structure in terms of the correlations induced between the number of copies, n iA and n jA , of a diallelic genetic variant carried by two individuals i and j. In Chap. 3 we discussed the requirement for association studies of unrelated subjects that the outcomes of interest, Y i , be independent between study subjects. In this chapter we will expand on this initial discussion (1) to examine the impact of non-independence on the distribution of statistical tests for the influence of alleles (here a and A) on phenotype or disease risk, and (2) how non-independence between individuals’ outcomes can arise as a direct result of correlation among the genotypes of study subjects due to hidden strata or relatedness or due to other factors (e.g., cultural/behavioral) that act as confounders of genetic associations. The chapter introduces several basic approaches for dealing with population structure in single marker association analyses and shows how all these methods deal, at least in part, with the fundamental problem of the analysis of correlated phenotypes. At the heart of these methods is the empirical estimation of a relationship matrix (more precisely a covariance structure matrix) that describes the relative relatedness of individuals. The statistical methods for dealing with covariances in estimation of single marker effects fall into three categories: fixed effects models utilizing adjustment for eigenvectors (“principal components”) of this matrix; random effects methods dealing explicitly with the relationship matrix as a covariance matrix of random effects in extended generalized linear modeling; and retrospective methods, which invert the usual generalized linear modeling procedures so that the conditional distribution of the genetic markers given the phenotypes (rather than the reverse) is used for inference in genetic association studies. Our discussion of all these approaches is unified around the theme of dealing with false-positive associations that are due to unrecognized inflation of the variance of estimators relied upon in traditional regression methods when correlated data are analyzed. Finally the relative performance of the various methods is described in various settings.
Prediction of the Time of Ovulation

Prediction of ovulation was established by correlation of clinical parameters, follicular development by ultrasound, and estradiol, progesterone, and luteinizing hormone (LH) determination in 71 menstrual cycles. Laparoscopic follicular aspiration was accomplished in 41 of those cycles. A 28-hour interval from the ascending limb of the LH seems to be the "ideal time" for retrieval of a preovulatory oocyte. The variability in the amount of LH to which the follicle is exposed during the LH surge seems to indicate that there is a relatively low specific value necessary for ovulation. Ovulation occurs approximately 10 +/- 5 hours from the LH peak. Progesterone occurs in relation to the LH surge and is helpful for the retrospective analysis of the menstrual cycle.
Guanine nucleotide exchange catalyzed by dbl oncogene product

Publisher Summary This chapter describes methods for the expression of Dbl and the Dbl homology (DH) domain in baculovirus expression systems and discusses the in vitro assays to demonstrate that Dbl and its DH domain contain guanine nucleotide exchange factors (GEFs) activity for the Cdc42Hs and Rho GTP-binding proteins. GEFs activate Ras family members of GTP-binding proteins by accelerating their rate of GDP release and, therefore, facilitating their GTP binding in cells. Unlike the case for Ras–GEFs for which the in vivo activities can be examined by the extent of conversion of Ras-bound GDP to GTP by the immunoprecipitation of Ras and thin-layer chromatography separation of the bound nucleotides, the GEF activities for Rho-type GTPases are difficult to determine in this manner because of the fast hydrolysis rates of the members of this family and the presence of abundant Rho–GDP-dissociation inhibitor (GDI), which renders most of the Rho-type proteins cytosolic and blocks the GEF action. Thus, the in vitro reconstituted assay is indispensable for detecting and quantitating the activities of potential Rho family GEF molecules.
Chapter 15 The role of G-protein coupled receptor kinases in the regulation of muscarinic cholinergic receptors

Publisher Summary This chapter focuses exclusively on molecular events underlying homologous desensitization of muscarinic acetylcholine receptors (mAChR) by a unique family of protein kinases that appear to specifically recognize GPRs. Other protein kinases, such as protein kinase C, may also be involved in mAChR desensitization. The term “desensitization”, when applied to the GPRs, actually refers to a collection of events that may be independently regulated, and not necessarily sequential. The hallmarks of desensitization of the GPRs include uncoupling of the receptors from G-proteins and/or loss of high affinity agonist binding. These events occur rapidly and appear to involve phosphorylation of the GPRs by specific and/or generic protein kinases. This phosphorylation induced uncoupling is proposed to play a physiological role in terminating signalling in the sensory receptor systems. The chapter identifies the kinases that phosphorylate the mAChRs in vivo employs a system, whereby it attempts to take apart the system and reconstitutes agonist-dependent phosphorylation and desensitization of the receptors in vitro . For this system, the chapter purifies chick heart or recombinant human m2 mAChRs and reconstitutes the receptors into phospholipid vesicles.
Secure dynamic distributed routing algorithm for ad hoc wireless networks

An ad hoc wireless network permits wireless mobile nodes to communicate without prior infrastructure. Due to the limited range of each wireless node, communication sessions between two nodes are usually established through a number of intermediate nodes. Unfortunately, some of these intermediate nodes might be malicious, forming a threat to the security or confidentiality of exchanged data. While data encryption can protect the content exchanged between nodes, analysis of communication patterns may reveal valuable information about end users and their relationships. Using anonymous paths for communication provides security and privacy against traffic analysis. To establish these anonymous paths, all nodes build a global view of the network by exchanging routing information. In dynamic ad hoc networks, building this global view is not an option. In this paper, we propose and analyze a distributed route construction algorithm for use in the establishment of anonymous routing paths in ad hoc wireless networks.
Hesitation phenomena in the spontaneous speech of normal and articulatory-defective children.

The utterances of 40 children aged five to six and equally distributed as to age, sex, and group — normal or articulatory-defective - were recorded unobtrusively. Samples of each recording were analyzed for eight categories of hesitation phenomena. Retest recordings were made and analyzed for 16 of the subjects to assess temporal reliability of the hesitation phenomena. The results showed that, like adults, the children used ah phenomena and repetitions/stutters significantly more often than other hesitation phenomena. Articulatory-defectives, by contrast, used more non-ah phenomena. Articulatory-defective males exhibited significantly more hesitation phenomena generally than the other groups. Hesitation phenomena decreased with age for the males in the study but increased for females.
Walk the talk: connecting language, knowledge, and action in route instructions

Following verbal route instructions requires knowledge of language, space, action and perception. We present MARCO, an agent that follows free-form, natural language route instructions by representing and executing a sequence of compound action specifications that model which actions to take under which conditions. MARCO infers implicit actions from knowledge of both linguistic conditional phrases and from spatial action and local configurations. Thus, MARCO performs explicit actions, implicit actions necessary to achieve the stated conditions, and exploratory actions to learn about the world. We gathered a corpus of 786 route instructions from six people in three large-scale virtual indoor environments. Thirtysix other people followed these instructions and rated them for quality. These human participants finished at the intended destination on 69% of the trials. MARCO followed the same instructions in the same environments, with a success rate of 61%. We measured the efficacy of action inference with MARCO variants lacking action inference: executing only explicit actions, MARCO succeeded on just 28% of the trials. For this task, inferring implicit actions is essential to follow poor instructions, but is also crucial for many highly-rated route instructions.
Timed Ethernet: Real-Time Formal Specification of Ethernet

The goal of this paper is to show how formal specification can be applied to a full-fledged, real-world protocol while maintaining, or even enhancing, readability. The system we formally specify is Ethernet as it appears in IEEE 802.3. We focus on the specification of the Medium Access Control (MAC) layer—the part of the Data Link Layer that implements a 1-persistent CSMA/CD protocol — and its interfaces with adjacent layers. The specification method is based on one of Henzinger's real-time models. We believe that the readability of our specification is due to the graphical presentation using transition graphs of real-time programs.
Unique populations of lung mast cells are required for antigen-mediated bronchoconstriction.

Background Studies in both human and mouse indicate that mediators released by mast cells can lead to bronchoconstriction, and thus these are important effector cells in life threatening anaphylaxis. Much of our understanding of the various functions of mast cells emanates from the study of mice lacking theses cells, particularly mice carrying mutations in the tyrosine kinase gene Kit. Definitive evidence for the role of mast cells in the altered immune response requires the demonstration that this response can be normalized by reconstitution of the mice with cultured bone marrow-derived mast cells (BMMCs). While many mast cell niches can be restored with BMMCs, this has not been demonstrated for mast cells present in the airways of the lung, cells poised to mediate bronchoconstriction during allergic responses.
Localization of the genes encoding the melanocortin-2 (Adrenocorticotropic hormone) and melanocortin-3 receptors to chromosomes 18p11. 2 and 20q13. 2-q13. 3 by fluorescence in situ hybridization

Adrenocorticotropic hormone (ACTH) and [alpha]-, [beta]-, and [gamma]-melanocyte-stimulating hormone (MSH) are products of propiomelanocortin post-translational processing. These compounds are collectively labeled as melanocortins (MC). Aside from their established effects on the regulation of the adrenal cortex (ACTH) and melanocytes ([alpha]-MSH), the melanocortins have been implicated in a broad array of physiological events. Melanocortins mediate their effects through cell membrane receptors belonging to the superfamily of seven transmembrane G-protein-linked receptors. Using the technique of polymerase chain reaction with primers based on conserved areas of the seven transmembrane G-protein-linked receptor family, the authors recently isolated an [open quotes]orphan[close quotes] subfamily of this receptor group. Within the past year, two of these receptors were identified as specific for [alpha]-MSH (MC1) and ACTH (MC2). They have recently described a third melanocortin receptor (MC3) that appears to recognize the core heptapeptide sequence of melanocortins with equal potency and efficacy and identified its presence in the brain, placenta, and gut. Using the FISH technique, they localized the ACTH and the melanocortin-3 receptors to chromosome loci 18p11.2 and 20q12.3-q13.2, respectively. 19 refs., 1 fig.
P-selectin expression in myocardium of children undergoing cardiopulmonary bypass.

Cardiopulmonary bypass is a planned support technique that results in a period of myocardial ischemia and reperfusion. In addition, it is associated with an inflammatory response likely involving endothelial cell activation. In previous studies, we showed that E-selectin and intercellular adhesion molecule-1 (ICAM-1) messenger ribonucleic acid (mRNA) are increased in human myocardium after cardiopulmonary bypass. We have now examined the expression of P-selectin mRNA by ribonuclease protection in paired atrial biopsy specimens from 12 patients before and after cardiopulmonary bypass. By means of immunocytochemistry, we have also examined the endothelial cell surface expression of P-selectin protein, as well as that of E-selectin and ICAM-1 in three additional patients. Patient ages ranged from 1 day to 8.5 years (median 12 months), and cardiopulmonary bypass times ranged from 46 to 196 minutes (median 144 minutes). By ribonuclease protection, there was marked variability in the expression of P-selectin in biopsy specimens before bypass. However, when compared with prebypass levels, P-selectin mRNA decreased modestly in 10 of 12 patients after bypass (median decrease 1.5-fold, p = 0.016). As seen with immunocytochemistry, P-selectin protein was distributed diffusely through the vascular bed on large vessels and small vessels before bypass but was virtually absent on capillaries in specimens taken after bypass. E-selectin, which was absent in prebypass biopsy specimens, was induced in one of the three specimens after bypass, but no change in ICAM-1 protein expression above baseline was noted. We also find that cultured human endothelial cells treated with tumor necrosis factor-α in doses which induce ICAM-1 mRNA simultaneously decrease their expression of P-selectin mRNA as compared with untreated cells. These observations suggest that endothelial P-selectin is transcriptionally downregulated after cardiopulmonary bypass at times when E-selectin and ICAM-1 are induced. Furthermore, we find that E-selectin and ICAM-1 are expressed at times and at sites where P-selectin is absent. Although it is possible that P-selectin may have been induced and lost at early times before reperfusion, these data suggest that endothelial P-selectin plays a limited role in the inflammatory response that ensues after cardiopulmonary bypass.
Overexpression of Pref-1 in pancreatic islet β-cells in mice causes hyperinsulinemia with increased islet mass and insulin secretion.

Preadipocyte factor-1 (Pref-1) is made as a transmembrane protein containing EGF-repeats at the extracellular domain that can be cleaved to generate a biologically active soluble form. Pref-1 is found in islet β-cells and its level has been reported to increase in neonatal rat islets upon growth hormone treatment. We found here that Pref-1 can promote growth of pancreatic tumor derived AR42J cells. To examine Pref-1 function in pancreatic islets in vivo, we generated transgenic mouse lines overexpressing the Pref-1/hFc in islet β-cells using rat insulin II promoter (RIP). These transgenic mice exhibit an increase in islet mass with higher proportion of larger islets in pancreas compared to wild-type littermates. This is in contrast to pancreas from Pref-1 null mice that show higher proportion of smaller islets. Insulin expression and insulin secretion from pancreatic islets from RIP-Pref-1/hFc transgenic mice are increased also. Thus, RIP-Pref-1/hFc transgenic mice show normal glucose levels but with higher plasma insulin levels in both fasting and fed conditions. These mice show improved glucose tolerance. Taken together, we conclude Pref-1 as a positive regulator of islet β-cells and insulin production.
Structure of the single-stranded polyribonucleotide poly(2'-O-methylcytidylic acid).

Abstract X-ray diffraction studies have been made on oriented polycrystalline fibres of poly(2′- O -methylcytidylic acid). A form observed at 66% relative humidity has orthorhombic ( P 2 1 2 1 2 1 ) symmetry and unit cell dimensions a = 1.58 nm, b = 2.16 nm, c = 1.89 nm (fibre repeat). In this form the molecules are singlestranded, 6-fold (6 1 ) helices with a conformation very similar to that observed for polycytidylic acid. Evidently methylation at O-2′ does not necessarily cause a change in the pucker of the sugar ring. Nor are the intermolecular hydroxyl-hydroxyl hydrogen bonds observed in the polycytidylic acid rhombohedral crystal structure necessary to maintain the 6-fold helical symmetry. However, they may be necessary to maintain the symmetry at very high relative humidities where the polycytidylic acid structure is conserved but poly(2′- O -methylcytidylic acid) undergoes a transition to a form in which the rotation per residue is reduced from 60 ° to a value near 50 °.