cssi/SciSciGPT-SciSciNet huggingface dataset:
Evolving understanding of the renin-angiotensin-aldosterone system: pathophysiology and targets for therapeutic intervention.

Since its discovery in the late 19th century, our conceptual understanding of the renin-angiotensin-aldosterone system (RAAS) has undergone a process of continuous evolution. Renin was first described by Tigerstedt and Bergman, 1 who, in 1898, documented pressor effects of tissue extracts from rabbit kidneys. Later investigators established that the downstream products of renin's enzymatic activity functioned as key physiologic regulators of vascular tone, salt and water balance, and blood pressure (BP). It was later found that the most important of these products, angiotensin II (AII), also regulates cellular processes at the tissue level that are central to cardiovascular structure and function. Recently, discovery of the (pro)renin receptor and experimental evidence that binding to this receptor amplifies renin's enzymatic activity, activates prorenin, and directly stimulates important intracellular signaling pathways has added a further dimension to an evolving comprehension of exactly how the RAAS works and the mechanisms by which it contributes to human disease. The development of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) has allowed RAAS suppression to be extensively tested as a therapeutic strategy for both the prevention and treatment of cardiovascular disease. The ACEIs and ARBs reduce the effects of AII either by reducing its production or by directly blocking its interaction with the angiotensin-1 (AT1) receptor. Agents from both classes have proven effective in reducing the risk of serious cardiovascular events in patients with hypertension, heart failure (HF), and proteinuric renal disease. When given as monotherapy, ACEIs and ARBs increase renin secretion by interfering with feedback inhibition of its release. This leads to downstream RAAS activation that may limit the degree of RAAS suppression that is achievable with these drugs. Recognition of this phenomenon has led to the hypothesis that blocking multiple RAAS targets might produce more complete RAAS blockade and further improve cardiovascular outcomes. This article and others in this supplement will review the concepts and data that support and oppose this hypothesis as well as their clinical implications.
The Krüppel-like zinc finger protein Glis3 directly and indirectly activates insulin gene transcription

Glis3 is a member of the Kruppel-like family of transcription factors and is highly expressed in islet β cells. Mutations in GLIS3 cause the syndrome of neonatal diabetes and congenital hypothyroidism (NDH). Our aim was to examine the role of Glis3 in β cells, specifically with regard to regulation of insulin gene transcription. We demonstrate that insulin 2 (Ins2) mRNA expression in rat insulinoma 832/13 cells is markedly increased by wild-type Glis3 overexpression, but not by the NDH1 mutant. Furthermore, expression of both Ins1 and Ins2 mRNA is downregulated when Glis3 is knocked down by siRNA. Glis3 binds to the Ins2 promoter in the cell, detected by chromatin immunoprecipitation. Deletion analysis of Ins2 promoter identifies a sequence (5′-GTCCCCTGCTGTGAA-3′) from −255 to −241 as the Glis3 response element and binding occur specifically via the Glis3 zinc finger region as revealed by mobility shift assays. Moreover, Glis3 physically and functionally interacts with Pdx1, MafA and NeuroD1 to modulate Ins2 promoter activity. Glis3 also may indirectly affect insulin promoter activity through upregulation of MafA and downregulation of Nkx6-1. This study uncovers a role of Glis3 for regulation of insulin gene expression and expands our understanding of its role in the β cell.
Understanding implicit feedback and document preference: a naturalistic user study

As the amount of online information increases every day, tailoring system responses to individual interests is becoming an important problem in information systems research. This dissertation seeks to understand how an online information system can automatically predict which Web documents users prefer by monitoring their online behaviors with documents. The dissertation is further concerned with understanding how these behaviors are related to the context in which users seek information. Behaviors under investigation include how long users display documents in their browser windows (display time) and if users save, print or bookmark documents (retention). A user's preference for a document is measured by a user-assigned usefulness score. Information-seeking context is characterized by users' self-identified tasks and topics, and several attributes of these, such as the length of time the user expects to be working on a task and the user's familiarity with a topic. To observe users in natural information-seeking situations, users were provided with new laptops and printers, and their online interactions were unobtrusively monitored for fourteen weeks with client- and proxy-side logging software. At weekly intervals, subjects evaluated the usefulness of the documents that they viewed, classified these documents according to their tasks and topics, and characterized other information-seeking context attributes. Results demonstrated no direct relationship between display time and usefulness, and that display time was significantly related to information-seeking context in different ways, for different subjects. Most notably, display times differed significantly according to task and topic, and topic familiarity. In addition, retention was not always a good indicator of document preference, and subjects were more likely to retain documents related to particular tasks and topics. Finally, results showed no correlation between proxy- and client-generated display times, and that erroneous results are likely to occur when using proxy-generated display times. Overall, these results indicate that for an online information system to use behaviors to infer document preference, it is necessary for the system to model the user's information-seeking context, and that approaches to modeling should be personal rather than general. Furthermore, the integrity of behavior-based metrics used by such systems is an important issue that deserves special attention.
Doxercalciferol Treatment of Secondary Hyperparathyroidism

Objective:To review the pharmacology, pharmacokinetics, effectiveness, safety, and therapeutic considerations related to the use of doxercalciferol in the treatment of secondary hyperparathyroidism.Data Sources:A MEDLINE search (1966–June 2006) was conducted using the key words vitamin D, ergocalciferols, and secondary hyperparathyroidism. Text word searches were also performed for the terms 1-ά-hydroxy-vitamin D2,1-ά-hydroxyergocalciferol, Hectorol, and doxercalciferol. Searches were limited to studies published in English and conducted in human subjects.Study Selection and Data Extraction:All published clinical studies evaluating the safety and effectiveness of doxercalciferol in secondary hyperparathyroidism were reviewed, and anecdotal patient reports were also evaluated. Selected clinical studies involving the use of calcitriol and/or paricalcitol in the treatment of secondary hyperparathyroidism were also included.Data Synthesis:Doxercalciferol effectively reduces parathyroid hormone levels in patie...
Human Becoming Theory With Children

As a nurse practitioner, I am often challenged with providing care for children in the traditional medical model. Struggling with these challenges has created new ways of being with patients and their families. Working with children is gratifying, stimulating, and life changing. Living true presence with children as they draw images of their realities gives rise to a powerful interconnectedness that facilitates greater understanding of their meaning about what is important to them as they create new ways of seeing health opportunities. Bearing witness to children as they use art and words to describe their feelings encourages and fosters new ways of becoming for the nurse and the child and the child's family. This column describes a dialogical-engagement of this nurse practitioner and a young child and how this process transformed the nurse practitioner as she moves to be with children and families in new ways.
Dynamic implications of mantle hotspots

MOVEMENT of lithosphere plates over hotspots which are fixed relative to the mantle could explain the origin of island chains and aseismic ridges1–4. Observations of phase velocities against epicentral distances for Tonga–Samoa earthquakes5 show anomalies which can be interpreted as a radial and lateral inhomogeneity in the lower mantle beneath Hawaii. That indicates the possible existence of deep mantle plumes.
Estrogen, Estrogen Plus Progestin Therapy, and Risk of Breast Cancer

Epidemiologic evidence relating use of postmenopausal hormones to risk of breast cancer by nature relies on trends in prescribing practices. Data on the adverse effect of combination estrogen plus progestin used for long durations has only become available over the past decade. Evidence is reviewed relating estrogen alone and estrogen plus progestin to increased risk of breast cancer. Whereas current evidence indicates that longer duration of use increases risk of invasive breast cancer regardless of formulation, the rate of increase in risk is greater for combination estrogen plus progestin therapy. Although data are limited, continuous combined therapy and sequential therapy seem to have comparable impact on breast cancer risk. Combination therapy is more strongly related to lobular breast cancer than is estrogen alone. Unresolved issues remain about dose of estrogen and progestin in relation to risk, and about identification of women for whom short-term use to relieve menopausal symptoms may be safe and effective.
ICU versus Non-ICU Hospital Death: Family Member Complicated Grief, Posttraumatic Stress, and Depressive Symptoms.

Abstract Background: Family members of patients who die in an ICU are at increased risk of psychological sequelae compared to those who experience a death in hospice. Objective: This study explored differences in rates and levels of complicated grief (CG), posttraumatic stress disorder (PTSD), and depression between family members of patients who died in an ICU versus a non-ICU hospital setting. Differences in family members' most distressing experiences at the patient's end of life were also explored. Methods: The study was an observational cohort. Subjects were next of kin of 121 patients who died at a large, Midwestern academic hospital; 77 died in the ICU. Family members completed measures of CG, PTSD, depression, and end-of-life experiences. Results: Participants were primarily Caucasian (93%, N = 111), female (81%, N = 98), spouses (60%, N = 73) of the decedent, and were an average of nine months post-bereavement. Forty percent of family members met the Inventory of Complicated Grief CG cut-off, 31%...
Perceived Organizational Structure And Alienation Among Management Trainees

The article discusses a study on perceived organizational structure and alienation among management trainees. The results indicated that the sentiments of management trainees with regard to their c...
Graphics Hardware Acceleration for Rotorcraft Brownout Simulation

The past several years have seen the growing adoption of programmable graphics hardware as an important new technology in high performance computing. Relative to traditional CPU-based approaches, these devices have extremely high floating point operation capability and memory bandwidth at considerably lower cost than typical computer clusters. Modern GPUs are massively parallel, comprised of a unique hierarchy of computational units and memory management. Fully exploiting this architecture for computational fluid dynamics solvers requires the development of new algorithms tailored to the devices. To that end, this paper presents an efficient method for implementing an implicit solution algorithm on structured grids using the well-known SIMPLER scheme. Two distinct levels of parallelism are used to mirror the GPU architecture. This approach is then applied to the study of turbulent rotorcraft aerodynamics in ground effect and the brownout phenomenon, resulting in execution times on a single GPU in excess of 40× faster than an equivalent serial CPU implementation.
A part of something: The importance of transitional living programs within a Housing First framework for youth experiencing homelessness

Abstract Young people experiencing homelessness face severe threats to their health and well-being and while we know quite a bit about these risks, much less is understood about the usefulness of the services currently being provided to mitigate them. Transitional living programs (TLPs) are one of three core strategies executed by the federal government of the United States to address youth homelessness. The purpose of this phenomenological, qualitative study was to understand the impact over time of the housing and support services provided by a TLP directly from the perspectives of formerly homeless youth. Data was collected through in-depth, semi-structured interviews with 32 young people who exited a TLP located in Chicago, Illinois between 1 and 11 years ago. Participants believed TLPs to be an essential part of our solution to address youth homelessness, identifying themes of family, individual connections, community and preparedness that they believe uniquely qualify TLPs as a developmentally-appropriate program model for youth in times of housing crisis.
Search and Breast Cancer: On Episodic Shifts of Attention over Life Histories of an Illness

We seek to understand the evolving needs of people who are faced with a life-changing medical diagnosis based on analyses of queries extracted from an anonymized search query log. Focusing on breast cancer, we manually tag a set of Web searchers as showing patterns of search behavior consistent with someone grappling with the screening, diagnosis, and treatment of breast cancer. We build and apply probabilistic classifiers to detect these searchers from multiple sessions and to identify the timing of diagnosis using temporal and statistical features. We explore the changes in information seeking over time before and after an inferred diagnosis of breast cancer by aligning multiple searchers by the estimated time of diagnosis. We employ the classifier to automatically identify 1,700 candidate searchers with an estimated 90p precision, and we predict the day of diagnosis within 15 days with an 88p accuracy. We show that the geographic and demographic attributes of searchers identified with high probability are strongly correlated with ground truth of reported incidence rates. We then analyze the content of queries over time for inferred cancer patients, using a detailed ontology of cancer-related search terms. The analysis reveals the rich temporal structure of the evolving queries of people likely diagnosed with breast cancer. Finally, we focus on subtypes of illness based on inferred stages of cancer and show clinically relevant dynamics of information seeking based on the dominant stage expressed by searchers.
In-Clinic Blood Pressure Prediction of Normal Ambulatory Blood Pressure Monitoring in Pediatric Hypertension Referrals.

Objective Since younger patients have low pretest probability of hypertension and are susceptible to reactive and masked hypertension, ambulatory blood pressure monitoring (ABPM) can be useful. To better target use in referred patients, we sought to define in-clinic systolic blood pressure (SBP) measures that predicted normal ABPM and target end organ damage. Design, Setting, Patients, Outcome Measures. Data were collected on consecutive patients referred for high BP undergoing an ambulatory BP monitor from 2010 to 2013 (n = 248, 33.9% female, mean age 15.5 ± 3.6 years). Candidate in-clinic predictors were systolic maximum, minimum, or average BPs obtained by auscultative, oscillometric, or both. Multivariable logistic regression models were used to determine the prediction of normal ABPM by in-clinic BP predictors. Separate models considered predicting left ventricular hypertrophy (LVH) by in-clinic SBP vs. ABPM-defined hypertension. Identified predictor utility was tested with receiver operator characteristic curves. Results Maximum (OR 0.97 [95% CI 0.94–0.99]; P = .047), minimum (0.96 [0.94–0.99]; P = .002), and average (0.97 [0.95–1.00]; P = .04) in-clinic auscultative SBP predicted normal ABPM. Each had a c-statistic of 0.58. LVH was associated with in-clinic auscultative minimum SBP treated continuously (1.05, [1.01–1.10], P = .01) or dichotomized at the 90th percentile (8.23, [1.48–45.80], P = .02), as well as ABPM-defined hypertension (3.31, [1.23–8.91], P = .02). Both predictors had poor sensitivity and specificity. Conclusion In youth, normal auscultative in-clinic systolic blood pressure indices weakly predicted normal ambulatory blood pressure and target end organ damage.
Collision avoidance at sea

The problem of collision avoidance between surface ships may be examined from the perspective of either macro or micro collision avoidance. In macro collision avoidance the pilot of a ship would try for maintaining a given mileage separation between his own ship and others. Micro collision avoidance would be concerned with manoeuvres between ships of less than a given separation distance. Analysis of the two situations is different. In macro collision avoidance the other ships would often be maintaining constant speed and heading. Attention would be focused on keeping other ships out of an appropriate circle about the center of ones own ship. In micro collision avoidance other ships would in general be manoeuvering. The actual shape of the ships may be important in determining appropriate manoeuvers for own ship. In both macro and micro collision avoidance, qualitative game/control theory is useful for the determination of critical barriers and manoeuvre Results obtained this way for two ships are compared with some collision avoidance guidelines in actual use.
Perceptions of Soviet Power and Influence

Concepts like power and influence, however precisely they might be defined, have many intangible elements. I hope therefore you will be tolerant of my imprecisions and impressionistic judgments. Moreover, the notion of perceptions has become a fashionable way to describe any problem or inconsistency — one simply says: ‘that’s my perception and somebody else may have a different perception’. Nothing is what it really is; it is only a perception. Thus that part of my topic, too, lends itself to a certain amount of vagueness.
Gene-culture co-inheritance of a behavioral trait.

Human behavioral traits are complex phenotypes that result from both genetic and cultural transmission. But different inheritance systems need not favor the same phenotypic outcome. What happens when there are conflicting selection forces in the two domains? To address this question, we derive a Price equation that incorporates both cultural and genetic inheritance of a phenotype where the effects of genes and culture are additive. We then use this equation to investigate whether a genetically maladaptive phenotype can evolve under dual transmission. We examine the special case of altruism using an illustrative model, and show that cultural selection can overcome genetic selection when the variance in culture is sufficiently high with respect to genes. Finally, we show how our basic result can be extended to nonadditive effects models. We discuss the implications of our results for understanding the evolution of maladaptive behaviors.
Inappropriate Fentanyl Prescribing Among Nursing Home Residents in the United States.

Abstract Objective We quantified transdermal fentanyl prescribing in elderly nursing home residents without prior opioid use or persistent pain, and the association of individual and facility traits with opioid-naive prescribing. Design Cross-sectional study. Setting Linked Minimum Data Set (MDS) assessments; Online Survey, Certification and Reporting (OSCAR) records; and Medicare Part D claims. Participants From a cross-section of all long-stay US nursing home residents in 2008 with an MDS assessment and Medicare Part D enrollment, we identified individuals (≥65 years old) who initiated transdermal fentanyl, excluding those with Alzheimer disease, severe cognitive impairment, cancer, or receipt of hospice care. Measurements We used Medicare Part D to select beneficiaries initiating transdermal fentanyl in 2008 and determined whether they were “opioid-naive,” defined as no opioid dispensing during the previous 60 days. We obtained resident and facility characteristics from MDS and OSCAR records and defined persistent pain as moderate-to-severe, daily pain on consecutive MDS assessments at least 90 days apart. We estimated associations of patient and facility attributes and opioid-naive fentanyl initiation using multilevel mixed effects logistic regression modeling. Results Among 17,052 residents initiating transdermal fentanyl, 6190 (36.3%) were opioid-naive and 15,659 (91.8%) did not have persistent pain. In the regression analysis with adjustments, residents who were older (ages ≥95 odds ratio [OR] 1.69, 95% confidence interval [CI] 1.46–1.95) or more cognitively impaired (moderate-to-severe cognitive impairment, OR 1.99, 95% CI 1.73–2.29) were more likely to initiate transdermal fentanyl without prior opioid use. Conclusion Most nursing home residents initiating transdermal fentanyl did not have persistent pain and many were opioid-naive. Changes in prescribing practices may be necessary to ensure Food and Drug Administration warnings are followed, particularly for vulnerable subgroups, such as the cognitively impaired.
From sedentary to active school commute: Multi-level factors associated with travel mode shifts

Previous research has examined personal, social, and environmental correlates of active commuting to school, but most were cross-sectional and mode choice studies. This exploratory case study utilized a retrospective natural experiment opportunity, where a group of students transferred to a new school, and therefore experienced changes in their home-to-school travel environments. It examined whether such changes led to mode shifts from sedentary (car or school bus) to active (walking and bicycling) and what factors were associated with those shifts. Retrospective parental survey data (n=165, response rate=46%) were collected in 2011 from a new elementary school that opened in 2010 in Austin, Texas. The survey asked about the child's school travel mode and parental perceptions of home-to-school travel environments before and after the transfer, as well as personal and social factors. Multivariate logistic regressions were used to predict the odds of shifting from sedentary to active modes, using personal, social, and physical environmental variables. Sixty-eight (41.2%) respondents reported a sedentary-to-active mode shift for school commuting. Such shifts were associated with changes in school travel environments (e.g., shorter travel distance, improved safety, and decreased availability of bike lanes/paths) and relevant programs/services (e.g., increase in walking-promotion programs, and decrease in school bus service due to shortened distances). Targeting the current sedentary mode users is important to bring health benefits through increased physical activity and environmental benefits from reduced automobile use. Sedentary-to-active mode shifts may be encouraged by providing walking-promotion programs and by reducing travel distances and safety threats en route to school.
Asymmetric S/D contacts with BN tunneling barrier on black phosphorous FETs

This paper reveals the significance of contact tunneling barrier for narrow bandgap black phosphorus (BP) PMOSFETs. Without the tunneling barrier, record high I on of 940µA/μm is achieved however I off is also increased due to the reverse electron tunneling current. With an asymmetric BN tunneling barrier at source side, I off is reduced by a factor of 5×103 at a cost of 20% I on reduction.
Automated Fabrication of Foldable Robots Using Thick Materials

Designing complex machines such as robots often requires multiple iterations of design and prototyping. Folding has recently emerged as a method to both simplify fabrication and accelerate assembly of such machines. However, the robots so far produced by folding have often been made of thin, flexible materials that limit their size and strength. We introduce a folding-based fabrication process that uses thick materials layered with flexible film to enable folding while maintaining high stiffness in the folded structure. We use this process to fabricate multiple solid bodies, as well as two hexapods, one of which can carry up to 2.50 kg payloads. Each folded structure took less than 3 h to construct. Our results indicate that folding using thick materials can be a viable method for rapidly fabricating and prototyping larger and sturdier robots.
Molecular Structure and Dynamics of Bacterial Nucleoids

This chapter summarizes recent evidence about the composition, structures, and function of components that form supercoil domains in bacterial nucleoids. Nucleoid formation enables a cell to move a compact DNA ensemble of dynamic transcription complexes and multiple replisomes efficiently into daughter cells during the cell division. In the past 10 years advances were made in many bacterial systems, but this review focuses on work carried out in the closely related clades of Escherichia coli and Salmonella typhimurium. New information indicates most of the chromosome has a stochastic domain structure but that transcription organizes unique topological zones in a small fraction of the genome. Nucleoid formation becomes critical when cells constrict the cell cycle to carry out dichotomous replication. Under very short doubling times of dichotomous growth, cell division requires intricate coordination of multiple factors to promote chromosome segregation. The most crucial enzyme for nucleoid formation is DNA gyrase, which not only removes positive links during DNA replication, it also establishes the supercoil tension that promotes correct compaction. Important enzymes including Topo IV, FtsK, and XerCD recombinases are tuned to promote nucleoid segregation only when appropriate levels of supercoiling are present. Surprisingly, gyrase establishes significantly different supercoiling levels in E. coli and Salmonella typhimurium, which makes the enzyme a barrier for horizontal gene transfer between the species.
Observations on human ova and the fertilization process

The mammalian fertilization process was reviewed, with emphasis on recent laboratory developments. Maturation stages of the human follicular oocyte which are requisite to fertilization were explored with in vitro culture methods. The experience of other investigators was confirmed in that, on removal from the follicle, nuclear maturation through polar body release was observed. Available information on the human tubal ovum was summarized and the recorded attempts at in vitro fertilization of the human oocyte analyzed. Time lapse in cinematography used successfully in the rabbit was suggested as a means for establishing the validity of in vitro fertilization in man. It was predicted, based on experience in other mammals, that placement of in vitro cultured human oocytes into the uterus for implantation would eventually be carried out successfully. Further studies in the subhuman primate were suggested as a requisite to such experiments, in order to insure conditions which would yield normal young.
Properties and Edible Applications of Soybean Oil

During the twentieth century, vegetable oil consumption in the developed countries increased dramatically with advances in oil extraction and processing. Innovations like hydrogenation and interesterification have been used to modify vegetable oils to obtain variable functional properties required for different edible applications. This is particularly true of soybean oil, which has become the world’s leading vegetable oil for edible consumption. For example, between 1994 and 1995, the annual world’s consumption of soybean oil was estimated at 18.93 million metric tons, representing about 29.2% of all the major vegetable oils consumed worldwide (Fig. 7.1).
Synchronous distance learning via the Internet experience and status report

Remote conferencing via the Internet will soon provide a cost effective and convenient avenue for distance learning. Used in conjunction with the asynchronous methods that are currently popular, both virtual classrooms and virtual office visits will provide ready access to instruction from a student's home or office. While some short-term technical impediments exist, the real bottlenecks are more likely to be in the areas of preparing institutions and instructors to use the technology and to use it effectively. This paper describes some of the technology involved, some of the current impediments, technical and otherwise. It also shares some experience and lessons learned in the use of this technology through a project funded by NSF and Louisiana Board of Regents grants.
Azygous Anterior Cerebral Artery Acute Occlusion Managed With Endovascular Mechanical Thrombectomy: 2-Dimensional Operative Video.

Mechanical thrombectomy has become the standard of care for management of most acute large-vessel occlusion (LVO) strokes. Most intracranial occlusions are located in the middle cerebral and internal carotid arteries. We present a unique case of acute occlusion of an azygous anterior cerebral artery (ACA). A 59-yr-old man with known hypertension and alcoholism presented with right hemiparesis, right facial palsy, aphasia, and dysarthria. His initial National Institutes of Health Stroke Scale (NIHSS) score was 20. Computed tomographic angiography and perfusion imaging demonstrated acute bilateral ACA occlusion with viable penumbra and preserved cerebral blood volume. The patient was not a candidate for intravenous tissue plasminogen activator because he presented with a wake-up stroke. After consent was obtained from his family, the patient was taken urgently for endovascular recanalization. Digital subtraction angiography confirmed acute azygous ACA occlusion. Under conscious sedation, the patient underwent mechanical thrombectomy with a stent retriever and a large-bore aspiration catheter. Successful revascularization (thrombolysis in cerebral infarction [TICI] grade 3) of the azygous ACA and both A2 arteries was obtained after 2 attempts and the use of a different stent retriever (first a 3 × 30 mm Trevo [Stryker Neurovascular, Kalamazoo, Michigan] and then a 4 × 40 mm Solitaire Platinum [Medtronic, Dublin, Ireland]). A reperfusion catheter was used during both attempts. No procedure-related complications occurred. The patient was discharged to a rehabilitation facility 3 d after the procedure with an NIHSS score of 2. In this video, we present the operative nuances of an uncommon location of LVO and its endovascular management.
Toward an Open, Sustainable National Advanced Computing Ecosystem

For over three decades, a largely organic process has brought into existence a somewhat disjointed and chaotic national research computing ecosystem supporting a collection of computational resources, services, and support. Consequently, much of the national advanced research computing environment can be characterized by pockets of more coherent resources and services in a larger, less coherent ecosystem. The rise in deployment of research computing resources on university campuses has added complexity to the situation. The National Science Foundation has made a foray into developing a more coherent environment via investments in XSEDE, the associated research computing resources, and critical common services and support for researchers. XSEDE can be viewed as a model for creating scalable, stable, and well-supported cyberinfrastructure. The NCSI provides an opportunity to catalyze a national discussion to carefully consider the state of the current ecosystem, the desired state moving forward, and how we will attain that desired state.
Yes-associated protein (YAP) is required in maintaining normal ovarian follicle development and function

Yes-associated protein (YAP) is one of the major components of the Hippo signaling pathway, also known as the Salvador/Warts/Hippo (SWH) pathway. Although the exact extracellular signal that controls the Hippo pathway is currently unknown, increasing evidence supports a critical role of the Hippo pathway in embryonic development, regulation of organ size, and carcinogenesis. The ovary is one of few adult tissues that exhibit cyclical changes. Ovarian follicles, the basic units of ovary, are composed of a single oocyte surrounded by expanding layers of granulosa and theca cells. Granulosa cells (GCs) produce sex steroids and growth factors, which facilitate the development of the follicle and maturation of the oocyte. It has been reported that YAP is highly expressed in human GC tumors, but the role of YAP in normal ovarian follicle development is largely unknown. In current study, we examined YAP expression in bovine ovaries. We demonstrate that downstream hippo signaling effector protein, YAP and transcription co-activator, TAZ, are present and localization of both YAP and TAZ are density-dependent. Likewise, YAP and TAZ are critically involved in granulosa cell proliferation. Furthermore, reducing YAP in granulosa cells inhibits FSH-induced aromatase expression and estradiol biosynthesis. The data suggest that YAP plays an important role in the development of ovarian follicles and estradiol synthesis, which are necessary for maintaining normal ovarian function.
Burali-Forti as a Purely Logical Paradox

Russell’s paradox is purely logical in the following sense: a contradiction can be formally deduced from the proposition that there is a set of all non-self-membered sets, in pure first-order logic—the first-order logical form of this proposition is inconsistent. This explains why Russell’s paradox is portable—why versions of the paradox arise in contexts unrelated to set theory, from propositions with the same logical form as the claim that there is a set of all non-self-membered sets. Burali-Forti’s paradox, like Russell’s paradox, is portable. I offer the following explanation for this fact: Burali-Forti’s paradox, like Russell’s, is purely logical. Concretely, I show that if we enrich the language $\mathcal {L}$ of first-order logic with a well-foundedness quantifier W and adopt certain minimal inference rules for this quantifier, then a contradiction can be formally deduced from the proposition that there is a greatest ordinal. Moreover, a proposition with the same logical form as the claim that there is a greatest ordinal can be found at the heart of several other paradoxes that resemble Burali-Forti’s. The reductio of Burali-Forti can be repeated verbatim to establish the inconsistency of these other propositions. Hence, the portability of the Burali-Forti’s paradox is explained in the same way as the portability of Russell’s: both paradoxes involve an inconsistent logical form—Russell’s involves an inconsistent form expressible in $\mathcal {L}$ and Burali-Forti’s involves an inconsistent form expressible in $\mathcal {L} + \mathsf {W}$ .
Effects of Deception on the Deceiver: An Interdisciplinary View

Deceivers are not protected from the effects of deception, and this chapter considers the effects on the deceiver from the biological adaptation, neuroscience, psychology, and communication perspectives. While deception is adaptive, it is constrained by the truth bias and the deceiver’s understanding of the target’s detection of deception. When deception occurs, multiple neuro-processes are activated in the brain. Those changes lead to cognitive and emotional loads that impair the deceiver’s ability to manage communication. Self-deception is an inevitable outcome of deception and, along with deception outcomes, alters the deceiver’s sense of self and sense of reality. These changes in the deceiver manifest in the interpersonal communication context.
Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with idiopathic gastroparesis

Gastric emptying is impaired in patients with gastroparesis whereas it is either unchanged or accelerated in obese individuals. The goal of the current study was to identify changes in gene expression in the stomach muscularis that may be contributing to altered gastric motility in idiopathic gastroparesis and obesity. Quantitative real time RT-PCR and whole transcriptome sequencing were used to compare the transcriptomes of lean individuals, obese individuals and either lean or obese individuals with idiopathic gastroparesis. Obesity leads to an increase in mRNAs associated with muscle contractility whereas idiopathic gastroparesis leads to a decrease in mRNAs associated with PDGF BB signaling. Both obesity and idiopathic gastroparesis were also associated with similar alterations in pathways associated with inflammation. Our findings show that obesity and idiopathic gastroparesis result in overlapping but distinct changes in the gastric muscularis transcriptome. Increased expression of mRNAs encoding smooth muscle contractile proteins may be contributing to the increased gastric motility observed in obese subjects, whereas decreased PDGF BB signaling may be contributing to the impaired motility seen in subjects with idiopathic gastroparesis.
Juvenile homicide offenders: a 35-year-follow-up study

Murders committed by juveniles have been a major concern in the USA for more than 40 years. Due to decisions in the 21st century by the United States Supreme Court, the likelihood of juvenile homicide offenders being sentenced to life without parole (LWOP) is less than in past decades. In addition, hundreds of individuals in prison who were sentenced to LWOP under mandatory sentencing statutes or their equivalent as juveniles for murder are now eligible for resentencing and may be released. Given these changes in sentencing policies and practices, follow-up research on juveniles involved in murder is needed. This study is a 35-year follow-up study of 59 boys who were convicted of murder and sentenced to adult prisons in a southeastern state, and initially interviewed in the early 1980s. Twenty-two of these men agreed to participate in clinical interviews about their experiences in prison and upon return to the community if released. The experiences in prison are highlighted for all men. Thereafter, attention focuses on the 19 juvenile homicide offenders who have been released. Of these 19 men, 11 were classified as failures given that they were sent back to prison at least once. Length of time served and completion of GED were the best predictors of post-release success. Clinical observations, implications of the findings, limitations of the study, and directions for future research are discussed.
Congenital diarrhea in a newborn infant: A case report

Background Microvillus inclusion disease (MVID) is a rare autosomal recessive cause of severe congenital diarrhea with significant morbidity and mortality. Definitive treatment involves bowel transplant. The diagnosis of this condition can be challenging and a few genetic panels are available for the identification of the most common mutations. We present the case of an infant with MVID due to a mutation not reported in the literature before. Case summary We report the case of an infant transferred to our institution with severe diarrhea of unknown etiology, failure to thrive, and significant metabolic derangements. An extensive work-up including stool studies for common gastrointestinal pathogens, abdominal ultrasound, esophagogastroduodenoscopy with duodenal biopsy and flexible sigmoidoscopy failed to reveal a diagnosis. Multiple dietary and formula regimens were introduced but all resulted in voluminous diarrhea. She remained on total parenteral nutrition (TPN) for the duration of her hospital stay. Genetic testing was done and she was subsequently found to have a novel mutation in the MYO5B gene [homozygous mutation for MYO5B c.1462del, p. (Ile488Leufs*93)] giving us the diagnosis of MVID. She remains on TPN while awaiting bowel transplant at the time of the compilation of this case report. Conclusion We report a novel mutation involved in MVID and highlight the importance of considering this disease when faced with a newborn presenting with life threatening diarrhea. At the time of this publication, 232 allelic variations of this gene (MIM#606540) exist in National Center for Biotechnology Information's database. Our patient's mutation has not been reported in literature as a cause of MVID.
Intrinsically musical game worlds: abstract music generation as a result of gameplay

This poster submission explores the concept of nuanced dynamic music generation as a core game mechanic. The world in which this game is set is intrinsically musical. All events and actions in the world add to the music rather than being sound effects that are layered over top of a soundtrack. The music that is generated is often more of a rhythmic soundscape than a song in this game. The goal of the game is not to play a song correctly. Rather, it is to navigate a world, complete puzzles and kill enemies. Playing the game well will sound more musical than playing it poorly. This concept explores a new realm of creative opportunity for game designers. For example, musically cohesive audio can provide clues to a player for how to progress through a level. This core mechanic has the potential to engage a player in ways that most games do not.
Oncogenic TLS-ERG Fusion Protein Promotes Differentiation of Myeloid Progenitors into Myeloblasts but Blocks Their Terminal Differentiation.

Abstract In a subset of acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML) in blast crisis, the TLS (translocation liposarcoma) gene is fused to the ERG (ets-related gene) gene through a recurrent t(16;21) translocation. This chromosomal translocation results in the generation of the TLS-ERG fusion protein. More recently, the same TLS-ERG fusion protein has also been identified in Ewing's sarcoma in children. To investigate the oncogenic mechanism of TLS-ERG, we stably expressed TLS-ERG or its mutant TLS-ERGΔets in mouse L-G myeloid progenitor cells through retroviral transduction. L-G cells normally proliferate in the presence of IL-3 and undergo terminal differentiation into hypersegmented neutrophils when treated with G-CSF. In contrast, expression of TLS-ERG in L-G cells led to spontaneous differentiation into immature myeloblasts but G-CSF treatment of these cells failed to induce terminal differentiation. L-G myeloblasts harboring TLS-ERG were characterized by high levels of myeloperoxidase (MPO), a phenomenon also observed in immature myeloblasts isolated from human leukemia patients with the t(16;21) translocation. As deletion of the ets DNA-binding domain from TLS-ERG abolished its ability to promote spontaneous myeloblast differentiation or the ability to up-regulate the MPO gene, we further examined how TLS-ERG fusion protein might affect the functions of other regulators such as PU.1, an ets transcription factor known to play a critical role in the differentiation of myeloid progenitors. Though both proteins have similar DNA-binding property, TLS-ERG differs from PU.1 through binding directly to RNA polymerase II as well as through escaping repression by histone modification enzymes. Together, these findings suggest that the TLS-ERG fusion protein can cause blockage of myeloid differentiation by interfering with the gene expression program normally controlled by key regulators.
What You See is NOT What You Get: Discovering and Tracking Social Engineering Attack Campaigns

Malicious ads often use social engineering (SE) tactics to coax users into downloading unwanted software, purchasing fake products or services, or giving up valuable personal information. These ads are often served by low-tier ad networks that may not have the technical means (or simply the will) to patrol the ad content they serve to curtail abuse.In this paper, we propose a system for large-scale automatic discovery and tracking of SE Attack Campaigns delivered via Malicious Advertisements (SEACMA). Our system aims to be generic, allowing us to study the SEACMA ad distribution problem without being biased towards specific categories of ad-publishing websites or SE attacks. Starting with a seed of low-tier ad networks, we measure which of these networks are the most likely to distribute malicious ads and propose a mechanism to discover new ad networks that are also leveraged to support the distribution of SEACMA campaigns.The results of our study aim to be useful in a number of ways. For instance, we show that SEACMA ads use a number of tactics to successfully evade URL blacklists and ad blockers. By tracking SEACMA campaigns, our system provides a mechanism to more proactively detect and block such evasive ads. Therefore, our results provide valuable information that could be used to improve defense systems against social engineering attacks and malicious ads in general.
Early Communication Skills and Special Education Outcomes at School Entry: Implications for Pediatric Care and Screening.

Objective. To examine whether children’s early communication skills at age 3 predict special education outcomes at kindergarten entry. Methods. Data from 139 children eligible for early interventio...
The Social Construction of Transgender Individuals and U.S. Military Policy

This article aims to apply the social construction of target populations to policy regarding transgender individuals in the U.S. military. After presenting an overview on diversity in the military,...
Human‐associated species dominate passerine communities across the United States

AIM: Human development and agriculture can have transformative and homogenizing effects on natural systems, shifting the composition of ecological communities towards non‐native and native species that tolerate or thrive under human‐dominated conditions. These impacts cannot be fully captured by summarizing species presence, as they include dramatic changes to patterns of species abundance. However, how human land use patterns and species invasions intersect to shape patterns of abundance and dominance within ecological communities is poorly understood even in well‐known taxa. LOCATION: Conterminous United States. TIME PERIOD: 2010–2012. MAJOR TAXA STUDIED: Passeriformes. METHODS: We analyse continental‐scale monitoring data to study the proportional abundance of non‐native and native synanthropic species within passerine bird communities. Synanthropic species are those that benefit from an association with humans. We estimate how the amount and configuration of human development and agriculture relate to the degree to which human‐associated species dominate passerine communities across the continent. RESULTS: Human‐associated species comprised the majority of detected passerine individuals across two‐thirds of bird surveys. Non‐native and synanthropic species responded differently to land cover and reached highest relative abundance in different portions of the continent. The proportional abundance of synanthropic birds increased rapidly with development, but was not related to the configuration of land cover. The proportion of non‐native individuals was higher when intensively‐used land cover was more aggregated. MAIN CONCLUSIONS: Even low amounts of intensively‐used lands were associated with a dramatic reshaping of passerine communities, with consequences for patterns of relative abundance across the continent.