cssi/SciSciGPT-SciSciNet huggingface dataset:
Identifying the determinants of response to MDM2 inhibition

// Anne Y. Saiki 1 , Sean Caenepeel 1 , Elissa Cosgrove 2, 5 , Cheng Su 3 , Michael Boedigheimer 4 , Jonathan D. Oliner 1 1 Oncology Research, Amgen, Inc., Thousand Oaks, California, USA 2 Genome Analysis Unit, Amgen, Inc., South San Francisco, California, USA 3 Biostatistics, Amgen, Inc., Seattle, Washington, USA 4 Molecular Sciences, Amgen, Inc., Thousand Oaks, California, USA 5 Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA Correspondence to: Jonathan D. Oliner, e-mail: jonoliner@hotmail.com Keywords: TP53 , MDM2 , amplification Received: October 28, 2014 Accepted: January 08, 2015 Published: February 03, 2015 ABSTRACT Previous reports have provided evidence that p53 mutation is a strong negative predictor of response to MDM2 inhibitors. However, this correlation is not absolute, as many p53 Mutant cell lines have been reported to respond to MDM2 inhibition, while many p53 WT cell lines have been shown not to respond. To better understand the nature of these exceptions, we screened a panel of 260 cell lines and noted similar discrepancies. However, upon extensive curation of this panel, these apparent exceptions could be eliminated, revealing a perfect correlation between p53 mutational status and MDM2 inhibitor responsiveness. It has been suggested that the MDM2 -amplified subset of p53 WT tumors might be particularly sensitive to MDM2 inhibition. To facilitate clinical testing of this hypothesis, we identified a rationally derived copy number cutoff for assignment of functionally relevant MDM2 amplification. Applying this cutoff resulted in a pan-cancer MDM2 amplification rate far lower than previously published.
Quantitative analyses of intracellularly characterized and labeled thalamocortical projection neurons in the ventrobasal complex of primates

This study describes the architecture of neurons and individual dendritic arbors of thirteen intracellularly labeled thalamocortical projection neurons that respond to non-noxious stimuli from the primate (Macaca fascicularis or Macaca mulatta) ventrobasal complex (VB). The neurons compose a homogeneous morphological class with total dendritic lengths from 10,169 microns to 21,711 microns (mean 17,615 microns +/- 3,705). The labeled neurons were remarkably similar in most measured parameters including the number of dendrites (7.5 +/- 1.2), percentage of dichotomous branching (89.8% +/- 3.4), and contribution of terminal branches to total dendritic length (88.4% +/- 2.0). The individual dendrites ranged in total length from 443 microns to 7,657 microns with a mean of 2,346 microns (+/- 137, n = 98). There was a positive correlation between stem dendrite diameter and total dendrite length, making it possible to estimate the total size of an individual dendrite by measuring the stem dendrite diameter. There was only a small increase in mean path distance with increasing dendritic size at the whole neuron and individual dendritic levels, so that for individual dendrites the mean path distance of a dendrite consisting of only two segments was 199 microns, while the mean path distance for a dendrite with eight segments was only 45 microns longer. Analysis of dendrite diameter, segment order, and path distance shows that dendritic diameter is not reliable for determining the location of synaptic contacts viewed by electron microscopy onto dendritic trees. The small variation of measured parameters between these neurons presents a powerful tool for future developmental, plasticity and comparative studies of VB neurons.
A layered approach to stereo reconstruction

We propose a framework for extracting structure from stereo which represents the scene as a collection of approximately planar layers. Each layer consists of an explicit 3D plane equation, a colored image with per-pixel opacity (a sprite), and a per-pixel depth offset relative to the plane. Initial estimates of the layers are recovered using techniques taken from parametric motion estimation. These initial estimates are then refined using a re-synthesis algorithm which takes into account both occlusions and mixed pixels. Reasoning about such effects allows the recovery of depth and color information with high accuracy even in partially occluded regions. Another important benefit of our framework is that the output consists of a collection of approximately planar regions, a representation which is far more appropriate than a dense depth map for many applications such as rendering and video parsing.
Do patients wish to be involved in decision making in the consultation? A cross sectional survey with video vignettes

Abstract Objective: To determine patients9 preferences for a shared or directed style of consultation in the decision making part of the general practice consultation. Design: Structured interview, with video vignettes of acted consultations. Setting: 5 practices in Lothian, Scotland. Participants: 410 patients (adults and adults accompanying children) attending surgery appointments. Main outcome measures: Preference for shared or directed form of video vignette for five different presenting conditions. Results: Patients varied in their preference for involvement in decision making in the consultation. Under multiple regression analysis, patients9 preference was found to be independently predicted by the problem viewed (patients presented with physical problems preferred a directed approach), patients9 age (patients aged 61 or older were more likely to prefer the directed approach), social class (social classes I and II were more likely to prefer the shared approach), and smoking status (smokers more likely to prefer the shared approach). Those patients who were able to answer (or who thought their doctor9s style similar to those in the vignettes) were more likely to describe their own doctor9s style as similar to their preferred style. No major association in preference was found with sex, frequency of attendance, or perceived chronic ill health. Conclusion: Patients may vary in their desire for involvement in decision making in consultations. Although this variation seems to depend on the presenting problem, age, social class, and smoking status, these associations are not absolute, with large minorities in each group. Doctors need the skills, knowledge of their patients, and the time to determine on which occasions, with which illnesses, and at which level their patients wish to be involved in decision making.
Determinants of perceived risk for HIV infection among police officers

Abstract Police officers often come into contact with persons who are considered members of high risk groups for HIV infection, such as intravenous drug users and prostitutes. The present exploratory study employs field research methodology to observe patrol officers in their work settings in urban and rural locations to investigate contributing factors to their perceived risk of HIV infection. Four notable findings emerged. First, departmental training may not lower fear or perceived risk of HIV infection among police officers. Second, awareness of modes of transmission may increase perceived risk among officers but awareness of and access to protective measures may decrease fear and perceived risk. Third, access to protective measures is not always perceived as enough to ensure safety for officers who are faced with administering first aid to bleeding persons who may be HIV positive. Fourth, “street wisdom” may give police officers an illusion of safety.
Interfacial Design of Anisotropic Conductive Adhesive Based Interconnects Using Molecular Wires and Understanding of Their Electrical Conduction

Anisotropic conductive adhesives (ACAs) have been considered a promising interconnect material for next generation high performance devices. However, high joint resistance and low current carrying capability of ACA interconnects have been the limitations to utilizing ACAs in high power devices. In this study, we have introduced conjugated dithiols into ACA formulations to create molecular wire junctions between conductive fillers and metal pads as a means to facilitate the electron transport through the ACA joints. With the introduction of molecular wires, there is evidence of measured improvements in both the electrical conductivity and current carrying capability. The factors leading to these improvements in electrical properties are also discussed.
Does exercise induce hypoalgesia through conditioned pain modulation

Pain sensitivity decreases with exercise. The mechanisms that underlie this exercise-induced hypoalgesia (EIH) are unclear. Our purpose was to investigate conditioned pain modulation (CPM) as a potential mechanism of EIH. Sixteen women completed pain testing during three sessions: painful exercise, nonpainful exercise, and quiet rest. Intensity and unpleasantness ratings to noxious heat stimuli were assessed at baseline and during and following each session. Results showed that pain sensitivity decreased significantly during both exercise sessions (p < .05), but not during quiet rest. Effect size calculations showed that the size of the hypoalgesic response was greater following painful exercise than nonpainful exercise. Our results suggest that exercise-induced muscle pain may contribute to the magnitude of EIH. However, as pain sensitivity also decreased following nonpainful exercise, CPM is not likely the primary mechanism of EIH.
Purification and Characterization of Astrocyte Precursor Cells in the Developing Rat Optic Nerve

The signaling interactions that control oligodendrocyte generation from their precursor cells have been studied intensively. Much less is known about how astrocyte generation is normally controlled. Here we report the purification and characterization of astrocyte precursor cells (APCs) from the developing rat optic nerve. APCs are antigenically distinct from astrocytes. Both cell types are Pax2(+) and vimentin+, whereas astrocytes are GFAP+ and S100beta+, and the precursor cells are A2B5(+). In contrast to purified astrocytes, purified APCs rapidly die in serum-free culture but can be saved by basic fibroblast growth factor (bFGF) and glial growth factor 2 (GGF2). Unlike oligodendrocyte precursor cells, APCs do not differentiate by default; their differentiation into GFAP+ cells is induced by ciliary neurotrophic factor (CNTF) or by leukemia inhibitory factor (LIF). Finally, the survival, proliferation, and differentiation of APCs were promoted by coculture with other embryonic optic nerve cell types but not with purified embryonic retinal ganglion cells, indicating that interactions with non-neuronal cells are likely to play an important role in controlling astrocyte generation in the developing optic nerve.
Systemic Reform Efforts in the U.S.

While data-based decision making and decision support systems are making inroads into educational management, the human capacity to evaluate programs, curricula, and other reform efforts has not kept pace. The latest generation of collaborative systems that support knowledge exchange and expertise location services hold great promise for building communities around these issues and supporting emerging research capacity in schools and districts.
Sparse feedback structures for control of civil systems

Summary Modern structural control systems use centralized, wired sensor feedback to impart counter forces based on measurement of the response. However, centralized systems can be sensitive to sensor failure, controller failure, and the reliability of sensor links. The recent study of wireless control systems has encouraged decentralized control approaches to overcome wireless structural control challenges, including limiting the wireless communication required and the associated slow sampling rate and time delays in the control system. Decentralized control offers the additional advantages of multiple independent controllers and small subsets of measurement feedback. Previous decentralized structural control algorithms, both Ad-Hoc and Heuristic, enforce a spatial sparsity pattern during the design, which is assumed a priori. Therefore, the optimal feedback structure is not considered in the design. This work explores a decentralized optimal LQR design algorithm where the sparsity of the feedback gain is incorporated into the objective function. The control approach is compared with previous decentralized control techniques on 5- and 20-story control benchmark structures fitted with active or semi-active systems. Additionally, the sparsity and control requirements are compared with centralized designs to gain insight on the overall performance of sparse feedback systems. The optimal sparse feedback design offers the best balance of performance, measurement feedback, and control effort. Additionally, the feedback structure identified is not easily identifiable a priori in the reduced order model of the 20-story structure, highlighting the significance of particular measurements in this feedback framework. Copyright © 2016 John Wiley & Sons, Ltd.
An automated local and regional seismic event detection and location system using waveform correlation

Abstract We report on the development of an automated Local Waveform Correlation Event Detection System (LWCEDS) and its application to the New Mexico Tech Seismic Network. LWCEDS is an adaptation of a global system, WCEDS, a matched filtering algorithm for global Comprehensive Test Ban Treaty (CTBT) monitoring applications developed at Sandia National Laboratories and New Mexico Tech. Although the current CTBT monitoring system is based on teleseismic phase detection, effort is being placed on research to highlight specific areas of the globe for which local and regional seismic networks could be employed. An automated waveform correlation regional location system could also serve as a rapid alert and automated location system by providing magnitude and hypocenter information within a few minutes of the occurrence of a hazardous earthquake. In the LWCEDS algorithm, processed waveforms are correlated with theoretical travel-time envelopes, and a grid search is performed to identify the space-time solutions that yield the highest correlations. High correlation indicates that an event has occurred and that a good approximation to the correct origin time and hypocenter has been determined; explicit phase identification is not required. To avoid the large computational expense of calculating a complete correlation for each grid point, we use a laterally homogeneous velocity model and reformulate the problem into a single matrix multiplication and matrix assessment for each time step. LWCEDS has been successfully tested on a suite of local and regional seismic events selected to span the range of expected event quality. Preliminary results from our sparse network show typical epicentral errors of less than 3 km for local events and, with notable exceptions, to within 10 to 20 km for regional events. Similar results were obtained during an on-line experiment conducted to generate daily bulletins during the time period from 3 December 1996 through 7 January 1997. Data from 156 triggers were processed, including 33 teleseisms, 102 regional events (includes explosions), and 21 local earthquakes. Results from this expanded test set are encouraging but reveal the need for a method to mask or flag various electronic and telemetry spikes.
Prevalence and Characteristics of Adverse Drug Reactions in Neurosurgical Intensive Care Patients

OBJECTIVE: To evaluate the prevalence and characteristics of adverse drug reactions (ADRs) in neurosurgical intensive care patients. METHODS: Retrospective analysis of ADR data obtained from a spontaneous reporting system in a tertiary care university hospital. Reports of suspected ADRs in adult patients admitted emergently or electively to the neurosurgical service were included. RESULTS: Over the 3 year period, 3496 neurosurgical intensive care unit (ICU) patient admissions accounted for 5% of all hospital admissions. A total of 10% of all neurosurgical patients developed a suspected ADR, with three patients experiencing multiple reactions. Other adult ICU patients developed ADRs at a comparable rate (9%, P > 0.05). Overall, neurosurgery patients accounted for 12% of all spontaneously reported ADRs. Preventable reactions were observed in 43 (13%) cases, and treatment was required for 76%. The majority (96%) of ADRs resolved or improved at the time of the ADR report. Nausea, pruritus, thrombocytopenia, and vomiting were most frequently noted. Therapies most often associated with reported events were analgesics, antipyretics, antibiotics, anticonvulsants, and histamine H2 antagonists. The relationship between central nervous system disease and adverse event occurrence is not clear. CONCLUSION: Despite the narrow scope of drug regimens in neurosurgical ICU patients, ADRs can complicate therapy in this critically ill population. Neurosurgical ICU patients seem to experience ADRs no more frequently than their adult ICU counterparts.
Stability of Thermoelectromagnetic Convection

The role of thermoelectromagnetic convection (TEMC) on the stability of a range of flows is investigated. Here we discuss the general features of TEMC, and describe experiments in which this effect is thought to have significance. The general formulation for TEMC at a solid-liquid interface is presented. Initial results are benchmarked with existing analytical and numerical solutions.Copyright © 2006 by ASME
The effect of fire on a small mammal community

Information is provided on the survival of a small mammal community monitored before and after fire passed through part of a grassland study area. Praomys natalensis and Lem- niscomys griselda populations were not affected by the fire itself. Possible survival strategies are discussed. All the L. griselda survivors were retrapped in the unburnt grassland after the fire. Some of the P. natalensis survivors were re- trapped in unburnt grassland whilst some remained in the burnt area. Post-burn mortality of the latter group was high. Factors involved in post-burn habitat selection are discussed.
342 PHYSICIAN INTERACTION STYLE AND HEMOGLOBIN A1C: DOES IT MAKE A DIFFERENCE?

Purpose This study was conducted to evaluate if the style of physician interaction during primary care visits was associated with control of glucose, blood pressure, and lipids in patients with type 2 diabetes. Methods This was a cross-sectional observational study conducted in 20 primary care clinics. Thirty consecutive adult patients presenting with a diagnosis of type 2 diabetes were enrolled in each clinic. Of these patients, the first 8-10 physician visits in each clinic were audio-recorded. One investigator coded the predominant activity for each 15-second interval of all visits using the Davis Observation Code (DOC). Physician practice interaction style was calculated by taking the mean value of each code for each physician across all visits. In order to develop a more stable estimate of physician interaction style, only physicians with three or more visits were used for analysis. Patients9 charts were abstracted to collect data on demographics and most recent values of HbA1c, blood pressure (BP), and LDL cholesterol. Multilevel modeling was used to account for the nesting of patients within physician. Results A total of 188 physician-patient encounters to 43 different physicians were recorded, 162 in English, 26 in Spanish. Of these physicians, 24 had three or more patient visits recorded and these were used for analysis (total of 137 visits). Multilevel analysis revealed that time spent on health education was inversely associated with HbA1c values (p = .036). Each minute the physician discussed health education was associated with a 0.24 decrease in the HbA1c. Time spent on health education was not associated with LDL cholesterol (p = .2) or blood pressure (p = .1). Time spent on evaluation and feedback of laboratory and study results was inversely associated with HbA1c (p = .001), LDL cholesterol (p = .017), and blood pressure (p = .015). Conclusions Patients seen by primary care physicians who spend more time on health education during the visit have better control of their glucose. Future research is needed to see if evaluation and feedback of laboratory and study results encourage patient participation in their care leading to improved control of blood pressure, lipids, and glucose.
Progress on treatment of osteoporosis with recombinant human parathyroid hormones

The progress on treatment of osteoporosis with recombinant human parathyroid hormones was reviewed in this paper,mainly on pharmacology,toxicology,and clinical pharmacology of recombinant human parathyroid hormone(1-34)and recombinant human parathyroid hormone(1-84)in order to provide refer- ences for the research and development of parathyroid hormone.
Efficiency of coupling between the beta adrenergic receptor and adenylate cyclase.

Under experimental conditions in which the coupling between the beta adrenergic receptor and adenylate cyclase was altered in S49 lymphoma cell membranes, changes were observed in the ratio of KD to Kact for beta adrenergic agonists and in the effects of guanine nucleotide on the binding of agonists. The KD for isoproterenol binding to the beta adrenergic receptor was greater than the Kact for enzyme activation, despite the use of a simultaneous assay technique. The ratio of KD to Kact was decreased under conditions of less efficient coupling, such as in the presence of filipin or stimulation by partial agonists. However, cholera toxin treatment, which improves coupling efficiency, increased the ratio of KD to Kact for both full and partial agonists. The ability of guanine nucleotides to decrease the affinity of the beta adrenergic receptor for agonists was lost when membranes were treated with filipin or 10 mM N-ethylmaleimide. However, 1 mM N-ethylmaleimide, a concentration sufficient to inhibit over 90% of adenylate cyclase activity in this membrane preparation, was ineffective in altering the binding characteristics. The effect of guanine nucleotide can thus be observed in the absence of a functional catalytic unit of adenylate cyclase.
On simulating the high-resolution radar image of a wind turbine

The high-resolution inverse synthetic aperture radar (ISAR) image of a utility-class wind turbine is simulated. Physical optics (PO) with shadowing is used to generate the broadband backscattered fields over a complete turbine revolution. The backscattering phenomenology is examined in the spectrogram, sinogram, and ISAR image domains. The resulting ISAR image provides additional insights into the blade scattering phenomenology that are not as apparent in either the spectrogram or sinogram alone.
Continuous quality improvement (CQI): solution to QA shortcomings?

In the previous decade, quality assurance gained prominence in an effort to ensure optimal medical care. Some experts, as Avedis Donabedian, M.D.--a leading scholar in the area of quality assessment--characterized its dimensions as falling into three categories: structure (inputs), process and outcome. Paul Ellwood, M.D., in 1988, further promoted the latter by introducing an "outcomes management" system. Now Berwick, James, O'Leary and others advocate the incorporation of certain industrial insights advocated by Deming, Juran and others to improve traditional QA Methods and develop a process of Continuous Quality Improvement (CQI). The goal is to have patients (and other customers) better served.
Cell volume analysis of gramicidin-treated eccrine clear cells to study regulation of Cl channels.

Using voltage-current-clamp methods, we determined membrane potentials, relative ionic permeability, and membrane conductance of gramicidin (GC)-treated freshly dissociated eccrine clear cells. GC depolarized the membrane potential by 58 mV, increased the membrane conductance progressively over the time of exposure (mean of 1.7 times at 60 s and 4.6 times at 3 min), and increased the Na conductance of the membrane (from near 0 in control to 0.75 nS after GC). Image analysis coupled with GC treatment was then employed to study the regulation of Cl channels based on the premise that cell swelling was due to activation of Cl channels. Cell swelling was stimulated by methacholine (MCh, 3 microM) in the presence of GC. GC+MCh-induced cell swelling was inhibited by atropine, low extracellular Ca ([Ca]o
Eine einfache neue Bypaßtechnik für die chirurgische Behandlung der traumatischen Aortenruptur

Die operative Versorgung einer traumatischen Aortenruptur ist nur nach vorubergehendem Abklemmen des Blutstromes distal der Arteria carotis communis sinistra moglich. An dieser Stelle fuhrt aber die Aortenabklemmung infolge akuter maximaler Widerstandserhohung und Blutstauung im Herzen in etwa 2 bis 3 Minuten zum Lungenodem und Herzstillstand. Diese gefahrlichen Folgen lassen sich bekanntlich durch einen intravasalen Shunt (Einfuhren eines Flanschs in das Gefasrohr) oder durch Anwendung einer extracorporalen Pumpe verhindern. Das Einfuhren eines intravasalen Shunts durfte aber bei der traumatischen Aortenruptur wegen des ausgedehnten mediastinalen Haematoms technisch recht schwierig sein und auserdem droht bei der Darstellung der Aorta jederzeit die Gefahr der freien Ruptur und Verblutung. Dem von COOLEY entwickelten Verfahren mit Entnahme des arterialisierten Blutes aus dem linken Vorhof mit einer DE BAKEY-Pumpe und Beinfusion durch die Arteria femoralis wird heute allgemein wegen seiner technischen Einfachheit der Vorzug gegeben. Dieser Links-Links-Bypass kann aber nur an grosen Kliniken durchgefuhrt werden, die uber eine entsprechende Ausrustung mit extracorporalen Pumpen verfugen und er erfordert weiterhin die Heparinisierung des Verletzten, die wegen zusatzlicher Nebenverletzungen (Schadel-Hirntrauma, stumpfes Bauchtrauma) zu diffusen Blutungen fuhren kann.
Searching for Silver Linings: Is Perceived Medical Discrimination Weaker in Segregated Areas?

An ongoing obstacle in dealing with minority health disparities is discriminatory behavior from healthcare practitioners, also known as medical discrimination. It is not clear, however, if the effects of medical discriminations onto health are constant across space. For example, there is evidence to suspect minorities in racially segregated neighborhoods suffer less from discrimination compared to those living elsewhere. To determine the presence of spatial heterogeneity underlying medical discrimination, we implement logistic geographically weighted regression (GWR) using individual data in the city of Philadelphia from the 2006 and 2008 Public Health Management Corporation’s Southeastern Pennsylvania Household Health Surveys. Evaluating the potential role residential segregation has in offsetting medical discrimination, we compare the GWR results to tract data from the 2005–2009 American Community Survey. Through this comparison, we find that the effects of medical discrimination on self-rated health are weaker in magnitude in areas that are mostly minority. However, evidence of direct health benefits for minorities in segregated communities is inconclusive. Thus, while we cannot say living in segregated neighborhoods leads to better minority health, the sting of medical discrimination can be weaker in these places. These results emphasize the importance of local variation, even within a city like Philadelphia, challenging the aspatial one-model-fits-all approach normally found in population studies.
Modeling a virtual enterprise simulation game

A manufacturing organization is a complex entity operating in in competitive market, utilizing its structure, management and operations to achieve its objectives. The purpose of this research is to model the essential components of a firm and their interrelationships to build a strategy simulation exercise that models an airplane manufacturer. The user will determine how to invest money, schedule production, set prices and manage resources to meet the organization's objectives. The system will allow competition between multiple users or simulate competing organizations.
Can GaAs ICs achieve Si VLSI reliability

The authors compare and contrast the failure modes in GaAs and Si IC technology, assess the demonstrated levels of reliability achieved in these technologies, and compare the distinct challenges facing the GaAs and Si communities as they attempt to quality chips of increasing complexity. It is concluded that there appears to be no fundamental property of GaAs limiting its reliability to be less than that offered by Si technology for present or future technology levels. Each technology has thus far met the challenge of increasing the device and interconnect component lifetimes to maintain or improve overall chip reliability. The future reliability challenges for both technologies will be in heat management and in the interconnect and contacts, which may be slightly more difficult for GaAs; the thermal conductivity of GaAs is only approximately 1/4 that of Si and the ohmic contacts of GaAs have traditionally been an area of concern. The future reliability challenges of the gate oxide in Si technology will require a continued reduction in supply voltage and continued large effort to improve gate insulator quality and device design. >
Sensory Aspects of Trail-Following Behaviors in the Asian Longhorned Beetle, Anoplophora glabripennis

Anoplophora glabripennis has a complex suite of mate-finding behaviors, the functions of which are not entirely understood. These behaviors are elicited by a number of factors, including visual and chemical cues. Chemical cues include a male-produced volatile semiochemical acting as a long-range sex pheromone, a female-produced cuticular hydrocarbon blend serving as a sex-identification contact pheromone, and a recently identified female-produced trail sex pheromone that is followed by mate-seeking males. However, the sensory appendages and sensilla on these appendages used to detect the trail sex pheromone are unknown. We evaluated the ability of virgin male A. glabripennis to follow a sex pheromone trail after removal of the terminal four antennal segments and/or the maxillary and labial palps using a two-choice behavioral bioassay. We also tested the ability of males to follow the trail sex pheromone using volatile pheromone cues only, without physical contact with the pheromone. Results indicate that the palps are primarily responsible for sensing the pheromone, with males lacking palps unable to respond behaviorally to the trail sex pheromone. Under the conditions of this study, males could not follow the sex pheromone trail without direct contact, suggesting that olfaction may not be involved in detection of this pheromone. However, we did not determine to what degree the trail pheromone chemicals can volatilize under our experimental conditions. This work is important in elucidating the behaviors and sensory structures involved in mate-finding by this species on host trees, and these studies may help determine whether the trail sex pheromone has applications for monitoring and management.
A unique combination of micronutrients rejuvenates cognitive performance in aged mice

It is widely believed that diet can influence the onset and severity of cognitive aging, but the optimal combination of micronutrients and molecular and cellular mechanisms remain elusive. The purpose of this study was to compare the effects of eight distinct diets, consisting of various concentrations of selected micronutrients, on learning and memory as well as markers of neuronal plasticity, and metabolic and neuro-immune status of the aged hippocampus. Eighteen-month-old male and female C57BL/6J mice were fed the diets for 16 weeks, followed by learning and memory trials on the active avoidance task. Number of immature neurons were measured by immunohistochemical detection of doublecortin (DCX+) in the granule layer of the dentate gyrus. Amount of mitochondrial DNA (mtDNA) and gene expression of molecular markers of mitochondrial biogenesis (Ppargc1α, Sirt1, Tfam), and neuroinflammation (IL-10, Alox15, Ptgs2, IL-1β, IL-6 and Tnf) were assessed by quantitative real time polymerase chain reaction (qRT-PCR) of hippocampal samples. Tissue levels of selected micronutrients and a number of metabolites were measured by liquid chromatography-mass spectrometry. The diet supplemented with RRR d-alpha tocopheryl acetate, citicholine, 5-methyltetrahydrofolic acid, quercetin and the n-3 fatty acid phosphatidylserine-docosahexaenoic acid, improved performance on the active avoidance learning and memory task compared to all the other less-complex diets. This diet also increased IL-10 expression and attenuated the age-related change in mtDNA content in the hippocampus without affecting metabolite levels. Results suggest cognitive benefits of wholesome diets are partially mediated through combined antioxidant and anti-inflammatory activities of optimized mixtures of micronutrients.
VEGFA activates an epigenetic pathway upregulating ovarian cancer‐initiating cells

The angiogenic factor, VEGFA, is a therapeutic target in ovarian cancer (OVCA). VEGFA can also stimulate stem‐like cells in certain cancers, but mechanisms thereof are poorly understood. Here, we show that VEGFA mediates stem cell actions in primary human OVCA culture and OVCA lines via VEGFR2‐dependent Src activation to upregulate Bmi1, tumor spheres, and ALDH1 activity. The VEGFA‐mediated increase in spheres was abrogated by Src inhibition or SRC knockdown. VEGFA stimulated sphere formation only in the ALDH1+ subpopulation and increased OVCA‐initiating cells and tumor formation in vivo through Bmi1. In contrast to its action in hemopoietic malignancies, DNA methyl transferase 3A (DNMT3A) appears to play a pro‐oncogenic role in ovarian cancer. VEGFA‐driven Src increased DNMT3A leading to miR‐128‐2 methylation and upregulation of Bmi1 to increase stem‐like cells. SRC knockdown was rescued by antagomir to miR‐128. DNMT3A knockdown prevented VEGFA‐driven miR‐128‐2 loss, and the increase in Bmi1 and tumor spheres. Analysis of over 1,300 primary human OVCAs revealed an aggressive subset in which high VEGFA is associated with miR‐128‐2 loss. Thus, VEGFA stimulates OVCA stem‐like cells through Src‐DNMT3A‐driven miR‐128‐2 methylation and Bmi1 upregulation. ![][1] VEGFA is not only a key mediator of angiogenesis during tumor progression, but can also act to expand the population of ovarian cancer‐initiating cells with stem‐like properties. [1]: /embed/graphic-1.gif
Passive Institutional Ownership, R2 Trends, and Price Informativeness

A distinctive trend in the capital markets over the past two decades is the rise in equity ownership of passive financial institutions. We propose that this rise has a negative effect on price informativeness. By not trading around firm-specific news, passive investors reduce the firm-specific component of total volatility and increase stock correlations. Consistent with this hypothesis, we find that the growth in passive institutional ownership is robustly associated with the growth in market model R2s of individual stocks since the early 1990s. Additionally, we find a negative relation between passive ownership and earnings predictability, an informativeness proxy.
Are the new EPA regulations concerning intentional exposure studies involving children overprotective

On February 6, zoo6, the Environmental Protection Agency (EPA) adopted new regulations regarding research with human subjects, after an eight-year battle among environmental groups and pesticide companies concerning human pesticide testing.1 The new regulations: * extend the ethical rules found in 45 CFR 46, Subpart A ("Basic HHS Policy for Protection of Human Research Subjects," also known as the Common Rule) to all EPA research, including studies submitted to the EPA by private companies (i.e., third parties) for regulatory purposes; * establish a Human Studies Review Board to review research sponsored by the EPA or by third parties and to provide the EPA with advice concerning its human protection program; * provide extra protections for pregnant women or children participating in observational research; * prevent the EPA from accepting data submitted by third parties for regulatory purposes that derived from exposing children, pregnant or nursing women, or fetuses to pesticides; and * prohibit the EPA from conducting or funding intentional exposure research involving children, pregnant women, or fetuses. Political interests had a major impact on the EPA's decision-making. In the late 199os, pesticide companies began conducting experiments with human subjects to generate pesticide safety data to submit to the EPA for regulatory purposes. Private companies sued the EPA when it refused to accept these data. In 2003, a federal court sided with the plaintiffs and ordered the EPA to develop regulations pertaining to human data submitted by private companies for regulatory purposes. Environmental groups opposed the EPA's decision to develop new regulations and argued that the EPA should never accept pesticide data from human experiments.
Anxiety: a Primer for the Pediatrician

This paper focuses on the assessment and treatment of pediatric anxiety disorders targeted at pediatricians. It reviews the prevalence, role of the pediatrician in differentiating anxiety disorders from age-appropriate fears or normative responses to stressors, use of assessment tools, evidence-based treatment, and provides psychoeducation resources for children, parents, and clinicians. It reviews considerations for treatment modality and evidence for use of cognitive-behavioral therapy and psychopharmacology. First-line treatment of mild severity anxiety disorders is guided by well-established evidence and supported by randomized controlled trials that includes psychoeducation and psychotherapy, particularly cognitive-behavioral therapy (CBT). When anxiety is moderate to severe in intensity or impairment, initiation of psychopharmacology is considered in combination with CBT. Selective serotonin reuptake inhibitors (SSRIs) have the most evidence in randomized double-blind placebo-controlled trials and are recommended as first line for anxiety disorders, starting with low doses. It is important to discuss and monitor for potential adverse effects. Complementary and alternative medical (CAM) therapies are often used by youth, though there is limited evidence for benefit in children and adolescents with anxiety disorders, and potential risks need to be considered. Pediatric anxiety disorders are among the most common psychiatric disorders in children and adolescents and can result in significant impairment and morbidity. Pediatricians have an important role in identifying and facilitating treatment for youth with anxiety disorders, and CBT and psychopharmacology, particularly SSRIs, have the most evidence. However, accessing CBT for many families remains challenging. Pediatricians can provide psychoeducation and resources as a first step and initiate medications if indicated. Further research into integration of mental healthcare in pediatric settings could increase access to CBT and decrease morbidity. In addition, more randomized controlled trials and comparison studies for medications, CAM therapies, and combination treatments for pediatric anxiety disorders are needed.
Direct-to-adolescent text messaging for vaccine reminders: What will parents permit?

BACKGROUND Direct-to-adolescent text messaging may be a consideration for vaccine reminders, including human papilloma virus (HPV), but no studies have explored the minimum age at which parents would allow adolescents to receive a text message. METHODS We distributed a survey to parents of 10-17 year olds during any office visit in two practice based research networks in South Carolina and Oklahoma. We asked about parental preference for receiving vaccine reminders for their adolescent, whether they would allow the healthcare provider to directly message their adolescent, and if so, what would be the acceptable minimum age. RESULTS In 546 surveys from 11 practices, parents of females were more supportive of direct-to-teen text message reminders than were parents of males, (75% v. 60%, p < .001). The median age at which parents would allow direct text messages from physicians' offices was 14 in females compared to 15 in males, p = .049. We found a correlation between the child's age and the youngest age at which parents would allow a direct text message. Of the parents who permitted a text message directly to their adolescent, most reported an allowable age higher than their adolescent's current age until the age of 15. CONCLUSION Our study suggests that direct-to-adolescent text messaging would be allowed by parents for older adolescents. This supports an intervention aimed at older adolescents, such as for receipt of MCV4 dose #2, delayed HPV vaccine series completion and annual influenza vaccination.
Cerebral arteriolar dilation to hypoxia: role of prostanoids

Experiments addressed the hypothesis that dilator prostanoids contribute to maintenance of low cerebral microvascular tone during hypoxia in the newborn. Anesthetized newborn pigs equipped with closed cranial windows were used to measure responses of pial arterioles (approximately 60 microns) to treatments. Hypoxia (Pao2 approximately equal to 25 mmHg) caused dilation of pial arterioles (approximately 50% increase in diameter). Hypoxia (5 min) caused an increase in cortical cerebrospinal fluid 6-ketoprostaglandin F1 alpha concentration from 907 +/- 171 (normoxia) to 1,408 +/- 213 pg/ml (hypoxia). Pretreatment with indomethacin (5 mg/kg) did not affect pial arteriolar dilation to hypoxia. Conversely, indomethacin treatment during hypoxia caused a rapid decrease in arteriolar diameter to nearly the normoxia diameter within 3 min, returning to the original hypoxia diameter by 10 min. Ibuprofen treatment (30 mg/kg) had no effect on pial arteriolar diameter during normoxia or hypoxia, and pretreatment did not alter dilation to hypoxia. However, pretreatment with ibuprofen abolished the constrictor effect of indomethacin given during hypoxia. These data suggest that the primary mechanism by which hypoxia produces cerebral vasodilation does not involve prostanoids, but prostanoids can contribute to cerebral vasodilation in response to hypoxia.
Preserving Principal: Programming for Faculty Health and Well-Being

Programs in faculty health have elements that vary in scope and depth. Some elements focus on services for individuals, some on education for the whole faculty. Some focus on interventions for the impaired, others on prevention of impairment. This chapter describes these aspects of programs and their various formats. As a resource for new or expanding efforts, the review is meant to be sug- gestive rather than prescriptive and to support imagination and creativity available in every setting.
Majority Rule and the Wisdom of Crowds: the Task-Specificity of Majority Rule as aPredictive Tool

This paper argues that majority rule not just a fair way to aggregate and adjudicate between diverse preferences, but also, and perhaps primarily, a predictive tool tapping the famous “wisdom of crowds.” The assumption is here that the crowd is wise not primarily because it is numerous but because of the cognitive diversity likely correlated with the presence of many people. The epistemic case for majority rule is built on Scott Page’s model of cognitive diversity (Page 2007) rather than on either the Condorcet Jury Theorem or the Miracle of Aggregation. On this view, the virtue of majority rule is to turn diverse individual judgments into accurate collective predictions. The paper further argues that this task-specificity of majority rule makes it a useful complement rather than a rival to deliberation, whose epistemic properties are more suited to the multi-facetted task of problem-solving. On this view, the virtue of majority rule is to turn diverse individual judgments into accurate collective predictions. The paper further argues that this task-specificity of majority rule makes it a useful complement rather than a rival to deliberation, whose epistemic properties are more suited to the multi-facetted task of problem-solving.
Structural Basis for Rare Earth Element Recognition by Methylobacterium extorquens Lanmodulin.

Lanmodulin (LanM) is a high-affinity lanthanide (Ln)-binding protein recently identified in Methylobacterium extorquens, a bacterium that requires Lns for the function of at least two enzymes. LanM possesses four EF-hands, metal coordination motifs generally associated with CaII binding, but it undergoes a metal-dependent conformational change with a 100 million-fold selectivity for LnIIIs and YIII over CaII. Here we present the nuclear magnetic resonance solution structure of LanM complexed with YIII. This structure reveals that LanM features an unusual fusion of adjacent EF-hands, resulting in a compact fold to the best of our knowledge unique among EF-hand-containing proteins. It also supports the importance of an additional carboxylate ligand in contributing to the protein’s picomolar affinity for LnIIIs, and it suggests a role of unusual Ni+1–H···Ni hydrogen bonds, in which LanM’s unique EF-hand proline residues are engaged, in selective LnIII recognition. This work sets the stage for a detailed mech...
The Depth of Sternal Fracture Displacement Is Not Associated With Blunt Cardiac Injury.

Abstract Background: Little evidence exist associating displaced sternal fractures with blunt cardiac injury (BCI), especially regarding the depth and severity of sternal fracture displacement and risk of BCI. The purpose of this study was to quantify sternal fracture severity by the degree of displacement and to evaluate the association of fracture severity with BCI. Materials and methods A single institution retrospective review was performed from 2011 to 2014. All adult patients with sternal fracture were identified from the trauma registry, and sternal fracture displacement was quantified as mild (>0 mm, Results Two hundred thirty-five patients with sternal fractures were included in the study. Forty-five percentage of patients suffered a displaced fracture, and 42.6% were diagnosed with BCI. There was no difference in mean fracture displacement when compared to patients without BCI (2.4 versus 1.6 mm, P = 0.07). There was no significant increase in BCI with sternal fracture displacement when compared to patients with nondisplaced fractures (44.3% versus 41.1%, P = 0.62). Neither fracture displacement (OR 1.10, CI 95% 0.65-1.88) nor severe displacement (OR 2.34, CI 95% 0.64-8.54) was associated with significantly increased risk of BCI. Conclusions There is no significant association between the depth of sternal fracture displacement and BCI. Further evaluation and management for BCI should be reserved in the absence of additional symptoms or findings.