cssi/SciSciGPT-SciSciNet huggingface dataset:
Metformin‐mediated increase in DICER1 regulates microRNA expression and cellular senescence

Metformin, an oral hypoglycemic agent, has been used for decades to treat type 2 diabetes mellitus. Recent studies indicate that mice treated with metformin live longer and have fewer manifestations of age-related chronic disease. However, the molecular mechanisms underlying this phenotype are unknown. Here, we show that metformin treatment increases the levels of the microRNA-processing protein DICER1 in mice and in humans with diabetes mellitus. Our results indicate that metformin upregulates DICER1 through a post-transcriptional mechanism involving the RNA-binding protein AUF1. Treatment with metformin altered the subcellular localization of AUF1, disrupting its interaction with DICER1 mRNA and rendering DICER1 mRNA stable, allowing DICER1 to accumulate. Consistent with the role of DICER1 in the biogenesis of microRNAs, we found differential patterns of microRNA expression in mice treated with metformin or caloric restriction, two proven life-extending interventions. Interestingly, several microRNAs previously associated with senescence and aging, including miR-20a, miR-34a, miR-130a, miR-106b, miR-125, and let-7c, were found elevated. In agreement with these findings, treatment with metformin decreased cellular senescence in several senescence models in a DICER1-dependent manner. Metformin lowered p16 and p21 protein levels and the abundance of inflammatory cytokines and oncogenes that are hallmarks of the senescence-associated secretory phenotype (SASP). These data lead us to hypothesize that changes in DICER1 levels may be important for organismal aging and to propose that interventions that upregulate DICER1 expression (e.g., metformin) may offer new pharmacotherapeutic approaches for age-related disease.
Preparation of Cross-Sectional TEM Samples of PbTe and CdxPb1-x Te on BaF2

Epitaxial PbTe and CdxPb1-xTe films have been grown on single crystal (111) BaF2 by low energy bias sputtering, and have been analyzed by transmission electron microscopy (TEM) and transmission electron diffraction (TED). Preparation of suitable cross-sectional TEM samples was made difficult by the tendency of the substrate to cleave apart during dimpling, and by the epoxy forming bridges across the sample during atom milling. Suitable preparation techniques were developed employing back-polishing the BaF2 substrates to <0.2 mm thickness, using a suitable epoxy, and shielding the argon atom beam during milling to prevent milling parallel to the surface. In cases where an epoxy bridge did form across the sample, the bridge was broken manually or by atom milling, depending upon the area of sample which was being investigated. These techniques are applicable to other materials which produce similar problems during TEM sample preparation.
Adaptation to Flooding in Urban Areas An Economic Primer

New Orleans and Bangkok are vivid examples of major urban areas recently affected by massive inundations of floodwaters. The pending effects of climate change may exacerbate this problem; yet, local decision makers lack a clear and consistent framework for analyzing the costs and benefits of alternative modes of adaptation. This article offers a primer on the economic analysis of three distinct modes of adaptation, with a view to assist planners in determining the best course of action for their respective cities. These responses include (a) physical modifications to the environment through adaptive topography and adaptive infrastructure, (b) modify land uses to locate or relocate vulnerable populations away from flood-prone areas, and (c) concentrate more efforts on clean up and recovery after the fact. Our analysis is designed to help planners determine which of these three adaptive responses to urban flooding are best suited to their own local circumstances.
Study on Implementation of Performance Evaluation of ERP Logistics Information System of Steel Enterprises in China

In this paper,we established the ERP implementation performance evaluation index system and used the AHP to determine the weights of the index,on the basis of which we used the multi-level fuzzy comprehensive evaluation method to analyze empirically the implementation performance of the ERP logistics information system of a certain steel-making enterprise in Hunan.
STUDY OF INCENTIVE MECHANISM IN PROCUREMENT OF GOVERNMENT OF PUBLIC GOODS

Based on the procurement economy of government,it analysed the reason of efficiency loss in procurement of government.It established the most optimization incentive mechanism on government procurement through combining the practice of government procurement of primary and middle school′s teaching materials and leading Laffont-Tirole′s anti-choice and moral risk model,explored the relationship between the agent′s risk attitude and incentive effects,and concluded as follows.Because of indirect agent mechanism,it exists efficiency loss in our current model of government procurement,and the incentive effects are highly related to the agent′s risk attitude.The more the agent hates risk, the lower the incentive effects will be.The opposite it also right.
Surgery for Sphenoid Sinus Disease

Sphenoid sinus surgery is an important component of the management paradigm of inflammatory sinus disease as well as integral to the approaches to the sellar and parasellar regions for skull base lesions. Given this dual perspective, the surgeon must carefully appraise the surgical goals in the setting of the patient’s anatomy and pathology. Successful surgery requires these considerations, in addition to knowledge of the variable anatomy and anatomic relationships in the region. While complications can occur in any surgical procedure, complications in this delicate region can be devastating and are best managed with prevention. If encountered, rapid identification and initiation of further diagnostic and/or therapeutic measures is critical. This chapter presents the various surgical techniques, considerations, and anatomic relationships that are necessary for the endoscopic sinus and skull base surgeon to master surgery within this critical region. Multiple different approaches for successfully finding the sphenoid ostium are also discussed. Understanding these key anatomic features allows surgical management of an array of extracranial and intracranial pathology. Careful preoperative clinical and radiographic examinations significantly aid the surgical approach and allow the surgeon to be proactive rather than reactive when addressing the area.
Advanced Imaging, Teleproctoring, and Off-Site Surgery

Since its introduction into clinical practice in 2000, robotic-assisted surgery has become rapidly adopted worldwide. The future of robotic surgery holds much promise for ongoing technological advancement. In particular, the robotic platform allows for development into other areas of the computer integrated surgery spectrum, from introducing imaging data into the operating room console to expanding surgical expertise outside the operating room to remote areas. This chapter will discuss the future of robotic surgery, focusing on the integration of advanced imaging systems, teleproctoring, and telesurgery.
Risk Factors for Thrombosis and the Beneficial Effect of Aspirin in Patients with Antiphospholipid Antibodies (aPL).

Introduction: Some subjects with aPL remain healthy while others develop thrombosis. We hypothesize that coexisting risk factors (inherited or acquired) may influence the incidence and rate of arterial and venous thrombosis in these individuals. Methods: After institutional review aboard approval, subjects with two positive aPL tests (lupus anticoagulant, IgG or IgM anticardiolipin antibodies) at least 3 weeks apart were identified and invited to participate in a one-time study visit conducted at three medical centers. Consenting subjects were interviewed and/or their medical chart reviewed for definitive evidence of thrombotic events and documentation of risk (inherited and acquired) factors thought to determine outcome (thrombosis) in aPL. Inherited risk factor evaluation included testing for Factor V Leiden (FVL), prothrombin gene (3′PTG) and methyltetrahydrofolate reductase (MTHFR) gene polymorphisms. Acquired risk factors evaluated included estrogen therapy, hypertension, hyperlipidemia, tobacco use, and diabetes mellitus. In addition, subjects were also queried regarding the use of daily aspirin, non-steroidal anti-inflammatory agents, and/or hydroxychloroquine, currently and at the time of thrombosis; subjects without thrombosis were contacted one year later to document if any thrombotic events had occurred in the interim. Statistical analysis included the chi-square test of significance, and summary odds ratios (OR) for venous and arterial thrombosis calculated using the Mantel-Haenszel method. Results: 222 patients (157 females, 65 males) with aPL were included in our multi-center study. 83/222 (37.4%) patients with aPL had venous thromboembolic disease (VTE), and 90/222 (40.5%) subjects had documented evidence of arterial thrombosis. In patients with aPL and VTE, the presence of either FVL or 3′PTG polymorphism was associated with a higher risk of thrombosis (OR: 2.88, 95% CI: 1.01–8.24; p Conclusions: These results confirm our earlier finding that inherited thrombophilic states (FVL and 3′PTG) confer an additional risk of VTE in patients with aPL, and that hypertension, hyperlipidemia, and tobacco use appear to be risk factors for arterial thrombosis. In addition, aspirin use appears to protect from both venous and arterial thrombosis in patients with aPL. Awaiting future controlled trials aimed at evaluating the independent beneficial effect of aspirin, our results suggest that patients with aPL should be encouraged to take a daily aspirin, and adhere to optimal antihypertensive therapy, smoking cessation, and cholesterol lowering measures. Such disease modifying strategies may decrease their incidence of venous and arterial thrombotic events.
Emerging photobiomodulation therapeutics

The current status of photobiomodulation therapy will be presented. The importance of device parameters, wavelength selection related to the target tissue, photon dose related to cellular mechanisms, and opportunities for collaboration will be discussed.
Pittsburgh myth, Paris reality.

When announcing his decision to withdraw the United States from the Paris Agreement, President Trump reminded the world that, “I was elected to represent the citizens of Pittsburgh, not Paris.” In doing so, he repeated a tired trope: that Pittsburgh is a rusty urban relic—a manufacturing city of steel that has fallen on hard times, held back by unfair global competition and onerous environmental regulation. But such a nostalgic version of Pittsburgh, and of many other communities across the country, is a myth. If the president truly wants to represent the interests of Americans, he would learn from the real histories of these regions and promote economic and environmental progress through research, education, and innovation.
Infection: a Cause of and Cure for Cancer

This article provides a brief overview of the role that infections play in cancer emergence and cancer treatment. A select number of pathogens have been reported to increase the incidence of specific cancers (directly through altering gene expression or indirectly through inducing chronic inflammation). These have been referred to as oncogenic pathogens. Conversely, a subset of pathogens has been demonstrated to preferentially cause lysis of tumor cells, leading to tumor regression and improved anti-tumor immunity. These have been termed oncolytic pathogens. However, the contribution of non-oncogenic, non-oncolytic pathogens to both tumor growth and regression is likewise being increasingly recognized. Pathogens have both the ability to cause and cure cancer. However, the mechanisms underlying these pathogen-mediated outcomes are not fully understood. With the recent emergence of interest in the immunotherapy of cancer, it is important that future studies focus specifically on preventing the negative effects of oncogenic infections, deconstructing the positive role of oncolytic pathogens, and finally providing insight into the dual roles of non-oncolytic, non-oncogenic pathogens so that anti-pathogen immune responses can be harnessed as a transformative means to treat cancer.
MicroRNAs and miRceptors: a new mechanism of action for intercellular communication

MicroRNAs (miRs) are small non-coding RNAs (ncRNAs) that control the expression of target genes by modulating (usually inhibiting) their translation into proteins. This 'traditional' mechanism of action of miRs has been recently challenged by new discoveries pointing towards a role of miRs as 'hormones', capable of binding to proteic receptors (miRceptors) and triggering their downstream signalling pathways. These findings harbour particular significance within the tumour microenvironment (TME), defined as the variety of non-cancerous cells surrounding cancer cells, but are relevant also for other diseases. In recent years it has become clearer that the TME does not passively assist the growth of cancer cells but contributes to its biology. Some of the mediators of the intercellular communication between cancer cells and TME are miRs shuttled within exosomes, a subtype of cellular released extracellular vesicles. This article will highlight the most recent findings on the biological implications of miR-miRceptor interactions for the biology of the TME and other diseases, and will provide some perspectives on the future development of this fascinating research.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.
Functional Outcomes of Symptomatic Implant Removal Following Ankle Fracture Open Reduction and Internal Fixation.

Background:Orthopedic implant removal following open reduction internal fixation of a fracture is a common procedure, especially in the foot and ankle. The purpose of this study was to evaluate fun...
The Adaptive In Combo Strategy

In silico techniques for absorption, distribution, metabolism, and excretion (ADME) prediction invariably fail in their use when new compounds are presented that depart the compound space of the training set. The proposed adaptive modeling technique builds models with continuous training to cover the compound space addressed by new syntheses. This continuous combination of screening, training, and prediction may provide the solution to the failure of models and meet the need to reduce the total number of compounds screened.
Toxicological Research and Related Programs under Superfund

We must be one with our environment. With industrialization and modern agriculture have come great benefits, but with these advances also have come burdens on the fragile environment that sustains us. We derive great economic gain from the industrial and agricultural products that we in industrialized countries have come to expect. Products that make our lives easier, safer, and longer: automobiles, convenience foods, packaged products, pharmaceuticals and such. But these commercial successes and products of industrialization have an environmental consequence--the dimensions of which are still being assessed. One of the environmental consequences has been the dumping of unwanted, sometimes hazardous, waste into the environment. In many instances this has resulted in contamination of soil, ground water, air, and the human food chain. What gets into these media has the potential for getting into people. And that has implications for public health.
Copper-Catalyzed C(sp 3 )-H Amidation: Sterically Driven Primary and Secondary C-H Site-Selectivity.

Undirected C(sp3 )-H functionalization reactions often follow site-selectivity patterns that mirror the corresponding C-H bond dissociation energies (BDEs). This often results in the functionalization of weaker tertiary C-H bonds in the presence of stronger secondary and primary bonds. An important, contemporary challenge is the development of catalyst systems capable of selectively functionalizing stronger primary and secondary C-H bonds over tertiary and benzylic C-H sites. Herein, we report a Cu catalyst that exhibits a high degree of primary and secondary over tertiary C-H bond selectivity in the amidation of linear and cyclic hydrocarbons with aroyl azides ArC(O)N3 . Mechanistic and DFT studies indicate that C-H amidation involves H-atom abstraction from R-H substrates by nitrene intermediates [Cu](κ2 -N,O-NC(O)Ar) to provide carbon-based radicals R. and copper(II)amide intermediates [CuII ]-NHC(O)Ar that subsequently capture radicals R. to form products R-NHC(O)Ar. These studies reveal important catalyst features required to achieve primary and secondary C-H amidation selectivity in the absence of directing groups.
International Law as a Wedge Between Legal Systems

The big question that this volume addresses is whether international law can bridge gaps between the world’s principal legal systems. There are many pathways that such bridging might take, and others explore them in this book. What I want to do is discuss the ways that international law might serve as an obstacle to convergence between the common law and civil law. This essay draws on a larger scholarly enterprise in which I have played a part, namely the exploration of the concept of comparative international law. International law aspires to universality and uniformity. It applies independently of municipal (domestic) law. Yet in practice states and regions have distinct, and sometimes radically different, approaches to both the process of making international law and the products of that process. Claims about what international law requires and how one can tell vary a lot, depending on who makes the claim. This paper first will outline the general features of comparative international law. It then will discuss the particular features of the international human rights system that can exacerbate the gaps between common-law and civilian jurists. It demonstrates how these features play out through an example, an important human rights dispute that implicates the differences between the common law and civil law. It concludes by showing how these differences bring about discord and block international cooperation to the detriment of the international law project.
The effect of two-photon absorption on the dynamic range of integrated microwave photonics links

Recently, Integrated Microwave Photonics (IMWP) on Silicon-on-Insulator (SOI) platform has attracted much attention. SOI as a platform for passive devices has been studied for operation at a wavelength of 1.55 μm. It has been acknowledged that Si suffers from Two-Photon Absorption (TPA) at this wavelength, which potentially limits the dynamic range of microwave photonic links. The TPA effect diminishes at longer wavelengths, and completely vanishes at a wavelength of 2.2 μm. So far, the detailed effects of TPA on the performance of the SOI platform in the context of IMWP have not been well-explored. In this work, a systemic simulation has been performed in order to investigate the effects of nonlinear TPA on the performance of SOI microwave photonic links at 1.55 μm, particularly the dynamic range of the system was studied in-depth. Furthermore, system performance at wavelengths from 1.55 to 2.2 μm was investigated by scaling the device design, where the parasitic effects of TPA are avoided. Based on theoretical analysis, the result showing microwave photonic links at 2.2 μm outperform that at 1.55 μm was obtained as expected. Strip and rib waveguides at 1.55 μm show P1dB points of 3.75 mW and 69.54 mW, respectively, and at 2.2 μm, these waveguides performed linearly throughout the simulated range (up to 1 W of input power) which is due to the dramatically reduced TPA effect. It is noted that the wavelengths at which SOI avoids parasitic TPA match well with the working wavelengths of emerging GeSn lasers and photodetectors.
Precision nicotine metabolism-informed care for smoking cessation in Crohn's disease: A pilot study.

INTRODUCTION Smoking is a strong risk factor for disease severity in Crohn's disease (CD) and cessation improves outcomes. The nicotine metabolite ratio (NMR) predicts cessation success with pharmacotherapy: varenicline doubles cessation over nicotine replacement therapy (NRT) for "normal", but not "slow" metabolizers. Varenicline side effects are heightened in slow metabolizers. Methods using NMR to optimize cessation pharmacotherapy have not been evaluated in CD. AIMS We aim to determine the prevalence of smoking in a CD population and then assess these smokers' attitudes toward a personalized metabolism-informed care (MIC) approach to cessation. METHODS In this observational study, we surveyed 1098 patients visiting an inflammatory bowel disease center about their smoking history. We then evaluated a subgroup of individuals with CD (n = 32) who participated in a randomized controlled trial of smoking cessation using MIC versus usual care. For MIC, medication selection was informed by the NMR (normal ≥0.31 vs. slow <0.31). The primary outcomes were intervention satisfaction and match rates between NMR and medication choice. RESULTS The baseline prevalence of smoking in our CD population was 13%. Intervention participants reported high rates of satisfaction (85%) and chose a medication that matched their NMR result more often in the MIC group (100% vs. 64%, p = 0.01). Six of 16 (37.5%) patients prescribed varenicline discontinued due to side effects. CONCLUSION MIC produced high rates of satisfaction and matching between NMR and medication in CD patients, supporting patient acceptance and feasibility of precision smoking cessation in this population. To reduce smoking in CD, therapies such as MIC are needed to maximize efficacy and minimize side effects.
Dance improvisation research: embodied self-esteem and self confidence through glass art

‘Dancing Glass: Reflection of Art through Dance’ was a collaborative project using artwork from the glass gallery at the Lowe Art Museum of the University of Miami, as a springboard for artistic in...
Lightweight longitudinal colorimetric fiber sensing platform with optimized dye/polymer thickness for remote sensing and reconnaissance (Conference Presentation)

Combinatorial colorimetry has detected chemical compounds and uniquely identifies toxic industrial compounds at the ppmv level. We investigate colorimetric dyes, coated with polymers, on long fibers for lightweight remote/standoff fiber-based sensing (unmanned monitoring points, UAVs) exploiting optical fibers’ quality, length, low weight; retaining performance and low power needs. We model/ investigate an advanced longitudinal lightweight polymer fiber colorimetric sensing platform, sensitivity to fiber length, light propagation, and loss of light and sensitivity due to losses in the cladding, the spatial transient’s effect, and predict long lightweight fiber sensor sensitivity/selectivity. Visible light from illuminating LEDs travels along the polymer or silica fiber core and evanescently interacts with colorimetric dyes. Dyes are in porous, mechanically strong polymers with optimized thickness in order to enable analytes to reach the cladding/core interface yet mechanically strong.
Millennials’ Intention to Use Self-Checkout Technology in Different Fashion Retail Formats: Perceived Benefits and Risks:

With an increase in automation, fashion retailers started to offer a self-checkout option in their stores to meet diverse consumers’ demand. Self-checkout technology has great potential to enhance ...
Overview to Part I: Fathers, Developmental Systems, and Relationships

In his fascinating historical account on the “Origins of Fatherhood,” Kraemer (1991, p. 377) asserts that “Fatherhood is a human social invention and patriarchy, the rule of the father” emerged from recognition that males played an essential role in procreation. While patriarchy rapidly, in historical time, replaced matriarchy and men created male gods to rule over all of the dominions, child rearing during infancy and early childhood became the sole responsibility of women. Therefore, in a more contemporary world it should not be surprising that most theories of early human development were developed by men, they gave special importance to the quality of the mother-child relationship with respect to child outcomes, particularly the negative ones as implied by the concept of “mother blame.” Kraemer references Goodall’s work with Chimpanzee’s, with whom humans share about 99% of their DNA, to illustrate that for non-human primates there is no such concept as “father.” What a difference 1% makes for human primates, who socially constructed the concept of father. Alas, the social construction of fatherhood that humans (men) created did not include having males play any major role in child rearing during the early years of their life. As Kraemer notes, “within a space of a few thousand years, the idea of male parent became the divine leader who could do his own creating by inventing things and controlling people” (p. 390).
Associations between living alone, depression, and falls among community-dwelling older adults in the US.

Abstract Social isolation is closely linked to depression and falls in late life and are common among seniors. Although the literature has highlighted age-related variations in these three geriatric conditions, evidence on heterogeneities across older adult age categories is lacking. To address this gap, we present cross-sectional analyses using indicators of social isolation, depression, and falls of older adults constructed from the most recent Behavioral Risk Factor Surveillance System (BRFSS) data. An age-based understanding is critical to improve health interventions since health changes occur at a faster rate among seniors than in any other population subgroup. We included all adults 60 years and older (n = 113,233) in the 2018 BRFSS landline dataset and used the status of living alone, depressive disorder diagnosis, and fall incidences reported by these seniors to respectively create the social isolation, depression, and fall indicators. We conducted multivariable logistic regressions to compare findings on these indicators across the three age categories of 60–69, 70–79, and 80 and above after adjusting for a common set of covariates. Results indicate that the likelihood of seniors living alone and reporting depression is the highest among those 80 years and above. Conversely, the odds of depressed seniors reporting falls is the greatest among the 60–69 year olds. Accordingly, we highlight key implications for targeted health promotion and care delivery to seniors.
Do Biological Constraints Impair Dendritic Computation

Abstract Computations on the dendritic trees of neurons have important constraints. Voltage dependent conductances in dendrites are not similar to arbitrary direct-current generation, they are the basis for dendritic nonlinearities and they do not allow converting positive currents into negative currents. While it has been speculated that the dendritic tree of a neuron can be seen as a multi-layer neural network and it has been shown that such an architecture could be computationally strong, we do not know if that computational strength is preserved under these biological constraints. Here we simulate models of dendritic computation with and without these constraints. We find that dendritic model performance on interesting machine learning tasks is not hurt by these constraints but may benefit from them. Our results suggest that single real dendritic trees may be able to learn a surprisingly broad range of tasks.
Container Closure and Delivery Considerations for Intravitreal Drug Administration

Intravitreal (IVT) administration of therapeutics is the standard of care for treatment of back-of-eye disorders. Although a common procedure performed by retinal specialists, IVT administration is associated with unique challenges related to drug product, device and the procedure, which may result in adverse events. Container closure configuration plays a crucial role in maintaining product stability, safety, and efficacy for the intended shelf-life. Careful design of primary container configuration is also important to accurately deliver small volumes (10-100 μL). Over- or under-dosing may lead to undesired adverse events or lack of efficacy resulting in unpredictable and variable clinical responses. IVT drug products have been traditionally presented in glass vials. However, pre-filled syringes offer a more convenient administration option by reducing the number of steps required for dose preparation there by potentially reducing the time demand on the healthcare providers. In addition to primary container selection, product development studies should focus on, among other things, primary container component characterization, material compatibility with the formulation, formulation stability, fill volume determination, extractables/leachables, and terminal sterilization. Ancillary components such as disposable syringes and needles must be carefully selected, and a detailed administration procedure that includes dosing instructions is required to ensure successful administration of the product. Despite significant efforts in improving the drug product and administration procedures, ocular safety concerns such as endophthalmitis, increased intraocular pressure, and presence of silicone floaters have been reported. A systematic review of available literature on container closure and devices for IVT administration can help guide successful product development.
Combined Electric and Acoustic Stimulation (EAS) in Children: Investigating Benefit Afforded by Bilateral Versus Unilateral Acoustic Hearing.

Purpose Electric and acoustic stimulation (EAS) with preserved hearing in the implanted ear provides benefit for speech understanding, spatial hearing, and quality of life in adults. However, there is limited research on EAS outcomes in children. The aims of this study were to estimate the magnitude of EAS-related benefit on speech understanding in children with preserved acoustic hearing and to determine what role acoustic interaural time difference (ITD) sensitivity may have on said EAS benefit. Methods Six children with acoustic hearing preservation and 20 children with normal hearing (NH) were recruited to participate. Speech recognition was assessed via an eight-loudspeaker array with speech presented from one loudspeaker at 0 degree and restaurant noise from all other loudspeakers (45-315 degrees). ITD thresholds were measured for a 250-Hz signal presented acoustically via insert earphones. Results Only one EAS listener demonstrated significant benefit from bilateral acoustic hearing as compared with acoustic hearing from a single ear. ITD thresholds were poor in the range of 302 to 1000+ ms and were considerably poorer than ITD thresholds for the NH group. Conclusion These data suggest that children with acoustic hearing preservation may not exhibit initial EAS benefit for speech recognition in semi-diffuse noise; however, because none exhibited a decrement in performance with bilateral acoustic stimulation, EAS fittings are recommended to provide binaural acoustic access allowing for EAS adaptation to binaural cues over time. Future research should address the emergence of EAS benefit, binaural cue sensitivity, and the role of EAS experience in children and adults.
Rapid, Presumptive Identification of Seed-Based Toxins using Direct Analysis in Real Time Mass Spectrometry (DART-MS) and its Variants

Detection of seed-based toxins is a need for forensic chemists when suspected poisonings occur. The evidence that is found is often physically unidentifiable, as the seeds are mashed to extract the toxins. This work investigates potential strategies for rapid detection of seed-based toxins using chemical signatures obtained by direct analysis in real time mass spectrometry (DART-MS). Seven toxins (digoxin, digitoxin, hypaconitine, hyoscyamine, lanatoside, oleandrin, and scopolamine) and six seeds containing these toxins were studied. While detection of four of the toxins was readily attainable, detection of digoxin, digitoxin, and lanatoside was hindered by the inability to thermally desorb these larger compounds under normal operating conditions. The use of DART-MS variants capable of higher temperature analysis (thermal desorption (TD)-DART-MS and infrared thermal desorption ((IRTD)-DART-MS) enabled detection of these compounds. The low-level toxin concentrations and limited number of seeds available for analysis led to detection difficulties from both seed mashes and methanolic seed mash extracts. Principal component analysis (PCA) of generated mass spectra enabled differentiation of seed species, even in the cases when the toxins were undetectable.
Window+: Electrostatic levitation enabled Polymer-Air multilayer (EPAM) structures for highly transparent energy efficient windows

Abstract The poor thermal insulating building windows, especially single-pane windows, are wasting ∼ 7% of the total energy consumed by the U.S. every year. This paper presents an electrostatic levitation enabled polymer-air multilayer (EPAM) structure as a highly transparent and energy efficient window retrofitting solution for low-income single-pane window users. To provide controllable and stable suspension force between large size compliant polymer films without deteriorating their visual transmittance (Vt) in the multilayer polymer/air structure, corona discharge (CD) was used to induce quasi-permanent charges for non-conductive polymer films, leading to controllable and long-lasting surface electric potential difference between two sides of CD charged films. Liquid-solid contact electrification (LS-CE) was combined with CD to realize precise control of the electrical potential of each side of polymer films. CD + CE treated films can obtain programmable and stable electrostatic forces to form resilient EPAM structures for cost and energy effective window retrofitting purpose. The resilient EPAM retrofitted clear windows can provide U-factor lower than 3 W·m−2·K−1, Vt higher than 70%, haze lower than 1.6% at cost lower than $79.7/m2, at least 10 times cheaper than double pane windows. The energy saved by EPAM can reach as much as the order of 106 kJ/m2 per year. The CD + CE surface potential programming solution also provides a highly repeatable and controllable way for other electrical potential related technologies, such as energy harvesting and storage.
Evolution of Palliative Care in the Department of Veterans Affairs: Lessons from an Integrated Health Care Model

Palliative care (PC) is beneficial, however, in many settings it is under-resourced and unable to consistently meet the needs of patients and their families. A lack of national health policy suppor...
Focused Ultrasound-Mediated Blood-Brain Barrier Opening Enhances Panobinostat Efficacy in a Murine Diffuse Intrinsic Pontine Glioma Model.

Purpose/Objective(s) Diffuse intrinsic pontine glioma (DIPG) is the most lethal brain tumor in children with no effective treatment options to date. The prognosis remains poor with a median overall survival of less than 1 year. Recent in vitro drug screening studies found the histone deacetylase (HDAC) inhibitor, panobinostat, to be highly effective against DIPG. However, as panobinostat has poor blood-brain barrier (BBB) penetration, phase 1 clinical trials using systemic administration of panobinostat have been unsuccessful. Therefore, improved efficacy will require enhancement of delivery into the brain. Focused ultrasound (FUS), a non-ionizing acoustic form of radiation, has been shown to safely and non-invasively open the BBB, which can increase drug delivery. In this study, we hypothesize that FUS-mediated BBB opening (BBBO) can enhance the delivery of panobinostat for a therapeutic benefit in DIPG. Materials/Methods A syngeneic DIPG model was established by injecting mouse DIPG cells (PDGFB+, H3.3K27M, p53−/−) intracranially. A single-element, spherical-segment FUS transducer (center frequency: 0.5 MHz) driven by a function generator through a power amplifier was used with concurrent microbubble injection to perform BBBO. We then utilized magnetic resonance imaging to evaluate BBBO and tumor progression. Results We first demonstrated that FUS-mediated BBBO is safe and feasible in mice with DIPG tumors by MRI and passive cavitation detection. Our DIPG cell line was shown to be very sensitive to panobinostat in cell viability assay (IC50 = 0.012 μM). The combined treatment of FUS-mediated BBBO and panobinostat showed benefits in both local control and overall survival. Conclusion The current results demonstrate that FUS could increase the treatment efficacy of panobinostat in a DIPG animal model due to the improved targeted dose of systemic panobinostat in the DIPG tumors. We believe these data establish a strong preclinical rationale to assess the combination of FUS-mediated BBB opening with panobinostat in pediatric patients with DIPG.
Software Geography: Physical and Economic Aspects

To the metaphors of software engineering and software physics can be added that of software geography. We examine the physical and economic aspects of the Software Glacier (once an innocent bubbling brook, now a vast frozen mass of applications imperceptibly shaping both the Hardware Shelf below and User City above), Quantum Planet (colonization of which could be fruitful if and when it becomes practical), and Concurrency Frontier (an inaccessible land with rich resources that we project will be exploited to profound economic effect during the next half-century).
The substitution of calcium for magnesium in H+,K+-ATPase catalytic cycle. Evidence for two actions of divalent cations.

Abstract In order to determine the role of divalent cations in the reaction mechanism of the H+,K+-ATPase, we have substituted calcium for magnesium, which is required by the H+,K+-ATPase for phosphorylation from ATP and from PO4. Calcium was chosen over other divalent cations assayed (barium and manganese) because in the absence of magnesium, calcium activated ATP hydrolysis, generated sufficiently high levels of phosphoenzyme (573 +/- 51 pmol.mg-1) from [gamma-32P]ATP to study dephosphorylation, and inhibited K+-stimulated ATP hydrolysis. The Ca2+-ATPase activity of the H+,K+-ATPase was 40% of the basal Mg2+-ATPase activity. However, the Ca2+,K+-ATPase activity (minus the Ca2+ basal activity) was only 0.7% of the Mg2+,K+-ATPase, indicating that calcium could partially substitute for Mg2+ in activating ATP hydrolysis but not in K+ stimulation of ATP hydrolysis. Approximately 0.1 mM calcium inhibited 50% of the Mg2+-ATPase or Mg2+,K+-ATPase activities. Inhibition of Mg2+,K+-ATPase activity was not competitive with respect to K+. Inhibition by calcium of Mg2+,K+ activity p-nitrophenyl phosphatase activity was competitive with respect to Mg2+ with an apparent Ki of 0.27 mM. Proton transport measured by acridine orange uptake was not detected in the presence of Ca2+ and K+. In the presence of Mg2+ and K+, Ca2+ inhibited proton transport with an apparent affinity similar to the inhibition of the Mg2+, K+-ATPase activity. The site of calcium inhibition was on the exterior of the vesicle. These results suggest that calcium activates basal turnover and inhibits K+ stimulation of the H+,K+-ATPase by binding at a cytosolic divalent cation site. The pseudo-first order rate constant for phosphoenzyme formation from 5 microM [gamma-32P]ATP was at least 22 times slower in the presence of calcium (0.015 s-1) than magnesium (greater than 0.310 s-1). The Ca.EP (phosphoenzyme formed in the presence of Ca2+) formed dephosphorylated four to five times more slowly that the Mg.EP (phosphoenzyme formed in the presence of Mg2+) in the presence of 8 mm trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (CDTA) or 250 microM ATP. Approximately 10% of the Ca.EP formed was sensitive to a 100 mM KCl chase compared with greater than 85% of the Mg.EP. By comparing the transient kinetics of the phosphoenzyme formed in the presence of magnesium (Mg.EP) and calcium (Ca.EP), we found two actions of divalent cations on dephosphorylation.(ABSTRACT TRUNCATED AT 400 WORDS)
Time with friends and physical activity as mechanisms linking obesity and television viewing among youth

Though bivariate relationships between childhood obesity, physical activity, friendships and television viewing are well documented, empirical assessment of the extent to which links between obesity and television may be mediated by these factors is scarce. This study examines the possibility that time with friends and physical activity are potential mechanisms linking overweight/obesity to television viewing in youth. Data were drawn from children ages 10-18 years old (M = 13.81, SD = 2.55) participating in the 2002 wave of Child Development Supplement (CDS) to the Panel Study of Income Dynamics (PSID) (n = 1,545). Data were collected both directly and via self-report from children and their parents. Path analysis was employed to examine a model whereby the relationships between youth overweight/obesity and television viewing were mediated by time spent with friends and moderate-to-vigorous physical activity (MVPA). Overweight/obesity was directly related to less time spent with friends, but not to MVPA. Time spent with friends was directly and positively related to MVPA, and directly and negatively related to time spent watching television without friends. In turn, MVPA was directly and negatively related to watching television without friends. There were significant indirect effects of both overweight/obesity and time with friends on television viewing through MVPA, and of overweight/obesity on MVPA through time with friends. Net of any indirect effects, the direct effect of overweight/obesity on television viewing remained. The final model fit the data extremely well (χ2 = 5.77, df = 5, p<0.0001, RMSEA = 0.01, CFI = 0.99, TLI =0.99). We found good evidence that the positive relationships between time with friends and physical activity are important mediators of links between overweight/obesity and television viewing in youth. These findings highlight the importance of moving from examinations of bivariate relationships between weight status and television viewing to more nuanced explanatory models which attempt to identify and unpack the possible mechanisms linking them.
Coordinated launching of an ornithopter with a hexapedal robot

In this work, we develop a cooperative launching system for a 13.2 gram ornithopter micro-aerial vehicle (MAV), the H2Bird, by carrying it on the back of a 32 gram hexapedal millirobot, the VelociRoACH. We determine the necessary initial velocity and pitch angle for take off using force data collected in a wind tunnel and use the VelociRoACH to reach these initial conditions for successful launch. In the wind tunnel predicted success region, we were able to complete a successful launch for 75 percent of the 12 trials in that region. Although carrying the H2Bird on top of the VelociRoACH at a stride frequency of 17 Hz increases our average power consumption by about 24.5 percent over solo running, the H2Bird, in turn, provides stability advantages to the VelociRoACH. We observed that the variance in pitch and roll velocity with the H2Bird is about 90 percent less than without. Additionally, with the H2Bird flapping at 5 Hz during transport, we observed an increase of 12.7 percent of the steady state velocity. Lastly, we found that the costs of transport for carrying the H2Bird flapping and without (6.6 and 6.8) are lower than the solo costs of transport for the VelociRoACH and for the H2Bird (8.1 and 10.1).
Vacuum polarization in the Szekeres Class of colliding plane wave space-times

We study the quantization of a scalar field on a classical background given by the Szekeres Class of solutions, which represent the collision of two gravitational plane waves with constant polarization. These solutions consist of two approaching gravitational plane waves moving in a flat background and an interaction region which always contains a curvature singularity. Following a suitable approximate procedure, introduced in a previous paper, we propose a way to compute the vacuum expectation value of the stress-energy tensor throughout the causal past region of the collision center in the quantum state which corresponds to the vacuum before the arrival of the waves.
How the WTO Shapes Regulatory Governance

The World Trade Organization (WTO) arguably shapes regulatory governance in more countries to a greater extent than any other international organization. This article provides a framework for assessing the broader transnational regulatory implications of the WTO as part of a transnational legal order (TLO) in terms of four dimensions of regulatory change that permeate the state: (i) changes in the boundary between the market and the state (involving concomitantly market liberalization and growth of the administrative state); (ii) changes in the relative authority of institutions within the state (promoting bureaucratized and judicialized governance); (iii) changes in professional expertise engaging with state regulation (such as the role of lawyers); and (iv) changes in normative frames and accountability mechanisms for national regulation (which are trade liberal and transnational in scope). In practice, these four dimensions of change interact and build on each other. The article presents what we know to date and a framework for conducting further study of such transnational legal ordering.
Purification of somatic pili

Publisher Summary This chapter discusses the procedure for the purification of somatic pili. Somatic pili mediate a multiplicity of other functions which, in the most general sense, enable bacteria to colonize host surfaces or to occupy inanimate environmental habitats. Depending on the bacterial species and pilus type, somatic pill have been implicated as effectors of the following functions: specific, that is, ligand-receptor based, adherence of bacteria to host cell surfaces; nonspecific adsorptive binding of bacteria to abiotic surfaces; translocation of attached bacteria across surfaces by twitching motility; resistance to phagocytosis; transformation competence; and the formation of interbacterial linkages within colonies. The purification of pili is carried out (1) to determine the structural basis for these functional attributes, (2) to identify antigenic determinants, and (3) to study pili as vaccines. The chapter describes a general pilus purification method based on the capacity to cause pili to form paracrystalline aggregates under one set of conditions and their solubilization into separate, nonaggregated pilus filaments under a different set of conditions. Solubilization does not refer to disassembly of the pilus filament into its constituent subunits, but rather to the retention of individual pilus filaments in the supernatant during a centrifugation experiment. Stepwise purification is achieved through centrifugation and alternate cycles of pilus aggregation and solubilization.
Embryonic Responses to Structurally Related Inhibitors

Many of the so-called nucleic acid antagonists inhibit amphibian development (Bieber, 1954; Bieber, Nigrelli, & Hitchings, 1952; Waddington, Feldman, & Perry, 1955); a number of them affect embryological processes differentially (Liedke, Engelman, & Graff, 1954, 1955), some of them interfering primarily with early cleavage stages where synthesis is not appreciable, others affecting most drastically only late development in which differentiation and synthesis are marked. These compounds, which bear some structural resemblance to the naturally occurring purines, affect other biological systems also, among them Tetrahymena gelii, Escherichia coli , and tissue cultures of mammalian cells (Gillespie, Engelman, & Graff, 1954). This paper reports the study of the effects of 35 compounds, substituted benzothiadiazoles, benzimidazoles, quinoxalines, and other related compounds. While 8 of these compounds had been used previously (Liedke, Engelman, & Graff, 1954), 27 are additional new compounds, some of them only newly synthesized. The structures of the parent compounds are illustrated in Text-fig. 1.