cssi/SciSciGPT-SciSciNet huggingface dataset:
Predicting the Cost and Pace of Pharmacogenomic Advances: An Evidence-Based Study

BACKGROUND: Adverse outcomes associated with prescription drug use are common and costly. Many adverse outcomes can be avoided through pharmacogenomics: choosing and dosing of existing drugs according to a person9s genomic variants. Finding and validating associations between outcomes and genomic variants and developing guidelines for avoiding drug-related adverse outcomes will require further research; however, no data-driven estimates yet exist for the time or money required for completing this research. METHODS: We identified examples of associations between adverse outcomes and genomic variants. We used these examples to estimate the time and money required to identify and confirm other associations, including the cost of failures, and to develop and validate pharmacogenomic dosing guidelines for them. We built a Monte Carlo model to estimate the time and financial costs required to cut the overall rate of drug-related adverse outcomes by meaningful amounts. We analyzed the model9s predictions for a broad range of assumptions. RESULTS AND CONCLUSIONS: Our model projected that the development of guidelines capable of cutting overall drug-related adverse outcomes by 25%–50% with current approaches will require investment of single-digit billions of dollars and take 20 years. The model forecasts a pump-priming phase of 5–7 years, which would require expenditures of hundreds of millions of dollars, with little apparent return on investment. The single most important parameter was the extent to which genomic variants cause adverse outcomes. The size of the labor force was not a limiting factor. A “50 000 Pharmacogenomes Project” could speed progress. Our approach provides a template for other areas of genomic research.
Analytical Model for Sheathing-to-Framing Connections in Wood Shear Walls and Diaphragms

A new analytical model for sheathing-to-framing connections in wood shear walls and diaphragms is discussed in this paper. The model represents sheathing-to-framing connections using an oriented pair of nonlinear springs. Unlike previous models, the new analytical model is suitable for both monotonic and cyclic analyses and does not need to be scaled or adjusted. Furthermore, the analytical model may be implemented in a general purpose finite element program, such asABAQUS, or in a specialized structural analysis program, such as CASHEW. To illustrate, the responses of a 4.88 3 14.6 m plywood diaphragm and a 2.443 2.44 m oriented strand board shear wall are predicted using the new analytical model.
Influence of Nest Pad Color on Nest Preference, Percentage of Floor Eggs, and Egg Production of Broiler Breeder Hens

Abstract Conventional brown AstroTurf® nest pads were compared with black, green, and gray AstroTurf® nest pads in paired preference tests. Broiler breeder hens were offered a choice between brown and one of the other three colors within a single pen, and eggs laid per week per nest hole were counted. Hens significantly preferred gray over brown, and this preference persisted even when the pad color arrangement was reversed at 49 wk of age. No discrimination between the other colors and brown was found, and reversing the color scheme had no effect on nest position selection. A second study was conducted in which hens were allowed to lay in nests equipped either with brown or gray nest pads. The hens exposed only to gray nest pads laid significantly fewer floor eggs between 25 and 40 wk of age. The birds laying on gray AstroTurf® nest pads also exhibited significantly improved egg production and feed conversion.
Implementation of steerable spatiotemporal image filters on the focal plane

This paper presents an architectural overview of a pseudogeneral image processor (GIP) chip for realizing steerable spatial and temporal filters at the focal-plane. The convolution of the image with programmable kernels is realized with area-efficient and real-time circuits. The chip's architecture allows photoreceptor cells to be small and densely packed by performing all analog computations on the read-out, away from the array. The size, configuration, and coefficients of the kernels can be varied on the fly. In addition to the raw intensity image, the chip outputs four processed images in parallel. The convolution is implemented with a digitally programmable analog processor, resulting in very low-power consumption at high-computation rates. A 16/spl times/16 pixels prototype of the GIP has been fabricated in a standard 1.2-/spl mu/m CMOS process and its spatiotemporal capabilities have been successfully tested. The chip exhibits 1 GOPS/mW at 20 kft/s while computing four spatiotemporal convolutions in parallel.
Mapping groundwater contamination using dc resistivity and VLF geophysical methods; a case study

Geophysical methods can be helpful in mapping areas of contaminated soil and groundwater. Electrical resistivity and very low-frequency electromagnetic induction (VLF) surveys were carried out at a site of shallow hydrocarbon contamination in Utah County, Utah. Previously installed monitoring wells facilitated analysis of water chemistry to enhance interpretation of the geophysical data. The electrical resistivity and VLF data correlate well, and vertical cross-sections and contour maps generated from these data helped map the contaminant plume, which was delineated as an area of high interpreted resistivities.
Observations of ultraviolet light reflection and transmission by first‐year sea ice

As part of a comprehensive program investigating the electromagnetic properties of sea ice, measurements were made of the optical properties of young ice and first-year sea ice at ultraviolet wavelengths. Young sea ice observations were made in a specially designed sea ice pond at the Cold Regions Research and Engineering Laboratory (Hanover, NH), while first-year sea ice was examined in the Chukchi Sea and Beaufort Sea near Barrow, Alaska. The results indicated that, in general, albedo increased with increasing wavelength from 305 to 380 nm, with values for first-year ice in the 0.4 to 0.6 range. Transmittance through bare first-year ice was roughly 0.5 to 2 percent. Extinction coefficients for bare sea ice were between 2 and 4 m−1 and decreased with increasing wavelength. The presence of a snow cover had a profound impact on ultraviolet light levels under sea ice, with even a thin (0.1-m-thick) snow cover reducing transmitted ultraviolet light by more than an order of magnitude. Observed transmittances indicated that the attenuation of ultraviolet light by sea ice and snow was greater than that of the photosynthetically active radiation.
REGULATION BY SALT OF ACTIVITY OF CITRATE SYNTHASES FROM OSMOREGULATORS AND OSMOCONFORMERS

Citrate synthases from an osmoregulator and 2 osmoconforming animals were purified and studied with respect to interaction with salt levels. Catalytic activity of the shrimp (osmoregulator) citrate synthase was markedly affected by buffer concentrations, and its apparent Km with respect to acetyl coenzyme A was increased almost 60-fold by increased concentration of salt. The osmoconformer citrate synthases showed slight effects of concentration of salt: the apparent Km of the sea anemone citrate synthase was increased fractionally by salt and about 6-fold for citrate synthase of the oyster. Citrate synthase from the osmoregulator shrimp had the conventional hyperbolic kinetics of saturation by acetyl coenzyme A in the presence of moderate concentrations of any salt, but the sea anemone and oyster citrate synthases had sigmoid kinetics in the same saline environment. The oyster was shown to regulate the levels of magnesium, potassium, and chloride in its tissues. The ecoadaptive significance of these findings is discussed and the generally standing concern of investigators is supported that biologically and physiologically realistic interpretations of enzyme regulation by ionic strength and any other factors can be derived only from studies of enzyme activities in situ.
Nonorthogonal signal representation by Gaussians and Gabor functions

This paper describes a novel approach for nonorthogonal representation of signals using Gaussians and an extension of this method for Gabor representation of signals, based on the equivalence of Gabor expansion to Gaussian expansion in the frequency domain. The Gaussian expansion scheme yields an efficient representation of signals for low number of bits per pixel and is better than the corresponding Discrete Cosine Transform (DCT) representation for very low bit rates. This advantage diminishes gracefully for higher bit rates where the residual approximation error signal to be represented is more random and less structured. It is proved in this paper that a finite number of Gaussians can theoretically approximate sinusoids in a bounded region with arbitrarily small error, and therefore any finite support L/sup 2/(R) signal as well. Two methods for Gaussian representation of signals are outlined. The first, called the Max-Energy paradigm, involves successive extraction of the highest energy Gaussian that best "fits" the signal. The second is a parallel approach and uses an adaptive projection algorithm to first derive the Gaussian basis set to be used in parallel, and then optimizes the coefficients for minimum squared error. >
College Origins and Patterns of Status Attainment: Schooling Among Professional Andbusiness-Managerial Occupations

A longitudinal study of the occupational attainments of a national sample of male college graduates suggests, contrary to prevailing thought, that college origins do have a direct impact upon status attainment. They do so, however, only among professional occupations, rather than among business-managerial ones. Institutional sponsorship, should it occur, is more properly viewed as a latent rather than active capacity of collegiate institutions, one which is occupational situs-specific in character, rather than occupation-general. Nor does it appear to apply equally well to all members of the institution. Simply being at a prestigious institution is no guarantee of sponsorship to elite occupational positions. Individuals must demonstrate competence in order to activate the sponsorship capacities inherent in institutions.
Intrinsically motivated model learning for a developing curious agent

Reinforcement Learning (RL) agents are typically deployed to learn a specific, concrete task based on a pre-defined reward function. However, in some cases an agent may be able to gain experience in the domain prior to being given a task. In such cases, intrinsic motivation can be used to enable the agent to learn a useful model of the environment that is likely to help it learn its eventual tasks more efficiently. This paper presents the TEXPLORE with Variance-And-Novelty-Intrinsic-Rewards algorithm (TEXPLORE-VANIR), an intrinsically motivated model-based RL algorithm. The algorithm learns models of the transition dynamics of a domain using random forests. It calculates two different intrinsic motivations from this model: one to explore where the model is uncertain, and one to acquire novel experiences that the model has not yet been trained on. This paper presents experiments demonstrating that the combination of these two intrinsic rewards enables the algorithm to learn an accurate model of a domain with no external rewards and that the learned model can be used afterward to perform tasks in the domain. While learning the model, the agent explores the domain in a developing and curious way, progressively learning more complex skills. In addition, the experiments show that combining the agent's intrinsic rewards with external task rewards enables the agent to learn faster than using external rewards alone.
Tandem mass spectrometry of fatty acid methyl esters. Evidence for bicyclic product ions

Product-ion spectra derived from both protonated and hydride-abstracted molecules of long chain esters have revealed an unusual homologous series of ions which suggest a cyclization mechanism to form stabilized bicyclodecenes or bicyclononenes.
Vascular Health Profile predicts cardiovascular outcomes in patients with diabetes.

BACKGROUND We previously reported the development of a novel high dimensional cytomic assay, the Vascular Health Profile (VHP) based on measurements of angiogenic circulating hematopoietic stem and progenitor cells (CHSPCAng ) and extracellular vesicles (EVs), that discovered a unique signature, differentiating the vascular status of diabetics and normal healthy controls. Here, we present data from a 3-year follow-up to evaluate the power of the VHP to identify individuals at risk for cardiovascular (CV) events. METHODS The original data were generated as previously described by measuring a broad panel of progenitor cells and EVs and profiled using cytometric fingerprinting. Subjects were classified into groups according to the occurrence of adjudicated CV events including myocardial infarction, stroke, major adverse cardiovascular events, revascularization, and irregular rhythm. Cross-validated Linear Discriminate Analysis (LDA) models were constructed and used to predict the occurrence of events, and were evaluated for predictive accuracy (AUC, area under the curve) using receiver operating characteristic (ROC) analysis. RESULTS Over the period of this analysis, follow-up data was obtained on 87 subjects, with 32 events occurring overall, and only in the diabetic group. In all cases, the VHP added significant predictive power, in the form of ROC analysis, for all evaluated outcomes with the exception of irregular rhythm. CONCLUSIONS The VHP, a relatively simple blood test, can provide sensitive and clinically relevant information on the vascular status of a patient that may be useful for a variety of applications including drug development, clinical risk assessment, and companion diagnostics. © 2015 International Clinical Cytometry Society.
Morphology and Anatomy of Palm Seedlings

A historical survey of studies of seedling morphology and anatomy in the palm family is given. The traditional three germination types—adjacent ligular, remote ligular, and remote tubular—that have been commonly recognized are reevaluated. The study includes seedlings of 63 species, representing the six subfamilies of palms. Morphological characteristics of germination patterns and the anatomy of the eophyll are described. The results of this survey show that germination types determined by the length of the hyperphyll (cotyledonary petiole) are not completely valid. Instead, a combination of characters such as primary root orientation, coleoptile length, number of cataphylls, and eophyll plication correspond to the most recent classification of the family, and represent a better way of describing germination.
How Structure-Directing Agents Control Nanocrystal Shape: Polyvinylpyrrolidone-Mediated Growth of Ag Nanocubes

The importance of structure-directing agents (SDAs) in the shape-selective synthesis of colloidal nanostructures has been well documented. However, the mechanisms by which SDAs actuate shape control are poorly understood. In the polyvinylpyrrolidone (PVP)-mediated growth of {100}-faceted Ag nanocrystals, this capability has been attributed to preferential binding of PVP to Ag(100). We use molecular dynamics simulations to probe the mechanisms by which Ag atoms add to Ag(100) and Ag(111) in ethylene glycol solution with PVP. We find that PVP induces kinetic Ag nanocrystal shapes by regulating the relative Ag fluxes to these facets. Stronger PVP binding to Ag(100) leads to a larger Ag flux to Ag(111) and cubic nanostructures through two mechanisms: enhanced Ag trapping by more extended PVP films on Ag(111) and a reduced free-energy barrier for Ag to cross lower-density films on Ag(111). These flux-regulating capabilities depend on PVP concentration and chain length, consistent with experiment.
Significant Theories, Principles, and Approaches that Emerged Within Landscape Ecology During the Previous Thirty Years

This chapter presents an overview of landscape-level research developments during the past 30 years; addresses how landscape-level ecological changes, instrumentation refinement, and large-scale perturbations have changed the field of landscape ecology . The chapter relates these changes to significant theories, principles, and approaches that have emerged in landscape ecology during the past three decades (i.e., since the Allerton Park Workshop).
Purging my friends list. Good luck making the cut

Examined the perceptions of narcissistic statements on Facebook.Narcissistic status updates viewed negatively relative to neutral updates.Narcissism and gender of the perceiver played a role in ratings of status updates. Social media sites such as Facebook are thought to act as a platform for narcissistic behavior, such as posting self-promoting status updates or attractive photos. Narcissism is identifiable via social media, and it has been associated with negative peer appraisals. This article presents three studies with undergraduate students that examined the interpersonal implications of narcissism on Facebook in light of gender and perceiver narcissism. Results indicated that hypothetical targets who posted narcissistic status updates were perceived as less likeable, less successful, and less worthy of friendship than those who posted neutral status updates. Across the three studies, perceiver narcissism and target gender had some apparent influences on ratings. Implications regarding social media behavior and the interpersonal consequences of narcissism are discussed.
Changes in UTI Hospitalizations after the 2011 AAP UTI Guidelines

Outpatient management of urinary track infections (UTI) as a treatment option was firmly established by Hoberman's study in 1999 and confirmed in Cochrane reviews in 2003 and 2007; yet admission rates remained constant through 2009. Our objective is to see if the 2012 KID data would reflect …
Big Data Transforms Discovery–Utilization Therapeutics Continuum

Enabling omic technologies adopt a holistic view to produce unprecedented insights into the molecular underpinnings of health and disease, in part, by generating massive high-dimensional biological data. Leveraging these systems-level insights as an engine driving the healthcare evolution is maximized through integration with medical, demographic, and environmental datasets from individuals to populations. Big data analytics has accordingly emerged to add value to the technical aspects of storage, transfer, and analysis required for merging vast arrays of omic-, clinical-, and eco-datasets. In turn, this new field at the interface of biology, medicine, and information science is systematically transforming modern therapeutics across discovery, development, regulation, and utilization.
Safety and efficacy of transcatheter aortic valve replacement in intermediate risk patients sets the stage for contemporary trials in lower risk groups.

Since first performed in 2002 by Alan Cribier (1), transcatheter aortic valve replacement (TAVR) has emerged as an attractive alternative for the treatment of patients with severe symptomatic aortic stenosis (AS) who are inoperable or at high-risk for complications with surgical aortic valve replacement (SAVR), based in large part on the results of the three seminal randomized control trials (2-4). The procedure has indeed been a true transformative technology in the treatment of severe AS, and has expanded the range of options for these complex patients, many of whom had no prior options. As such, there has been a rapid dissemination of the TAVR technology for widespread utilization among these patients.
The trend of transmitted drug resistance in newly diagnosed antiretroviral-naive HIV/AIDS patients during 1999-2012 in South Korea.

Abstract Background The use of antiretroviral drugs has reduced the mortality and morbidity of patients with HIV/AIDS. More than 20 antiretroviral drugs have been used in patients with HIV/AIDS since zidovudine was first introduced in 1991 in South Korea. Objectives To investigate and estimate the annual prevalence of transmitted drug resistance and drug-resistant variants of HIV-1 in newly diagnosed antiretroviral-naive patients in South Korea during 1999–2012. Study design Plasma specimens were collected from 928 antiretroviral-naive patients during 1999–2012. Mutations in the protease and reverse transcriptase sections of the HIV-1 pol gene were identified using the Stanford HIV Drug Resistance Database (Stanford DB). Results Among 928 HIV-1 isolates from antiretroviral-naive patients, 45 (4.8%) showed ‘intermediate’ or ‘resistant’ drug resistance. The predicted prevalence of drug resistance among isolates was 2.2%, 2.7%, and 0.3% for resistance to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors, respectively. Conclusions There was no significant increase in the prevalence of drug resistance among antiretroviral-naive patients infected with HIV-1 during 1999–2012 in South Korea, although there was a slight increase during 2009–2012. The emergence of drug-resistant variants will continue to be monitored by national surveys.
Monitoring pulmonary function.

A unit for monitoring ventilation, ventilational mechanics, gas distribution, gas diffusion, and pulmonary capillary perfusion of the lungs, suitable for bedside investigation of these functions in very ill patients, is described. This study will hopefully have the same impact on descriptive clinical pathophysiology and treatment of pulmonary disease as bedside measurement of hemodynamics has had in the decade just past.
Postharvest noninvasive assessment of undesirable fibrous tissue in fresh processing carrots using computer tomography images

Abstract This research was designed to develop and test an automatic image analysis method (algorithm) to classify CT images obtained from 1233 carrot (Daucus carota L.) sections (samples), collected during the 2013 and 2014 harvesting seasons. Classification accuracy was evaluated by comparing the classes obtained using eighteen CT images per carrot section to their undesirable fibrous tissue class, based on the industry-simulated invasive quality assessment (% of fiber). Class-0 represents fibrous-free samples, and class-1 denotes samples containing fibrous tissue. After CT image preprocessing, cropping, and segmentation, 3762 grayscale intensity and textural features were extracted from the eighteen CT images per sample. A 4-fold cross-validation linear discriminant classifier with a performance accuracy of 87.9% was developed using 95 relevant features, which were selected using a sequential forward selection algorithm with the Fisher discriminant objective function. This objective method is accurate in determining the presence of undesirable fibrous tissue in pre-processed carrots.
Microsurgical resection of vestibular schwannomas: complication avoidance

Vestibular schwannoma (VS) surgery requires appropriate patient selection, meticulous microsurgical technique and optimal post-operative care. Focused radiation is an effective alternative for the treatment of smaller VSs. For VS surgery to remain a reasonable option, surgery must be performed with a limited number of complications. Complication rates for VS surgery have increased over the last decade. This is likely due to (1) decreased surgical volume and as a result decreased microsurgical experience, (2) larger tumors undergoing surgery while smaller tumors are reserved for radiation, and (3) surgery for previously radiated tumors resulting in more difficult anatomic dissection. Appropriate management of complications is paramount. Herein, we discuss complications related to VS microsurgery and methods of avoidance. Specifically, we discuss the most frequently encountered complications, intraoperative monitoring and finally, methods of addressing these complications. With meticulous microsurgical technique, careful intraoperative monitoring and vigilant perioperative care one will ensure optimal patient outcomes.
PREVALENCE AND POTENTIAL IMPACT OF TOXOPLASMA GONDII ON THE ENDANGERED AMARGOSA VOLE (MICROTUS CALIFORNICUS SCIRPENSIS), CALIFORNIA, USA

Abstract We investigated the prevalence of Toxoplasma gondii in 2011–15 to assess its potential threat on the endangered Amargosa vole (Microtus californicus scirpensis) in California, US. Surveillance was simultaneously performed on populations of syntopic rodent species. We detected antibodies to T. gondii in sera from 10.5% of 135 wild-caught Amargosa voles; 8% of 95 blood samples were PCR-positive for the T. gondii B1 gene, and 5.0% of 140 sympatric rodent brain samples were PCR-positive. Exposure to T. gondii did not change the probability that an animal would be recaptured in the field study. Behavioral response to domestic cat (Felis catus) and bobcat (Lynx rufus) urine was evaluated in five nonendangered Owens Valley voles (Microtus californicus vallicola) as surrogates for Amargosa voles and seven uninfected controls. Voles showed mild attraction to mouse urine and had neutral reactions to domestic cat urine whether or not infected. Time spent near bobcat urine was approximately twice as high in ...
ABCG2 Expression as Prospective Marker for Hematopoeitic Stem Cell Purification.

Abstract ABCG2 (BCRP/MXR/ABCP) is an ABC transporter that effluxes Hoechst 33342 and is required for the side population (SP) phenotype of hematopoietic stem cells (HSCs). Although SP cells are enriched for HSC activity, they are not a pure stem cell population and contain a significant number of differentiated and committed cells. We hypothesized that expression of ABCG2 would provide a more specific marker for HSCs, given our prior results showing that other ABC transporters were expressed in committed SP cells. To test this hypothesis, we have generated a mouse strain in which an IRES-GFP element was inserted immediately after the stop codon of Abcg2, so that GFP and the endogenous Abcg2 gene were co-expressed from the same transcriptional regulatory elements. Immunohistochemical analysis using an anti-GFP antibody showed that Abcg2/GFP allele was strongly expressed in proximal tubule cells of kidney, in the epithelial cells of small intestine, and in vascular endothelium, recapitulating the normal expression pattern of Abcg2. Using flow cytometry to analyze GFP expression in bone marrow cells, we found that 48% of SP cells expressed GFP. In the distal tip of the SP region, previously shown to have the highest concentration of HSCs, 93% of cells expressed GFP. In gated Lin- GFP+ cells within the whole bone marrow population, 55 % of the cells expressed c-Kit and Sca1, a previously identified phenotype for HSCs. We sorted Lin- cells into GFP+ and GFP− subpopulations and determined repopulation frequencies in a limiting dilution assay. Fifteen percent of recipient mice were reconstituted with 10 Lin- GFP+ cells, and 50% mice with 60 Lin- GFP+ cells. In groups transplanted with 125 to 1000 Lin- GFP+ cells, 100% of the mice were reconstituted. In contrast, no reconstitution was seen in any mice transplanted with 60,000 Lin− GFP− cells, indicating that most if not all HSCs expressed the Abcg2/GFP allele. Secondary transplant experiments and individual lineage analysis of peripheral blood cells confirmed that the Lin- GFP+ cells were long-term HSCs. These results demonstrate that expression of Abcg2 in Lin- cells defines a highly enriched population of HSCs, and is a more specific HSC marker than the SP phenotype. We are now increasing the stringency of the GFP sorting gate and transplanting mice with single cells to determine if a pure HSC population can be isolated with this simple 2 marker system.
Replication study: BET bromodomain inhibition as a therapeutic strategy to target c-Myc

In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Kandela et al., 2015) that described how we intended to replicate selected experiments from the paper "BET bromodomain inhibition as a therapeutic strategy to target c-Myc" (Delmore et al., 2011). Here we report the results of those experiments. We found that treatment of human multiple myeloma (MM) cells with the small-molecular inhibitor of BET bromodomains, (+)-JQ1, selectively downregulated MYC transcription, which is similar to what was reported in the original study (Figure 3B; Delmore et al., 2011). Efficacy of (+)-JQ1 was evaluated in an orthotopically xenografted model of MM. Overall survival was increased in (+)-JQ1 treated mice compared to vehicle control, similar to the original study (Figure 7E; Delmore et al., 2011). Tumor burden, as determined by bioluminescence, was decreased in (+)-JQ1 treated mice compared to vehicle control; however, while the effect was in the same direction as the original study (Figure 7C-D; Delmore et al., 2011), it was not statistically significant. The opportunity to detect a statistically significant difference was limited though, due to the higher rate of early death in the control group, and increased overall survival in (+)-JQ1 treated mice before the pre-specified tumor burden analysis endpoint. Additionally, we evaluated the (-)-JQ1 enantiomer that is structurally incapable of inhibiting BET bromodomains, which resulted in a minimal impact on MYC transcription, but did not result in a statistically significant difference in tumor burden or survival distributions compared to treatment with (+)-JQ1. Finally, we report meta-analyses for each result.
Modeling the Effect of Imperfections in Glassblown Micro Wineglass Fused Quartz Resonators

Author(s): Wang, Y; Asadian, MH; Shkel, AM | Abstract: In this paper, we developed an analytical model, supported by experimental results, on the effect of imperfections in glassblown micro-wineglass fused quartz resonators. The analytical model predicting the frequency mismatch due to imperfections was derived based on a combination of the Rayleigh's energy method and the generalized collocation method. The analytically predicted frequency of the n = 2 wineglass mode shape was within 10% of the finite element modeling results and within 20% of the experimental results for thin shells, showing the fidelity of the predictive model. The postprocessing methods for improvement of the resonator surface quality were also studied. We concluded that the thermal reflow of fused quartz achieves the best result, followed in effectiveness by the RCA-1 surface treatment. All the analytical models developed in this paper are to guide the manufacturing methods to reduce the frequency and damping mismatch, and to increase the mechanical quality factor of the device.
Functional Fitting of Freeform Optics

Functional fitting with orthonormal polynomials of point-cloud freeform optics is investigated. The amount of asymmetry of the optic drives the selection of Cartesian and/or polar basis sets. This parameterization allows design refinement, optimization, and tolerancing.
Sculpting Fano Resonances To Control Photonic–Plasmonic Hybridization

Hybrid photonic–plasmonic systems have tremendous potential as versatile platforms for the study and control of nanoscale light–matter interactions since their respective components have either high-quality factors or low mode volumes. Individual metallic nanoparticles deposited on optical microresonators provide an excellent example where ultrahigh-quality optical whispering-gallery modes can be combined with nanoscopic plasmonic mode volumes to maximize the system’s photonic performance. Such optimization, however, is difficult in practice because of the inability to easily measure and tune critical system parameters. In this Letter, we present a general and practical method to determine the coupling strength and tailor the degree of hybridization in composite optical microresonator–plasmonic nanoparticle systems based on experimentally measured absorption spectra. Specifically, we use thermal annealing to control the detuning between a metal nanoparticle’s localized surface plasmon resonance and the wh...
Superconducting state in M3C60: Strong vs. weak coupling

The superconducting state in the doped fullerenes is due to strong coupling (e.g.,λ≈2.1 for Rb3C60) to low-frequency intramolecular modes Ω≅Ω L ≈250 cm−1 (Ω≡〈Ω2〉1/2). The analysis is based on an equation describingT c for any strength of the coupling and on recent isotope effect and NMR data.
Interactive compression to external information

We describe a new way of compressing two-party communication protocols to get protocols with potentially smaller communication. We show that every communication protocol that communicates C bits and reveals I bits of information about the participants’ private inputs to an observer that watches the communication, can be simulated by a new protocol that communicates at most poly(I) · loglog(C) bits. Our result is tight up to polynomial factors, as it matches the recent work separating communication complexity from external information cost.
Using Adaptive Frequency Sampling for More Efficient Determination of Broad Band Transfer Functions

The goal of most wave-equation modeling (electromagnetics, acoustics, seismics, etc.) is to obtain some response of interest as a function of time or frequency. The basic response, at low frequencies at least, is normally obtained from a first-principles numerical model whose order (e.g., number of unknowns) vastly exceeds the order of the physical problem (related to problem length, area, or volume in wavelengths) it is intended to represent. This means that describing the behavior of observables of interest should be possible using aggregated models of a much lower order than those required for the numerical model itself.
Specificity and Biological Role of Cathepsin D

Cathepsin D was originally isolated from bovine spleen by Press, Porter and Cebra in 1960 (1). My interest in this enzyme was aroused by the observation of its high levels of activity in the involuting post-partum uterus (2); in fact, the uterus contains high levels of this enzyme even in the normal nongravid condition. This led to the purification of cathepsin D from the bovine uterus (3). Uterine cathepsin D was insensitive to a large number of inhibitors specific for thiol, serine, and metallo-proteases, and incapable of cleaving a large group of synthetic peptide substrates typically used for the known proteases (4). Strong inhibition could be obtained only by the use of heavy metals such as Pb2+ and Hg2+. The specificity was determined by the use of the S-sulfo B chain of insulin. Most rapid splitting was at the bonds Leu15-Tyr16, Phe24-Phe25 and Phe25-Tyr26; secondary splitting was found at G1u13-Ala14, and Tyr16-Leu17. These points of cleavage are the same as reported by Press et al. (1). Minor splits were also observed at Phel-Va12 and Ala14-Leu15 (4).
Gene Expression and Endothelial Cell Differentiation

Regulation of the vascular wall is an essential process that allows normal blood flow and facilitates the exchange of soluble gases, ions and vital macromolecules. Normally all vessels are composed of a nonthrombogenic layer of endothelial cells which line the intimai surface of the vessel walls. The differentiation state of this cell layer is maintained by components (factors) present in the blood the extravascular stroma and the extracellular matrix. The contribution of the matrix to vascular wall homeostasis has been unclear in the past, even though matrix comprise a significant portion of the vasculature. In fact, the endothelium is adherent to a thin, specialized extracellular layer know as a basement membrane. The basement membrane provides not only support and an adhesive surface for the endothelium but also maintains the normal differentiated phenotype of the cell layer. Vessel walls also are comprised of other vascular cells such a smooth muscle cells, pericytes and fibroblasts. The former two also have their own basement membrane, and the latter is surrounded by a collagenous insterstitium (the adventitia) and in some cases elastic fibers. Studies which examine the cells comprising the vessel walls must also evaluate the role of the matrix in the maintenance of its structure as well.
The Trouble With Implementing TMDLs

Last year, the Environmental Protection Agency finalized a Total Maximum Daily Load (TMDL) rule that would require states to establish water quality standards for American waterways. The new rule, which is currently under congressional scrutiny, would place emphasis on the rightful goal of water quality policy 3/4 meeting ambient water quality standards. But the rule also restricts one of the most promising methods of meeting that goal: the establishment of allowance markets for discharge rights. Such allowance markets, which have been used successfully in air quality improvement efforts, lower the cost of achieving water quality standards. Moreover, they provide incentive for dischargers to reduce their discharge below their permitted levels.
Biological versus inorganic processes in stromatolite morphogenesis: Observations from mineralizing sedimentary systems

Morphogenesis in stromatolites refers to the pattern of development that creates a megascopic laminated form through repeated cycles of sediment accretion. In general, all sedimentary laminations reflect periodic interruptions in deposition. For example, in stromatolites formed in detrital sedimentary systems, laminations may arise through variations in current velocity and rates of sedimentation (Farmer and Des Marais 1993). In mineralizing sedimentary systems, laminae may form by fluctuations of temperature, pH, or saturation (Guo and Riding 1992), or by seasonal growth cycles of organisms (Chafetz et al. 1991). Laminations can also originate by post-depositional (diagenetic) processes, such as dissolution (Ekdale and Bromley 1988).
Effect of Human Albumin on TCD Vasospasm, DCI, and Cerebral Infarction in Subarachnoid Hemorrhage: The ALISAH Study

Background and Purpose: The neuroprotective effects of human albumin have been studied in animal models of stroke and in humans with various intracranial disorders. We investigated the effect of 25 % human albumin (ALB) on mean cerebral blood flow velocities (MCBFV), delayed cerebral ischemia (DCI), and cerebral infarction.
Advanced mirror construction: ULE replication

With more rapid, affordable access to space and the emerging availability of large-volume fairings, owners and users of current and future space-based optical systems are desiring large-aperture or segmented-aperture primary mirrors for their missions. This demand is driving the need for new approaches to optical component fabrication to produce mirrors and mirror segments that are more cost-efficient with faster manufacturing lead times than traditional optical components. Harris Corporation is executing a mirror development strategy called Advanced Mirror Construction (AMC) to meet this need while still meeting the challenging requirements of space-based optics. A key component of this strategy is the utilization of replication to produce precision lightweight mirror components. We present the motivation and initial results for lightweight replicated, ultra-stable mirrors and mirror segments as well as other key elements of the AMC strategy.
Cobalt(III)-Catalyzed Diastereoselective Three-Component C-H Bond Addition to Butadiene and Activated Ketones.

A highly diastereoselective three-component C–H bond addition across butadiene and activated ketones is described. This transformation provides homoallylic tertiary alcohols through the formation of two C–C σ-bonds and with complete selectivity for an E-alkene isomer. The reaction exhibits good scope with respect to activated ketone inputs, including highly strained cyclic and electron-deficient cyclic and acyclic ketones. Additionally, high diastereoselectivities were achieved for alcohols prepared from unsymmetrical ketones.
Evidence of precursive compression for two deep earthquakes (reply)

DRS DZIEWONSKI AND GILBERT REPLY: Although Geller discusses the problem of the rate of release of seismic energy, his criticism of our paper is concerned with our statement that the isotropic part of the moment rate tensor is precursive by 80 s. In this reply, we address ourselves to this precursive behaviour.
Parents Allowing Drinking Is Associated With Adolescents' Heavy Alcohol Use.

Background Using intergenerational prospective data from the Millennium Cohort Study (MCS), we examine whether parents allowing 14-year-olds to drink alcohol is associated with greater likelihood of early adolescents' heavy episodic drinking (i.e., lifetime, rapid escalation from first drink, and frequent past year), beyond shared risk factors for parental alcohol permissiveness and adolescent alcohol use. Methods The MCS is a unique, contemporary, nationally representative study with mother, father, and child data from infancy through age 14 years (n = 11,485 children and their parents). In a series of multivariate logistic regressions, we estimated whether teenagers whose parents allowed them to drink alcohol (16% of parents said "yes") faced an elevated likelihood of heavy alcohol use at age 14, controlling for a large host of likely child and parent confounders measured when children were age 11. To further assess plausible intergenerational associations of parental alcohol permissiveness and offspring heavy alcohol use, coarsened exact matching (CEM) was used to match 14-year-olds whose parents allowed them to drink alcohol with teens whose parents did not allow them to drink on these childhood antecedent variables. Results Adolescents whose parents allowed them to drink had higher odds of heavy drinking (odds ratio [OR] = 2.40; 95% confidence interval [CI] = 1.96 to 2.94), rapidly escalating from initiation to heavy drinking (OR = 1.94; CI = 1.52 to 2.49), and frequent heavy drinking (OR = 2.32; 1.73 to 3.09), beyond child and parent confounders and using CEM methods. Conclusions Adolescents who were allowed to drink were more likely to have transitioned quickly from their first drink to consuming 5 or more drinks at 1 time and to drinking heavily 3 or more times in the past year. Given well-documented harms of adolescent heavy drinking, these results do not support the idea that parents allowing children to drink alcohol inoculates them against alcohol misuse.
Airway basal cell injury after acute diacetyl (2,3-butanedione) vapor exposure.

Abstract Rationale Diacetyl (DA; 2,3-butanedione) is a chemical found commonly in foods and e-cigarettes. When inhaled, DA causes epithelial injury, though the mechanism of repair remain poorly understood. The objective of this study was to evaluate airway basal cell repair after DA vapor exposure. Methods Primary human bronchial epithelial cells were exposed to DA or PBS for 1 h. Lactate dehydrogenase, cleaved caspase 3/7 and trans-epithelial electrical resistance were measured prior to and following exposure. Exposed cultures were analyzed for the airway basal cell markers keratin 5 and p63 as well as ubiquitin and proteasome activity. Cultures were also treated with a proteasome inhibitor (MG132). Results DA vapor exposure caused a transient decrease in trans-epithelial electrical resistance in all DA-exposed cultures. Supernatant lactate dehydrogenase and cleaved caspase 3/7 increased significantly at the highest DA concentration but not at lower DA concentrations. Increased keratin 5 ubiquitination occurred after DA exposure but resolved by day 3. Damage to airway basal cells persisted at day 3 in the presence of MG132. Conclusions Diacetyl exposure results in airway basal cell injury with keratin 5 ubiquitination and decreased p63 expression. The ubiquitin-proteasome-pathway partially mediates airway basal cell repair after acute DA exposure.
Low-Speed Turbulent Shear-Driven Mixing Layers with Large Thermal and Compositional Density Variations

Low speed shear-driven mixing layers involving fluid streams of different densities due to temperature or compositional variations are described by remarkably similar equations with some differences in the formulations of the molecular transport terms. These differences are related to specifics of the heat conduction and mass diffusion operators, as well as viscosity dependence on mixture molar mass and temperature in the low Mach number limit. Direct numerical simulations are performed in incompressible/low-speed limits to study the differences and similarities in mixing behavior associated with these configurations. The results demonstrate both subtle and significant changes in the mixing behavior for variable composition versus variable temperature mixing. Higher-order statistics related to density field reveal greater differences than are apparent from mean profiles; these differences can be extremely important when the physics is sensitive to mixing, such as in combustion problems. Therefore, conclusions regarding the mixing dynamics drawn from variable temperature mixing are not necessarily applicable to multi-species mixing.
A Smartphone-Interfaced, Flexible Electrochemical Biosensor Based on Graphene Ink for Selective Detection of Dopamine

This study reports the fabrication of flexible electrochemical dopamine sensors using a facile, low temperature (300°C) process based on spin-coating of commercially available graphene ink onto a polyimide (PI) substrate. The electrochemical testing and surface characterization were achieved using cyclic voltammetry (CV), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). The graphene-ink based biosensor demonstrated a limit of detection (LoD) of 100 nM of dopamine in PBS and a dynamic concentration range up to 1 mM, with excellent specificity against uric acid and ascorbic acid. The sensor is also resilient against mechanical deformation ( $1~\mu \text{m}$ to 5 nM in artificial sweat. Wireless data transfer via Wi-Fi in tandem with an on-chip sensor integrated with an in-house built potentiostat is also developed to demonstrate the applicability of the platform for point-of-care applications.
Validation of aorta–lesion–attenuation difference on preoperative contrast-enhanced computed tomography scan to differentiate between malignant and benign oncocytic renal tumors

We previously noted that the aorta–lesion–attenuation difference (ALAD) determined on CT scan discriminated well between chromophobe RCC and oncocytoma. The current evaluation seeks to validate these initial findings in a second cohort of nephrectomy patients. A retrospective review of preoperative CT scans and surgical pathology was performed on patients undergoing nephrectomy for small, solid renal masses. ALAD was calculated by measuring the difference in Hounsfield units (HU) between the aorta and the lesion of interest on the same image slice on preoperative CT scan. The discriminative ability of ALAD to differentiate malignant pathology from oncocytoma was evaluated by sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve (AUC) using ROC analysis. Twenty-one preoperative CT scans and corresponding pathology reports were reviewed and included in the validation cohort. ALAD values were calculated during the excretory and nephrographic phases. Compared to the training cohort, patients in the validation cohort were significantly older (62 versus 59 years old), had larger tumors (3.7 versus 2.7 cm), and higher stage disease (59% versus 79% T1a disease). Nephrographic ALAD was able to differentiate malignant pathology from oncocytoma in the training and validation cohorts with a sensitivity of 84% versus 73%, specificity of 86% and 67%, PPV of 98% versus 91%, and NPV of 33% versus 35%. The AUC for malignant pathology versus oncocytoma in the validation cohort was 0.72 (95% CI 0.63–0.82). Nephrographic ALAD was able to differentiate chromophobe RCC from oncocytoma in the training and validation cohorts with a sensitivity of 100% versus 67%, specificity of 86% versus 67%, PPV of 75% versus 43%, and NPV of 100% versus 84%. The AUC for chromophobe RCC versus oncocytoma in the validation cohort was 0.72 (95% CI 0.48–0.96). The ability of ALAD to discriminate between chromophobe RCC and oncocytoma was diminished in the validation cohort compared to the training cohort, but remained significant. The current findings support further investigation in the role of ALAD in the management of patients with indeterminate diagnoses of oncocytic neoplasm.