cssi/SciSciGPT-SciSciNet huggingface dataset:
Global models of surface wave attenuation

[1] A large data set of fundamental mode Rayleigh wave amplitudes is analyzed to derive global models of surface wave attenuation (1/Q). The data set consists of measurements of Rayleigh wave amplitude anomalies in the period range 50–250 s for 347 earthquakes observed at 179 seismic stations. The amplitude anomalies are considered to depend on four factors: intrinsic attenuation along the ray path, elastic focusing effects along the ray path, a source factor accounting for uncertainties in the strength of excitation, and a receiver factor accounting for uncertainties in the response at the station. The amplitude data are inverted simultaneously for global maps of attenuation expanded in spherical harmonics up to degree 12, global maps of phase velocity expanded to degree 20, and source and receiver correction factors. All four variable types are shown to be important in explaining the amplitude anomalies. A data set of phase delay measurements provides additional constraints on velocity structure. The maps of attenuation obtained by simultaneous inversion for elastic and anelastic models contain important features that are not robustly imaged when the effect of focusing on wave amplitude is ignored. These include high attenuation along western North America and along the East Pacific Rise and other ridge systems and low attenuation associated with stable continental interiors. The global attenuation maps exhibit a strong correlation with phase velocity maps corrected for the effect of the crust, particularly for periods <200 s. The correlation suggests that the variability in both Q and velocity in the shallow upper mantle is primarily thermal in origin.
A Comparative Study of ZnO−CuO−Al2O3/SiO2−Al2O3 Composite and Hybrid Catalysts for Direct Synthesis of Dimethyl Ether from Syngas

Two different strategies for the preparation of active dimethyl ether catalysts are evaluated using CuO−ZnO−Al2O3 and SiO2−Al2O3 as methanol synthesis and methanol dehydration catalysts components,...
Grain size, strain rate, and temperature dependence of flow stress in ultra-fine grained and nanocrystalline Cu and Al: Synthesis, experiment, and constitutive modeling

Abstract For the first time, high quality bulk nanocrystalline (nc) fcc metals, with least amounts of imperfections, exhibiting high strength and ductility at room and different temperatures, under quasi-static and dynamic types of loading, were prepared and a comprehensive study on their post-yield mechanical properties was performed. This investigation included study of the effect of temperature on stress–strain responses of mechanically milled bulk nc Cu and Al. The samples after preparation through mechanical milling and consolidation processes were subjected to uniaxial compressive loading at quasi-static and dynamic strain rates of 10−2 s−1 and 1840–3105 s−1, respectively, at temperatures ranging from 223 to 523 K. In both materials strong dependency of flow stress to temperature was observed; this dependency was rather more pronounced when the materials were tested at the quasi-static strain rate. Further, a new grain size and temperature dependent viscoplastic phenomenological constitutive equation, Khan–Liang–Farrokh (KLF) model was developed based on the Khan–Huang–Liang (KHL) constitutive equation. The model was featured to correlate different characteristic behaviors of polycrystalline materials in the plastic regime, as the result of grain refinement. In addition, the viscoplastic responses of bulk Cu and Al of different grain sizes (from sub-micron to nanometer range), and those from bulk nc Cu and Al at different strain rates (quasi-static to dynamic), recently published ( Khan et al., 2008b , Khan et al., 2008a ), were simulated using the newly developed equation. The results confirmed reasonable capability of the developed model to correlate a wide spectrum of the viscoplastic responses of these fcc metals.
Stressors and child and adolescent psychopathology: Evidence of moderating and mediating effects.

This paper reviews studies that have tested for moderators or mediators of the relation between stressors and child and adolescent psychopathology. Many studies have tested for moderation, but results of research studying moderators have been inconclusive. There have been few theory-based studies and there have been few consistent findings. Far fewer studies have tested for mediation effects, but these studies have generally been theory-driven, have more often built upon one another in an incremental fashion, and have yielded consistent results. In particular, there is substantial evidence for the mediating role of family relationship in the relation between stressors and child and adolescent psychological symptoms. Future studies should integrate moderator and mediator research by testing for specific mediators in relation to particular moderating contexts, so that we can better understand the complex ways in which stressful life experiences affect the well-being of children and adolescents.
Spatial and temporal analysis of weather radar reflectivity images

This paper illustrates the use of a primitive symbolic description of an image to obtain more robust identification of amorphous objects than would be possible with more conventional edge or gradient-based segmentation techniques. An algorithm is described which uses a simple multi-level thresholding operation to form a symbolic representation of weather radar reflectivity images. This representation allows the use of detailed rules for the detection and quantification of the image features. A method is described for using this information to identify significant intensity peaks in an image, and examples of its performance are shown.
Molecular Mimicry and the Pathogenesis of Insulin-dependent Diabetes Mellitus: Still Just an Attractive Hypothesis

An abundant body of literature suggests that the cellular immune system plays a key role in the autoimmune destruction of insulin-secreting pancreatic β cells that results in insulin-dependent diabetes mellitus (IDDM). For years, studies have supported the concept that molecular mimicry, a process of antigenic crossreactivity resulting from similarity in amino acid sequence or structure, could be one pathway whereby this disease is induced or its natural history modulated. However, the transfer of this ‘hypothesis’ to that of a proven mechanism underlying this clinical disorder has been slow and never fully achieved. This article reviews the theoretical basis for molecular mimicry in autoimmune disease and the evidence supporting its role in the pathogenesis of IDDM.
Vegetally localized Xenopus trim36 regulates cortical rotation and dorsal axis formation.

Specification of the dorsoventral axis in Xenopus depends on rearrangements of the egg vegetal cortex following fertilization, concomitant with activation of Wnt/β-catenin signaling. How these processes are tied together is not clear, but RNAs localized to the vegetal cortex during oogenesis are known to be essential. Despite their importance, few vegetally localized RNAs have been examined in detail. In this study, we describe the identification of a novel localized mRNA, trim36, and characterize its function through maternal loss-of-function experiments. We find that trim36 is expressed in the germ plasm and encodes a ubiquitin ligase of the Tripartite motif-containing (Trim) family. Depletion of maternal trim36 using antisense oligonucleotides results in ventralized embryos and reduced organizer gene expression. We show that injection of wnt11 mRNA rescues this effect, suggesting that Trim36 functions upstream of Wnt/β-catenin activation. We further find that vegetal microtubule polymerization and cortical rotation are disrupted in trim36-depleted embryos, in a manner dependent on Trim36 ubiquitin ligase activity. Additionally, these embryos can be rescued by tipping the eggs 90° relative to the animal-vegetal axis. Taken together, our results suggest a role for Trim36 in controlling the stability of proteins regulating microtubule polymerization during cortical rotation, and subsequently axis formation.
Photocurrents in a metal-semiconductor-metal photodetector

Photocurrents in a metal-semiconductor-metal (MSM) photodetector have been analyzed in a one-dimensional structure using both time-dependent and steady-state continuity equations. Analytical solutions are presented for the carrier concentrations as well as for the currents, which form a valuable tool for the investigation of the detector behavior under various bias conditions. Applying these expressions to a GaAs device, we have studied the influence of carrier diffusion, recombination, and drift on the photocurrents as a function of the applied bias voltage. We also show that the switching time at low bias voltage is dominated by a voltage-independent diffusion time constant which is of particular interest when using the device as an optoelectronic sampling gate. On the other hand, carrier recombination is found to have minimal influence on DC characteristics and pulse response.
An experimental investigation of nitrogen gas produced during denitrification.

In situ denitrification relies on indigenous microorganisms to reduce nitrate to N2 gas. However, when initial nitrate concentrations are large, produced gas volumes also can be very large, potentially resulting in reduced water saturation and hydraulic conductivity in the treatment zone. In this study, we investigated the fate of N2 and other gases produced during denitrification in a laboratory flow cell containing packed sediment. Denitrifying activity was stimulated by additions of nitrate and ethanol. Microbial activity was monitored by measuring nitrate, nitrite, and ethanol concentrations; gas saturations were measured during the experiment using a gamma imaging system. Biomass was measured using phospholipid fatty acid analysis of sediment samples. Bioenergetic calculations calibrated to measured nitrate consumed and biomass produced predicted that 1.2 L N2 gas/L water should have been produced following the addition of 100 mM nitrate. However, the maximum measured gas saturation was only 23%, indicating substantial gas loss from the sediment pack. Temporal gamma images and visual observations confirm that small gas bubbles formed in the sediment pack coalesced into larger bubbles and migrated upward through gas-filled channels to the sediment pack surface. Although gas saturations increased, there was no significant change in sediment pack hydraulic conductivity. These results suggest that in permeable reactive barriers used for in situ denitrification, gas production will not necessarily lead to unlimited gas accumulation in the pore space and that the effects of gas production on water saturation and hydraulic conductivity may be relatively minor.
A topological algorithm for continuous grasp planning

Consideration is given to the planning of multifingered dexterous grasps to meet the physical constraints of some anticipated action. Most of the existing dexterous grasp planning schemes operate on a finite and discrete set of grasps. Such a discrete set obviously hinders the applicability of grasp planning schemes to complex and versatile task requirements. A description is given of a hierarchy of topological and geometrical spaces representing the set of grasps, and a topological algorithm is proposed for the planning of continuous grasps using computational techniques drawn from point-set, combinatorial, and algebraic topology. The topological algorithm is illustrated by a pinch grasp example using a stick model of a four-fingered hand. >
Three Forms of Agential Commitment: Reply to Cullity and Gerrans

uman agents are purposive agents who are also capable of stronger forms of agency, including forms of self-governance. Or so it seems. A central problem in the philosophy of action is how to understand these stronger forms of agency, and what further philosophical commitments are required for their understanding. Recent work in Frankfurt-influenced philosophy of action on ownership, identification, internality, authority, and endorsement are, at least in large part, efforts to develop a sufficiently rich theoretical apparatus for this task. At bottom is the idea that strong forms of agency that are of interest can be modelled within, as Cullity and Gerrans put it, a 'nonhomuncular causal account of agency'.1 Self-governance is constituted by forms of psychological functioning that appropriately involve identification and the like. And we explain these phenomena within a 'non-homuncular causal account'. If this is our project, then our main concern will be whether any such model can provide sufficient conditions for selfgovernment and related phenomena, or whether these come with a higher philosophical cost. If we do succeed in providing such sufficient conditions, but also conclude there are several different kinds of functioning that are each sufficient for these strong forms of agency (but neither of which is necessary),2 or that some actions inherit their status as autonomous by way of their relation to more basic cases and capacities, these would be important but non-threatening insights. The essays of mine that are the concern of Cullity and Gerrans's probing discussion aim to contribute to this project by
Delay-bounded packet scheduling of bursty traffic over wireless channels

In this paper, we study minimal power transmission of bursty sources over wireless channels with constraints on mean queuing delay. The power minimizing schedulers adapt power and rate of transmission based on the queue and channel state. We show that packet scheduling based on queue state can be used to trade queuing delay with transmission power, even on additive white Gaussian noise (AWGN) channels. Our extensive simulations show that small increases in average delay can lead to substantial savings in transmission power, thereby providing another avenue for mobile devices to save on battery power. We propose a low-complexity scheduler that has near-optimal performance. We also construct a variable-rate quadrature amplitude modulation (QAM)-based transmission scheme to show the benefits of the proposed formulation in a practical communication system. Power optimal schedulers with absolute packet delay constraints are also studied and their performance is evaluated via simulations.
Rate of Tension Development in Cardiac Muscle Varies With Level of Activator Calcium

Abstract In skeletal muscle, the rate of transition from weakly bound to force-generating crossbridge states increases as calcium concentration is increased. To examine possible calcium sensitivity of this transition in cardiac muscle, we determined the kinetics of isometric tension development during steady activation in detergent-permeabilized rat ventricular trabeculae (n=7) over a range of calcium concentrations. Force-generating crossbridges in activated trabeculae were disrupted by a brief, rapid release and restretch equivalent to 20% muscle length (15°C), which resulted in a subsequent phase of tension redevelopment that was well fit by a monoexponential function (rate constant, ktr). Sarcomere length was monitored by laser diffraction and held constant during tension redevelopment by an iterative adaptive feedback control system. The ktr increased from 3.6±0.8 s−1 at the lowest calcium concentration studied (pCa 5.9) to 9.5±1.3 s−1 during maximal activation (pCa 4.5). The relationship between rel...
Serotonin transporter knockout mice have a reduced ventilatory response to hypercapnia (predominantly in males) but not to hypoxia

Medullary serotonergic (5-HT) neurons are implicated in central chemoreception and 5-HT abnormalities are present in many cases of the sudden infant death syndrome (SIDS). Mice with a targeted disruption of the serotonin transporter (5-HTT) develop in the presence of excess 5-HT in brain extracellular fluid (ECF). As adults they exhibit reduced 5-HT neuron activity and 5-HT1A receptor binding with varying changes in postsynaptic 5-HT receptor function. They exhibit behavioural phenotypes (anxiety, reduced aggression) but little is known about their control of breathing. We show that conscious adult male and female 5-HTT knockout mice breathing air at room temperature have a higher resting , breathing frequency and but a normal body temperature and ratio (the ventilatory equivalent) compared to wild-type (WT) controls. In hypercapnia, there is a reduced ventilatory response (expressed as the ratio) that is much more prominent in males (−68%) than females (−22%). In hypoxia, both males and females exhibit a higher , and body temperature but their ratio is normal. We conclude that 5-HTT knockout mice have a diminished function of the medullary 5-HT system, which is manifest most remarkably in a substantial loss of CO2 sensitivity predominantly in males. This finding supports the importance of medullary 5-HT neurons in central chemoreception. Females either rely less on 5-HT neurons in chemoreception or adapt more readily to the loss of 5-HT function. This genetic model allows examination of the role of excess 5-HT in ECF in the development of the control of breathing and central chemoreception, which may be pertinent to SIDS.
AITVS: Advanced Interactive Traffic Visualization System

Transportation and the highway network form the backbone of the total public infrastructure system. As such, planning and monitoring for an effective transportation system is crucial in the building and maintenance of a regions economy and safety. However, demand for road travel continues to expand as population increases (particularly in the metropolitan areas) while new constructions have not kept pace. According to the Federal Highway Administration, it is forecasted that the volume of freight movement alone is to nearly double by 2020 [1]. Congestion and looming gridlock crises seriously threaten any regions mobility, safety and economic vitality. A crucial component in addressing these concerns is the development of specific technologies to monitor, model, and optimize traffic flow.
Copper-, palladium-, and platinum-containing complexes of an asymmetric dinucleating ligand.

The coordination chemistry of an asymmetric dinucleating hexadentate ligand LH2 comprising neutral alkyltriamine and potentially dianionic dicarboxamido-pyridyl donor sets with copper, palladium, and platinum has been explored. Monometallic, dicopper, and heterodinuclear Cu–Pd and −Pt complexes have been prepared and characterized, including by NMR, EPR, UV–vis, and IR spectroscopy and X-ray crystallography. For example, the monometallic complexes [(LH2)MCl]X (M = Cu, X = OTf; M = Pd or Pt, X = Cl) were prepared, wherein the metal(II) ions are coordinated to the triamine portion and the pyridyldicarboxamide is unperturbed. Treatment of LH2 with [MesCu]x (Mes = mesityl) provided a monocopper(I) complex, again with the metal coordinated only to the trialkylamine donor set. Reaction of [(LH2)CuCl]OTf with NaOMe resulted in an unexpected migration of the copper(II)–chloride fragment to the pyridyldicarboxamide site to yield Na[LCuCl], from which a dicopper complex LCu2Cl2 and mixed-metal complexes LCu(Cl)M(Cl...
Postglacial vegetation, fire, and climate history of the Siskiyou Mountains, Oregon, USA

The forests of the Siskiyou Mountains are among the most diverse in North America, yet the long-term relationship among climate, diversity, and natural disturbance is not well known. Pollen, plant macrofossils, and high-resolution charcoal data from Bolan Lake, Oregon, were analyzed to reconstruct a 17,000-yr-long environmental history of high-elevation forests in the region. In the late-glacial period, the presence of a subalpine parkland of Artemisia, Poaceae, Pinus, and Tsuga with infrequent fires suggests cool dry conditions. After 14,500 cal yr B.P., a closed forest of Abies, Pseudotsuga, Tsuga, and Alnus rubra with more frequent fires developed which indicates more mesic conditions than before. An open woodland of Pinus, Quercus, and Cupressaceae, with higher fire activity than before, characterized the early Holocene and implies warmer and drier conditions than at present. In the late Holocene, Abies and Picea were more prevalent in the forest, suggesting a return to cool wet conditions, although fire-episode frequency remained relatively high. The modern forest of Abies and Pseudotsuga and the present-day fire regime developed ca. 2100 cal yr B.P. and indicates that conditions had become slightly drier than before. Sub-millennial-scale fluctuations in vegetation and fire activity suggest climatic variations during the Younger Dryas interval and within the early Holocene period. The timing of vegetation changes in the Bolan Lake record is similar to that of other sites in the Pacific Northwest and Klamath region, and indicates that local vegetation communities were responding to regional-scale climate changes. The record implies that climate-driven millennial- to centennial-scale vegetation and fire change should be considered when explaining the high floristic diversity observed at present in the Siskiyou Mountains.
Emergent literacy in print and electronic contexts: The influence of book type, narration source, and attention.

Abstract Young children learn from traditional print books, but there has been no direct comparison of their learning from print books and tablet e-books while controlling for narration source. The current project used a between-subjects design and examined how 4-year-olds (N = 100) learned words and story content from a print book read aloud by a live adult, a print book narrated by an audio device, an e-book read aloud by a live adult, and an e-book narrated by an audio device. Attention to the book and prior experience with tablet e-books were also measured and included in analyses. When controlling for vocabulary, the overall pattern of results revealed that children learned more words from the e-book and from the audio narrator, but story comprehension did not differ as a function of condition. Attention predicted learning, but only in some print book contexts, and significant effects of prior experience did not emerge.
Freewheeling sisters cause problems

The factors that lead to errors in chromosome segregation during the production of egg cells in humans are becoming clearer.
Pharmacokinetic findings from the phase I study of Quarfloxin (CX-3543): a protein-rDNA quadruplex inhibitor, in patients with advanced solid tumors.

B93 Background: Ribosomal RNA (rRNA) biosynthesis and subsequent ribosome assembly determine the proliferative state of cells, and these processes are highly amplified in cancer due to mutations in regulatory signaling pathways that control rRNA biogenesis. Quarfloxin, a novel fluoroquinolones derivative, directly inhibits aberrant rRNA biogenesis in cancer cells by disrupting an essential protein-ribosomal DNA interaction that is over-expressed, thereby selectively triggering apoptotic cell death in tumor cells but not in normal cells. A phase I study of quarfloxin has been completed in patients with solid tumors, including an elucidation of this agent’s pharmacokinetic attributes. Material and Methods: This phase I study was designed to identify the maximum tolerated dose (MTD), the dose limiting toxicities and the pharmacokinetic profile of quarfloxin when administered as an IV infusion for 5 consecutive days every 21 days, to patients with advanced solid tumors. Serial blood samples were collected for analysis on Day 1 and Day 5 of dosing during the first cycle of drug administration. A twelve hour urine sample was also collected with Day 1 drug administration to determine urinary clearance of quarfloxin. Results: A total of 48 patients from 8 escalating dose cohorts of quarfloxin had samples collected for pharmacokinetic analysis. Twenty of these patients were dosed at the maximum tolerated dose level (360 mg/m2). Area under the plasma concentration versus time curve generally increased in proportion with each dose level escalation. Urinary clearance was noted to be consistent throughout all dose levels. Plasma terminal half life was observed to be longer on Day 5 when compared with Day 1, and a trend of increasing plasma terminal half life with each subsequent dose escalation was also evident. The increase in plasma terminal half lives did not result in significant plasma quarfloxin accumulation, and were thought unlikely to be due to saturated elimination. In vitro tests using human whole blood revealed that quarfloxin associates reversibly with blood cells, and that whole blood concentration could be up to five fold more than plasma quarfloxin concentration. The pharmacokinetic analysis protocol was amended to include assessments of whole blood and plasma concentration in ten phase I patients at the MTD level of 360 mg/m2. At the MTD, Day 5 quarfloxin plasma and whole blood terminal half lives are 75.1 hours and 28.3 hours, respectively. Conclusions: Thereversible association of quarfloxin with blood cells creates a “reservoir” of drug that is gradually released into plasma, thus extending the plasma terminal half life. This attribute supports drug administration on a weekly basis, and a phase I study of weekly quarfloxin administration is in progress.
Sequenced versus coordinated treatment for adolescents with comorbid depressive and substance use disorders.

Objective We evaluated 3 methods of integrating interventions for depression (Adolescent Coping With Depression Course; CWD) and substance use disorders (Functional Family Therapy; FFT), examining (a) treatment sequence effects on substance use and depression outcomes and (b) whether the presence of major depressive disorder (MDD) moderated effects. Method Participants were 170 adolescents (ages 13-18; 22% female; 61% non-Hispanic White) with comorbid depressive disorder (54% MDD, 18% dysthymia) and substance use disorders who were randomized to (a) FFT followed by CWD (FFT/CWD), (b) CWD followed by FFT (CWD/FFT), or (c) coordinated FFT and CWD (CT). Acute treatment (24 treatment sessions provided over 20 weeks) and 6- and 12-month follow-up effects are presented for substance use (percentage of days of substance use; Timeline Followback) and depression (Children's Depression Rating Scale-Revised). Results FFT/CWD achieved better substance use outcomes than CT at posttreatment, and 6- and 12-month follow-ups; substance use effects for CWD/FFT were intermediate. For participants with baseline MDD, the CWD/FFT sequence resulted in lower substance use than either FFT/CWD or CT. Depressive symptoms decreased significantly in all 3 treatment sequences with no evidence of differential effectiveness during or following treatment. Attendance was lower for the second of both sequenced interventions. A large proportion of the sample received treatment outside the study, which predicted better outcomes in the follow-up. Conclusions Depression reductions occurred early in all 3 treatment sequences. Of the examined treatment sequences, FFT/CWD appeared most efficacious for substance use reductions but addressing depression early in treatment may improve substance use outcomes in the presence of MDD.
Cultural Techniques and Major Characteristics of New Japonica Rice Huayu 446

Huayu 446 is new japonica rice that Tianjin Rice Research Institute pr oduced by means of biotechnology. It has the characteristics of suitable maturit y, good grain quality, high and stable yield, good blast resistance and fine syn thesize properties. And it is suitable for planting for early cropping season in Beijing, Tianjin and Tangshan etc.
The role of quantitative policy analysis in HIV prevention technology transfer.

Public Health Reports / January–February 2004 / Volume 119 19 © 2004 Association of Schools of Public Health There has been an increasing emphasis in public health on the delivery of services with a strong empirical foundation.1 This attention to evidence-based public health is manifest in the field of HIV prevention, where technology transfer efforts have recently been expanded.2–5 These efforts have focused largely on critically reviewing the HIV prevention intervention literature, identifying high quality scientific tests of interventions, summarizing the literature on effective interventions (either qualitatively or via meta-analysis), recommending these interventions to service providers, and providing some level of support to assist the service providers in adopting the science-based interventions (via supportive documentation, workshop-style training, or on-site technical assistance).2–7 Albeit scarce, some research has been conducted on the best method of delivering HIV prevention intervention technical assistance to service provision organizations.8 While these technology transfer efforts are important and useful, service provision organizations—especially community-based organizations—have encountered several barriers in adopting science-based HIV prevention interventions.8–10 These barriers include: (1) lack of financial, human, and temporal resources to deliver what tend to be relatively intensive HIV prevention interventions; (2) lack of resources to pay the enrollment incentives that characterize HIV prevention intervention trials; (3) high levels of staff turnover; (4) lack of sufficient training opportunities; and (5) lack of science-based interventions specifically focused on a particular community being served (thereby requiring adaptation of the intervention for the community at hand).8–10 Of key importance is that service provision organizations need to decide whether they can afford a particular science-based HIV prevention intervention.9–11 Policy makers who must allocate resources across disease areas also encounter difficulties when confronted with HIV prevention intervention literature syntheses. While they need to know if HIV prevention interventions are effective, they must also know the relative public health return on investment if funds are allocated to HIV prevention relative to some other important health area (such as cancer prevention or heart disease).11 The Role of Quantitative Policy Analysis in HIV Prevention Technology Transfer
Behavioral effects of opioid peptides:implications for future clinical research

In the previous chapter, the findings from the clinical studies conducted by our group at the University of California, San Diego, are described and commented upon. Davis et al. (1977) reported a decline in unusual thought content and Berger et al. (1977) noted a reduction in auditory hallucinations in schizophrenics following naloxone infusion. This short chapter will highlight the way in which animal work generated the human investigations and describe the overall conceptual framework which has guided our research in this area.
Monte Carlo Markov Chains

Monte Carlo Markov Chains (MCMC) are a powerful method to analyze scientific data that has become popular with the availability of modern-day computing resources. The basic idea behind an MCMC is to determine the probability distribution function of quantities of interest, such as model parameters, by repeatedly querying datasets used for their measurement. The resulting sequence of values form a Markov chain that can be analyzed to find best-fit values and confidence intervals. The modern-day data analyst will find that MCMCs are an essential tool that permits tasks that are simply not possible with other methods, such as the simultaneous estimate of parameters for multi-parametric models of virtually any level of complexity, even in the presence of correlation among the parameters.
Therapeutic Drug Monitoring (TDM) of IV Busulfan in Patients with Severe Obesity.

Abstract It has been previously reported that increases in relapse and graft rejection can be associated with a low busulfan area under the curve (AUC) and hepatic toxicities are associated with a high AUC. This has lead to strategies to adjust busulfan dosing to achieve a target AUC. A retrospective analysis was performed in patients with severe obesity, defined as a Body Mass Index (BMI) greater than 40, to evaluate the reliability of IV busulfan dosed using the package insert dosing strategy to reach a targeted AUC. The study included 11 females and 8 males who received IV busulfan as part of their hematopoietic progenitor cell transplant preparative regimen. There were 11 autologous and 8 allogeneic transplants for lymphoma (10) and leukemia (9). The mean and median ages were 38 and 41 years (range 19–51). The mean and median BMIs for this population were 47.8 and 46.2 (range 40.4–62.7). The mean and median weights were 139.5 kg and 142.5 kg (range 107–192.3). TDM was performed with the first dose of busulfan along with subsequent dosage adjustments to achieve a target AUC of 1150–1350 micromol X min/L. Busulfex package insert dosing recommendations are for 16 doses of 0.8 mg/kg (12.8 mg/kg) using an adjusted ideal body weight (AIBW) for obese patients. AIBW = 0.25 × (actual weight − ideal body weight) + ideal body weight. Using the AIBW dosing, the mean starting dose to actual body weight ratio was 0.48 mg/kg (range 0.40–0.55 mg/kg). Based on the AUC analysis, the predicted mean AUC using the AIBW dosing was 972 (range 702–1356). Six AUCs were below 900, 10 AUCs were above 900 but below 1150, 2 AUCs were within the target range and 1 AUC was greater than 1350. Thirteen of the patients had repeat AUC analyses following a subsequent dose to confirm that the dose adjustments achieved the targeted AUCs. Seven of these patients had further dose adjustments following the repeat AUC analysis. Five patients with a busulfan mean half-life of 235 minutes (range 218–247 minutes) had higher AUCs than the rest of the group. The mean and median AUCs for these 5 patients were 1177 and 1223 (range 997–1357). The remaining 14 patients with a mean busulfan half-life of 177 minutes (range 151–201) had mean and median AUCs of 899 and 903 (range 702–1105). The total therapy delivered ranged from 12.7 to 21.4 mg/kg based on the AIBW. When calculated on actual weight, the range was 6.9 to 11.24 mg/kg. Conclusion: The AIBW dosing strategy of IV busulfan is inadequate to achieve the targeted AUC of 1150–1350 in severely obese patients. Severely obese patients require dose increases in the majority of cases, while those with delayed clearance could be overdosed if higher doses are administered without TDM. Severely obese patients require TDM and the majority will require dosage adjustments to administer IV busulfan in the targeted therapeutic range.
Synchronization Synthesis for Network Programs

In software-defined networking (SDN), a controller program updates the forwarding rules installed on network packet-processing devices in response to events. Such programs are often physically distributed, running on several nodes of the network, and this distributed setting makes programming and debugging especially difficult. Furthermore, bugs in these programs can lead to serious problems such as packet loss and security violations. In this paper, we propose a program synthesis approach that makes it easier to write distributed controller programs. The programmer can specify each sequential process, and add a declarative specification of paths that packets are allowed to take. The synthesizer then inserts enough synchronization among the distributed controller processes such that the declarative specification will be satisfied by all packets traversing the network. Our key technical contribution is a counterexample-guided synthesis algorithm that furnishes network controller processes with the synchronization constructs required to prevent any races causing specification violations. Our programming model is based on Petri nets, and generalizes several models from the networking literature. Importantly, our programs can be implemented in a way that prevents races between updates to individual switches and in-flight packets. To our knowledge, this is the first counterexample-guided technique that automatically adds synchronization constructs to Petri-net-based programs. We demonstrate that our prototype implementation can fix realistic concurrency bugs described previously in the literature, and that our tool can readily scale to network topologies with 1000+ nodes.
Designing assessments to track student progress

Learning scientists have embraced the idea of using learning progressions for the development of assessments to monitor learning over time. Using LPs to develop assessments requires an iterative, process-oriented approach, and involves design products that work in real contexts. This proposal illustrates a design research process, Construct-Centered Design, for the development of assessment tasks to track the long-term development of student learning for a core idea in science -- the transformation of matter. Fifty-six items of various types were designed to measure student understanding along the lower levels of a LP. We iteratively collected cross-sectional data from 500 middle students for developing, piloting, and revising the assessment items. We conclude the paper by discussing the strengths of and weaknesses of this process for measuring students' understanding across levels of the LP. The ultimate value of this work will propose the design process of assessment to track student learning.
TDP1 is required for efficient non-homologous end joining in human cells

Tyrosyl-DNA phosphodiesterase 1 (TDP1) can remove a wide variety of 3' and 5' terminal DNA adducts. Genetic studies in yeast identified TDP1 as a regulator of non-homologous end joining (NHEJ) fidelity in the repair of double-strand breaks (DSBs) lacking terminal adducts. In this communication, we show that TDP1 plays an important role in joining cohesive DSBs in human cells. To investigate the role of TDP1 in NHEJ in live human cells we used CRISPR/cas9 to produce TDP1-knockout (TDP1-KO) HEK-293 cells. As expected, human TDP1-KO cells were highly sensitive to topoisomerase poisons and ionizing radiation. Using a chromosomally-integrated NHEJ reporter substrate to compare end joining between wild type and TDP1-KO cells, we found that TDP1-KO cells have a 5-fold reduced ability to repair I-SceI-generated DSBs. Extracts prepared from TDP1-KO cells had reduced NHEJ activity in vitro, as compared to extracts from wild type cells. Analysis of end-joining junctions showed that TDP1 deficiency reduced end-joining fidelity, with a significant increase in insertion events, similar to previous observations in yeast. It has been reported that phosphorylation of TDP1 serine 81 (TDP1-S81) by ATM and DNA-PK stabilizes TDP1 and recruits TDP1 to sites of DNA damage. We found that end joining in TDP1-KO cells was partially restored by the non-phosphorylatable mutant TDP1-S81A, but not by the phosphomimetic TDP1-S81E. We previously reported that TDP1 physically interacted with XLF. In this study, we found that XLF binding by TDP1 was reduced 2-fold by the S81A mutation, and 10-fold by the S81E phosphomimetic mutation. Our results demonstrate a novel role for TDP1 in NHEJ in human cells. We hypothesize that TDP1 participation in human NHEJ is mediated by interaction with XLF, and that TDP1-XLF interactions and subsequent NHEJ events are regulated by phosphorylation of TDP1-S81.
Chest Wall Metastasis from Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most common renal neoplasm with the majority of cases having the clear cell histological subtype. Although renal cell carcinoma can metastasize to any site, spread to skeletal muscle is uncommon. FDG PET/MR imaging provides increased accuracy for metastatic renal carcinoma detection and characterization, especially in unusual sites due to its combination of superior anatomic detail and functional information.
Risk factors for failing to achieve improvement after anatomic total shoulder arthroplasty for glenohumeral osteoarthritis.

Background Although anatomic total shoulder arthroplasty (TSA) successfully improves pain and function, not all patients improve clinically. This study was conducted to determine patient-related factors for failure to achieve improvement after primary TSA for osteoarthritis at 2 years postoperatively. Methods This prospective study reviewed an institutional shoulder registry for consecutive patients who underwent primary TSA for osteoarthritis from 2007 to 2013 with baseline and 2-year postoperative American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form scores. A failed outcome was defined as (1) a failure to reach the ASES minimal clinically important difference of 16.1 points or (2) revision surgery within 2 years of the index procedure, or both. Univariate and multivariable analyses of clinical and demographic patient factors were performed using logistic regression. Results Of 459 arthroplasties that met inclusion criteria, 411 were deemed successful by the aforementioned criteria, and 48 (10.5%) failed to achieve a desirable outcome. Clinical risk factors associated with failure included previous surgery to the shoulder (P = .047), presence of a torn rotator cuff (P = .025), and presence of diabetes (P = .036), after adjusting for age, sex, race, and body mass index. A higher preoperative ASES score at baseline was associated with failure (P Conclusion Previous shoulder surgery, a rotator cuff tear requiring repair during TSA, presence of diabetes, surgery on the nondominant arm, and a higher baseline ASES score were associated with a higher risk of failing to achieve improvement after anatomic TSA.
EFFECTIVENESS AND SAFETY OF DIRECT ORAL ANTICOAGULANTS COMPARED TO WARFARIN: THE REAL WORLD EXPERIENCE

It remains unknown whether the comparative effectiveness and safety of direct oral anticoagulants (DOACs) and warfarin differ across levels of stroke risk. We compared the effectiveness and safety of DOACs and warfarin in three subgroups of atrial fibrillation (AF) patients defined by CHA2DS2-VASc
Improving Outcomes: Big Data and Predictive Analytics

Abstract The Computational Neurosurgery Outcomes Center at Brigham and Women's Hospital focuses on new knowledge creation and value-based innovation with big data, predictive analytics, patient-reported outcomes, and national databases. Work with artificial intelligence, including machine learning for structured data such as online medical records and natural language processing for unstructured data such as clinic notes, allows for analysis of high-velocity, high-volume, and high-complexity neurosurgical data. Use of mobile-based actively collected patient reported outcomes has been paralleled by the development of digital phenotyping and passive data collection. The study of surgical outcomes has evolved tremendously since the work of Ernest Amory Codman and big data, predictive analytics, and passively collected patient reported outcomes are the next frontier for outcomes research.
A planar array capacitive imaging system for detecting damage in composite structures: a numerical study

Fiber-reinforced polymer (FRP) composites are widely used in the aerospace industry, but they are also susceptible to different types of damage. In particular, impact is a serious concern, since they can cause subsurface damage that can be hidden from visual inspection and jeopardize structural safety and performance. In addition, the complex geometries of FRP components can limit the use of current nondestructive inspection techniques. Thus, the objective of this study is to develop a portable, noncontact, surface scanning tool for technicians to rapidly detect, characterize, and localize subsurface structural features and damage in structural components. The technique is centered around the theory of electrical capacitance tomography (ECT). Unlike conventional ECT, an array of noncontact electrodes is arranged in a planar fashion. Electric field is propagated between electrodes to interrogate the sensing region, which is defined as the region of space underneath the plane of electrodes. Meanwhile, the corresponding mutual capacitance between excitation and other electrodes are measured. The recorded datasets are then used as inputs to solve the ECT inverse problem in which the electrical permittivity of the 3D sensing region can be reconstructed. In this work, numerical modeling was employed to demonstrate the sensing performance of the planar array capacitive imaging system. First, several composite components with different types of damage were simulated using finite element modeling. Damage was introduced by selectively changing the electrical permittivity at different regions. Second, the planar capacitive electrode array, which was placed near the composite component, was also modeled. Electric field was propagated between different electrodes while the corresponding mutual capacitance of other electrodes were determined. The simulated data was then used as inputs to solve the ECT inverse problem. The numerical simulation results showed that the planar array capacitive imaging system was able to detect, quantify, and locate damage-induced changes in electrical permittivity distributions in composite structures, thereby demonstrating its potential for use as a nondestructive inspection tool.
Existence and Stability of Multidimensional Transonic Shocks for the Euler Equations for Steady Potential Fluids in Unbounded Domains

We are concerned with the existence and stability of multidimensional transonic shocks in inviscid compressible fluid dynamics. In this paper, we focus on inviscid steady potential fluid flows, which are governed by the Euler equations consisting of the conservation law of mass and the Bernoulli law for velocity. Then the Euler equations for the velocity potential ϕ: Ω ⊂ Rn → R can be formulated into the following second order nonlinear equation of mixed elliptic-hyperbolic type: $$ div(\rho (|D\varphi {{|}^{2}})D\varphi ) = 0, $$ (1) where the density function ρ(q 2) has the form: $$ \rho ({{q}^{2}}) = {{\left( {1 - \frac{{\gamma - 1}}{2}{{q}^{2}}} \right)}^{{\frac{1}{{\gamma - 1}}}}} $$ (2) with the adiabatic exponent ψ>1.
HIV/AIDS knowledge among female migrant farm workers in the midwest.

The rate of HIV infection in the migrant farm worker community is 10 times the national average. A survey was conducted of 106 female migrant farm workers in rural Northwest Ohio to assess HIV knowledge. The average participant's age was 28.7 years, 78 spoke Spanish, and 47 had an ≤8th- grade education. Fifty-six women received their information on HIV/AIDS from television. Eighty-seven women identified sexual contact as the major source of HIV transmission and 54 women identified the combination of sex, use of needles, and blood contact as the important routes. Sixty-nine women identified both homosexual and heterosexual intercourse as risk factors. Only 58 women identified perinatal infection as a route of HIV transmission and 59 women knew that treatment was available to prevent perinatal transmission. Although the majority of women had a good general knowledge of HIV transmission, further prevention education on perinatal transmission is needed among this population.