cssi/SciSciGPT-SciSciNet huggingface dataset:
Comprehensive structural and functional characterization of the human kinome by protein structure modeling and ligand virtual screening.

The growing interest in the identification of kinase inhibitors, promising therapeutics in the treatment of many diseases, has created a demand for the structural characterization of the entire human kinome. At the outset of the drug development process, the lead-finding stage, approaches that enrich the screening library with bioactive compounds are needed. Here, protein structure based methods can play an important role, but despite structural genomics efforts, it is unlikely that the three-dimensional structures of the entire kinome will be available soon. Therefore, at the proteome level, structure-based approaches must rely on predicted models, with a key issue being their utility in virtual ligand screening. In this study, we employ the recently developed FINDSITE/Q-Dock ligand homology modeling approach, which is well-suited for proteome-scale applications using predicted structures, to provide extensive structural and functional characterization of the human kinome. Specifically, we construct stru...
Amputación mayor de la extremidad inferior después de múltiples revascularizaciones: ¿merecían la pena?

Con frecuencia, la indicacion de revascularizacion de la extremidad inferior se centra demasiado en el aspecto de las lesiones, prestando una atencion insuficiente al contexto del paciente. Investigamos las perspectivas de los pacientes acerca de multiples procedimientos para el salvamento de la extremidad que culminaron en una amputacion mayor de la extremidad inferior. Se efectuo una busqueda prospectiva en una base de datos de cirugia vascular desde enero de 2000 a diciembre de 2005 para pacientes que se habian sometido a una amputacion infragenicular (AIG) o supragenicular (ASG) despues del fracaso de la revascularizacion de la extremidad inferior. Una enfermera experta en procedimientos vasculares entrevisto por telefono a los pacientes formulandoles preguntas acerca de su opinion sobre los multiples procedimientos a los que se sometieron para el salvamento de la extremidad, su participacion en la toma de decisiones, estado funcional (trabajo, preparacion de las comidas, ir de compras, y conducir), el uso de una protesis y la autonomia. Para verificar la supervivencia de los pacientes se uso el Social Security Death Index. Se excluyeron las amputaciones por infeccion. Se sometieron a ASG o AIG tras fracaso de la revascularizacion 78 pacientes. A los 5 anos seguian vivos 46 (59%) pacientes. Se perdieron para el seguimiento 13 pacientes, quedando 33 disponibles para la encuesta. En estos pacientes se efectuo un total de 142 revascularizaciones de la extremidad inferior (mediana = 4/paciente), incluidos 94 bypass quirurgicos (mediana = 3/paciente) y 48 intervenciones percutaneas (mediana = 1/paciente). El 85% (28 de 33 pacientes) de los amputados encuestados haria lo que fuera por salvar la pierna si se enfrentara de nuevo a una situacion similar, con independencia del numero de procedimientos a los que tuviera que someterse. El 54% (18/33) de pacientes usaba activamente una protesis, y el 91% (30/33) residia en su domicilio. Retrospectivamente, los pacientes estan dispuestos a someterse a multiples revascularizaciones percutaneas o abiertas, en una tentativa de salvamento de la extremidad aun cuando el resultado final sea una amputacion mayor. En la mayoria de pacientes, se consiguio una independencia y estado funcional suficientes. Se requieren resultados orientados al paciente para indicar los procedimientos de revascularizacion, con independencia de que se efectuen con una tecnica percutanea o abierta.
Molecular Basis of Genetic Heterogeneity: Role of the Clinical Neurologist

Advances in molecular genetics have disclosed many different explanations for allelic heterogeneity, how different clinical syndromes arise from mutations in the same gene. The converse, how similar clinical syndromes arise from mutations of different genes on different chromosomes is called locus heterogeneity. Both, however, give rise to some disease-defining mutations, as in childhood spinal muscular atrophy or Duchenne muscular dystrophy. Nevertheless, new problems have been created, including what might be called "diagnosis by the number," diverse syndromes from mutations in the same gene without current explanation, or siblings with different clinical syndromes. These discoveries have transformed the clinical neurology of heritable diseases. They also provide clinicians with new responsibilities and opportunities in defining clinical syndromes and influencing the evolution of our clinical language.
Child passenger injury risk in motor vehicle crashes: a comparison of nighttime and daytime driving by teenage and adult drivers.

Abstract Introduction To examine the association between child passenger injury risk, restraint use, and crash time (day vs. night) for children in crashes of vehicles driven by teenage versus adult drivers. Methods Cross-sectional study involving telephone interviews with insured drivers in a probability sample of 6,184 crashes involving 10,028 children. Results Child passengers in teen nighttime crashes had an increased injury risk and an increased risk of restraint nonuse compared with those in teen daytime crashes. This increased injury risk can be explained by differences in the age of child passengers, collision type, and child passenger's restraint status associated with time of day. Conclusions In order to limit the risk of injury to child passengers driven by teens, Graduated Driver Licensing (GDL) laws should include provisions restricting nighttime driving, as well as mandates for age-appropriate restraint for child passengers. Consideration should also be given for education in child passenger safety for novice teen drivers as part of the licensing process. Impact on Industry Results of this study can be used to support advocacy efforts by the automotive industry and others to promote nighttime driving restrictions on novice drivers. In addition, given that both driver groups were more likely to be involved in a single-vehicle collision during the night, technologies such as electronic stability control may offer opportunities for protection. Further reseach on specific circumstances of teen nighttime crashes is needed to inform industry efforts to improve visibility or vehicle operation under poor lighting conditions.
Correction of congenital deformations of the hand

Abstract It is obvious from the foregoing report that the multiplicity of congenital lesions presents problems in treatment which require accurate knowledge concerning which of the bones and soft tissues are involved. By means of surgical treatment and postoperative physical therapy many of these deformities can be remedied, with benefit both in appearance and function.
One-time or repeat offenders? An examination of the patterns of alcohol-related consequences experienced by college students across the freshman year

Recent studies have examined alcohol-related consequences in college students as an independent outcome variable, rather than as a result of heavy drinking. The present study examined the patterns of consequences experienced by first-year college students (n = 169). Specifically, the number of distinct consequences and the frequency of repeated consequences were evaluated as well as the combination of the two. Results revealed that 80% of participants reported experiencing multiple consequences, with over 34% of students reporting 6 or more unique consequences over the course of their freshmen year. In addition, nearly 50% of the sample reported experiencing 3 or more consequences repeatedly. Further, 23% of the sample reported experiencing 5 or more repeated consequences and 6 or more multiple consequences. These individuals experienced 38% of the multiple consequences and 54% of the repeated consequences reported by the entire sample, suggesting individuals who endorsed experiencing multiple consequences repeatedly also experienced a disproportionate number of the total consequences reported by the sample. The findings suggest there are specific high-risk patterns of alcohol-related consequences and demonstrate a need for further examination of additional variables that predict consequences.
Acceleration of convergence in Monte Carlo simulations of aqueous solutions using the metropolis algorithm. Hydrophobic hydration of methane

Convergence problems encountered in the computer simulations of aqueous solutions are discussed. Solute–solvent radial distribution functions are shown to converge very poorly when the standard Metropolis Monte Carlo procedure is applied. To overcome this difficulty, several modifications are made in the Metropolis method. Optimum maximum step sizes are determined for simulations of liquid water. A scheme is employed for preferential sampling of both the solvent and the solute molecules. To test these modifications, a simulation is carried out for pure liquid water, treating a single water molecule as a “solute.” The convergence of the radial distribution functions is found to be accelerated significantly. A further test is made by simulating an aqueous solution of methane, consisting of one methane molecule (using the EPEN/2 potential for methane–water interactions) and 124 water molecules (using the MCY potential for water–water interactions). Again, the convergence of solute–solvent radial distribution functions is found to be accelerated. The computation of partial molar thermodynamic quantities, however, still suffers from convergence difficulties. This problem is discussed in detail. The EPEN/2 potential is found to yield structural and thermodynamic features of hydrophobic hydration that are consistent with available experimental and theoretical results for aqueous solutions of methane.
Utilizing Network Processors in Distributed Enterprise Environments

The integration of legacy systems and enterprise applications with novel communications, internet, or networking services creates the problems of mismatches, information integration and possibly, problems from the evolution of the systems themselves. Enterprise services to solve these problems are currently implemented via commodity server hardware or Application Specific Integrated Circuits (ASICs), which suffer from either poor performance or a lack of flexibility. This paper presents an alternative to implementing these services by using Network Processors (NPs) as fast, flexible, and cost-efficient network appliances. It characterizes the hardware and software requirements of NP-based enterprise services, and presents a case study of a real-world enterprise problem. We implement a solution service to the problem on the Intel IXP2400, and present evaluation results that generalize the strengths, weaknesses, and requirements of the NPs role as a platform for enterprise service deployment.
Design of Launch Vehicle Flight Control Systems Using Ascent Vehicle Stability Analysis Tool

A launch vehicle represents a complicated flex-body structural environment for flight control system design. The Ascent-vehicle Stability Analysis Tool (ASAT) is developed to address the complicity in design and analysis of a launch vehicle. The design objective for the flight control system of a launch vehicle is to best follow guidance commands while robustly maintaining system stability. A constrained optimization approach takes the advantage of modern computational control techniques to simultaneously design multiple control systems in compliance with required design specs. "Tower Clearance" and "Load Relief" designs have been achieved for liftoff and max dynamic pressure flight regions, respectively, in the presence of large wind disturbances. The robustness of the flight control system designs has been verified in the frequency domain Monte Carlo analysis using ASAT.
Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene

Osteoarthritis in horses and in humans is a significant social and economic problem and continued research and improvements in therapy are needed. Because horses have naturally occurring osteoarthritis, which is similar to that of humans, the horse was chosen as a species with which to investigate gene transfer as a potential therapeutic modality for the clinical treatment of osteoarthritis. Using an established model of equine osteoarthritis that mimics clinical osteoarthritis, the therapeutic effects resulting from intra-articular overexpression of the equine interleukin-1 receptor antagonist gene through adenoviral-mediated gene transfer were investigated. In vivo delivery of the equine IL-IRa gene led to elevated intra-articular expression of interleukin-1 receptor antagonist for approximately 28 days, resulting in significant improvement in clinical parameters of pain and disease activity, preservation of articular cartilage, and beneficial effects on the histologic parameters of synovial membrane and articular cartilage. Based on these findings, gene transfer of interleukin-1 receptor antagonist is an attractive treatment modality for the equine patient and also offers future promise for human patients with osteoarthritis.
Improvement in Isometric Strength of the Quadriceps Femoris Muscle After Training with Electrical Stimulation

The purpose of this investigation was to determine if training isometrically with electrical stimulation (ES) alone would significantly increase isometric strength of the quadriceps femoris muscle. The relationships between the strength changes and the relative force and duration of training contractions were also studied. An experimental group (Group 1) and a control group (Group 2), 12 subjects in each, underwent pretesting and posttesting to obtain their maximum voluntary isometric contractions (MVICs). Group 1 trained with maximally tolerable isometric contractions induced by ES, three days a week for four weeks. Results showed that although both groups demonstrated increases in isometric strength of their quadriceps femoris muscles, training isometrically with ES produced a significantly greater increase (p less than .01) than not training with ES. The relative strength improvement in Group 1 was positively and significantly correlated with training-contraction intensity and duration. The relative increase in isometric strength, using only ES, may be determined by the ability of the subjects to tolerate longer and more forceful contractions. Suggestions for further research and implications for the clinical use of ES for strength-training are discussed.
A literature survey on the stability and significance of residual stresses during fatigue

Many manufacturing processes can induce residual stresses in components. These residual stresses influence the mean stress during cyclic loading and so can influence the fatigue life. However, the initial residual stresses induced during manufacturing may not remain stable during the fatigue life. This paper provides a broad and extensive literature survey addressing the stability of surface and near-surface residual stress fields during fatigue, including redistribution and relaxation due to static mechanical load, repeated cyclic loads, thermal exposure and crack extension. The implications of the initial and evolving residual stress state for fatigue behaviour and life prediction are addressed, with special attention to fatigue crack growth. This survey is not a critical analysis; no detailed attempt is made to evaluate the relative merits of the different explanations and models proposed, to propose new explanations or models or to provide quantitative conclusions. Primary attention is given to the residual stresses resulting from four major classes of manufacturing operations: shot peening and related surface treatments, cold expansion of holes, welding and machining.
Cohort Change and Racial Differences in Educational and Income Mobility

Policy reforms and rising income inequality transformed educational and economic opportunities for Americans approaching midlife in the 1990s. Rising income inequality may have reduced mobility, as income gaps increased between rich and poor children. Against the effects of rising inequality, Civil Rights reforms may have increased mobility, as opportunities expanded across cohorts of black students and workers. We compare educational and income mobility for two cohorts of black and white men, the older born in the late 1940s and the younger born in the early 1960s. We find that educational mobility increased for black men, but income mobility declined for both races. Economic mobility declined despite unchanged or improved educational mobility because of increased returns to schooling and increased intergenerational income correlations, independent of schooling.
Fast methods for analysis of neurotransmitters from single cell and monitoring their releases in central nervous system by capillary electrophoresis, fluorescence microscopy and luminescence imaging

Fast methods for separation and detection of important neurotransmitters and the releases in central nervous system (CNS) were developed. Enzyme based immunoassay combined with capillary electrophoresis was used to analyze the contents of amino acid neurotransmitters from single neuron cells. The release of amino acid neurotransmitters from neuron cultures was monitored by laser induced fluorescence imaging method. The release and signal transduction of adenosine triphosphate (ATP) in CNS was studied with sensitive luminescence imaging method. A new dual-enzyme on-column reaction method combined with capillary electrophoresis has been developed for determining the glutamate content in single cells. Detection was based on monitoring the laser-induced fluorescence of the reaction product NADH, and the measured fluorescence intensity was related to the concentration of glutamate in each cell. The detection limit of glutamate is down to 10{sup {minus}8} M level, which is 1 order of magnitude lower than the previously reported detection limit based on similar detection methods. The mass detection limit of a few attomoles is far superior to that of any other reports. Selectivity for glutamate is excellent over most of amino acids. The glutamate content in single human erythrocyte and baby rat brain neurons were determined with this method and resultsmore » agreed well with literature values.« less
A Simulation of a Squall Line Using a Nonhydrostatic Cloud Model with a 5-km Horizontal Grid

Abstract A three-dimensional nonhydrostatic cloud model is used to simulate the squall line observed in central Texas on 11 April 1979. The cloud model covers an area 400 × 400 km2 with a 5-km horizontal resolution and is supplied initial and boundary conditions by a larger hydrostatic mesoscale model. The model produces a back-building squall line ahead of the surface cold front, as would be expected based on an analysis of the pre-squall-line environment. A well-defined gust front and cold pool develop with the squall line. At the end of the 5-h simulation, deep convection is found along a line nearly 400 km long. The simulated squall line compares favorably both with observations and with a higher-resolution model simulation in an environment of similar shear, suggesting that the 5-km horizontal resolution is adequately representing the significant features of the squall line. The major shortcoming of this study is the failure of the cloud model to produce the observed squall line at the proper time. W...
Etiology, natural history, management and molecular genetics of hereditary nonpolyposis colorectal cancer (Lynch syndromes): genetic counseling implications.

We estimate that 5-10% of virtually all forms of cancer are due to a primary hereditary etiology. However, a hereditary cancer diagnosis is often missed because the family history of cancer is given short shrift in medical practice. Hereditary nonpolyposis colorectal cancer (HNPCC) certainly fits this estimate, although some studies suggest that a minimum of 2% with a range as high as 10% of the total colorectal cancer burden is due to HNPCC. Mutations in one of the four mismatch repair genes, i.e., hMSH2, hMLH1, hPMS1, and hPMS2, account for about 70% of HNPCC kindreds. Other germ-line mutations are likely to be identified to account for the remainder of HNPCC patients. By far the most common HNPCC mutations involve hMSH2 and hMLH1, with hPMS1 and hPMS2 accounting for only about 3% of such families. Prior to these molecular genetic discoveries, the genetic counselor could only provide the patient with an estimate of a 50% likelihood of manifesting HNPCC based on the counselee having one or more first-degree relatives manifesting syndrome cancers in their direct genetic lineage. Because DNA testing has become available in families with known mutations, we have provided pretest group education in the form of a family information service with intensive education about the natural history, genetic risk, surveillance, and options for management of HNPCC, as well as discussion of the potential for fear, anxiety, apprehension, and insurance or employer discrimination that might impact on this DNA testing. Following informed consent, these relatives were then counseled on a one-to-one basis. Using DNA-based genetic counseling involving hMSH2 or hMLH1, we have provided this service to four extended HNPCC kindreds. Details of this genetic counseling experience on these four kindreds will be discussed.
Rights, Reforms, and the Health Care Crisis: Problems and Prospects

I am not sure that health care can profitably be discussed in the context of rights. For one thing, it is a term of many and shifting meanings, and thus virtually guarantees some degree of misunderstanding and confusion. For another, the very uttering of “rights” carries tones of ethical seriousness, if not outright superiority, that gives its advocates a substantial and unearned advantage in debate. Contemporary political scientists, as a result, have tended to feel more comfortable with “claims” (cf. [82]). Yet “rights” is what this book is about, and so “rights” must set the terms of the discussion.
Trehalose, an mTOR-Independent Inducer of Autophagy, Inhibits Human Cytomegalovirus Infection in Multiple Cell Types.

ABSTRACT Human cytomegalovirus (HCMV) is the major viral cause of birth defects and a serious problem in immunocompromised individuals and has been associated with atherosclerosis. Previous studies have shown that the induction of autophagy can inhibit the replication of several different types of DNA and RNA viruses. The goal of the work presented here was to determine whether constitutive activation of autophagy would also block replication of HCMV. Most prior studies have used agents that induce autophagy via inhibition of the mTOR pathway. However, since HCMV infection alters the sensitivity of mTOR kinase-containing complexes to inhibitors, we sought an alternative method of inducing autophagy. We chose to use trehalose, a nontoxic naturally occurring disaccharide that is found in plants, insects, microorganisms, and invertebrates but not in mammals and that induces autophagy by an mTOR-independent mechanism. Given the many different cell targets of HCMV, we proceeded to determine whether trehalose would inhibit HCMV infection in human fibroblasts, aortic artery endothelial cells, and neural cells derived from human embryonic stem cells. We found that in all of these cell types, trehalose induces autophagy and inhibits HCMV gene expression and production of cell-free virus. Treatment of HCMV-infected neural cells with trehalose also inhibited production of cell-associated virus and partially blocked the reduction in neurite growth and cytomegaly. These results suggest that activation of autophagy by the natural sugar trehalose or other safe mTOR-independent agents might provide a novel therapeutic approach for treating HCMV disease. IMPORTANCE HCMV infects multiple cell types in vivo , establishes lifelong persistence in the host, and can cause serious health problems for fetuses and immunocompromised individuals. HCMV, like all other persistent pathogens, has to finely tune its interplay with the host cellular machinery to replicate efficiently and evade detection by the immune system. In this study, we investigated whether modulation of autophagy, a host pathway necessary for the recycling of nutrients and removal of protein aggregates, misfolded proteins, and pathogens, could be used to target HCMV. We found that autophagy could be significantly increased by treatment with the nontoxic, natural disaccharide trehalose. Importantly, trehalose had a profound inhibitory effect on viral gene expression and strongly impaired viral spread. These data constitute a proof-of-concept for the use of natural products targeting host pathways rather than the virus itself, thus reducing the risk of the development of resistance to treatment.
Design feature opinion cause analysis: a method for extracting design intelligence from web reviews

Web reviews are a readily available source of product intelligence. The hypothesis of this research is that web reviews also contain significant amounts of design information for product designers. The authors introduce the design-feature-opinion-cause relationship DFOC method, which effectively extracts design intelligence from unstructured web reviews. The DFOC method: 1 creates a sentence-based web review database; 2 mines the database to identify design features that are of interest to both designers and users; 3 extracts and estimates the significance and polarity of the customer opinions; 4 identifies the likely design cause of the customer opinion. DFOC utilises an association rule-based opinion mining procedure for capturing and extracting noun-adjective and noun-verb relationships. Application of the DFOC method utilising RapidMiner is demonstrated for an automobile. Example features and feature-opinion-cause associations are shown along with the observed opinion polarity score and cause association strength.
Abstract LB-134: Analysis of restored FFPE samples on high-density SNP arrays

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Millions of Formalin Fixed Paraffin Embedded (FFPE) cancer tissue samples currently present in the US and worldwide provide an enormous, invaluable repository to the discovery of biomarkers in cancer research, drug development, diagnosis and treatment of diseases. However, the processes of fixation and storage of FFPE samples lead to degradation and base modification with chemical residues. This degraded FFPE DNA is inefficiently amplified in the Infinium® whole genome amplification (WGA) step leading to poor performance in the Infinium® assay. In this study, FFPE DNA (100 ng input) was restored through a treatment with DNA polymerase, DNA repair enzyme, ligase, and modified Infinium® WGA reaction conditions. Canonical genotype cluster files were generated by creating artificially degraded Coriell DNAs and processing the samples through the restoration process and Infinium® assay. Results of genotyping on high density HumanCytoSNP-12 BeadChip®, featuring approximately 300k SNPs indicated that even highly degraded samples which show initial call rates of 40-70% can be successfully restored to a state that achieved call rates of greater than 90%, at a concordance greater than 99.0%, and associated standard deviation of log intensity less than 0.4. In general, over 80% of FFPE samples, which passed a QC assay metric were successfully restored and genotyped. Infinium® genotyping of restored DNA from a collection of tumor FFPE samples confirmed the presence of genomic aberrations around known cancer genes. Finally, we further demonstrated that paired sample analysis using canonical genotype clusters provide improved precision in CNV and LOH analysis compared to single sample analysis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-134.
Cassette dosing pharmacokinetics: valuable tool or flawed science?

The article in this issue by [White and Manitpisitkul (2001)][1] is an excellent and balanced discussion of an important yet specialized technology, cassette dosing pharmacokinetic screening. This approach, developed in the early 1990s at Glaxo, is both widely used and vigorously debated. While this
Desorption Ionization and Fourier Transform Mass Spectrometry for the Analysis of Large Biomolecules

The recent developments in biomolecule mass spectrometry can be traced to progress made in new ionization methods and instruments having extended mass range. Early in the development of Fourier transform mass spectrometry (FTMS) Comisarow and Marshall [1] Gross and Wilkins [2] and McIver [3] noted the applicability of this method for the analysis of large molecules. The principle limitation to developing these capabilities was in adapting the available desorption ionization methods to FTMS. High-mass FTMS requires the use of super-conducting magnets, the design of which imposes mechanical limitations in designing such systems, and ultra-high vacuum (less than 10−8 torr) which is not compatible with many desorption ionization sources and methods, e.g., gaseous discharge primary ion sources and liquid matrices. The first successful demonstration of desorption ionization with FTMS was the laser desorption ionization by Gross [4]. Subsequent to this work our laboratory reported on the use of Cs+ ion SIMS with FTMS detection of high-mass ions, e.g., greater than m/z 2000 [5]. These preliminary results demonstrated the feasibility for performing desorption ionization with FTMS,and more recent work from these two laboratories clearly establishes the analytical utility of the method. Also, Wilkins [6] has reported impressive results for laser desorptionFTMS of a variety of biomolecules, and McIver and Hunt [7,8] have obtained excellent data on biomolecules with tandem quadrupole-FTMS system and fast-atom bombardment (FAB) ionization.
THE EVALUATION OF THE OPTIMUM SPACE OF SQUARE HERLMHOLTZ COIL

The optimum space of square Helmholtz coil was evaluated on the basis of mathematic deduction.
Simulation Vibration Analysis of Train and Railway Continuous Steel Truss Bridge

To solve the matrices of stiff,mass and damping varying with time in vehicle-bridge vibration equations,the train and bridge were coupled together as one composite system.The vibration equations of vehicle-bridge time varying system were established by means of potential energy principle.The vibration responses of a continuous truss girder bridge were analyzed by using this method.The lateral vibration calculation results of a truss girder bridge are close to the testing values.This confirms the reliability of the method.
HybridCell: Cellular connectivity on the fringes with demand-driven local cells

While cellular networks connect over 3.7 billion people worldwide, their availability and quality is not uniform across regions. Under-provisioned and overloaded networks lead to poor network performance and an aggravated user experience. To address this problem we propose HybridCell: a system that leverages locally-owned small-scale cellular networks to augment the operation of overloaded commercial networks. HybridCell is the first system to allow a user with their existing SIM card and mobile phone to seamlessly switch between commercial and local networks in order to maintain continuous connectivity. Hybrid-Cell accomplishes this by identifying poorly-performing networks and taking action to provide seamless cellular connectivity to end users. Using traces collected from observing the cellular infrastructure during our visit to the Za'atari refugee camp in Jordan, we demonstrate HybridCell's capability to detect and act upon commercial network overload, offering an alternate communication channel during times of congestion. We show that even in scenarios where provider networks deny calls due to overload, HybridCell is able to accommodate users and facilitate local calling.
Different strokes for different folks: Tapping into the hidden potential of serious games

Digital game-based learning experiences are typically presented to a captive audience that has to play, as opposed to entertainment games that players can select themselves and choose to play. The captive nature of learning games introduces an interesting issue: not everyone may be familiar with the genre of the game they have to play or be motivated to play it. Students have individual differences that may make a learning game particularly ineffective, uninteresting, or inappropriate for some learners. We present work that frames important differences between students in terms of their game literacy, motivation, goal orientation, and mindset. This understanding leads us to envision game design variations to serve specific combinations of particular individual differences at the intersection of learning and gaming. We present our initial work on identifying and automatically accommodating these differences within a single digital game-based learning experience.
New imaging tools to study synaptogenesis

The study of synaptogenesis is hampered by the difficulty of visualizing the formation of small subcellular specializations involving the coordinated recruitment and organization of hundreds of proteins. Advances in fluorescence microscopy that improve its resolving power by an order of magnitude are discussed. Innovations in electron microscopy that ameliorate the three-dimensional reconstruction of neuronal processes and allow its combination with fluorescence microscopy are discussed. Novel genetically encoded photosensitive tools to visualize neuronal circuitry and synaptic contacts and to modulate the activity of synaptic proteins are also examined. Finally, new strategies for culturing neurons in a simplified and controlled environment are presented.
Physiologically Based Pharmacokinetic Prediction of Linezolid and Emtricitabine in Neonates and Infants

Modeling and simulation approaches are increasingly being utilized in pediatric drug development. Physiologically based pharmacokinetic (PBPK) modeling offers an enhanced ability to predict age-related changes in pharmacokinetics in the pediatric population. In the current study, adult PBPK models were developed for the renally excreted drugs linezolid and emtricitabine. PBPK models were then utilized to predict pharmacokinetics in pediatric patients for various age groups from the oldest to the youngest patients in a stepwise approach. Pharmacokinetic predictions for these two drugs in the pediatric population, including infants and neonates, were within a twofold range of clinical observations. Based on this study, linezolid and emtricitabine pediatric PBPK models incorporating the ontogeny in renal maturation describe the pharmacokinetic differences between adult and pediatric populations, even though the contribution of renal clearance to the total clearance of two drugs was very different (30 % for linezolid vs. 86 % for emtricitabine). These results suggest that PBPK modeling may provide one option to help predict the pharmacokinetics of renally excreted drugs in neonates and infants.
PyVar: An Extensible Framework for Variant Annotator Comparison

Modern genomics projects are generating millions of variant calls that must be annotated for predicted functional consequences at the level of gene expression and protein function. Many of these variants are of interest owing to their potential clinical significance. Unfortunately, state-of-the-art methods do not always agree on downstream effects for any given variant. Here we present a readily extensible python framework (PyVar) for comparing the output of variant annotator methods in order to aid the research community in quickly assessing differences between methods and benchmarking new methods as they are developed. We also apply our framework to assess the annotation performance of ANNOVAR, VEP, and SnpEff when annotating 81 million variants from the "1000 Genomes Project" against both RefSeq and Ensembl human transcript sets.
Caveats Using Natriuretic Peptide Levels

Acute heart failure is difficult to diagnosis by history and physical exam alone. B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide are useful in both the diagnosis and prognosis of heart failure. However, there are various clinical situations that can cause elevations and depressions in the concentrations of natriuretic peptides. This can make clinical diagnoses very difficult, especially in patients with mildly elevated, or “gray zone” levels. Understanding the caveats of using natriuretic peptides is essential for predicting, diagnosing, and treating heart failure. This chapter discusses the causes of “gray zone” natriuretic peptide levels, establishes adjusted cutoffs to be used in patients with specific comorbidities, and applies the information to the interpretation of a case study.
Speed of recovery after arthroscopic rotator cuff repair

Background The purpose of this study was to delineate the time taken to achieve maximum improvement (plateau of recovery) and the degree of recovery observed at various time points (speed of recovery) for pain and function after arthroscopic rotator cuff repair. Methods An institutional shoulder surgery registry query identified 627 patients who underwent arthroscopic rotator cuff repair between 2006 and 2015. Measured range of motion, patient satisfaction, and patient-reported outcome measures were analyzed for preoperative, 3-month, 6-month, 1-year, and 2-year intervals. Subgroup analysis was performed on the basis of tear size by retraction grade and number of anchors used. Results As an entire group, the plateau of maximum recovery for pain, function, and motion occurred at 1 year. Satisfaction with surgery was >96% at all time points. At 3 months, 74% of improvement in pain and 45% to 58% of functional improvement were realized. However, only 22% of elevation improvement was achieved ( P P Conclusion The plateau of maximum recovery after rotator cuff repair occurred at 1 year with high satisfaction rates at all time points. At 3 months, approximately 75% of pain relief and 50% of functional recovery can be expected. Larger tears have a slower speed of recovery.
Intestinal microbiota, fecal microbiota transplantation, and inflammatory bowel disease

Inflammatory bowel disease (IBD) is a complex set of diseases that lead to chronic inflammation in the gastrointestinal tract. Although the etiology of IBD is not fully understood, it is well-known that the intestinal microbiota is associated with the development and maintenance of IBD. Manipulation of the gut microbiota, therefore, may represent a target for IBD therapy. Fecal microbiota transplantation (FMT), where fecal microbiota from a healthy donor is transplanted into a patient's GI tract, is already a successful therapy for Clostridium difficile infection. FMT is currently being explored as a potential therapy for IBD as well. In this review, the associations between the gut microbiota and IBD and the emerging data on FMT for IBD will be discussed.
Brillouin microspectroscopy assessment of tissue differentiation during embryonic development

Changes in mechanical properties represent one of the driving factors behind cell differentiation during embryonic development. However, measuring these changes without disrupting the normal progression of morphogenesis or destroying the developing organism is not trivial. Brillouin microspectroscopy has been shown to be capable of nocontact, non-destructive and non-disruptive assessment of elastic properties in developing zebrafish embryos. The present study builds upon the previous work, and observes the changes in elasticity during the development of heart and brain in zebrafish embryos from 8 to 28 hpf (hours post-fertilization) at regular intervals. Brillouin microspectroscopy has proved to be a suitable technique to continuously monitor tissue differentiation and the development of individual organs with high spatial resolution without harming the developing organism.
Kathy Rose y Miwa Matreyek: danza animada y representación

Live performance combined with projected animation is both very new, with advances in projection mapping and motion sensors, and very old, harkening back to pre-cinematic projected seances, magic lantern shows, and to Winsor McCay’s vaudeville performances with his ‘trained’ animated dinosaur, Gertie. Two contemporary artists create and choreograph one-woman performances populated not only with their own bodies, but also with various animated figures, forms, and designs. Kathy Rose began as an animator, and then later performed with her projections. Miwa Matreyek uses her own figure as a silhouette in her performances, and creates remarkable imagery with two projectors and a screen. In their creative work they both project themselves as characters into their animated performances, and reference magic, dream, and mythology in their work and their imagery. They choreograph their movements to synch with their animated images. Both women play a role behind the camera, and in front of the screen, and play with the dual nature of creator/director and subject/performer.
Role of the VlsE Lipoprotein in Immune Avoidance by the Lyme Disease Spirochete Borrelia burgdorferi

Borrelia burgdorferi is the causative bacterial agent of Lyme disease, the most prevalent tick-borne infection in North America. The ability of B. burgdorferi to cause disease is highly dependent on its capacity to evade the immune response during infection of the mammalian host. One of the ways in which B. burgdorferi is known to evade the immune response is antigenic variation of the variable major protein (VMP)-like sequence (Vls) E lipoprotein. Past research involving the B. burgdorferi antigenic variation system has implicated a gene-conversion mechanism for vlsE recombination, analyzed the long-term dynamic changes occurring within VlsE, and established the critical importance of antigenic variation for persistent infection of the mammalian host. However, a role for the VlsE protein other than providing an antigenic disguise is currently unknown, but it has been proposed that the protein may function in other forms of immune evasion. Although a substantial number of additional proteins reside on the bacterial surface, VlsE is the only known antigen that exhibits ongoing variation of its surface epitopes. This suggests that B. burgdorferi may use a VlsE-mediated system for immune avoidance of its surface antigens. Several recent experimental studies involving host reinfection, superinfection, and the importance of VlsE antigenic variation during the pathogen's enzootic cycle have been used to address this question. Here, the cumulative results from these studies are reviewed, and the knowledge gaps that remain regarding the role of VlsE for immune avoidance are discussed.
Synthetic Deconvolution of Interfaces and Materials Components in Hybrid Nanoparticles

Interfaces between nanoscale solids can facilitate coupling between dissimilar materials, leading to emergent and synergistic properties as well as mix-and-match multifunctionality. Seeded-growth methods, whereby one material is grown directly off of the surface of another, can lead to the formation of hybrid nanoparticles containing such solid-state heterojunctions. Successfully applying seeded-growth methods to the synthesis of hybrid nanoparticles, however, requires a precise balance of competing reaction variables, which limits the scope of materials that can be routinely incorporated into them and, accordingly, the types of achievable interfaces. Here, we describe an alternate pathway that overcomes key limitations of seeded-growth methods by synthetically deconvoluting the formation of particle–particle interfaces and the incorporation of desired materials components. Readily accessible hybrid nanoparticles can be rationally modified using sequential anion and cation exchange reactions which transfo...
Imaging of Tumor Metabolism: MR Spectroscopy

Reprogrammed tumor metabolism, which is characterized by alterations in glucose/lactate, glutamate/glutamine, choline, and glycine metabolism, is a hallmark of cancer. Recent findings are starting to unravel the interplay between oncogenic signaling pathways and aberrant tumor metabolism, and this has renewed the interest in imaging tumor metabolism. Changes in tumor metabolism modify the microenvironment and lead to the evolution and progression of primary tumors, as well as the development of tumor metastases. Magnetic resonance spectroscopy (MRS) provides a noninvasive way to examine tumor metabolism in living systems, ranging from cultured cancer cells, to tumor models in experimental animals, to humans in the clinical setting. In addition, the use of stable nonradioactive MR-active isotopes such as 31P, 19F, and 13C allows us to track the metabolism of molecular probes that contain these nuclei in tumors. With its high translational potential, MRS can provide prognostic information and can be used to monitor treatment responses in tumors. This book chapter covers the breadths of multinuclear MRS of tumor metabolism with a focus on preclinical studies.
COMPASS| Critical Communication Policy Research and the Attention Economy: From Digital Labor Theory to Digital Class Struggle

In this essay, I use a critical political economy of the attention economy to develop an understanding of the ways in which communication policies distribute communicative power. The policy issues I consider are Internet regulation, copyright, paracopyright, and advertising. Communication policies are analyzed in terms of their role in determining the conditions of audience practices and distributing power in the attention economy. I use Google’s efforts to capitalize on attention to illustrate the communicative power struggle in each area, within a U.S. context.
Improved line facility location in weighted subdivisions

We present an improved solution for the line facility location problem in a planar weighted subdivision. Our solution makes use of a key observation that improves on some theoretical bounds, and can be much faster in practice when compared to the previously published solutions. The weighted region setup is a more realistic model for many facility location problems that arise in practical applications, and yet it has not received significant treatment due to the complexity associated with the model.
Southern Romance: Relationship Quality, Consensus, and Context among Cohabiting Couples in the Gulf States

AbstractRelationships are significantly stressed in the Southeastern United States. Of the six states in the Gulf region (Florida, Georgia, Alabama, Mississippi, Louisiana, and Texas), four are in ...