cssi/SciSciGPT-SciSciNet huggingface dataset:
Characterization of granularity and redundancy for SRAMs for optimal yield-per-area

Memories are significant proportions of most digital systems and memory-intensive chips continue to lead the migration to new nano-fabrication processes. As these processes have increasingly higher defect rates, especially when they are first adopted, such early migration necessitates the use of increasing levels of redundancy to obtain high yield (per area). We show that as we move into nanometer processes with high defect rates, the level of redundancy needed to optimize yield-per-area is sufficiently high so as to significantly influence design tradeoffs. We then report a first step towards considering the overheads of redundancy during design optimization by characterizing the tradeoffs between the granularity of a design and the level of redundancy that optimizes the yield-per-area of static RAMs (SRAMs). Starting with physical layouts of cells and the desired memory size, we derive probabilities of failure at a range of abstractions - transistor level, cell level, and system level. We then estimate optimal memory granularity, i.e., the size of memory blocks, as well as the optimal number of spare rows and columns that maximize yield-per-area. In particular, we demonstrate the non-monotonic nature of these tradeoffs and present efficient designs for large SRAMs. Our ongoing research is characterizing several other specific tradeoffs, for SRAMs as well as logic blocks.
PERTURB: A special-purpose algebraic manipulation program for classical perturbation theory

Classical perturbation theory provides a particularly promising route to EBK quantization of nonseparable systems. However, the number of terms generated when implementing perturbation theory for systems with more than two degrees of freedom can prove too large for general purpose symbolic manipulators to handle. We describe PERTURB, a specialized algebraic manipulation program written in C for quantization of multidimensional systems. A review of operator based classical perturbation theory is given, and the relationship between this type of perturbation theory and quantum mechanical Van Vleck perturbation theory discussed. The relative performance of the Dragt–Finn and Lie transform algorithms is assessed.
In search of better statistics for traffic characterization

We model and simulate stochastic traffic based on two established statistics: marginal distribution and autocorrelation function. Although apparently equivalent to each other in these aspects, the three different synthetic models produce notably different behavior in a G/D/1/¥ queue. As an alternative modeling strategy, we measure the log-moment generating function of the synthetic models. Our results indicate that recent works related to Effective Bandwidth functions may provide the discriminatory statistic required to explain the noted inconsistency.
Interactivity, Information Processing, and Learning on the World Wide Web.

This study examines the role of interactivity in the presentation of science news on the World Wide Web. The authors propose and test a model of interactive information processing that suggests a relationship between interactivity, cognitive elaboration, and learning. A think-aloud method was employed to provide insight into study participants' mental processes during Web use.
Meta-analytic methods for pooling rates when follow-up duration varies: a case study

Background: Meta-analysis can be used to pool rate measures across studies, but challenges arise when follow-up duration varies. Our objective was to compare different statistical approaches for pooling count data of varying follow-up times in terms of estimates of effect, precision, and clinical interpretability. Methods: We examined data from a published Cochrane Review of asthma self-management education in children. We selected two rate measures with the largest number of contributing studies: school absences and emergency room (ER) visits. We estimated fixed- and random-effects standardized weighted mean differences (SMD), stratified incidence rate differences (IRD), and stratified incidence rate ratios (IRR). We also fit Poisson regression models, which allowed for further adjustment for clustering by study. Results: For both outcomes, all methods gave qualitatively similar estimates of effect in favor of the intervention. For school absences, SMD showed modest results in favor of the intervention (SMD -0.14, 95% CI -0.23 to -0.04). IRD implied that the intervention reduced school absences by 1.8 days per year (IRD -0.15 days/child-month, 95% CI -0.19 to -0.11), while IRR suggested a 14% reduction in absences (IRR 0.86, 95% CI 0.83 to 0.90). For ER visits, SMD showed a modest benefit in favor of the intervention (SMD -0.27, 95% CI: -0.45 to -0.09). IRD implied that the intervention reduced ER visits by 1 visit every 2 years (IRD -0.04 visits/child-month, 95% CI: -0.05 to -0.03), while IRR suggested a 34% reduction in ER visits (IRR 0.66, 95% CI 0.59 to 0.74). In Poisson models, adjustment for clustering lowered the precision of the estimates relative to stratified IRR results. For ER visits but not school absences, failure to incorporate study indicators resulted in a different estimate of effect (unadjusted IRR 0.77, 95% CI 0.59 to 0.99). Conclusions: Choice of method among the ones presented had little effect on inference but affected the clinical interpretability of the findings. Incidence rate methods gave more clinically interpretable results than SMD. Poisson regression allowed for further adjustment for heterogeneity across studies. These data suggest that analysts who want to improve the clinical interpretability of their findings should consider incidence rate methods.
Image mensuration by maximum a posteriori probability estimation

We present an algorithm for pulse width estimation from blurred and nonlinear observations in the presence of signal dependent noise. The main application is the accurate measurement of image sizes on film. The problem is approached by modeling the signal as a discrete position finite state Markov process, and then determining the transition location that maximizes the a posteriori probability. It turns out that the blurred signal can be represented by a trellis, and the maximum a posteriori probability (MAP) estimation is obtained by finding the minimum cost path through the trellis. The latter is done by the Viterbi algorithm. Several examples are presented. These include the measurement of the width of a road in an aerial photo taken at an altitude of 5000 ft. The resulting width estimate is accurate to within a few inches.
ecology and human ecology: a comparison of theories in the biological and social sciences1

Ecology has been used frequently by social scientists as a source of theoretical models, and biological ecologists have often applied their theory to human populations. Several problems have attended these cross-disciplinary enterprises, including inappropriate uses of teleological models and a failure by both biologists and social scientists to understand the theoretical implications of culture and technology for ecological models. Attention to these problems will increase the applicability of ecological theories in the social sciences.
Electromagnetic Analysis of Radiometer Calibration Targets Using Dispersive 3D FDTD

Accurate electromagnetic and thermal analysis is essential for designing wideband radiometer calibration targets as well as for understanding the electromagnetic wave interaction with these highly absorbing structures. To serve this purpose, a three dimensional dispersive finite difference time domain (FDTD) engine has been developed. We present the various aspects associated with this FDTD formulation, including modeling of dispersive lossy media using piecewise linear recursive convolution (PLRC) and application of uniaxial perfectly matched layer (UPML) absorbing boundary condition and symmetry/periodic boundary conditions to provide high accuracy using moderate computational resources. Time domain modeling of the dispersive radar absorbent material is performed by fitting the measured complex permittivity and permeability data to a series of Debye like terms using genetic algorithm (GA) optimization. The broadband reflectivity spectrum of the calibration target is obtained by transient plane wave excitation. The reflectivity spectra of pyramidal calibration targets in the frequency range [6, 200] GHz is obtained and compared to the geometrical optics limit and a finite element solution. The spectrum depends significantly on the height to base ratio and coating thicknesses of the absorbent material.
Capturing Crime The Qualitative Analysis of Individual Cases for Advancing Criminological Knowledge

The qualitative analysis of individual cases has a prominent place in the development of criminological theory, yet progression in the scientific study of crime has largely been viewed as a distinctly quantitative endeavor. In the process, much of the theoretical depth and precision supplied by earlier methods of criminological knowledge production have been sacrificed. The current work argues for a return to our criminological roots by supplementing quantitative analyses with the qualitative inspection of individual cases. We provide a specific example of a literature (i.e., criminal specialization/versatility) that has become increasingly quantitative and could benefit from the use of the proposed approach. We conclude by offering additional areas of research that might be advanced by our framework presented here.
IL-1 Induces Expression of WAF1 mRNA in Human Fibroblasts: Mechanisms of Accumulation

WAF1 inhibits cyclin-cyclin dependent kinase complexes, causing arrest in the cell cycle. We report that interleukin-1 (IL-1) regulates the levels of WAF1 protein and mRNA in human fibroblasts. Further studies showed that 12-O-tetradecanoyl phorbol 13-acetate (TPA) enhanced the accumulation of WAF1; cells refractory to TPA still increased their levels of WAF1 mRNA when exposed to IL-1. IL-1 also increased transcription of WAF1 by 13-fold and WAF1 mRNA became 2-fold more stable in cells stimulated with IL-1 (t1/2 = 2 h) as compared to untreated cells (t1/2 = 1 h). In summary, IL-1 induces expression of WAF1, and this occurs by increased transcription of WAF1 and stabilization of WAF1 mRNA. Our data also indicate that the induction of WAF1 mRNA by IL-1 occurs through a pathway independent of protein kinase C activation.
Veterinary and Human Biobanking Practices: Enhancing Molecular Sample Integrity

Animal models have historically informed veterinary and human pathophysiology. Next-generation genomic sequencing and molecular analyses using analytes derived from tissue require integrative approaches to determine macroanalyte integrity as well as morphology for imaging algorithms that can extend translational applications. The field of biospecimen science and biobanking will play critical roles in tissue sample collection and processing to ensure the integrity of macromolecules, aid experimental design, and provide more accurate and reproducible downstream genomic data. Herein, we employ animal experiments to combine protein expression analysis by microscopy with RNA integrity number and quantitative measures of morphologic changes of autolysis. These analyses can be used to predict the effect of preanalytic variables and provide the basis for standardized methods in tissue sample collection and processing. We also discuss the application of digital imaging with quantitative RNA and tissuebased protein measurements to show that genomic methods augment traditional in vivo imaging to support biospecimen science. To make these observations, we have established a time course experiment of murine kidney tissues that predicts conventional measures of RNA integrity by RIN analysis and provides reliable and accurate measures of biospecimen integrity and fitness, in particular for time points less than 3 hours post–tissue resection.
Enriched space–time finite element method: a new paradigm for multiscaling from elastodynamics to molecular dynamics

SUMMARY The main objective of this paper is to present an enriched version of the space–time FEM method to incorporate multiple temporal scale features with a focus on dynamics problems. The method is established by integrating the basic framework of the space–time discontinuous Galerkin method with the extended finite element method. Two versions of the method have been developed: one at the continuum scale (elastodynamics) and the other focuses on the dynamics at the molecular level. After an initial outline of the formulation, we explore the incorporation of different types of enrichments based on the length scale of interest. The effects of both continuous and discontinuous enrichments are demonstrated through numerical examples involving wave propagations and dynamic fracture in harmonic lattice. The robustness of the method is evaluated in terms of convergence and the ability to capture the fine scale features. It is shown that the enriched space–time FEM leads to an improvement in the convergence properties over the traditional space–time FEM for problems with multiple temporal features. It is also highly effective in integrating atomistic with continuum representations with a coupled framework. Copyright © 2012 John Wiley & Sons, Ltd.
Intranet Boundaries: Social Actors and Systems Integration

Systems integrations (SI) have been examined from two main vantage points. External B2B SI has focused primarily on transactional interactions between customers and suppliers in the value chain. Internal intra-organizational SI has focused on structural interactions between functional units of the firm. Both approaches present problems for intranet integrations that serve communities of practice which often cross organizational boundaries, and that support nontransactional types of interactions. In this paper, I present four vignettes of intranet integration that highlight the value of a project-based approach to SI, and also suggest how a newly developed framework for social actor analysis can help to foster that approach.
Mental Health Policies, International

A mental health policy is an official statement by a government or health authority that provides the overall direction for improving mental health of people by defining a vision, values, principles, and objectives, and by establishing a broad model for action to achieve that vision. A policy is distinguished from a plan, or a strategy for implementing actions to achieve objectives of a policy. International health authorities, such as the World Health Organization, develop and establish guidelines for the development of mental health policy, strategic plans, and health care services at the country level. The key recommendations for developing mental health policy currently are to deinstitutionalize mental health care, to integrate mental health into general health care, and to develop community mental health services. There are similarities and differences among countries in mental health policies and systems. Similarities include shared international principles and guidelines. Differences are visible in the scope/type of services, financing, workforce development, and approaches to prevention, intervention, and ongoing care. Notably, low- and middle-income countries are less likely to have policies although they carry a disproportionate burden of mental health conditions. Inequity in mental health care is also present within countries and linked to policies and system type. Keywords: health care; mental health; sociology of mental health
From Global Cities to the Lands’ End: The Relocation of Corporate Headquarters and the New Company Towns of Rural America

Since the 1970s, a number of major corporations have located their corporate headquarters in rural and non-metropolitan areas. I interrogate this phenomenon, based on a case study of Lands’ End, a global apparel firm in Wisconsin. Much research has exposed how firms insulate themselves from claims made by workers and communities through organizational and spatial distance (i.e. global sourcing, casualization of employment structures). Corporate headquarters relocation presents a paradox, bringing key decision-makers in the global economy into new, face-to-face relationships with workers and communities. Negotiated against a radical transformation of local class structure, I argue that new forms of social regulation are emerging—in particular, a hybrid version of the Fordist-era company towns.
Drug-Induced Urticaria

Urticaria, often referred to as hives, is one of the most commonly diagnosed dermatologic disorders in emergency departments and urgent care facilities. Due to the wide variety of manifestations and etiologies, it is of great importance to rapidly recognize the condition, work up potential causes, and institute appropriate clinical treatment. In this chapter we aim to educate clinicians about the etiology, presentation, and management of the three subtypes of urticaria commonly induced by drugs: acute, chronic, and contact urticaria.
Front waves in the early RNA world: The Schlögl model and the logistic growth model.

Front wave solutions of nonlinear reaction-diffusion models describing the spatio-temporal growth of RNA populations in the early RNA world are discussed. A two-variable model for RNA enzymes and enzyme complex molecules as well as single-variable models obtained via adiabatic elimination of the complex molecules are considered. In both models, the focus is on enzyme diffusion in one spatial dimension, assuming that the diffusion of complex molecules can be neglected. It is shown that one of the single-variable models corresponds to a Schlogl model of front propagation. In general, for the single-variable models it is found that front speed corresponds to the minimal speed of traveling fronts. In contrast, the two-variable model exhibits even slower front propagation. Front propagation might be an important factor in competitive evolutionary processes in the early RNA world.
Signaling Molecules Derived from the Cholesterol Biosynthetic Pathway

The isolation and characterization of many of the enzymes involved in the synthesis of cholesterol represented a major tour de force in the 1950s and 1960s (Mead et al., 1986; Porter and Spurgeon, 1981). These early studies led to the realization that the cyclic cholesterol molecule was derived from a polyisoprenoid, which in turn was shown to be composed of repeating five-carbon branched-chain building blocks derived from isopentenyl diphosphate (Rilling, 1985). The condensation of one or more isopentenyl diphosphate molecules with an allylic isoprenoid diphosphate (e.g., dimethylallyl diphosphate, geranyl diphosphate) is catalyzed by a family of related prenyl transferases that differ in their specificity for the allylic substrate (Edwards et al., 1992; Chen et al., 1994). The resulting linear isoprenoids are intermediates in the synthesis of a number of important compounds, including sterols, dolichols, heme a, steroid hormones, 1,25-dihydroxy vitamin D, bile acids, and geranylgeranyl diphosphate (Figure 1). Isoprenoid moieties, such as farnesyl and geranylgeranyl, are also post-translationally attached to certain proteins to produce prenylated proteins (Figure 1). Such modifications affect the localization and functions of the lipidated proteins. Recent studies indicates that isoprenoid alcohols or acids may also functions as novel signaling molecules.
Okubo-Zweig-Iizuka rule and lack of evidence for glueballs in. pi. /sup -/p. -->. phiphin

The Okubo-Zweig-Iizuka rule is a consequence of QCD. It is shown that in general disconnected diagrams are suppressed only if the gluons couple to the quark-antiquark pair of a single vector or tensor meson. Other disconnected diagrams are not strongly suppressed. It is shown that the threshold enhancement observed in ${\ensuremath{\pi}}^{\ensuremath{-}}p\ensuremath{\rightarrow}\ensuremath{\varphi}\ensuremath{\varphi}n$ is consistent with phenomenological expectations in the absence of resonances and thus does not contain any evidence for glueballs.
P1-10-07: Comparing Breast Cancer Screening Guidelines: A Stage-Survival-Cost Model in a Public Hospital.

Background: Despite advances in diagnosis and treatment of breast cancer in the United States, racial disparities in survival persist. Female breast cancer represented the costliest cancer site in 2010 with further increases projected to 2020. Mammography screening guidelines reflect the inherent difficulty in reconciling mortality reduction with potential harms to patients and cost-effectiveness concerns. Controversy still surrounds the 2009 updated USPSTF recommendations, as critics and advocates alike evaluate lives saved, costs, and how best to compare screening strategies. This study simulates USPSTF and ACS guidelines’ effects on stage, 5-year survival, and cost of treatment vs. usual practice in women treated in an urban public hospital. Methods: Charts of 84 patients diagnosed with Stage I-III breast cancer in 2008 were reviewed. Published tumor doubling times guided a retrospective model to predict size at diagnosis by simulated ACS or USPSTF guidelines. AJCC-7 stages were then assigned to produce 3 distributions: 1) actual stage; 2) stage under ACS; and 3) stage under USPSTF. Survival estimates by stage and year from diagnosis were drawn from NCDB statistics and applied to each stage distribution, yielding average predicted survival for the actual and hypothetical scenarios. Finally, treatment costs for women continuously enrolled in Medicaid for 18 months were calculated from merged claims and registry data and similarly applied. Results: Study patients averaged 55 years; 85% were African American. Forty-nine percent were covered by Medicaid and 23% by Medicare. Comparing actual and predicted stages at diagnosis showed significant shifts in stage distribution between all three scenarios (Table 1). ACS guidelines predicted higher survival (87.5% at 5 years) than actual (85.5%; p Discussion: To our knowledge, no studies have compared the impact of alternative screening guidelines on outcomes in a predominantly African-American, public hospital population. These data support continued use of and adherence to ACS screening recommendations for inner city patients to achieve the best survival and the lowest cost. Given the likelihood of patients to be uninsured or covered by federal programs, this study carries implications for public policy and patient education, especially in low-resource programs caring for underserved patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-10-07.
Non-communicable diseases and human rights: Global synergies, gaps and opportunities

The incorporation of human rights in health policy and programmes is known to strengthen responses to health problems and help address disparities created or exacerbated by illness yet this remains underexplored in relation to non-communicable diseases (NCDs). Aiming to understand existing synergies and how they might be further strengthened, we assessed the extent to which human rights are considered in global NCD policies and strategies and the degree of attention given to NCDs by select United Nations human rights mechanisms. Across global NCD policies and strategies, rhetorical assertions regarding human rights appear more often than actionable statements, thus limiting their implementation and impact. Although no human rights treaty explicitly mentions NCDs, some human rights monitoring mechanisms have been paying increasing attention to NCDs. This provides important avenues for promoting the incorporation of human rights norms and standards into NCD responses as well as for accountability. Linking NCDs and human rights at the global level is critical for encouraging national-level action to promote better outcomes relating to both health and human rights. The post-2015 development agenda constitutes a key entry point for highlighting these synergies and strengthening opportunities for health and rights action at global, national and local levels.
Case Report: Prolonged Vancomycin-Associated Neutropenia in a Chronic Hemodialysis Patient

ABSTRACT A chronic hemodialysis patient developed severe marrow granulocytic hypoplasia and peripheral blood neutropenia related to vancomycin therapy for an infected arteriovenous fistula. Neutropenia was prolonged and associated with sustained serum levels of vancomycin that persisted for more than 4 weeks following the last dose of vancomycin. No vancomycin-dependent leukoagglutinins were demonstrable in the patient’s serum. Although a direct toxic effect on marrow granulocyte production seems likely, a vancomycin-dependent immune suppression of granulopoiesis cannot be ruled out.
Monitoring of drinking water quality in Chengguan District of Lanzhou City from 2009 to 2011

Aim:To investigate the hygienic quality of drinking water in Chengguan District of Lanzhou City,and provide the scientific basis for monitoring and managing of drinking water quality.Methods:The samples of source water and secondary water supply were collected,detected and evaluated in Chengguan District from 2009 to 2011 according to the national standards.Results:The qualified rates of drinking water in Chengguan District in 2009,2010 and 2011 were 98.71%,98.28% and 100%,respectively.Conclusion:Drinking water in Chengguan District of Lanzhou City from 2009 to 2011 present high qualified rates,and can satisfy the sanitary requirement of drinking water.
Ruptured abdominal aortic aneurysm: Is endovascular aneurysm repair the answer for everybody?

Abstract Treatment paradigms for elective repair of asymptomatic abdominal aortic aneurysms (AAA) have evolved during the past 2 decades, with endovascular aneurysm repair as the preferred treatment modality. The patient care strategy for emergent treatment for ruptured AAA is not as straightforward, due in part to surgeon expertise and stent-graft availability at the institution. Although most reports have extrapolated elective endovascular aneurysm repair feasibility data to the ruptured AAA patient and the aneurysm anatomy, these expectations should be interpreted with caution. In the absence of level I evidence, and lack of adequate local hospital resources, endovascular aneurysm repair−first policy might not be feasible for all the patients who present with ruptured AAA.
[An analysis on the quality of information regarding online reporting system of notifiable diseases in Zhoushan city, Zhejiang province in 2007 ].

舟山市传染病网络直报执行5年来,在报告的及时性、敏感性和准确性上逐年提高,为进一步分析该市传染病网络直报工作状况,探讨直报信息质量评价方法,更好地改进今后工作,根据2007年全市网络直报数据,对传染病直报信息质量进行综合评价与分析。
On the use of mathematical programs with complementarity constraints in combined topological and parametric design of biochemical enzyme networks

ABSTRACTA new method is presented for biochemical enzyme network design based on direct transcription and mathematical programs with complementarity constraints. Topology and continuous parameters are optimized simultaneously. The case study design objective is to optimize adaptability while maintaining sufficient sensitivity to ensure input change detection. A three-node problem is solved using both simultaneous and single-shooting approaches. The simultaneous approach enables solution of four-node problems; this is a new capability not available through existing approaches such as exhaustive enumeration, and is a step toward designing larger systems. A conventional nested solution strategy was also investigated for a four-node problem where an outer loop solves the discrete topology optimization problem, and an inner loop solves the continuous problem for each candidate topology. The simultaneous approach yields robust network topological designs that are superior to those identified through the single-...
TWO SITES OF SYNTHESIS OF MACROMOLECULES IN NEURONS

Publisher Summary Nerve ending function in the central nervous system might be rapidly regulated by protein synthesis and the addition of carbohydrates to preformed polypetide chains could play a particularly important role in modifying the surface of the nerve ending that might be crucial for synaptic function. This chapter discusses the transport of proteins to nerve endings, protein synthesis by isolated nerve ending fractions, incorporation of radioactive carbohydrates into glycoproteins at nerve endings, and implications of glycoprotein synthesis at nerve endings. The rate of appearance of labeled proteins in various components of the nerve ending of mouse cerebrum after the administration of labeled leucine or glucosamine has been determined. The studies show that at least some protein associated with the soluble, mitochondrial, membranous, and synaptic vesicle components of the nerve ending are transported there from a proximal site of synthesis. Some of this protein arrives at nerve endings within one or a few hours of synthesis, making possible relatively rapid regulation of nerve ending function by perikaryal protein synthesis. There is evidence for the synthesis of some mitochondrial protein at nerve endings, but it is uncertain whether other polypeptide chains are synthesized at this site. However, there is considerable evidence that carbohydrates may be added to polypeptide chains that have been transported to the nerve ending, to produce new macromolecules. Therefore, nerve endings have the potentiality for local regulation of function by at least partial macromolecular synthesis.
Maximizing the number of x-colorings of 4-chromatic graphs

Abstract Let C 4 ( n ) be the family of all connected 4 -chromatic graphs of order n . Given an integer x ≥ 4 , we consider the problem of finding the maximum number of x -colorings of a graph in C 4 ( n ) . It was conjectured that the maximum number of x -colorings is equal to ( x ) ↓ 4 ( x − 1 ) n − 4 and the extremal graphs are those which have clique number 4 and size n + 2 . In this article, we reduce this problem to a finite family of graphs. We show that there exists a finite family F of connected 4 -chromatic graphs such that if the number of x -colorings of every graph G in F is less than ( x ) ↓ 4 ( x − 1 ) | V ( G ) | − 4 then the conjecture holds to be true.
Discovery of G Protein-Biased D2 Dopamine Receptor Partial Agonists

Biased ligands (also known as functionally selective ligands) of G protein-coupled receptors are valuable tools for dissecting the roles of G protein-dependent and independent signaling pathways in health and disease. Biased ligands have also been increasingly pursued by the biomedical community as promising therapeutics with improved efficacy and reduced side effects compared with unbiased ligands. We previously discovered first-in-class β-arrestin-biased agonists of dopamine D2 receptor (D2R) by extensively exploring multiple regions of aripiprazole, a balanced D2R agonist. In our continuing efforts to identify biased agonists of D2R, we unexpectedly discovered a G protein-biased agonist of D2R, compound 1, which is the first G protein-biased D2R agonist from the aripiprazole scaffold. We designed and synthesized novel analogues to explore two regions of 1 and conducted structure–functional selectivity relationship (SFSR) studies. Here we report the discovery of 1, findings from our SFSR studies, and ch...
311. In Vivo Zinc Finger Nuclease-Mediated Targeted Integration of a Glucose-6-Phosphatase Transgene Enhances Biochemical Correction in Mice with Glycogen Storage Disease Type IA

Glycogen storage disease type Ia (GSD Ia) is caused by glucose-6-phosphatase (G6Pase) deficiency in association with severe, life-threatening hypoglycemia that necessitates lifelong dietary therapy. Here we show that use of a zinc-finger nuclease (ZFN) targeted to the ROSA26 safe harbor locus and a ROSA26-targeting vector containing a G6PC donor transgene, both delivered with adeno-associated virus (AAV) vectors, markedly improved survival of G6Pase knockout (G6Pase-KO) mice compared with mice receiving the donor vector alone (p<0.04) out to 8 months of age. Transgene integration has been confirmed by sequencing in the majority of the mice treated with both vectors. Surviving G6Pase-KO mice at 8 months of age had decreased glycogen content compared with young untreated G6Pase-KO controls, which correlated with the long-term survival of these mice that otherwise perish before weaning. A short-term experiment resolved difficulty observing biochemical differences between the dual-vector and single-vector groups, caused by a selective advantage for strongly-responding mice: 3-month-old mice receiving the ZFN had significantly reduced hepatic glycogen accumulation and improved G6Pase activity, compared with mice that received the donor vector alone. These data demonstrate that the use of ZFNs to drive integration of G6Pase at a safe harbor locus might improve transgene persistence and efficacy, and lower mortality in GSD Ia.
The Poetics of a “Check Out” Place: Preventing Burnout and Promoting Self-Renewal

This article emphasizes the importance of a “check out” place within a professional therapist’s life in order to prevent burnout and promote positive wellness and self-renewal. Three time periods-past, present, and future-are concentrated on and specific metaphorical and poetic exercises that clinicians can use in dealing with each are recommended.
Differentiating the Effects of Familial Risk for Alcohol Dependence and Prenatal Exposure to Alcohol on Offspring Brain Morphology

Background Offspring with a family history of alcohol dependence (AD) have been shown to have altered structural and functional integrity of corticolimbic brain structures. Similarly, prenatal exposure to alcohol is associated with a variety of structural and functional brain changes. The goal of this study was to differentiate the brain gray matter volumetric differences associated with familial risk and prenatal exposure to alcohol among offspring while controlling for lifetime personal exposures to alcohol and drugs. Methods A total of 52 high-risk (HR) offspring from maternal multiplex families with a high proportion of AD were studied along with 55 low-risk (LR) offspring. Voxel-based morphometric analysis was performed using statistical parametric mapping (SPM8) software using 3T structural images from these offspring to identify gray matter volume differences associated with familial risk and prenatal exposure. Results Significant familial risk group differences were seen with HR males showing reduced volume of the left inferior temporal, left fusiform, and left and right insula regions relative to LR males, controlling for prenatal exposure to alcohol drugs and cigarettes. HR females showed a reduction in the right fusiform but also showed a reduction in volume in portions of the cerebellum (left crus I and left lobe 8). Prenatal alcohol exposure effects, assessed within the familial HR group, was associated with reduced right middle cingulum and left middle temporal volume. Even low exposure resulting from mothers drinking in amounts less than the median of those who drank (53 drinks or less over the course of the pregnancy) showed a reduction in volume in the right anterior cingulum and in the left cerebellum (lobes 4 and 5). Conclusions Familial risk for AD and prenatal exposure to alcohol and other drugs show independent effects on brain morphology.
Sudden death due to aortic pathology

Sudden death from aortic dissection of an ascending aortic aneurysm is an uncommon but important finding in all series of sudden death in young, apparently healthy athletes. Individuals at risk include those having any of a variety of conditions in which structural weakness of the ascending aorta predisposes to pathological dilation under prolonged periods of increased wall stress. These conditions include Marfan syndrome, Loeys-Dietz syndrome, bicuspid aortic valve, and the vascular form of Ehlers-Danlos syndrome. Diagnostic criteria, surveillance strategies, medical management, and surgical indications are discussed. Finally, the current recommendations for sports participation are provided.
How Far do Ciliate Flagships Sail? A Proposed Gondawanaland Endemic Species at Anchor in Idaho Soils.

In terms of protist biogeography, “flagship species” (Foissner 2005) have been defined as those so remarkable or “showy” that they are unlikely to be overlooked when present in a given habitat. On this basis, flagship species have been suggested as an ideal or ultimate test for the existence of protist endemism. One example of a flagship ciliate is the terrestrial lepidosome-bearing trachelophyllid, Luporinophrys micelae, previously thought to be a Gondwanan endemic. This report comprises a morphologic description of two populations of L. micelae from Laurentian soils (Idaho, Northwest USA). The flagship concept is briefly reviewed and ciliate biogeography is discussed in light of these findings.
Magnetic particle translation as a surrogate measure for synovial fluid mechanics.

Abstract The mechanics of synovial fluid vary with disease progression, but are difficult to quantify quickly in a clinical setting due to small sample volumes. In this study, a novel technique to measure synovial fluid mechanics using magnetic nanoparticles is introduced. Briefly, microspheres embedded with superparamagnetic iron oxide nanoparticles, termed magnetic particles, are distributed through a 100 μL synovial fluid sample. Then, a permanent magnet inside a protective sheath is inserted into the synovial fluid sample. Magnetic particles translate toward the permanent magnet and the percentage of magnetic particles collected by the magnet in a given time can be related to synovial fluid viscosity. To validate this relationship, magnetic particle translation was demonstrated in three phases. First, magnetic particle translation was assessed in glycerol solutions with known viscosities, demonstrating that as fluid viscosity increased, magnetic particle translation decreased. Next, the relationship between magnetic particle translation and synovial fluid viscosity was assessed using bovine synovial fluid that was progressively degenerated via ultrasonication. Here, particle collection in a given amount of time increased as fluid degenerated, demonstrating that the relationship between particle collection and fluid mechanics holds in non-Newtonian synovial fluid. Finally, magnetic particle translation was used to assess differences between healthy and OA affected joints in equine synovial fluid. Here, particle collection in a given time was higher in OA joints relative to healthy horses (p
FAP and Behavioral Activation

Depression is at the same time extremely common and extremely serious. In fact, depression is one of the most frequent presenting problems in outpatient psychotherapy, was listed as the single most burdensome disease in the world by the World Health Organization (Murray & Lopez, 1996 ), creates significant economic costs at the societal level, and results in major functional impairment and distress for depressed persons and those close to them. Suicide, of course, is the ultimate cost. How may FAP be used specifically with clients who present with depression? On the one hand, Tsai et al. (2008) present a working FAP model for the clinician to use with clients exhibiting diverse diagnoses, including depression, and it is our hope and belief that such a model will be useful.
Accumulation of PBDEs in stranded harp (Pagophilus groenlandicus) and hooded seals (Cystophora cristata) from the Northeastern United States.

Abstract Polybrominated diphenyl ethers (PBDEs) are highly lipophilic components of brominated flame retardants that are environmentally persistent and bioaccumulate. PBDEs are taken up from the gastrointestinal tract and accumulate mainly in fat depots and liver tissues. Seal species inhabiting Arctic and sub-Arctic regions can have upwards of 30% of their body mass composed of blubber. When those blubber stores are mobilized for energy, stored toxicants are also released into circulation. Most studies reporting accumulation of PBDEs in seals have focused on harbor and grey seals with few examining harp and hooded seals. In this study, PBDEs concentrations were analyzed in seal blubber from 21 stranded harp and 9 stranded hooded seals sampled along the northeast coast of the U.S. (1999–2010). A PBDE congener profile was determined for each individual. The results show that both species of seals are accumulating PBDEs with BDE-47 being the dominant congener. Mean ƩPBDE concentrations in harp seals were 70.55 ± 33.59 ng/g ww and for hooded seals 94.28 ± 42.65 ng/g ww. The results of this study are consistent with previous studies reporting a decrease in bioaccumulation with an increase in bromination. For both species, BDE-47 represented the highest percentage of the ƩPBDEs, composing over 50% of the ƩPBDEs in harp seals. When compared to stranding condition code, animals found alive had overall higher PBDE concentrations than those found in a state of moderate decomposition. This difference could be due to decreased blubber levels in the decomposed animals or potential degradation of the compounds in the blubber. Almost all seals used in this study were yearlings which is the most likely age class to strand. Yearling seals are at a crucial stage of development, especially of their immune system, which can be impacted by high levels of contaminants like PBDEs and increase the susceptibility to disease.
Thinking relationally about digital inequality in rural regions of the U.S.

This article reconsiders the concept of digital inequality drawing from recent developments in science and technology studies, including evolving theories of materiality (Barad, 2003; Bennett, 2010; Ingold, 2012), work on critical media infrastructures (Parks and Starosielski, 2015), and on maintenance and repair (Jackson, 2014; Edgerton, 2007). New ways of thinking about the material world move away from an examination of the cultural significance of ‘objects’ to consider the relationality, vibrancy, and continual “becoming” of materials that we live amidst and interact through. These innovative theoretical developments offer new ways of framing present-day problems and consequences of disparate connectivity by drawing attention to connecting infrastructures instead of the end points of access. I draw from ethnographic fieldwork on Internet access and use in a rural and remote part of northern California to show how the uneven and patchy deployment of the Internet and its physical infrastructures across space shapes rural experiences of the Internet.
A systems engineering approach to automated failure cause diagnosis in space power systems

Automatic failure-cause diagnosis is a key element in autonomous operation of space power systems such as Space Station's. A rule-based diagnostic system has been developed for determining the cause of degraded performance. The knowledge required for such diagnosis is elicited from the system engineering process by using traditional failure analysis techniques. Symptoms, failures, causes, and detector information are represented with structured data; and diagnostic procedural knowledge is represented with rules. Detected symptoms instantiate failure modes and possible causes consistent with currently held beliefs about the likelihood of the cause. A diagnosis concludes with an explanation of the observed symptoms in terms of a chain of possible causes and subcauses.
Instituições de Ensino Superior Católicas:: perspectivas para a educação e a formação integral

O artigo, resultado de um Estudo de Caso, focaliza as perspectivas para a educacao e a formacao integrais dos academicos pautadas pela etica, o respeito i vida e a construcao de uma sociedade mais justa e solidaria. Participaram do estudo sessenta e seis gestores que atuam em alguma das cinco Instituicoes de Ensino Superior de cunho confessional e comunitario, situadas no Brasil e mantidas pelo Instituto dos Irmaos das Escolas Cristas (conhecidos como Irmaos Lassalistas). Os dados coletados por meio da analise documental e do questionario e analisados com base na Tecnica de Analise de Conteudo, indicam como perspectiva para a oferta de um itinerario formativo que contribua para a educacao e a formacao integrais dos academicos a articulacao entre ensino, pesquisa e extensao, focalizando: a) a interacao com a comunidade, comprometimento e corresponsabilidade na melhoria do entorno, com uma atencao especial i s questoes ambientais; b) a postura etica nos modos de atuacao da IES; c) um ambiente institucional de acolhimento, cuidado e valorizacao dos atores da acao educativa; d) o fortalecimento do protagonismo pessoal e coletivo. Palavras-chave: Ensino Superior – Educacao Catolica – Educacao e Formacao Integral - Ensino, Pesquisa e Extensao.
Spectral sensitivity in ray-finned fishes: diversity, ecology and shared descent

A major goal of sensory ecology is to identify factors that underlie sensory-trait variation. One open question centers on why fishes show the greatest diversity among vertebrates in their capacity to detect color (i.e. spectral sensitivity). Over the past several decades, λmax values (photoreceptor class peak sensitivity) and chromacy (photoreceptor class number) have been cataloged for hundreds of fish species, yet the ecological basis of this diversity and the functional significance of high chromacy levels (e.g. tetra- and pentachromacy) remain unclear. In this study, we examined phylogenetic, physiological and ecological patterns of spectral sensitivity of ray-finned fishes (Actinoptergyii) via a meta-analysis of data compiled from 213 species. Across the fishes sampled, our results indicate that trichromacy is most common, ultraviolet λmax values are not found in monochromatic or dichromatic species, and increasing chromacy, including from tetra- to pentachromacy, significantly increases spectral sensitivity range. In an ecological analysis, multivariate phylogenetic latent liability modeling was performed to analyze correlations between chromacy and five hypothesized predictors (depth, habitat, diet, body coloration, body size). In a model not accounting for phylogenetic relatedness, each predictor with the exception of habitat significantly correlated with chromacy: a positive relationship in body color and negative relationships with body size, diet and depth. However, after phylogenetic correction, the only remaining correlated predictor was depth. The findings of this study indicate that phyletic heritage and depth are important factors in fish spectral sensitivity and impart caution about excluding phylogenetic comparative methods in studies of sensory trait variation.
Knee Disarticulations Versus Transfemoral Amputations: Functional Outcomes.

Objectives:To determine whether there is a patient-reported functional difference between combat-related knee disarticulations (KDs) and transfemoral amputations (TFAs).Setting:Role 3 Military Trauma Centers.Patients:We identified and contacted all KDs and TFAs performed at the Walter Reed National