cssi/SciSciGPT-SciSciNet huggingface dataset:
Exercise in the End-Stage Renal Disease Population

Many of the known benefits of exercise in the general population are of particular relevance to the ESRD population. In addition, the poor physical functioning that is experienced by patients who are on dialysis is potentially addressable through exercise interventions. The study of exercise in the ESRD population dates back almost 30 yr, and numerous interventions, including aerobic training, resistance exercise training, and combined training programs, have reported beneficial effects. Recently, interventions during hemodialysis sessions have become more popular and have been shown to be safe. The risks of exercise in this population have not been rigorously studied, but there have been no reports of serious injury as a result of participation in an exercise training program. It is time that we incorporate exercise into the routine care of patients who are on dialysis, but identification of an optimal training regimen or regimens, according to patient characteristics or needs, is still needed to facilitate implementation of exercise programs.
Mothering, fathering, and infant negativity as antecedents of boys' externalizing problems and inhibition at age 3 years: Differential susceptibility to rearing experience?

To examine the effects of infant negative emotionality and of mothering and fathering during the toddler years on 3-year-old boys' externalizing problems and inhibition, as well as explore the proposition that children vary in their susceptibility to rearing influence, 125 first-born, Caucasian boys from maritally intact families were studied. Results revealed that when infant negativity is measured with objective, replicable, and discriminantly valid procedures, no relation obtains between it and externalizing problems (nor inhibition). Moreover, as hypothesized on the basis of prior work, parenting was a stronger predictor of externalizing problems and inhibition in the case of children who were highly negative as infants. Mothering proved a stronger predictor of externalizing problems and fathering of inhibition, with more negative mothering in the 2nd and 3rd year forecasting higher CBCL-externalizing scores and less negative fathering in the 2nd and 3rd year and more positive fathering in the 2nd year forecasting more inhibition at age 3. Implications of these findings for studies of parental influence are considered. Correspondence: Jay Belsky, Human Development and Family Studies, 110 Henderson Building South, Pennsylvania State University, University Park, PA 16802; E-mail: [email protected]/* */
Interlaboratory Comparability Study of Cancer Gene Expression Analysis Using Oligonucleotide Microarrays

A key step in bringing gene expression data into clinical practice is the conduct of large studies to confirm preliminary models. The performance of such confirmatory studies and the transition to clinical practice requires that microarray data from different laboratories are comparable and reproducible. We designed a study to assess the comparability of data from four laboratories that will conduct a larger microarray profiling confirmation project in lung adenocarcinomas. To test the feasibility of combining data across laboratories, frozen tumor tissues, cell line pellets, and purified RNA samples were analyzed at each of the four laboratories. Samples of each type and several subsamples from each tumor and each cell line were blinded before being distributed. The laboratories followed a common protocol for all steps of tissue processing, RNA extraction, and microarray analysis using Affymetrix Human Genome U133A arrays. High within-laboratory and between-laboratory correlations were observed on the purified RNA samples, the cell lines, and the frozen tumor tissues. Intraclass correlation within laboratories was only slightly stronger than between laboratories, and the intraclass correlation tended to be weakest for genes expressed at low levels and showing small variation. Finally, hierarchical cluster analysis revealed that the repeated samples clustered together regardless of the laboratory in which the experiments were done. The findings indicate that under properly controlled conditions it is feasible to perform complete tumor microarray analysis, from tissue processing to hybridization and scanning, at multiple independent laboratories for a single study.
Controlled substitution of soy protein for meat protein: effects on calcium retention, bone, and cardiovascular health indices in postmenopausal women.

In a controlled feeding study, the effects of substituting 25 g soy protein for meat on calcium retention and bone biomarkers were determined. Postmenopausal women (n 13) ate two diets that were similar, except that, in one diet, 25 g highisoflavonesoyprotein(SOY)wassubstitutedforanequivalent amount of meat protein (control diet), for 7 wk each in a randomizedcrossoverdesign.After3wkofequilibration,calcium retention was measured by labeling the 2-d menu with 47 Ca, followed by whole-body counting for 28 d. Urinary calcium and renal acid excretion were measured at wk 3, 5, and 7. Biomarkers of bone and cardiovascular health were measured at the beginning and end of each diet. Calcium was similarly retained during the control and SOY diets (d 28, percent dose, mean pooled SD: 14.1 and 14.0 1.6, respectively).Despitea15–20%lowerrenalacidexcretionduringthe SOY diet, urinary calcium loss was unaffected by diet. Diet also did not affect any of the indicators of bone or cardiovascular health. Substitution of 25 g high isoflavone soy protein for meat, in the presence of typical calcium intakes, did not improveorimpaircalciumretentionorindicatorsofboneand cardiovascular health in postmenopausal women. (J Clin Endocrinol Metab 90: 181–189, 2005)
Analysis and role of oligosaccharides in milk

Milk is an important fluid in glycobiology because it contains a number of short carbohydrate chains either free or as glycoconjugates. These compounds as a class are the most abundant component and benefit the infant by developing and maintaining the infant's gut flora. New and emerging methods for oligosaccharide analysis have been developed to study milk. These methods allow for the rapid profiling of oligosaccharide mixtures with quantitation. With these tools, the role of oligosaccharide in milk is being understood. They further point to how oligosaccharide analysis can be performed, which until now has been very difficult and have lagged significantly those of other biopolymers.
The strength of anticipatory spatial biasing predicts target discrimination at attended locations: a high-density EEG study

Cueing relevant spatial locations in advance of a visual target results in modulated processing of that target as a consequence of anticipatory attentional deployment, the neural signatures of which remain to be fully elucidated. A set of electrophysiological processes has been established as candidate markers of the invocation and maintenance of attentional bias in humans. These include spatially-selective event-related potential (ERP) components over the lateral parietal (around 200–300 ms post-cue), frontal (300–500 ms) and ventral visual (> 500 ms) cortex, as well as oscillatory amplitude changes in the alpha band (8–14 Hz). Here, we interrogated the roles played by these anticipatory processes in attentional orienting by testing for links with subsequent behavioral performance. We found that both target discriminability (d’) and reaction times were significantly predicted on a trial-by-trial basis by lateralization of alpha-band amplitude in the 500 ms preceding the target, with improved speed and accuracy resulting from a greater relative decrease in alpha over the contralateral visual cortex. Reaction time was also predicted by a late posterior contralateral positivity in the broad-band ERP in the same time period, but this did not influence d’. In a further analysis we sought to identify the control signals involved in generating the anticipatory bias, by testing earlier broad-band ERP amplitude for covariation with alpha lateralization. We found that stronger alpha biasing was associated with a greater bilateral frontal positivity at 390 ms but not with differential amplitude across hemispheres in any time period. Thus, during the establishment of an anticipatory spatial bias, while the expected target location is strongly encoded in lateralized activity in parietal and frontal areas, a distinct non-spatial control process seems to regulate the strength of the bias.
Further evidence for coadaptation in crosses between geographic populations of Drosophila pseudoobscura.

Body size in Drosophila pseudoobscura is a continuously varying character with a high heritability; it is almost certainly related to fitness. Natural populations of D. pseudoobscura from Canada to Mexico have been sampled and found to vary geographically in body size. The geographic variation for the genes determining size is to some extent correlated with the physiographic division of the West. The populations from the Pacific coast have genetically smaller flies than do those from the interior provinces. Experimental populations derived from the samples of seven widely separated natural populations were crossed to yield F1 and F2 hybrid generations. Body size in the F1's varied irregularly, while the F2's showed a consistent ‘breakdown’, the F2's being significantly smaller than their F1 parents. The F1's were significantly less variable than their parents, while the F2's were significantly more variable than their parents of the F1 generation. The natural populations possess coadapted genetic systems, with genes mutually adjusted by selection for favorable interactions. Recombination disrupted the balanced genic complexes to give the F2 breakdown and the increased F2 variability. D. pseudoobscura differs from D. subobscura in showing the effects expected in crosses between coadapted systems. This species difference lends additional support to the hypothesis that the gene pools of these two successful species respond in different ways to environmental variation. The gene pool of D. pseudoobscura is flexible and changes readily, while that of D. subobscura is relatively rigid.
Paleomagnetism of the Upper Devonian Catskill Formation from the southern limb of the Pennsylvania Salient: Possible evidence of oroclinal rotation

Multiple components of magnetization were isolated in the natural remanent magnetiza- tion of samples of the Upper Devonian Catskill Formation red beds taken from the southern limb of the Pennsylvania Salient. The dominant, ther- mally distributed component (SF), previously thought to predate folding, is demonstrably syn- folding in origins The mean direction for SF based on data from the current study and a pre- vious study is Declination/Inclination = 161.6o/7.9 o, a95 = 3.9 o (pole position 127.3oE, 43.1oN, A95 = 3.1 o, N = 14 sites). Although the remagnetization is clearly synfolding in most areas, the relative ages of folding and remagne- tization vary locally. A subordinate high unblocking temperature component (HT) has a mean tilt corrected direction of 160o/36 o, a95 = 16 o (pole position 123.5oE 26 ioN, A95 = 15.4 o , s , n m 7 samples). Comparison of HT with the prefolding magnetization isolated in the northern limb of the salient suggests that the paleolatitude of this part of North America was about 16oS and that part of the curvature of the salient was acquired during orogenesis.
Higher than standard radiation doses (≥72 Gy) with or without androgen deprivation in the treatment of localized prostate cancer

Abstract Purpose: To study the effect on biochemical relapse-free survival (bRFS) and clinical disease-free survival of radiation doses delivered to the prostate and periprostatic tissues for localized prostate cancer. Methods and Materials: A total of 1041 consecutive localized prostate cancer cases treated with external beam radiotherapy (RT) at our institution between 7/86 and 2/99 were reviewed. All cases had available pretreatment parameters including pretreatment prostate-specific antigen (iPSA), biopsy Gleason score (bGS), and clinical T stage. The median age was 69 years. Twenty-three percent of cases ( n = 238) were African-American. The distribution by clinical T stage was as follows: T1 in 365 cases (35%), T2 in 562 cases (54%), and T3 in 114 cases (11%). The median iPSA level was 10.1 ng/ml (range: 0.4–692.9). The distribution by biopsy Gleason score (bGS) was as follows: ≤6 in 580 cases (56%) and ≥7 in 461 cases (44%). Androgen deprivation (AD) in the adjuvant or neoadjuvant setting was given in 303 cases (29%). The mean RT dose was 71.9 Gy (range: 57.6–78.0 Gy). The median RT dose was 70.2 Gy, with 458 cases (44%) receiving at least 72.0 Gy. The average dose in patients receiving Results: The 5- and 8-year bRFS rates were 61% (95% CI 55–65%) and 58% (95% CI 51–65%), respectively. The 5-year bRFS rates for patients receiving radiation doses ≥72 Gy versus p p p p p p = 0.74), race ( p = 0.96), radiation technique ( p = 0.15), and use of AD ( p = 0.31) were not. We observed 11% clinical failures (local, distant, or both) at 5 years and 15% at 8 years for the entire cohort. There was a statistically significant improvement with higher radiation doses ( p = 0.032). The 5-year clinical relapse rates for patients receiving ≥72 Gy versus p = 0.026). Conclusion: Patients receiving radiation doses exceeding 72 Gy had significantly better bRFS and clinical disease-free survival rates. Although results need to be confirmed with longer follow-up, these preliminary results are extremely encouraging. If these results are confirmed by other institutions and by longer follow-up, RT doses exceeding 72 Gy should be considered as standard of care.
Changes in hemiplegic grasp following distributed repetitive intervention: a case series.

The purpose of this pilot study was to investigate the efficacy of a distributed model of repetitive and focused intervention on grasp force, and clinical and functional hand measures in persons with chronic hemiplegia and limited hand recovery from self-reported stroke. A case series design was used. Focused repetitive unilateral and bilateral interventions were provided in a distributed manner (three times a week for 6 weeks) to three persons with upper limb hemiplegia of more than 1 year. Data from instrumented grasp force, and clinical and functional measures were obtained at weeks 0, 3, 6 and 9. Each participant improved in at least one measure of grasp force, as well as in clinical skill and function. All participants improved in the quality of handwriting. Improved outcomes remained above baseline levels following 3 weeks of non-intervention. The findings are compatible with current evidence of adaptive cortical plasticity following increased repetition. The findings show that, for these three persons, distributed repetitive practice was sufficient to effect change. Localization by cerebral area affected is not possible, nor is it possible to parse the effectiveness of any component of the intervention. A larger group study is warranted to determine whether similar results may be found for other persons with chronic hemiplegia. Future studies should incorporate kinematic handwriting analysis and a greater range of functional tasks. Copyright © 2009 John Wiley & Sons, Ltd.
Adjusting global extinction rates to account for taxonomic susceptibility

Abstract Studies of extinction in the fossil record commonly involve comparisons of taxonomic extinction rates, often expressed as the percentage of taxa (e.g., families or genera) going extinct in a time interval. Such extinction rates may be influenced by factors that do not reflect the intrinsic severity of an extinction trigger. Two identical triggering events (e.g., bolide impacts, sea level changes, volcanic eruptions) could lead to different taxonomic extinction rates depending on factors specific to the time interval in which they occur, such as the susceptibility of the fauna or flora to extinction, the stability of food webs, the positions of the continents, and so on. Thus, it is possible for an extinction event with a higher taxonomic extinction rate to be caused by an intrinsically less severe trigger, compared to an event with a lower taxonomic extinction rate. Here, we isolate the effects of taxonomic susceptibility on extinction rates. Specifically, we quantify the extent to which the taxo...
Error Control Coding: An Overview

Reliable transmission of information is one of the central topics in digital communications. While the advent of powerful digital computing and storage technologies has made the data traffic increasingly digital, the reality of inherently noisy communication channels persists and has thus made error control coding an important and necessary step in achieving reliable communication. Coding in this case refers to systematically introducing redundancy in a message prior to transmission and using this redundancy to recover the original message from the erroneously received one. There are two basic types of error control codes: block codes and convolutional codes. Convolutional codes, techniques for decoding them and their applications are the focus of this book. This introductory chapter begins with a brief historical background of the development of information theory, a field of study that established the utility of error control coding.
Integrating livestock manure with a corn-soybean bioenergy cropping system improves short-term carbon sequestration rates and net global warming potential.

Abstract Carbon cycling and the global warming potential (GWP) of bioenergy cropping systems with complete biomass removal are of agronomic and environmental concern. Corn growers who plan to remove corn stover as a feedstock for the emerging cellulosic ethanol industry will benefit from carbon amendments such as manure and compost, to replace carbon removed with the corn stover. The objective of this research was to determine the effect of beef cattle feedlot manure and composted dairy manure on short-term carbon sequestration rates and net global warming potential (GWP) in a corn–soybean rotation with complete corn-stover removal. Field experiments consisting of a corn–soybean rotation with whole-plant corn harvest, were conducted near East Lansing, MI over a three-year period beginning in 2002. Compost and manure amendments raised soil carbon (C) at a level sufficient to overcome the C debt associated with manure production, manure collection and storage, land application, and post-application field emissions. The net GWP in carbon dioxide equivalents for the manure and compost amended cropping systems was −934 and −784 g m−2 y−1, respectively, compared to 52 g m−2 y−1 for the non-manure amended synthetic fertilizer check. This work further substantiates the environmental benefits associated with renewable fuels and demonstrates that with proper management, the integration of livestock manures in biofuel cropping systems can enhance greenhouse gas (GHG) remediation.
An Introduction to Association Analysis

This chapter focuses on techniques commonly used in GWAS studies to estimate single SNP marker associations in samples of unrelated individuals; when the phenotype is discrete (disease/no disease) then case–control methods, conditional and unconditional logistic regression, are typically utilized. Maximum likelihood estimation for generalized linear models is reviewed, and the score, Wald, and likelihood ratio tests are defined and discussed. The analysis of data from nuclear family-based designs is also briefly introduced. Issues regarding confounding, measurement error, effect mediation, and interactions are described. Control for multiple comparisons is reviewed with an emphasis placed on the behavior of the Bonferroni criteria for multiple correlated tests. The effects on statistical estimation and inference of the loss of independence between outcomes are characterized for a specific model of loss of independence, which is relevant to the presence of hidden population structure or relatedness. These last results build on a basic theme described in Chap. 2 and are then carried forward in Chap. 4.
What Makes Tom Hanks Look Like Tom Hanks

We reconstruct a controllable model of a person from a large photo collection that captures his or her persona, i.e., physical appearance and behavior. The ability to operate on unstructured photo collections enables modeling a huge number of people, including celebrities and other well photographed people without requiring them to be scanned. Moreover, we show the ability to drive or puppeteer the captured person B using any other video of a different person A. In this scenario, B acts out the role of person A, but retains his/her own personality and character. Our system is based on a novel combination of 3D face reconstruction, tracking, alignment, and multi-texture modeling, applied to the puppeteering problem. We demonstrate convincing results on a large variety of celebrities derived from Internet imagery and video.
High-Order Diffusion Tensor Connectivity Mapping on the GPU

We present an efficient approach to computing white matter fiber connectivity on the graphics processing unit (GPU). We utilize a high-order tensor model of fiber orientation computed from high angular resolution diffusion imaging (HARDI) and a stochastic model of white matter fibers to compute and display global white matter connectivity in real time. The high-order tensor model overcomes limitations of the 2nd-order tensor model in regions of crossing or fanning fibers. By utilizing modern GPU features exposed in recent versions of the OpenGL API we can perform processing and visualization without costly GPU-CPU data transfers.
Photodecomposition of MnO4 - : A Theoretical Study

The electronic and geometrical structures of the ground states and low-lying isomers of MnO4 and MnO4- have been calculated as a function of spin-multiplicities by using the molecular orbital theor...
An Iterative Eigenvector Updating Method for Structural Damage Detection using Piezoelectric Transducer Circuitry with Tunable Inductance

The concept of using tunable piezoelectric transducer circuitry to enhance the performance of frequency-shift based damage detection has been recently explored. While previous studies have shown promising features, the advantage of such an approach has not been fully realized due to the limitations in the associated damage identification algorithms. This research aims at advancing the state-of-the-art of this concept, where an iterative eigenvector updating method is developed to improve the accuracy of the damage detection scheme. The basic principle of this method is to iteratively update the eigenvectors of the damaged structure such that the information of the damage-induced eigenvector change can be included in the damage detection formulation without actually measuring the vibration modes. The inductance tuning method is extended to structures with multiple transducers and circuits. Numerical analysis on a plate structure demonstrated the effectiveness and accuracy of the new method in detecting both the location and severity of the structural damage. Nomenclature K = generalized stiffness matrix of the electro-mechanical integrated system e j K = elemental stiffness matrix of the j th element c K = coupling matrix between the mechanical structure and piezoelectric circuit p K = inverse capacitance matrix of the piezoelectric circuit s K = stiffness matrix of the mechanical structure only M = generalized mass matrix of the electro-mechanical integrated system s M = mass matrix of the mechanical structure only q = displacement vector of the mechanical structure Q = electrical charge flow vector in the circuit i ω = i th resonant frequency of the healthy integrated electro-mechanical system () d i ω = i th resonant frequency of the damaged integrated electro-mechanical system i λ = i th eigenvalue of the healthy integrated electro-mechanical system
From calculus to wavelets: A new mathematical technique

A ‘wavelet’ is a function that exhibits oscillatory behaviour in some interval and then decays rapidly to zero outside this interval. A remarkable discovery of recent years is that the translations and dilations of certain wavelets can be used to form sets of ‘basic’ functions for expanding general functions into infinite series, and these expansions have many theoretical and practical applications.
Insecticides and Spray Schedules for the Control of Cabbage Leaf Feeding Lepidoptera

Insecticides and schedules of application were evaluated in Iowa for the control of the cabbage leaf-feeding complex of the diamondback moth, Plutella maculipennis (Curt.), the imported cabbage worm, Pieris rapae (L.), and the cabbage looper, Trichoplusia in (Hbn.), infesting cabbage grown for fresh market sales in July. Relative amounts of leaf damage caused by the combined feeding of these insects was visually rated in five classes. The data obtained were suited to statistical analysis. The method of evaluation was economical of time. Endrin, 0.25 pound per acre, was superior to other compounds tested. Guthion, parathion and Thiodan at 0.75, 0.33 and 0.50 pound per acre, respectively, were superior to DDT, 1 pound per acre. Endrin and parathion at 0.3 pound per acre applied weekly were equally and extremely effective. Phosdrin, 0.3 pound per acre, was nearly as good as endrin, Biweekly applications of DDT, 1 pound per acre, were inferior to weekly applications of DDT at the same rate, or to toxaphene, 2 pounds per acre, and to parathion applied weekly or biweekly. Methoxychlor, 2 pounds per acre, frequently recommended in the North Central States, was of little value in preventing the leaf damage.
Consenting Adults, Sex, and Natural Law Theory

This paper argues for the superiority of natural law theory over consent-based approaches to sexual morality. I begin by criticizing the “consenting adults” sexual ethic that is dominant in contemporary Western culture. I then argue that natural law theory provides a better account of sexual morality. In particular, I will defend the “perverted faculty argument” (PFA), according to which it is immoral to use one’s bodily faculties contrary to their proper end.
Ladies, Gentlemen, and Skulls: Hamlet and the Iconographic Traditions

T HE SCENE OF HAMLET CONTEMPLATING the skull of Yorick in the graveyard of Elsinore is one of the most famous in the Shakespearean canon. For actors and playgoers alike, it is a lasting favorite, and it has been engraved on the popular mind as the most memorable single image of the melancholy Prince. As far as we can now tell, Shakespeare's presentation of that scene was a striking innovation on the London stage when he introduced it in or about the year 1600.1 But Shakespeare was not creating de novo. There was a long and very popular tradition in which a young man was shown contemplating a skull, or commenting upon it, and scores of examples of this visual topos exist in various art forms. The greatest of these is Frans Hals's oil of A Young Man with a Skull [Figure I ]-which was once confidently identified as Hals's painting of Shakespeare's Hamlet. That identification has now given way to a recognition that-there was a broad and encompassing tradition which included both Shakespeare and Hals.2 That tradition was well known to the audiences for whom Shakespeare wrote. It was readily accessible in England as on the Continent through prints
Advance in search for effects of the ethnic on the pharmacokinetics

The objective of the ICH E5 guidance is to develop strategies for determining whether a drug is likely to be "ethnically sensitive", and to reasonably extrapolating clinical data from one region to another. One of the major concerns in evaluating ethic differences is the potential impact of ethnicity on a drug's pharmacokinetics. Supported by the available literature, the purpose of this review is to discuss whether the effects of race or ethnicity on pharmacokinetics can be predictable by major pharmacokinetic proce- sses, such as bioavailability (absorption), distribution, metabolism and renal elimination.
A Method for Estimating the Profitability of a Product Disassembly Operation

Disassembly is the process of physically separating the parts in a product. End-of-life product disassembly is slowly growing into a common and worthwhile industrial practice. There are several reasons for this, including, (i) the recovery of valuable and reusable parts or subassemblies, (ii) product separation to facilitate the downstream material recovery process, (iii) the removal of hazardous or toxic materials, (iv) to remanufacture the product for another useful life, and (v) to destroy the proprietary parts or subassemblies. In combination these reasons also help the environmental and ecological detriments associated with product disposal. The process of disassembly tends to be predominantly manual, and the overall economics is still not well understood. In this paper our goal is to introduce a method which will support the “direct disposal?” versus “disassemble?” decision making process. We present a model to compute the disassembly return on investment. This model considers the costs associated with product sortation into disassembly families, disassembly operation costs, and the market value of the output streams. We use this model to generate both a threshold for the disassembly return on investment, and also the maximum allowable disassembly labor time. The model is constructed from empirical evidence gathered from several industrial disassembly facilities. This model can be used to evaluate new and old designs.
Carotenoid to Chlorophyll a Singlet Energy Transfer: Direct Evidence for Involvement of the Carotenoid ‘A’ State in an Algal Light-Harvesting System

Carotenoids are an important component of the light-harvesting antenna in photosynthetic systems [1]. Their intense blue-green absorptions, together with carotenoid to chlorophyll energy transfer, allow photosynthetic systems to utilize incident radiation that would otherwise be wasted. Measurement of carotenoid to chlorophyll energy transfer efficiency and energy transfer rates provides important information about the details of the function of carotenoids in light harvesting. In this work we report a measurement of carotenoid to chlorophyll a singlet energy transfer efficiency in thylakoid membranes of the algal diatom P. tricornutum. We also present a two-photon excitation spectrum that directly verifies the in vivo existence and energy transfer capability of an energetically low-lying carotenoid electronic state (A state) not seen in the absorption spectrum. Mechanistic considerations arising from these results and from time-resolved measurements of carotenoid to chlorophyll a energy transfer [2] are discussed.
Organelle, Protein and Peptide Fractionation in Cardiovascular Proteomics

Proteomics experiments are as diverse as the scientists who perform them. Goals range from the desire to understand a subcellular structure or an individual protein in greater depth, to identification of novel protein-protein interactions. Or perhaps, the goal is to obtain a global protein abundance profile from an animal model of cardiovascular disease or from patient biopsies. Regardless of scale or objective, inevitably, the tools of organelle isolation, protein purification or peptide fractionation will play an integral role. In this chapter, we survey both time-honored and state-of-the-art fractionation techniques, with an emphasis on underlying physical and chemical principles.
A Statistical Direct Volume Rendering Framework for Visualization of Uncertain Data

With uncertainty present in almost all modalities of data acquisition, reduction, transformation, and representation, there is a growing demand for mathematical analysis of uncertainty propagation in data processing pipelines. In this paper, we present a statistical framework for quantification of uncertainty and its propagation in the main stages of the visualization pipeline. We propose a novel generalization of Irwin-Hall distributions from the statistical viewpoint of splines and box-splines, that enables interpolation of random variables. Moreover, we introduce a probabilistic transfer function classification model that allows for incorporating probability density functions into the volume rendering integral. Our statistical framework allows for incorporating distributions from various sources of uncertainty which makes it suitable in a wide range of visualization applications. We demonstrate effectiveness of our approach in visualization of ensemble data, visualizing large datasets at reduced scale, iso-surface extraction, and visualization of noisy data.
Integrated Circuit Cooling Using Heterogeneous Micropin-Fin Arrays for Nonuniform Power Maps

As microelectronic system density continues to increase, cooling with conventional technologies continues to become more challenging and is often a limiter of performance and efficiency. The challenge arises due to both large heat fluxes generated across entire chips and packages, and localized hotspots with even higher heat flux. In this paper, nonuniform micropin-fin heat sinks are investigated for the cooling of integrated circuits with nonuniform power maps. Four heterogeneous micropin-fin samples were fabricated and tested in single-phase experiments with deionized water to investigate the effectiveness of local micropin-fin clustering for the cooling of hotspots. Cylindrical and hydrofoil micropin-fins were tested, as well as two types of heterogeneous arrays: those with pin-fins clustered directly over the hotspot and those with the high density cluster spanning the entire width of the channel to prevent flow bypass around the cluster. Samples were tested with a uniform nominal heat flux of 250 W/cm2 as well as a hotspot heat flux of 500 W/cm2. Local micropin-fin clustering was found to be an effective method of reducing local thermal resistance with a modest pressure drop penalty.
Gestational diabetes exacerbates maternal immune activation effects in the developing brain

Maternal inflammation and diabetes increase the risk for psychiatric disorders in offspring. We hypothesized that these co-occurring risk factors may potentiate each other. To test this, we maternally exposed developing mice in utero to gestational diabetes mellitus (GDM) and/or maternal immune activation (MIA). Fetal mouse brains were exposed to either vehicle, GDM, MIA or GDM+MIA. At gestational day (GD) 12.5, GDM produced a hyperglycemic, hyperleptinemic maternal state, whereas MIA produced significant increases in proinflammatory cytokines and chemokines. Each condition alone resulted in an altered, inflammatory and neurodevelopmental transcriptome profile. In addition, GDM+MIA heightened the maternal inflammatory state and gave rise to a new, specific transcriptional response. This exacerbated response was associated with pathways implicated in psychiatric disorders, including dopamine neuron differentiation and innate immune response. Based on these data, we hypothesize that children born to GDM mothers and exposed to midgestation infections have an increased vulnerability to psychiatric disorder later in life, and this should be tested in follow-up epidemiological studies.
Identification of the I38T PA Substitution as a Resistance Marker for Next-Generation Influenza Virus Endonuclease Inhibitors

The clinical severity and annual occurrence of influenza virus epidemics, combined with the availability of just a single class of antivirals to treat infections, underscores the urgent need to develop new anti-influenza drugs. The endonuclease activity within the viral acidic polymerase (PA) protein is an attractive target for drug discovery due to the critical role it plays in viral gene transcription. RO-7 is a next-generation PA endonuclease inhibitor of influenza A and B viruses, but its drug resistance potential is unknown. Through serial passage of influenza A(H1N1) viruses in MDCK cells under selective pressure of RO-7, we identified an I38T substitution within the PA endonuclease domain that conferred in vitro resistance to RO-7 (up to a 287-fold change in 50% effective concentration [EC50]). I38T emerged between 5 and 10 passages, and when introduced into recombinant influenza A(H1N1) viruses, alone conferred RO-7 resistance (up to an 81-fold change in EC50). Cocrystal structures of mutant and wild-type endonuclease domains with RO-7 provided the structural basis of resistance, where a key hydrophobic interaction between RO-7 and the Ile38 side chain is compromised when mutated to the polar threonine. While Ile38 does not have a crucial role in coordinating the endonuclease active site, the switch to threonine does affect the polymerase activity of some viruses and influences RO-7 affinity for the PAN target (i.e., the ≈200-residue N-terminal domain of PA). However, the change does not lead to a complete loss of replication activity in vitro Our results predict that RO-7-resistant influenza viruses carrying the I38T substitution may emerge under treatment. This should be taken into consideration for clinical surveillance and in refinement of these drugs.IMPORTANCE The effectiveness of antiviral drugs can be severely compromised by the emergence of resistant viruses. Therefore, determination of the mechanisms by which viruses become resistant is critical for drug development and clinical use. RO-7 is a compound that potently inhibits influenza virus replication and belongs to a new class of drugs in late-stage clinical trials for treatment of influenza virus infection. Here we demonstrate that a single amino acid change acquired under prolonged virus exposure to RO-7 renders influenza viruses significantly less susceptible to its inhibitory effects. We have discovered how the mutation can simultaneously interfere with drug activity and still maintain efficient virus replication. These findings have important implications for the development of more effective derivatives of RO-7-like drugs and provide guidance for how to monitor the emergence of resistance.
Luke's Portrayal of the Social Dimension in the Ministry of Jesus and the Apostles (Luke-Acts) According to Isaiah's Message of Social Justice in Chapters 61:1–2 and 58:6

This article seeks to explore the manner in which Luke depicts the social aspects of the ministry of Jesus and the apostles in Luke-Acts based on his citations from Isa. 61.1–2 and 58.6. In essence...
Towards a Phenomenology of Empathy

Deeper insight into the advantages of the Husserlian phenomenological standpoint for psychoanalysis is gained through correction and augmentation of Varghese's analysis drawn from his 1988 paper in this journal. In particular, insight into the radicality of both phenomenology and empathy shows that empathy cannot be understood outside of the phenomenological perspective, and that thus Husserlian phenomenology is the appropriate theoretical framework for psychoanalysis.
Prior Probabilities (1968)

The fundamentally different problems of doing maximum entropy with continuous variables, noted already in a footnote in ITSM I, continued to plague the theory after the recognition of the proper continuous entropy expression in Brandeis. Introducing the ‘measure’ m(x) achieved the needed invariance of the results with respect to parameter changes, but left the practical problem untouched. Given m(x) in one parameter space, the mathematics tells us how to transform it to any other; but first we need a principle to find it in one space. If there is no obvious limiting process from some discrete set, what defines this measure?
An Energy-Efficient Wirelessly Powered Millimeter-Scale Neurostimulator Implant Based on Systematic Codesign of an Inductive Loop Antenna and a Custom Rectifier

In this work, a switched-capacitor-based stimulator circuit that enables efficient energy harvesting for neurostimulation applications is presented, followed by the discussion on the optimization of the inductive coupling front-end through a codesign approach. The stimulator salvages input energy and stores it in a storage capacitor, and, when the voltage reaches a threshold, releases the energy as an output stimulus. The dynamics of the circuit are automatically enabled by a positive feedback, eliminating any stimulation control circuit blocks. The IC is fabricated in a 180 nm CMOS process and achieves a quiescent current consumption of 1.8 μA. The inductive coupling front-end is optimized as a loaded resonator, in which the input impedance of the custom rectifier directly loads the inductive loop antenna. The loaded quality factor and the rectifier's efficiency determine the reception sensitivity of the stimulator, while a balance should be achieved for the robustness of the system against dielectric medium variations by increasing the reception bandwidth. The finalized stimulator adopts a 4.9 mm × 4.9 mm inductive loop antenna and achieves an overall assembly dimension of 5 mm × 7.5 mm. Operating at the resonant frequency of 198 MHz, the stimulator works at a 14 cm distance from the transmitter in the air. An animal experiment was performed, in which a fully implanted stimulator excited the sciatic nerve of a rat that consequently triggered the movement of the limb.
Reconsidering the Link Between Depression and Crime: A Longitudinal Assessment:

A long line of research has uncovered a link between depression and delinquency. However, much of this research has been unable to disentangle the temporal ordering of the depression and crime rela...
Sequential MRI in pontine and extrapontine myelinolysis following rapid correction of hyponatremia.

This study describes the MRI changes associated with pontine and extrapontine myelinolysis secondary to rapid correction of hyponatremia in dogs. The authors discuss the relevance of the results for theories of pathogenesis and for diagnosis of patients. MRI changes associated with pontine and extrapontine myelinolysis first occur on diffusion-weighted imaging. As a generalization, gadolinium enhancement, flair image change and T2 weighted image abnormality appear sequentially.
Preventing hospital-acquired Legionnaires’ disease: A snapshot of clinical practices and water management approaches in US acute-care hospitals

In 2017, we surveyed 101 SHEA Research Network hospitals regarding Legionnaires' disease (LD). Of 29 respondents, 94% have or are developing a water management plan with varying characteristics and personnel engaged. Most LD diagnostic testing is limited to urine antigen testing. Many opportunities to improve LD prevention and diagnosis exist.
Toxicity-Free Hematopoietic Stem Cell Engraftment Achieved with Anti-CD117 Monoclonal Antibody Conditioning

Successful hematopoietic cell transplantation (HCT) requires vacating recipient hematopoietic stem cell (HSC) niches to permit donor HSC engraftment to provide life-long hematopoietic and immune function. Currently HCT relies on DNA damaging radiation or chemotherapy to achieve HSC niche clearance. We have pursued a non-toxic approach to target and deplete HSC using humanized monoclonal antibody, AMG 191, that binds human CD117 (c-Kit). We opened a Phase 1 dose escalation trial using AMG 191 as the sole conditioning agent to achieve donor HSC engraftment in patients undergoing HCT for severe combined immunodeficiency (SCID). The primary endpoint is to assess the safety of administering AMG 191. Secondary endpoints include AMG 191 pharmacokinetics (PK), host HSC depletion, and determination of the dose of AMG 191 that achieves adequate donor HSC engraftment, defined as >5% donor granulocyte chimerism at 24 weeks. We have completed the first dose cohort of patients receiving 0.1 mg/kg AMG 191 and treated the first two patients in the second cohort (0.3 mg/kg). All five patients tolerated the AMG 191 infusion and the subsequent infusion of their CD34-selectd donor cells without clinical problems. Here we report efficacy in the first two patients, who have reached the 24-week timepoint. Both patients had T-B-NK+ SCID with mutations in the DCLRE1C (Artemis) gene. Both previously received unconditioned HCT as infants, failed to develop donor B cells and remained dependent on exogenous immunoglobulin. CD34-selected mobilized peripheral blood cells from the original donors were infused when the AMG 191 serum level was Conclusion: These data are proof of concept that a humanized monoclonal antibody targeting CD117 can safely clear human HSC niches and facilitate donor HSC engraftment. This study is ongoing and open for enrollment.
Elastic waves in Floquet topological insulators (Conference Presentation)

Floquet Topological Insulators (FTIs) have inspired analogues in photonics, optics, and acoustics, in which non-reciprocal wave propagation in topologically protected materials, with topological immunity against structural defects and disorder, is achieved due to the breaking of time-reversal symmetry induced by time-modulation. This study aims at investigating a possibility for the existence of a mechanical analogue to the Quantum Hall Effect (QHE) in one and two-dimensional periodically modulated lattices. In 1D, the system shows topologically protected one-way edge modes as the time-modulation is turned on, which is demonstrated by the principle of bulk-edge correspondence and transient numerical simulations. The study is then extended to 2D hexagonal lattices to demonstrate the existence of Floquet topological edge modes. The band diagram and helical edge states characteristic of QHE are obtained by using the Plane Wave Expansion (PWE) method. Given the breakage of the time-reversal symmetry, the system switches from the trivial state to the nontrivial topological one that is quantified in terms of topological invariant Chern numbers. Last, the robustness of one-way edge modes and their immunity to backscattering by sharp corners, defects and modulation disorders are analyzed and assessed numerically.
Emerging Roles of DNA Glycosylases and the Base Excision Repair Pathway

The base excision repair (BER) pathway historically has been associated with maintaining genome integrity by eliminating nucleobases with small chemical modifications. In the past several years, however, BER was found to play additional roles in genome maintenance and metabolism, including sequence-specific restriction modification and repair of bulky adducts and interstrand crosslinks. Central to this expanded biological utility are specialized DNA glycosylases – enzymes that selectively excise damaged, modified, or mismatched nucleobases. In this review we discuss the newly identified roles of the BER pathway and examine the structural and mechanistic features of the DNA glycosylases that enable these functions.
The Clamshell: Rethinking the Virtual Reality Interface

This project seeks to challenge the dominance of button-based interfacing with Virtual Reality by creating a platform with which anyone can customize their own virtual reality controller based on any sensors of their choosing. After two prototypes and as many demonstrations, the project has successfully yielded a proof of concept that showed results both in the technical creation of a custom VR controller and in the effects of creative rethinking of the physical interface on the VR experience.