cssi/SciSciGPT-SciSciNet huggingface dataset:
Spatiotemporal quantification of gait in common marmosets.

Abstract Background Objective gait evaluation in humans is used as a predictive disability outcome measure as well as an indicator for intervention effectiveness. Parallel methods of gait analysis in nonhuman primate models are essential for clinical translation. The goal of this study was to first assess whether marmosets’ gait data could be reliably collected in a Noldus CatWalk XT10.6 and second, establish a testing protocol to assess gait and the intraindividual variability during repeated testing. New method The CatWalk, originally developed for rodents, was modified and used to assess gait in eight adult common marmoset monkeys across multiple days and trials. Data was first analyzed to identify valid runs. Repeated measures ANOVA was completed for the following gait measures: mean base of support, average stride length, average swing time, and average stance time. Results Raters had a high level of concurrence of usable data across all trials with successful trials including four consecutive hindfoot footfalls, during a continuous, uninterrupted segment of walking. A significant main effect of time (p Comparison with existing method(s) Gait has been assessed using force-plate and video data. The CatWalk allowed reproducible, automated and translational locomotor data to be collected at multiple time points with detailed analyses that identified a diagonal gait pattern. Conclusions The CatWalk system, similar to those used in humans, can be effectively used to quantify spatiotemporal characteristics of gait in the common marmoset.
Chapter 6 – Determinants

Publisher Summary This chapter discusses the fundamentals of the theory of determinants. A permutation of a set {xι, x2, …,xn} is simply an arrangement of the elements of the set into a particular sequence or order. For example, the arrangements 1,4,5,3,2,6 and 6,3,2,1,4,5 are permutations of the set {1,2,3,4,5,6}. If an element xi appears to the left of an element xj in a permutation of {x1, x1, …, xn}, then it is clear that xi precedes xj. The permutation 1,2,3, …,n is referred to as the natural ordering. If a given permutation of {1, 2,…, n} is carried into another permutation by an odd number of interchanges of elements, then the index of the given permutation differs from the index of the final permutation by an odd number. If a given permutation of {1,2,…, n} is carried into another permutation by an even number of interchanges of elements, then the index of the given permutation differs from the index of the final permutation by an even number.
PET imaging of soluble epoxide hydrolase in non-human primate brain with [18F]FNDP

Soluble epoxide hydrolase (sEH) is a promising candidate positron emission tomography (PET) imaging biomarker altered in various disorders, including vascular cognitive impairment (VCI), Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke, and depression, known to regulate levels of epoxyeicosatrienoic acids (EETs) and play an important role in neurovascular coupling. [18F]FNDP, a PET radiotracer for imaging sEH, was evaluated through quantitative PET imaging in the baboon brain, radiometabolite analysis, and radiation dosimetry estimate. Baboon [18F]FNDP dynamic PET studies were performed at baseline and with blocking doses of the selective sEH inhibitor AR-9281 to evaluate sEH binding specificity. Radiometabolites of [18F]FNDP in mice and baboons were measured by high-performance liquid chromatography. Regional brain distribution volume (VT) of [18F]FNDP was computed from PET using radiometabolite-corrected arterial input functions. Full body distribution of [18F]FNDP was studied in CD-1 mice, and the human effective dose was estimated using OLINDA/EXM software. [18F]FNDP exhibited high and rapid brain uptake in baboons. AR-9281 blocked [18F]FNDP uptake dose-dependently with a baseline VT of 10.9 ± 2.4 mL/mL and a high-dose blocking VT of 1.0 ± 0.09 mL/mL, indicating substantial binding specificity (91.70 ± 1.74%). The VND was estimated as 0.865 ± 0.066 mL/mL. The estimated occupancy values of AR-9281 were 99.2 ± 1.1% for 1 mg/kg, 88.6 ± 1.3% for 0.1 mg/kg, and 33.8 ± 3.8% for 0.02 mg/kg. Murine biodistribution of [18F]FNDP enabled an effective dose estimate for humans (0.032 mSv/MBq). [18F]FNDP forms hydrophilic radiometabolites in murine and non-human primate plasma. However, only minute amounts of the radiometabolites entered the animal brain (< 2% in mice). [18F]FNDP is a highly sEH-specific radiotracer that is suitable for quantitative PET imaging in the baboon brain. [18F]FNDP holds promise for translation to human subjects.
Abstract A44: Comparative gene expression analysis for identification and prioritization of therapeutic targets in a cohort of childhood cancers

Here we describe the utility of comparative RNA sequencing (RNA-seq) analysis in identifying cancer driver pathways and relevant therapeutics in childhood cancer, and we introduce a novel system for prioritizing gene targets based on analytical and published evidence. The purpose of our study was to evaluate the clinical utility of comparative N-of-1 gene expression analysis in identifying therapeutic options for pediatric patients with relapsed or recurrent cancers. The comparative analysis framework and large cancer background cohorts were developed at the Treehouse Childhood Cancer Initiative at UC Santa Cruz. We employed this analysis in a pilot study of 26 patients at the Lucile Packard Children’s Hospital. We analyzed RNA-seq data from 30 biopsied samples from 26 patient donors, including 16 sarcomas, 5 CNS tumors, 3 hematopoietic cancers, 1 liver, and 1 colon cancer. We compared gene expression from each child’s tumor biopsy to a background cohort of RNA-seq data from over 11,000 cancer patients, and also to a smaller cohort defined by molecular and histopathologic similarity to the child’s tumor biopsy. This comparison yielded outlier gene activations in the child’s biopsy compared to those in the background cohorts, reflecting cancer driver pathways in the child’s tumor that are actionable. We stratified each of the resulting therapeutic leads into 5 baskets: RTK activation, JAK/STAT signaling, PI3K/AKT/mTOR signaling, Cell Cycle activation, or Other. Because 27 of the 30 samples had more than one lead, we developed a novel scoring system to prioritize each sample’s therapeutic gene targets based on the analytical strength of the gene expression analysis result, and on published literature evidence for each gene as a biomarker indicative of drug response. We presented the results of our analysis in genomic consensus meetings at Stanford and surveyed the responses of clinicians and families on the utility of our analysis for treatment decisions. Here we report our experience with the method and highlight case studies in which this analysis informed treatment decisions. Citation Format: Lauren M. Sanders, A. Geoffrey Lyle, Holly C. Beale, Ellen Towle Kephart, Katrina Learned, Jennifer Peralez, Norman Lacayo, Arun Rangaswami, Sheri L. Spunt, Isabel Bjork, David Haussler, Sofie R. Salama, Olena M. Vaske. Comparative gene expression analysis for identification and prioritization of therapeutic targets in a cohort of childhood cancers [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A44.
A novel algorithm to accurately classify metagenomic sequences

Abstract Widespread availability of next-generation sequencing (NGS) technologies has prompted a recent surge in interest in the microbiome. As a consequence, metagenomics is a fast growing field in bioinformatics and computational biology. An important problem in analyzing metagenomic sequenced data is to identify the microbes present in the sample and figure out their relative abundances. In this article we propose a highly efficient algorithm dubbed as “Hybrid Metagenomic Sequence Classifier” (HMSC) to accurately detect microbes and their relative abundances in a metagenomic sample. The algorithmic approach is fundamentally different from other state-of-the-art algorithms currently existing in this domain. HMSC judiciously exploits both alignment-free and alignment-based approaches to accurately characterize metagenomic sequenced data. To demonstrate the effectiveness of HMSC we used 8 metagenomic sequencing datasets (2 mock and 6 in silico bacterial communities) produced by 3 different sequencing technologies (e.g., HiSeq, MiSeq, and NovaSeq) with realistic error models and abundance distribution. Rigorous experimental evaluations show that HMSC is indeed an effective, scalable, and efficient algorithm compared to the other state-of-the-art methods in terms of accuracy, memory, and runtime. Availability of data and materials The implementations and the datasets we used are freely available for non-commercial purposes. They can be downloaded from: https://drive.google.com/drive/folders/132k5E5xqpkw7olFjzYwjWNjyHFrqJITe?usp=sharing
Estimating models with binary dependent variables: Some theoretical and empirical observations

Abstract Many mathematically similar models are being used by business researchers to link binary dependent variables with a set of predictor variables. Typical research results indicate little difference between models in their ability to properly classify observations. But, there appear to be major differences in the interpretation of coefficients resulting from the calibration of these competing models. The empirical results in this article clearly show that when the assumptions underlying binary-dependent-variable techniques are violated, parameter estimates may be misleading. This can be true even when the goodness-of-fit statistics are not substantially affected.
Differences in web structure of Tetragnatha tenuissima (Araneae: Tetragnathidae) due to environmental conditions

Spiders can modify their web construction behaviour according to environmental conditions. Here, we examined how the web structure of Tetragnatha tenuissima differentiates depending on habitat type (swamp or river edge) at La Selva Biological Station, Costa Rica. We characterized the web architecture based on length, number of radii, and the spiral spacing relative to web length. There were no significant differences on the length or number of radii between the webs present in the swamp and river habitats. In terms of the spiral spacing relative to web length, there was a significant difference between habitats, with less distance in river-side webs than in the ones on swamps. This could be explained by the potential differential resource availability on each environment. Therefore, habitat type appears as an explanatory variable for differences on the web structure of T. tenuissima. Due to the small number of identifiable individuals of other Tetragnatha species, the effect of congeneric species co-occurrence on web structure remains as a factor to be tested in future research.
Characteristics and Predictors of Transfer and Withdrawal Among Students Who Begin College at Bachelor’s Granting Institutions

This study models reverse transfer, lateral transfer, and college withdrawal behavior for a national sample of students who began college at bachelor’s granting institutions. Descriptive data illustrate statistical differences in the characteristics, habitus, early college experiences and supports, and institutional characteristics of students who do not transfer when compared to students who reverse transfer, laterally transfer, or drop out before the third year of college. Additionally, multi-level regression findings advance theoretical understanding of the ways in which predictors of reverse transfer, lateral transfer, and withdrawal from bachelor’s granting institutions are both similar and different. Implications for research, theory, and practice are offered.
D2-Like Receptor Expression in the Hippocampus and Amygdala Informs Performance on the Stop-Signal Task in Parkinson's Disease.

The stop-signal task is a well-established assessment of response inhibition, and in humans, proficiency is linked to dorsal striatum D2 receptor availability. Parkinson’s disease (PD) is characterized by changes to efficiency of response inhibition. Here, we studied 17 PD patients (6 female and 11 male) using the stop-signal paradigm in a single-blinded D-amphetamine (dAMPH) study. Participants completed [18F]fallypride positron emission topography (PET) imaging in both placebo and dAMPH conditions. A voxel-wise analysis of the relationship between binding potential (BPND) and stop-signal reaction time (SSRT) revealed that faster SSRT is associated with greater D2-like BPND in the amygdala and hippocampus (right cluster qFDR-corr = 0.026, left cluster qFDR-corr = 0.002). A region of interest (ROI) examination confirmed this association in both the amygdala (coefficient = −48.26, p = 0.005) and hippocampus (coefficient = −104.94, p = 0.007). As healthy dopaminergic systems in the dorsal striatum appear to regulate response inhibition, we interpret our findings in PD to indicate either nigrostriatal damage unmasking a mesolimbic contribution to response inhibition, or a compensatory adaptation from the limbic and mesial temporal dopamine systems. These novel results expand the conceptualization of action-control networks, whereby limbic and motor loops may be functionally connected. SIGNIFICANCE STATEMENT While Parkinson’s disease (PD) is characteristically recognized for its motor symptoms, some patients develop impulsive and compulsive behaviors (ICBs), manifested as repetitive and excessive participation in reward-driven activities, including sex, gambling, shopping, eating, and hobbyism. Such cognitive alterations compel a consideration of response inhibition in PD. To investigate inhibitory control and assess the brain regions that may participate, we assessed PD patients using a single-blinded D-amphetamine (dAMPH) study, with [18F]fallypride positron emission topography (PET) imaging, and stop-signal task performance. We find a negative relationship between D2-like binding in the mesial temporal region and SSRT, with greater BPND associated with a faster stop-signal reaction time (SSRT). These discoveries indicate a novel role for mesolimbic dopamine in response inhibition, and advocate for limbic regulation of action control in this clinical population.
Role of Fractional-Flow Reserve in Guiding Percutaneous Revascularization in Stable Coronary Artery Disease

Optimal medical therapy unarguably forms the cornerstone of management for patients with stable coronary artery disease. There is, however, a significant body of evidence suggesting that reduction of ischemia can be achieved more effectively with revascularization than medical therapy and can confer significant symptomatic and prognostic advantages. Nonetheless, owing to limitations of coronary angiography and conventional non-invasive functional testing for myocardial ischemia, targeting of hemodynamically significant coronary stenoses for revascularization is often difficult. We discuss the role of invasive fractional-flow reserve evaluation in guiding percutaneous revascularization procedures for patients with stable coronary artery disease and its potential impact on outcomes for these patients.
A Novel Pupillometric Method for Indexing Word Difficulty in Individuals With and Without Aphasia

Purpose Cognitive effort is a clinically important facet of linguistic processing that is often overlooked in the assessment and treatment of people with aphasia (PWA). Furthermore, there is a pauc...
The evolution of molluscan photosymbioses: a critical appraisal

Partnerships between animals and photosynthesizing microbes have evolved repeatedly, although their history, adaptations, and ecology remain controversial and little understood. In a critical review of 17 fossil and living clades of shell-bearing molluscs with photosymbionts (two of them newly inferred), adaptive shell modifications and ecological aspects are discussed in the broader context of photosymbioses in other phyla. Fossil candidates have characteristics that are rare or unknown in living photosymbiotic molluscs, including cementation, porous shell microstructure, and epifaunal habits on carbonate muds. Many ancient photosymbioses may have lived in planktonically more productive environments than are typical of living tropical forms. This may be related to the late appearance (Early Eocene) of the dinoflagellate Symbiodinium, which can thrive under highly oligotrophic conditions. Living photosymbiotic molluscs represent a small and atypical sample of all the photosymbiotic clades that have evolved. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, 109, 497–511.
Dividend Restrictions and Accounting Choices

Accounting changes of firms surrounding a tightening of the dividend constraint are examined for evidence of debt-contract-induced, income-increasing accounting changes. No meaningful difference in the number of material income-increasing accounting changes was detected between the sample of firms experiencing near-binding dividend constraints and a control group of firms. Weak evidence suggests that these results may be sensitive to the definition of near-binding and the persistence of the firm's downturn.
Preparing and Presenting a Poster

A poster is one method of informing the world about results from a research project. Whether serving as an aid for a presentation or standing alone, it should provide information about a project. Both substantive and stylistic qualities should contribute to effectively communicating one's conclusions. This appendix gives general guidelines and suggestions for poster content, layout, and design to assist in preparing an effective poster. Keywords: poster; presentation; communication
Monetary Policy, Investment Dynamics, and the Intertemporal Approach to the Current Account

This paper applies the intertemporal approach to the current account to the case of monetary shocks. A two-country dynamic general equilibrium model with predetermined wages is proposed as a means to bridge the gap between Mundell-Fleming and modern intertemporal models. Early versions of Mundell- Fleming implied that a monetary expansion must necessarily improve the current account; the alternative result became a possibility in more contemporary versions when intertemporal features were introduced into the asset market. The present model suggests that when intertemporal features are also introduced into the other markets of the economy, the model's prediction is transformed yet further. A calibrated version of the model suggests a beggar-thy-neighbor improvement in the current account becomes unlikely for reasonable parameter values.
Three-dimensional dynamics of vortex-induced reconnection and comparison with THEMIS observations

[1] The entry of solar wind into the magnetosphere is strongly influenced by kinetic-scale boundary layers where the rapid variation in the magnetic field and/or velocity can drive transport. In current layers with strong Alfvenic velocity shear, the generation of vortices from the Kelvin-Helmholtz instability can drive magnetic reconnection even in broader current sheets by locally compressing these layers as the vortices develop. Previous two-dimensional (2-D) fully kinetic simulations of this vortex-induced reconnection process have demonstrated the copious formation of magnetic islands in regions of strongly compressed current between the vortices. Here we describe the first three-dimensional (3-D) fully kinetic simulations of this process and demonstrate that the compressed current sheets give rise to magnetic flux ropes over a range of oblique angles and along the entire extent of the compressed current layer around the periphery of the vortex. These flux ropes propagate with the shear flow and eventually merge with the vortex. Over longer time scales, this basic scenario is repeated as the vortices drive new compressed current sheets. In the final stage, the vortices undergo a merging process that drives new compressed current sheets and flux ropes. Based on these simulations, a simple model is proposed that predicts the size of these flux ropes relative to their parent vortex. Both the relative sizes as well as the structure of the profiles across the vortex are in reasonable agreement with Time History of Events and Macroscale Interactions (THEMIS) observations at the Earth's low-latitude magnetopause.
Content Area Readers: Helping Middle-Level Students Become Word Aware (and Enjoy It!)

Abstract For many years, practitioners have heard that middle level teachers are teachers of reading. As the standards movement gains strength, it is even more crucial that teachers explicitly teach key vocabulary that makes their students “insiders” when it comes to understanding the content areas. This article reminds the reader of the principles for vocabulary development, followed by “high utility” strategies that works well for early adolescents. Middle level students are ripe for word work with a proper balance of choice and challenge.
Macrophage uptake of low-density lipoprotein bound to aggregated C-reactive protein: Possible mechanism of foam-cell formation in atherosclerotic lesions

Foam cells found in atherosclerotic lesions are believed to derive from macrophages that take up aggregated low-density lipoprotein (LDL) particles bound to the extracellular matrix of arterial walls. C-reactive protein (CRP) is an acute-phase protein found in atherosclerotic lesions, which when immobilized on a solid phase, can bind and cluster LDL particles in a calcium-dependent manner. In the present study, we examined whether CRP-bound aggregated LDL could be taken up by macrophages in culture. CRP molecules were aggregated in the presence of calcium and immobilized on the surface of polystyrene microtitre wells. Human LDL added to the wells bound to and aggregated on the immobilized CRP, also in a calcium-dependent manner. On incubation with macrophages, the immobilized CRP-bound LDL aggregates were readily taken up by the cells, as demonstrated by immunofluorescence microscopy, by the cellular accumulation of cholesterol and by the overexpression of adipophilin. Immunofluorescence microscopy and flow-cytometry analysis established that the uptake of the LDL-CRP complex was not mediated by the CRP receptor CD32. These observations with immobilized CRP and LDL, approximating the conditions that exist in the extracellular matrix of the arterial wall, thus suggest that CRP may contribute to the formation of foam cells in atherosclerotic lesions by causing the aggregation of LDL molecules that are then taken up by macrophages through a CD32-independent pathway.
Effective measurements using digital signal analysis

In order to be effective, measurements must be unambiguous and quantitative, which is only possible when such measurements yield numerical values that can attach to a given aspect of the system being measured in only one way and have only one interpretation. This article discusses the use of correlation, transfer, and coherence functions in obtaining such measurements.
Extent of protein-protein interactions and quasi-equivalence in viral capsids

Viral capsids are composed of multiple copies of one or a few gene products that self-assemble on their own or in the presence of the viral genome and/or auxiliary proteins into closed shells (capsids). We have analyzed 75 high-resolution virus capsid structures by calculating the average fraction of the solvent-accessible surface area of the coat protein subunits buried in the viral capsids. This fraction ranges from 0 to 1 and represents a normalized protein–protein interaction (PPI) index and is a measure of the extent of protein–protein interactions. The PPI indices were used to compare the extent of association of subunits among different capsids. We further examined the variation of the PPI indices as a function of the molecular weight of the coat protein subunit and the capsid diameter. Our results suggest that the PPI indices in T=1 and pseudo-T=3 capsids vary linearly with the molecular weight of the subunit and capsid size. This is in contrast to quasi-equivalent capsids with T≥3, where the extent of protein–protein interactions is relatively independent of the subunit and capsid sizes. The striking outcome of this analysis is the distinctive clustering of the “T=2” capsids, which are distinguished by higher subunit molecular weights and a much lower degree of protein–protein interactions. Furthermore, the calculated residual (Rsym) of the fraction buried surface areas of the structurally unique subunits in capsids with T>1 was used to calculate the quasi-equivalence of different subunit environments. Proteins 2005. © 2004 Wiley-Liss, Inc.
A heterogenous, pore-vesicle membrane model for protein transfer from blood to cerebrospinal fluid at the choroid plexus.

Abstract A negative relation exists between the steady-state, cerebrospinal fluid/blood concentration ratio and the hydrodynamic radius of blood-derived proteins. This negative relation can be explained if blood proteins enter spinal fluid only at the choroid plexus (and not at other sites within the brain), and if transfer at the plexus is limited by the choroidal epithelium and not by demonstrably leaky capillaries within the choroidal stroma. The most likely interpretation of the data is that there are two pathways for protein transfer at the plexus epithelium, a set of 117-A-radius pores which allow transfer of smaller proteins by diffusion, ultrafiltration, or both mechanisms, and a set of 250-A-radius pinocytotic vesicles which account for exchange of larger proteins as well. On the basis of the data, it is possible to calculate permeability and/or osmotic reflection coefficients associated with porous transfer, as well as a rate of vesicular transport. The latter is estimated to be so low that ultrastructural studies would be expected to demonstrate only occasional vesicular discharge from the choroidal epithelium into cerebrospinal fluid. Pores with a 117-A-radius have not been described at the choroidal epithelium, but may represent a 0.08% defect in the normally continuous tight junctions that surround and closely connect choroidal epithelial cells.
Hydrothermal recrystallization of Bi2WO6

Abstract The feasibility of growing single crystal Bi 2 WO 6 by the hydrothermal method is reported. Single domain crystals (∼1mm) were readily grown at 400°C, well below the disruptive high temperature phase transformation, from 2N aqueous KF solutions. Data is given for X-ray diffraction and hot-stage microscopy observations. The significance of preparing strain-free, single domain, highly acentric polar crystals for new device applications is discussed.
Mechanical properties of in situ composites based on polycarbonate and a liquid crystalline polymer

The mechanical properties of in situ composites based on blends of polycarbonate and a liquid crystalline copoly(ester amide) (Vectra B950) have been studied as functions of the liquid crystalline polymer (LCP) concentration and the draw ratio, a processing parameter. It is shown that both the elastic modulus and the tensile strength of the in situ composites increase steadily with the LCP concentration and the draw ratio. However, the ultimate tensile strain decreases with these two parameters. A model is proposed for the longitudinal elastic modulus of the in situ composites, which is based on the Halpin-Tsai equation and Northolt's model for the LCP phase. The experimental elastic moduli of the in situ composites are found to conform fairly well with the theoretical values derived from the model.
Effect of Organic Acids on the IGSCC of Sensitized AISI 304 Stainless Steel in High Temperature Aqueous Solutions

Abstract The effect of low molecular weight carboxylic acids on the intergranular stress corrosion cracking (IGSCC) of sensitized AISI 304 stainless steel (SS) in high temperature (275 C) water was investigated using slow strain rate tests (SSRTs). Significant differences were found by comparing the effect of formic, acetic, and oxalic acids at a concentration of 4.35×10−4M over a wide range of oxygen contents (0.005 to 8.0 ppm). At intermediate dissolved oxygen concentrations (0.2 and 0.6 ppm), formic and oxalic acids suppressed IGSCC, whereas acetic acid accelerated it. The IGSCC behavior was correlated with the corrosion potential of the alloy. The presence of formic and oxalic acids shifted the potential below the critical potential for IGSCC in pure water. It is suggested that the potential shift is caused by the enhanced reduction of oxygen on the alloy surface, prompted by the adsorption and electro-oxidation of the acids or intermediate products of their decomposition, such as carbon monoxide. How...
A novel addition to the T cell repertory: cell surface expression of tumor necrosis factor/cachectin by activated normal human T cells

Expression of the pluripotent molecule TNF in a focused and antigen-restricted fashion might provide an advantage to the host organism. Given the central role of T cells in antigen-specific immunity, we examined whether activated T cells express TNF on their cell surface. FACS analysis of highly purified normal human T cells labeled with an anti-TNF mAb revealed that T cells express cell surface TNF when signaled with the synergistic combination of a calcium ionophore, ionomycin, and a protein kinase C activator, 12-o-tetradecanoyl phorbol acetate. Cell surface radioiodination studies of stimulated T cells demonstrated the presence of 26-kD transmembrane protein, a size predicted by TNF cDNA and different from that of the 17-kD secreted TNF molecule. The induced cell surface expression of TNF could be blocked with cyclosporine and/or methylprednisolone, and Northern analysis for TNF-specific transcripts revealed that this inhibitory effect occurs pretranslationally. Our demonstration for the first time that stimulated normal human T cells display cell surface TNF provides a mechanistic basis for the realization of effects of TNF in an antigen-specific fashion.
Sexually transmitted diseases: epidemic cycling and immunity.

Are syphilis epidemics caused by external factors such as human sexual behaviour, or are factors intrinsic to the pathogen more important? Comparing the dynamics of syphilis and gonorrhoea provides some clues.
Precursor molecules of both human 5S ribosomal RNA and transfer RNAs are bound by a cellular protein reactive with anti-La Lupus antibodies

The small ribonucleoproteins recognized by anti-La autoantibodies contain a heterogeneous mixture of small RNAs from uninfected mammalian cells. The identity of many of these has now been established by the discovery of precursor forms of 5S rRNA and of certain tRNAs among La RNAs from HeLa cells. The small fraction of 5S rRNA molecules that exist as La ribonucleoproteins in vivo possess 1 or 2 additional U residues at their 3' ends. Such 5S molecules bound to the La protein have also been identified with in vitro nuclear transcription systems. Pulse-chase experiments performed both in vivo and in vitro support the idea that most newly synthesized 5S rRNA molecules are transiently associated with the La protein. Cell extracts contain a processing activity that converts longer in vitro-synthesized 5S RNA transcripts into molecules of mature size. The presence of in vivo tRNA precursors in the heterogeneous mixture of La RNAs is demonstrated by the identification of precursor forms of five different specific tRNAs (Meti, Asp, Gly, Glu, Asn). After in vitro transcription of a tRNA gene (tRNAiMet), only products the size of precursor molecules are precipitable by anti-La antibodies. The realization that virtually every known RNA polymerase III product associates at least initially with the La antigen suggests that this protein plays an essential role in the synthesis or maturation of all class III transcripts.
Culture, Memory, Context: Reenactments of Traumatic Histories in Europe and Eurasia

In this article, I discuss what I term “Jewface” minstrelsy performance and “Jewfacade” display in three contemporary contexts with highly divergent historical backgrounds: East-Central Europe, the Iberian Peninsula, and the Jewish Autonomous Republic, a fictitious-sounding but real colony established by Stalin in far eastern Russia near China and still extant today. Jewface encompasses music, dance, theater, and extra-theatrical modes of performance, in which non-Jews dress up and act like “Jews,” as historically imagined; Jewfacade encompasses museum-type installations, as well as architectural and decorative constructions, depicting imagined “Jewish” life. These “Diaspora Disneys” vary from the education- and tolerance-oriented to the crassly exploitative and commercial to the bizarrely confused. None have much to do with actual Jews, but all convey a tremendous amount regarding dominant “host” cultures’ anxieties over not only their roles in past persecution and genocide but also their own present cultures, politics, and positions in the wider world today. Further, they present a wide array of models of memoriological projection and desire, in what I explicate as spectra of “plethoric” to “voidic” memoriological scenarios and “negotiatory” to “constitutory” memoriological strategies.
High-speed telescopic imaging of sprites

[1] Telescopic video observations of sprites at high frame rates show very complex structures in both space and time, including bead and streamer-like formations and propagation. Observed streamers rarely persist for more than 1–2 ms, while observed beads persist up to tens of ms and do not appear to propagate in this data set. Additionally, images show that streamer-like channels often contain many bead-like structures. While the time resolution cannot directly observe propagation, images show that the so-called “streamers” presented here do seem to exhibit signs of propagation. These results are compared to previous measurements and discussed in the context of streamer modeling and laboratory streamers.
Risk Aversion, Technology Choice, and Equity Effects of Agricultural Policy

The agricultural industries of many countries, while otherwise competitive in nature, are subject to heavy government regulation. Increasing concerns have surfaced about the equity effects of policies such as price support, stabilization, insurance, subsidization, extension, and research in both developed and developing countries. In the United States, these concerns are manifested by wide interest in the survival of the family farm, in the structure of the agricultural industry, and in the extent and implications of farm bankruptcy precipitated by recent economic phenomena. In many developing countries, concerns are focused on the distributional implications of the green revolution and proposals for land reform and management of the agrarian structure. Most of the literature on these issues evaluates the equity effects of agricultural policies in a historical case study context. For the most part, these studies are not theoretically based (except heuristically); and conclusions are drawn from intuitive and descriptive analyses. Unfortunately, these analyses "have not been able convincingly to establish a connection ... between policy and the structure of agricultural production" which is crucial for policy selection (Gardner, p. 842). Of the studies that have attempted to examine analytically the welfare effects of agricultural policy, most have relied on standard aggregate concepts of welfare economics which emphasize the notions of Pareto optimality and efficiency. These studies typically assume identical firms and examine equity implications only between broad groups, e.g., between producers and consumers.
Optimized carry lookahead adders with direct feeding

Abstract This paper describes improvements to the parallel prefix adder designs and optimization algorithms of Chan, Oklobdzija, Schlag, Thomborson and Wei. Our “direct feeding” (DF) adder design avoids large signal fanouts along critical adder paths. Our “random pruning” heuristic limits the time and space required to find near-optimal DF adders, so that the search process runs in a few minutes on a Sun-4 workstation. Our improved carry lookahead adders are well suited for static CMOS implementation; our improvements may be applied to other parallel prefix CMOS circuits. Simulations with Mentor Graphics' Lsim indicate that our best DIP adders are 12% to 20% faster than the carry lookahead adders presented by Chan et al.
Wetlands preservation and management on Chesapeake Bay: The role of science in natural resource policy

Abstract Wetlands preservation has recently become a favored cause of conservationists. Protection of wetlands is justified primarily on grounds of their beneficial biological and hydrological effects, so it is to the physical sciences that government and the public turn for the formulation of management policies. But scientific knowledge cannot be translated directly into good resource policy for society. Despite growing scientific sophistication, we are limited in our ability to understand and to predict the effects of man‐induced change on natural systems, especially ones as complex as the Chesapeake Bay and its associated wetlands. Moreover, an obsession with the exploration of physical processes obscures the more important task of understanding and controlling the social processes that lead man to alter nature. That is, natural resource management implies the management of social and economic, as well as natural, systems.
Quantum mechanical quantitative structure–activity relationships to avoid mutagenicity

Abstract Objective The purpose of this work is to develop a quantum mechanically based quantitative structure–activity relationship (QMQSAR or QSAR hereafter) adequate to predict and explain Ames TA100-derived mutagenicities for a number of organic molecules. Methods A set of 35 structurally similar molecules with epoxide (oxirane) functionalities and systematic, reliable experimental data were selected to construct a QSAR model. The SAM1 quantum mechanical method was used to perform conformational analysis and properties calculations. This QM information was used to compute a variety of descriptors. From this a two-descriptor regression model was constructed. Results The two descriptors are ESP-HACA-1/TMSA and HOMO-LUMO energy gap. Statistical results for the model: R2 = 0.857, R adj 2 = 0.818 , R cv 2 = 0.848 , s2 = 0.0618. The variance inflation factor and significance for both descriptors were 1.082 and Significance The model we have presented here facilitates design of non-mutagenic monomers that may be useful for dental restorative composites. The model also serves as a screening tool for rating the mutagenicity of new candidate materials.
Enhanced transient recombinant protein production in CHO cells through the co-transfection of the product gene with Bcl-xL.

Transient gene expression is gaining popularity as a method to rapidly produce recombinant proteins in mammalian cells. Although significant improvements have been made, in terms of expression, more improvements are needed to compete with the yields achievable in stable gene expression. Much progress has come from optimization of transfection media and parameters, as well as altering culturing conditions to enhance productivity. Recent studies have included cell lines engineered for apoptosis resistance through the constitutive expression of an anti-apoptotic protein, Bcl-xL. In this study, we examine an alternative method of using the benefits of anti-apoptotic gene expression to enhance the transient expression of biotherapeutics, namely, through the co-transfection of Bcl-xL and the product-coding gene. CHO-S cells were co-transfected with the product-coding gene and a vector containing Bcl-xL using polyethylenimine. Cells co-transfected with Bcl-xL showed reduced levels of apoptosis, increased specific productivity, and an overall increase in product yield of approximately 100%. Similar results were produced by employing another anti-apoptotic protein, Bcl-2 delta, in CHO cells, or through the co-transfection with Bcl-xL using HEK-293E cells. This work provides an alternative method for increasing yields of therapeutic proteins in TGE applications without generating a stable cell line and subsequent screening, which are both time- and resource-consuming. See accompanying commentary by Matthias Hackl and Nicole Borth DOI: 10.1002/biot.201400104
Presence and stoichiometry of two forms of subunit 6 of the mitochondrial ATPase complex of yeast

One of the mitochondrically coded components of the yeast mitochondrial ATPase complex (subunit 6) can be resolved into two components on certain polyacrylamide gels in the presence of sodium dodecyl sulfate. Purification of the ATPase complex from commercially processed yeast as well as immunoprecipitation of the holo-enzyme from cells labeled in vivo with 14C-labeled amino acids demonstrate that both forms of subunit 6 are physically associated with the assembled enzyme and present in two copies each per complex. One-dimensional papain-generated peptide maps of the two components are identical except for the mobility of a single fragment. It is concluded that the two components of subunit 6 are different forms of a single protein and are present on an average of two copies each per complex.
Neuronale Modelle zur Offboard-Diagnostik in komplexen Fahrzeugsystemen

Zunehmend vernetzte Fahrzeugfunktionen, steigende Variantenvielfalt und kurzere Entwicklungszyklen fuhren dazu, dass etablierte Expertenbasierte Verfahren an ihre Grenzen stosen. Die Folge sind hohere Kosten durch langere Fehlersuchzeiten, unnotig getauschte Teile und uberforderte Kundendienstmitarbeiter. In dieser Arbeit wird ein Offboard-Diagnostik-System entwickelt, welches zuerst in einem automatisierten Prozess aus aufgezeichneten Reparaturfallen Diagnostik-Modelle erlernt. In den Servicewerkstatten erzeugen die Modelle auf Basis von Fahrzeuginformationen und Fehlersymptomen Hypothesen uber schadhafte Komponenten und sinnvolle Reparaturmasnahmen. Das Ergebnis der Reparatur wird wiederum aufgezeichnet, wodurch ein iterativer Feedback- und Losungsprozess zur automatischen kontinuierlichen Verbesserung der Modelle entsteht. Zur Modellbildung werden zunachst deskriptive und inferenzielle statistische Diagnostik-Modelle analysiert, die jedoch aufgrund der Art und Qualitat der Daten unzureichend sind. Als Losung wird zunachst das inferenzielle statistische Modell in ein einschichtiges neuronales Netz uberfuhrt, welches dann mit einer neuen Konstruktions- und Trainingsmethode um verdeckte Neuronen und Verbindungen derart erweitert wird, dass nur diejenigen Abhangigkeiten abgebildet werden konnen, die erforderlich sind. Die spezielle Struktur des Netzes ermoglicht weiterhin eine Interpretation der Verbindungsgewichte und Neuronen und wirkt damit dem typischen Black-Box-Charakter neuronaler Netze entgegen. Als Vergleich wird ein Standard-MLP-Netz herangezogen. Die resultierenden Diagnostik-Modelle werden einer ausfuhrlichen Evaluierung bestehend aus einer Konzeptbewertung, einer Evaluierung mit realen Falldaten und einem Prototypen zur Praxiserprobung am Fahrzeug unterzogen. Die Ergebnisse zeigen, dass trotz der mangelnden Qualitat und Anzahl der im Projekt zur Verfugung stehenden Reparaturfalldaten sehr gute Ergebnisse erzielt werden.
Structure of the diterpene portion of a novel base from the sponge Agelas mauritiana

Abstract The structure of purino-diterpene 2, derived from an unknown antimicrobial metabolise of Agelas mauritiana, was determined by X-ray analysis.
Effects of Dehydration on Blood Viscosity and on Distribution of Plasma Proteins in Experimental Macroglobulinaemia

A GREAT variety of plasma cell tumours has been induced in mice and transplanted in successive generations of these animals1,2. The tumours secrete large amounts of myeloma proteins and make it possible to examine various problems concerning the myelomas and dysproteinaemias. Usually, as the concentration of myeloma protein rises in the plasma of affected animals, the concentration of normal protein diminishes2. A similar reduction of normal plasma proteins in humans with dysproteinaemias has been related either to decreased synthesis or to increased catabolism of normal protein fractions3. As yet, no data have appeared concerning the plasma concentrations of abnormal and normal proteins in experimental macroglobulinaemia. The plasma cell tumour designated MOPC-104E secretes large amounts of macroglobulin (IgM)4. Mice bearing this tumour resemble humans with macroglobulinaemia, in that both display an elevated blood viscosity which is related to the plasma concentration of IgM and modified by the haematocrit5–7. It was of additional interest to determine whether these mice also resembled human macroglobulinaemics3 with respect to the relative intravascular concentrations of IgM and non-macroglobulin (non-IgM). This investigation examines this question. In addition, an attempt was made to alter the intravascular distribution of proteins by changing the osmotic balance of the animals through dehydration.
Characterization of Ischemic Index Using Ultra-widefield Fluorescein Angiography in Patients With Focal and Diffuse Recalcitrant Diabetic Macular Edema

Purpose To explore the association of angiographic nonperfusion in focal and diffuse recalcitrant diabetic macular edema (DME) in diabetic retinopathy (DR). Design A retrospective, observational case series of patients with the diagnosis of recalcitrant DME for at least 2 years placed into 1 of 4 cohorts based on the degree of DR. Methods A total of 148 eyes of 76 patients met the inclusion criteria at 1 academic institution. Ultra-widefield fluorescein angiography (FA) images and spectral-domain optical coherence tomography (SD OCT) images were obtained on all patients. Ultra-widefield FA images were graded for quantity of nonperfusion, which was used to calculate ischemic index. Main outcome measures were mean ischemic index, mean change in central macular thickness (CMT), and mean number of macular photocoagulation treatments over the 2-year study period. Results The mean ischemic index was 47% (SD 25%; range 0%-99%). The mean ischemic index of eyes within Cohorts 1, 2, 3, and 4 was 0%, 34% (range 16%-51%), 53% (range 32%-89%), and 65% (range 47%-99%), respectively. The mean percentage decrease in CMT in Cohorts 1, 2, 3, and 4 were 25.2%, 19.1%, 11.6%, and 7.2%, respectively. The mean number of macular photocoagulation treatments in Cohorts 1, 2, 3, and 4 was 2.3, 4.8, 5.3, and 5.7, respectively. Conclusions Eyes with larger areas of retinal nonperfusion and greater severity of DR were found to have the most recalcitrant DME, as evidenced by a greater number of macular photocoagulation treatments and less reduction in SD OCT CMT compared with eyes without retinal nonperfusion. Areas of untreated retinal nonperfusion may generate biochemical mediators that promote ischemia and recalcitrant DME.
Sperm entry into zona-free oocytes in the hamster oviduct: implications for the mechanisms of acrosome reaction induction.

The possible importance of the zona pellucida for induction of the acrosome reaction (AR) and establishment of sperm/egg associations in the fallopian tube was investigated by instilling zona-free eggs into the oviductal ampulla of hamsters that had been inseminated with epididymal spermatozoa 6–7 hours previously. The eggs were recovered only 60–90 minutes later because of increasing difficulty with time of collecting zona-free eggs from the oviduct. In the zona-free group, 41 (4%) of 1,101 transferred eggs were recovered, of which 20% contained spermatozoa with decondensing nuclei (mean 4.4/egg). A similar (22%) fertilization rate (mean 3.2 spermatozoa/egg) was found among intact (control) eggs recovered after instillation into the contralateral oviduct. Mammalian spermatozoa are not incorporated even into zona-free eggs before AR occurs. These results thus demonstrate that an AR in functional hamster spermatozoa in vivo and establishment of sperm/egg associations in vivo require no interaction with the zona pellucida nor with other products of ovulation.