cssi/SciSciGPT-SciSciNet huggingface dataset:
Mapping croplands of Europe, Middle East, Russia, and Central Asia using Landsat, Random Forest, and Google Earth Engine

Abstract Accurate and timely information on croplands is important for environmental, food security, and policy studies. Spatially explicit cropland datasets are also required to derive information on crop type, crop yield, cropping intensity, as well as irrigated areas. Large area – defined as continental to global – cropland mapping is challenging due to differential manifestation of croplands, wide range of cultivation practices and limited reference data availability. This study presents the results of a cropland extent mapping of 64 countries covering large parts of Europe, Middle East, Russia and Central Asia. To cover such a vast area, roughly 160,000 Landsat scenes from 3351 footprints between 2014 and 2016 were processed within the Google Earth Engine (GEE) platform. We used a pixel-based Random Forest (RF) machine learning algorithm with a set of satellite data inputs capturing diverse spectral, temporal and topographical characteristics across twelve agroecological zones (AEZs). The reference data to train the classification model were collected from very high spatial resolution imagery (VHRI) and ancillary datasets. The result is a binary map showing cultivated/non-cultivated areas ca. 2015. The map produced an overall accuracy of 93.8% with roughly 14% omission and commission errors for the cropland class based on a large set of independent validation samples. The map suggests the entire study area has a total 546 million hectares (Mha) of net croplands (nearly 30% of global net cropland areas) occupying 18% of the study land area. Comparison between national cropland area estimates from United Nations Food and Agricultural Organizations (FAO) and those derived from this work also showed an R-square value of 0.95. This Landsat-derived 30-m cropland product (GFSAD30) provided 10–30% greater cropland areas compared to UN FAO in the 64 Countries. Finally, the map-to-map comparison between GFSAD30 with several other cropland products revealed that the best similarity matrix was with the 30 m global land cover (GLC30) product providing an overall similarity of 88.8% (Kappa 0.7) with producer’s cropland similarity of 89.2% (errors of omissions = 10.8%) and user’s cropland similarity of 81.8% (errors of commissions = 8.1%). GFSAD30 captured the missing croplands in GLC30 product around significantly irrigated agricultural areas in Germany and Belgium and rainfed agriculture in Italy. This study also established that the real strengths of GFSAD30 product, compared to other products, were: 1. identifying precise location of croplands, and 2. capturing fragmented croplands. The cropland extent map dataset is available through NASA’s Land Processes Distributed Active Archive Center (LP DAAC) at https://doi.org/10.5067/MEaSUREs/GFSAD/GFSAD30EUCEARUMECE.001 , while the training and reference data as well as visualization are available at the Global Croplands https://croplands.org > website, GEE code is accessible at: https://code.earthengine.google.com/1666e8bed34e0ce2b2aaf1235ad8c6bd .
Design and Prototyping of a Portable Metasurface-Based Refractive Index Sensor

Demonstration of nanophotonic platform for metasurface-based refractive index sensing. Prototype results indicate that dramatic cost (∼$5, 000) and scale (e.g. portable, handheld) reductions are attainable in comparison to existing technologies with comparable sensitivity (Δn = 10−6).
Direct Aspiration Thrombectomy for Acute Stroke: Evolution of Technique and Evidence

Direct aspiration, a thrombectomy approach that originally evolved from a modified stent retriever-based technique, is now accepted as a frontline modality. We outline the evolution of thrombectomy techniques leading to ADAPT (A Direct Aspiration First-Pass Technique), as well as the current literature to support its use.
Analysis of electrification strategies for rural renewable electrification in developing countries using agent-based models

Abstract This paper presents an Agent-Based Model that determines the minimum cost strategy for rural electrification delivery systems and associated decentralized generation focusing entirely on renewable resources. The model creates generalized scenarios examining stakeholders' preferences for renewable resources to deploy and preferences between centralized and decentralized generation. Literature suggests that low demand, topographical challenges and distance from the grid are the main drivers for decentralized generation. This work shows that available energy potential is an important driver as well by introducing the concepts of stress (the percentage of renewable energy potential taken up by demand) and centrality (the ratio between size of resources and average distance to demand) and demonstrating that these parameters influence the minimum cost strategy despite distance and demand. At very low stress levels the lowest cost networks result from emphasizing decentralized generation. At stress levels above 2%, least cost delivery systems result from emphasizing grid extension of clusters created around resources with high centrality and the decentralized mix is high due to the geographical limitations of renewables. Results show that in every case, while deploying renewable energy for rural electrification, a mixture of grid extension and decentralized generation coexist for universal electrification in the least cost strategies.
Use of Sources in Newspaper Coverage of the 2009 Bulgarian Parliamentary Election

Although the importance of news sources is widely acknowledged in journalism and political communication, few studies have examined source use in election news reporting in Bulgaria. Bsed on a content analysis of the two national dailies with the highest circulation, the present study demonstrates that domestic politicians vastly outnumber other types of sources. In addition, election news articles rarely incorporate more than one news source, thus limiting the diversity of opinions in the press. Such coverage may potentially lead to a narrowing of the range of discussion about political issues and give national political elites the power to define the issues for the public.
ppe51 variants promote non-replicating Mycobacterium tuberculosis to grow at acidic pH by selectively promoting glycerol uptake

Abstract In defined media supplemented with single carbon sources, Mycobacterium tuberculosis (Mtb) exhibits carbon source specific growth restriction. When supplied glycerol as the sole carbon source at pH 5.7, Mtb establishes a metabolically active state of nonreplicating persistence known as acid growth arrest. We hypothesized that acidic growth arrest on glycerol is not a metabolic restriction, but rather an adaptive response. To test this hypothesis, we conducted forward genetic screens that identified several Mtb mutants that could grow under these restrictive conditions. All of the mutants were mapped to the ppe51 gene and resulted in three amino acid substitution – S211R, E215K, and A228D. Expression of the PPE51 variants in Mtb promoted growth at acidic pH showing that the mutant alleles are sufficient to cause the dominant gain-of-function, enhanced acid growth (eag) phenotype. Testing growth on other single carbon sources showed the PPE51 variants specifically enhanced growth on glycerol, suggesting ppe51 plays a role in glycerol uptake. Using radiolabeled glycerol, enhanced glycerol uptake was observed in Mtb expressing the PPE51 (S211R) variant, with glycerol overaccumulation in triacylglycerol. Notably, the eag phenotype is deleterious for growth in macrophages, where the mutants have selectively faster replication and reduced in virulence in activated macrophages as compared to resting macrophages. Recombinant PPE51 protein exhibited differential thermostability in the WT or S211R variants in the presence of glycerol, supporting the eag substitutions alter PPE51-glycerol interactions. Together, these findings support that PPE51 variants selectively promote glycerol uptake and that slowed growth at acidic pH is an important adaptive mechanism required for macrophage pathogenesis.
The effects of the subjective-experiential knowledge gap on consumers’ information search behavior and perceptions of consumption risk

Abstract This research examines how the Subjective-Experiential Knowledge Gap (SEKG) influences perceptions of consumption risk and the importance of external information search. Guided by information processing theories, we identify some determinants of SEKG and show that the perceived importance of external information search is significantly different across levels of SEKG. Motivated by this, we then investigate the moderating role of SEKG in relationships among consumption risk, its determinants, and the importance of external information search. Results show that individuals low and high on SEKG differ in what product characteristics they view as sources of consumption risk. Moreover, only in the high-SEKG group, increased consumption risk leads to an increased importance placed on external information search. This research expands our understanding of what determines SEKG and how this metacognitive construct affects perceptions of consumption risk and information search. Businesses and public policymakers can increase the receptiveness toward their communications by leveraging SEKG.
Internal Control Quality: The Role of Critical Audit Matters Reporting

We examine whether the 2019 introduction of critical audit matter (CAM) reporting in audit reports in the United States is associated with improvements in issuers’ internal controls over financial reporting. We propose that increased scrutiny by auditors on CAM-related matters may lead to early identification and client remediation of material weaknesses in internal control (ICMW). Analyses show that compared to control companies, treatment companies (those with CAM reporting) experience a statistically significant decrease in both the likelihood of having an ICMW and the number of ICMWs after the CAM is reported. This result is driven primarily by account-level ICMWs rather than entity-level ICMWs. We also find that issuers with revenue-recognition CAMs have significantly fewer revenue-related ICMWs compared to other issuers, consistent with the notion that ICMWs related to revenue recognition are identified and remediated through the auditor’s CAM evaluation process. Results show that the positive association between CAM disclosure and internal control quality—that is, the negative association between CAMs and ICMWs—is more pronounced when more auditor effort is involved in CAM reporting. We conclude that by focusing auditor attention on areas of potential concern, CAM reporting leads to improvements in the quality of internal control over financial reporting.
Institutional chart review on same-day pegfilgrastim administration in small cell lung cancer (SCLC) patients receiving myelotoxic chemotherapy.

71Background: Pegfilgrastim administration is recommended at least 24 hours after the end of chemotherapy (CTX) treatment for prevention of chemotherapy-induced (febrile) neutropenia (CIN/FN). Publ...
SR-Mitochondria Crosstalk Shapes Ca Signalling to Impact Pathophenotype in Disease Models Marked by Dysregulated Intracellular Ca Release

AIMS Diastolic Ca release (DCR) from sarcoplasmic reticulum (SR) Ca release channel ryanodine receptor (RyR2) has been linked to multiple cardiac pathologies, but its exact role in shaping divergent cardiac pathologies remains unclear. We hypothesize that the SR-mitochondria interplay contributes to disease phenotypes by shaping Ca signaling. METHODS AND RESULTS A genetic model of catecholaminergic polymorphic ventricular tachycardia (CPVT2 model of CASQ2 knockout) and a pre-diabetic cardiomyopathy model of fructose fed mice (FFD), both marked by DCR, are employed in this study. Mitochondria Ca (mCa) is modulated by pharmacologically targeting mitochondria Ca uniporter (MCU) or permeability transition pore (mPTP), mCa uptake and extrusion mechanisms, respectively. An MCU activator abolished Ca waves in CPVT2 but exacerbated waves in FFD cells. Mechanistically this is ascribed to mitochondria's function as a Ca buffer or source of reactive oxygen species (mtROS) to exacerbate RyR2 functionality, respectively. Enhancing mCa uptake reduced and elevated mtROS production in CPVT2 and FFD respectively. In CPVT2, mitochondria took up more Ca in permeabilized cells, and had higher level of mCa content in intact cells vs FFD. Conditional ablation of MCU in the CPVT2 model caused lethality and cardiac remodeling, but reduced arrhythmias in the FFD model. In parallel, CPVT2 mitochondria also employ upregulated mPTP-mediated Ca efflux to avoid mCa overload, as seen by elevated incidence of MitoWinks (an indicator of mPTP-mediated Ca efflux) vs FFD. Both pharmacological and genetic inhibition of mPTP promoted mtROS production and exacerbation of myocyte Ca handling in CPVT2. Further, genetic inhibition of mPTP exacerbated arrhythmias in CPVT2. CONCLUSION In contrast to FFD, which is more susceptible to mtROS-dependent RyR2 leak, in CPVT2 mitochondria buffer SR-derived DCR to mitigate Ca-dependent pathological remodeling and rely on mPTP-mediated Ca efflux to avoid mCa overload. SR-mitochondria interplay contributes to the divergent pathologies by disparately shaping intracellular Ca signaling. TRANSLATIONAL PERSPECTIVE It is well-established that RyR2 dysfunction is involved in a spectrum of pathological conditions including cardiac arrhythmias. In this study, two disease models marked by RyR2 dysfunction were employed to explore how the interplay between SR and mitochondria contributes to divergent cardiac pathologies. We found mitochondria act as essential Ca buffer to absorb SR-derived Ca to mitigate pathological remodeling in the genetic arrhythmic syndrome CPVT, but they are more susceptible to Ca overload or ROS-related exacerbation of RyR2 dysfunction in pre-diabetic cardiomyopathy. Thus, tailored therapies should be developed to target SR-mitochondria interplay in the aims of treating these diseases.
Accelerating Variant Calling on Human Genomes Using a Commodity Cluster

Variant calling is a fundamental task that is performed to identify variants in an individual's genome compared to a reference human genome. This task can enable better understanding of an individual's risk to diseases and eventually lead to new innovations in precision medicine and drug discovery. However, variant calling on a large number of human genome sequences requires significant computing and storage resources. While access to such resources is possible today (e.g., through cloud computing), reducing the cost of analyzing genomes has become a major challenge. Motivated by these reasons, we address the problem of accelerating the variant calling pipeline on a large number of human genome sequences using a commodity cluster. We propose a novel approach that synergistically combines data and task parallelism for different stages of the variant calling pipeline across different sequences with minimal synchronization. Our approach employs futures to enable asynchronous computations in order to improve the overall cluster utilization and thereby, accelerate the variant calling pipeline. On a 16-node cluster, we observed that our approach was 3X-4.7X faster than the state-of-the-art Big Data Genomics software.
Middle Eastern Women and the Invisible Economy

Middle Eastern Women and the Invisible Economy. Richard A. Lobban Jr. ed. Gainesville: University Press of Florida, 1998. 302 pp.
Microsoft Antitrust Case: United States

This article presents an examination of the antitrust case brought by the US Department of Justice against the Microsoft Corporation. The article addresses the primary issues of market definition, market power and anticompetitive behavior which were central to the case. The economic arguments behind the government's positions and Microsoft's defenses are provided. The decisions of the US District and Circuit courts with respect to the legality of Microsoft's behavior regarding the monopolizing of the operating system market, attempting to monopolize the browser market and the tying of its operating system to its browser are also provided. Keywords: antitrust; market power; monopoly; Microsoft; tying
Autonomous robotic strategies for urban search and rescue

This dissertation proposes autonomous robotic strategies for urban search and rescue (USAR) which are map-based semi-autonomous robot navigation and fully-autonomous robotic search, tracking, localization and mapping (STLAM) using a team of robots. Since the prerequisite for these solutions is accurate robot localization in the environment, this dissertation first presents a novel grid-based scan-to-map matching technique for accurate simultaneous localization and mapping (SLAM). At every acquisition of a new scan and estimation of the robot pose, the proposed technique corrects the estimation error by matching the new scan to the globally defined grid map. To improve the accuracy of the correction, each grid cell of the map is represented by multiple normal distributions (NDs). The new scan to be matched to the map is also represented by NDs, which achieves the scan-to-map matching by the ND-to-ND matching. In the map-based semi-autonomous robot navigation strategy, a robot placed in an environment creates the map of the environment and sends it to the human operator at a distant location. The human operator then makes decisions based on the map and controls the robot via tele-operation. In case of communication loss, the robot semi-autonomously returns to the home position by inversely tracking its trajectory with additional optimal path planning. In the fully-autonomous robotic solution to USAR, multiple robots communicate one another while operating together as a team. The base station collects information from each robot and assigns tasks to the robots. Unlike the semi-autonomous strategy there is no control from the human operator. To further enhance the efficiency of their cooperation each member of the team specifically works on its own task. A series of numerical and experimental studies were conducted to demonstrate the applicability of the proposed solutions to USAR scenarios. The effectiveness of the scan-to-map matching with the multi-ND representation was confirmed by analyzing the error accumulation and by comparing with the single-ND representation. The applicability of the scan-to-map matching to the real SLAM problem was also verified in three different real environments. The results of the map-based semi-autonomous robot navigation showed the effectiveness of the approach as an immediately usable solution to USAR. The effectiveness of the proposed fully-autonomous solution was first confirmed by two real robots in a real environment. The cooperative performance of the strategy was further investigated using the developed platform- and hardware-in-the-loop simulator. The results showed significant potential as the future solution to USAR.
A Flexible Design for Accessible Spoken Math

MathPlayer is a plug-in to Microsoft Internet Explorer (IE) and Adobe Acrobat/Reader that renders MathML visually and converts it to textual speech strings. The version under development has a unique architecture that allows multiple styles of speech, easy internationalization/localization, and the generation of a user interface that allows user customization of the words spoken based upon external rule files. It includes many other accessibility features such as individual magnification of expressions, synchronized highlighting of text and speech, and conversion to Braille math codes.
Uptake and Silica and Carbon Nanotubes by Human Macrophages/Monocytes Induces Activation of Fibroblasts in vitro — Potential Implication for Pathogenesis of Inflammation and Fibrotic Diseases

The potential pathogenic effects of silica and carbon nanotubes (CNTs) on fibroblasts, macrophages/monocytes, and T cells were investigated. Human macrophage/monocytes were cultured and stimulated with silica, CNTs, or titanium particles. After adding human T cells to the stimulated macrophages/monocytes, the cells were added to cultured human fibroblasts. Upon microscopic examination, CNT stimulation after 24 hours showed centralization of macrophages/monocytes around the CNTs. Silica stimulation showed a significant increase of IL-1α and IL-1β in cultured medium, and an increased gene expression of CTGF in cultured fibroblasts at 1 hour, as well as an up-regulation of the COL1A2 gene at 24-hour time point. In addition to the same changes of IL-1α, IL-1β and the COL1A2 by silica, CNT stimulation showed an increase of IL-8 in cultured medium at 1-hour time point. Titanium stimulation yielded no significant changes. The results indicate a proinflammatory and/or profibrotic effect of silica and CNTs to cultured human cells including macrophages/monocyte, T cells and fibroblasts.
Beyond the Courtroom: Alternatives for Resolving Press Disputes

This chapter describes an experimental alternative program for resolving media libel disputes out of court and explains why the program was created. The chapter first discusses the findings of an empirical study of the libel litigation system. That study found that the primary objectives of plaintiffs who sue for libel are not met by the current system and that the media incur large financial and other costs in defending libel suits. The experimental, voluntary, alternative program that was created in response to these findings is described, along with the potential benefits that it could offer both parties relative to the current system and to other media libel litigation reform proposals.
Decreased RXRα is Associated with Increased β-Catenin/TCF4 in 56Fe-Induced Intestinal Tumors

Although it is known that accumulation of oncogenic β-catenin is critical for intestinal tumorigenesis, the underlying mechanisms have not yet been fully explored. Post-translational β-catenin level is regulated via the adenomatous polyposis coli (APC)-dependent as well as the APC-independent ubiquitin proteasome pathway (UPP). Employing an APC-mutant mouse model (APCMin/+) the present study aimed to investigate the status of RXRα, an APC-independent factor involved in targeting β-catenin to UPP for degradation, in tumor-bearing and tumor-free areas of intestine after exposure to energetic 56Fe ions. APCMin/+ mice were exposed to energetic 56Fe ions (4 or 1.6 Gy) and intestinal tumor samples and tumor-free normal intestinal samples were collected 100 to 110 days after exposure. The status of TCF4, β-catenin, cyclin D1, and RXRα was examined using immunohistochemistry and immunoblots. We observed increased accumulation of the transcription factor TCF4 and its co-activator β-catenin as well as their downstream oncogenic target protein cyclin-D1 in 56Fe-ion induced intestinal tumors. Further, decreased expression of RXRα in tumors as well as in adjacent normal epithelium was indicative of perturbations in β-catenin proteasomal targeting machinery. This indicates that decreased UPP targeting of β-catenin due to downregulation of RXRα can contribute to further accumulation of β-catenin and to 56Fe-induced tumorigenesis.
Dynamic modeling and mobility analysis of the transforming roving–rolling explorer (TRREx) as it Traverses Rugged Martian Terrain

Abstract All planetary surface exploration missions thus far have employed traditional rovers with a rocker-bogie suspension. These rovers can navigate moderately rough and flat terrain, but are not designed to traverse rugged terrain with steep slopes. The fact is, however, that the most scientifically interesting missions require exploration platforms with capabilities for navigating such types of rugged terrain. This issue motivates the development of new kinds of rovers that take advantage of the latest advances in robotic technologies to traverse rugged terrain efficiently. This work analyzes one such rover concept called the Transforming Roving–Rolling Explorer (TRREx) that is principally aimed at addressing the above issue. Biologically inspired by the way the armadillo curls up into a ball when threatened, and the way the golden wheel spider uses the dynamic advantages of a sphere to roll down hills when escaping danger, the TRREx rover can traverse like a traditional 6-wheeled rover over conventional terrain, but can also transform itself into a sphere, when necessary, to travel down steep inclines, or navigate rough terrain. This paper investigates the mobility of the TRREx when it is in its rolling mode, i.e. when it is a sphere and can steer itself through actuations that shift its center of mass to achieve the desired direction of roll. A mathematical model describing the dynamics of the rover in this spherical configuration is presented, and actuated rolling is demonstrated through computer simulation. Parametric analyzes that investigate the rover’s mobility as a function of its design parameters are also presented. This work highlights the contribution of the spherical rolling mode to the enhanced mobility of the TRREx rover and how it could enable challenging surface exploration missions in the future.
Efficient model selection for speech enhancement using a deflation method for Nonnegative Matrix Factorization

We present a deflation method for Nonnegative Matrix Factorization (NMF) that aims to discover latent components one by one in order of importance. To do so we perform a series of individual decompositions, each of which stands for a deflation step. In each deflation we obtain a dominant component and a nonnegative residual, and then the residual is further used as an input to the next deflation in case we want to extract more components. With the help of the proposed additional inequality constraint on the residual during the optimization, the accumulated latent components at any given deflation step can approximate the input to some degree, whereas NMF with an inaccurate rank assumption often fail to do so. The proposed method is beneficial if we need efficiency in deciding the model complexity from unknown data. We derive multiplicative update rules similar to those of regular NMF to perform the optimization. Experiments on online speech enhancement show that the proposed deflation method has advantages over NMF: namely a scalable model structure, reusable parameters across decompositions, and resistance to permutation ambiguity.
Quantitative flow visualization technique for measurements in combustion gases.

A quantitative flow visualization technique for combustion research is described. The method uses sheet illumination from a tunable laser to excite planar laser-induced fluorescence (PLIF) which is detected using 2-D detector. This technique has been used to make single-shot simultaneous multiple-point measurements of species concentration and has recently been extended to measurements of other properties such as temperature and velocity. The light sources, image intensifiers, detector arrays, computer hardware, and computer software needed to implement this scheme are described. The detectivity, dynamic range, spatial resolution, and temporal resolution of the technique are discussed and a recent application of the technique (to view the OH concentration in a rod-stabilized flame) is presented.
How to use the computing environment R to analyze ATP-induced ribonucleotide reductase R1 hexamerization data

R is an object oriented free and open source statistical computing environment. The R package Combinatorially Complex Equilibrium Model Selection is being developed to meet the analysis challenges of ribonucleotide reductase (RNR). An example of its use is given here. This example involves ATP-induced R1 hexamerization dynamic light scattering data that suggests that R1 hexamers have two types of a-sites, one that binds ATP and another that does not (here, R1 is the large subunit of RNR).
The structure and stability of small mammal faunas

I examined questions about the local and global stability and resilience characteristics of six small mammal faunas and their relationship to connectance, average interaction strength, community covariance, and indirect competitive pathways. Community matrices estimated elsewhere were used in the analyses. The faunas had from three to nine species and represented several habitat types. The following properties were observed: (1) all community matrices were globally stable, (2) return rates to equilibrium were generally maximized, and (3) competitive interactions were strictly hierarchical. Global stability resulted from a reduction in connectance with increasing species and not from structural characteristics (i.e., community covariance). Average interaction strength did not change with the number of species in these faunas. Increased resilience was due largely to reduced community covariance. Two of the six faunas showed some evidence for indirect pathways, but this appeared to be artifactual. Randomizations of the original community matrices showed that indirect pathways have a high probability of occurrence. Monte Carlo simulations indicated that the probability of indirect pathways increases with increasing number of species or magnitude of competition. These results bring into question previous observational studies invoking indirect competitive pathways. Communities without indirect pathways have a special linear hierarchical structure. This structure has greater resilience than when indirect pathways are present. The observed patterns in community structure are discussed with regard to current theories of habitat selection.
Biochemistry of enteric parasitic protozoa

Abstract Although the enteric parasitic protozoa are of world-wide public health concern little is known of their physiology and biochemistry. These protozoa were previously considered to be anaerobic, but recent studies show that they have an active respiration. The parasites lack mitochondria and heme proteins; terminal electron transfer to molecular oxygen is accomplished by flavins and non-heme iron-sulfur proteins.
A Measure of the Ability to Identify Emotion in Children's Tone of Voice

This paper introduces a test of the ability to decode emotion of varying intensity in the voices of children. Construction of the measure, the Diagnostic Analysis of Nonverbal Accuracy Child Paralanguage (DANVA2-CP), is described. An initial study using elementary-school-aged children found that accuracy scores increased with age, were internally consistent, and were correlated, as expected, with indices of personality and social competence. Data from 20 additional studies, using participants from across the age range, provided further evidence of construct validity for the DANVA2-CP. Based on the results, it was concluded that the DANVA2-CP may be an appropriate measure of the ability to identify emotion in children's paralinguistic presentations.
Vercirnon for the treatment of Crohn's disease.

Introduction: CCR9 antagonism is a promising new therapeutic approach for the treatment of Crohn's disease. CCR9 is expressed on the cell surface of memory/effector CD4+ T cells and selectively binds to the small intestinal lymphocyte chemoattractant CCL25 (TECK). Blockade of the CCR9/CCL25 interaction inhibits lymphocyte homing to the intestinal mucosa, thereby limiting inflammation and disease at this site. Areas covered: This review details the current research on CCR9 antagonism and summarizes available clinical trial data for vercirnon, a selective CCR9 antagonist currently under development. Expert opinion: If the results of ongoing large-scale clinical trials of vercirnon are in line with preliminary reports, CCR9 antagonism may have comparable efficacy to anti-TNF therapies and a potentially superior safety profile, making it the latest addition to the growing arsenal of immunomodulatory drug therapies available to combat Crohn's disease. Moreover, since vercirnon is an oral drug, its associated c...
A new class of universal multiple description lattice quantizers

We propose a new class of universal multiple description lattice quantizers based on the method of quantization splitting. For Gaussian sources and squared error distortion measure, our scheme can achieve the whole multiple description rate-distortion region, as the dimension of the (optimal) lattice quantizers becomes large
Production and Persistence of Antibodies in Chickens to Sheep Erythrocytes. 2. Resistance to Infectious Diseases

Abstract A line of chickens selected for ability to produce high antibody titers to sheep red blood cells exhibited stronger antibody to Newcastle disease, was more resistant to Mycoplasma gallisepticum, Eimeria necatrix, a splenomeglia virus, and feather mites and less resistant to Escherichia coli and Staphylococcus aureus infection than a line selected for a lack of ability to produce antibody titers. A line of chickens selected for a nonpersistence of antibody titers to sheep red blood cells was relatively more susceptible to all infectious agents tested than a line selected for a persistence of antibody titers.
Adsorption and reaction of NO2 on a (√3×√3)R30° Sn/Pt(111) surface alloy

Abstract Adsorption of nitrogen dioxide (NO 2 ) on a (√3×√3) R 30° Sn/Pt(1 1 1) surface alloy has been investigated using temperature programmed desorption (TPD), Auger electron spectroscopy (AES), high-resolution electron energy loss spectroscopy (HREELS), and low energy electron diffraction (LEED). At 120 K, NO 2 is adsorbed molecularly as the N , N -bonded dimer, N 2 O 4 , interacting with the surface through a single oxygen atom in an upright but tilted geometry. However, no N 2 O 4 or NO 2 desorbs molecularly from the monolayer state. The dimer completely dissociates at 300 K, leaving coadsorbed NO 2 , NO, and O on the surface. Adsorbed NO 2 further dissociates to coadsorbed NO and O at 300–400 K. The maximum oxygen atom coverage obtained by heating the N 2 O 4 monolayer was about θ O =0.4 ML, but this can be increased to θ O =1.1 ML by NO 2 dosing on the alloy surface at 600 K to remove inhibition by coadsorbed NO. Under these latter conditions, adsorbed oxygen desorbs as O 2 in three clear desorption states, the lowest of which is associated with O 2 desorption from Pt sites and the other two are from decomposition of reduced tin oxide phase(s), SnO x . Shifts in Sn AES peaks were used to follow Sn oxidation.
Competition between collateral vessels.

The number of collateral vessels that supplies a given vascular bed tends to decrease. We suggest that this results from effects of the hydrodynamic drag of the stream on the endothelium. A mathematical model forms the basis for the argument. Some implications of this thesis on the natural history of clinical arterial stenoses are discussed.
Detailed prediction for the BYORP effect on binary near-Earth Asteroid (66391) 1999 KW4 and implications for the binary population

Abstract A previous theory by the authors for detailed modeling of the binary YORP effect is reviewed and expanded to accommodate doubly-synchronous binary systems, as well as a method for non-dimensionalizing the coefficients for application to binary systems where a shape model to compute its own coefficients is not available. The theory is also expanded to account for the effects of primary J2 and the Sun’s 3rd body perturbation on the secular orbit evolution. The newly expanded theory is applied to the binary near-Earth Asteroid 1999 KW4, for which a detailed shape model is available. The result of simulation of the secular evolutionary equations shows that the KW4 orbit will be double in size in approximately 22,000 years, and will reach the Hill radius in approximately 54,000 years. The simulation also shows that the eccentricity will alternate growing and shrinking in magnitude, depending on the location of the solar node in the body-fixed frame. Therefore the eccentricity is not fixed to evolve in the opposite sign as the semi-major axis unless the circulation of the node (with a period of 500 years) is averaged out as well. The current orbit expansion rate for KW4 of 7 cm per year is shown to be detectable with observations of the mean anomaly which grows quadratically in time with an expanding orbit. Finally, the KW4 results are scaled for application to a number of other binary systems for which detailed shape models are not available. This application shows that the orbits considered can expand to their Hill radius in the range of 104–106 years. This implies rapid formation of binary systems is necessary to support the large percentage of binaries observed in the NEA population.
Delayed radiotherapy following dose intensive chemotherapy for parameningeal rhabdomyosarcoma (PM-RMS) of childhood

Abstract Purpose To evaluate the local control rates and survival rates of patients with Group III parameningeal rhabdomyosarcoma (PM-RMS) treated with a dose intensive chemotherapy regimen followed by irradiation. Materials and methods Twenty-six patients with group III, PM-RMS were enrolled in a prospective pilot trial at the Mayo Clinic, Rochester, MN and Children’s Hospital and Regional Medical Center Seattle, WA. The median age at diagnosis was 8.5 years (range 1.5–19 years). The male to female patient ratio was 1.6:1. Twenty-three patients had embryonal histology with the remaining three alveolar. Risk factors indicating high risk disease included intracranial extension (10 patients), base of skull erosion (12 patients), and cranial nerve palsy (10 patients). The median follow-up period for all patients was 82 months (range 17–148 months). Patients were treated with an intensified chemotherapy regimen followed by definitive local irradiation at week 12 following further chemotherapy. The median time from initiation of chemotherapy to irradiation was 16 weeks (range 6–23). The median dose delivered was 50.4 Gy (50.4–66.6 Gy). Results Response was assessed after the fourth course of chemotherapy. Three patients exhibited a complete response, 22 a partial response, and 1 patient had no response after two cycles of chemotherapy and proceeded to irradiation at week 6. The 5-year estimated event free survival was 81% (±15%, 95% CI). Two patients died from progressive metastatic disease; 1 patient died from secondary malignancy; and 2 patients died from locally progressive disease. The 5-year local control rate was 92% (±10.6%, 95% CI). Conclusions Treatment of group III PM-RMS patients with neo-adjuvant, intensive chemotherapy with a delay in irradiation resulted in excellent local-regional control rates and survival rates and may allow for a response-based radiotherapy approach.
Hemoglobin Structural Dynamics as Monitored by Resonance Raman Spectroscopy

Resonance Raman spectra of the heme group are now understood at a level sufficient to provide a useful monitor of several heme structural features. Some porphyrin vibrational frequencies are sensitive to Fe oxidation state, or π-electron distribution, and give insight into the electronic structure of 02, CO and NO hemes. Others are sensitive to Fe spin-state, via the associated geometry variation, and provide an accurate index of the porphyrin core size. When examined during the photolysis of CO-hemoglobin via short laser pulses, these frequencies indicate that conversion from low- to high-spin Fe11 takes place within 30 ps of photolysis, presumably via intersystem-crossing in the excited state, but that the subsequent relaxation of the Fe atom out of the heme plane takes longer than 20 ns, probably because of restraint by the protein. Axial ligand modes have been identified for several heme derivatives. The Fe-imidazole frequency in deoxyhemoglobin is appreciably lowered in the T quaternary structure, as determined in both static and kinetic experiments, suggesting molecular tension or proximal imidazole H-bond weakening in the T state.
Crystallization and preliminary diffraction studies of the ectodomain of the envelope glycoprotein D from herpes simplex virus 1 alone and in complex with the ectodomain of the human receptor HveA

Gycoprotein D (gD) is a glycoprotein expressed on the surface of several human and animal alpha herpes viruses. Binding of gD to cell-surface receptors has been shown to be necessary for herpes simplex virus 1 and 2 (HSV-1 and HSV-2) cell entry. The gD ectodomain consists of 316 residues and has no sequence homology to any other proteins of known structure. Two fragments of the HSV-1 gD ectodomain (gD22–260: residues 22–260 and gD285: residues 1–285) have been crystallized in two crystal forms. The complex between gD285 and the ectodomain of HveA, a gD cellular receptor member of the tumor necrosis factor (TNFR) superfamily, has also been crystallized. Moreover, insect-cell-expressed selenomethionine-substituted gD285 has been purified and crystallized alone and in complex with HveA.
Levels of immunoglobulin G, M, A, and E at various ages in allergic and nonallergic black and white individuals

Studies were conducted to detect major differences in immunoglobulin levels between allergic and nonallergic individuals. Immunoglobulins G, M, A, and E were quantitated in members of 63 families selected for the presence of children with asthma or allergic rhinitis and compared with a larger group of healthy individuals and families. Mean IgE levels were significantly higher in healthy black than in white individuals. No significant difference was found in IgE levels between healthy parents with and without allergic children. Mean IgE levels were significantly higher in asthmatic children than in healthy children and also much higher in asthmatic children than in their healthy siblings. Asthma occurred more frequently in boys than in girls. IgE levels in healthy children increased rapidly early in childhood, reached a peak before 10 yr of age, and decreased during the teens. This decrease in IgE during the teens may provide the immunologic mechanism by which some children can "outgrow" certain childhood allergies. IgA levels were very low in young children and not significantly different between allergic and healthy individuals. The low IgA level in young children may be of importance in the development of childhood allergies.
Relationships of Serum Plant Sterols (Phytosterols) and Cholesterol in 595 Hypercholesterolemic Subjects, and Familial Aggregation of Phytosterols, Cholesterol, and Premature Coronary Heart Disease in Hyperphytosterolemic Probands and Their First-Degree Relatives

To assess relationships of serum phytosterols (plant sterols [P]) to serum cholesterol (C), P were measured by gas-liquid chromatography (GLC) in 595 hypercholesterolemics (top C quintile in screening of 3,472 self-referred subjects). A second specific aim was to determine whether high serum P would track over time and whether they would predict familial aggregation of high C, high low-density lipoprotein cholesterol (LDLC), high apolipoprotein (apo) B, and increased premature coronary heart disease (CHD) in hyperphytosterolemic probands and their first-degree relatives. Mean +/- (SD) C was 260 +/- 56 mg/dL, campesterol (CAMP) was 2.10 +/- 1.6 micrograms/mL, stigmasterol (STIG) 1.71 +/- 1.67, sitosterol (SIT) 2.98 +/- 1.61, and total P 6.79 +/- 3.66 micrograms/mL. Serum C correlated with CAMP (r = .15, P less than or equal to .001), STIG (r = .10, P less than or equal to .02), SIT (r = .34, P less than or equal to .0001), and total P (r = .29, P less than or equal to .0001). High serum CAMP and STIG were associated with a personal or family history of CHD in subjects less than or equal to age 55 years (premature CHD). In 21 hyperphytosterolemic probands who initially had at least one P at or above the 95th percentile and a second P at or above the 75th percentile, P were remeasured 2 years later. Initial and 2-year follow-up CAMP, STIG, and SIT did not differ (P greater than .7). Initial and follow-up CAMP were correlated (r = .47, P = .03).(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of age and dietary fat (fish, corn and coconut oils) on tocopherol status of C57BL/6Nia mice.

The effect of age and dietary fat type on tocopherol status was investigated using young and old C57BL/6Nia mice fed semipurified diets containing 5% (by weight) fish, corn or coconut oils and supplemented with 30, 100 or 500 ppm dl-α-tocopheryl acetate for 6 wk. Tocopherol levels in the diets, plasma, liver, kidney and lung were measured by high performance liquid chromatography following appropriate extractions. The results indicate that mice fed fish oil maintain lower plasma and tissue tocopherol concentrations than those fed corn and cononut oils (fish<corn oil<coconut oil). The difference was not due to a loss of tocopherol prior to consumption, but rather appeared to occur during the absorption process. Old mice had lower plasma and liver tocopherol concentrations than young mice. Old mice fed fish oil, however, maintained plasma tocopherol levels better than young mice fed fish oil, presumably due to their larger tocopherol pool. No age effect was detected on kidney and lung tocopherol levels. It is concluded that tocopherol status is affected by age and dietary fat type, especially fish oil.
SITE-DIRECTED MUTAGENESIS OF HUMAN DIHYDROLIPOAMIDE DEHYDROGENASE : ROLE OF LYSINE-54 AND GLUTAMATE-192 IN STABILIZING THE THIOLATE-FAD INTERMEDIATE

The roles of lysine-54 (K54) and glutamate-192 (E192) of human dihydrolipoamide dehydrogenase (E3) in stabilizing the thiolate-FAD intermediate during electron transfer were investigated by site-directed mutagenesis. Recombinant human E3s, wild-type, K54E, S53K54-K53S54 (SK-KS), and E192Q, were overexpressed, purified, and characterized. Only K54E and SK-KS E3s had about 25% less bound FAD compared to wild-type, implicating that K54 is crucial for the protein-FAD interaction. The specific activities of all mutant E3s were markedly decreased (<5% wild-type). In the case of K54E E3, the Km for lipoamide in the reverse reaction was increased by about twofold. Surprisingly, for both SK-KS and E192Q E3s, the Kms for both dihydrolipoamide (forward reaction) and lipoamide (reverse reaction) were markedly reduced. The catalytic rate constants (kcat/Km) for both reactions for SK-KS E3 were significantly lower than wild-type, indicating that K54 is crucial for the catalytic efficiency of the enzyme. Fluorescence spectral analyses showed that the FAD in E3s were reduced by the addition of dihydrolipoamide, and that its reoxidation by NAD+ in the mutant E3s was slower than wild-type E3. Interestingly, in K54E E3 dihydrolipoamide reduced FAD efficiently only when NAD+ was present, indicating that K54 stabilizes the thiolate-FAD interaction. The lack of the formation of thiolate-FAD intermediate in the absence of NAD+ in K54E E3 was also confirmed by CD spectra. The SK-KS mutation demonstrates that the correct sequence of residues is as critical as the nature of the amino acid residues. These results suggest that K54 plays an important role in stabilizing the thiolate-FAD intermediate during the electron transfer in the reaction, and E192 is involved in maintaining correct orientation of K54 during catalysis.