cssi/SciSciGPT-SciSciNet huggingface dataset:
Heparanase-1 activity in pancreatic cancer patient serum decreases after gemcitabine therapy

Introduction: Heparanase-1 (HPR) is an endoglycosidase that specifically degrades the heparan sulfate side chains of proteoglycan, a chief component of the extracellular matrix (ECM). HPR plays an important role in tumor metastases. HPR expression is increased in up to 70% of pancreatic cancer patients and correlates with a shorter survival time. Since HPR expressed in tumor tissue can be secreted into blood, we sought to determine if HPR expression in tumor tissue resulted in increased HPR activity in the serum of pancreatic cancer patients. We also evaluated the serum of pancreatic cancer patients for HPR activity before and after gemcitabine therapy as a potential indicator of tumor response to chemotherapy. Methods: Six blood samples were collected from pancreatic cancer patients before and after chemotherapy. Serum HPR activity was measured using a novel ELISA and compared against a standard (activity of purified HPR). Serum samples from 36 pancreatic cancer patients who did not receive chemotherapy were also tested for HPR activity. Serum samples from 18 healthy volunteers were run as negative controls. Data was analyzed using ANOVA to determine statistical significance. Results: HPR activity in the serum samples of pancreatic cancer patients was increased approximately 3-fold, compared to that in the serum of healthy donors. HPR activity decreased in the serum of all 6 patients who received gemcitabine by 2 weeks after initiation of chemotherapy (p < 0.01). Conclusion: A novel ELISA was used to quantitate serum HPR activity in pancreatic cancer patients. HPR activity was markedly increased in the serum of pancreatic cancer patients, but decreased after initiation of chemotherapy. Serum HPR levels may potentially be used as a marker of tumor response to adjuvant treatment.
GROWTH OF LIVERWORTS FROM KATMAI IN NITROGEN‐FREE MEDIA

A previous paper of this series (Griggs, 1933) has given an account of field work of the National Geographic Expedition of I930 on the revegetation of the country covered by ash from the eruption of Katmai in 19I2, wherein it was shown that the pioneer plants on pure ash deposits were leafy liverworts of the family Jungermanniaceae. The outstanding peculiarity of the ash upon which these plants were growing was the practical absence of nitrogen compounds. The obstacle to revegetation was, then, the difficulty of obtaining in available form the nitrogen necessary for the construction of protoplasm in conditions where the ordinary sources of such material almost totally fail. The field work showed that where even very slight organic contamination occurred ordinary plants could grow on the ash, but that in the pure uncontaminated ash nothing except the liverworts obtained a foothold. Thus, secondary deposits of wind-blown or water-laid ash were occupied by plants of many species, but the flora of the undisturbed ash consisted of a pure stand of liverworts. These in places bore a copious crop of sporophytes. The liverwort beds, covering acre after acre of ground, developed a heavy carpet far denser and more extensive than any liverwort growth in normal habitats. It was found, further, that the liverworts were the forerunners of other plants. Where they had occupied the ground longest, first mosses, then willows, and then grasses and other seed plants were coming in. It was clear that an understanding of the nitrogen relations of these plants could not be gained from field observations alone but would require cultural studies under controlled conditions in the laboratory. The present paper presents the results obtained to date on this problem.
Abstract 4292:In vivoandin vitroimaging of Cyclooxygenase-2 in tumor

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Cyclooxygenase-2 (Cox-2) is a biomarker for tumor progression and inflammatory diseases. It is known that normal tissues express minimal amounts of Cox-2 proteins while inflammatory and malignant tumor cells express high levels. Thus, inhibition of Cox-2 is a strategy in the treatment of tumor progression and inflammatory diseases. Recently, many different kinds of molecular imaging reagents for Cox-2 have been developed. Among them, an indomethacin-based Cox-2 probe, fluorocoxib, has been shown to bind to Cox-2 in vitro and in vivo. The binding specificity to Cox-2 was shown using cell culture and tumor xenograph models. In our present study, in order to optimize fluorocoxib imaging conditions, we utilized HCT116 and HT29 cells as low and high Cox-2 expressers, respectively. First, cultured cells were grown overnight on cover slips. Cells were then fixed with paraformaldehyde and incubated with fluorocoxib probe. Multispectral images were taken using a camera equipped with liquid crystal tunable filters. Spectral unmixing was applied to these images to enhance fluorocoxib signals. Our results indicate that HCT116 cells express fair amounts of Cox-2 protein. We also transplanted HCT116 and HT29 cells into the flank regions of nu/nu mice subcutaneously. After tumors grew to sufficient size (∼100 mm3) we injected fluorocoxib intravenously and monitored probe binding to the tumors. Whole animal in vivo imaging indicated that fluorocoxib binds to HT29 tumors after 3 hours. All the probes were eliminated from the animals by 24 hours. On the other hand, HCT116 tumors did not show strong binding of fluorocoxib as expected. However, HCT116 tumors did show some weak binding at the 3 and 6 hr time points. Once there was no longer any probe detected in vivo, we dissected the primary tumors from the HCT116 and HT29 implantations. Tissue sections were made with paraffin embedded tumors. After deparaffinization, tissue sections were incubated with fluorocoxib and fluorescent images were taken using multispectral imaging technology. Spectral unmixing data confirmed that HCT116 tumor sections showed fair amounts of Cox-2 probe expression. The amount of binding was also quantitated using a corresponding software package. Our results demonstrated that fluorescent biomarker probes can be imaged in vitro and in vivo non-invasively. Furthermore, we showed that the expression level can be quantitated using spectral unmixing imaging technology. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4292. doi:1538-7445.AM2012-4292
Da Pasque a Meteo: intersezioni di soggetto, linguaggio, e paesaggio nei versi di Andrea Zanzotto

AbstractA partire da una breve serie di riflessioni sul presunto lacanianesimo di Zanzotto, questo studio, piuttosto che tentare un consuntivo dell'opera poetica zanzottiana, ne analizza alcuni momenti specifici (in particolare Pasque ed il piu recente Meteo) per mostrare come in essa siano sempre in atto nuovi equilibri tra tre vertici in movimento: paesaggio, linguaggio e soggetto. L'analisi dimostra inoltre come non ci sia, tra questi tre vertici, un elemento generatore, e che cioe non e la frammentazione del soggetto o del paesaggio a generare il linguaggio frammentato e sperimentale, o viceversa il linguaggio spigoloso ed arduo a dar forma, lacanianamente, al reale; piuttosto, ognuno dei tre elementi tende verso gli altri trasformandoli e trasformandosi allo stesso tempo, in un sistema rizomatico e spesso incomunicante ma allo stesso tempo continuamente generante senso.
Midwest/western/eastern U.S. precipitation and aerosol sulfate: Differences attributable to natural source inputs?

Factor analysis comparisons between the MAP3S network and Minnesota precipitation chemistry data show marked differences. An assessment of ambient aerosol and precipitation chemistry data obtained at several Colorado and Minnesota sites suggests that natural source inputs may contribute to the sulfate observed in ambient aerosol and at least partly, explain the marked differences of Minnesota and Colorado precipitation chemistry data from that of MAP3S (eastern U.S.). However, a recently proposed mechanism, SO2 to SO4 conversion on the surface of dust particles, may be more important than natural sources in explaining western and midwestern precipitation chemistry data. It is concluded that these predominantly non-acidic SO4 sources may explain the poor association between the H+ and SO4 in many western and some midwestern precipitation chemistry data sets.
A Hormonal Interpretation of Collins's Micro‐sociological Theory of Violence

Collins (2008) provides a grand theory that unifies all forms of human violence occurring in face-to-face situations, ranging from spousal abuse to medieval warfare. Laitin (2008) appreciates Collins's microscopic analysis of diverse data but points to important shortcomings in the theory, especially Collins's metaphoric explanations that are not testable. Here Collins's theory is merged with an existing biosocial model of dominance, replacing the metaphors with tangible, measurable hormonal mechanisms.
Dissolution of Al-substituted goethites by an aerobic Pseudomonas mendocina var. bacteria

Abstract Goethite particles in soil environments often contain Al 3+ substituted for Fe 3+ in octahedrally coordinated sites. Al substitution has been shown to alter mineral stability and abiotic dissolution rates. This study focused on the effects of Al substitution (to 8.8 mol%) on synthetic goethite dissolution by an aerobic Pseudomonas mendocina var. bacteria. In contrast to dissimilatory iron reducing bacteria (DIRB), this bacteria is not capable of using Fe as a terminal electron acceptor for oxidative phosphorylation, and hence only requires μM concentrations of Fe for metabolism. Pure and substituted goethites were reacted with microorganisms in Fe-limited growth media wherein the only source of Fe was the solid phase, so that microbial populations could only grow by obtaining Fe through mineral dissolution. Because at least some Fe was taken up by the bacteria, we could not measure Fe release rates directly from dissolved Fe concentrations. Rather, we relied upon microbial growth measurements as indirect indicators of mineral dissolution. Increasing Al substitution resulted in particles with progressively decreasing mean particle length and aspect ratios, as well as fewer domains, as measured by atomic-force microscopy (AFM); but with increasing structural order as determined by XRD line widths. Experiments conducted in the dark at 22°C, exposed to the atmosphere, showed that maximum microbial population did not correlate with particle specific surface area, which is in contrast with previous studies using DIRB. Maximum microbial population increased a small amount with increasing Al content of the goethites, in contrast with several previous investigations of abiotic dissolution. Because dense biofilms formed, we were unable to use AFM to observe mineral dissolution features. AFM imaging suggested that more highly substituted goethites formed denser aggregates, and previous investigations have shown that aggregate structure is important for microbial attachment, which is prerequisite for dissolution. Hence, effects of Al substitution on aggregate structure is a focus of ongoing research.
A review of the gross structural effects of energetic atomic particles on vitreous and crystalline silica

Abstract The course of the changes resulting from irradiation and also those found on post-irradiation heating are reviewed. A hypothesis of the atomic behavior which will account for the observations is given.
Ontogeny of fetal rabbit upper gastrointestinal motility.

Background. The gastrointestinal (GI) tract performs the digestion, propulsion, and absorption of nutrients both pre- and postnatally, although little is known about the development of fetal motility. We evaluated the development of GI motility using a novel fetal rabbit model. Methods. Nine pregnant rabbits were obtained and three litters were studied at day 24 (n = 24), 27 (n = 29), and 30 (n = 24) of their 31-day gestation. Under ultrasound guidance fetal position was identified, a spinal needle was percutaneously inserted into each fetal stomach, and fluorescein, labeled with color-coded microspheres, was injected. Two hours later, fetuses were delivered and weighed, and the small intestine was harvested. The absolute length of fluorescein traveled was measured by ultraviolet light optical density and the percentage motility was calculated by dividing the absolute length of fluorescein traveled by the total small intestinal length. Results. All injected fetuses survived. The length of fluorescein traveled significantly increased from day 24 (8.1 ± 2.1 cm) to day 27 (18.8 ± 4.6 cm) and 30 (22.6 ± 5.2 cm). The length of fluorescein traveled significantly correlated with body weight on day 27 and 30. Calculated percentage motility significantly increased from day 24 to 30. However, percentage motility showed no correlation with fetal weight. Conclusions. This study describes a novel rabbit model for the assessment of in vivo fetal GI motility. Motility matured during the last third of gestation when assessed by the absolute length of fluorescein travel and the percentage motility. These results confirm that late-gestation fetuses have developed sufficient motility to propel potential nutrients, drugs, or gene therapy vectors to the small intestinal absorptive surface area.
RNA binding and R-loop formation by the herpes simplex virus type-1 single-stranded DNA-binding protein (ICP8)

In an effort to decipher the molecular mechanisms of homologous recombination during herpes simplex virus type-1 replication, we recently demonstrated that the virus-encoded single-stranded (ss) DNA-binding protein (ICP8) promotes the salt-dependent assimilation of ssDNA into a homologous plasmid, resulting in the formation of a displacement loop. In this paper, the results presented show for the first time a direct interaction between ICP8 and RNA. ICP8 binds to RNA with positive cooperativity but with approximately 5-fold lower affinity than to ssDNA. In addition, competition experiments indicate that the dissociation rate of ICP8 from RNA is faster than from ssDNA, although it is also dependent on the nature of the challenger. Importantly, ICP8 can promote the salt-dependent assimilation of RNA into a homologous acceptor plasmid to generate a joint molecule in which the RNA is stably paired with the complementary strand of the acceptor DNA, indicative of an R-loop. These findings have important implications on the role of ICP8 in mediating recombination reactions using viral transcripts. The RNA-binding activity of ICP8 also provides a molecular basis for its role in the regulation of viral gene expression.
Objectives for a system of health care delivery for HIV infected people.

Abstract This paper assumes that the effectiveness and efficiency of an integrated community system of care for HIV infected people may depend to a large extent on common perceptions of the objectives of such a system among three sets of actors—the patient, the professional care manager, and the continual care giver. It discusses a decision analytic inquiry into that concurrence on objectives. The conclusion is that within the community studied there is strong evidence of a significant lack of such common purpose.
Apparent generation of a segmented mRNA from two separate tandem gene families in Trypanosoma cruzi

Abstract Using a cDNA for an abundant Trypanosoma cruzi mRNA as probe, we have cloned and sequenced a gene which is organized in at least 20 nearly perfect tandem repeats of 940 base pairs. The 5' end of the mRNA has been sequenced by primer extension and found to contain a 35 nucleotide mini-exon (or spliced-leader) sequence that is ubiquitous in trypanosome mRNAs. This sequence, however, is not present in the tandem genomic repeats which encode the exon containing the major portion of the mRNA. Previous studies have shown that the 35-nucleotide sequence is encoded by a separate tandem gene family. One model to explain the formation of a segmented mRNA invokes priming of transcription by a small RNA which contains the leader sequence at its 5' end. However, northern blot analysis of total trypanosome RNA reveals a ladder of molecules larger than the mature mRNA, which appear to be faithful multimeric copies of the tandem gene. The discrete sizes of these RNAs correspond to those expected for partially processed precursors. These observations lend credence to the possibility of an alternative model where segmented mRNAs are generated by inter-molecular splicing.
Extraction of metallic cations by mono-acidic orthophosphate esters in a monomerizing diluent

Abstract The extraction of M2+ (Ca and U(VI) as UO22+), M3+ (Am(III), Eu(III), Er, Tm, Y and Sc) and M4+ (Th) from an aqueous HCl phase into an extractant phase consisting of a monoacidic orthophosphate ester in n-decyl alcohol as diluent has been studied. The extractants, di 2-ethyl hexyl phosphoric acid, (C8H17O)2PO(OH), HDEHP, and di[p-(1,1,3,3-tetra-methyl butyl) phenyl] phosphoric acid, [(C8H17)C6H4O]2PO(OH), HDOΦP, are monomeric in the alcohol diluent, forcing the extraction by a monomeric mechanism in the low concentration range, so that the extractant dependency is the same as the charge of the cation under study. (In contrast, the extractant dependency in corresponding systems employing hydrocarbon diluent in which these extractants are dimeric have been reported as 2·5 and 3·0 for Ca2+ and 3·0 for Th4+, the former dependencies being greater and the latter dependency less than the charge on the ion.) A simultaneous extraction with an extractant dependency equal to twice the charge of the cation is operative for the M2+ and M3+ cations studied. For Th(IV), this extraction is sixth-power rather than eight-power extractant dependent. A study of the variation of log K with Z, including all lanthanides(III) except Gd, for which a suitable radiochemical tracer was not available, revealed an old-even effect, the plot of log K vs. Z being best represented as separate odd-Z and even-Z curves for both HDEHP and HDOΦP.
Crospovidone interactions with water. I. Calorimetric study of the effect of Polyplasdone particle size on its uptake and distribution of water.

ABSTRACT The ability of crospovidone to take up and distribute water in the polymer samples was studied using differential scanning calorimetry (DSC). Polyplasdone® is an example of crospovidone that, although insoluble in water, serves as a superdisintegrant. Three samples of Polyplasdone® with different mean particle size were studied to see the effect of particle size on the water uptake and distribution characteristics. Water was shown to plasticize Polyplasdone® samples by a reduction in the glass transition temperature as the water content was increased. Although the particle sizes covered a wide range, there was essentially no difference in the ability to take up or distribute water. Three types of water were observed, namely water closely associated with the polymer, water built up as multilayers, and bulk water. Although the water closely associated with the polymer could not be detected by DSC, it could be calculated by mass balance and by extrapolation of the data to the x -axis in a plot of freezable water content as a function of the actual water content. A split in the melting endotherm of water that freezes supported the premise of two forms of freezable water. The number of water molecules per repeating unit could be calculated.
Genial tubercle advancement for obstructive sleep apnea syndrome: a modification of design.

Mandibular advancement in conjunction with genial tubercle advancement has gained the attention of surgeons involved in the treatment of obstructive sleep apnea syndrome. 1 The principle behind this technique involves the fact that mandibular advancement along with genial tubercle advancement pulls the geniohyoid and genioglossus muscles forward, causing a forward movement of the base of the tongue and the hyoid bone. This shift enlarges the posterior airway space and avoids the collapse of its walls during the rapid eye movement phase of sleep. 2 The genioglossus muscle originates from the superior mental spine or genial tubercles and then fans posteriorly to insert at the tip of the tongue, at the dorsum of the tongue, and into the body of the hyoid bone. The superior fibers retract the tip of the tongue, whereas the middle fibers depress the dorsum of the tongue. The inferior fibers advance the hyoid antero
Sole Sourcing, Competitive Sourcing, Parallel Sourcing: Mechanisms for Supplier Performance

Quality management practitioners in the USA such as W. Edwards Deming, strongly advocate the Japanese model of supplier relationships-recommending substantial specific investment in a single supplier for improved co-ordination and higher quality. But the strategy literature and conventional wisdom favor multiple sourcing, suggesting that a high level of specific investment in a sole source will lead to problems with supplier performance. Using agency theory, we construct a model to evaluate the tradeoff between the costs to set up and coordinate with suppliers and the incentive for performance provided by competition. We find that the validity of Deming's Point Four, that sole sourcing is more profitable than competitive sourcing, depends on parameters such as profit sensitivity to supplier performance.
Replication of euchromatin and heterochromatin in a mealybug

Asynchronous DNA replication of euchromatic (E) and heterochromatic (H) chromosomes and heterochromatic B chromosomes (B) were studied in the mealybug, Pseudococcus obscurus Essig (Homoptera: Coccoidea). The study was carried out on mycetocytes of adult females and on spermatocytes of mid-second instar males by employing tritiated thymidine labeling and autoradiography. In the mycetocytes the incorporation of the labeled thymidine began and ended later in the B's than in the E chromosomes. The S period was found to be about 21 hours. The DNA replication of the E chromosomes occupied about 86% of the S period and that of the B's 33%; during 18% of the mid-S period the replication of the two types of chromosomes overlapped. In the meiotic S period of the spermatocytes, the DNA of the E chromosomes started to replicate earlier than that of the H chromosomes and the B's, but the replication of the E chromosomes, the H chromosomes, and the B's overlapped. The H chromosomes completed their replication much later than the E chromosomes and slightly later than the B's.
Scanner hunter: understanding HTTP scanning traffic

This paper focuses on detecting and studying HTTP scanners, which are malicious entities that explore a website selectively for "opportunities" that can potentially be used for subsequent intrusion attempts. Interestingly, there is practically no prior work on the detection of these entities, which are different from web crawlers or machines performing network-level reconnaissance activities such as port scanning. Detecting HTTP scanners is challenging as they are stealthy and often only probe a few key places on a website, so finding them is a needle-in-the-haystack problem. At the same time, they pose serious risk because they perform the first, exploratory step to provide the seed information that may allow hackers to compromise a website. Our work makes two main contributions. First, we propose Scanner Hunter, arguably the first method to detect HTTP scanners efficiently. The novelty and success of the method lies in the use of community structure, in an appropriately constructed bipartite graph, in order to expose groups of HTTP scanners. The rationale is that the aggregated behavior makes identifying groups of scanners easier than attempting to profile and label IP addresses individually. Scanner Hunter achieves an impressive 96.5% detection precision, which is roughly twice as high as the precision of the Machine Learning-based methods that we use as reference. Second, we provide an extensive study of HTTP scanners in an effort to understand: (a) their spatial and temporal properties, (b) the techniques and tools used by the scanners, and (c) the types of resources they are looking for, which can provides hints as to what the subsequent penetration attempt may target. We use six months worth of web traffic logs collected in 2012 from a University campus, the websites hosted by which received over 1.9 billion requests from 12.8 million IPs. We found that the number of HTTP scanners is non-trivial with roughly 4,000 IPs engaging in this type of activity per week. Our work will hopefully raise the awareness of the community regarding this problem while at the same time provide a promising detection technique that can provide the basis for mitigating the risk posed by HTTP scanners.
Avatars to Mavatars: The Role of Marketing Avatars and Embodied Representations in Consumer Profiling

Recent trends in advertising and social media that include facial and body recognition technologies will change how people need to think about their digital representations and privacy and how managers can use these technologies to interact with customers. The term avatar is usually associated with a video game character or a pictorial representation on a social network and among other components of the definition of the concept is the notion that users control the avatar’s appearance and actions. Facial recognition and video analytic technologies being applied in public digital signage displays and on social networks like Facebook capture and create an embodied biometric database that is essentially an avatar-like profile that will be used for marketing products and supporting consumer applications. In this paper we discuss the nature of these new “marketing avatars,” which we call mavatars, and offer a framework for understanding where and how these embodied profiles are and will be used. We also discuss and speculate about how these representations and the applications they will spawn will evolve, where they will be used, and the ramifications of these embodied representations for consumers, managers, and society at large.
The effect of immigrants on natives' incomes through the use of capital.

Abstract This paper deals with questions about the effects of immigrants on three types of capital: the private capital immigrants work with, the public (government) capital that immigrant workers use, and the public capital used for services by immigrants. Private capital dilution is unimportant. The overall effect is an addition to the incomes of natives of a sum equal to perhaps 1% or 2% of the incomes of the immigrants for some number of years, small enough to ignore in this context. In the government sector, workers can be assumed to obtain all the returns to capital, and about 8% of immigrants work in this sector. Therefore, for productive capital taken altogether, we estimate that immigrants capture the returns from only 8% of the capital they work with, the government capital; the result is a loss of perhaps 2% of an immigrant family's income for one year, which is considerably smaller (being for only one year) than the above-mentioned gain to natives through the private capital that immigrants work with. The cost to natives of equipping an immigrant family with ‘demographic capital’ — schools, hospitals, and local roads — turns out to be much more important. This quantity depends upon the cost of such equipment, the proportion financed by bonds, the average length of life of the capital, and the average life of the bonds. We develop an estimating equation, and calculate that the cost to natives in 1975 dollars is $4172, about a fifth of a year's income for an average family. This is not insignificant in magnitude. But this amount — together with the effect through productive capital dilution discussed in the first part of the paper — is considerably smaller than the benefits of immigrants to natives through their relatively low use of welfare services and their relatively high contribution of taxes.
A basic program to compute statistical power for atypical values of alpha

Statistical power analysis is becoming an increasingly routine procedure when planning experiments and assessing the validity of tests of hypotheses following statistical analysis. For those situations where Type I error rate is not set to .10, .05, or .01 the task is impeded by the unavailability of tables for computation. A BASIC computer program is described that computes power for any combination of effect size, degrees of freedom for hypothesis, degrees of freedom for error. and a level. As a consequence of the algorithm an approximation to the critical value of the Bonferroni F-test is also computed.
All-Metal Antiaromatic Molecule: Rectangular Al44- in the Li3Al4- Anion

We report the experimental and theoretical characterization of antiaromaticity in an all-metal system, Li3Al4–, which we produced by laser vaporization and studied with the use of photoelectron spectroscopy and ab initio calculations. The most stable structure of Li3Al4– found theoretically contained a rectangular Al44– tetraanion stabilized by the three Li+ ions in a capped octahedral arrangement. Molecular orbital analyses reveal that the rectangular Al44– tetraanion has four π electrons, consistent with the 4n Huckel rule for antiaromaticity.
Altered regulation of extrinsic apoptosis pathway in HCV-infected HCC cells enhances susceptibility to mapatumumab-induced apoptosis.

Background: Hepatitis C virus (HCV)-infected patients, including those co-infected with human immunodeficiency virus (HIV), are at increased risk of developing hepatocellular carcinoma (HCC). We evaluated the ability of agonistic human monoclonal antibodies to tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptors, mapatumumab and lexatumumab, respectively, to induce TRAIL-receptor mediated apoptosis (TRMA) in HCC (HCV-infected and -uninfected) cells and in peripheral blood cells (HIV-infected and -uninfected). Methods: Susceptibility to antibody-mediated TRMA was measured by caspase 3/7 activity and by confocal microscopy. Surface expression of receptors on HCV-uninfected and -infected Huh7.5 cells was measured by flow cytometry and confocal microscopy. Inhibitor of Apoptosis Protein (IAP) RNA levels were quantified by RT-PCR. DNA Microarray was performed using RNA isolated from Huh7.5 cells (HCV-infected and uninfected) using Affymetrix U133A chips. Results: Mapatumumab preferentially induces TRMA of HCV-infected Huh7.5 cells by binding to TRAIL-R1. Higher basal expression of TRAIL-R2 compared to that of TRAIL-R1 on HCV-uninfected Huh7.5 cells were observed. Lexatumumab induces TRMA of both HCV-infected and -uninfected cells by binding to TRAIL-R2. IFN-α has minimal effect on mapatumumab- and lexatumumab-induced TRMA. HCV infection of Huh7.5 cells up-regulates TRAIL-R1 expression and X-linked Inhibitor of apoptosis protein and survivin gene expression. Neither antibody had a pro-apoptotic effect on PBMCs from patients with HIV infection ex vivo. Conclusion: Both mapatumumab and lexatumumab are excellent candidates for therapy of HCC. HCV infection of Huh7.5 cells selectively up-regulates TRAIL-R1 receptor, associated with increased susceptibility to mapatumumab-mediated TRMA. HCV infection up-regulated IAP genes, offering promise for future combination therapy using TRAIL agonists and IAP inhibitors.
A variant of the myosin light chain kinase gene is associated with severe asthma in African Americans.

Asthma is a complex phenotype influenced by environmental and genetic factors for which severe irreversible structural airway alterations are more frequently observed in African Americans. In addition to a multitude of factors contributing to its pathobiology, increased amounts of myosin light chain kinase (MLCK), the central regulator of cellular contraction, have been found in airway smooth muscle from asthmatics. The gene encoding MLCK (MYLK) is located in 3q21.1, a region noted by a number of genome-wide studies to show linkage with asthma and asthma-related phenotypes. We studied 17 MYLK genetic variants in European and African Americans with asthma and severe asthma and identified a single non-synonymous polymorphism (Pro147Ser) that was almost entirely restricted to African populations and which was associated with severe asthma in African Americans. These results remained highly significant after adjusting for proportions of ancestry estimated using 30 unlinked microsatellites (adjusted odds ratio: 1.76 [95% confidence interval, CI: 1.17–2.65], p = 0.005). Since all common HapMap polymorphisms in ∼500 kb contiguous regions have low-to-moderate linkage disequilibrium with Pro147Ser, we speculate that this polymorphism is causally related to the severe asthma phenotype in African Americans. The association of this polymorphism, located in the N-terminal region of the non-muscle MLCK isoform, emphasizes the potential importance of the vascular endothelium, a tissue in which MLCK is centrally involved in multiple aspects of the inflammatory response, in the pathogenesis of severe asthma. This finding also offers a possible genetic explanation for some of the more severe asthma phenotype observed in African American asthmatics. Genet Epidemiol 2007. © 2007 Wiley-Liss, Inc.
The protective effect of OP-1 on articular cartilage in the development of osteoarthritis

Summary Objective The purpose of this study was to determine whether osteogenic protein 1 (OP-1) would protect articular cartilage from degeneration during the development of osteoarthritis (OA) in the rabbit anterior cruciate ligament transection (ACLT) model. Previous studies have shown that OP-1 is vital to cartilage matrix integrity and repair, stimulates synthesis of cartilage matrix components, proteoglycans, and collagen, and has a protective effect against catabolic mediators like matrix metalloproteinases and interleukin-1. Methods The rabbit ACLT model was used in which the anterior cruciate ligament was transected leading to OA. OP-1 was delivered to the joint surgically for approximately 6 weeks by implantation of an Alzet osmotic pump into the medial thigh with a catheter threaded from the pump into the knee joint. Forty rabbits (20 control and 20 experimental) had the ACLT surgery and implantation of the pump performed simultaneously. They were sacrificed after 9 weeks for analysis. The OA was graded using the Outerbridge classification with India Ink staining. Histological staining and histomorphometry with Hematoxylin & Eosin and Safranin O were performed to analyze OA progression and semi-quantitative polymerase chain reaction (PCR) was performed for anabolic and catabolic genes. Results The experimental group had an average Outerbridge score of 1.8 vs 2.5 for the controls ( P P Conclusions OP-1 may have a potential benefit in protecting articular cartilage during the development of OA.
High Field Transport in a-Si:H

Electric field dependent DC-dark and transient photoconductivity data measured over a broad temperature (10 K≤T≤300 K) and field regime (102V/cm≤F≤6×105V/cm) in phosphorus and boron doped and intrinsic amorphous hydrogenated silicon (a-Si:H) are described. The data demonstrate the strong influence of the electric field on carrier propagation. Enhancements over 6 orders of magnitude in conductivity (σ) are achieved for fields greater than 105V/cm, which changes a-Si:H films from highly insulating to very conductive at low temperatures. The field dependence is described empirically by a power law a~Fy with y in the range 10≤y≤17. The enhancement and y depend on doping level with significant differences between electron and hole currents. These results are confirmed by transient photoconductivity experiments on intrinsic a-Si:H from which the carrier mobility (μD) and the μτ-product are deduced. The drift mobility is enhanced by many orders of magnitude up to values of μD>10−2cm2/Vs and is identified as parameter which dominates high field transport. The increase in mobility is comparable to the increase in conductivity and shows a time- and thickness dependence indicative of dispersive transport. The data is interpreted introducing a field-enhanced nearest neighbor hopping model which is governed by ballistic capture and field induced re-emission.
α1-Antitrypsin deficiency · 5: Intravenous augmentation therapy: current understanding

The biochemical and clinical efficacy of intravenous augmentation therapy in alpha(1)-antitrypsin deficiency is reviewed, adverse events experienced with this treatment are considered, and its cost effectiveness is discussed.
A social network of hospital acquired infection built from electronic medical record data.

Objective Social networks have been used in the study of outbreaks of infectious diseases, including in small group settings such as individual hospitals. Collecting the data needed to create such networks, however, can be time consuming, costly, and error prone. We sought to create a social network of hospital inpatients using electronic medical record (EMR) data already collected for other purposes, for use in simulating outbreaks of nosocomial infections. Materials and methods We used the EMR data warehouse of a tertiary academic hospital to model contact among inpatients. Patient-to-patient contact due to shared rooms was inferred from admission-discharge-transfer data, and contact with healthcare workers was inferred from clinical documents. Contacts were used to generate a social network, which was then used to conduct probabilistic simulations of nosocomial outbreaks of methicillin-resistant Staphylococcus aureus and influenza. Results Simulations of infection transmission across the network reflected the staffing and patient flow practices of the hospital. Simulations modeling patient isolation, increased hand hygiene, and staff vaccination showed a decrease in the spread of infection. Discussion We developed a method of generating a social network of hospital inpatients from EMR data. This method allows the derivation of networks that reflect the local hospital environment, obviate the need for simulated or manually collected data, and can be updated in near real time. Conclusions Inpatient social networks represent a novel secondary use of EMR data, and can be used to simulate nosocomial infections. Future work should focus on prospective validation of the simulations, and adapting such networks to other tasks.
Computing illumination-invariant descriptors of spatially filtered color image regions

Spatial filters provide a useful and efficient means of analyzing an input color image into components that capture different spatial properties. Representations based on spatial filtering have restricted usefulness for recognition, however, because the output of a spatial filter across an image depends on the scene illumination conditions. We use a physically accurate linear model for spectral reflectance to derive invariants of distributions in spatially filtered color images that do not depend on the scene illumination. These invariants can be used for the illumination-invariant recognition of regions following an arbitrary linear filtering operation. We describe a method for illumination correction based on color distributions and introduce an illumination change consistency constraint that is useful for verifying matches obtained using the invariants. We show, using a set of classification experiments, that the filtered distribution invariants can significantly improve the capability of a recognition system in environments where illumination cannot be controlled.
The record of Middle Jurassic volcanism in the Carmel and Temple Cap Formations of southwestern Utah

Altered volcanic ash beds in the Middle Jurassic Temple Cap and Carmel Formations in southwestern Utah record a pulse of active arc-related volcanism between 166 and 171 Ma. A second pulse between 148 and 155 Ma has previously been documented in the Upper Jurassic Morrison Formation. Volcanic and volcaniclastic rocks of these same ages have also been identified closer to or within the arc in California in the Inyo Mountains, the Cowhole Mountains, the Palen Mountains, and the central Mojave Desert. The upper part of the volcaniclastic Mount Wrightson Formation and the strata of Cobre Ridge in southern Arizona are ca. 170 Ma in age and appear to be time correlative with the Middle Jurassic formations in southwestern Utah. The altered ash beds found in the Temple Cap and Carmel Formations typically contain phenocrysts of sanidine, quartz, biotite, apatite, zircon, and titanite. Plagioclase was likely present originally in all of the ashes, but was removed by alteration and is now found only in the Temple Cap red beds. Quartz and sanidine are absent in two crystal-poor ash beds that contain two pyroxenes, hornblende, and biotite. Although major and trace element concentrations in the ash beds have been substantially modified, compositions of relict phenocrysts reveal that the magmas were calc-alkaline rhyolites to andesites. Two-pyroxene, two-feldspar, biotite, and biotite-apatite thermometers suggest that crystallization occurred at temperatures ranging from 740 to 910 8C. Hornblende geobarometry yields pressures of 1‐2 kilobars for the two ash beds that contain the appropriate buffer assemblage. The mafic silicates all have moderately high Mg/Fe ratios. This fact, combined with the presence of hornblende, biotite, and titanite, suggests that the phenocrysts crystallized at high oxygen fugacities similar to those of the granites of the batholiths of California. The ash probably erupted from a low-lying arc cut by strikeslip faults in what is now southern California and western Nevada. Major Jurassic unconformities occur near or within the ash-bearing formations in southwestern Utah. Laser-fusion singlecrystal 40 Ar/ 39 Ar measurements have defined the ages of the unconformities and the associated volcanism. The age of the J-1 unconformity, found at the base of the Temple Cap Formation in southwestern Utah, is older than ca. 170.5 Ma. The J-2 unconformity, which lies between the Temple Cap and Carmel Formations, formed between ca. 169 and 168 Ma. The origin of these unconformities is still unclear, but may be related to the Middle Jurassic pulse of magmatism and the oblique plate convergence along the western margin of North America. The age range of ash beds in the Carmel Formation between 166.3 and 168.0 6 ;0.5 Ma is consistent with a Bajocian-Bathonian boundary of ca. 166 Ma.
Infection of endothelial cells with Anaplasma marginale and A. phagocytophilum

Anaplasma marginale and A. phagocytophilum are obligate intracellular, tick-borne pathogens that target erythrocytes and neutrophil granulocytes, respectively. Because ticks do not directly tap blood vessels, an intermediate tissue may mediate infection of blood cells. We considered that vascular endothelium interacts with circulating blood cells in vivo, and could be involved in pathogenesis and dissemination of the organisms. We used light and electron microscopy and immune labeling to show that A. phagocytophilum invaded rhesus (RF/6A), human (HMEC-1, MVEC), as well as bovine (BCE C/D-1b) endothelial cell lines, whereas A. marginale infected rhesus and bovine endothelial cells. A. marginale formed large intracellular inclusions that appeared smooth and solid at first, and subsequently coalesced into discrete granules. A. phagocytophilum formed numerous smaller inclusions in each cell. Within 1-3 weeks, the monolayers were destroyed, and lysed cultures were diluted onto fresh monolayers. Electron microscopy demonstrated uneven distribution of A. marginale inside large inclusions, with reticulated forms grouped more tightly than denser cells, whereas in A. phagocytophilum individual organisms appeared more evenly spaced. Specific polyclonal and monoclonal antibodies both labeled A. marginale and A. phagocytophilum in endothelial cells, and oligonucleotide primers complimentary to either A. marginale or A. phagocytophilum amplified their expected target from these cultures. In conclusion, we demonstrate that relevant microvascular endothelium is susceptible to anaplasmas in vitro and may present a link that could explain development of the immune response and persistent infection.
Paraneoplastic syndromes of the spinal cord, nerve, and muscle.

Cancer can affect the peripheral nervous system by non-metastatic, sometimes immune-mediated mechanisms. Recognition of these paraneoplastic syndromes is important because it can lead to the detection of the tumor, and also helps to avoid unnecessary studies to determine the cause of the neurologic symptoms in patients with cancer. Many paraneoplastic syndromes of the peripheral nervous system are not associated with serum antibodies that serve as markers of paraneoplasia. For this group of disorders the diagnosis depends on the clinician's index of suspicion and conventional electrophysiologic and laboratory tests. Treatment of the tumor, immunotherapy, or both may improve some of these syndromes. This review focuses on paraneoplastic syndromes of the spinal cord, peripheral nerve, and muscle.
Postural and gait stability of a planar five link biped by simulation

Postural and gait stability of a planar five-link model of a biped is considered. Equations of motion, in which external torques appear explicitly are derived by d'Alembert's principle. Postural stability is achieved at arbitrary equilibrium points by open and closed loop torques in order to create the equilibrium point and to make the equilibrium point stable. Television recording of angles and angle rates of all five segments of a human in normal walk is taken and used as reference input to the system in order to generate the open and closed loop torques needed for locomotion. It is shown that one equilibrium point and one set of constant feedback gains suffice. It is also demonstrated that this method can be utilized to compute the forces at the joints and the components of the applied torques as functions of the state of the system. Simulations results of the nonlinear system with linear feedback and added disturbances are presented. The two main applications of this work are in the design of powered prostheses for the handicapped and, more importantly, in nondestructive testing to estimate feedback gains utilized by human beings in standing and in walking.
Polyethylene Glycol (PEG)-induced Mouse Model of Choroidal Neovascularization

In this study, we describe a new method for inducing choroidal neovascularization (CNV) in C57BL/6 mice, an animal model of wet age-related macular degeneration (AMD). AMD is a disease that causes central blindness in humans. We injected PEG-8 subretinally in different doses (0.125–2 mg) to induce CNV. After PEG-8 injection, we examined CNV at several time points (days 3–42). We also used Western blotting, immunohistochemistry, and ELISA to examine the complement component C3 split products, C9, VEGF, TGF-β2, and basic FGF. As early as day 1 after treatment, we found that a single subretinal injection of 1 mg of PEG-8 increased the C3 split products and the C9, TGF-β2, and basic FGF levels in the retinal pigment epithelium-choroid tissue. By day 3 after PEG-8 injection, the intraocular activation of the complement system caused induction and progression of CNV, including new vessels penetrating the Bruch's membrane. At day 5 after PEG-8 injection, we observed a fully developed CNV and retinal degeneration. Thus, in this study, we present a new, inexpensive, and accelerated mouse model of CNV that may be useful to study AMD.