cssi/SciSciGPT-SciSciNet huggingface dataset:
Host matrix metalloproteinase-9 contributes to tumor vascularization without affecting tumor growth in a model of prostate cancer bone metastasis

Matrix metalloproteinases (MMPs) have been associated with initiation, progression and vascularization of a number of tumors. However, clinical trials using MMP inhibitors failed to meet expectations. Previously, we demonstrated the potential importance of MMP-9 activity in experimental prostate cancer bone tumor tissue. However, the particular roles of host- and tumor-derived MMP-9 remains to be defined. Herein, we examined the role of host MMP-9 in subcutaneous and intraosseous growth of the human androgen independent prostate cancer cell line PC3 in MMP-9 deficient mice. In the subcutaneous model, the tumor incidence in the control (RAG-1 ko/ko ) and experimental (RAG-1 ko/ko /MMP-9 ko/ko ) group was 100%, with similar tumor growth kinetics and microvascular densities. In the intraosseous tumor model, the tumor incidence was higher in RAG-1 ko/ko /MMP-9 ko/ko mice than in RAG-1 ko/ko mice (67% and 39%, respectively), though no statistical differences were found. The intraosseous tumor areas were similar in both groups, and the number of tumor-associated osteoclasts did not differ significantly. However, the microvascular density of intraosseous tumors was higher in RAG-1 ko/ko than in RAG-1 ko/ko /MMP-9 ko/ko mice, though no changes in tumor growth could be detected. In an in vitro assay, we found that bone marrow (BM) cells increased the invasiveness of PC3 cells, and that this enhancement was independent of MMP-9 expression by marrow cells. Our results with the RAG-1 model suggest that host-derived MMP-9 is neither necessary nor sufficient for subcutaneous or intraosseous PC3 tumor growth, osteoclastic response, or in vitro invasiveness of tumor cells.
Using phage display selected antibodies to dissect microbiomes for complete de novo genome sequencing of low abundance microbes

Single cell genomics has revolutionized microbial sequencing, but complete coverage of genomes in complex microbiomes is imperfect due to enormous variation in organismal abundance and amplification bias. Empirical methods that complement rapidly improving bioinformatic tools will improve characterization of microbiomes and facilitate better genome coverage for low abundance microbes. We describe a new approach to sequencing individual species from microbiomes that combines antibody phage display against intact bacteria with fluorescence activated cell sorting (FACS). Single chain (scFv) antibodies are selected using phage display against a bacteria or microbial community, resulting in species-specific antibodies that can be used in FACS for relative quantification of an organism in a community, as well as enrichment or depletion prior to genome sequencing. We selected antibodies against Lactobacillus acidophilus and demonstrate a FACS-based approach for identification and enrichment of the organism from both laboratory-cultured and commercially derived bacterial mixtures. The ability to selectively enrich for L. acidophilus when it is present at a very low abundance ( 99.8%) de novo genome coverage whereas the standard single-cell sequencing approach is incomplete (<68%). We show that specific antibodies can be selected against L. acidophilus when the monoculture is used as antigen as well as when a community of 10 closely related species is used demonstrating that in principal antibodies can be generated against individual organisms within microbial communities. The approach presented here demonstrates that phage-selected antibodies against bacteria enable identification, enrichment of rare species, and depletion of abundant organisms making it tractable to virtually any microbe or microbial community. Combining antibody specificity with FACS provides a new approach for characterizing and manipulating microbial communities prior to genome sequencing.
The effects of self-instruction on writing deficiencies

Children with writing deficiencies were taught to print using either self-instructional or direct training. Social reinforcement was given contingent upon correct writing in both conditions. A third no-treatment control was included to assess the role of reinforced practice. Self-instruction proved superior to direct training while both treatments proved superior to no-treatment. A generalization test revealed no differences between any of the three groups. Reliable data were presented to indicate that subjects did in fact self-instruct but that self-instructing was not correlated with correct letter copying. Serious practical difficulties arose in the application of self-instruction, including difficulty in shaping verbalizations and the cumbersomeness of the procedure. It was concluded that self-instruction, while statistically effective, may be impractical for routine use at the present time.
Molecular Mechanism of Photoactivation and Structural Location of the Cyanobacterial Orange Carotenoid Protein

The orange carotenoid protein (OCP) plays a photoprotective role in cyanobacterial photosynthesis similar to that of nonphotochemical quenching in higher plants. Under high-light conditions, the OCP binds to the phycobilisome (PBS) and reduces the extent of transfer of energy to the photosystems. The protective cycle starts from a light-induced activation of the OCP. Detailed information about the molecular mechanism of this process as well as the subsequent recruitment of the active OCP to the phycobilisome are not known. We report here our investigation on the OCP photoactivation from the cyanobacterium Synechocystis sp. PCC 6803 by using a combination of native electrospray mass spectrometry (MS) and protein cross-linking. We demonstrate that native MS can capture the OCP with its intact pigment and further reveal that the OCP undergoes a dimer-to-monomer transition upon light illumination. The reversion of the activated form of the OCP to the inactive, dark form was also observed by using native MS. F...
Computer Implication and the Curry Paradox

There are theoretical limitations to what can be implemented by a computer program. In this paper we are concerned with a limitation on the strength of computer implemented deduction. We use a version of the Curry paradox to arrive at this limitation.
Mining millions of metaphors

One of the first decisions made in any research concerns the selection of an appropriate scale of analysis-are we looking out into the heavens, or down into atoms? To conceive a digital library as a collection of a million books may restrict analysis to only one level of granularity. In this article, we examine the consequences and opportunities resulting from a shift in scale, where the desired unit of interpretation is something smaller than a text: it is a keyword, a motif, or a metaphor. A million books distilled into a billion meaningful components become raw material for a history of language, literature, and thought that has never before been possible. While books herded into genres and organized by period remain irregular, idiosyncratic, and meaningful in only the most shifting and context-dependent ways, keywords or metaphors are lowest common denominators. At the semantic level-the level of words, images, and metaphors-long-term regularity and patterns emerge in collection, analysis, and taxonomy. This article follows the foregoing course of thought through three stages: first, the manual curation of a high quality database of metaphors; second, the expansion of this database through automated and human-assisted techniques; finally, the description of future experiments and opportunities for the application of machine learning, data mining, and natural language processing techniques to help find patterns and meaning concealed at this important level of granularity.
Strength of Signal through BCR Determines the Fate of Cycling B Cells by Regulating the Expression of the Bcl-2 Family of Survival Proteins

Abstract Cycling, splenic B cells were recultured with: (1) no stimulant to reflect poorly competitive clones; (2) soluble, whole anti-μ to reflect clones that bind soluble immune complexes; (3) soluble F(ab′) 2 anti-μ to reflect clones that bind soluble antigen; and (4) immobilized anti-μ to reflect clones that bind antigen presented by FDC. All four groups displayed similar levels of the death proteins Bax and Bcl-x S . In contrast, cycling B cells restimulated with either soluble F(ab′) 2 or immobilized anti-μ expressed heightened levels of the survival protein Bcl-x L , and only cells restimulated with immobilized anti-μ expressed the survival protein Bcl-2. Cycling B cells restimulated with either soluble F(ab′) 2 or immobilized anti-μ displayed a selective survival advantage over cycling B cells receiving no stimulus or soluble, whole anti-μ by both enhancing their responsiveness to CD40 ligand, a Th-cell-derived signal, and increasing the period that the cycling B cells remained responsive to this Th-cell-derived signal. The Th-cell-derived signal did not appreciably alter cycling B cell expression of Bcl-2 family members.
A study of the influence of electron beam on electrical characteristics of LOCOS device

Electrical characteristic changes in scaled MOSFET devices have been widely reported due to electron beam (EB) irradiation. For local oxidation of silicon (LOCOS) devices, the effects of EB-induced damage when performing measurements using an SEM based nanoproer, however, have rarely been reported. EB penetration into the dielectrics, resulting in the modification of the physical properties of the dielectric layer, could be a concern, not only for scaled devices, but also for LOCOS devices. This study reveals that the effect of EB on LOCOS devices can be measured using a scanning electron microscope (SEM) based nanoprober with inducing electrical characteristic changes. These changes are accounted for by the hole trapping at the birdsbeak, which has a significant effect on both the junction electrical characteristics and punchthrough characteristics in LOCOS isolation structures when an SEM is employed for probe guidance. Further, some preliminary experimental results, not included in this paper, show that lowering the EB acceleration voltage is found to not be able to significantly eliminate the effects of EB-induced damage during device inspections in failure analysis procedures. More advanced studies are currently under investigation.
COMPARATIVE TOXICITY OF OIL, DISPERSANT, AND DISPERSED OIL TO TEXAS MARINE SPECIES

ABSTRACT Dispersants are one class of chemical response agents currently approved for use on offshore oil spills. However, questions persist regarding potential environmental risks of nearshore dispersant applications. To address these questions, the relative toxicity of weathered crude oil, dispersant, and weathered crude oil plus dispersant were compared. This study included one luminescent marine bacteria (Vibrio fisheri), two marine vertebrate (Cyprinodon variegatus and Menidia beryllina), and one invertebrate test species (Mysidopsis bahia). Both the vertebrate and invertebrate species were tested under spiked (short episodic) exposure regimes and 96-hour continuous exposure regimes using protocols developed by the Chemical Response to Oil Spills: Ecological Effects Research Forum (CROSERF) and U.S. Environmental Protection Agency (EPA), respectively. Toxicity to the marine bacteria was evaluated after a 15-minute exposure using the Microbics Microtox® system. Results showed no significant variance b...
Early life-stage toxicity test methods for gulf toadfish (Opsanus beta) and results using chlorpyrifos

Gulf toadfish (Opsanus beta) were continuously exposed as embryos, sac fry, and juveniles to technical chlorpyrifos in two 49-day early life-stage toxicity tests. Survival was significantly (alpha = 0.05) reduced only in 150 micrograms/liter. However, toadfish exposed to chlorpyrifos concentrations from 3.7 to 150 micrograms/liter weighted significantly less than control fish: 9% lower in 3.7 micrograms/liter to 62% lower in 150 micrograms/liter. The 96-hr LC50 for juvenile fish was 520 micrograms/liter. Concentrations of chlorpyrifos in toadfish and bioconcentration factors increased with increasing exposure concentration, a condition not generally observed with other marine fishes and other test chemicals. These results demonstrated the procedures for, and the practicality of, early life-stage tests with this marine species. We recommend the use of the gulf toadfish for comparative toxicity testing and for evaluating the toxicity of substances in conjunction with ontogenetical, physiological, and histological investigations of this considerably studied genus. We do not recommend it for routine effects testing.
Surface Characterization Of Cold-Rolled Steel By Grazing-Angle Reflection-Absorption FT-IR Spectroscopy

Residues from the oil-in-water emulsions used in the cold-rolling of steel are responsible in large part for an undesirable film of contamination sometimes found on the steel surface, even after the annealing stage. This contamination can have significant effects on the adhesion and corrosion resistance of paint coatings subsequently applied to the surface. The object of the work reported here was to determine the potential of grazing-angle reflection-absorption FT-IR spectroscopy for qualitative and quantitative analysis of the residues left on the surface.
Exercise and Physical Health: Cancer and Immune Function

Over the last decade, there has been accumulating epidemiological data suggesting that exercise may decrease the risk of cancer, particularly colon cancer. However, exercise appears unrelated to rectal cancer risk. With regard to other cancers, because physical activity can alter levels of reproductive hormones, investigators have hypothesized that active individuals should experience decreased incidence of breast or prostate cancer. The better conducted studies suggest that exercise may reduce the risk of developing breast cancer. However, the epidemiological data on prostate cancer have been inconsistent. Meanwhile, data on other site-specific cancers have been sparse. An exciting and emerging body of research has suggested that exercise, at least in moderate amounts, can enhance the human immune system. Theoretically, then, this provides a further biological basis for expecting an inverse relationship between physical activity and cancer risk. However, the changes seen in immune function tend to be transient in nature; thus, the physiological significance with respect to cancer development is uncertain. Preliminary data also suggest that exercise may be beneficial for cancer patients by improving the quality of life and enhancing immune function. Although promising, this needs more careful research. Again, it is unclear whether the enhanced immune function is of any clinical significance in retarding the spread of cancer that has already developed. Finally, with regard to URTIs, moderate exercise appears to decrease the risk of this infection, although high-endurance exercise may increase the risk. This finding parallels the changes seen in the immune system in response to exercise and comes as no surprise, as the immune system also regulates susceptibility to infections.
Binding of Destabilized βB2-Crystallin Mutants to α-Crystallin: THE ROLE OF A FOLDING INTERMEDIATE

Age-related changes in protein-protein interactions in the lens play a critical role in the temporal evolution of its optical properties. In the relatively non-regenerating environment of the fiber cells, a critical determinant of these interactions is partial or global unfolding as a consequence of post-translational modifications or chemical damage to individual crystallins. One type of attractive force involves the recognition by α-crystallins of modified proteins prone to unfolding and aggregation. In this paper, we explore the energetic threshold and the structural determinants for the formation of a stable complex between α-crystallin and βB2-crystallin as a consequence of destabilizing mutations in the latter. The mutations were designed in the framework of a folding model that proposes the equilibrium population of a monomeric intermediate. Binding to α-crystallin is detected through changes in the emission properties of a bimane fluorescent probe site-specifically introduced at a solvent exposed site in βB2-crystallin. α-Crystallin binds the various βB2-crystallin mutants, although with a significantly lower affinity relative to destabilized T4 lysozyme mutants. The extent of binding, while reflective of the overall destabilization, is determined by the dynamic population of a folding intermediate. The existence of the intermediate is inferred from the biphasic bimane emission unfolding curve of a mutant designed to disrupt interactions at the dimer interface. The results of this paper are consistent with a model in which the interaction of α-crystallins with substrates is not solely triggered by an energetic threshold but also by the population of excited states even under favorable folding conditions. The ability of α-crystallin to detect subtle changes in the population of βB2-crystallin excited states supports a central role for this chaperone in delaying aggregation and scattering in the lens.
Prospective evaluation of adjunctive ketamine on sphincter of Oddi motility in humans.

Background and Aim: Performance of sphincter of Oddi manometry (SOM) at endoscopic retrograde cholangio-pancreatogram (ERCP) is technically demanding and requires that the patient be well sedated. Droperidol is used as an adjunctive agent in patients who are difficult to sedate. Concerns regarding the safety profile of droperidol and its effects on sphincter of Oddi motility has resulted in the search for other potent sedative agents that do not influence SOM readings. Ketamine, a dissociative anesthetic, is increasingly being used as an adjunctive agent for conscious sedation. This study evaluates the effect of ketamine on sphincter of Oddi motility when used as an adjunctive sedative agent during ERCP. Patients and Methods: This is a prospective study of 30 consecutive patients undergoing SOM who were difficult to sedate and required adjunctive ketamine. Manometry was initially performed with intravenous administration of diazepam plus meperidine or a combination of diazepam plus meperidine and midazolam. After the initial two pull-throughs, 20 mg of ketamine was administered intravenously and the measurements were repeated 5 min later. Results: The basal pressures of the biliary sphincter and of the pancreatic sphincter were not significantly altered by ketamine. By using a definition for sphincter of Oddi dysfunction of a basal pressure ≥40 mmHg, concordance (normal vs abnormal) between the basal sphincter pressure before and after ketamine was seen in 28 patients (93%). Ketamine also did not lead to a difference in phasic wave amplitude, duration, or frequency. No complication was associated with ketamine use. Conclusions: Ketamine at 20 mg did not significantly affect SOM parameters. Further studies are required to confirm our preliminary findings before ketamine can be added to the armamentarium of agents used for performance of sphincter of Oddi manometry.
On solving boundary value problems for multi-scale systems using asymptotic approximations and multiple-shooting

This paper describes a method for obtaining the numerical solution of certain singularly perturbed boundary value problems for linear systems of ordinary differential equations whose solutions involve dynamics with multiple time scales. A technique to decouple different time scales using a Riccati transformation is presented. For the slow modes, which provide smooth solutions, regular perturbation expansion and multiple shooting strategies are combined. Fast modes, which are assumed to be significant only in endpoint layers, are computed after appropriate stretchings have been made in the system. Advantages of this approach include adaptability, flexible use of output points, and automatic determination of layer thicknesses.
IGM is required for efficient complement mediated phagocytosis of apoptotic cells in vivo

A variety of complement components have been detected on apoptotic cells and proposed to facilitate recognition and/or ingestion by phagocytes. The triggers for complement activation remain uncertain. To determine the role of IgM in classical pathway activation and clearance of apoptotic cells in vitro and in vivo, we quantified these parameters in mice deficient in serum IgM (sIgM). Phagocytosis by bone marrow-derived macrophages of apoptotic cells incubated with serum deficient in sIgM was markedly reduced, similar to apoptotic cells incubated with C1q deficient serum in vitro. Similarly, intraperitoneal clearance of apoptotic cells and cellular C3 deposition were significantly reduced in mice deficient in sIgM compared to wild-type mice. Clearance and C3 deposition were reconstituted by addback of IgM. In mice deficient in both sIgM and Clq, addback of both serum factors was required for restoration of clearance. These findings indicate that, on a quantitative basis, sIgM is a potent factor required for intraperitoneal phagocytosis of apoptotic cells, and further demonstrate that IgM and C1q work in concert to activate complement, resulting in C3 deposition on the apoptotic cell surface and ultimately, efficient clearance of the apoptotic cell by macrophages.
Tumor Necrosis Factor-α Decreases Insulin-Like Growth Factor-I Messenger Ribonucleic Acid Expression in C2C12 Myoblasts via a Jun N-Terminal Kinase Pathway

IGF-I is a major anabolic hormone for skeletal muscle in vivo. Yet the mechanisms by which GH and cytokines regulate IGF-I expression remain obscure. Lipopolysaccharide (LPS) dramatically alters the circulating concentration of both TNF alpha and IGF-I, and TNF alpha in part mediates the cachectic activity of LPS. Little is known about the local synthesis of IGF-I and TNF alpha in skeletal muscle per se. The purpose of the present study was to determine whether LPS alters the expression of TNF alpha and IGF-I in mouse skeletal muscle and whether TNF alpha directly inhibits IGF-I mRNA expression in C2C12 myoblasts. Intraperitoneal injection of LPS in C3H/SnJ mice increased the expression of TNF alpha protein in plasma (16-fold) and TNF alpha mRNA in skeletal muscle (8-fold). LPS also decreased the plasma concentration of IGF-I (30%) and IGF-I mRNA in skeletal muscle (50%, between 6 and 18 h after LPS administration). Addition of LPS or TNF alpha directly to C2C12 myoblasts decreased IGF-I mRNA by 50-80%. The TNF alpha-induced decrease in IGF-I mRNA was both dose and time dependent and occurred in both myoblasts and differentiated myotubes. TNF alpha selectively decreased IGF-I but not IGF-II mRNA levels, and the effect of TNF alpha was blocked by a specific TNF-binding protein. TNF alpha did not alter IGF-I mRNA levels in the presence of the protein synthesis inhibitor cycloheximide. TNF alpha did not change the half-life of IGF-I mRNA. TNF alpha completely prevented GH-inducible IGF-I mRNA expression, but this GH resistance was not attributable to impairment in signal transducer and activator of transcription-3 or -5 phosphorylation. TNF alpha increased both nitric oxide synthase-II mRNA and protein, and the nitric oxide donor sodium nitroprusside decreased IGF-I mRNA levels in C2C12 cells. Yet inhibitor studies indicate that nitric oxide did not mediate the effect of TNF alpha on IGF-I mRNA expression. TNF alpha stimulated the phosphorylation of c-Jun and specific inhibition of the Jun N-terminal kinase pathway, but not other MAPK pathways, completely prevented the TNF alpha-induced drop in IGF-I mRNA. These data suggest that LPS stimulates TNF alpha expression in mouse skeletal muscle and autocrine-derived cytokines may contribute to the reduced expression of IGF-I in this tissue.
Ionic conductivity in wide-range halide-pyrophosphate glasses

Abstract Recently we have reported the existence of fast ionic conduction in silver halide-rich all-halide glasses. In the present paper we report glass formation from x = 0.08−1.0 in a pseudobinary halide-pyrophosphate system x(AgCl) 0.64 (CsI) 0.36 + (1− x )( Ag 2 PO 3.5 ) and study the composition dependence of the conductivity. Glass transition temperatures and activation energies for d.c. conductivity increases smoothly as the pyrophosphate concentration increases, while the conductivity correspondingly decreases. The frequency dependence of the conduction process has been analysed. The conductivity relaxation process becomes increasingly non-exponential as the conductivity at some fixed temperature (eg. 298 K) increases.
Source distribution of ocean microseisms and implications for time-dependent noise tomography

Abstract A qualitative analysis of ocean microseism source distribution observed in North America during fall and winter months was carried out. I review the theory of the origin of ocean microseisms and show that it can be used in conjunction with wave-wave interaction maps to quantify the source distribution anisotropy. It is demonstrated that microseisms generation in the North Atlantic and in the North Pacific Oceans are inherently different. North Atlantic microseisms are generated predominantly in the deep ocean, while North Pacific microseisms are dominated by coastal reflections. In spite of these differences both result from repeated ocean wave patterns that give rise to an anisotropic noise pattern, which cannot be randomized by time averaging. Considering time-varying ambient noise imaging, which aims to resolve a fraction of a percent changes in the crust over short distances, the source anisotropy would introduce a relatively significant error that needs to be accounted for.
Spatial working memory for locations specified by vision and audition: Testing the amodality hypothesis

Spatial working memory can maintain representations from vision, hearing, and touch, representations referred to here as spatial images. The present experiment addressed whether spatial images from vision and hearing that are simultaneously present within working memory retain modality-specific tags or are amodal. Observers were presented with short sequences of targets varying in angular direction, with the targets in a given sequence being all auditory, all visual, or a sequential mixture of the two. On two thirds of the trials, one of the locations was repeated, and observers had to respond as quickly as possible when detecting this repetition. Ancillary detection and localization tasks confirmed that the visual and auditory targets were perceptually comparable. Response latencies in the working memory task showed small but reliable costs in performance on trials involving a sequential mixture of auditory and visual targets, as compared with trials of pure vision or pure audition. These deficits were statistically reliable only for trials on which the modalities of the matching location switched from the penultimate to the final target in the sequence, indicating a switching cost. The switching cost for the pair in immediate succession means that the spatial images representing the target locations retain features of the visual or auditory representations from which they were derived. However, there was no reliable evidence of a performance cost for mixed modalities in the matching pair when the second of the two did not immediately follow the first, suggesting that more enduring spatial images in working memory may be amodal.
Volume Recruitment and Oxygenation in Pulmonary Edema: A Comparison Between HFOV and CMV

Abstract Purpose: In acute lung injury, edema floods alveoli decreasing mean lung volume (MLV) and increasing pulmonary venous admixture (Qva/Qt). We reasoned that a ventilatory strategy that uses large tidal volumes (V t ) might recruit volume differently than a strategy that uses very small V t (high-frequency oscillatory ventilation, HFOV) which may require an inflation maneuver to total lung capacity (TLC) for full recruitment. Materials and Methods: We studied six dogs with pulmonary edema induced by oleic acid injury and compared HFOV with conventional mechanical ventilation (CMV). Increasing mean airway opening pressure (Pao) from 6 to 14 cm H2O raised MLV from 932 ± 162 to 1,550 ± 210 mL and from 872 ± 145 to 1,242 ± 192 mL during CMV and HFOV, respectively, whereas Qva/Qt decreased from 24.1 ± 8.5 to 9.3 ± 4.3% and from 42.2 ± 6.8 to 30.4 ± 9.3%. We repeated our measurements at a Pao of 14 cm H2O after an inflation maneuver to TLC. Results: Intlation to TLC recruited additional lung volume and decreased Qva/Qt further only during HFOV. After an inflation to TLC, we observed a rapid isobaric volume loss from the deflation limb of the pressure-volume curve during both CMV and HFOV. Conclusions: We conclude that after oleic acid injury in dogs pressure-volume hysteresis has two components: a recruitable portion associated with gas exchange improvement and a nonrecruitable portion. At the level of PEEP used in this study (8.5 cm H2O), full lung recruitment during HFOV required inflation to TLC, whereas during CMV it was accomplished by the relatively large VT.
Incorporating Science, Technology, Fairness, and Accountability in Environmental, Health, and Safety Decisions

Abstract The Precautionary Principle is in sharp political focus today because (1) the nature of scientific uncertainty is changing and (2) there is increasing pressure to base governmental action on more “rational” schemes, such as cost-benefit analysis and quantitative risk assessment, the former being an embodiment of ‘rational choice theory’ promoted by the Chicago school of law and economics. The Precautionary Principle has been criticized as being both too vague and too arbitrary to form a basis for rational decision making. The assumption underlying this criticism is that any scheme not based on cost-benefit analysis and risk assessment is both irrational and without secure foundation in either science or economics. This paper contests that view and makes explicit the rational tenets of the Precautionary Principle within an analytical framework as rigorous as uncertainties permit, and one that mirrors democratic values embodied in regulatory, compensatory, and common law. Unlike other formulations ...
Cytomegalovirus retinitis and FK 506.

Abstract Purpose To report a case of cytomegalovirus (CMV) retinitis in a patient immunosuppressed with FK 506. Design Interventional case report. Methods Retrospective institutional study. One patient, diagnosed with bilateral CMV retinitis while on immunosuppressive treatment with FK 506, received systemic ganciclovir and intravitreal, slow-release ganciclovir implant in one eye, combined with reduction in FK 506 dose. Main outcome measures were visual acuity and regression of CMV retinitis. Results Visual acuity at presentation was 20/20 in the right eye and 20/50 in the left eye. During the 6 months of follow-up, there was no change in visual acuity in either eye. The areas of CMV retinitis demonstrated progressive regression, leaving diffuse retinal atrophy. Conclusions Cytomegalovirus retinitis can be a sight-threatening complication of immunosuppressive treatment with FK 506. Ganciclovir treatment together with a reduction in FK 506 dose was effective in preserving vision.
Comparison of replication complexes synthesizing poliovirus RNA

Abstract Poliovirus RNA replication complexes prepared by homogenization or detergent-extraction of infected cells have been used to study RNA replication in vitro . We show that the products are different depending on the method of extraction. Complexes derived from homogenized cells synthesize full-length single-stranded poliovirus RNA, replicative intermediate (RI), and replicative form (RF) RNA species, whereas only RI and RF are made by detergent-extracted complexes. Both complexes synthesize predominantly plus-strand strand RNA in vitro . Detergent treatment of complexes from homogenized cells inhibits synthesis of full-length, single-stranded RNA. The data suggest that the poliovirus replication complex contains several enzymatic activities and that the ability to synthesize full-length single-stranded RNA requires the association of a labile, possibly membrane associated, factor with the core elongation complex. Furthermore, RNase T 1 -resistant oligonucleotide fingerprints of the products of detergent-extracted complexes are missing a specific internal oligonucleotide, which has been mapped near, but not identical to, oligonucleotides missing in fingerprints of DI virus genome.
Developing a self‐consistent description of Titan's upper atmosphere without hydrodynamic escape

In this study, we develop a best fit description of Titan's upper atmosphere between 500 km and 1500 km, using a one-dimensional (1-D) version of the three-dimensional (3-D) Titan Global Ionosphere-Thermosphere Model. For this modeling, we use constraints from several lower atmospheric Cassini-Huygens investigations and validate our simulation results against in situ Cassini Ion-Neutral Mass Spectrometer (INMS) measurements of N2, CH4, H2, 40Ar, HCN, and the major stable isotopic ratios of 14N/15N in N2. We focus our investigation on aspects of Titan's upper atmosphere that determine the amount of atmospheric escape required to match the INMS measurements: the amount of turbulence, the inclusion of chemistry, and the effects of including a self-consistent thermal balance. We systematically examine both hydrodynamic escape scenarios for methane and scenarios with significantly reduced atmospheric escape. Our results show that the optimum configuration of Titan's upper atmosphere is one with a methane homopause near 1000 km and atmospheric escape rates of 1.41–1.47 ×1011 CH4 m−2 s−1 and 1.08 ×1014 H2 m−2 s−1 (scaled relative to the surface). We also demonstrate that simulations consistent with hydrodynamic escape of methane systematically produce inferior fits to the multiple validation points presented here.
Activation of histone gene transcription from chromatin of G1 HELA cells by S-phase non-histone chromosomal proteins.

Non-histone chromosomal proteins have been implicated as having an important function in the regulation of gene expression [l-9] . Specifically, these proteins have been shown to be involved in controlling the transcription of globin genes in erythroid cells [ 1 O-l 2] and histone genes during the cell cycle [ 13-141. In HeLa cells, synthesis of histones is restricted to the period of the cell cycle during which DNA is replicated (S-phase) [15-l 81, and translation [15-17, 19-211 as well as hybridization data [22] indicate that histone mRNAs are associated with polysomes only at this time. Using a 3H-labeled single stranded complementary DNA as a probe for histone mRNA sequences [23], we have recently demonstrated that histone genes are transcribed in vitro from chromatin isolated from S-phase cells, but that chromatin isolated from Gr phase cells does not serve as a template for the transcription of histone sequences [24]. These results suggest that histone genes are transiently expressed during the period of DNA replication and that regulation of histone gene expression occurs at least in partat the transcriptional level. We have shown through chromatin in reconstitution studies that the non-histone chromosomal protein component of the genome is responsible for the difference in the in vitro transcription of histone sequences from Gi and S-phase chromatin [ 131. The present study demonstrates that when chromatin from Gr phase HeLa cells is reconstituted in the presence of nonhistone chromosomal proteins isolated from S-phase cells, a dose dependent activation of histone gene transcription is observed.
Convexity and absolute continuity of the Laplace-Beltrami operator

On montre que l'existence de bonnes fonctions convexes implique l'absolue continuite (par rapport a la mesure de Lebesgue) des mesures spectrales de l'extension auto-adjointe du laplacien Δ/C 0 ∞ (M) dans L 2 (M)
Interactive Visualizations to Improve Bayesian Reasoning

Proper Bayesian reasoning is critical in a variety of domains that require practitioners to make predictions about the probability of events contingent upon earlier actions or events. However, much research on judgment has shown that people who are unfamiliar with Bayes’ Theorem often reason quite poorly with conditional probabilities due to various cognitive biases. Owing to previous successes of visualization techniques for debiasing judges and improving judgment performance, we created an interactive computer visualization designed to aid Bayes-naive people in solving conditional probability problems that would not require a training period to use, and would be flexible enough to accommodate many problem types. Results are suggestive that participants using our interactive visualization were able to substantially improve their Bayesian reasoning performance above that of previous debiasing methods. This finding has significant implications for expanding the toolbox of techniques that can be used to mor...
Cell-mapping techniques applied to the rf-driven Josephson junction.

We apply the technique of simple cell mapping to the problem of the rf-driven Josephson junction, and show that this technique is a computation-efficient method of exploring attractors and basins in this system. We show attractors, basins, and Poincar\'e maps of a previously reported interior crisis, and we also explore the phase plane of a junction with extreme underdamping---an impractical problem by any other technique.
Water-soluble [2.2]paracyclophane chromophores with large two-photon action cross sections.

A series of α,ω-donor-substituted distyrylbenzene dimers held together by the [2.2]paracyclophane core were designed, synthesized, and characterized. Different substituents were chosen to modulate the strength of the donor nitrogen groups and to allow the molecules to be either neutral and soluble in nonpolar organic solvents or charged and water-soluble. The specific neutral structures are (in order of decreasing donor strength) 4,7,12,15-tetra[N,N-bis(6‘ ‘-chlorohexyl)-4‘-aminostyryl]-[2.2]paracyclophane (1N), 4,7,12,15-tetra[(N-(6‘ ‘-chlorohexyl)carbazol-3‘-yl)vinyl]-[2.2]paracyclophane (2N), and 4,7,12,15-tetra[N,N-bis(4‘ ‘-(6‘ ‘‘-chlorohexyl)phenyl)-4‘-aminostyryl]-[2.2]paracyclophane (3N). The charged species are 4,7,12,15-tetra[N,N-bis(6‘ ‘-(N,N,N-trimethylammonium)hexyl)-4‘-aminostyryl]-[2.2]paracyclophane octaiodide (1C), 4,7,12,15-tetra[(N-(6‘ ‘-(N,N,N-trimethylammonium)hexyl)carbazol-3‘-yl)vinyl]-[2.2]paracyclophane octaiodide (2C), and 4,7,12,15-tetra[N,N-bis(4‘ ‘-(6‘ ‘‘-(N,N,N-trimethylammoni...
Northern Eurasia Earth Science Partnership Initiative

The Northern Eurasia Earth Science Partnership Initiative (NEESPI) was launched five years ago with the release of its Science Plan (http://neespi.org). Gradually, the Initiative was joined by numerous international projects and launched in the European Union, Russia, United States, Canada, Japan, and China. Currently, serving as an umbrella for more than 130 individual research projects (always with international participation) and with a $15M annual budget, this highly diverse initiative is in full swing. Since the first NEESPI focus issue (Pavel Groisman et al 2007 Environ. Res. Lett. 2 045008 (1pp)) in December 2007, several NEESPI Workshops and Sessions at International Meetings have been held that strengthen the NEESPI grasp on biogeochemical cycle and cryosphere studies, climatic and hydrological modeling, and regional NEESPI components in the Arctic, non- boreal Eastern Europe, Central Asia, northern Siberia, and mountainous regions of the NEESPI domain. In May 2009, an overview NEESPI paper was published in the Bulletin of the American Meteorological Society (BAMS) (Pavel Groisman et al 2009 Bull. Am. Met. Soc. 90 671). This paper also formulated a requirement to the next generation of NEESPI studies to work towards attaining a higher level of integration of observation programs, process studies, and modeling, across disciplines. Three books devoted to studies in different regions of Northern Eurasia prepared by the members of the NEESPI team have appeared and/or are scheduled to appear in 2009. This (second) ERL focus issue dedicated to climatic and environmental studies in Northern Eurasia is composed mostly from the papers that were presented at two NEESPI Open Science Sessions at the Annual Fall Meeting of the American Geophysical Union (December 2008, San Francisco, CA) and at the General Assembly of the European Geosciences Union (April 2009, Vienna, Austria), as well as at the specialty NEESPI Workshops convened in Jena, Helsinki, Odessa, Urumqi, Krasnoyarsk, St Petersburg, and Bishkek during the past two years. As in the first NEESPI focus issue, papers that make up this second issue can be divided into five major topics: climate and hydrology; land cover and land use; the biogeochemical cycle and its feedbacks; cryosphere; human dimension. However, this partitioning is less rigid compared to the partitioning in the first Issue. Following the requirement of a higher level of integration outlined in the BAMS paper, many papers in this issue respond to two or even three of the topics listed above.
Rheology and structure development during gelation of low-methoxyl pectin gels: the effect of sucrose

Abstract A non-isothermal kinetic model described G′ values during gelation induced by cooling dispersions of low-methoxyl (LM) pectin+Ca2+, and 10 and 30% (wb) sucrose at pH 4 and {2(Ca2+)/(COO−)}=0.58. Two different gelation regimes, corresponding to two different temperature ranges, were observed. During the aging process, increasing the pectin concentration resulted in a significant increase in G′ increasing the sucrose content also increased G′. Using the plateau values of G′ and the rubber elasticity theory, the number average molecular weight of chains between cross-links, Mc, was estimated. At the same pectin concentration, Mc of 0% sucrose gels was greater than those of 10 and 30% sucrose gels. These results reflect the important role of the hydroxyl groups of sucrose in gel formation and that sucrose may stabilize the structure of junction zones.
Women as ‘sex workers,’ men as ‘boyfriends’: Shifting identities in Philippine go‐go bars and their significance in STD/AIDS control

Abstract Research and intervention programs for AIDS prevention place people within ‘risk groups’ to target specific populations that are believed to be more prone to contract and transmit HIV and other STDs. The ‘sex worker’ is one of these convenient constructions used to label women who exchange sex for money or other material gains. Research presented in this paper examines the activities of female go‐go dancers in the Philippines and their relationships with male customers, showing how women attempt to distance themselves from the stigmatized ‘sex worker’ identity. Health personnel and government officials consider these women to be ‘sex workers,’ yet they do not situate themselves within this category. Their activities also challenge the accepted definition regarding prostitution, as many sexual encounters occur with men they identify as ‘boyfriends.’ In these situations they are less likely to request condom use because of the social and emotional ambiguities concerning their relationships.
Pair grammars, graph languages and string-to-graph translations

Translation between string and graph representations of programs and data may be formally defined by means of pair grammars. A pair grammar is composed of a pair of grammars whose rules and nonterminals are paired. The pair grammar defines a correspondence between elements of the languages defined by the two grammars. This correspondence may be viewed as a definition of the translation of the elements of one language into the elements of the other. Of particular interest is the case in which the first language is a set of strings and the second is a set of directed graphs with labeled arcs and nodes. Preliminary to the definition of pair grammars, a class of graph grammars are defined which are a generalization of ordinary context-free grammars. A graph grammar defines a language composed of a set of directed graphs. Pair grammars are constructed from pairs of graph grammars. Each unambiguous pair grammar defines a reversible function mapping one graph language onto another. Special cases of interest include string-to-graph, graph-to-string, and string-to-string mappings. In the general case a pair grammar defines a transformation on a set of graphs. Two extensions to the elementary pair grammars allow representation of hierarchies of graphs and constructs such as labels and go to statements. Examples are given of the translation of a major subset of Algol into flowchart graphs and the translation of Lisp S-expressions into list structure graphs with structured atoms.
INCOMMENSURABILITY, RELATIVISM, SCEPTICISM: REFLECTIONS ON ACQUIRING A CONCEPT

The definitive version is available at www3.interscience.wiley.com and website listed below.
Repression of tumor suppressor miR-451 is essential for NOTCH1-induced oncogenesis in T-ALL

The NOTCH1 signaling pathway is a critical determinant of cell fate decisions and drives oncogenesis through mechanisms that are incompletely understood. Using an established mouse model of T cell acute lymphoblastic leukemia (T-ALL), here we report that induction of intracellular Notch1 (ICN1) leads to repression of miR-451 and miR-709. ICN1 decreases expression of these miRNAs by inducing degradation of the E2a tumor suppressor, which transcriptionally activates the genes encoding miR-451 and miR-709. Both miR-451 and miR-709 directly repress Myc expression. In addition, miR-709 directly represses expression of the Akt and Ras-GRF1 oncogenes. We also show that repression of miR-451 and miR-709 expression is required for initiation and maintenance of mouse T-ALL. miR-451 but not miR-709 is conserved in humans, and human T-ALLs with activating NOTCH1 mutations have decreased miR-451 and increased MYC levels compared with T-ALLs with wild-type NOTCH1. Thus, miR-451 and miR-709 function as potent suppressors of oncogenesis in NOTCH1-induced mouse T-ALL, and miR-451 influences MYC expression in human T-ALL bearing NOTCH1 mutations.
Effectiveness of the 23-Valent Polysaccharide Vaccine against Invasive Pneumococcal Disease in Navajo Adults

Invasive pneumococcal disease occurs 2-3-fold more often among Navajo adults than among adults in the general United States population. The objective of this observational study was to determine the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) among Navajo adults. Active surveillance identified cases of invasive pneumococcal disease during 1996-1997. Three control patients per case patient were matched according to underlying medical conditions, sex, age, and location of medical care. Effectiveness was calculated by regression analysis of case-control sets and by indirect cohort methodology. Diabetes and alcoholism occurred in 41% and 43% of 108 case patients, respectively; 62% of case patients and 64% of control patients were immunized. Overall vaccine effectiveness was 26% (95% confidence interval [CI], -29% to 58%); 15% (95% CI, -116% to 67%) for patients with diabetes and -5% (95% CI, -141% to 54%) for patients with alcoholism. Overall vaccine effectiveness, as determined by use of the indirect cohort methodology, was 35% (95% CI, -33% to 69%). PPV23 was not significantly effective among Navajo adults and may be inadequate to prevent serious pneumococcal disease in this population.
Towards a tool for predicting user exploration

CogTool-Explorer is a tool to predict user exploration choices given a user interface and task. We describe the integration of components that make up CogTool-Explorer, and how it interprets the text of both the task description and interface elements to make its exploration choices. We present CogTool-Explorer's performance on a web navigational search task compared to human performance.