Miracle-dz/UniFAR-FTUs huggingface dataset:
Fibroblast Growth Factor 19 Activates the Unfolded Protein Response and Mitogen-Activated Protein Kinase Phosphorylation in H-69 Cholangiocyte Cells.

Background Cholangiocytes are injured in many biliary tract diseases that result in cirrhosis, cholangiocarcinoma and need for liver transplantation. Recent studies demonstrate that the hormone Fibroblast Growth Factor 19 (FGF19) is produced in the ileum and regulates hepatic gene expression via the enterohepatic circulation. However, the role of FGF19 on cholangiocytes remains largely unknown. The purpose of this study was to elucidate the effect of FGF19 on cholangiocyte gene and protein expression. Methods Cultured human cholangiocyte-derived H69 cells were treated with FGF19 (0-50ng/ml) and expression of genes and proteins involved in the Unfolded Protein Response (UPR) and mitogen-activated protein kinase (MAPK) pathways were studied using RT-PCR and Western blot analysis. Results FGF19-induced gene and protein expression of the UPR genes BiP and CHOP increased in a dose-responsive pattern. The UPR protein P-eIF2a displayed a bimodal pattern of protein expression, with 10ng/ml of FGF19 maximally reducing and 50ng/ml maximally increasing expression. MAPK pathway protein expression (P-JNK, P-ERK, P-38) displayed a similar bimodal pattern of expression with 2.5ng/ml of FGF19 decreasing expression and 25ng/ml of FGF19 increasing expression. Conclusions FGF19 treatment of H69 cells selectively activates BiP and CHOP in a dose-dependent manner. FGF19 also regulates P-eIF2a and MAPK protein expression with a bimodal response. We speculate that FGF19 has an important role in the pathogenesis of many human cholangiopathies and cholestatic liver disorders.
Studying Black Holes in the Internet with Hubble

We present Hubble, a system that operates continuously to find Internet reachability problems in which routes exist to a destination but packets are unable to reach the destination. Hubble monitors at a 15 minute granularity the data-path to prefixes that cover 89% of the Internet's edge address space. Key enabling techniques include a hybrid passive/active monitoring approach and the synthesis of multiple information sources that include historical data. With these techniques, we estimate that Hubble discovers 85% of the reachability problems that would be found with a pervasive probing approach, while issuing only 5.5% as many probes. We also present the results of a three week study conducted with Hubble. We find that the extent of reachability problems, both in number and duration, is much greater than we expected, with problems persisting for hours and even days, and many of the problems do not correlate with BGP updates. In many cases, a multi-homed AS is reachable through one provider, but probes through another terminate; using spoofed packets, we isolated the direction of failure in 84% of cases we analyzed and found all problems to be exclusively on the forward path from the provider to the destination. A snapshot of the problems Hubble is currently monitoring can be found at http://hubble.cs. washington.edu.
A DISTINCTIVE DISK–JET COUPLING IN THE SEYFERT-1 ACTIVE GALACTIC NUCLEUS NGC 4051

We report on the results of a simultaneous monitoring campaign employing eight Chandra X-ray (0.5–10 keV) and six Very Large Array/Extended Very Large Array (8.4 GHz) radio observations of NGC 4051 over seven months. Evidence for compact jets is observed in the 8.4 GHz radio band; this builds on mounting evidence that jet production may be prevalent even in radio-quiet Seyferts. Assuming comparatively negligible local diffuse emission in the nucleus, the results also demonstrate an inverse correlation of Lradio ∝ L−0.72±0.04X-ray. If the A configuration is excluded in the case where diffuse emission plays a significant role, the relation is still . Current research linking the mass of supermassive black holes and stellar-mass black holes in the “low/hard” state to X-ray luminosities and radio luminosities suggests a “fundamental plane of accretion onto black holes” that has a positive correlation of Lradio ∝ L0.67±0.12X-ray. Our simultaneous results differ from this relation by more than 11σ (6σ excluding the A configuration), indicating that a separate mode of accretion and ejection may operate in this system. A review of the literature shows that the inverse correlation seen in NGC 4051 is seen in three other black hole systems, all of which accrete at near 10% of their Eddington luminosity, perhaps suggesting a distinct mode of disk–jet coupling at high Eddington fractions. We discuss our results in the context of disks and jets in black holes and accretion across the black hole mass scale.
The role of carboxyhemoglobin measured with CO-oximetry in the detection of hemolysis in newborns with ABO alloimmunization

Abstract Objectives: To evaluate carboxyhemoglobin (COHb) values measured with a CO-oximeter (Roche-cobas b 221) in jaundiced newborns with or without hemolysis and healthy controls in order to assess whether COHb measurement determined with a CO-oximeter could be used as an indicator of hemolysis in newborns with ABO alloimmunization. Methods: A total of 86 term newborn infants were prospectively studied. The study cohort consisted of three subgroups: 18 infants with ABO HDN, 21 infants with hyperbilirubinemia without hemolytic disease who required phototherapy, and 47 healthy controls. The COHb, bilirubin, and Hb levels were measured. Results: The three subgroups did not differ significantly with respect to birth weight, gestational age, gender, Apgar score, or mode of delivery. The ABO HDN infants had significantly higher COHb values than the healthy controls (median 2.4% versus 1.3%, p < 0.0005) and the group with hyperbilirubinemia without hemolytic disease (median 2.4% versus 1.3%, p < 0.0005), although the infants with hyperbilirubinemia without hemolytic disease did not have significantly higher COHb values compared with the healthy controls. The cut-off value of 1.7% COHb had 72% sensitivity and 97% specificity for confirming hemolysis in ABO alloimmunization. Conclusions: Our data show that COHb values determined with CO-oximeters are higher in newborns with hemolysis than in those without hemolysis. COHb measured with CO-oximeters could be used to confirm hemolysis in infants with ABO alloimmunization.
IL-33 Induces IL-13–Dependent Cutaneous Fibrosis

IL-33 is constitutively expressed in epithelial barrier tissues, such as skin. Although increased expression of IL-33/IL-33R has been correlated with fibrotic disorders, such as scleroderma and progressive systemic sclerosis, the direct consequences of IL-33 release in skin has not been reported. To determine the effects of dysregulated IL-33 signaling in skin, we administered IL-33 s.c. and monitored its effects at the injection site. Administration of IL-33 resulted in IL-33R–dependent accumulation of eosinophils, CD3+ lymphocytes, F4/80+ mononuclear cells, increased expression of IL-13 mRNA, and the development of cutaneous fibrosis. Consistent with extensive cutaneous tissue remodeling, IL-33 resulted in significant modulation of a number of extracellular matrix-associated genes, including collagen VI, collagen III, and tissue inhibitor of metalloproteases-1. We establish that IL-33–induced fibrosis requires IL-13 using IL-13 knockout mice and eosinophils using ΔdblGATA mice. We show that bone marrow-derived eosinophils secrete IL-13 in response to IL-33 stimulation, suggesting that eosinophil-derived IL-13 may promote IL-33–induced cutaneous fibrosis. Collectively, our results identify IL-33 as a previously unrecognized profibrotic mediator in skin and highlight the cellular and molecular pathways by which this pathology develops.
Inhibition of rot translation by RNAIII, a key feature of agr function

RNAIII is a 514 nt regulatory RNA that is the effector molecule of the staphylococcal agr quorum‐sensing system, regulating a large set of virulence and other accessory genes at the level of transcription. RNAIII was discovered nearly 20 years ago and we long ago hypothesized that it would function by regulating the synthesis or activity of one or more intermediary transcription factors. We have finally confirmed this hypothesis, showing that Staphylococcus aureus RNAIII regulates the synthesis of a major pleiotropic transcription factor, Rot, by blocking its translation. RNAIII has a complex secondary structure with several stable hairpins that have highly C‐rich end loops, unusual in an AT‐rich organism. We noted that these loops are complementary to two G‐rich stem loops of the rot mRNA translation initiation region (TIR). Pairing of the complementary RNAs would be predicted to occlude the rot Shine–Dalgarno (SD) site and to block rot translation. Through a combination of transcriptional and translational fusions and Northern and Western blot hybridization analyses, we show that RNAIII does, indeed, block rot translation. Through alterations in the C‐rich loops of RNAIII and the G‐rich loops of rot, we show that the sequences of these loops are critical for inhibition of rot translation and suggest that this inhibition is affected by pairing between the complementary stem loops, followed by the cleavage of rot mRNA. We propose that the RNAIII–rot mRNA interaction plays a key role in agr regulation of staphylococcal virulence.
Women ’ s Social Rights : Untapped Economic Potential Political Science 303 : Gender and Development

This paper analyzes whether women’s social rights play a role in fostering higher levels of economic development. Prior development initiatives and economic policies failed to account for the productive capacities of women by discriminating against their basic rights to things such as an equitable education, equal inheritance, and marital rights. Applying the CIRI (Cingranelli-Richards Human Rights) dataset for women’s social rights, I found that improvements in these areas of human rights leads to significant increases in real GDP per capita, which highlights the need for development analysts and economists to focus their attention on countries’ most viable productive resource, women. Comments This paper was written for Professor Caroline Hartzell's course, POL 303: Women and the Political Economy of Development, Spring 2015. This student research paper is available at The Cupola: Scholarship at Gettysburg College: http://cupola.gettysburg. edu/ student_scholarship/353 Women’s Social Rights: Untapped Economic Potential Political Science 303: Gender and Development Monae Evans 4/14/2015 This paper analyzes whether women’s social rights play a role in fostering higher levels of economic development. Prior development initiatives and economic policies failed to account for the productive capacities of women by discriminating against their basic rights to things such as an equitable education, equal inheritance, and marital rights. Applying the CIRI (CingranelliRichards Human Rights) dataset for women’s social rights, I found that improvements in these areas of human rights leads to significant increases in real GDP per capita, which highlights the need for development analysts and economists to focus their attention on countries’ most viable productive resource, women.
Age- and disease-related methylation of multiple genes in nonneoplastic duodenum and in duodenal juice.

PURPOSE Methylation of CpG islands contributes to gene silencing during cancer development, and although some methylation alterations are promising diagnostic markers of cancer, some CpG islands are also methylated in normal tissues. We have previously observed that some normally unmethylated CpG islands that undergo methylation in pancreatic cancers are normally methylated in the adjacent duodenum. Because duodenal methylation patterns are an important consideration when sampling pancreatic tissues for pancreatic cancer methylation alterations, we determined the DNA methylation patterns of 24 genes in the normal duodenum of patients with pancreatic disease and related these patterns to demographic factors. EXPERIMENTAL DESIGN The nonneoplastic duodenal mucosa of 158 patients with pancreatic carcinoma and 41 patients with chronic pancreatitis was analyzed using methylation-specific PCR and combined bisulfite restriction analysis. Secretin-stimulated pancreatic/duodenal juice from 15 individuals undergoing endoscopic investigation for upper gastrointestinal disease was also analyzed. RESULTS Low-level methylation was detectable by methylation-specific PCR in the nonneoplastic duodenum of many patients with pancreatic cancer and chronic pancreatitis as well as in the pancreaticoduodenal secretions of patients without pancreaticobiliary disease. For many genes, the prevalence of methylation increased with age and was more prevalent in patients with pancreatic cancer than in age-matched patients with chronic pancreatitis. Our results indicate that strategies to detect pancreatic cancer using aberrantly methylated genes should rely on analysis of pure pancreatic juice rather than on pancreatic juice collected within the duodenal lumen. Patients who develop pancreatic cancer may have a greater propensity to methylate CpG islands than age-matched controls.
Dynamic Shading in Image-Based Rendering

Image-based rendering techniques have been used to improve image quality, increase frame rate, and reduce modeling time. However, once the images have been acquired, they are bound to the light conditions of the scene during acquisition time. This paper describes how the Plenoptic Modeling approach can be extended to support applications that allow users to arti cially change the original light conditions. A hybrid (geometric and image-based) solution is presented for producing shadows and view-dependent e ects, such as specular highlights. The technique has been successfully tested with synthetic images and, under special lighting conditions, can also be applied to natural images.
A novel mutation in UDP‐N‐acetylglucosamine‐1‐phosphotransferase gamma subunit (GNPTAG) in two siblings with mucolipidosis type III alters a used glycosylation site

The N‐acetylglucosaminyl‐1‐phosphotransferase (termed phosphotransferase) catalyzes the initial step in the formation of mannose 6‐phosphate (M6P) residues required for the efficient transport of soluble lysosomal enzymes. The phosphotransferase is a multisubunit enzyme composed of three subunits (α2β2γ2) that are products of two genes. The gene encoding the γ‐subunit (GNPTAG) appears to be defective in patients with mucolipidosis type III (ML III). We have analyzed the GNPTAG gene in two siblings with ML III showing elevated activities of several lysosomal enzymes in cultured fibroblasts serum and diminished activities in cultured fibroblasts. Immunoprecipitation of metabolically labeled cathepsin D (CtsD) from fibroblasts revealed that the sorting/transport of this lysosomal protease was affected. Addition of ammonium chloride inhibiting pH‐dependent processes, such as the CtsD‐M6P receptor interaction, indicated that 15 to 20% of the newly synthesized CtsD is transported in ML III fibroblasts in an M6P‐dependent manner. By direct sequencing a novel homozygous mutation, c. 347_349delACA (p.Asn116del), was identified affecting a potential N‐linked glycosylation site. Western blot analysis of extracts from control fibroblasts detect a 97 kDa glycosylated dimer whereas ML III cells contain a GNPTAG dimer of reduced molecular mass. These data suggest that the loss of the used glycosylation site in the gamma subunit may affect the intracellular localization of GNPTAG and the overall efficiency of M6P formation. © 2004 Wiley‐Liss, Inc.
Revision Hip Arthroscopy

Background Hip arthroscopy has become increasingly popular; however, little is known about revision hip arthroscopy. Hypothesis Revision hip arthroscopy is associated with unaddressed femoroacetabular impingement. The purpose of this study was to describe reasons for revision hip arthroscopy. Study Design Case series; Level of evidence, 4. Methods Between March 2005 and March 2006, 37 revision hip arthroscopies were performed by the senior author. Data were collected through retrospective review of clinical and operative notes. Results All patients required revision surgery because of persistent hip pain. There were 25 women and 12 men with an average age of 33 years (range, 16-53 years). The average time from prior surgery to revision was 20.5 months (range, 2.9-84 months). Common findings among patients needing revision were hip pain, decreased range of motion, and functional disability. The average modified Harris Hip Score was 53 (range, 22-99). Thirty-six patients had radiographic evidence of femoroacetabular impingement at the time of revision. Revision procedures included 34 (95%) for femoroacetabular impingement, 32 (87%) for labral lesions, 26 (70%) for a chondral defect, 23 (62%) for lysis of adhesions, and 13 (35%) for previously unaddressed instability. Two patients had total hip arthroplasty after revision, and 3 patients required further revision. Of the remaining 32 patients, early follow-up was obtained on 27 (84%) at an average of 12.7 months postoperatively (range, 6-19 months). Outcomes showed patients regained some of their lost function within the first year. Conclusion Patients commonly required revision hip arthroscopy because of persistent impingement.
Regulated Apoptosis and Immunogene Therapy for Prostate Cancer

Abstract : The central tenet of this proposal was that methods to effectively trigger apoptosis within prostate tumors can both reduce tumor burden and elicit adaptive immunity, provided a pro-inflammatory environment can be created. We created inducible caspases (iCaspases) that were the basis of both a prophylactic vaccine and as a treatment for pre-existing subcutaneous (sc) and autochthonous (TRAMP) prostate tumors. While these studies were centered on prostate cancer, they should also be relevant to other tumor types. Major findings: The combination of iCaspases and IL-12 can completely eliminate small (less than or equal to 40 mm3) sc tumors and largely eliminate larger (less than or equal to 100 mm3) tumors while IL-12 alone had minimal effect and iCaspase alone had no significant effect. Anti-tumor efficacy mirrored expansion of anti-tumor cytotoxic T lymphocytes and IFN-(Gamma)-producing cells from splenocytes of vaccinated animals. Further, orthotopic injections into the prostates of tumor-bearing TRAMP mice trigger apoptosis, secondary necrosis and inflammation, and significantly extend survival. In transgenic animals, the hK2-E3/P, PSA-E2/P and ARR2PB composite promoters are highly active in prostate epithelial cells and are largely prostate specific; however, they are somewhat attenuated as tumor progression occurs, potentially reducing efficacy in tumor cells. Finally, we developed ubiquitous and tissue-specific clinical candidate vectors that are being tested for a potential clinical trial. This work lays the groundwork for an "off-the-shelf" injectable immunogene therapy that could treat prostate cancer as a neoadjuvant therapy or possible less mutagenic treatment for metastatic disease.
A randomised trial comparing the i‐gelTM with the LMA ClassicTM in children

We performed a prospective, randomised trial comparing the i‐gelTM with the LMA ClassicTM in children undergoing general anaesthesia. Ninety‐nine healthy patients were randomly assigned to either the i‐gel or the LMA Classic. The outcomes measured were airway leak pressure, ease of insertion, time taken for insertion, fibreoptic examination and complications. Median (IQR [range]) time to successful device placement was shorter with the i‐gel (17.0 (13.8−20.0 [10.0−20.0]) s) compared with the LMA Classic (21.0 (17.5−25.0 [15.0−70.0]) s, p = 0.002). There was no significant difference in oropharyngeal leak pressure between the two devices. A good fibreoptic view of the glottis was obtained in 74% of the i‐gel group and in 43% of the LMA Classic group (p < 0.001). There were no significant complications. In conclusion, the i‐gel provided a similar leak pressure, but a shorter insertion time and improved glottic view compared with the LMA Classic in children.
Integration of Satellite Telemetry Data and Land Cover Imagery: A Study of Migratory Cranes in Northeast Asia

The present study describes a procedure for quantitatively analyzing satellite telemetry data to identify interspecific land use differences among four threatened crane species. The inherent inaccuracy of satellite telemetry data points, the temporal autocorrelation of those points, and the resolution of two land‐cover imagery products from the IGBP‐DISCover Global Land‐Cover Characterization Project (derived from AVHRR data) were assessed and integrated in a GIS. Satellite telemetry is a system where animals are tracked using battery‐operated transmitters and locations are calculated using triangulation from satellites. Using the variable spatial inaccuracy of the telemetry locations, each point was buffered using a radius based on the accuracy of the point, and then intersected with the land cover imagery. The research concluded that the methodology is valuable for studies of birds at a regional scale, with interspecific differences clearly evident, but that diurnal and nocturnal differences were not discernable due to the coarse resolution of both satellite telemetry and land‐cover data.
Placental malaria-associated inflammation disturbs the insulin-like growth factor axis of fetal growth regulation.

BACKGROUND The pathogenetic mechanisms of fetal growth restriction associated with placental malaria are largely unknown. We sought to determine whether placental malaria and related inflammation were associated with disturbances in the insulin-like growth factor (IGF) axis, a major regulator of fetal growth. METHOD We measured IGF-1 and IGF-2 concentrations in plasma from 88 mother-neonate pairs at delivery and IGF binding proteins 1 and 3 (IGFBP-1 and IGFBP-3, respectively) in cord plasma from a cohort of Papua New Guinean women with and without placental malaria. Messenger RNA levels of IGF-1, IGF-2, and the IGF receptors were measured in matched placental biopsy specimens. RESULTS Compared with those for uninfected pregnancies, IGF-1 levels were reduced by 28% in plasma samples from women with placental Plasmodium falciparum infection and associated inflammation (P = .007) and by 25% in their neonates (P = .002). Levels of fetal IGFBP-1 were elevated in placental malaria with and without inflammation (P = .08 and P = .006, respectively) compared with uninfected controls. IGF-2 and IGFBP-3 plasma concentrations and placental IGF ligand and receptor messenger RNA transcript levels were similar across groups. CONCLUSION Placental malaria-associated inflammation disturbs maternal and fetal levels of IGFs, which regulate fetal growth. This may be one mechanism by which placental malaria leads to fetal growth restriction.
Impacts of educational programming at Dolphins Plus on visitor knowledge, attitude and behavior

vii Chapter 1 – Introduction . 1 1. Significance of Study . 1 2. History of Environmental Education in the US . 3 3. Scope of Work . 6 4. Role as A Pilot Study . 9 Chapter 2 – Literature Review . 10 1. Zoos, Aquariums, and Natural Resource Conservation . 10 2. Environmental Education and the Informal Sector . 16 3. Swim with Dolphins Programs . 20 4. Conclusions . 23 Chapter 3 – Methods . 24