Miracle-dz/UniFAR-FTUs huggingface dataset:
Biased Agonism as a Mechanism for Differential Signaling by Chemokine Receptors*

Background: Chemokines have been thought to act in a redundant fashion through their shared receptors. Results: Chemokines can display different efficacies for G proteins and β-arrestins, resulting in different chemotactic profiles. Conclusion: Chemokines can behave as biased agonists at their receptors, leading to functionally distinct, not redundant, responses. Significance: Biased agonism plays an important role in biological signaling. Chemokines display considerable promiscuity with multiple ligands and receptors shared in common, a phenomenon that is thought to underlie their biochemical “redundancy. ” Their receptors are part of a larger seven-transmembrane receptor superfamily, commonly referred to as G protein-coupled receptors, which have been demonstrated to be able to signal with different efficacies to their multiple downstream signaling pathways, a phenomenon referred to as biased agonism. Biased agonism has been primarily reported as a phenomenon of synthetic ligands, and the biologic prevalence and importance of such signaling are unclear. Here, to assess the presence of biased agonism that may underlie differential signaling by chemokines targeting the same receptor, we performed a detailed pharmacologic analysis of a set of chemokine receptors with multiple endogenous ligands using assays for G protein signaling, β-arrestin recruitment, and receptor internalization. We found that chemokines targeting the same receptor can display marked differences in their efficacies for G protein- or β-arrestin-mediated signaling or receptor internalization. This ligand bias correlates with changes in leukocyte migration, consistent with different mechanisms underlying the signaling downstream of these receptors induced by their ligands. These findings demonstrate that biased agonism is a common and likely evolutionarily conserved biological mechanism for generating qualitatively distinct patterns of signaling via the same receptor in response to different endogenous ligands.
Accuracy of three electronic monitors for metered-dose inhalers.

BACKGROUND Prior studies indicate that some devices used to monitor metered-dose inhaler (MDI) use are not accurate. OBJECTIVE To assess the accuracy of the Doser CT (NEW-MED Corporation; Waltham, MA), the MDILog (Medtrac Technologies; Lakewood, CO), and the SmartMist (Aradigm Corporation; Hayward, CA) in a bench-top study. DESIGN One, two, and four puffs of fluticasone propionate MDI (Flovent; GlaxoWellcome; Research Triangle Park, NC) were actuated twice daily for 30 days with two units of each device. The date and time of each actuation were recorded in a log and then compared with the output of the device. The percentage of doses recorded accurately was compared by analysis of variance. MEASUREMENTS AND RESULTS The SmartMist was 100% accurate, while both the Doser CT and MDILog devices occasionally recorded spurious actuations. The Doser CT also had missed actuations after the counter had prematurely reached zero secondary to the spurious recordings. The accuracy (mean plus minus SD) was 94.3 plus minus 2.9% for the Doser CT and 90.1 plus minus 6.9% for the MDILog (p = 0.21). The dose regimen actuated and duration of use did not significantly affect accuracy. CONCLUSION All three devices are sufficiently accurate to monitor adherence in most clinical settings.
Intramuscular Dermatan Sulfate MF701 in Patients with Hip Fracture: Relationship between Pharmacokinetics and Antithrombotic Efficacy

Summary Two groups of 23 and 84 patients with hip fracture received intramuscularly 100 and 300 mg dermatan sulfate (MF701) b. i. d. , respectively, for the prophylaxis of deep vein thrombosis. Median duration of treatment was 17 and 16 days, respectively. Four blood samples were collected from each patient while under treatment. Plasma levels of dermatan sulfate were determined by a chromogenic substrate assay. A one-compartment model for multiple doses was employed to estimate the pharmacokinetic parameters. Fitting was applied to mean plasma concentrations calculated for each sampling time and weighted according to the number of samples available at each time. Thrombin clotting time was measured on the same plasma samples. Antithrombotic efficacy was assessed by bilateral venography. Plasma levels of dermatan sulfate increased gradually throughout the treatment, indicating a marked accumulation process. Time to reach steady-state was 14 or 9 days with 100 or 300 mg b. i. d. , respectively. This was due to an apparent prolonged terminal half-life (68 or 43 h), which actually reflected slow absorption from the injection sites. The clinical efficacy of MF701 in preventing DVT was found to be dependent on the plasma concentration of the drug and also, but less significantly, on the prolongation of thrombin clotting time. Dermatan sulfate plasma levels greater than 9 μ/ml are advisable to optimize efficacy in hip fracture patients.
Evidence for an Activation Domain at the Amino Terminus of Simian Immunodeficiency Virus Vpx

ABSTRACT Vpx and Vpr are related lentiviral accessory proteins that enhance virus replication in macrophages and dendritic cells. Both proteins are packaged into virions and mediate their effects in the target cell through an interaction with an E3 ubiquitin ligase that contains DCAF1 and DDB1. When introduced into primary macrophages and dendritic cells in viruslike particles, Vpx can enhance the efficiency of a subsequent infection. Here, we confirm the ability of Vpx to enhance simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) infection of macrophages up to 100-fold by using single-cycle reporter viruses and by pretreatment of the cells with Vpx-containing viruslike particles. Vpx was also active in differentiated THP-1 cells but not in other cell lines. Induction of an antiviral state in macrophages with type I interferon significantly magnified the effect of Vpx on HIV-1 infection, suggesting that Vpx helps the virus to overcome an inducible intracellular restriction. Quantitative PCR quantitation of SIV and HIV-1 reverse transcripts in newly infected macrophages showed that the block was at an early step in reverse transcription. In spite of its structural similarity, Vpr was inactive. This difference allowed us to map the functional domains of Vpx with a panel of Vpr/Vpx chimeras. Analysis of the chimeras demonstrated that the amino-terminal domain of Vpx is important for the enhancement of infection. Fine mapping of the region indicated that amino acids at positions 9, 12, and 15 to 17 were required. Although the mutants failed to enhance infection, they retained their ability to interact with DCAF1. These findings suggest that the Vpx amino terminus contains an activation domain that serves as the binding site for a cellular restriction factor.
Efficiency of Islamic Banks in Indonesia: Data Envelopment Analysis

This paper measures the efficiency of Islamic commercial banks in Indonesia by analyzing factors that affect the level of efficiency using the two-stage data envelopment analysis (DEA) method. The objects of this study are 10 Islamic commercial banks in Indonesia which are analyzed from 2011 to 2014. Two methods are used in this study, namely nonparametric method of DEA in the first stage and Tobit model in the second stage. The actual average efficiency of Islamic commercial banks in Indonesia is at fairly good level with an average score 91.82, which means that although relatively inefficient, Islamic commercial banks in Indonesia are able to optimize their resource inputs to produce outputs as an intermediary institution. The application of the Tobit model uses asset (ASSET), non-performing financing (NPF), capital adequacy ratio (CAR), number of bank branches (BRANCH) and return on asset (ROA) as the explanatory variables. The results showed that the variables of assets, number of bank branches, and ROA significantly affect Islamic commercial bank efficiency, while CAR and NPF empirically do not have a significant effect on efficiency.
Comparative analysis of microsatellite loci in four fruit fly species of the genus Ceratitis (Diptera: Tephritidae)

Abstract The possibility to cross-species amplify microsatellites in fruit flies of the genus Ceratitis was tested with the polymerase chain reaction (PCR) by analysing 23 Ceratitis capitata (Wiedemann) microsatellite markers on the genomic DNA of three other economically important, congeneric species: C. rosa (Karsch), C. fasciventris (Bezzi) and C. cosyra (Walker). Twenty-two primer pairs produced amplification products in at least one of the three species tested. The majority of the products were similar, if not identical in size to those expected in C. capitata. The structures of the repeat motifs and their flanking sequences were examined for a total of 79 alleles from the three species. Sequence analysis revealed the same repeat type as the homologous C. capitata microsatellites in the majority of the loci, suggesting their utility for population analysis across the species range. A total of seven loci were differentially present/absent in C. capitata, C. rosa, C. fasciventris and C. cosyra, suggesting that it may be possible to differentiate these four species using a simple sequence repeat-based PCR assay. It is proposed that medfly-based microsatellite markers could be utilized in the identification and tracing of the geographical origins of colonist pest populations of the four tested species and in the assessment of their risk and invasive potentials; thereby assisting regulatory authorities in implementing quarantine restrictions and other pest control measures.
Rentz’s Student Affairs Practice in Higher Education, 5th ed.

The fifth edition of this work arrived six years from the previous edition, demonstrating a trend by the publisher to shorten the time between revisions. Staying true to the book’s heritage, the editor retained the focus of providing an introduction to the history and philosophy of the field as well as an overview of student affairs functional areas. There are 17 chapters, 13 focused on what might be considered traditional functional areas of student affairs practice, such as career services, student conduct, and residence life. The remaining four chapters addressed the philosophical heritage (Chapter 1), an historical perspective (Chapter 2), assessment (Chapter 15), and imagining the future of the profession (Chapter 17). All chapters from the previous edition remain, accompanied by three new chapters addressing Greek life, collegiate recreation, and assessment. Eight chapters included new authors, most of them practitioners in the respective functional areas, along with several faculty in professional preparation programs. The breadth and depth of the authors is a continued hallmark of this text’s legacy.
JustClick: Personalized Image Recommendation via Exploratory Search From Large-Scale Flickr Images

In this paper, we have developed a novel framework called JustClick to enable personalized image recommendation via exploratory search from large-scale collections of Flickr images. First, a topic network is automatically generated to summarize large-scale collections of Flickr images at a semantic level. Hyperbolic visualization is further used to enable interactive navigation and exploration of the topic network, so that users can gain insights of large-scale image collections at the first glance, build up their mental query models interactively and specify their queries (i.e., image needs) more precisely by selecting the image topics on the topic network directly. Thus, our personalized query recommendation framework can effectively address both the problem of query formulation and the problem of vocabulary discrepancy and null returns. Second, a small set of most representative images are recommended for the given image topic according to their representativeness scores. Kernel principal component analysis and hyperbolic visualization are seamlessly integrated to organize and layout the recommended images (i.e., most representative images) according to their nonlinear visual similarity contexts, so that users can assess the relevance between the recommended images and their real query intentions interactively. An interactive interface is implemented to allow users to express their time-varying query intentions precisely and to direct our JustClick system to more relevant images according to their personal preferences. Our experiments on large-scale collections of Flickr images show very positive results.
Characterization of Arginine Decarboxylase in Rat Brain and Liver

Abstract: We compared the properties of mammalian arginine decarboxylase (ADC) and ornithine decarboxylase (ODC) in rat liver and brain. Mammalian ADC is thermally unstable and associated with mitochondrial membranes. ADC decarboxylates both arginine (Km = 0.75 mM) and ornithine (Km = 0.25 mM), a reaction not inhibited by the specific ODC inhibitor, difluoromethylornithine. ADC activity is inhibited by Ca2+, Co2+, and polyamines, is present in many organs being highest in aorta and lowest in testis, and is not recognized by a specific monoclonal antibody to ODC. In contrast, ODC is thermally stable, cytosolic, and mitochondrial and is expressed at low levels in most organs except testis. Although ADC and ODC are expressed in cultured rat C6 glioma cells, the patterns of expression during growth and confluence are very different. We conclude that mammalian ADC differs from ADC isoforms expressed in plants, bacteria, or Caenorhabditis elegans and is distinct from ODC. ADC serves to synthesize agmatine in proximity to mitochondria, an organelle also harboring agmatine's degradative enzyme, agmatinase, and a class of imidazoline receptor (I2) to which agmatine binds with high affinity.
Changes in messenger RNA and protein levels of proteoglycans and link protein in human osteoarthritic cartilage samples.

OBJECTIVE To determine the steady-state messenger RNA (mRNA) levels and corresponding protein contents of major matrix components in osteoarthritic (OA) cartilage. METHODS Steady-state levels of gene-specific mRNA (relative to GAPDH) were measured by quantitative polymerase chain reaction (PCR), and the relative levels of the corresponding proteins were determined by Western blotting. RESULTS All mRNA levels and corresponding protein contents of aggrecan and versican (hyaluronan-binding large proteoglycans), decorin, biglycan, fibromodulin, and lumican (small proteoglycans), and link protein were higher in OA cartilage samples than in age-matched normal samples. The ratio of increase, however, was different for each component. The mRNA and protein levels of biglycan, decorin, and fibromodulin increased synchronously, whereas message for link protein and lumican were several-fold higher than expected by their measured protein contents. Versican was also detected in OA cartilage; however, the versican protein content was associated with a relatively low mRNA level. CONCLUSION The expression of matrix components was increased in chondrocytes of OA cartilage, especially the expression of small proteoglycans, most likely due to the repair processes. A discoordinate gene expression accompanied with imbalanced accumulation of noncollagenous matrix components may contribute to the disorganization of the cartilage and the development of OA processes.
Easy Bruisability

Physicians often see patients who complain of “easy bruising. ” The skill of the clinician is to identify those patients likely to have a potentially serious underlying disorder from those who do not. A detailed history often provides sufficient information. A comprehensive physical examination and possibly some baseline laboratory studies can add more data. These tools should permit the clinician to decide if the patient is either basically normal, may have simple contributing factors that lead to bruising, or is at significant risk of bleeding due to the presence of an underlying disorder. In certain circumstances, the situation will prompt the referral to a hematologist or other specialist (gastroenterologist, nephrologist, rheumatologist, endocrinologist, etc.).
The CPH1 Gene of Chlamydomonas reinhardtii Encodes Two Forms of Cryptochrome Whose Levels Are Controlled by Light-Induced Proteolysis1[w]

Cryptochromes are proteins related to DNA photolyases and have been shown to function as blue-light photoreceptors and to play important roles in circadian rhythms in both plants and animals. The CPH1 gene from Chlamydomonas reinhardtii was originally predicted to encode a putative cryptochrome protein of 867 amino acids with a predicted molecular mass of 91 kD (Small et al., 1995). However, western blotting with antibodies specific to the CPH1 protein revealed the presence of two proteins that migrate at apparent molecular mass of approximately 126 and 143 kD. A reexamination of the assigned intron-exon boundaries has shown that the previously assigned intron 7 is in fact part of exon 7 which leads to a predicted protein of 1,007 amino acids corresponding to a size of 104.6 kD. The two forms of CPH1 that migrate slower on SDS-PAGE presumably result from unknown posttranslational modifications. In C. reinhardtii cells synchronized by light to dark cycles, the two slow migrating forms of CPH1 protein accumulate in the dark and disappear rapidly in the light. Both red and blue light are effective at inducing the degradation of the CPH1 proteins. Proteasomes are implicated because degradation is inhibited by MG132, a proteasome inhibitor. Studies with deletion mutants indicate that the C-terminal region is important for both the posttranslational modification and the protein's stability under both light and dark conditions.
Serum cystatin C level is a good prognostic marker in patients with cirrhotic ascites and normal serum creatinine levels

Background/Aims: Serum creatinine (Cr) is not a reliable marker for early detection of renal dysfunction in patients with cirrhotic ascites. Several reports have suggested that cystatin C (CysC) is more sensitive than Cr for detecting reduced renal function in these patients. This study evaluated the clinical significance of CysC in patients with cirrhotic ascites and a normal serum Cr level.
Priming in Behavioral Public Administration: Methodological and Practical Considerations for Research and Scholarship

ABSTRACT: Despite its ubiquity in psychology and behavioral economics, and its utility in the assessment of cognitive processes, decisions, behavior, and actions, priming as a technique embedded in experimental designs is novel in behavioral public administration. And there is no clear guidance on how it should be done. We address this gap. Based on an illustrative study involving the priming of three institutional logics among public and private sector workers, and on a supplemental review of the literature, we present a synopsis of the theoretical underpinnings of priming research, and highlight methodological and practical considerations for experimental research using priming techniques. We additionally provide guidance for subsequent research and scholarship, and foreground the development of a methodology for conducting high-quality experimental research using priming techniques.
Population Analysis of the Perfect Breast: A Morphometric Analysis

Background: The authors previously identified key objective parameters that define the aesthetic ideal of the breast in a study of 100 models with natural breasts. In this follow-up article, the opinion of the general public on ideal breast proportions was surveyed. Methods: One thousand three hundred fifteen respondents were asked to rank the attractiveness of images of four women with varying breast sizes. Each of the women’s breasts were morphed into four different proportions. One of the key features was the upper pole–to–lower pole percentage proportion, corresponding to ratios of 35:65, 45:55, 50:50, and 55:45. Rankings were analyzed according to population demographics. Effects of age, sex, nationality, and ethnicity were evaluated. The responses of 53 plastic surgeons were included. Results: Breasts with an upper pole–to–lower pole ratio of 45:55 were universally scored highest, in particular, by 87 percent of women in their thirties (n = 190), 90 percent of men (n = 655), 94 percent of plastic surgeons (n = 53), 92 percent of North Americans (n = 89), 95 percent of South Americans (n = 23), 86 percent of Europeans (n = 982), 87 percent of Caucasians (n = 1016), and 87 percent of Asians (n = 209). Conclusions: This study reaffirms the authors’ previous findings that the 45:55 ratio has universal appeal in defining the ideal breast. The authors propose that this proportion should be used as a basis for design in aesthetic surgery.
Measurement of Axial Rotation of Vertebrae in Scoliosis

The authors report a radiographic method for measuring the axial rotation of vertebrae in degrees and its use in 99 patients with adolescent idiopathic scoliosis. The offset of the pedicle images from the vertebral body center and a “depth” estimate measured radiographically in a population of patients with scoliosis permitted calculation of axial rotation by means of a simple mathematical formula. It was found that measurements of vertebral rotation can be made clinically from single-plane radiographs with a standard deviation of 3.6° (95% confidence limit ±7.1°) based on a study of known rotations of a radiographic phantom, and with a standard deviation of 2.44° (95% confidence limit ±4.8°) based on comparisons with three-dimensional measurements of the orientation of each vertebra derived from low-dose stereo films of a group of patients. Measurements from clinical films are unlikely to be made more accurately than this, because of inherent geometric constraints.
Structural Requirement of Heparan Sulfate for Interaction with Herpes Simplex Virus Type 1 Virions and Isolated Glycoprotein C*

Cell surface heparan sulfates mediate primary attachment of herpes simplex virus type 1, the first step in virus invasion of the cells. Removal of the host cell heparan sulfate results in a significantly diminished susceptibility of the cell to virus infection. On the virus envelope, glycoprotein C has been identified as the major binding site for heparan sulfate in the primary attachment of the virus to host cells. Using selectively desulfated heparins and metabolically labeled host cell heparan sulfate, we have analyzed the structural requirements of heparan sulfate to provide binding sites for glycoprotein C and the whole virus. Employing glycoprotein C affinity chromatography and a virus binding assay, we subfractionated oligosaccharides derived from heparan sulfate and partially desulfated heparin into selectively bound and unbound pools. These were chemically depolymerized and analyzed at the disaccharide level. The shortest glycoprotein C-binding fragment consisted of 10–12 monosaccharide units containing at least one 2-O- and one 6-O-sulfate group that have to be localized in a sequence-specific way, based on the finding that bound and unbound HS fragments do not differ in charge or composition. The binding sequence is found within N-sulfated blocks of heparan sulfate, although several N-acetyl groups can be tolerated within the minimal binding sequence. These minimal requirements for herpes simplex virus type 1 binding to heparan sulfate are clearly distinct from other identified protein binding sites.