Miracle-dz/UniFAR-FTUs huggingface dataset:
Insulin‐like growth factor binding protein secretion by muscle cells: Effect of cellular differentiation and proliferation

Several cell types have been shown to secrete insulin‐like growth factor binding proteins (IGF‐BP) in vitro. Since IGF‐BP influences cell responsiveness to IGF, three muscle cell types were investigated to determine if they produced IGF‐BP and to identify factors that regulate IGF‐BP secretion. Porcine smooth muscle cells (pSMC), rat L6 skeletal muscle cells, and mouse BC3H‐1 myocytes were used. IGF‐BP activity in serum‐free conditioned media was quantitated with a polyethylene glycol precipitation method. All three cell types secreted IGF‐BP activity into the medium. Insulin was a potent stimulant of IGF‐BP secretion for each cell type. Specifically, 1 ug/ml insulin increased the IGF‐BP concentration in conditioned media from 10.5 ± 1.3 to 15.0 ± 1.5 ng/ml in confluent L6 myotubes, from 42.5 ± 11.1 to 90.5 ± 9.8 ng/ml in confluent BC3H‐1 cells, and from 2.1 ± 0.1 to 3.8 ± 0.1 ng/ml in confluent pSMC. L6 myotubes required more insulin (8 ug/ml) to achieve a half‐maximal stimulation of IGF‐BP secretion than confluent pSMC, differentiation deficient L6.DD cells or BC3H‐1 cells, where half‐maximal stimulation occurred between 125 and 300 ng/ml. L6 myoblasts were 40‐fold more sensitive to insulin stimulation of IGF‐BP secretion than L6 myotubes. IGF‐I, although it interferes with the assay and thereby lowers the amount of detectable IGF‐BP, stimulated the secretion of IGF‐BP from all three cell types. Dexamethasone, (10−7 M) decreased IGF‐BP secretion into the media by approximately 50% for all three cell types. Affinity cross‐linking and ligand blotting of 125I‐IGF‐I to conditioned media from each cell type showed (IGF‐BP)‐(IGF‐I) complexes with molecular weights ranging 32–40 kDa (24–32 kDa for IGF‐BP and 7.5 kDa for IGF‐I). Insulin stimulated cell proliferation for both L6 myoblasts and BC3H‐1 myocytes. This cell proliferative response was associated with an increase in IGF‐BP secretion/cell in response to insulin. In contrast dexamethasone decreased L6 myoblast proliferation and decreased IGF‐BP secretion/cell. We conclude that IGF‐BP is secreted by each muscle cell type and that the state of cellular differentiation or quiescence influences its basal and insulin‐stimulated secretion. Insulin and IGF‐I are stimulators of IGF‐BP secretion, whereas dexamethasone inhibits IGF‐BP secretion. Because these hormones control muscle cell growth and differentiation, the IGF‐BP may play an important regulatory role in these processes.
DRUG PROBLEM RECOGNITION, DESIRE FOR HELP, AND TREATMENT READINESS IN A SOUP KITCHEN POPULATION

This study determined hypothesized predictors of three components of motivation for change—drug problem recognition, desire for help, and treatment readiness—in a high-risk, drug-using population. The sample consisted of 190 guests at two inner-city soup kitchens in Brooklyn, NY who reported drug/alcohol use and were not participating in substance dependency treatment. Ever receiving addiction treatment, having no trade/job skills, and more severe symptoms of depression were associated with greater drug problem recognition. More recent days of drug/alcohol use, intensive pattern of drug use, and greater problem recognition were associated with greater desire for help. Caring for children, more recent days of drug/alcohol use, physical health problems, and desire for help were the direct predictors of treatment readiness. Problem recognition had a strong indirect effect on readiness mediated through desire for help. Knowledge of a drug user's motivational state and the factors leading to it can help guide the development of more effective interventions.
Productivity Growth: Towards a Sociological Synthesis

Abstract As a means of increasing living standards productivity growth now features as a key element in state economic and industrial relations policy. But how successful have economists and labour market specialists been in identifying the sources of productivity growth? The paper looks at this question as well as examining analyses provided by management researchers and sociologists. It concludes that productivity growth depends a great deal on management but that management behaviour needs to be situated empirically in relation to the role of the state and major economic institutions. Hence the importance of a sociological approach that is historically grounded and combines macro and micro analysis.
The Carotenoid Cleavage Dioxygenase 1 Enzyme Has Broad Substrate Specificity, Cleaving Multiple Carotenoids at Two Different Bond Positions*

In many organisms, various enzymes mediate site-specific carotenoid cleavage to generate biologically active apocarotenoids. These carotenoid-derived products include provitamin A, hormones, and flavor and fragrance molecules. In plants, the CCD1 enzyme cleaves carotenoids at 9,10 (9′,10′) bonds to generate multiple apocarotenoid products. Here we systematically analyzed volatile apocarotenoids generated by maize CCD1 (ZmCCD1) from multiple carotenoid substrates. ZmCCD1 did not cleave geranylgeranyl diphosphate or phytoene but did cleave other linear and cyclic carotenoids, producing volatiles derived from 9,10 (9′,10′) bond cleavage. Additionally the Arabidopsis, maize, and tomato CCD1 enzymes all cleaved lycopene to generate 6-methyl-5-hepten-2-one. 6-Methyl-5-hepten-2-one, an important flavor volatile in tomato, was produced by cleavage of the 5,6 or 5′,6′ bond positions of lycopene but not geranylgeranyl diphosphate, ζ-carotene, or phytoene. In vitro, ZmCCD1 cleaved linear and cyclic carotenoids with equal efficiency. Based on the pattern of apocarotenoid volatiles produced, we propose that CCD1 recognizes its cleavage site based on the saturation status between carbons 7 and 8 (7′ and 8′) and carbons 11 and 12 (11′ and 12′) as well as the methyl groups on carbons 5, 9, and 13 (5′, 9′, and 13′).
La dengue : un vaccin à l'horizon 2015

La dengue est une maladie recente dans l'histoire de l'homme mais sa forte expansion lors des dernieres decennies (en 2008, les experts estimaient que 40% de la population mondiale est exposee), fait de cette arbovirose un probleme de sante publique majeur. Alors que la maladie s'exprime faiblement dans la plupart des cas (ou sous la forme d'une simple fievre), la dengue donne de plus en plus des formes severes avec fuite vasculaire et hemorragies. L'explosion de ces cas sous forme d'epidemies a conduit les autorites de sante a mettre au point des moyens de lutte efficaces contre la dengue. La recherche d'un vaccin est donc devenue une priorite. Les caracteristiques de la maladie, la presence de quatre serotypes, le role de la reponse immunitaire dans la pathogenese, l'absence de modele animal sont des difficultes auxquelles les laboratoires ont du faire face. Malgre ces problemes, un panel de candidats vaccins existe comprenant des vaccins vivants attenues, chimeriques, inactives, vaccin ADN nu et vaccin vectorise ou enfin vaccin a replication incompetente. Parmi ceux-ci, certains sont a des stades de developpement clinique bien avance, dont le vaccin chimerique VJF17D de Acambis/Sanofi-Pasteur qui s'impose comme le leader actuel. Il est entre en phase clinique III et pourrait etre commercialise d'ici 4 ou 5 ans.
Student Development through student- monitored projects and volunteerism: Effat University Case Study

The prime goal of liberal arts philosophy in education is the acquisition of transferable skills and competencies that transform students to life-long learners. Liberal arts philosophy yields itself to learning theories that consider the learner as an active member in a community of learners. "All the higher functions originate as actual relationships between individuals". Effat University in Saudi Arabia adopts a holistic approach to educating students. This approach embraces student development in four areas; academic, personal, professional, and social, which are developed through a specially tailored leadership program known as the "Effat Ambassadors Program" (EAP). A variety of methods starting with direct instruction in classrooms, and using technology platforms, and lately utilizing the cascade model in education and training which allows students to learn as they practice, and enhance their learning by training others.
Pathology of Inhalation Anthrax in Cynomolgus Monkeys (Macaca fascicularis)

Anthrax is considered a serious biowarfare and bioterrorism threat because of its high lethality, especially by the inhalation route. Rhesus macaques (Macaca mulatta) are the most commonly used nonhuman primate model of human inhalation anthrax exposure. The nonavailability of rhesus macaques necessitated development of an alternate model for vaccine testing and immunologic studies. This report describes the median lethal dose (LD50) and pathology of inhalation anthrax in cynomolgus macaques (Macaca fascicularis). Gross and microscopic tissue changes were reviewed in 14 cynomolgus monkeys that died or were killed after aerosol exposure of spores of Bacillus anthracis (Ames strain). The LD50 and 95% confidence intervals were 61,800 (34,000 to 110,000) colony-forming units. The most common gross lesions were mild splenomegaly, lymph node enlargement, and hemorrhages in various organs, particularly involving the meninges and the lungs. Mediastinitis, manifested as hemorrhage or edema, affected 29% of the monkeys. Microscopically, lymphocytolysis occurred in the intrathoracic lymph nodes and spleens of all animals, and was particularly severe in the spleen and in germinal centers of lymph nodes. Hemorrhages were common in lungs, bronchial lymph nodes, meninges, gastrointestinal tract, and mediastinum. These results demonstrate that the Ames strain of B. anthracis is lethal by the inhalation route in the cynomolgus macaque. The LD50 of the Ames strain of B. anthracis was within the expected experimental range of previously reported values in the rhesus monkey in an aerosol challenge. The gross and microscopic pathology of inhalation anthrax in the cynomolgus monkey is remarkably similar to that reported in rhesus monkeys and humans. The results of this study are important for the establishment of an alternative nonhuman primate model for evaluation of medical countermeasures against inhalational anthrax.
Improving Cutaneous Scar Formation by Controlling the Mechanical Environment: Large Animal and Phase I Studies

Objective: To test the hypothesis that the mechanical environment of cutaneous wounds can control scar formation. Background: Mechanical forces have been recognized to modulate myriad biologic processes, but the role of physical force in scar formation remains unclear. Furthermore, the therapeutic benefits of offloading cutaneous wounds with a device have not been rigorously tested. Methods: A mechanomodulating polymer device was utilized to manipulate the mechanical environment of closed cutaneous wounds in red Duroc swine. After 8 weeks, wounds subjected to different mechanical stress states underwent immunohistochemical analysis for fibrotic markers. In a phase I clinical study, 9 human patients undergoing elective abdominal surgery were treated postoperatively with a stress-shielding polymer on one side whereas the other side was treated as standard of care. Professional photographs were taken between 8 and 12 months postsurgery and evaluated using a visual analog scale by lay and professional panels. This study is registered with ClinicalTrials.gov, number NCT00766727. Results: Stress shielding of swine incisions reduced histologic scar area by 6- and 9-fold compared to control and elevated stress states, respectively (P < 0.01 for both) and dramatically decreased the histologic expression of profibrotic markers. Closure of high-tension wounds induced human-like scar formation in the red Duroc, a phenotype effectively mitigated with stress shielding of wounds. In the study on humans, stress shielding of abdominal incisions significantly improved scar appearance (P = 0.004) compared with within-patient controls. Conclusions: These results indicate that mechanical manipulation of the wound environment with a dynamic stress-shielding polymer device can significantly reduce scar formation.
Human Immunodeficiency Virus Type 1 Subtype C Molecular Phylogeny: Consensus Sequence for an AIDS Vaccine Design?

ABSTRACT An evolving dominance of human immunodeficiency virus type 1 subtype C (HIV-1C) in the AIDS epidemic has been associated with a high prevalence of HIV-1C infection in the southern African countries and with an expanding epidemic in India and China. Understanding the molecular phylogeny and genetic diversity of HIV-1C viruses may be important for the design and evaluation of an HIV vaccine for ultimate use in the developing world. In this study we analyzed the phylogenetic relationships (i) between 73 nonrecombinant HIV-1C near-full-length genome sequences, including 51 isolates from Botswana; (ii) between HIV-1C consensus sequences that represent different geographic subsets; and (iii) between specific isolates and consensus sequences. Based on the phylogenetic analyses of 73 near-full-length genomes, 16 “lineages” (a term that is used hereafter for discussion purposes and does not imply taxonomic standing) were identified within HIV-1C. The lineages were supported by high bootstrap values in maximum-parsimony and neighbor-joining analyses and were confirmed by the maximum-likelihood method. The nucleotide diversity between the 73 HIV-1C isolates (mean value of 8.93%; range, 2.9 to 11.7%) was significantly higher than the diversity of the samples to the consensus sequence (mean value of 4.86%; range, 3.3 to 7.2%, P < 0.0001). The translated amino acid distances to the consensus sequence were significantly lower than distances between samples within all HIV-1C proteins. The consensus sequences of HIV-1C proteins accompanied by amino acid frequencies were presented (that of Gag is presented in this work; those of Pol, Vif, Vpr, Tat, Rev, Vpu, Env, and Nef are presented elsewhere [http://www.aids.harvard.edu/lab_research/concensus_sequence.htm ]). Additionally, in the promoter region three NF-κB sites (GGGRNNYYCC) were identified within the consensus sequences of the entire set or any subset of HIV-1C isolates. This study suggests that the consensus sequence approach could overcome the high genetic diversity of HIV-1C and facilitate an AIDS vaccine design, particularly if the assumption that an HIV-1C antigen with a more extensive match to the circulating viruses is likely to be more efficacious is proven in efficacy trials.
Novel antibacterial strategies to combat biomaterial-associated infection

The scarcity of current antibiotic-based strategies to prevent biomaterial-associated infections (BAI) and their risk of resistance development prompted us to develop a novel antimicrobial implant-coating to prevent Staphylococcus aureus-induced BAI. We incorporated the antimicrobial peptide OP-145 into a Polymer-Lipid Encapsulation MatriX (PLEX)-coating to obtain high peptide levels for prolonged periods at the implant-tissue interphase. We first confirmed that OP-145 was highly effective in killing S. aureus and inhibiting biofilm formation in vitro. OP-145 injected along S. aureus-inoculated implants in mice significantly reduced the number of culture-positive implants. OP-145 was released from the PLEX coating in a controlled zero-order kinetic rate after an initial 55%-burst release and displayed bactericidal activity in vitro. In a rabbit intramedullary nail-related infection model, 67% of rabbits with PLEX-OP-145-coated nails had culture-negative nails after 28 days compared to 29% of rabbits with uncoated nails. In rabbits with PLEX-OP-145-coated nails, bone and soft tissue samples were culture-negative in 67% and 80%, respectively, whereas all bone samples and 71% of the soft tissue samples of rabbits with uncoated nails were infected. Together, PLEX-OP-145 coatings, of which both compounds have already been found safe in man, can prevent implant colonization and S. aureus-induced BAIs.
Black-Scholes: What’s Next?

In 1973 Fisher Black and Myron Scholes published their seminal paper "The Pricing of Options and Corporate Liabilities". Many authors have since tried to factor in one or more of these imperfections while seeking to retain the broad framework constructed by Black and Scholes. This has resulted in an abundant literature that can often leave the reader totally at sea. In this issue of Quants, we offer a synoptic and original vision of the subject that will, we hope, act as a practical guide to these complex notions.
Institutional Characteristics and State Policy Priorities

This article examines how the institutional characteristics of state legislatures and governors affect state policy priorities. We argue that differences in the nature of their respective constituencies lead legislators to press for particularized benefits while governors favor collective goods. Empirical analysis of state-level data from 1982 through 2011 confirms that this is the case. The organizational arrangements of the two branches of government have an impact that is usually greater than that of state public opinion but generally less than that of state interest groups. The results from this analysis are important because they show that institutional structure has systematic effects that are independent of ideology, partisanship, and the other factors that are known to shape state policy making.
Sequence Diversity of Treponema pallidum subsp. pallidum tprK in Human Syphilis Lesions and Rabbit-Propagated Isolates

ABSTRACT The tprK gene of Treponema pallidum subsp. pallidum, the causative agent of venereal syphilis, belongs to a 12-member gene family and encodes a protein with a predicted cleavable signal sequence and predicted transmembrane domains. Except for the Nichols type strain, all rabbit-propagated isolates of T. pallidum examined thus far are comprised of mixed populations of organisms with heterogeneous tprK sequences. We show that tprK sequences in treponemes obtained directly from syphilis patients are also heterogeneous. Clustering analysis demonstrates that primary chancre tprK sequences are more likely to cluster within a sample than among samples and that tighter clustering is seen within chancre samples than within rabbit-propagated isolates. Closer analysis of tprK sequences from a rabbit-propagated isolate reveals that individual variable regions have different levels of diversity, suggesting that variable regions may have different intrinsic rates of sequence change or may be under different levels of selection. Most variable regions show increased sequence diversity upon passage. We speculate that the diversification of tprK during infection allows organisms to evade the host immune response, contributing to reinfection and persistent infection.
The Higher Education Contribution Scheme - a HECS on the Family?

It is generally well accepted amongst the demographic community that policy does not have to be even remotely concerned with population for it to have important demographic outcomes. This paper argues that the Higher Education Contribution Scheme (HECS), which has potentially strong antinatal elements, may be one such policy. Because of a lack of data, the purpose of the paper is to establish the hypothesis, rather than to test it.
Why Not Fight and Trade? Dissecting the Logic of the Opportunity Cost Mechanism

Massachusetts Institute of Technology 2008-2015 PhD in Political Science (International Relations) Dissertation: Red Lines and Faits Accomplis in Interstate Coercion and Crisis Committee: Barry Posen (Chair), Kenneth Oye, Vipin Narang, Phil Haun Brown University 2004-2008 BA in International Relations with Honors, magna cum laude, Phi Beta Kappa Stanton Predoctoral Fellow (Stanford – CISAC) 2013-2014 MacArthur Pre/Postdoctoral Fellow (Stanford – CISAC) 2014-2015 Postdoctoral Fellow (Dartmouth – Dickey Center) 2015-2016
Positive Selection of T Cells Induced by Viral Delivery of Neopeptides to the Thymus

The relation between an antigenic peptide that can stimulate a mature T cell and the natural peptide that promoted selection of this cell in the thymus is still unknown. An experimental system was devised to address this issue in vivo—mice expressing neopeptides in thymic stromal cells after adenovirus-mediated delivery of invariant chain-peptide fusion proteins. In this system, selection of T cells capable of responding to a given antigenic peptide could be promoted by the peptide itself, by closely related analogs lacking agonist and antagonist activity, or by ostensibly unrelated peptides. However, the precise repertoire of T cells selected was dictated by the particular neopeptide expressed.
The MOOCs: origin, characterization, principal problems and challenges in Higher Education

MOOCs (Massive Open Online Courses) are an innovation that have attracted public academic attention in recent times, and which have resulted in the evolution of e-learning (electronic learning) and so far have not achieved their expectations in Higher Education. This is due to the fact that from the outset these courses have faced a number of problems and questions regarding their acceptance, credibility, quality, methods of assessment, learning outcomes and more; which has generated controversy among their opponents, fans and even the creators of MOOCs. This work forms part of a doctoral investigation; in essence these are the results of the preliminary and exploratory stages in the research process, in which projections on the solution of some problems will be included. MOOCs: Their evolution, problems and challenges up to 2015, will surely help to minimize the high dropout rates of students in MOOCs, supported by mobile technology.
Left ventricular inotropic responses to stimulation of carotid body chemoreceptors in anaesthetized dogs.

1. Dogs were anaesthetized with chloralose and artificially ventilated. The regions of both carotid bifurcations were vascularly isolated and perfused at constant pressure with arterial blood or with venous or hypoxic blood. 2. Inotropic responses were assessed by measuring the maximum rate of change of left ventricular pressure (dP/dtmax) with aortic pressure and heart rate held constant. 3. Stimulation of the chemoreceptors with venous blood from the inferior vena cava resulted in a decrease in dP/dtmax from 510 +/‐ 27 kPa.s‐1 to 418 +/‐ 21 kPa.s‐1 (mean +/‐ S.E.): a change of 17.9 +/‐ 1.0% 4. In experiments in which the oxygen tension of the blood perfusing the carotid chemoreceptors was decreased in steps between 10 and 3 kPa, by use of an oxygenator, graded responses of dP/dtmax were obtained at each step. 5. The inotropic responses to chemoreceptor stimulation were abolished by raising carotid pressure. 6. The inotropic responses were abolished either by crushing both carotid bodies or both ansae subclaviae, indicating that the reflex originates from the carotid bodies and that the efferent pathway is in the cardiac sympathetic nerves.