Workplace Organization and Innovation

This study uses data on Canadian establishments to test whether particular organizational structures are correlated with the likelihood of adopting process and product innovations, controlling for the endogeneity of the predictors. We find that establishments with decentralized decision-making, information-sharing programs, or incentive pay plans are significantly more likely to innovate than other establishments. Larger establishments and those with a high vacancy rate are also more likely to innovate. These findings are consistent with a model in which workers hold information about production inefficiencies or consumer demands that can lead to productive innovations and that workplace organization attributes facilitate the communication and implementation of those ideas.Innovation, Decision-Making, Information-Sharing

Cell-Specific Aptamers as Emerging Therapeutics

Aptamers are short nucleic acids that bind to defined targets with high affinity and specificity. The first aptamers have been selected about two decades ago by an in vitro process named SELEX (systematic evolution of ligands by exponential enrichment). Since then, numerous aptamers with specificities for a variety of targets from small molecules to proteins or even whole cells have been selected. Their applications range from biosensing and diagnostics to therapy and target-oriented drug delivery. More recently, selections using complex targets such as live cells have become feasible. This paper summarizes progress in cell-SELEX techniques and highlights recent developments, particularly in the field of medically relevant aptamers with a focus on therapeutic and drug-delivery applications

Prospectus, September 12, 1979

VOTE!; Arlo Guthrie is reviewed -- onstage and off; Cobras to star on TV; Bloodsucking auditions to be held next week; Real estate workshop Sat.; Join the Circle K; International rep. speaks out; Support the candidate of your choice: Vote today; Start a write-in campaign; The two faces of Arlo; Top 10 For WPCD; Classifieds; Chanute celebrates Hispanic week; \u27Pal\u27 program trying to get a start; STO will have formal Rush; Circus reservations still available; New art shop in St. Joseph; Krannert events thru 16th; Freddy is upset; Sport shortssportshortsportshortsport; Fast Freddy Contesthttps://spark.parkland.edu/prospectus_1979/1013/thumbnail.jp

Streptokinase Treatment Reverses Biofilm-Associated Antibiotic Resistance in Staphylococcus aureus

Biofilms formed by Staphylococcus aureus is a serious complication to the use of medical implants. A central part of the pathogenesis relies on S. aureus’ ability to adhere to host extracellular matrix proteins, which adsorb to medical implants and stimulate biofilm formation. Being coagulase positive, S. aureus furthermore induces formation of fibrin fibers from fibrinogen in the blood. Consequently, we hypothesized that fibrin is a key component of the extracellular matrix of S. aureus biofilms under in vivo conditions, and that the recalcitrance of biofilm infections can be overcome by combining antibiotic treatment with a fibrinolytic drug. We quantified S. aureus USA300 biofilms grown on peg-lids in brain heart infusion (BHI) broth with 0%–50% human plasma. Young (2 h) and mature (24 h) biofilms were then treated with streptokinase to determine if this lead to dispersal. Then, the minimal biofilm eradication concentration (MBEC) of 24 h old biofilms was measured for vancomycin and daptomycin alone or in combination with 10 µg/mL rifampicin in the presence or absence of streptokinase in the antibiotic treatment step. Finally, biofilms were visualized by confocal laser scanning microscopy. Addition of human plasma stimulated biofilm formation in BHI in a dose-dependent manner, and biofilms could be partially dispersed by streptokinase. The biofilms could be eradicated with physiologically relevant concentrations of streptokinase in combination with rifampicin and vancomycin or daptomycin, which are commonly used antibiotics for treatment of S. aureus infections. Fibronolytic drugs have been used to treat thromboembolic events for decades, and our findings suggest that their use against biofilm infections has the potential to improve the efficacy of antibiotics in treatment of S. aureus biofilm infections

Interleukin-6 receptor specific RNA aptamers for cargo delivery into target cells

Aptamers represent an emerging strategy to deliver cargo molecules, including dyes, drugs, proteins or even genes, into specific target cells. Upon binding to specific cell surface receptors aptamers can be internalized, for example by macropinocytosis or receptor mediated endocytosis. Here we report the in vitro selection and characterization of RNA aptamers with high affinity (Kd = 20 nM) and specificity for the human IL-6 receptor (IL-6R). Importantly, these aptamers trigger uptake without compromising the interaction of IL-6R with its natural ligands the cytokine IL-6 and glycoprotein 130 (gp130). We further optimized the aptamers to obtain a shortened, only 19-nt RNA oligonucleotide retaining all necessary characteristics for high affinity and selective recognition of IL-6R on cell surfaces. Upon incubation with IL-6R presenting cells this aptamer was rapidly internalized. Importantly, we could use our aptamer, to deliver bulky cargos, exemplified by fluorescently labeled streptavidin, into IL-6R presenting cells, thereby setting the stage for an aptamer-mediated escort of drug molecules to diseased cell populations or tissues

The Ursinus Weekly, April 28, 1977

Ursinus news in brief: Mattress team takes second; Chemistry delegates tapped; Cub & Key chooses officers; Classes elect officers; Economics Club elects officers; Library announces new hours; Pre-legal Society elections held • SFARC discusses Weekly • Meal popularity surveyed • GRE revised • Food service names liaison • Comment: After orientation, what then? • Curriculum review urged • Letters to the editor • Musical gobs • Perfection personified • Movie attack: Airport 77 • Band holds concert • Presidential memo • Weekly special: Fidel interested in assassination probe • Songfest \u2777 • Faculty promotions announced • More on food • Sum. Eve. School • Baseball team excites fans • Lacrosse undefeated • Tennis times • Women\u27s tennis • Amateur boxing • Track • Golf • Correction • Mexico triphttps://digitalcommons.ursinus.edu/weekly/1070/thumbnail.jp

Negative impacts of invasive predators used as biological control agents against the pest snail Lissachatina fulica: the snail Euglandina ‘rosea’ and the flatworm Platydemus manokwari

Since 1955 snails of the Euglandina rosea species complex and Platydemus manokwari flatworms were widely introduced in attempted biological control of giant African snails (Lissachatina fulica) but have been implicated in the mass extinction of Pacific island snails. We review the histories of the 60 introductions and their impacts on L. fulica and native snails. Since 1993 there have been unofficial releases of Euglandina within island groups. Only three official P. manokwari releases took place, but new populations are being recorded at an increasing rate, probably because of accidental introduction. Claims that these predators controlled L. fulica cannot be substantiated; in some cases pest snail declines coincided with predator arrival but concomitant declines occurred elsewhere in the absence of the predator and the declines in some cases were only temporary. In the Hawaiian Islands, although there had been some earlier declines of native snails, the Euglandina impacts on native snails are clear with rapid decline of many endemic Hawaiian Achatinellinae following predator arrival. In the Society Islands, Partulidae tree snail populations remained stable until Euglandina introduction, when declines were extremely rapid with an exact correspondence between predator arrival and tree snail decline. Platydemus manokwari invasion coincides with native snail declines on some islands, notably the Ogasawara Islands of Japan, and its invasion of Florida has led to mass mortality of Liguus spp. tree snails. We conclude that Euglandina and P. manokwari are not effective biocontrol agents, but do have major negative effects on native snail faunas. These predatory snails and flatworms are generalist predators and as such are not suitable for biological control

Anti-inflammatory activity and neutrophil reductions mediated by the JAK1/JAK3 inhibitor, CP-690,550, in rat adjuvant-induced arthritis

<p>Abstract</p> <p>Background</p> <p>The Janus kinase (JAK) family of tyrosine kinases includes JAK1, JAK2, JAK3 and TYK2, and is required for signaling through Type I and Type II cytokine receptors. CP-690,550 is a potent and selective JAK inhibitor currently in clinical trials for rheumatoid arthritis (RA) and other autoimmune disease indications. In RA trials, dose-dependent decreases in neutrophil counts (PBNC) were observed with CP-690,550 treatment. These studies were undertaken to better understand the relationship between JAK selectivity and PBNC decreases observed with CP-690,550 treatment.</p> <p>Methods</p> <p>Potency and selectivity of CP-690,550 for mouse, rat and human JAKs was evaluated in a panel of <it>in vitro </it>assays. The effect of CP-690,550 on granulopoiesis from progenitor cells was also assessed <it>in vitro </it>using colony forming assays. <it>In vivo </it>the potency of orally administered CP-690,550 on arthritis (paw edema), plasma cytokines, PBNC and bone marrow differentials were evaluated in the rat adjuvant-induced arthritis (AIA) model.</p> <p>Results</p> <p>CP-690,550 potently inhibited signaling through JAK1 and JAK3 with 5-100 fold selectivity over JAK2 in cellular assays, despite inhibiting all four JAK isoforms with nM potency in <it>in vitro </it>enzyme assays. Dose-dependent inhibition of paw edema was observed <it>in vivo </it>with CP-690,550 treatment. Plasma cytokines (IL-6 and IL-17), PBNC, and bone marrow myeloid progenitor cells were elevated in the context of AIA disease. At efficacious exposures, CP-690,550 returned all of these parameters to pre-disease levels. The plasma concentration of CP-690,550 at efficacious doses was above the <it>in vitro </it>whole blood IC50 of JAK1 and JAK3 inhibition, but not that of JAK2.</p> <p>Conclusion</p> <p>Results from this investigation suggest that CP-690,550 is a potent inhibitor of JAK1 and JAK3 with potentially reduced cellular potency for JAK2. In rat AIA, as in the case of human RA, PBNC were decreased at efficacious exposures of CP-690,550. Inflammatory end points were similarly reduced, as judged by attenuation of paw edema and cytokines IL-6 and IL-17. Plasma concentration at these exposures was consistent with inhibition of JAK1 and JAK3 but not JAK2. Decreases in PBNC following CP-690,550 treatment may thus be related to attenuation of inflammation and are likely not due to suppression of granulopoiesis through JAK2 inhibition.</p

Connexin43 Mimetic Peptide Improves Retinal Function and Reduces Inflammation in a Light-Damaged Albino Rat Model

PURPOSE. Drugs that regulate connexin43 (Cx43) gap junction channels can reduce the spread of injury and improve functional outcomes after nervous system trauma. In the eye, Cx43 expression increases in the choroid following light damage. The aim of this study was to investigate whether Cx43 hemichannel block could preserve retinal function postinjury. METHODS. Light damage was induced by exposure of adult albino Sprague-Dawley rats to 2700 Lux light for 24 hours. Intravitreal injections of a Cx43 mimetic peptide hemichannel blocker, Peptide5, or sham were administered 2 hours after the onset and at the end of the light damage period. Retinal function was assessed by electroretinogram and inflammatory responses in the choroid and retina were assessed using immunohistochemistry (ionized calcium binding adaptor molecule 1 [Iba-1], leukocyte common antigen [CD45], glial fibrillary acidic protein [GFAP]). RESULTS. Light-damaged rat eyes had (1) reduced neuronal responses in both the rod and cone pathways and (2) marked inflammatory responses in the choroid and retina. Peptide5 significantly preserved function of photoreceptoral and postphotoreceptoral neurons in these animals. This was evident 24 hours after injury and 2 weeks later, as shown by improved mixed a-wave and mixed b-wave amplitudes, isolated rod PII and PIII amplitudes, and cone PII responses when compared with sham-treated controls. Retinal thinning and inflammation were also significantly reduced in Peptide5-treated eyes when compared with sham-treated controls. CONCLUSIONS. Blocking Cx43 hemichannels after light damage can significantly improve functional outcomes of neurons in both the rod and cone photo-transduction pathways in the light-damaged animal model, likely by reducing choroid inflammation and suppressing the glial-mediated inflammatory response. These data may have relevance for the treatment of conditions such as diabetic retinopathy and age-related macular degeneration

The Rat Genome Database (RGD): developments towards a phenome database

The Rat Genome Database (RGD) (http://rgd.mcw.edu) aims to meet the needs of its community by providing genetic and genomic infrastructure while also annotating the strengths of rat research: biochemistry, nutrition, pharmacology and physiology. Here, we report on RGD's development towards creating a phenome database. Recent developments can be categorized into three groups. (i) Improved data collection and integration to match increased volume and biological scope of research. (ii) Knowledge representation augmented by the implementation of a new ontology and annotation system. (iii) The addition of quantitative trait loci data, from rat, mouse and human to our advanced comparative genomics tools, as well as the creation of new, and enhancement of existing, tools to enable users to efficiently browse and survey research data. The emphasis is on helping researchers find genes responsible for disease through the use of rat models. These improvements, combined with the genomic sequence of the rat, have led to a successful year at RGD with over two million page accesses that represent an over 4-fold increase in a year. Future plans call for increased annotation of biological information on the rat elucidated through its use as a model for human pathobiology. The continued development of toolsets will facilitate integration of these data into the context of rat genomic sequence, as well as allow comparisons of biological and genomic data with the human genomic sequence and of an increasing number of organisms