Free in, free out? Outbound transfer of user innovations in small UK firms

Small firms develop user innovations, with some going on to become viable new industrial products - the challenge to industrial suppliers being to identify and absorb such innovations from their existing or potential customer base. In this paper we: i) analyse which small firms more likely develop user innovations; ii) investigate how the outbound knowledge transfer of user innovations is related to inbound knowledge sourcing and acquisition; and iii) explore why small firms may reveal user innovations. Drawing on a survey of 1004 small firms in the United Kingdom, of which 23 revealed their user innovations, the research confirms that the incidence of this phenomenon is related to firm size and general innovation activity. However, in direct contrast to innovating consumers or open-source contributors, the revealing of locally-created innovations was shown to be selective and motivated by optional future benefits. Further, it emerged that small firms barely freely reveal at all, suggesting that further research of this phenomena in the context of small firms is required. These in-depth insights into small firm revealing behaviour are of great value to industrial suppliers who wish to draw on innovations that emerge within their existing or potential customer base

PIP5KIβ Selectively Modulates Apical Endocytosis in Polarized Renal Epithelial Cells

Localized synthesis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] at clathrin coated pits (CCPs) is crucial for the recruitment of adaptors and other components of the internalization machinery, as well as for regulating actin dynamics during endocytosis. PtdIns(4,5)P2 is synthesized from phosphatidylinositol 4-phosphate by any of three phosphatidylinositol 5-kinase type I (PIP5KI) isoforms (α, β or γ). PIP5KIβ localizes almost exclusively to the apical surface in polarized mouse cortical collecting duct cells, whereas the other isoforms have a less polarized membrane distribution. We therefore investigated the role of PIP5KI isoforms in endocytosis at the apical and basolateral domains. Endocytosis at the apical surface is known to occur more slowly than at the basolateral surface. Apical endocytosis was selectively stimulated by overexpression of PIP5KIβ whereas the other isoforms had no effect on either apical or basolateral internalization. We found no difference in the affinity for PtdIns(4,5)P2-containing liposomes of the PtdIns(4,5)P2 binding domains of epsin and Dab2, consistent with a generic effect of elevated PtdIns(4,5)P2 on apical endocytosis. Additionally, using apical total internal reflection fluorescence imaging and electron microscopy we found that cells overexpressing PIP5KIβ have fewer apical CCPs but more internalized coated structures than control cells, consistent with enhanced maturation of apical CCPs. Together, our results suggest that synthesis of PtdIns(4,5)P2 mediated by PIP5KIβ is rate limiting for apical but not basolateral endocytosis in polarized kidney cells. PtdIns(4,5)P2 may be required to overcome specific structural constraints that limit the efficiency of apical endocytosis. © 2013 Szalinski et al

The Ultra-luminous M81 X-9 source: 20 years variability and spectral states

The source X-9 was discovered with the {\it Einstein Observatory} in the field of M81, and is located in the dwarf galaxy Holmberg IX. X-9 has a 0.2-4.0 keV luminosity of $\sim 5.5\times 10^{39}$ ergs~s$^{-1}$, if it is at the same distance as Holmberg IX (3.4 Mpc). This luminosity is above the Eddington luminosity of a 1~$M_{\odot}$ compact accreting object. Past hypotheses on the nature of this Super-Eddington source included a SNR or supershell, an accreting compact object and a background QSO. To shed light on the nature of this source, we have obtained and analyzed archival data, including the {\it Einstein} data, 23 ROSAT observations, Beppo-SAX and ASCA pointings. Our analysis reveals that most of the emission of X-9 arises from a point-like highly-variable source, and that lower luminosity extended emission may be associated with it. The spectrum of this source changes between low and high intensity states, in a way reminiscent of the spectra of galactic Black Hole candidates. Our result strongly suggest that X-9 is not a background QSO, but a bonafide `Super-Eddington' source in Ho IX, a dwarf companion of M81.Comment: 31 pages, 10 figures, ApJ - accepted for publicatio

3,4-Methylenedioxymethamphetamine Alters Left Ventricular Function and Activates Nuclear Factor-Kappa B (NF-κB) in a Time and Dose Dependent Manner

3,4-Methylenedioxymethamphetamine (MDMA) is an illicit psychoactive drug with cardiovascular effects that have not been fully described. In the current study, we observed the effects of acute MDMA on rabbit left ventricular function. We also observed the effects of MDMA on nuclear factor-kappa B (NF-κB) activity in cultured rat ventricular myocytes (H9c2). In the rabbit, MDMA (2 mg/kg) alone caused a significant increase in heart rate and a significant decrease in the duration of the cardiac cycle. Inhibition of nitric oxide synthase (NOS) by pretreatment with L-NAME (10 mg/kg) alone caused significant dysfunction in heart rate, systolic pressure, diastolic pressure, duration of relaxation, duration of cardiac cycle, and mean left ventricular pressure. Pretreatment with L-NAME followed by treatment with MDMA caused significant dysfunction in additional parameters that were not abnormal upon exposure to either compound in isolation: duration of contraction, inotropy, and pulse pressure. Exposure to 1.0 mM MDMA for 6 h or 2.0 μM MDMA for 12 h caused increased nuclear localization of NF-κB in cultured H9c2 cells. The current results suggest that MDMA is acutely detrimental to heart function and that an intact cardiovascular NOS system is important to help mitigate early sequelae in some functional parameters. The delayed timing of NF-κB activation suggests that this factor may be relevant to MDMA induced cardiomyopathy of later onset

Consumo de drogas ilegales, apoyo familiar y factores relacionadosen estudiantes universitarios. Un estudio transversal basado en datosdel Proyecto uniHcos

Objective: To assess the prevalence of illegal drug use in college students on any previous occasion, duringthe previous year and the previous month, and to analyze the relationship between illegal drug use andfamily support and other factors.Methods: A cross-sectional study using data from students participating in the uniHcos project (n = 3767)was conducted. The prevalence and age of onset of consumption of cannabis, non-prescription sedatives,stimulants and depressants was evaluated. Polyconsumption was also assessed. The independent vari-ables were: family support, age, residence, and employment status. To determine the factors related todrug use multivariate logistic regression models stratified by gender were fitted.Results: Differences between men and women in prevalence of illegal drug use except non-prescriptionsedatives were observed. In both genders, less family support was associated with higher consumptionof all drugs, except depressants, and with polyconsumption. To be studying and looking for work wasrelated to cannabis and stimulant use and to polyconsumption among women, but only to cannabis useamong men.Conclusions: These results support the notion that the start of university studies is a particularly relevantstage in the onset of illegal drug use and its prevention, and that consumption may be especially associatedwith family support.Objetivo: Evaluar la prevalencia del consumo de drogas ilegales en estudiantes universitarios y analizarla relación entre dicho consumo, el apoyo familiar y otros factores.Método: Se realizó un dise?no transversal basado en datos de participantes en el proyecto uniHcos (n =3767). Se evaluaron la prevalencia y la edad de inicio del consumo de cannabis, tranquilizantes sin receta,estimulantes y depresores, y el policonsumo. Como variables independientes se consideraron el apoyofamiliar, la edad, la residencia y la situación laboral. Para la determinación de los factores asociados alconsumo de drogas se ajustaron modelos de regresión logística estratificados por sexo.Resultados: Se observaron diferencias entre hombres y mujeres en la prevalencia del consumo de todaslas drogas ilegales, excepto tranquilizantes sin receta. En ambos sexos, cuanto peor apoyo familiar, mayorconsumo de todas las drogas, excepto depresores y policonsumo. Encontrarse estudiando y buscandotrabajo se relacionó con el consumo de cannabis, estimulantes y policonsumo en las mujeres, y solo concannabis en los hombres.Conclusiones: Los resultados de este estudio aportan nueva evidencia a favor de que el inicio de la etapauniversitaria es un momento de especial relevancia en el inicio del consumo de drogas ilegales y suprevención, pudiendo este consumo estar especialmente relacionado con el apoyo familiar

Trends in semen parameters of infertile men in South Africa and Nigeria

There are conflicting reports on trends of semen parameters from different parts of the globe. However, in recent times there is dearth of information on the trend in Sub-Saharan countries. Therefore, in this study we aimed at determining the trends in semen parameters in Nigeria and South Africa between 2010 and 2019. A retrospective study of semen analyses of 17,292 men attending fertility hospitals in Nigeria and South Africa in 2010, 2015 and 2019. Patients who had undergone vasectomy and those who had a pH less than 5 or greater than 10 were excluded from this study. The following variables were assessed: ejaculate volume, sperm concentration, progressive motility, total progressively motile sperm count (TPMSC), total sperm count, and normal sperm morphology. Between 2010 and 2019, significant trends of decreasing values were observed in normal sperm morphology (− 50%), and the ejaculatory volume (− 7.4%), indicating a progressive deterioration of the values in both countries. In Nigeria, there were significant decreases in progressive motility (− 87%), TPMSC (− 78%), and sperm morphology (− 55%) between 2010 and 2019 (P < 0.001). Spearman`s rank correlation revealed significant negative associations between age and morphology (ρ =  − 0.24, P < 0.001), progressive motility (ρ =  − 0.31. P < 0.001), and TPMSC (ρ =  − 0.32, P < 0.001). Patients in South Africa were younger than those from Nigeria, with also a significantly higher sperm morphology, sperm concentration, progressive motility, total sperm count and TPMSC. Our findings provide a quantitative evidence of an alarming decreasing trend in semen parameters in Nigeria and South Africa from 2010 to 2019. It also proves that astheno- and teratozoospermia are the leading causes of male infertility in these regions. In addition to this, it also shows empirically that semen parameters decrease with advancement in age. These findings are the first report of temporal trends in semen parameters in Sub-Saharan countries, necessitating a thorough investigation on the underlying factors promoting this worrisome decline

Suppression of Steady-state, but not Stimulus-induced NF-κB Activity Inhibits Alphavirus-induced Apoptosis

Recent studies have established cell type– specific, proapoptotic, or antiapoptotic functions for the transcription factor NF-κB. In each of these studies, inhibitors of NF-κB activity have been present before the apoptotic stimulus, and so the role of stimulus- induced NF-κB activation in enhancing or inhibiting survival could not be directly assessed. Sindbis virus, an alphavirus, induces NF-κB activation and apoptosis in cultured cell lines. To address whether Sindbis virus– induced NF-κB activation is required for apoptosis, we used a chimeric Sindbis virus that expresses a superrepressor of NF-κB activity. Complete suppression of virus-induced NF-κB activity neither prevents nor potentiates Sindbis virus–induced apoptosis. In contrast, inhibition of NF-κB activity before infection inhibits Sindbis virus–induced apoptosis. Our results demonstrate that suppression of steady-state, but not stimulus-induced NF-κB activity, regulates expression of gene products required for Sindbis virus–induced death. Furthermore, we show that in the same cell line, NF-κB can be proapoptotic or antiapoptotic depending on the death stimulus. We propose that the role of NF-κB in regulating apoptosis is determined by the death stimulus and by the timing of modulating NF-κB activity relative to the death stimulus

Comparison of digital and conventional impression techniques: evaluation of patients’ perception, treatment comfort, effectiveness and clinical outcomes

Background: The purpose of this study was to compare two impression techniques from the perspective of patient preferences and treatment comfort.Methods: Twenty-four (12 male, 12 female) subjects who had no previous experience with either conventional or digital impression participated in this study. Conventional impressions of maxillary and mandibular dental arches were taken with a polyether impression material (Impregum, 3 M ESPE), and bite registrations were made with polysiloxane bite registration material (Futar D, Kettenbach). Two weeks later, digital impressions and bite scans were performed using an intra-oral scanner (CEREC Omnicam, Sirona). Immediately after the impressions were made, the subjects' attitudes, preferences and perceptions towards impression techniques were evaluated using a standardized questionnaire. The perceived source of stress was evaluated using the State-Trait Anxiety Scale. Processing steps of the impression techniques (tray selection, working time etc.) were recorded in seconds. Statistical analyses were performed with the Wilcoxon Rank test, and p < 0.05 was considered significant.Results: There were significant differences among the groups (p < 0.05) in terms of total working time and processing steps. Patients stated that digital impressions were more comfortable than conventional techniques.Conclusions: Digital impressions resulted in a more time-efficient technique than conventional impressions. Patients preferred the digital impression technique rather than conventional techniques

Transcriptomic Analysis of Host Immune and Cell Death Responses Associated with the Influenza A Virus PB1-F2 Protein

Airway inflammation plays a major role in the pathogenesis of influenza viruses and can lead to a fatal outcome. One of the challenging objectives in the field of influenza research is the identification of the molecular bases associated to the immunopathological disorders developed during infection. While its precise function in the virus cycle is still unclear, the viral protein PB1-F2 is proposed to exert a deleterious activity within the infected host. Using an engineered recombinant virus unable to express PB1-F2 and its wild-type homolog, we analyzed and compared the pathogenicity and host response developed by the two viruses in a mouse model. We confirmed that the deletion of PB1-F2 renders the virus less virulent. The global transcriptomic analyses of the infected lungs revealed a potent impact of PB1-F2 on the response developed by the host. Thus, after two days post-infection, PB1-F2 invalidation severely decreased the number of genes activated by the host. PB1-F2 expression induced an increase in the number and level of expression of activated genes linked to cell death, inflammatory response and neutrophil chemotaxis. When generating interactive gene networks specific to PB1-F2, we identified IFN-γ as a central regulator of PB1-F2-regulated genes. The enhanced cell death of airway-recruited leukocytes was evidenced using an apoptosis assay, confirming the pro-apoptotic properties of PB1-F2. Using a NF-kB luciferase adenoviral vector, we were able to quantify in vivo the implication of NF-kB in the inflammation mediated by the influenza virus infection; we found that PB1-F2 expression intensifies the NF-kB activity. Finally, we quantified the neutrophil recruitment within the airways, and showed that this type of leukocyte is more abundant during the infection of the wild-type virus. Collectively, these data demonstrate that PB1-F2 strongly influences the early host response during IAV infection and provides new insights into the mechanisms by which PB1-F2 mediates virulence