Rapamycin but not FK506 inhibits the proliferation of mononuclear phagocytes induced by colony-stimulating factors

FK506, CsA, and rapamycin are potent inhibitors of T lymphocyte activation; relatively little is known of their effects on cells of the monocyte/macrophage lineage. Studies were undertaken to determine the effects of these drugs on the proliferative response of bone marrow-derived mononuclear phagocytes (BMMP) to CSFs. Rapamycin inhibited the proliferation of BMMP cultured in the presence of 10% L cellconditioned medium, used as a source of macrophage CSF. The inhibition by rapamycin was dose dependent and apparent at concentrations of 0.1 nM or greater. In a similar fashion, rapamycin inhibited the proliferation of BMMP stimulated by the recombinant forms of murine IL-3 and murine granulocyte-macrophage CSF, and human macrophage CSF. In contrast, neither FK506 nor CsA at concentrations as high as 1000 nM diminished the proliferation of BMMP cultured under identical conditions. FK506, but not CsA, blocked the inhibitory effects of rapamycin on the response of BMMP to CSFs. In summary, these data indicate that rapamycin inhibits the proliferation of BMMP in response to CSFs. These results imply that patients receiving rapamycin, but not FK506 or CsA, may have an impaired ability to generate a functional mononuclear phagocyte population. © 1994 by Williams and Wilkins

Machine learning with the hierarchy‐of‐hypotheses (HoH) approach discovers novel pattern in studies on biological invasions

Research synthesis on simple yet general hypotheses and ideas is challenging in scientific disciplines studying highly context‐dependent systems such as medical, social, and biological sciences. This study shows that machine learning, equation‐free statistical modeling of artificial intelligence, is a promising synthesis tool for discovering novel patterns and the source of controversy in a general hypothesis. We apply a decision tree algorithm, assuming that evidence from various contexts can be adequately integrated in a hierarchically nested structure. As a case study, we analyzed 163 articles that studied a prominent hypothesis in invasion biology, the enemy release hypothesis. We explored if any of the nine attributes that classify each study can differentiate conclusions as classification problem. Results corroborated that machine learning can be useful for research synthesis, as the algorithm could detect patterns that had been already focused in previous narrative reviews. Compared with the previous synthesis study that assessed the same evidence collection based on experts' judgement, the algorithm has newly proposed that the studies focusing on Asian regions mostly supported the hypothesis, suggesting that more detailed investigations in these regions can enhance our understanding of the hypothesis. We suggest that machine learning algorithms can be a promising synthesis tool especially where studies (a) reformulate a general hypothesis from different perspectives, (b) use different methods or variables, or (c) report insufficient information for conducting meta‐analyses

Winter Ecosystem Respiration and Sources of CO2 From the High Arctic Tundra of Svalbard: Response to a Deeper Snow Experiment

Currently, there is a lack of understanding on how the magnitude and sources of carbon (C) emissions from High Arctic tundra are impacted by changing snow cover duration and depth during winter. Here we investigated this issue in a graminoid tundra snow fence experiment on shale-derived gelisols in Svalbard from the end of the growing season and throughout the winter. To characterize emissions, we measured ecosystem respiration (Reco) along with its radiocarbon (14C) content. We assessed the composition of soil organic matter (SOM) by measuring its bulk-C and nitrogen (N), 14C content, and n-alkane composition. Our findings reveal that greater snow depth increased soil temperatures and winter Reco (25 mg C m−2 d−1 under deeper snow compared to 13 mg C m−2 d−1 in ambient conditions). At the end of the growing season, Reco was dominated by plant respiration and microbial decomposition of C fixed within the past 60 years (Δ14C = 62 ± 8‰). During winter, emissions were significantly older (Δ14C = −64 ± 14‰), and likely sourced from microorganisms decomposing aged SOM formed during the Holocene mixed with biotic or abiotic mineralization of the carbonaceous, fossil parent material. Our findings imply that snow cover duration and depth is a key control on soil temperatures and thus the magnitude of Reco in winter. We also show that in shallow Arctic soils, mineralization of carbonaceous parent materials can contribute significant proportions of fossil C to Reco. Therefore, permafrost-C inventories informing C emission projections must carefully distinguish between more vulnerable SOM from recently fixed biomass and more recalcitrant ancient sedimentary C sources

The time-dependent expression of keratins 5 and 13 during the reepithelialization of human skin wounds

The time-dependent reepithelialization of 55 human surgical skin wounds with a wound age between 8h and more than 2 months was investigated by the immunohistochemical localization of cytokeratins 5 and 13. A complete, rebuilt epidermal layer over the wound area was first detectable in a 5-day-old wound, while all wounds of more than 18 days duration contained a completely reepithelialized wound area. Between 5 and 18 days the basal layer of keratinocytes showed — in contrast to normal skin — only some cells positive for cytokeratin 5. In some, but not all lesions with a wound age of 13 days or more, a basal cell layer completely staining for cytokeratin 5 was demonstrable. This staining pattern was found in all skin wounds with a wound age of more than 23 days. The immunohistochemical detection of cytokeratin 13 which can be observed regularly in non-cornifying squamous epithelia provides no information for the time-estimation of human skin wounds, since no significant temporary expression of this polypeptide seems to occur during the healing of human skin wounds

Extracting spacing-derived estimates of rod density in healthy retinae

Quantification of the rod photoreceptor mosaic using adaptive optics scanning light ophthalmoscopy (AOSLO) remains challenging. Here we demonstrate a method for deriving estimates of rod density and rod:cone ratio based on measures of rod spacing, cone numerosity, and cone inner segment area. Twenty-two AOSLO images with complete rod visualization were used to validate this spacing-derived method for estimating density. The method was then used to estimate rod metrics in an additional 105 images without complete rod visualization. The spacing-derived rod mosaic metrics were comparable to published data from histology. This method could be leveraged to develop large normative databases of rod mosaic metrics, though limitations persist with intergrader variability in assessing cone area and numerosity

Efficient Numerical Schemes for Computing Cardiac Electrical Activation over Realistic Purkinje Networks: Method and Verification

We present a numerical solver for the fast conduction system in the heart using both a CPU and a hybrid CPU/GPU implementation. To verify both implementations, we construct analytical solutions and show that the L2-error is similar in both implementations and decreases linearly with the spatial step size. Finally, we test the performance of the implementations with networks of varying complexity, where the hybrid implementation is, on average, 5.8 times faster

Expressing one’s feelings and listening to others increases emotional intelligence: a pilot study of Asian medical students

<p>Background: There has been considerable interest in Emotional Intelligence (EI) in undergraduate medical education, with respect to student selection and admissions, health and well-being and academic performance. EI is a significant component of the physician-patient relationship. The emotional well-being of the physician is, therefore, a significant component in patient care. The aim is to examine the measurement of TEIQue-SF in Asian medical students and to explore how the practice of listening to the feelings of others and expressing one’s own feelings influences an individual’s EI, set in the context of the emotional well-being of a medical practitioner.</p> <p>Methods: A group of 183 international undergraduate medical students attended a half-day workshop (WS) about mental-health and well-being. They completed a self-reported measure of EI on three occasions, pre- and post-workshop, and a 1-year follow-up.</p> <p>Result: The reliability of TEIQue-SF was high and the reliabilities of its four factors were acceptable. There were strong correlations between the TEIQue-SF and personality traits. A paired t-test indicated significant positive changes after the WS for all students (n=181, p= .014), male students (n=78, p= .015) and non-Japanese students (n=112, p= .007), but a repeated measures analysis showed that one year post-workshop there were significant positive changes for all students (n=55, p= .034), female students (n=31, p= .007), especially Japanese female students (n=13, p= .023). Moreover, 80% of the students reported that they were more attentive listeners, and 60% agreed that they were more confident in dealing with emotional issues, both within themselves and in others, as a result of the workshop.</p> <p>Conclusion: This study found the measurement of TEIQue-SF is appropriate and reliable to use for Asian medical students. The mental health workshop was helpful to develop medical students’ EI but showed different results for gender and nationality. The immediate impact on the emotional awareness of individuals was particularly significant for male students and the non-Japanese group. The impact over the long term was notable for the significant increase in EI for females and Japanese. Japanese female students were more conscious about emotionality. Emotion-driven communication exercises might strongly influence the development of students’ EI over a year.</p&gt