Exploring hypotheses of the actions of TGF-beta 1 in epidermal wound healing using a 3D computational multiscale model of the human epidermis

In vivo and in vitro studies give a paradoxical picture of the actions of the key regulatory factor TGF-beta 1 in epidermal wound healing with it stimulating migration of keratinocytes but also inhibiting their proliferation. To try to reconcile these into an easily visualized 3D model of wound healing amenable for experimentation by cell biologists, a multiscale model of the formation of a 3D skin epithelium was established with TGF-beta 1 literature-derived rule sets and equations embedded within it. At the cellular level, an agent-based bottom-up model that focuses on individual interacting units ( keratinocytes) was used. This was based on literature-derived rules governing keratinocyte behavior and keratinocyte/ECM interactions. The selection of these rule sets is described in detail in this paper. The agent-based model was then linked with a subcellular model of TGF-beta 1 production and its action on keratinocytes simulated with a complex pathway simulator. This multiscale model can be run at a cellular level only or at a combined cellular/subcellular level. It was then initially challenged ( by wounding) to investigate the behavior of keratinocytes in wound healing at the cellular level. To investigate the possible actions of TGF-beta 1, several hypotheses were then explored by deliberately manipulating some of these rule sets at subcellular levels. This exercise readily eliminated some hypotheses and identified a sequence of spatial-temporal actions of TGF-beta 1 for normal successful wound healing in an easy-to-follow 3D model. We suggest this multiscale model offers a valuable, easy-to-visualize aid to our understanding of the actions of this key regulator in wound healing, and provides a model that can now be used to explore pathologies of wound healing

Construction and Performance Monitoring of Various Asphalt Mixes in Illinois: 2015 Interim Report

A series of five experimental projects were constructed to better determine the life-cycle cost and performance of pavement overlays using various types and combinations of recycled materials—namely, reclaimed asphalt pavement (RAP), recycled asphalt shingles (RAS) and crushed concrete. The asphalt binder replacement (ABR) varied from 15% to 48% in the experimental sections. The study of these projects prior to construction, during construction, and for a short monitoring period after construction is intended to determine the impact of various pavement conditions, pavement cross-sections, mix designs, and material properties on the ultimate performance of the hot-mix asphalt (HMA) overlay. This interim report documents the construction and testing to date on two of the five projects in the study—Crawford Avenue/Pulaski Road and US 52 (IL 52 to Laraway Road)—that were constructed in 2014. Distress and profile surveys were conducted before and after construction. Samples were obtained of the HMA surface and binder courses and were tested for basic properties, plus Cantabro, stability/flow, Texas overlay cracking potential, fracture energy, flexibility index, fatigue, modulus, creep, and Hamburg rutting. Presented are early performance trends and baseline conditions that future performance can be compared against. Also included in this report is an update of performance on three total recycle asphalt (TRA) sections and a comparison section constructed in 2013 with ABR’s ranging from 20% to 60%.R27-161, Illinois Department of TransportationOpe

Construction and Performance Monitoring of Various Asphalt Mixes in Illinois: 2016 Interim Report

series of five experimental projects were constructed to better determine the life-cycle cost and performance of pavement overlays using various levels of asphalt binder replacement (ABR) from use of reclaimed asphalt pavement (RAP), recycled asphalt shingles (RAS) and crushed concrete. The ABR varies from 15% to 48% in the experimental sections. The study of these projects prior to construction, during construction, and for a short monitoring period after construction is intended to determine the impact of various pavement conditions, pavement cross-section, mix design, and material properties on the ultimate performance of the hot-mix asphalt (HMA) overlay. This second interim report documents the construction and initial testing of three of the five projects in the study—namely, Washington Street, US 52 (Laraway Road to Gougar Road) and US 52 (Gougar Road to Second Street)—which were constructed in 2015. Distress and profile surveys were conducted before and after construction. Samples were obtained of the HMA surface and binder courses and were tested for basic properties, plus Cantabro, stability/flow, Texas overlay cracking potential, fracture energy, Flexibility Index, fatigue, modulus, creep, and Hamburg rutting. Presented are early performance trends and baseline conditions that future performance can be compared with. Also included in this report is an update of performance on the sections constructed in 2014 and the total recycle asphalt (TRA) sections constructed in 2013.Illinois Department of Transportation, R27-161Ope

Minimally invasive stereotactic puncture and thrombolysis therapy improves long-term outcome after acute intracerebral hemorrhage

The purpose of this study was to judge the clinical value of minimally invasive stereotactic puncture and thrombolysis therapy (MISPTT) for acute intracerebral hemorrhage (ICH). A randomized control clinical trial was undertaken. According to the enrollment criteria, 122 acute ICH cases were analyzed, of which 64 cases received MISPTT (MISPTT group, MG) and 58 cases received conventional craniotomy (CC group, CG). The Glasgow coma scale (GCS) scores, postoperative complications (PC), and rebleeding incidences were compared. Moreover, 1 year postoperation, the long-term outcomes of patients with regard to hematoma volume (HV) <50 mL and HV ≥50 mL were judged, respectively, by the Glasgow outcome scale (GOS), Barthel index (BI), modified Rankin Scale (mRS), and case fatality (CF). MG patients showed obvious amelioration in GCS score compared with that of CG patients. The total incidence of PC in MG decreased compared with that of CG. The incidences of rebleeding in MG and CG were 9.4 and 17.2%, respectively (P = 0.243). There were no obvious differences between the CFs of MG and CG (17.2 and 25.9%, respectively, P = 0.199). The GOS, BI, and mRS representing long-term outcome for both HV <50 mL and HV ≥50 mL in MG were ameliorated significantly greater than that in CG patients (all P < 0.05). These data suggest that there are advantages with MISPTT not only in trauma and safety, but the MISPTT group had fewer complications and a trend toward improved short-term and long-term outcomes

RNA Methylation by the MIS Complex Regulates a Cell Fate Decision in Yeast

For the yeast Saccharomyces cerevisiae, nutrient limitation is a key developmental signal causing diploid cells to switch from yeast-form budding to either foraging pseudohyphal (PH) growth or meiosis and sporulation. Prolonged starvation leads to lineage restriction, such that cells exiting meiotic prophase are committed to complete sporulation even if nutrients are restored. Here, we have identified an earlier commitment point in the starvation program. After this point, cells, returned to nutrient-rich medium, entered a form of synchronous PH development that was morphologically and genetically indistinguishable from starvation-induced PH growth. We show that lineage restriction during this time was, in part, dependent on the mRNA methyltransferase activity of Ime4, which played separable roles in meiotic induction and suppression of the PH program. Normal levels of meiotic mRNA methylation required the catalytic domain of Ime4, as well as two meiotic proteins, Mum2 and Slz1, which interacted and co-immunoprecipitated with Ime4. This MIS complex (Mum2, Ime4, and Slz1) functioned in both starvation pathways. Together, our results support the notion that the yeast starvation response is an extended process that progressively restricts cell fate and reveal a broad role of post-transcriptional RNA methylation in these decisions