WTC2005-63308 A CRITICAL ASSESSMENT OF TRIBOPOLYMERIZATION AS AN ANTIWEAR MECHANISM

ABSTRACT By tribopolymerization, we mean the planned, intentional, and continuous formation of protective polymeric films on tribological surfaces by the use of minor concentrations of selected monomers capable of forming polymer films "in situ" by polycondensation or addition polymerization. The approach involves the design of molecules which will form polymeric surface films in critical regions of boundary lubrication. The concept has been shown to be effective in reducing wear with ceramics as well as metals in both liquid and vapor phase applications. The purpose of this paper is threefold, namely: 1. To review our key fundamental research on the topic of tribopolymerization, including more recent views based on measurements of triboelectron emission. 2. To summarize the applications of this concept to a variety of industrial problems, including the use of the compounds in fuels as well as in areas in which environmental issues are important. 3. To briefly outline future plans for fundamental research on tribopolymerization, including theoretical and experimental studies to examine the roles of surface temperature, triboelectron emission, and catalysis on surface polymerization

WTC2005-63308 A CRITICAL ASSESSMENT OF TRIBOPOLYMERIZATION AS AN ANTIWEAR MECHANISM

ABSTRACT By tribopolymerization, we mean the planned, intentional, and continuous formation of protective polymeric films on tribological surfaces by the use of minor concentrations of selected monomers capable of forming polymer films "in situ" by polycondensation or addition polymerization. The approach involves the design of molecules which will form polymeric surface films in critical regions of boundary lubrication. The concept has been shown to be effective in reducing wear with ceramics as well as metals in both liquid and vapor phase applications. The purpose of this paper is threefold, namely: 1. To review our key fundamental research on the topic of tribopolymerization, including more recent views based on measurements of triboelectron emission. 2. To summarize the applications of this concept to a variety of industrial problems, including the use of the compounds in fuels as well as in areas in which environmental issues are important. 3. To briefly outline future plans for fundamental research on tribopolymerization, including theoretical and experimental studies to examine the roles of surface temperature, triboelectron emission, and catalysis on surface polymerization

WTC2005-63304 BIOTRIBOLOGY: THE WEAR RESISTANCE OF REPAIRED HUMAN ARTICULAR CARTILAGE

ABSTRACT Normal, mature articular cartilage does not spontaneously repair itself back to hyaline cartilage after an injury or degenerative disease (e.g., osteoarthritis)-problems of increasing importance in an aging population. A promising new approach is to repair damaged cartilage by a method known as Autologous Chondrocyte Implantation (ACI)-a technique pioneered and further developed by the Cartilage Research Unit at Goteborg University in Sweden. However, the tribological properties of the repaired cartilage, including the important property wear-resistance, are unknown. How durable is the repaired cartilage? How long will it last? One of the co-authors, Dr. Mats Brittberg, has provided 16 samples of 2mm diameter human biopsies from the knees of eight Swedish patients for testing in our biotribology device. This paper presents results of wear experiments on cartilage repaired by Brittberg's ACI technique and, for comparison, two other methods. Four of these samples (2 pairs) were from patients who had undergone the ACI procedure while another four were from those who had other methods of repair. A pair consists of a biopsy from the repaired area of the joint along with a sample from nearby "healthy" cartilage from the same joint. Thus, each pair allowed for a direct comparison of the tribological properties of the repaired cartilage to those of "normal" cartilage from the same joint. The results of this study show that the ACI method of cartilage repair gave substantially less wear than that of normal cartilage while spontaneous repair and abrasion arthroplasty produced higher wear. Friction levels were in the boundary lubrication regime and, in line with our previous experience, had no correlation with wear. Results obtained with cartilage from the remaining patients will be discussed in future papers

Aberrant miR-29 is a predictive feature of severe phenotypes in pediatric Crohn’s disease

Funding Information: This work was supported by 5P01DK094779 (NIH/NIDDK) awarded to SZS, TSF, and PS; the NIDDK R01 DK136262 awarded to SZS; and 5R21HD104922-02 (NIH/NICHD) awarded to PS. We would also like to thank BioRender for its help in creating our graphical abstract.Peer reviewe

Identification and Characterization of Cell Type–Specific and Ubiquitous Chromatin Regulatory Structures in the Human Genome

The identification of regulatory elements from different cell types is necessary for understanding the mechanisms controlling cell type–specific and housekeeping gene expression. Mapping DNaseI hypersensitive (HS) sites is an accurate method for identifying the location of functional regulatory elements. We used a high throughput method called DNase-chip to identify 3,904 DNaseI HS sites from six cell types across 1% of the human genome. A significant number (22%) of DNaseI HS sites from each cell type are ubiquitously present among all cell types studied. Surprisingly, nearly all of these ubiquitous DNaseI HS sites correspond to either promoters or insulator elements: 86% of them are located near annotated transcription start sites and 10% are bound by CTCF, a protein with known enhancer-blocking insulator activity. We also identified a large number of DNaseI HS sites that are cell type specific (only present in one cell type); these regions are enriched for enhancer elements and correlate with cell type–specific gene expression as well as cell type–specific histone modifications. Finally, we found that approximately 8% of the genome overlaps a DNaseI HS site in at least one the six cell lines studied, indicating that a significant percentage of the genome is potentially functional

Two-Photon Excitation Spectroscopy of Silicon Quantum Dots and Ramifications for Bio-Imaging

Two-photon excitation in the near-infrared (NIR) of colloidal nanocrystalline silicon quantum dots (nc-SiQDs) with photoluminescence also in the NIR has the potential to open up new opportunities in the field of deep biological imaging. Spectra of the degenerate two-photon absorption (2PA) cross section of colloidal nc-SiQDs are measured using two-photon excitation over a spectral range 1.46λ>650 nm) above the two-photon band gap E(QD)g/2, and at a representative photon energy ℏω=0.99 eV (λ=1250 nm) below this gap. Two-photon excited photoluminescence (2PE-PL) spectra of nc-SiQDs with diameters d=1.8±0.2 and d=2.3±0.3 nm, each passivated with 1-dodecene and dispersed in toluene, are calibrated in strength against 2PE-PL from a known concentration of Rhodamine B dye in methanol. The 2PA cross section is observed to be smaller for the smaller diameter nanocrystals and the onset of 2PA is observed to be blueshifted from the two-photon indirect band gap of bulk Si, as expected for quantum confinement of excitons. The efficiencies of nc-SiQDs for bio-imaging using 2PE-PL are simulated in various biological tissues and compared to other quantum dots and molecular fluorophores and found to be superior at greater depths.This research was funded by Robert A. Welch Foundation Grants F-1038 and F-1464, and partially supported by the National Science Foundation through the Center for Dynamics and Control of Materials; an NSF MRSEC under Cooperative Agreement No. DMR-1720595. B. Mendoza acknowledges support from Consejo Nacional de Ciencia y Tecnología, México (Grant No. A1-S-9410).Center for Dynamics and Control of Material

Genome-Wide DNA Methylation Scan in Major Depressive Disorder

While genome-wide association studies are ongoing to identify sequence variation influencing susceptibility to major depressive disorder (MDD), epigenetic marks, such as DNA methylation, which can be influenced by environment, might also play a role. Here we present the first genome-wide DNA methylation (DNAm) scan in MDD. We compared 39 postmortem frontal cortex MDD samples to 26 controls. DNA was hybridized to our Comprehensive High-throughput Arrays for Relative Methylation (CHARM) platform, covering 3.5 million CpGs. CHARM identified 224 candidate regions with DNAm differences >10%. These regions are highly enriched for neuronal growth and development genes. Ten of 17 regions for which validation was attempted showed true DNAm differences; the greatest were in PRIMA1, with 12–15% increased DNAm in MDD (p = 0.0002–0.0003), and a concomitant decrease in gene expression. These results must be considered pilot data, however, as we could only test replication in a small number of additional brain samples (n = 16), which showed no significant difference in PRIMA1. Because PRIMA1 anchors acetylcholinesterase in neuronal membranes, decreased expression could result in decreased enzyme function and increased cholinergic transmission, consistent with a role in MDD. We observed decreased immunoreactivity for acetylcholinesterase in MDD brain with increased PRIMA1 DNAm, non-significant at p = 0.08

Multiomic analyses implicate a neurodevelopmental program in the pathogenesis of cerebral arachnoid cysts

Cerebral arachnoid cysts (ACs) are one of the most common and poorly understood types of developmental brain lesion. To begin to elucidate AC pathogenesis, we performed an integrated analysis of 617 patient-parent (trio) exomes, 152,898 human brain and mouse meningeal single-cell RNA sequencing transcriptomes and natural language processing data of patient medical records. We found that damaging de novo variants (DNVs) were highly enriched in patients with ACs compared with healthy individuals (P = 1.57 × 10-33). Seven genes harbored an exome-wide significant DNV burden. AC-associated genes were enriched for chromatin modifiers and converged in midgestational transcription networks essential for neural and meningeal development. Unsupervised clustering of patient phenotypes identified four AC subtypes and clinical severity correlated with the presence of a damaging DNV. These data provide insights into the coordinated regulation of brain and meningeal development and implicate epigenomic dysregulation due to DNVs in AC pathogenesis. Our results provide a preliminary indication that, in the appropriate clinical context, ACs may be considered radiographic harbingers of neurodevelopmental pathology warranting genetic testing and neurobehavioral follow-up. These data highlight the utility of a systems-level, multiomics approach to elucidate sporadic structural brain disease

Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this recordThere is another record in ORE for this publication: http://hdl.handle.net/10871/33419The choroid plexus epithelium (CPE) secretes higher volumes of fluid (cerebrospinal fluid, CSF) than any other epithelium and simultaneously functions as the blood-CSF barrier to gate immune cell entry into the central nervous system. Posthemorrhagic hydrocephalus (PHH), an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH), is a common disease usually treated by suboptimal CSF shunting techniques. PHH is classically attributed to primary impairments in CSF reabsorption, but little experimental evidence supports this concept. In contrast, the potential contribution of CSF secretion to PHH has received little attention. In a rat model of PHH, we demonstrate that IVH causes a Toll-like receptor 4 (TLR4)- and NF-κB-dependent inflammatory response in the CPE that is associated with a ∼3-fold increase in bumetanide-sensitive CSF secretion. IVH-induced hypersecretion of CSF is mediated by TLR4-dependent activation of the Ste20-type stress kinase SPAK, which binds, phosphorylates, and stimulates the NKCC1 co-transporter at the CPE apical membrane. Genetic depletion of TLR4 or SPAK normalizes hyperactive CSF secretion rates and reduces PHH symptoms, as does treatment with drugs that antagonize TLR4-NF-κB signaling or the SPAK-NKCC1 co-transporter complex. These data uncover a previously unrecognized contribution of CSF hypersecretion to the pathogenesis of PHH, demonstrate a new role for TLRs in regulation of the internal brain milieu, and identify a kinase-regulated mechanism of CSF secretion that could be targeted by repurposed US Food and Drug Administration (FDA)-approved drugs to treat hydrocephalus.We thank D.R. Alessi (Dundee) and R.P. Lifton (Rockefeller) for their support. K.T.K. is supported by the March of Dimes Basil O'Connor Award, a Simons Foundation SFARI Grant, the Hydrocephalus Association Innovator Award, and the NIH (4K12NS080223-05). J.M.S. is supported by the National Institute of Neurological Disorders and Stroke (NINDS) (NS060801; NS061808) and the US Department of Veterans Affairs (1BX002889); R.M. is supported by the Howard Hughes Medical Institute