Theory Summary and Future Directions

Summary talk at the Lepton-Photon Symposium, Cornell University, Aug. 10-15, 1993.Comment: (Talk presented at the Lepton-Photon Symposium, Cornell University, Aug. 10-15, 1993.) 19 page

Chapter 6 Parental marital dissolution and the intergenerational transmission of homeownership

Children of homeowners are more likely to enter homeownership than are children whose parents rent. We investigate whether this association is dependent on parental divorce, focusing on parental assistance as a conduit of intergenerational transmission. Event history analyses of data for England and Wales from the British Household Panel Survey (BHPS) show that the intergenerational transmission of homeownership is stronger for children of divorced parents compared with children of married parents. Such an eff ect may arise from two channels: (1) children of divorced parents are more in need of parental assistance due to socio-economic disadvantages associated with parental divorce; and (2) compared with married parents, divorced homeowning parents (mothers) rely more on housing wealth, rather than fi nancial wealth, for assisting children. Findings support both explanations. Children of divorced parents are furthermore less likely to co-reside. We fi nd limited evidence that when they do, co-residence is less conductive to homeownership compared with children from married parents

Chapter 6 Parental marital dissolution and the intergenerational transmission of homeownership

Children of homeowners are more likely to enter homeownership than are children whose parents rent. We investigate whether this association is dependent on parental divorce, focusing on parental assistance as a conduit of intergenerational transmission. Event history analyses of data for England and Wales from the British Household Panel Survey (BHPS) show that the intergenerational transmission of homeownership is stronger for children of divorced parents compared with children of married parents. Such an eff ect may arise from two channels: (1) children of divorced parents are more in need of parental assistance due to socio-economic disadvantages associated with parental divorce; and (2) compared with married parents, divorced homeowning parents (mothers) rely more on housing wealth, rather than fi nancial wealth, for assisting children. Findings support both explanations. Children of divorced parents are furthermore less likely to co-reside. We fi nd limited evidence that when they do, co-residence is less conductive to homeownership compared with children from married parents

Collaboratively Learning How To Use Data: The Process of Knowledge Creation

Data-based decision making in education has become increasingly important. In the Netherlands, school leaders and teachers work together in data teams to collaboratively create knowledge on data use to improve their education. However, more insight into the process of knowledge creation is required to further support data use in schools. We used Nonaka and Takeuchi’s model of knowledge creation to study this. All (21 and 24) meetings of two data teams were transcribed, coded and analyzed in this qualitative micro-process case study. Results showed, for example, that over time, both data teams reflected more often on their work and increasingly discussed the use of data. Differences existed as one team evaluated the quality of their data more often and thoroughly

Dual-Band Transmitter and Receiver with Bowtie-Antenna in 0.13 μm SiGe BiCMOS for Gas Spectroscopy at 222 - 270 GHz

This paper presents a transmitter (TX) and a receiver (RX) with bowtie-antenna and silicon lens for gas spectroscopy at 222-270 GHz, which are fabricated in IHP’s 0.13 μm SiGe BiCMOS technology. The TX and RX use two integrated local oscillators for 222 – 256 GHz and 250 – 270 GHz, which are switched for dual-band operation. Due to its directivity of about 27 dBi, the single integrated bowtie-antenna with silicon lens enables an EIRP of about 25 dBm for the TX, and therefore a considerably higher EIRP for the 2-band TX compared to previously reported systems. The double sideband noise temperature of the RX is 20,000 K (18.5 dB noise figure) as measured by the Y-factor method. Absorption spectroscopy of gaseous methanol is used as a measure for the performance of the gas spectroscopy system with TX- and RX-modules

Artificial intelligence-based classification of motor unit action potentials in real-world needle EMG recordings

ObjectiveTo develop an artificial neural network (ANN) for classification of motor unit action potential (MUAP) duration in real-word, unselected and uncleaned needle electromyography (n-EMG) recordings.MethodsTwo nested ANN models were trained, the first discerning muscle rest, contraction and artifacts in n-EMG recordings from 2674 individual muscles from 326 patients obtained as part of daily care. The second ANN model subsequently used segments labeled as contraction for prediction of prolonged, normal and shortened MUAPs. Model performance was assessed in one internal and two external validation datasets of 184, 30 and 50 muscles, respectively.ResultsThe first model discerned rest, contraction and artifacts with an accuracy of 96%. The second model predicted prolonged, normal and shortened MUAPs with an accuracy of 67%, 83% and 68% in the different validation sets.ConclusionsWe developed a two-step ANN that classifies rest, muscle contraction and artifacts from real-world n-EMG recordings with very high accuracy. MUAP duration classification had moderate accuracy.SignificanceThis is the first study to show that an ANN can classify MUAPs in real-world n-EMG recordings highlighting the potential for AI assisted MUAP classification as a clinical tool.Neurological Motor Disorder

Identification of an altered peptide ligand based on the endogenously presented, rheumatoid arthritis-associated, human cartilage glycoprotein-39(263–275) epitope: an MHC anchor variant peptide for immune modulation

We sought to identify an altered peptide ligand (APL) based on the endogenously expressed synovial auto-epitope of human cartilage glycoprotein-39 (HC gp-39) for modulation of cognate, HLA-DR4-restricted T cells. For this purpose we employed a panel of well-characterized T cell hybridomas generated from HC gp-39-immunized HLA-DR4 transgenic mice. The hybridomas all respond to the HC gp-39(263–275) epitope when bound to HLA-DR4(B1*0401) but differ in their fine specificities. First, the major histocompatibility complex (MHC) and T-cell receptor (TCR) contact residues were identified by analysis of single site substituted analogue peptides for HLA-DR4 binding and cognate T cell recognition using both T hybridomas and polyclonal T cells from peptide-immunized HLA-DR4 transgenic mice. Analysis of single site substituted APL by cognate T cells led to identification of Phe265 as the dominant MHC anchor. The amino acids Ala268, Ser269, Glu271 and Thr272 constituted the major TCR contact residues, as substitution at these positions did not affect HLA-DR4(B1*0401) binding but abrogated T cell responses. A structural model for visualisation of TCR recognition was derived. Second, a set of non-classical APLs, modified at the MHC key anchor position but with unaltered TCR contacts, was developed. When these APLs were analysed, a partial TCR agonist was identified and found to modulate the HC gp-39(263–275)-specific, pro-inflammatory response in HLA-DR4 transgenic mice. We identified a non-classical APL by modification of the p1 MHC anchor in a synovial auto-epitope. This APL may qualify for rheumatoid arthritis immunotherapy

Activation of Autophagy in a Rat Model of Retinal Ischemia following High Intraocular Pressure

Acute primary open angle glaucoma is an optic neuropathy characterized by the elevation of intraocular pressure, which causes retinal ischemia and neuronal death. Rat ischemia/reperfusion enhances endocytosis of both horseradish peroxidase (HRP) or fluorescent dextran into ganglion cell layer (GCL) neurons 24 h after the insult. We investigated the activation of autophagy in GCL-neurons following ischemia/reperfusion, using acid phosphatase (AP) histochemistry and immunofluorescence against LC3 and LAMP1. Retinal I/R lead to the appearance of AP-positive granules and LAMP1-positive vesicles 12 and 24 h after the insult, and LC3 labelling at 24 h, and induced a consistent retinal neuron death. At 48 h the retina was negative for autophagic markers. In addition, Western Blot analysis revealed an increase of LC3 levels after damage: the increase in the conjugated, LC3-II isoform is suggestive of autophagic activity. Inhibition of autophagy by 3-methyladenine partially prevented death of neurons and reduces apoptotic markers, 24 h post-lesion. The number of neurons in the GCL decreased significantly following I/R (I/R 12.21±1.13 vs controls 19.23±1.12 cells/500 µm); this decrease was partially prevented by 3-methyladenine (17.08±1.42 cells/500 µm), which potently inhibits maturation of autophagosomes. Treatment also prevented the increase in glial fibrillary acid protein immunoreactivity elicited by I/R. Therefore, targeting autophagy could represent a novel and promising treatment for glaucoma and retinal ischemia

Galectin-3 and prohibitin 1 are autoantigens in IgG4-related cholangitis without clear-cut protective effects against toxic bile acids

Background and aimsIgG4-related cholangitis (IRC) is the hepatobiliary manifestation of IgG4-related disease, a systemic B cell-driven fibro-inflammatory disorder. Four autoantigens have recently been described in IgG4-RD: annexin A11, galectin-3, laminin 511-E8, and prohibitin 1. We have previously reported a protective role of annexin A11 and laminin 511-E8 in human cholangiocytes against toxic bile acids. Here, we explored the potentially protective role of the carbohydrate-binding lectin galectin-3 and the scaffold proteins prohibitins 1 and 2.MethodsAnti-galectin-3, anti-prohibitin 1 and 2 autoantibody positivity in IRC and healthy and disease (primary sclerosing cholangitis (PSC)) control sera was assessed by ELISA/liquid chromatography–tandem mass spectrometry (LC-MS/MS). Human H69 cholangiocytes were subjected to short hairpin RNA (shRNA) knockdown targeting galectin-3 (LGALS3), prohibitin 1 (PHB1), and prohibitin 2 (PHB2). H69 cholangiocytes were also exposed to recombinant galectin-3, the inhibitor GB1107, recombinant prohibitin 1, and the pan-prohibitin inhibitor rocaglamide. Protection against bile acid toxicity was assessed by intracellular pH (pHi) measurements using BCECF-AM, 22,23-3H-glycochenodeoxycholic acid (3H-GCDC) influx, and GCDC-induced apoptosis using Caspase-3/7 assays.ResultsAnti-galectin-3 autoantibodies were detected in 13.5% of individuals with IRC but not in PSC. Knockdown of LGALS3 and galectin-3 inhibition with GB1107 did not affect pHi, whereas recombinant galectin-3 incubation lowered pHi. LGALS3 knockdown increased GCDC-influx but not GCDC-induced apoptosis. GB1107 reduced GCDC-influx and GCDC-induced apoptosis. Recombinant galectin-3 tended to decrease GCDC-influx and GCDC-induced apoptosis. Anti-prohibitin 1 autoantibodies were detected in 61.5% and 35.7% of individuals with IRC and PSC, respectively. Knockdown of PHB1, combined PHB1/2 KD, treatment with rocaglamide, and recombinant prohibitin 1 all lowered pHi. Knockdown of PHB1, PHB2, or combined PHB1/2 did not alter GCDC-influx, yet knockdown of PHB1 increased GCDC-induced apoptosis. Conversely, rocaglamide reduced GCDC-influx but did not attenuate GCDC-induced apoptosis. Recombinant prohibitin 1 did not affect GCDC-influx or GCDC-induced apoptosis. Finally, anti-galectin-3 and anti-prohibitin 1 autoantibody pretreatment did not lead to increased GCDC-influx.ConclusionsA subset of individuals with IRC have autoantibodies against galectin-3 and prohibitin 1. Gene-specific knockdown, pharmacological inhibition, and recombinant protein substitution did not clearly disclose a protective role of these autoantigens in human cholangiocytes against toxic bile acids. The involvement of these autoantibodies in processes surpassing epithelial secretion remains to be elucidated