Conformational Plasticity of HLA-B27 Molecules Correlates Inversely With Efficiency of Negative T Cell Selection

The development of autoimmune disorders is incompletely understood. Inefficient thymic T cell selection against self-peptides presented by major histocompatibility antigens (HLA in humans) may contribute to the emergence of auto-reactive effector cells, and molecular mimicry between foreign and self-peptides could promote T cell cross-reactivity. A pair of class I subtypes, HLA-B2705 and HLA-B2709, have previously been intensely studied, because they are distinguished from each other only by a single amino acid exchange at the floor of the peptide-binding groove, yet are differentially associated with the autoinflammatory disorder ankylosing spondylitis. Using X-ray crystallography in combination with ensemble refinement, we find that the non-disease-associated subtype HLA-B2709, when presenting the self-peptide pGR (RRRWHRWRL), exhibits elevated conformational dynamics, and the complex can also be recognized by T cells. Both features are not observed in case of the sequence-related self-peptide pVIPR (RRKWRRWHL) in complex with this subtype, and T cell cross-reactivity between pGR, pVIPR, and the viral peptide pLMP2 (RRRWRRLTV) is only rarely observed. The disease-associated subtype HLA-B2705, however, exhibits extensive conformational flexibility in case of the three complexes, all of which are also recognized by frequently occurring cross-reactive T cells. A comparison of the structural and dynamic properties of the six HLA-B27 complexes, together with their individual ability to interact with T cells, permits us to correlate the flexibility of HLA-B27 complexes with effector cell reactivity. The results suggest the existence of an inverse relationship between conformational plasticity of peptide-HLA-B27 complexes and the efficiency of negative selection of self-reactive cells within the thymus

Combinatorial Stokes formulas via minimal resolutions

We describe an explicit chain map from the standard resolution to the minimal resolution for the finite cyclic group Z_k of order k. We then demonstrate how such a chain map induces a "Z_k-combinatorial Stokes theorem", which in turn implies "Dold's theorem" that there is no equivariant map from an n-connected to an n-dimensional free Z_k-complex. Thus we build a combinatorial access road to problems in combinatorics and discrete geometry that have previously been treated with methods from equivariant topology. The special case k=2 for this is classical; it involves Tucker's (1949) combinatorial lemma which implies the Borsuk-Ulam theorem, its proof via chain complexes by Lefschetz (1949), the combinatorial Stokes formula of Fan (1967), and Meunier's work (2006).Comment: 18 page

Genes Encoding Structural Proteins of Epidermal Cornification and S100 Calcium-Binding Proteins Form a Gene Complex (“Epidermal Differentiation Complex”) on Human Chromosome 1q21

Chromosome 1 reveals in region 1q21 a most remarkable density of genes that fulfill important functions in terminal differentiation of the human epidermis. These genes encode the cornified envelope precursors loricrin, involucrin, and small proline-rich proteins (SPRR1, SPRR2, and SPRR3), the intermediate filament-associated proteins profilaggrin and trichohyalin, and several S100A calcium-binding proteins. Extending and refining our previous physical map of 1q21 we have now mapped two additional S100A genes as well as the three SPRR subfamilles and resolved the arrangement of involucrin, SPRRs, and loricrin. All genes are linked within 1.9 Mbp of human genomic DNA in the order: S100A10, trichohyalin, profilaggrin, involucrin, SPRR3, SPRR1B, SPRR2A, loricrin, S100A9, S100A8, S100A6. Co-localization of genes expressed late during maturation of epidermal cells together with genes encoding calcium-binding proteins is particularly intriguing since calcium levels tightly control the differentiation of epithelial cells and the expression of genes encoding epidermal structural proteins. Accounting for the close functional cooperation among these structurally and evolutionary related genes, we conclude that these loci constitute a gene complex, for which we propose the name epidermal differentiation complex

A 3-D Printed PCB Integrated TEM Horn Antenna

[EN] This paper presents a very broadband (5-40 GHz) novel three dimension (3-D) printed Transverse ElectroMagnetic (TEM) horn antenna. It is integrated with a planar Printed Circuit Board and radiates in a perpendicular direction of the Printed Circuit Board. The described antenna provides benefits in terms of cost and size for a two dimensional antenna array. Here the antenna and its corresponding transition to a regular 50 Omega microstrip line through Parallel Plate Waveguide and a 90 degrees bend are presented. Prototypes of back-to-back transitions and antenna are fabricated and measured. The antenna has a return loss below -10 dB and a gain of approximately 10 dBi over the targeted frequency range.Miralles-Navarro, E.; Shoenlinner, B.; Belenguer Martínez, A.; Esteban González, H.; Ziegler, V. (2019). A 3-D Printed PCB Integrated TEM Horn Antenna. Radio Science. 54(1):158-165. https://doi.org/10.1029/2018RS006594S158165541Ahmed, A., Zhang, Y., Burns, D., Huston, D., & Xia, T. (2016). Design of UWB Antenna for Air-Coupled Impulse Ground-Penetrating Radar. IEEE Geoscience and Remote Sensing Letters, 13(1), 92-96. doi:10.1109/lgrs.2015.2498404Garcia, C. R., Rumpf, R. C., Tsang, H. H., & Barton, J. H. (2013). Effects of extreme surface roughness on 3D printed horn antenna. Electronics Letters, 49(12), 734-736. doi:10.1049/el.2013.1528Gianesello , F. Bisognin , A. Titz , D. Luxey , C. Fernandes , C. A. Costa , J. R. Gloria , D. 2016 55 56Holloway, C. L., & Kuester, E. F. (2000). Power loss associated with conducting and superconducting rough interfaces. IEEE Transactions on Microwave Theory and Techniques, 48(10), 1601-1610. doi:10.1109/22.873886Liang, M., Shemelya, C., MacDonald, E., Wicker, R., & Xin, H. (2015). 3-D Printed Microwave Patch Antenna via Fused Deposition Method and Ultrasonic Wire Mesh Embedding Technique. IEEE Antennas and Wireless Propagation Letters, 14, 1346-1349. doi:10.1109/lawp.2015.2405054Liang , M. Yu , X. Shemelya , C. MacDonald , E. Xin , H. 2015 “3D printed multilayer MSL structure with vertical transition toward integrated systems" 2015 IEEE MTT-S International Microwave Symposium 1 4Local motors 2017 3D Printed Car Close-up Look, Mouser's Strati @ Westec 2017 https://localmotors.com/3d-printed-car/Malherbe , J. A. G. 2012 “Hybrid elliptic TEM horn with symmetric main beam" 15th International Symposium on 2012 Toulouse in Antenna Technology and Applied Electromagnetics (ANTEM), FR 1 4Nayeri, P., Liang, M., Sabory-Garcia, R. A., Tuo, M., Yang, F., Gehm, M., … Elsherbeni, A. Z. (2014). 3D Printed Dielectric Reflectarrays: Low-Cost High-Gain Antennas at Sub-Millimeter Waves. IEEE Transactions on Antennas and Propagation, 62(4), 2000-2008. doi:10.1109/tap.2014.2303195Petrick, I. J., & Simpson, T. W. (2013). 3D Printing Disrupts Manufacturing: How Economies of One Create New Rules of Competition. Research-Technology Management, 56(6), 12-16. doi:10.5437/08956308x5606193Shemelya , C. Zemba , M. Liang , M. Espalin , D. Kief , C. Xin , H. Wicker , R. B. MacDonald , E. W. 2015 “3D printing multi-functionality: Embedded RF antennas and components" 2015 9th European Conference on Antennas and Propagation (EuCAP) 1 5Tavik, G. C., Hilterbrick, C. L., Evins, J. B., Alter, J. J., Crnkovich, J. G., de Graaf, J. W., … Hagewood, S. M. (2005). The advanced multifunction RF concept. IEEE Transactions on Microwave Theory and Techniques, 53(3), 1009-1020. doi:10.1109/tmtt.2005.843485Tomlin , M. Meyer , J. 2011 “Topology optimization of an additive layer manufactured (ALM) aerospace part" The 7th Altair Technology Conference 2011 1 9Wheeler, H. A. (1965). Transmission-Line Properties of Parallel Strips Separated by a Dielectric Sheet. IEEE Transactions on Microwave Theory and Techniques, 13(2), 172-185. doi:10.1109/tmtt.1965.11259623DPrint.com. The Voice of 3D Printing/ Additive Manufacturing 2016 3D printed house https://3dprint.com/tag/3d-printed-house

Identification and purification of a bovine liver mitochondrial NAD+-glycohydrolase

AbstractNonenzymatic ADP-ribosylation of mitochondrial proteins is thought to play a role in the regulation of Ca2+ efflux from mitochondria. It has been shown that intramitochondrial ADP-ribose is generated by a specific NAD+ glycohydrolase, which catalizes hydrolysis of NAD+ to ADP-ribose and nicotinamide. We purified this enzyme from bovine liver mitochondrial membranes. The final preparation had a 1660-fold purified enzyme activity and contained a main protein band with an apparent molar mass of 32,000 in a SDS-polyacrylamide gel. The identity of this protein band with NAD+-glycohydrolase was verified by renaturation of its enzymatic activity. Partial amino acid sequence information was obtained from two enzyme fragments after proteolytic cleavage of the protein band in the SDS-polyacrylamide gel. Searches in protein databases revealed that an arginine ADP-ribosyl hydrolase harbours two stretches of amino acids that are highly similar to the partial NAD+-glycohydrolase sequences

A first-in-human, randomized, controlled, subject- and reviewer-blinded multicenter study of Actamax™ Adhesion Barrier

Purpose: Post-surgical adhesions remain a significant concern following abdominopelvic surgery. This study was to assess safety, manageability and explore preliminary efficacy of applying a degradable hydrogel adhesion barrier to areas of surgical trauma following gynecologic laparoscopic abdominopelvic surgery. Methods: This first-in-human, prospective, randomized, multicenter, subject- and reviewer-blinded clinical study was conducted in 78 premenopausal women (18–46 years) wishing to maintain fertility and undergoing gynecologic laparoscopic abdominopelvic surgery with planned clinically indicated second-look laparoscopy (SLL) at 4–12 weeks. The first two patients of each surgeon received hydrogel, up to 30 mL sprayed over all sites of surgical trauma, and were assessed for safety and application only (n = 12). Subsequent subjects (n = 66) were randomized 1:1 to receive either hydrogel (Treatment, n = 35) or not (Control, n = 31); 63 completed the SLL. Results: No adverse event was assessed as serious, or possibly device related. None was severe or fatal. Adverse events were reported for 17 treated subjects (17/47, 36.2%) and 13 Controls (13/31, 41.9%). For 95.7% of treated subjects, surgeons found the device “easy” or “very easy” to use; in 54.5%, some residual material was evident at SLL. For 63 randomized subjects who completed the SLL, adjusted between-group difference in the change from baseline adhesion score demonstrated a 41.4% reduction for Treatment compared with Controls (p = 0.017), with a 49.5% reduction (p = 0.008) among myomectomy subjects (n = 34). Conclusion: Spray application of a degradable hydrogel adhesion barrier during gynecologic laparoscopic abdominopelvic surgery was performed easily and safely, without evidence of clinically significant adverse outcomes. Data suggest the hydrogel was effective in reducing postoperative adhesion development, particularly following myomectomy

Clinical examination and patients’ history are not suitable for neonatal hip screening

PURPOSE: To assess the percentage of missed developmental dysplasia of the hip, which escape the German criteria for newborn hip high-risk screening, we analyzed our data gained from the general neonatal sonographic hip screening performed at our department. The aim of the study was to determine the number of potentially belatedly treated developmental dysplasia of the hip. METHODS: The data from 1145 standardized newborn hip ultrasound examinations according to the Graf technique were analyzed retrospectively comparing findings for general neonatal sonographic hip screening and high-risk screening subgroups. RESULTS: We diagnosed developmental dysplasia of the hip in 18 of the 1145 newborns via ultrasound. A total of 10 out of 18 developmental dysplasia of the hip would have been missed by high-risk screening, which corresponds to a proportion of 55.6% false-negative results. The sensitivity of high-risk screening was only 44.4% and specificity, 78.3%. The positive predictive value was 3.2%. Family history as a screening criterion yielded false-negative results in 77.8% and false-positive results in 16.8%. In all, 83.3% of the children who were born with developmental dysplasia of the hip but not from breech position as a risk factor were false negative. The clinical examination was false negative in 88.9% and false positive in 0.6%. CONCLUSION: High-risk screening detected less than every second developmental dysplasia of the hip, rendering the first month as the most effective treatment window unavailable for inapparent dysplastic hips, potentially resulting in the need for more invasive treatment. Due to the high sensitivity of ultrasound in the detection of developmental dysplasia of the hip, we recommend to replace the current German high-risk screening guidelines with a general newborn screening for all neonates using Graf ultrasound in the first week of life. LEVEL OF EVIDENCE: Level II

How often should we monitor for reliable detection of atrial fibrillation recurrence? Efficiency considerations and implications for study design

OBJECTIVE: Although atrial fibrillation (AF) recurrence is unpredictable in terms of onset and duration, current intermittent rhythm monitoring (IRM) diagnostic modalities are short-termed and discontinuous. The aim of the present study was to investigate the necessary IRM frequency required to reliably detect recurrence of various AF recurrence patterns. METHODS: The rhythm histories of 647 patients (mean AF burden: 12±22% of monitored time; 687 patient-years) with implantable continuous monitoring devices were reconstructed and analyzed. With the use of computationally intensive simulation, we evaluated the necessary IRM frequency to reliably detect AF recurrence of various AF phenotypes using IRM of various durations. RESULTS: The IRM frequency required for reliable AF detection depends on the amount and temporal aggregation of the AF recurrence (p<0.0001) as well as the duration of the IRM (p<0.001). Reliable detection (>95% sensitivity) of AF recurrence required higher IRM frequencies (>12 24-hour; >6 7-day; >4 14-day; >3 30-day IRM per year; p<0.0001) than currently recommended. Lower IRM frequencies will under-detect AF recurrence and introduce significant bias in the evaluation of therapeutic interventions. More frequent but of shorter duration, IRMs (24-hour) are significantly more time effective (sensitivity per monitored time) than a fewer number of longer IRM durations (p<0.0001). CONCLUSIONS: Reliable AF recurrence detection requires higher IRM frequencies than currently recommended. Current IRM frequency recommendations will fail to diagnose a significant proportion of patients. Shorter duration but more frequent IRM strategies are significantly more efficient than longer IRM durations. CLINICAL TRIAL REGISTRATION URL: Unique identifier: NCT00806689