Excessive Rejection Research Articles

Study on Immune Rejection of Xenotransplantation of Bone Fracture Hematoma Cells in Rabbits

Purpose — To explore the immune rejection of xenotransplantation of bone fracture hematoma cells in rabbits. Way — Lan Tu was used as the donor for allogeneic transplantation of fracture hematoma cells. Twelve New Zealand white rabbits were selected to establish the fracture model. The fracture hematoma cells of Lan Tu were transplanted to the broken end of the experimental group of New Zealand white rabbits, while the rabbits in the control group were not transplanted with allogeneic fracture hematoma cells. To observe the expression level of allogeneic fracture hematoma cells in the fracture site, and to analyze the rejection caused by xenotransplantation by observing the number of macrophages in the fracture model section and lymphoid follicles in the recipient spleen. Result — On the 7th and 12th day after transplantation, the hematoma cells in the fractured end of rabbits in the experimental group showed a decreasing trend, but their survival still met the needs of treatment. The results of immunohistochemical examination on the fractured bone tissue and spleen of the two groups of rabbits showed that there was no significant difference between the macrophage content in the fractured bone tissue and the lymphocyte follicular count in the spleen tissue of the two groups of rabbits in different transplantation time (P > 0.05). Conclusion — Using allogeneic hematoma cell transplantation to treat fractures will not cause excessive rejection of receptors, which is worthy of further clinical discussion and provides a favorable scientific reference for its application in clinical treatment of fractures.

Cream Skimming and Information Design in Matching Markets

Short-lived buyers arrive to a platform over time and randomly match with sellers. The sellers stay at the platform and decide whether to accept incoming requests. The platform designs what buyer information the sellers observe before deciding to form a match. We show full information disclosure leads to a market failure because of excessive rejections by the sellers. If sellers are homogeneous, then coarse information policies are able to restore efficiency. If sellers are heterogeneous, then simple censorship policies are often constrained efficient as shown by a method of calculus of variations. (JEL C78, D82, D83)

Clinical Outcomes of Perioperative Desensitization in Orthotopic Heart Transplant Recipients

Purpose Transplantation of sensitized recipients is associated with suboptimal post-transplant outcomes. This study assessed the effects of a perioperative desensitization strategy in virtual crossmatch (VXM)-positive orthotopic heart transplant (OHT) recipients compared to a historical cohort of VXM-negative OHT recipients. Methods This single-center, retrospective study included OHT recipients from 2010-2018. VXM-positive patients received perioperative plasmapheresis, intravenous immunoglobulin (IVIg), and antithymocyte globulin (rATG). VXM-negative historical controls received either high-dose steroids or alemtuzumab induction. Maintenance immunosuppression consisted of tacrolimus, mycophenolate, and a steroid taper. The primary endpoint was graft survival at 12 months. Secondary endpoints included freedom from acute rejection and freedom from severe (i.e., grade ≥ 2) acute cellular rejection or antibody-mediated rejection at 12 months. Results Of 91 patients included, 7 received desensitization. Baseline demographics, disease etiology, and comorbid conditions were similar between groups. VXM-positive recipients received a median of 5.1 (4.8-5.3) mg/kg of rATG, 0.9 (0-1.2) g/kg of IVIg, and 6 (3-7) plasmapheresis sessions. Maintenance immunosuppression was similar at all time points. There was one graft loss, which occurred in the VXM-negative cohort at 70 days post-OHT. The median time to rejection was 44.5 (16.5-93.5) days in the VXM-negative group versus 46.5 (10-83) days in the VXM-positive group (p=0.76). There were no differences in any other rejection outcomes. Six VXM-positive recipients cleared donor-specific antibodies (DSA) by day 21 and all cleared DSA by day 60 (Figure 1). Conclusion These data suggest that transplantation of VXM-positive OHT recipients receiving perioperative desensitization is feasible without excess graft loss or acute rejection at 12 months. The rapid clearance and lack of DSA recurrence is promising for long-term outcomes.

Cartilage regeneration using decellularized cartilage matrix: Long-term comparison of subcutaneous and intranasal placement in a rabbit model

Autologous cartilage as donor tissue for various surgical reconstructions such as nasal septum regeneration is limited and associated with donor site morbidity. Our goal was to evaluate a new resorbable chondroconductive biomaterial made of decellularized porcine nasal septum cartilage compared with autologous native auricular cartilage as the gold standard. In order to examine the material and determine its long-term outcome further, we used subcutaneous implantation and septal implantation in an orthotopic rabbit model. In addition to non-seeded decellularized xenogenic cartilage, chondrocyte-seeded decellularized xenogenic cartilage was implanted as a septal replacement. After a three- or six-month period, the formation of newly synthesized cartilage extracellular matrix was evaluated immunohistochemically, whereas septal integrity and biocompatibility were evaluated histologically. The formation of the implanted neoseptum and form stability was analyzed by using 7-Tesla Magnetic Resonance Imaging.Good biocompatibility with no excessive rejection was demonstrated in all groups. Long-term stable and reliable septal reconstruction could be achieved in the study groups with or without cell seeding with autologous auricular chondrocytes. Autologous cell seeding was advantageous only with regard to septal perforations. Thus, cell seeding provides a benefit regarding long-term stability. However, because of slightly better biocompatibility, less pronounced septum deviation and the markedly lower effort involved, the non-seeded scaffold is favoured for possible clinical application.

2'-O-methylation in mRNA disrupts tRNA decoding during translation elongation.

Chemical modifications of messenger RNA (mRNA) may regulate many aspects of mRNA processing and protein synthesis. Recently, 2′-O-methylation of nucleotides was identified as a frequent modification in translated regions of human mRNA, showing enrichment in codons for certain amino acid. Here, using single-molecule, bulk kinetics and structural methods, we show that 2′-O-methylation within coding regions of mRNA disrupts key steps in codon reading during cognate transfer RNA (tRNA) selection. Our results suggest that 2′-O-methylation sterically perturbs interactions of ribosomal monitoring bases (G530, A1492 and A1493) with cognate codon-anticodon helices, thereby inhibiting downstream GTP-hydrolysis by elongation factor Tu (EF-Tu) and A-site tRNA accommodation, leading to excessive rejection of cognate aminoacylated-tRNAs in initial selection and proofreading. Our current and prior findings highlight how chemical modifications of mRNA tune the dynamics of protein synthesis at different steps of translation elongation.

How 2'-O-Methylation in mRNA Disrupts tRNA Decoding during Translation Elongation

Chemical modifications of messenger RNA (mRNA) may regulate many aspects of mRNA processing and protein synthesis. Recently, 2'-O-methylation (Nm) of nucleotides was identified as a frequent modification in translated regions of human mRNA, showing enrichment in certain amino acid codons. Here, using single-molecule, bulk kinetics and structural methods, we show that Nm within coding regions of mRNA disrupts key steps in codon reading during cognate transfer RNA (tRNA) selection. Our results suggest that Nm sterically perturbs interactions of ribosomal monitoring bases (G530, A1492 and A1493 of 16S ribosomal RNA) with cognate codon-anticodon helices, thereby inhibiting downstream GTP-hydrolysis by elongation factor Tu (EF-Tu) and A-site tRNA accommodation, leading to excessive rejection of cognate aminoacylated-tRNAs in initial selection and proofreading. The observed effect of monitoring bases in decoding accuracy mirrors the effect of disturbed codon-anticodon pairing, previously studied using N6-methyladenoside (m6A) modified mRNA. Combined together, our findings highlight how chemical modifications of mRNA tune the dynamics of protein synthesis at different steps of translation elongation.

Cream Skimming and Information Design in Matching Markets

Short-lived buyers arrive to a platform over time and randomly match with sellers. The sellers stay at the platform and sequentially decide whether to accept incoming requests. The platform designs what buyer information the sellers observe before deciding to form a match. We show full information disclosure leads to a market failure because of excessive rejections by the sellers. If sellers are homogeneous, then coarse information policies are able to restore efficiency. If sellers are heterogeneous, then simple censorship policies are often constrained efficient as shown by a novel method of calculus of variations.

Statistical analyses of Global U-Pb Database 2017

The method of obtaining zircon samples affects estimation of the global U-Pb age distribution. Researchers typically collect zircons via convenience sampling and cluster sampling. When using these techniques, weight adjustments proportional to the areas of the sampled regions improve upon unweighted estimates. Here, grid-area and modern sediment methods are used to weight the samples from a new database of 418,967 U-Pb ages. Preliminary tests involve two age models. Model-1 uses the most precise U-Pb ages as the best ages. Model-2 uses the 206Pb/238U age as the best age if it is less than a 1000 Ma cutoff, otherwise it uses the 207Pb/206Pb age as the best age. A correlation analysis between the Model-1 and Model-2 ages indicates nearly identical distributions for both models. However, after applying acceptance criteria to include only the most precise analyses with minimal discordance, a histogram of the rejected samples shows excessive rejection of the Model-2 analyses around the 1000 Ma cutoff point. Because of the excessive rejection rate for Model-2, we select Model-1 as the preferred model. After eliminating all rejected samples, the remaining analyses use only Model-1 ages for five rock-type subsets of the database: igneous, meta-igneous, sedimentary, meta-sedimentary, and modern sediments. Next, time-series plots, cross-correlation analyses, and spectral analyses determine the degree of alignment among the time-series and their periodicity. For all rock types, the U-Pb age distributions are similar for ages older than 500 Ma, but align poorly for ages younger than 500 Ma. The similarities (>500 Ma) and differences (<500 Ma) highlight how reductionism from a detailed database enhances understanding of time-dependent sequences, such as erosion, detrital transport mechanisms, lithification, and metamorphism. Time-series analyses and spectral analyses of the age distributions predominantly indicate a synchronous period-tripling sequence of ∼91-Myr, ∼273-Myr, and ∼819-Myr among the various rock types.

Particularly compliance violations in patients with diabetes mellitus of 2nd type

Aim : to investigate and establish the specific complains violations in patients with diabetes mellitus (DM) of 2 nd type. Materials and methods : 543 patients with DM of 2 nd type were examined; the disease duration ranged from 2 to 27 years, average – (14.58 ± 1.82) years. Research methods: clinical-anamnestic, clinical-psychopathological, psycho diagnostic, statistical. Research results . We found that compliance to therapy in patients with DM of 2 nd type was broken in 90.49 % of cases. We highlighted three options for compliance violations to DM therapy of 2 nd type: dismedication (to 68.14 %), disdiet (88.40 %) and disexercise (90.49 %). The sub-variants of dismedication compliance violations to DM therapy of 2 nd type was hyper-curation type (8.29 %), which was developed according to surplus of appointments execution and hypo-curation type (59.85 %), which was developed according to deficiency of appointments execution. Among them it was possible to distinguish a third – mixed version (7.37 %), which brings together episodes of the surplus and the deficit of medical drugs usage. The sub-options of disdiet option of compliance violations was hyper-curation type (1.66 %), which manifested itself in pathologically excessive rejection of food and hypo-curation type (86.74 %), which manifested itself in a disregard for the restrictions in the diet. Disexercise variant of compliance violations was possible to divide into hyper-curation type (4,24 %), manifested in excessive physical activity and, in its turn, had three subtypes – inceptional (1.66 %), sub-hyper-curation (1.10 %) and procurationis (1.47 %), and hypo-curation type of compliance violations (87.48 %), which manifested itself in a disregard of physical exertion. Dominance of disdiet and disexercise compliance violations among patients with DM of 2 nd type (χ 2 = 117.258, p < 0.01), dismedication option among patients of all hyper-curation types of compliance violations with DM of 2 nd type (χ 2 = 26.936, p < 0.01), disdiet and disexercise options among patients of all hypo-curation types of compliance violations with DM of 2 nd type (χ 2 = 156.922, p < 0.01) and hypo-curation type of compliance violation for all of its variants have been established. The factors of compliance violations for each of the variants and types have been determined.

Dust in Lacquer, Evidence of Deviation of Process in Production Lines for Spray Painting

This paper concerns work carried with a view to reduce defect occurrence rate in the spray painting lines of MDF (medium density fibre cluster-medium density fibreboard) parts of a multinational mobile manufacturing. The determination of the causes for the excessive rejection values is elusive for the multiplicity of factors and parameters involved and the dispersion of application times, not always sufficiently or properly documented. A process analysis methodology was applied to diagnose possible causes of defect occurrences. Considering that the highest defect rate concerned impurities, data collected over a six months’ period was analysed using SPSS to find the correlation between parameters, to find optimal limits of some parameters and evidence of their influence. Kaizen-Lean actions were discussed and implemented conducing to an effective reduction of the existing impurities defect rate, which decreased ninefold related with initial work values.

Ambrosia Limited- A Cold Chain Dilemma

When a Zonal Sales Manager is seen fighting at a C&amp;F Office, it is an unusual sight. However at Ambrosia Limited, a renowned name in Poultry products, a simple supply chain dilemma has made it a regular affair. Though the policy of company officials of completely managing the C&amp;F’s has been smooth, there has always been a problem when it came to supply chain. Be it over stocking or excessive rejections from customers, such uncertain issues at times expose the weak link of poor supply chain policies in the company, thus creating potential rift between the company officials and the C&amp;F owner. Even last year the Zonal Sales Manager was greatly upset during the rainy season where great amount of products were not utilized thus creating losses, for which no body was ready to take the responsibility. The upcoming monsoon season might bring a whole new set of problems as the particular problem could again play a critical role in damaging profits.

EEG acquisition system based on active electrodes with common-mode interference suppression by Driving Right Leg circuit.

We present a system for the acquisition of EEG signals based on active electrodes and implementing a Driving Right Leg circuit (DgRL). DgRL allows for single-ended amplification and analog-to-digital conversion, still guaranteeing a common mode rejection in excess of 110 dB. This allows the system to acquire high-quality EEG signals essentially removing network interference for both wet and dry-contact electrodes. The front-end amplification stage is integrated on the electrode, minimizing the system's sensitivity to electrode contact quality, cable movement and common mode interference. The A/D conversion stage can be either integrated in the remote back-end or placed on the head as well, allowing for an all-digital communication to the back-end. Noise integrated in the band from 0.5 to 100 Hz is comprised between 0.62 and 1.3 μV, depending on the configuration. Current consumption for the amplification and A/D conversion of one channel is 390 μA. Thanks to its low noise, the high level of interference suppression and its quick setup capabilities, the system is particularly suitable for use outside clinical environments, such as in home care, brain-computer interfaces or consumer-oriented applications.

Response to Pagano et al.

In their letter, Pagano et al. appreciate the development of the Nox1, Nox2, and Nox4 triple (3N(-/-)) knockout mouse. They also agree on the view that chemiluminescence assays in general have severe limitations. However, they criticize the fact that the membrane assays in the particular study were restricted to chemiluminescence techniques. Moreover, Pagano et al. got the impression that statements concerning membrane assays of Nox activity in general were made. In addition to a lack of some technical details, Pagano et al. also found the characterization of the 3N(-/-) incomplete and some of the results to be incomprehensible. Although we are grateful for the interest of Pagano et al. in our work, we realized that basically each observation of our study was questioned. This is certainly an excessive rejection of the study in total and fails to appreciate the clear chain of evidences presented. Our work focused on chemiluminescence, and thus, any conclusions are restricted to this technique. Moreover, the 3N(-/-) mice were never developed to study the physiology of Nox enzymes, but rather to validate Nox specificity of NADPH-stimulated chemiluminescence assays. We are convinced that our findings are a valid demonstration that chemiluminescence-based assays in membrane preparations stimulated with NADPH do not measure Nox activity. This conclusion is based on both overexpression studies as well as genetic deficient mouse models. The criticisms of Pagano et al. thus might be justified in some aspects; they, however, cannot disprove the conclusions of our work. Antioxid. Redox Signal. 23, 1247-1249.

Re-evaluation of turbulent mixing vertical structure in the Bussol’ Strait and its impact on water masses in the Okhotsk Sea and the North Pacific

Distribution of the turbulent kinetic energy dissipation rate ε across the Bussol’ Strait was re-evaluated by applying an improved method using density inversions to tide-resolving density observations. The improved estimates without excessive rejection of density inversions provide about three-times higher mean values of ε (1.45×10−7W/kg), vertical diffusivity Kρ (153×10−4m2/s) and depth-integrated ε (187mW/m2) in comparison with previous estimates. One-day mean vertical profiles of ε in the potential density co-ordinate allows us to estimate diapycnal velocity at 3×10−5m/s downwards through the 26.85σθ isopycnal surface, and was almost zero through 26.7σθ, suggesting the thinning of Okhotsk Sea Mode Water or of the core of North Pacific Intermediate Water as the water flows through the Bussol’ Strait from the Sea of Okhotsk to the North Pacific. The re-evaluated turbulence and current distributions confirmed following previous knowledge but with quantitative improvements and/or expansion of coverage: (1) All-averaged ε and Kρ show distinctive mid-depth maxima at 800–1600m, 26.9–27.6σθ and at a height of 300–400m above the bottom, and enhanced ε within 500m of the bottom corresponding to the enhanced shear and low-Richardson number at vertical scales of less than 50m. (2) A significant amount of the ε variance (14%) is explained by the 50m-scale vertical shear composed of mean and diurnal tidal currents. (3) The diurnal tidal currents are well approximated by six low-mode topographically trapped waves.

Solving the optimal process target problem using computer-generated experimental designs

For any given manufacturing system, the initial setting of the process target is critical in preventing excessive product rejection and rework costs. Often referred to as the ‘process target problem’, the traditional approach relies first on the assumption of certain values for the process mean and variance, prior to identifying the optimal setting. This paper, in contrast, proposes integrating estimated response surface functions developed for the mean and variance based upon observations made on a given process, thus removing any assumption on the parameters. In addition, this paper considers non-standard experimental regions, where constraints may exist on the factor space or restrictions are implemented on the number of experimental runs conducted. In doing so, greater flexibility is obtained in finding solutions to process target problems and the scope of the research field is broadened. Non-linear programming methods are used to facilitate this approach, and numerical examples are provided to illust...

An active tri-band (AMPS/PCS/GPS) antenna with enhanced cellular-to-GPS isolation for automotive applications

The design and performance of an active tri-band antenna for automotive applications that includes the global positioning system (GPS), analog mobile phone service (AMPS), and personal communication service (PCS) is presented. For automotive emergency applications, the close proximity of the GPS and cellular antenna elements demands stringent isolation requirements on the GPS low noise amplifier (LNA) design to prevent interference to GPS during cellular transmissions. The GPS low-noise amplifier designed in this letter exhibited a power gain of 26.4 dB, an out of band rejection in excess of 31 dB at +/-50 MHz around the center frequency, a noise figure of 1.5 dB, a 1dB power compression of 9.7 dBm, isolation over the AMPS band in excess of 62 dB, isolation over the PCS band in excess of 48 dB, an input 3rd order intercept of −6.5 dBm and an output 3rd order intercept of 20.6 dBm while operating at 5 volts with a current draw of 20mA. In addition, the antenna patterns measured on a ground plane are presented for the active GPS antenna, AMPS passive antenna and the PCS passive antenna. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26117

A 2% Bandwidth C-Band Filter Using Cascaded Split Ring Resonators

A 2% bandpass filter with an out-of-band rejection in excess of 30 dB was demonstrated experimentally for operation in the C-band (central frequency at 4.5 GHz). Narrow bandwidth and high rejection were achieved by cascading three double split-ring resonators (SRRs) magnetically coupled to a coplanar waveguide (CPW) and three pairs of shunt wires between the central strip and the ground metal layers. This configuration, directly inspired from the so-called metamaterial technology, takes advantage of the high dispersion of the loaded transmission line, induced by a negative magnetic response via the resonators, and of a negative permittivity effect via the shunt wires. The optimization of: 1) the symmetry; 2) the out-of-band rejection; and 3) the fractional bandwidth was carried out in two stages, i.e., by engineering the plasma frequencies of the electrical and magnetic systems and by tapering the tightly coupled cascaded unit cells in order to achieve an overlap of their individual responses.

Multiple-input multiple-output over-the-horizon radar: experimental results

Results from an experiment that applied one class of multiple-input multiple-output (MIMO) waveform techniques to over-the-horizon radar (OTHR) are reported. The experiment objective was to demonstrate that adaptive transmitter beamforming could be used in an appropriately design radar to reject spatially discrete Doppler-spread clutter. In the particular MIMO radar architecture that the authors call non-causal transmit beamforming, conventional or adaptive transmitter beamforming occurs following waveform transmission, propagation, scatter from targets and clutter sources, return propagation and finally signal reception. In the case reported herein spatially discrete clutter was successfully rejected to the noise floor of the radar return with rejection in excess of 35 dB achieved using common adaptive algorithms and straightforward training data selection. As part of the rejection algorithm the transmitted waveform direction-of-departure (DOD) from the transmitter array to the target was estimated and used as the preserved steer direction in the adaptive beamformer. The DOD estimates agree well with the geometrically determined true values. The demonstration of non-causal transmit beamforming suggests that it will be possible to create multiple simultaneous adaptive range-dependent transmitter beams with an appropriately designed OTHR. This has several applications including for the mitigation of Doppler-spread clutter.

Randomized Trial of Tacrolimus Monotherapy: Tacrolimus In Combination, Tacrolimus Alone Compared (The TICTAC Trial)

Prior retrospective studies have suggested that tacrolimus monotherapy is an option associated with excellent outcomes and reduced toxicities. We conducted a prospective, randomized, 2-center study of tacrolimus combination therapy vs monotherapy. From April 16, 2004, to September 15, 2005, 58 adult heart transplant patients were studied. All received oral tacrolimus, mycophenolate mofetil, and corticosteroids. Patients were then randomized to a group where mycophenolate was maintained (COMBO) or to a group where it was discontinued (MONO) 14 days post-transplant. Corticosteroids were rapidly withdrawn in both groups between 8 and 12 weeks. The primary end point (mean 6-month International Society of Heart and Lung Transplantation biopsy score) was 0.44 +/- 0.04 in the MONO group and 0.60 +/- 0.05 in the COMBO group (p = 0.013, unpaired Student's t-test). The freedom from rejection grade of 2R or higher at 6 and 12 months was 93.3% with MONO and 92.9% with COMBO (p = NS). Tacrolimus monotherapy appears to be safe and efficacious in heart transplant recipients and is not associated with excess rejection in the first year post-transplant. Further studies of this approach are warranted.

Robustness of Coalescent Estimators to Between-Lineage Mutation Rate Variation

Data from HIV and from human neoplastic cells can show substantial between-lineage mutation rate variation even within a single population. Such variation may affect estimators of population quantities such as Theta = 4N(e)mu. Using simulated DNA data, I measured the effect of rate variation on recovery of Theta by the summary-statistic estimator of Watterson (Watterson GA. 1975. On the number of segregating sites in genetical systems without recombination. Theor Popul Biol. 7:256-276) and the coalescent maximum likelihood algorithm LAMARC (Kuhner MK. 2006. LAMARC 2.0: maximum likelihood and Bayesian estimation of population parameters. Bioinformatics. Advance Access doi: 10.1093/bioinformatics/btk051). Watterson's estimator showed a downward bias, as expected, with high values of Theta. LAMARC's mean estimate was accurate for all tested values of Theta and rate variation except for a downward bias when rate variation was maximal (i.e., the slow rate was zero). LAMARC had consistently narrower confidence intervals (CIs) than Watterson's estimator. Both methods tended to reject the truth too often when rate variation was 8x or greater and independent among branches, as well as when variation was 4x or greater and correlated among branches. In the case of Watterson's estimate, this excess rejection was fully attributable to variation among genealogies in the amount of total branch length associated with the fast and slow rates. However, in the case of LAMARC, some excess rejection was still observed even when between-genealogy variation was taken into account. Both estimators are robust to modest rate variation; however, their use should be coupled with a statistical test to rule out extreme rate variation as the resulting CIs may not be reliable.