Amorphous solids lack long-range order. Therefore identifying structural defects -- akin to dislocations in crystalline solids -- that carry plastic flow in these systems remains a daunting ...challenge. By comparing many different structural indicators in computational models of glasses, under a variety of conditions we carefully assess which of these indicators are able to robustly identify the structural defects responsible for plastic flow in amorphous solids. We further demonstrate that the density of defects changes as a function of material preparation and strain in a manner that is highly correlated with the macroscopic material response. Our work represents an important step towards predicting how and when an amorphous solid will fail from its microscopic structure.
In 2002, 1329 patients with functioning transplants were prospectively tested for HLA antibodies in the 13th International Histocompatibility Workshop. Four years after testing, deceased donor graft ...survival among 806 patients not having antibodies in 2002 was 81% compared to 58% for 158 patients with HLA antibodies (p < 0.0001) and 72% for 69 patients with MICA antibodies (p = 0.02). Hazard ratio (HR) using death‐censored graft survival from multivariate analysis of HLA antibodies was 3.3 (p < 0.00001) and 2.04 for MICA (p = 0.01).
In the 14th Workshop, at 1 year follow‐up, survival for 1319 patients receiving deceased donor grafts and no HLA antibodies was 96% compared to 94% for 344 patients with HLA antibodies (p = 0.0004) and 83% survival for 33 patients with MICA (p = 0.0005). HR from multivariate analysis: HLA antibodies was 3.6 (p < 0.00001) and 6.1 for MICA (p = 0.006). Twelve patients with donor specific antibodies tested by single antigen beads had a 1 year survival of 64% (p = 0.008), and 27 patients with non‐donor specific ‘strong’ antibodies had a 66% survival (p = 0.0003) compared to 92% survival in those with no antibodies.
In conclusion, these two prospective trials, after 1 and 4 years, provided strong evidence that HLA and MICA antibodies are associated with graft failure.
Two studies of functioning kidney transplants reported here demonstrate that patients with MICA antibodies, as well as those with HLA antibodies, have an increased risk of graft failure.
A remarkable observation that detonation of oxygen-deficient explosives in an inert medium produces ultra-fine diamond particles having diameters of 4–5 nm was made four decades ago, but this novel ...form of diamond has never been isolated in pure form thereafter. The reason for the difficulty was that the core aggregates having a diameter range of 100–200 nm are extremely tight and could not be broken up by any known method of de-aggregation. After a number of futile attempts, we were able to obtain primary particles by using the recently emerging technique of stirred-media milling with micron-sized ceramic beads. The milled aqueous slurry of nanodiamond gave a stable, thick and dark-coloured colloidal solution. After light sonication, dynamic light scattering measurements gave a sharp distribution in the single-digit nano-range, and HRTEM indicated separate particles having diameters of 4–5 nm, which agreed with the X-ray value of 4.4 nm for the primary particles. A model is presented for the core aggregates, which resembles the well-known grape-shaped ‘aggregate structure’ of the hardest type of carbon black.
Aims
Given the significance of Salmonella enterica in both human and animal health, and a recent global dissemination of Salmonella 4,5,12:i:‐, changes in the prevalent serovars and antimicrobial ...resistance in clinical isolates of Salmonella from cattle and pigs were investigated in Japan.
Methods and Results
The serovars and antimicrobial susceptibilities of 1605 Salmonella enterica isolated from cattle (n = 894) and swine (n = 711) between 2002 and 2016 were examined. The most common serovar among all samples was Salmonella Typhimurium. However, its monophasic variant with antigenic structure S. 4,5,12:i:‐, which was first detected in cattle in 2006 and swine in 2010, has been rapidly increasing in incidence and resistance. Resistance rates to cefotaxime and ciprofloxacin were generally low (<10% in the cattle isolates and <5% in the swine isolates); however, isolates resistant to more than five antimicrobials, which often include these antimicrobials, were recently detected in Salmonella Dublin, S. 4,5,12:i:‐, S. Typhimurium, Salmonella Newport, Salmonella Choleraesuis and Salmonella 6,7:c:‐. Among them, two S. 4,5,12:i:‐ isolates possessed extended‐spectrum β‐lactamase‐encoding genes; blaSHV‐12 or blaCTX‐M‐55, respectively, while all the five S. Typhimurium isolates possessed AmpC‐type β‐lactamase gene of blaCMY‐2.
Conclusions
S. 4,5,12:i:‐ has been rapidly increasing and exhibiting a remarkable change in antimicrobial resistance in Japan. Considering certain serovars are characterized by multidrug resistance including medically important antimicrobials, continuous monitoring and appropriate measures are required to protect public health and veterinary husbandry.
Significance and Impact of the Study
This study presents a trend in the serovars and antimicrobial resistance in clinical isolates of Salmonella from cattle and pigs in Japan, and showed that there were certain types of Salmonella serovars depending on the animal origin which needs more attention.
We introduce the concept of a handlebody decomposition of a three-manifold, a generalization of a Heegaard splitting, or a trisection. We show that two handlebody decompositions of a closed ...orientable three-manifold are stably equivalent. As an application to materials science, we consider a mathematical model of polycontinuous patterns and discuss a topological study of microphase separation of a block copolymer melt.
Preformed donor HLA‐specific antibodies are a known indicator for poor patient survival after cardiac transplantation. The role of de novo donor‐specific antibodies (DSA) formed after cardiac ...transplantation is less clear. Here we have retrospectively analyzed 243 cardiac transplant recipients, measuring HLA antibody production every year after transplantation up to 13 years post‐transplant. Production of de novo DSA was analyzed in patients who had been negative for DSA prior to their transplant. DSA including transient antibodies were associated with poor patient survival (p = 0.0018, HR = 3.198). However, de novo and persistent DSA was strongly associated with poor patient survival (p = 0.0001 HR = 4.351). Although complement fixing persistent DSA correlated with poor patient survival, this was not increased compared to noncomplement fixing persistent DSA. Multivariable analysis indicated de novo persistent DSA to be an independent predictor of poor patient survival along with HLA‐DR mismatch and donor age. Only increasing donor age was found to be an independent risk factor for earlier development of CAV. In conclusion, patients who are transplanted in the absence of pre‐existing DSA make de novo DSA after transplantation which are associated with poor survival. Early and regular monitoring of post‐transplant DSA is required to identify patients at risk of allograft failure.
A retrospective study of 243 cardiac transplant patients, followed annually for up to 13 years, shows that production of de novo donor‐specific HLA antibodies portends worse patient survival and is an independent risk factor for poor patient survival.
Summary Objective To investigate the inhibitory effects and the regulatory mechanisms of histone deacetylase (HDAC) inhibitors on mechanical stress-induced gene expression of runt-related ...transcription factor (RUNX)-2 and a d isintegrin a nd m etalloproteinase with t hrombo s pondin motif (ADAMTS)-5 in human chondrocytes. Methods Human chondrocytes were seeded in stretch chambers at a concentration of 5 × 104 cells/chamber. Cells were pre-incubated with or without HDAC inhibitors (MS-275 or trichostatin A; TSA) for 12 h, followed by uniaxial cyclic tensile strain (CTS) (0.5 Hz, 10% elongation), which was applied for 30 min using the ST-140-10 system (STREX, Osaka, Japan). Total RNA was extracted and the expression of RUNX-2, ADAMTS-5, matrix metalloproteinase (MMP)-3, and MMP-13 at the mRNA and protein levels were examined by real-time polymerase chain reaction (PCR) and immunocytochemistry, respectively. The activation of diverse mitogen-activated protein kinase (MAPK) pathways with or without HDAC inhibitors during CTS was examined by western blotting. Results HDAC inhibitors (TSA: 10 nM, MS-275: 100 nM) suppressed CTS-induced expression of RUNX-2, ADAMTS-5, and MMP-3 at both the mRNA and protein levels within 1 h. CTS-induced activation of p38 MAPK (p38), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) MAPKs was downregulated by both HDAC inhibitors. Conclusion The CTS-induced expression of RUNX-2 and ADAMTS-5 was suppressed by HDAC inhibitors via the inhibition of the MAPK pathway activation in human chondrocytes. The results of the current study suggested a novel therapeutic role for HDAC inhibitors against degenerative joint disease such as osteoarthritis.
We present a hard X-ray spectrum of unprecedented quality of the Galactic supernova remnant (SNR) W49B obtained with the Suzaku satellite. The spectrum exhibits an unusual structure consisting of a ...saw-edged bump above 8 keV. This bump cannot be explained by any combination of high-temperature plasmas in ionization equilibrium. We firmly conclude that this bump is caused by the strong radiative recombination continuum (RRC) of iron, detected for the first time in a SNR. The electron temperature derived from the bremsstrahlung continuum shape and the slope of the RRC is approx1.5 keV. On the other hand, the ionization temperature derived from the observed intensity ratios between the RRC and Kalpha lines of iron is approx2.7 keV. These results indicate that the plasma is in a highly overionized state. Volume emission measures independently determined from the fluxes of the thermal and RRC components are consistent with each other, suggesting the same origin of these components.
MicroRNAs derived from extracellular vesicles (EV-miRNAs) are circulating miRNAs considered as potential new diagnostic markers for cancer that can be easily detected in liquid biopsies. In this ...study, we performed RNA sequencing analysis as a screening strategy to identify EV-miRNAs derived from serum of clinically well-annotated breast cancer (BC) patients from the south of Brazil. EVs from three groups of samples (healthy controls (CT), luminal A (LA), and triple-negative (TNBC)) were isolated from serum using a precipitation method and analyzed by RNA-seq (screening phase). Subsequently, four EV-miRNAs (miR-142-5p, miR-150-5p, miR-320a, and miR-4433b-5p) were selected to be quantified by quantitative real-time PCR (RT-qPCR) in individual samples (test phase). A panel composed of miR-142-5p, miR-320a, and miR-4433b-5p distinguished BC patients from CT with an area under the curve (AUC) of 0.8387 (93.33% sensitivity, 68.75% specificity). The combination of miR-142-5p and miR-320a distinguished LA patients from CT with an AUC of 0.9410 (100% sensitivity, 93.80% specificity). Interestingly, decreased expression of miR-142-5p and miR-150-5p were significantly associated with more advanced tumor grades (grade III), while the decreased expression of miR-142-5p and miR-320a was associated with a larger tumor size. These results provide insights into the potential application of EVs-miRNAs from serum as novel specific markers for early diagnosis of BC.
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