C2～7颈椎振动特性的有限元分析

目的研究正常C2～7颈椎有限元模型的振动特性和颈椎小关节不同程度受损及切除的振动特性变化。方法基于颈椎CT扫描影像,建立正常C2～7颈椎有限元模型并验证有效性,提取前10阶固有频率和振型。颈椎小关节分别为无约束、有约束且摩擦系数分别为0.01、0.1和0.2,模拟颈椎小关节切除以及小关节轻度、中度、重度受损,研究颈椎受损程度不同对固有频率的影响。结果正常C2～7颈椎模型最低固有频率出现在后伸、侧弯振型,约为12Hz,大位移主要出现在寰椎齿凸。小关节有约束模型的固有频率高于无约束模型,小关节摩擦系数不同对颈椎固有频率无影响。结论研究颈椎的固有频率、振型和振幅等参数,是进一步研究颈椎动态特性的基础,对颈椎护理和治疗有重要意义。在生活和颈椎治疗中,应尽量避开12Hz环境,防止共振对颈椎造成大的损伤。     

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent and severe chronic disease drastically impairing life quality. The underlying pathomechanism is incompletely understood yet but there is convincing evidence that in at least a subset of patients ME/CFS has an autoimmune etiology. In this review, we will discuss current autoimmune aspects for ME/CFS. Immune dysregulation in ME/CFS has been frequently described including changes in cytokine profiles and immunoglobulin levels, T- and B-cell phenotype and a decrease of natural killer cell cytotoxicity. Moreover, autoantibodies against various antigens including neurotransmitter receptors have been recently identified in ME/CFS individuals by several groups. Consistently, clinical trials from Norway have shown that B-cell depletion with rituximab results in clinical benefits in about half of ME/CFS patients. Furthermore, recent studies have provided evidence for severe metabolic disturbances presumably mediated by serum autoantibodies in ME/CFS. Therefore, further efforts are required to delineate the role of autoantibodies in the onset and pathomechanisms of ME/CFS in order to better understand and properly treat this disease.     

Mucopolysaccharidosis III in Taiwan: Natural history,clinical and molecular characteristics of 28 patients diagnosed during a 21‐year period

Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) has a variable age of onset and variable rate of progression. However, information regarding the natural history of this disorder in Asian populations is limited. A retrospective analysis was carried out for 28 patients with MPS III (types IIIA [n = 3], IIIB [n = 23], and IIIC [n = 2]; 15 males and 13 females; median age, 8.2 years; age range, 2.7–26.5 years) seen in six medical centers in Taiwan from January 1996 through October 2017. The median age at confirmed diagnosis was 4.6 years. The most common initial symptom was speech delay (75%), followed by hirsutism (64%) and hyperactivity (54%). Both z scores for height and weight were negatively correlated with age (r = –.693 and ?0.718, respectively; p < .01). The most prevalent clinical manifestations were speech delay (100%) and intellectual disability (100%), followed by hirsutism (93%), hyperactivity (79%), coarse facial features (68%), sleep disorders (61%), and hepatosplenomegaly (61%). Ten patients (36%) had epilepsy, and the median age at the first seizure was 11 years. Thirteen patients (46%) experienced at least one surgical procedure. At the time of the present study, 7 of the 28 patients had passed away at the median age of 13.0 years. Molecular studies showed an allelic heterogeneity without clear genotype and phenotype correlations. MPS IIIB is the most frequent subtype among MPS III in the Taiwanese population. An understanding of the natural history of MPS III may allow early diagnosis and timely management of the disease facilitating better treatment outcomes.     

From the Cover: Spatiotemporal variations of seismicity before major earthquakes in the Japanese area and their relation with the epicentral locations

Using the Japan Meteorological Agency earthquake catalog, we investigate the seismicity variations before major earthquakes in the Japanese region. We apply natural time, the new time frame, for calculating the fluctuations, termed β, of a certain parameter of seismicity, termed κ₁. In an earlier study, we found that β calculated for the entire Japanese region showed a minimum a few months before the shallow major earthquakes (magnitude larger than 7.6) that occurred in the region during the period from 1 January 1984 to 11 March 2011. In this study, by dividing the Japanese region into small areas, we carry out the β calculation on them. It was found that some small areas show β minimum almost simultaneously with the large area and such small areas clustered within a few hundred kilometers from the actual epicenter of the related main shocks. These results suggest that the present approach may help estimation of the epicentral location of forthcoming major earthquakes.In this study, we investigate the evolution of seismicity shortly before main shocks in the Japanese region, N2546E125148, using Japan Meteorological Agency (JMA) earthquake catalog as in ref 1. For this, we adopted the new time frame called natural time since our previous works using this time frame made the lead time of prediction as short as a few days (see below). For a time series comprising N earthquakes (EQs), the natural time χ_k is defined as χ_k = k/N, where k means the k^th EQ with energy Q_k (Fig. 1). Thus, the raw data for our investigation, to be read from the earthquake catalog, are χ_k = k/N and pk=Qk/∑n=1NQn, where p_k is the normalized energy. In natural time, we are interested in the order and energy of events but not in the time intervals between events.Open in a separate windowFig. 1.EQ sequence in (A) conventional time and (B) natural time. In B, Q_k is given in units of the energy ε corresponding to a 3.5M_JMA EQ.We first calculate a parameter called κ₁, which is defined as follows (2, 3), from the catalog.κ1=∑k=1Npkχk2−(∑k=1Npkχk)2=〈χ2〉−〈χ〉2.[1]We start the calculation of κ₁ at the time of initiation of Seismic Electric Signals (SES), the transient changes of the electric field of Earth that have long been successfully used for short-term EQ prediction (4, 5). The area to suffer a main shock is estimated on the basis of the selectivity map (4, 5) of the station that recorded the corresponding SES. Thus, we now have an area in which we count the small EQs of magnitude greater than or equal to a certain magnitude threshold that occur after the initiation of the SES. We then form time series of seismic events in natural time for this area each time a small EQ occurs, in other words, when the number of the events increases by one. The κ₁ value for each time series is computed for the pairs (χ_k,p_k) by considering that χ_k is “rescaled” to χ_k = k/(N +1) together with rescaling pk=Qk/∑n=1N+1Qn upon the occurrence of any additional event in the area. The resulting number of thus computed κ₁ values is usually of the order 10² to 10³ depending, of course, on the magnitude threshold adopted for the events that occurred after the SES initiation until the main shock occurrence. When we followed this procedure, it was found empirically that the values of κ₁ converge to 0.07 a few days before main shocks. Thus, by using the date of convergence to 0.07 for prediction, the lead times, which were a few months to a few weeks or so by SES data alone, were made, although empirically, as short as a few days (6, 7). In fact, the prominent seismic swarm activity in 2000 in the Izu Island region, Japan, was preceded by a pronounced SES activity 2 mo before it, and the approach of κ₁ to 0.07 was found a few days before the swarm onset (8). However, when SES data are not available, which is usually the case, it is not possible to follow the above procedure. To cope with this difficulty, in the previous work (1), we investigated the time change of the fluctuation of the κ₁ values during a few preseismic months for each EQ (which we call target EQ) over the large area N2546E125148 (Fig. 2A) for the period from 1 January 1984 to 11 March 2011, the day of M9.0 Tohoku EQ. Setting a threshold M_JMA = 3.5 to assure data completeness of JMA catalog, we were left with 47,204 EQs in the concerned period of about 326 mo: ∼150 EQs per month. For calculating the β values, we chose 200 EQs before target EQs to cover the seismicity in almost one and a half months.Open in a separate windowFig. 2.(A) The 47,204 EQs with M_JMA ≥ 3.5 that occurred during the period of our study. (B) Contours of the number of EQs per month within R = 250 km. Solid diamonds show the epicenters of six shallow EQs investigated in this study. (C) Contours of the natural time window W used in each of the 12,476 areas of radius R = 250 km with offset 0.1° from one another that have at least eight EQs per month.To obtain the fluctuation β of κ₁, we need many values of κ₁ for each target EQ. For this purpose, we first took an excerpt comprised of W successive EQs just before a target EQ from the seismic catalog. The number W was chosen to cover a period of a few months. For this excerpt, we form its subexcerpts Sj={Qj+k−1}k=1,2,…,N of consecutive N = 6 EQs (since at least six EQs are needed (2) for obtaining reliable κ₁) of energy Q_j+k?1 and natural time χ_k = k/N each. Further, pk=Qj+k−1/∑k=1NQj+k−1, and by sliding S_j over the excerpt of W EQs, j=1,2,…,W−N+1 (= W − 5), we calculate κ₁ using Eq. 1 for each j. We repeat this calculation for N=7,8,…,W, thus obtaining an ensemble of [(W − 4)(W − 5)]/2 (= 1 + 2 +…+ W − 5) κ₁ values. Then, we compute the average μ(κ₁) and the SD σ(κ₁) of thus obtained ensemble of [(W − 4)(W − 5)]/2 κ₁ values. The variability β of κ₁ for this excerpt W is defined to be β ≡ σ(κ₁)/μ(κ₁) and is assigned to the (W + 1)^th EQ, i.e., the target EQ.The time evolution of the β value can be pursued by sliding the excerpt through the EQ catalog. Namely, through the same process as above, β values assigned to (W + 2)^th, (W + 3)^th, … EQs in the catalog can be obtained.We found in ref. 1 that the fluctuation β of κ₁ values exhibited minimum a few months before all of the six shallow EQs of magnitude larger than 7.6 that occurred in the study period. A minimum of β ≡ σ(κ₁)/μ(κ₁) means large average and/or small deviation of κ₁ values (e.g., see ref. 9).In the present work, we calculate the β values for small areas before the six large EQs, which showed β minima of the large area.     

Discovery of a novel amino acid racemase through exploration of natural variation in Arabidopsis thaliana

Plants produce diverse low-molecular-weight compounds via specialized metabolism. Discovery of the pathways underlying production of these metabolites is an important challenge for harnessing the huge chemical diversity and catalytic potential in the plant kingdom for human uses, but this effort is often encumbered by the necessity to initially identify compounds of interest or purify a catalyst involved in their synthesis. As an alternative approach, we have performed untargeted metabolite profiling and genome-wide association analysis on 440 natural accessions of Arabidopsis thaliana. This approach allowed us to establish genetic linkages between metabolites and genes. Investigation of one of the metabolite–gene associations led to the identification of N-malonyl-d-allo-isoleucine, and the discovery of a novel amino acid racemase involved in its biosynthesis. This finding provides, to our knowledge, the first functional characterization of a eukaryotic member of a large and widely conserved phenazine biosynthesis protein PhzF-like protein family. Unlike most of known eukaryotic amino acid racemases, the newly discovered enzyme does not require pyridoxal 5′-phosphate for its activity. This study thus identifies a new d-amino acid racemase gene family and advances our knowledge of plant d-amino acid metabolism that is currently largely unexplored. It also demonstrates that exploitation of natural metabolic variation by integrating metabolomics with genome-wide association is a powerful approach for functional genomics study of specialized metabolism.Plants have the ability to create over 200,000 small compounds known as secondary or specialized metabolites (1). These chemically diverse compounds help mediate plant adaptation to their environment and play important roles in plant defense mechanisms, pigmentation, and development. In addition, many of these metabolites are desirable to humans as medicinal and nutritional compounds. Therefore, furthering our understanding of plant specialized metabolism will have profound impacts on various applications from crop improvement to human health.To date, only a small fraction of the chemical and catalytic space in plant specialized metabolism has been explored. Even in the best-studied model plant Arabidopsis thaliana, there are still many uncharacterized metabolites, and the vast majority of genes encoding enzymes implied to be involved in specialized metabolism do not have known associations with any metabolites. Several studies of Arabidopsis natural accessions (individuals collected from wild populations) revealed considerable qualitative and quantitative variation in the accumulation of various compounds such as glucosinolates, terpenoids, and phenylpropanoids (2–4). This extensive metabolite variation can be attributed to genetic variation in genes encoding enzymes and regulatory factors of the pathways involved; quantitative trait locus (QTL) mapping has successfully uncovered several genes involved in the production of these metabolites (3–7). Liquid chromatography–mass spectrometry (LC-MS)–based untargeted metabolic profiling has further extended such analysis to unknown metabolites, finding genetic contribution to the variation in at least three-fourths of detected mass peaks (8).Here we describe an integrated transdisciplinary platform, combining metabolomics, genetics, and genomics, to exploit the biochemical and genetic diversity of natural accessions of the model plant A. thaliana to uncover associations between genes and metabolites. Using this platform, we linked a differentially accumulating metabolite, identified through chemical analysis as N-malonyl-d-allo-isoleucine (NMD-Ile), to a previously uncharacterized gene identified as an amino acid racemase through reverse genetics and biochemical analysis.Amino acids exist in two forms; l-amino acids, the proteogenic form, and their enantiomorphs, d-amino acids. d-amino acids also play important structural and physiological roles in diverse life systems. In bacteria, d-amino acids confer cell-wall protease resistance and regulate cell-wall remodeling (9–11). d-amino acids were also found to be involved in signaling mechanisms in animal nervous systems and plant pollination (12, 13). Enzymes that catalyze the conversion of l-amino acids to d-amino acids are a class of isomerases known as amino acid racemases (14). Amino acid racemases are categorized into pyridoxal 5′ phosphate (PLP)-dependent and PLP-independent families. PLP-dependent racemases include AlaR, SerR, ArgR, and AspR and are found in both bacteria and eukaryotes, including mammals and plants. PLP-independent amino acid racemases include bacterial ProR, GluR, AspR, and diaminopimelate (DAP) epimerase. Except for DAP epimerase, which is required for the biosynthesis of Lys in bacteria and plants, ProR in Trypanosoma cruzi, the protozoan parasite responsible for Chagas disease, has been the only known eukaryotic PLP-independent racemase (15). The Arabidopsis amino acid racemase that we describe in this paper is a new member of the PLP-independent family, making its identification a significant addition to this class of enzymes.     

The effect of non‐thermal atmospheric pressure plasma application on wound healing after gingivectomy

Recent studies have indicated the potential benefits of Non‐thermal atmospheric pressure plasma (NTAPP) as a novel therapeutic approach. The purpose of the current study was thus to assess the effect of NTAPP on gingival wound healing. Fifteen patients with bilaterally symmetrical gingival hyperplasia were included in the study. After gingivectomy and gingivoplasty, the left‐hand side of the symmetrical surgical area was irradiated with NTAPP (plasma jet kINPen 11). Digital photographs of the gingival wounds were taken at baseline and days 3, 7, and 14. Wound epithelialisation was evaluated. Landry Wound Healing Index (WHI) scores and visual analogue scale (VAS) scores were also recorded. There were significant differences between the epithelialisation of the NTAPP‐treated sites and the control sites after the surgical procedures. The NTAPP‐treated sites had significantly smaller stained surface areas compared with the control sites on the 3rd, 7^th, and 14th days (P < .05). The NTAPP‐treated sites had better WHI scores than the control sites throughout the follow‐up period (P < .05). It can be concluded that NTAPP enhances epithelialisation and stimulates wound healing after gingivectomy and gingivoplasty. However, further clinical studies with larger sample sizes are needed to determine the exact benefits of NTAPP for gingival wound healing.     

Local Discrete Velocity Grids for Multi-Species Rarefied Flow Simulations

This article deals with the derivation of an adaptive numerical method for mono-dimensional kinetic equations for gas mixtures. For classical deterministic kinetic methods, the velocity domain is chosen accordingly to the initial condition. In such methods, this velocity domain is the same for all time, all space points and all species. The idea developed in this article relies on defining velocity domains that depend on space, time and species. This allows the method to locally adapt to the support of the distribution functions. The method consists in computing macroscopic quantities by the use of conservation laws, which enables the definition of such local grids. Then, an interpolation procedure along with a upwind scheme is performed in order to treat the advection term, and an implicit treatment of the BGK operator allows for the derivation of an AP scheme, where the stability condition is independent of the relaxation rate. The method is then applied to a series of test cases and compared to the classical DVM method.