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关键词： Major depressive disorder   Schizophrenia   Bipolar disorder   Blood biomarker   Inflammation   GFAP  

摘要： Neuroinflammation has been connected to the pathophysiology of major depressive disorder (MDD) and neurochemical biomarkers of glial pathology could aid the diagnosis and might support patient stratification and monitoring in clinical trials. Our study aimed to determine the utility of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, for the differential diagnosis and monitoring of MDD. Employing Simoa technology we measured levels of GFAP in prospectively collected serum samples from 81 age-matched patients with MDD, schizophrenia (SZ), bipolar disorder (BP), and healthy controls (HC). Highest GFAP levels were determined for MDD. At a cut-off of 130 pg/ml, MDD could be discriminated with 87% sensitivity from SZ and BP (specificity 70%) and from HC (specificity 56%). GFAP levels increased with age (r = 0.5236, p = 0.0002) and with MDD severity quantified based on the Montgomery-angstrom sberg Depression Rating Scale (r = 0.4308, p = 0.0221). Neurofilament light chain serum levels were not different in the diagnostic groups and not associated with GFAP levels (r = 0.0911, p = 0.576) pointing to an independence of astrocyte activation on neurodegeneration. Our study provides first evidence that serum GFAP levels could improve the differential diagnosis of MDD and that depression severity could be objectively quantified using serum GFAP levels. Furthermore, serum GFAP might represent a marker to monitor astroglial pathology in the course of MDD.

关键词： Multiple sclerosis   Brain atrophy   Spinal cord atrophy   Disability worsening  

摘要： As atrophy represents the most relevant driver of progression in multiple sclerosis (MS), we investigated the impact of different patterns of brain and spinal cord atrophy on disability worsening in MS. We acquired clinical and MRI data from 90 patients with relapsing-remitting MS and 24 healthy controls (HC). Clinical progression at follow-up (mean 3.7 years) was defined according to the Expanded Disability Status Scale-Plus. Brain and spinal cord volumes were computed on MRI brain scans. After normalizing each participants' brain and spine volume to the mean of the HC, z-score cut-offs were applied to separate pathologically atrophic from normal brain and spine volumes (accepting a 2.5% error probability). Accordingly, MS patients were classified into four groups (Group I: no brain or spinal cord atrophy N = 40, Group II: brain atrophy/no spinal cord atrophy N = 11, Group III: no brain atrophy/ spinal cord atrophy N = 32, Group IV: both brain and spinal cord atrophy N = 7). All patients' groups showed significantly lower brain volume than HC (p < 0.0001). Group III and IV showed lower spine volume than HC (p < 0.0001 for both). Higher brain lesion load was identified in Group II (p = 0.049) and Group IV (p = 0.023) vs Group I, and in Group IV (p = 0.048) vs Group III. Spinal cord atrophy (OR = 3.75, p = 0.018) and brain + spinal cord atrophy (OR = 5.71, p = 0.046) were significant predictors of disability progression. The presence of concomitant brain and spinal cord atrophy is the strongest correlate of progression over time. Isolated spinal cord atrophy exerts a similar effect, confirming the leading role of spinal cord atrophy in the determination of motor disability.

关键词： differential equations   Fourier decomposition   neural networks  

摘要： We present a Fourier neural network (FNN) that can be mapped directly to the Fourier decomposition. The choice of activation and loss function yields results that replicate a Fourier series expansion closely while preserving a straightforward architecture with a single hidden layer. The simplicity of this network architecture facilitates the integration with any other higher-complexity networks, at a data pre- or postprocessing stage. We validate this FNN on naturally periodic smooth functions and on piecewise continuous periodic functions. We showcase the use of this FNN for modeling or solving partial differential equations with periodic boundary conditions. The main advantages of the current approach are the validity of the solution outside the training region, interpretability of the trained model, and simplicity of use.

关键词： Aerodynamic Coefficients   Yaw   Satellite Formation   Solution Algorithm   Atmospheric Environment   Earth   Model Predictive Control   Numerical Simulation   Attitude Dynamics   Aerodynamic Performance  

摘要： This paper investigates a formation control technique for low-Earth-orbit nanosatellites based on the differential aerodynamic drag and lift. An innovative method of using only the yaw angle deviation, instead of the three-axis attitude rotation, is proposed to simultaneously control the in-plane and out-of-plane relative motions. This method can be used for the formation control of the Earth-pointing satellite. A control scheme consisting of four steps is designed considering complex input constraints. In this scheme, two control inputs are defined based on the predicted atmospheric density, and the explicit expressions of their time-varying feasible regions are analyzed. To obtain the yaw angle of each nanosatellite, a yaw angle solution algorithm based on the grid interpolation method is designed with online solving nonlinear optimization avoided. A dynamic surface control algorithm based on the hyperbolic tangent function and a linear model predictive control algorithm are, respectively, used to limit two control inputs within their feasible regions. In addition, a nonlinear finite-time disturbance observer is used to track the total system disturbance. Numerical simulations are carried out for along-track and circular formations, in which the uncertainties of aerodynamic forces, the attitude dynamics, and the unknown perturbation are taken into account.

关键词： Ralstonia solanacearum   Pathogenesis-related genes   RT-PCR   Reactive oxygen species (ROS)   CLSM  

摘要： Phytopathogens induced pathogenesis-related (PR) proteins as well as defense-related signaling moleculesare imperative part of an innate immune system in plant especially for systemic acquired resistance. The present study was undertaken to find out the role of chemical elicitors on expression of pathogenicity related genes in susceptible and resistant cultivars of tomato (Solanum lycopersicum L) against bacterial wilt and alsoon reduction of disease incidence. Two chemical elicitors i.e. Salicylic acid (SA) and beta-amino butyric acid (BABA) were used in vitro, at 50, 100 and 150 mu M concentrations to observe their effect on the growth of Ralstonia solanacearum (Smith) (Yabuuchi et al.1995). The growth of R. solanacearum was significantly inhibited by BABA and SA at 50 mu M under in vitro conditions significantly. Furthermore, the relative differential expression of PR gene (PR1a, PR1b, PR2, and PR5 genes) transcripts were analyzed in both resistant (cv. Hawaii 7996) and susceptible (cv. Pusa Ruby) tomato cultivars when inoculated with R. solanacearum UTT-25 (RS)eitheralone or in combination with 50 mu M concentration of BABA and SA separately at 6, 24, 48 & 96 hpi using RT-PCR. The maximum 5.61 fold up-regulation of PR1a gene was observed with SA (50 mu M) + RS while 6.44 fold upregulation of PR1b gene was noticed with SA (50 mu M) alone at 48hpi in cv. Pusa Ruby. Whereas, resistant nature of cv. Hawaii7996 does not allow R. solanacearum UTT-25 to multiply, so it does not show any upregulation except with R. solanacearum alone at 96hpi of the treatment. The histochemical detection has also confirmed the minimal production of defence-related reactive oxygen species (ROS) in stems and leaves of cv. Pusa Ruby than cv. Hawaii7996 in the presence of chemical elicitors. The wilt incidences on both the cultivars at varied concentrations of the elicitors used were decreased or delayed as compared to control. In cv. Pusa Ruby with Beta-butyric acid (50 mu m) + R. solanace

关键词： Cartesian differential categories   Skew monoidal categories   Differential categories  

摘要： We exhibit the cartesian differential categories of Blute, Cockett and Seely as a particular kind of enriched category. The base for the enrichment is the category of commutative monoids-or in a straightforward generalisation, the category of modules over a commutative rig k. However, the tensor product on this category is not the usual one, but rather a warping of it by a certain monoidal comonad Q. Thus the enrichment base is not a monoidal category in the usual sense, but rather a skew monoidal category in the sense of Szlachanyi. Our first main result is that cartesian differential categories are the same as categories with finite products enriched over this skew monoidal base. The comonad Q involved is, in fact, an example of a differential modality. Differential modalities are a kind of comonad on a symmetric monoidal k-linear category with the characteristic feature that their co-Kleisli categories are cartesian differential categories. Using our first main result, we are able to prove our second one: that every small cartesian differential category admits a full, structure-preserving embedding into the cartesian differential category induced by a differential modality (in fact, a monoidal differential modality on a monoidal closed category-thus, a model of intuitionistic differential linear logic). This resolves an important open question in this area.

关键词： MYC   MYC mutants (T58A and T58I)   lymphoma   oncogene deregulation   cell cycle   ribosome biogenesis   DNA replication  

摘要： The MYC transcription factor regulates a vast number of genes and is implicated in many human malignancies. In some hematological malignancies, MYC is frequently subject to missense mutations that enhance its transformation activity. Here, we use a novel murine cell system to (i) characterize the transcriptional effects of progressively increasing MYC levels as normal primary B-cells transform to lymphoma cells and (ii) determine how this gene regulation program is modified by lymphoma-associated MYC mutations (T58A and T58I) that enhance its transformation activity. Unlike many previous studies, the cell system exploits primary B-cells that are transduced to allow regulated MYC expression under circumstances where apoptosis and senescence pathways are abrogated by the over-expression of the Bcl-xL and BMI1 proteins. In such cells, transition from a normal to a lymphoma phenotype is directly dependent on the MYC expression level, without a requirement for secondary events that are normally required during MYC-driven oncogenic transformation. A generalized linear model approach allowed an integrated analysis of RNA sequencing data to identify regulated genes in relation to both progressively increasing MYC level and wild type or mutant status. Using this design, a total of 7569 regulated genes were identified, of which the majority (n = 7263) were regulated in response to progressively increased levels of wild type MYC, while a smaller number of genes (n = 917) were differentially regulated, compared to wild type MYC, in T58A MYC- and/or T58I MYC-expressing cells. Unlike most genes that are similarly regulated by both wild type and mutant MYC genes, the set of 917 genes did not significantly overlap with known lipopolysaccharide regulated genes, which represent genes regulated by MYC in normal B cells. The genes that were differently regulated in cells expressing mutant MYC proteins were significantly enriched in DNA replication and G2 phase to mitosis transition gen

关键词： tear neutrophils   ocular stress   oxidative burst   reactive oxygen species   NADPH oxidase   intracellular pathway  

摘要： A large number of polymorphonuclear neutrophils (PMNs) invade the ocular surface during prolonged eye closure (sleep);these leukocytes are commonly referred as tear PMNs. PMNs contribute to homeostasis and possess an arsenal of inflammatory mediators to protect against pathogens and foreign materials. This study examined the ability of tear PMNs to generate reactive oxygen species (ROS), an essential killing mechanism for PMNs which can lead to oxidative stress and imbalance. Cells were collected after sleep from healthy participants using a gentle eye wash. ROS production in stimulated (phorbol-12-myristate-13-acetate (PMA), lipopolysaccharides (LPS) or N-Formylmethionyl-leucyl-phenylalanine (fMLP)) and unstimulated tear PMNs was measured using luminol-enhanced chemiluminescence for 60 min. A high level of constitutive/spontaneous ROS production was observed in tear PMNs in the absence of any stimulus. While tear PMNs were able to produce ROS in response to PMA, they failed to appropriately respond to LPS and fMLP, although fMLP-stimulated tear PMNs generated ROS extracellularly in the first three minutes. Higher ROS generation was observed in isolated tear PMNs which may be due to priming from the magnetic bead cell separation system. The differential responses of tear PMNs in ROS generation provide further evidence of their potential inflammatory roles in ocular complications involving oxidative stress.

摘要： Differential anti-proliferative and pro-apoptotic effects of aqueous extracts of green rooibos (Rg;Aspalathus linearis) and green tea (GT;Camellia sinensis) and an aspalathin-enriched extract of green rooibos (GRE), were investigated in primary rat hepatocytes (PH) and human liver (HepG2) and colon (HT-29) cancer cells. Rooibos flavonoids, aspalathin and luteolin, and the green tea flavanol, epigallocatechin gallate (EGCG), were included to assess their contribution relative to their extract concentrations. GRE was the most effective in reducing cell growth parameters which was associated with a high total polyphenol content and high ferric reducing potential. Differential cell responses were noticed with HepG2 cells more sensitive than PH toward the induction of apoptosis by GRE. Luteolin induced apoptosis in PH and HepG2 cells while aspalathin lacked any effect. EGCG induced apoptosis in HepG2 cells while PH were resistant. HT-29 cells were resistant to apoptosis induction by the tea and pure flavonoids. Differences existed in the individual effects of the major rooibos and GT flavonoids against cell growth parameters compared to their equivalent concentrations in the extract mixtures. Diversity of the flavonoid constituents, physicochemical properties and cellular redox status governing cell survival are likely to explain the differential cell responses.