Inferring gene regulatory networks from gene expression data by a dynamic Bayesian network-based model

Enabled by recent advances in bioinformatics, the inference of gene regulatory networks (GRNs) from gene expression data has garnered much interest from researchers. This is due to the need of researchers to understand the dynamic behavior and uncover the vast information lay hidden within the networks. In this regard, dynamic Bayesian network (DBN) is extensively used to infer GRNs due to its ability to handle time-series microarray data and modeling feedback loops. However, the efficiency of DBN in inferring GRNs is often hampered by missing values in expression data, and excessive computation time due to the large search space whereby DBN treats all genes as potential regulators for a target gene. In this paper, we proposed a DBN-based model with missing values imputation to improve inference efficiency, and potential regulators detection which aims to lessen computation time by limiting potential regulators based on expression changes. The performance of the proposed model is assessed by using time-series expression data of yeast cell cycle. The experimental results showed reduced computation time and improved efficiency in detecting gene-gene relationships

Inferring gene regulatory networks from gene expression data by a dynamic Bayesian network-based model

Enabled by recent advances in bioinformatics, the inference of gene regulatory networks (GRNs) from gene expression data has garnered much interest from researchers. This is due to the need of researchers to understand the dynamic behavior and uncover the vast information lay hidden within the networks. In this regard, dynamic Bayesian network (DBN) is extensively used to infer GRNs due to its ability to handle time-series microarray data and modeling feedback loops. However, the efficiency of DBN in inferring GRNs is often hampered by missing values in expression data, and excessive computation time due to the large search space whereby DBN treats all genes as potential regulators for a target gene. In this paper, we proposed a DBN-based model with missing values imputation to improve inference efficiency, and potential regulators detection which aims to lessen computation time by limiting potential regulators based on expression changes. The performance of the proposed model is assessed by using time-series expression data of yeast cell cycle. The experimental results showed reduced computation time and improved efficiency in detecting gene-gene relationships

Blade Loading Effects on Axial Turbine Tip Leakage Vortex Dynamics and Loss

umerical simulations have been carried out to define the loss generation mechanisms associated with tip leakage in un-shrouded axial turbines. Tip clearance vortex dynamics are a dominant feature of two mechanisms important in determining this loss: (i) decreased swirl velocity due to vortex line contraction in regions of decreasing axial velocity, i.e., adverse pressure gradient and (ii) vortex breakdown and reverse flow in the vortex core. The mixing losses behave differently from the conventional view of flow exiting a turbine tip clearance. More specifically, it is shown, through both control volume arguments and computations, that as a swirling leakage flow passes through a pressure rise, such as in the aft portion of the suction side of a turbine blade, the mixed-out loss can either decrease or increase. For turbines the latter typically occurs if the deceleration is large enough to initiate vortex breakdown, and it is demonstrated that this is the case in modern turbines. The effect of blade pressure distribution on clearance losses is illustrated through computational examination of two turbine blades, one with forward loading at the tip and one with aft loading. A 15% difference in leakage loss is found between the two, due to lower clearance vortex deceleration (lower core static pressure rise) with forward loading, and hence lower vortex breakdown loss. Additional computational experiments, carried out to define the effects of blade loading, incidence, and solidity, are found to be consistent with the proposed ideas linking blade pressure distribution, vortex breakdown and turbine tip leakage loss

Effects of non-axisymmetric tip clearance on axial compressor performance and stability

September 1997Statement of responsibility on title-page reads: M.B. Graf, T.S. Wong, E.M. Greitzer, F.E. Marble, C.S. Tan, H-W Shin, D.C. WislerIncludes bibliographical references (pages 34-35)The effects of circumferentially non-uniform tip clearance on axial compressor performance and stability have been investigated experimentally and analytically. A theoretical model for compressor behavior with non-axisymmetric tip clearance has been developed and used to design a series of first-of-a-kind experiments on a four-stage, low speed compressor. The experiments and computational results together show clearly the central physical features and controlling parameters of compressor response to non-axisymmetric tip clearance. It was found that the loss in stall margin was more severe than that estimated based on average clearance. The stall point was, in fact, closer to that obtained with uniform clearance at the maximum clearance level. The circumferential length scale of the tip clearance (and accompanying flow asymmetry) was an important factor in determining the stall margin reduction.For the same average clearance, the loss in peak pressure rise was 50% higher for an asymmetry with fundamental wavelength equal to the compressor circumference than with wavelength equal to one-half the circumference. The clearance asymmetry had much less of an effect on peak efficiency; the measured maximum efficiency decrease obtained was less than 0.4 percent compared to the 8% decrease in peak pressure rise due to the asymmetric clearance. The efficiency penalty due to non-axisymmetric tip clearance was thus close to that obtained with a uniform clearance at the circumferentially-averaged level. The theoretical model accurately captured the decreases in both steady-state pressure rise and stable operating range which are associated with clearance asymmetry.It also gave a good description of the observed trends of (i) increasing velocity asymmetry with decreasing compressor flow, and (ii) decreasing effect of clearance asymmetry with decreasing dominant wavelength of the clearance distribution. The time resolved data showed that the spatial structure of the pre-stall propagating disturbances in the compressor annulus was well represented and that the stability limiting process could be linked to the unsteady structure of these disturbance modes. The model was also utilized for parametric studies to define how compressor performance and stability is affected by the circumferential distribution of clearance, steady-state compressor pressure-rise characteristic, and system dynamic parameters. Sensitivity to clearance asymmetry was found to fall off strongly with the (asymmetry-related) reduced frequency and to increase with peak pressure rise and increasing curvature of the characteristic near the peak.Sponsored by the Air Force Office of Scientific Research, and the Air Force Aero Propulsion Technology (AFRAPT) Progra

Operator Algebra in Chern-Simons Theory on a Torus

We consider Chern-Simons gauge theory on a torus with both nonrelativistic and relativistic matter. It is shown that the Hamiltonian and two total momenta commute among themselves only in the physical Hilbert space. We also discuss relations among degenerate physical states, degenerate vacua, and the existence of multicomponent Schrodinger wavefunctions.Comment: 12 pages, TPI-Minn-92/41-T, UMN-TH-1105/9

Efficacy of spesolimab for the treatment of generalized pustular psoriasis flares across pre-specified patient subgroups in the Effisayil 1 study

Effisayil 1 was a multicentre, randomized, double‐blind, placebo‐controlled study of the anti‐interleukin (IL)‐36 receptor monoclonal antibody, spesolimab, in patients presenting with a generalized pustular psoriasis (GPP) flare. Previously published data from this study revealed that within 1 week, rapid pustular and skin clearance were observed in patients receiving spesolimab versus placebo. In this pre‐specified subgroup analysis, the efficacy of spesolimab was evaluated according to patient demographic and clinical characteristics at baseline in patients receiving spesolimab (n = 35) or placebo (n = 18) on Day 1. Efficacy was by assessed by achievement of primary endpoint (Generalized Pustular Psoriasis Physician Global Assessment [GPPGA] pustulation subscore of 0 at Week 1) and key secondary endpoint (GPPGA total score of 0 or 1 at Week 1). Safety was assessed at Week 1. Spesolimab was found to be efficacious and had a consistent and favourable safety profile in patients presenting with a GPP flare, regardless of patient demographics and clinical characteristics at baseline

Solitary osteochondroma of the twelfth rib with intraspinal extension and cord compression in a middle-aged patient

<p>Abstract</p> <p>Background</p> <p>Osteochondroma is a disease of growing bone and thus typically presents in younger patients. It has rarely been described in middle-aged and elderly patients. Data on the occurrence of osteochondroma show that the reported incidence of costal osteochondroma is very low. Moreover, costal osteochondroma arising at the costovertebral junction with neural foraminal extension and spinal cord compression is extremely rare.</p> <p>Case presentation</p> <p>This study reports the case of a 58-year-old patient with a solitary osteochondroma of the 12th rib with intraspinal extension and spinal cord compression. The clinical history, plain radiographs, computed tomography (CT), magnetic resonance imaging, and pathologic findings of the reported patient have been reviewed. The relevant medical literature has also been reviewed. The patient was treated with surgery for complete tumour excision to avoid tumour recurrence. After surgery, the patient's symptoms improved. An additional CT scan obtained at 1 year after surgery did not show any evidence of recurrence.</p> <p>Conclusions</p> <p>This patient is the oldest patient reported to have this rare form of costal osteochondroma. The age of the patient and the erosion of the adjacent bones raised clinical suspicion of malignancy; therefore, surgical management involved complete tumour excision with thoracolumbar fixation and fusion.</p

Epidemic and pandemic viral infections: impact on tuberculosis and the lung. A consensus by the World Association for Infectious Diseases and Immunological Disorders (WAidid), Global Tuberculosis Network (GTN) and members# of ESCMID Study Group for Mycobacterial Infections (ESGMYC).

Major epidemics including some that qualify as pandemics, such as Severe Acute Respiratory Syndrome (SARS), Middle-Eastern Respiratory Syndrome (MERS), Human Immunodeficiency Virus, pandemic H1N1/09 and most recently COVID-19 affect the lung. Tuberculosis (TB) remains the top infectious disease killer but apart from the TB-HIV syndemic, little is known regarding the interaction of viral epidemics and pandemics with TB. The aim of this consensus-based document is to describe the effects of the viral infections resulting in epidemics and pandemics that affect the lung (MERS, SARS, HIV, influenza A (H1N1)pdm/09 and COVID-19) and their interactions with TB. A search of the scientific literature was performed. A writing committee of international experts including the European Centre for Disease Prevention and Control Public Health Emergency (ECDC PHE) team, the World Association for Infectious Diseases and Immunological Disorders (WAidid), the Global Tuberculosis Network (GTN) and members of ESCMID Study Group for Mycobacterial Infections (ESGMYC) was established. Consensus was achieved after multiple rounds of revisions between the writing committee and a larger expert group. A Delphi process involving the core group of authors, excluding the ECDC PHE team identified the areas requiring review/consensus, followed by a second round to refine the definitive consensus elements. The epidemiology, immunology of these viral infections and their interactions with TB are discussed with implications on diagnosis, treatment and prevention of airborne infections (infection control, viral containment and workplace safety). This consensus document represents a rapid and comprehensive summary on what is known on the topic