Unbalanced Response Research Articles

Fluid-structure interaction analysis of annular seals and rotor systems in multi-stage pumps

Annular seals play an important role in determining the vibrational behavior of rotors in multi-stage pumps. To determine the critical speeds and unbalanced responses of rotor systems which consider annular seals, a fluid-structure interaction (FSI) method was developed, and the numerical method was verified by experiments conducted on a model rotor. In a typical FSI process, rotor systems are modeled based on a node-element method, and the motion equations are expressed in a type of matrix. To consider the influence of annular seals, dynamic coefficients of annular seals were introduced into the motion equations through matrix transformation. The test results of the model rotor showed good agreement with the calculated results. Based on the FSI method proposed here, the governing equations of annular seals were solved in two different ways. The results showed that the Childs method is more accurate in predicting a rotor’s critical speed. The critical speeds of the model rotor were calculated at different clearance sizes and length/diameter ratios. Tilting coefficients of long seals were added to the dynamic coefficients to consider the influence of tilting. The critical speeds reached their maximum value when the L/D ratio was around 1.25, and tilting enhanced the rotor’s stability when long annular seals were located in either end of the shaft.

Inflammatory disease and impaired antiviral immunity due to unbalanced NF-kB and IRF3 activation result from a de novo human NEMO mutation (P1415)

Abstract The RIG-I-like receptors mediate antiviral signaling through NEMO-dependent activation of transcription factors NF-kB and IRF3, which are recognized for their roles in inflammation and the induction of Type I Interferon, respectively. We identified an individual with increased susceptibility to viral infection and persistent inflammatory disease. Sanger sequencing revealed a de novo synonymous mutation in the gene encoding NEMO that results in an in-frame splicing event and exclusive production of a shortened protein. To understand the role of NEMO in regulating the antiviral response, we stimulated patient and healthy control fibroblasts with RIG-I-like receptor ligand poly(I:C), which mimics viral RNA. Induction of IRF3 response genes IFNB1 and CXCL10 was reduced 35-fold and 500-fold (n=2), respectively, compared to healthy control, and patient cells were unable to control viral infection. In contrast, TNF induced the expression of proinflammatory genes TNFSF10 and IL17 7-fold and 4-fold higher in patient cells than in healthy control cells. Increased TNF induced gene expression was accompanied by increased p65 nuclear translocation indicative of increased canonical IKK activation. These results suggest that aberrant expression of an alternately spliced NEMO isoform constitutes a novel autoinflammatory disease characterized by unbalanced NF-kB and IRF3 mediated responses to viral infection.

An AUC-based permutation variable importance measure for random forests

BackgroundThe random forest (RF) method is a commonly used tool for classification with high dimensional data as well as for ranking candidate predictors based on the so-called random forest variable importance measures (VIMs). However the classification performance of RF is known to be suboptimal in case of strongly unbalanced data, i.e. data where response class sizes differ considerably. Suggestions were made to obtain better classification performance based either on sampling procedures or on cost sensitivity analyses. However to our knowledge the performance of the VIMs has not yet been examined in the case of unbalanced response classes. In this paper we explore the performance of the permutation VIM for unbalanced data settings and introduce an alternative permutation VIM based on the area under the curve (AUC) that is expected to be more robust towards class imbalance.ResultsWe investigated the performance of the standard permutation VIM and of our novel AUC-based permutation VIM for different class imbalance levels using simulated data and real data. The results suggest that the new AUC-based permutation VIM outperforms the standard permutation VIM for unbalanced data settings while both permutation VIMs have equal performance for balanced data settings.ConclusionsThe standard permutation VIM loses its ability to discriminate between associated predictors and predictors not associated with the response for increasing class imbalance. It is outperformed by our new AUC-based permutation VIM for unbalanced data settings, while the performance of both VIMs is very similar in the case of balanced classes. The new AUC-based VIM is implemented in the R package party for the unbiased RF variant based on conditional inference trees. The codes implementing our study are available from the companion website: http://www.ibe.med.uni-muenchen.de/organisation/mitarbeiter/070_drittmittel/janitza/index.html.

Gut Microbiota as Potential Therapeutic Target for the Treatment of Cow’s Milk Allergy

Cow’s milk allergy (CMA) continues to be a growing health concern for infants living in Western countries. The long-term prognosis for the majority of affected infants is good, with about 80% naturally acquiring tolerance by the age of four years. However, recent studies suggest that the natural history of CMA is changing, with an increasing persistence until later ages. The pathogenesis of CMA, as well as oral tolerance, is complex and not completely known, although numerous studies implicate gut-associated immunity and enteric microflora, and it has been suggested that an altered composition of intestinal microflora results in an unbalanced local and systemic immune response to food allergens. In addition, there are qualitative and quantitative differences in the composition of gut microbiota between patients affected by CMA and healthy infants. These findings prompt the concept that specific beneficial bacteria from the human intestinal microflora, designated probiotics, could restore intestinal homeostasis and prevent or alleviate allergy, at least in part by interacting with the intestinal immune cells. The aim of this paper is to review what is currently known about the use of probiotics as dietary supplements in CMA.

The Roles of Asymmetric Inflow Forcing Induced by Outer Rainbands in Tropical Cyclone Secondary Eyewall Formation

Abstract This study analyzes the secondary eyewall formation (SEF) process in an idealized cloud-resolving simulation of a tropical cyclone. In particular, the unbalanced boundary layer response to asymmetric inflow forcing induced by outer rainbands (ORBs) is examined in order to understand the mechanisms driving the sustained convection outside the primary eyewall during the early phase of SEF. The enhancement of convection in the SEF region follows the formation and inward contraction of an ORB. The azimuthal distribution of the enhanced convection is highly asymmetric but regular, generally along a half circle starting from the downwind portion of the ORB. It turns out that the descending radial inflow in the middle and downwind portions of the ORB initiates/maintains a strong inflow in the boundary layer. The latter is able to penetrate into the inner-core region, sharpens the gradient of radial velocity, and reinforces convergence. Consequently, warm and moist air is continuously lifted up at the leading edge of the strong inflow to support deep convection. Moreover, the inflow from the ORB creates strong supergradient winds that are ejected outward downwind, thereby enhancing convergence and convection on the other side of the storm. The results provide new insight into the key processes responsible for convection enhancement during the early phase of SEF in three dimensions and suggest the limitations of axisymmetric studies. There are also implications regarding the impact of the asymmetric boundary layer flow under a translating storm on SEF.

비대칭적 신경근 훈련이 좌우 체간근 비대칭성에 미치는 영향

The purpose of this study was attempted to identify the changes in aymmetry of left/right trunk muscles during static and dynamic trunk stabilization. The subject of t his study were 16 adolescent women basketball players (training group: 8, control group: 8). The training gro up performed asymmetric neuromuscular training for 8 weeks, whereas the control group did not perform spec ific training. Electromyography was utilized to measure the asymmetrical muscular activities of left and right trunk muscles (rectus abdominis, external obliques, internal obliques, and erector spinae of lower back) during static and dynamic trunk stabilization. The measurement was performed before and after training period. Res ults of this study showed that the training changed the left and right trunk asymmetry in dynamic trunk stabilization (p.05). There wasno changes in the control group. This results indicate that the training can change the neuromuscular system, unilaterally. We expect that further study could demonstrate the decrease of the unbalanced muscular response between left and right trunk muscles, through the asymmetric neuromuscular training.

The Role of Mannose-Binding Lectin in Severe Sepsis and Septic Shock

Severe sepsis and septic shock are a primary cause of death in patients in intensive care unit (ICU). Investigations upon genetic susceptibility profile to systemic complications during severe infections are a field of increasing scientific interest. Particularly when adaptive immune system is compromised or immature, innate immunity plays a key role in the immediate defense against invasive pathogens. Mannose-binding lectin (MBL) is a serum protein that recognizes a wide range of pathogenic microorganisms and activates complement cascade via the antibody-independent pathway. More than 30% of humans harbor mutations in MBL gene (MBL2) resulting in reduced plasmatic levels and activity. Increased risk of infection acquisition has been largely documented in MBL-deficient patients, but the real impact of this form of innate immunosuppression upon clinical outcome is not clear. In critically ill patients higher incidence and worse prognosis of severe sepsis/septic shock appear to be associated with low-producers haplotypes. However an excess of MBL activation might be also harmful due to the possibility of an unbalanced proinflammatory response and an additional host injury. Strategies of replacement therapies in critically ill patients with severe infections are under investigation but still far to be applied in clinical practice.

Multi-objective optimisation of support characteristics of rotor bearing systems

Rotors today are made highly flexible with ever increasing demand for higher speeds, and it is important to predict the rotor dynamic behaviour accurately. Supports play an important role and influence the magnitude of vibration in response to external forces. In the present study, frequency dependent polymeric support characteristics have been found by using a multi objective optimisation scheme for minimising the unbalanced response and maximising the stability limit speed. This is an improvement over the previous papers where a simple equally weighted sum of two objective functions was used. A novel hybrid of particle swarm optimisation (PSO) and augmented Lagrangian has been used here to find the global minima. Using appropriate constraints, the slope of the support characteristics versus frequency is restricted to realistic values. Rotor systems with rolling element bearings and plain cylindrical journal bearings are studied using this approach and higher stability limits are obtained.

Polymorphisms in genes encoding nonsarcomeric proteins and their role in the pathogenesis of dilated cardiomyopathy

Dilated cardiomyopathy (DCM), clinically characterized by contractile dysfunction and ventricular chamber enlargement, is a heterogeneous heart disease leading to progressive systolic heart failure and sudden cardiac death. The etiology of the disease is multifactorial and involves genetic factors, viral infections, autoimmune phenomena, and toxic agents. Within the last two decades, a growing body of evidence has suggested that single-gene mutations play a pivotal role in the development of familial forms of dilated cardiomyopathies. Numerous genes encoding cytoskeletal, sarcomeric, and nuclear proteins have been linked to the pathogenesis of DCM, and most of the respective mutants disrupt the structural integrity of sarcomeres in cardiac myocytes. Frequently, point mutations in cytoskeletal proteins critically diminish force generation and interfere with mechanical transduction within the contractile apparatus of the myocardium, thereby ultimately leading to impaired systolic function. However, hitherto reported sarcomeric gene defects explain the etiology of the disease only in some families, leaving other forms of DCM subentities unresolved. Since one of the major factors in DCM pathogenesis involves autoimmune-mediated damage to cardiac tissue, candidate genes that are involved in controlling immune reactions have currently come into focus in genetic research. We and others have shown that a single-nucleotide polymorphism (SNP) in the gene encoding cytotoxic T-lymphocyte antigen 4 (CTLA4) is associated with the diagnosis of DCM. Cytotoxic T-lymphocyte antigen 4 is an inhibitory receptor molecule expressed on activated T lymphocytes, where it functions as an important negative regulator of T-cell activation by competing with the costimulatory CD28 receptor to bind to B7 receptors localized on the surface of antigen-presenting cells. The observed association between CTLA4 genotypes and DCM suggests that genetic factors contribute to both unbalanced immune responses in the myocardium and the development of left ventricular dysfunction. In this review, we will briefly discuss how these findings may stimulate the search for novel DCM-associated SNPs in human genes expressed in noncardiomyocytes.

Urea Amidolyase (DUR1,2) Contributes to Virulence and Kidney Pathogenesis of Candida albicans

The intracellular enzyme urea amidolyase (Dur1,2p) enables C. albicans to utilize urea as a sole nitrogen source. Because deletion of the DUR1,2 gene reduces survival of C. albicans co-cultured with a murine macrophage cell line, we investigated the role of Dur1,2p in pathogenesis using a mouse model of disseminated candidiasis. A dur1,2Δ/dur1,2Δ strain was significantly less virulent than the wild-type strain, showing significantly higher survival rate, better renal function, and decreased and less sustained fungal colonization in kidney and brain. Complementation of the mutant restored virulence. DUR1,2 deletion resulted in a milder host inflammatory reaction. Immunohistochemistry, flow cytometry, and magnetic resonance imaging showed decreased phagocytic infiltration into infected kidneys. Systemic cytokine levels of wild-type mice infected with the dur1,2 mutant showed a more balanced systemic pro-inflammatory cytokine response. Host gene expression and protein analysis in infected kidneys revealed parallel changes in the local immune response. Significant differences were observed in the kidney IL-1 inflammatory pathway, IL-15 signaling, MAP kinase signaling, and the alternative complement pathway. We conclude that Dur1,2p is important for kidney colonization during disseminated candidiasis and contributes to an unbalanced host inflammatory response and subsequent renal failure. Therefore, this Candida-specific enzyme may represent a useful drug target to protect the host from kidney damage associated with disseminated candidiasis.

THE ROLE OF BIOTECHNOLOGY IN DENGUE VIRAL INFECTION : Effort for The Development of A Dengue Vaccine

Introduction: Dengue fever and Dengue Haemorrhagic Fever (DF/DHF) are caused by dengue viruses (DENV). There are four antigenically related but distinct DENV serotypes (DENV-1 through DENV-4). Humans are the amplifying vertebrate host and Aedes mosquitos are the primarily mosquito vector as well as the reservoir of infection. DENV infection causes a spectrum of diseases, ranging from asymptomatic infections to infections complicated by haemorrhagic shock and death (Yoksan, 2008). Epidemiology: WHO (2008) estimates that about 2.5 billion people or 40% of the world’s population live in areas where there is a risk of dengue transmission. About 500,000 cases of dengue’s severest form (DHF/DSS) occur annually, resulting in about 24,000 deaths, mostly among children. Tropical and subtropical areas of South East Asia and Latin America are the hardest hit by dengue infection. Although dengue rarely occurs in the continental United States, it is endemic in Puerto Rico and Hawaii, a U.S. territory. Mosquitos capable of transmitting the virus have been found in the U.S. (in Florida, Georgia, Louisiana, Alabama, Mississippi, and Texas) over the last 10 years (Cano and Bannister, 2001; CDC, 2009; Science News, 2010). Facing this problem, vaccination is the answer. Vaccine Development: Dengue is an expanding public health problem, and an effective vaccine remains elusive. Significant influence of sequential infections with different dengue virus serotypes on the severity of disease can be viewed in terms of beneficial and detrimental effects of the heterologous immunity. A more complete understanding of these effects is likely to be critical for predicting optimal vaccine – induced immune responses, with the aim of protecting the global population from emerging infectious disease threats (Rothman, 2004). In 1980, Mahidol University committed to develop a live-attenuated tetravalent DENV vaccine. They were subjected to general safety test and monkey neurovirulence tests in accordance with the U.S. FDA requirements. (Yoksan 2008) Results: All vaccine recipients developed either a mild or no adverse reaction to the vaccine, the immunogenicity data were discussed. The current strategy of creating tetravalent DENV vaccine formulation can lead to an unbalanced immune response. This is attributed to viral interference that apparently comes into play when three monovirulent vaccine viruses DENV-1, DENV-2, DENV-4 are mixed with DENV-3 to create a tetravalent formulation (Yoksan, 2008). Summary: More research is needed on a priority basis to work out the viral interference factor in order to make the production of a tetravalent vaccine out of the attenuated DENV-3 candidate vaccine strain a success. Key words: Dengue Haemorrhagic Fever, Shock and death, tetravalent dengue vaccine, viral interference factor.

It’s not just bones anymore: The new and exciting world of vitamin D

The respiratory tract of human subjects is constantly exposed to harmful microbes and air pollutants. The immune system responds to these offenders to protect the host, but an unbalanced inflammatory response itself may promote tissue damage and ultimately lead to acute and chronic respiratory diseases. Deregulated inflammasome activation is emerging as a key modulator of respiratory infections and pathologic airway inflammation in patients with asthma, COPD, and pulmonary fibrosis. Assembly of these intracellular danger sensors in cells of the respiratory mucosa and alveolar compartment triggers a proinflammatory cell death mode termed pyroptosis and leads to secretion of bioactive IL-1β and IL-18. Here, we summarize and review the inflammasome and its downstream effectors as therapeutic targets for the treatment of respiratory diseases.

Analysis of Unbalanced Response for Coupled Double-Rotor Spindle System of High Speed Grinder

This study was focused on the theoretical modeling and numerical simulation about the unbalanced response for coupled double-rotor spindle system of high speed grinder. Based on the rotor dynamics, a theoretical model was established using the transfer matrix method. The moment balance equations, and the transition matrix, the state vector, field matrix of coupled double-rotor spindle system of high speed grinder were analyzed and calculated. The numerical results showed that the amplitude of unbalance response increased by the same multiple as that of the amount of unbalance at different locations and at different speeds. Furthermore, the position most sensitive to the unbalance was the front end of rotor 2, followed by the middle and back end of rotor 2. Rotor 2 was especially sensitive to unbalance. Moreover, the vibration amplitudes of the front end, front and back bearings of rotor 1 increased in response to unbalanced increase of rotate speed. The vibration amplitude abruptly increased at 17500r/min corresponding to first-order critical speed.

Non-whole beat correlation method for the identification of an unbalance response of a dual-rotor system with a slight rotating speed difference

The efficient identification of the unbalanced responses in the inner and outer rotors from the beat vibration is the key step in the dynamic balancing of a dual-rotor system with a slight rotating speed difference. This paper proposes a non-whole beat correlation method to identify the unbalance responses whose integral time is shorter than the whole beat correlation method. The principle, algorithm and parameter selection of the proposed method is emphatically demonstrated in this paper. From the numerical simulation and balancing experiment conducted on horizontal decanter centrifuge, conclusions can be drawn that the proposed approach is feasible and practicable. This method makes important sense in developing the field balancing equipment based on portable Single Chip Microcomputer (SCMC) with low expense.

The Potential Therapeutic Efficacy of Lactobacillus GG in Children with Food Allergies

Food allergy (FA) continues to be a growing health concern for infants living in Western countries. The long-term prognosis for the majority of affected infants is good, with 80–90% naturally acquiring tolerance by the age of five years. However, recent studies suggest that the natural history of FA is changing, with an increasing persistence until later ages. The pathogenesis of FA as well as oral tolerance is complex and not completely known, although numerous studies implicate gut-associated immunity and enteric microflora, and it has been suggested that an altered composition of intestinal microflora results in an unbalanced local and systemic immune response to food allergens. In addition, there are qualitative and quantitative differences in the composition of gut microbiota between patients affected by FA and healthy infants. These findings prompted the concept that specific beneficial bacteria from the human intestinal microflora, designated probiotics, could restore intestinal homeostasis and prevent or alleviate allergy, at least in part by interacting with the intestinal immune cells.

The Autophagy Regulator Rubicon Is a Feedback Inhibitor of CARD9-Mediated Host Innate Immunity

Assembly of a scaffold consisting of CARD9, BCL10, and MALT1 (CBM complex) is critical for effective signaling by multiple pattern recognition receptors (PRRs) including Dectin and RIG-I. The RUN domain Beclin-1-interacting cysteine-rich-containing Rubicon protein associates constitutively with the Beclin-UVRAG-Vps34 complex under normal conditions to regulate autophagy. Rubicon also interacts with the phagocytic NADPH-oxidase complex upon TLR stimulation to induce potent antimicrobial responses. Here, we show Rubicon is a physiological feedback inhibitor of CBM-mediated PRR signaling, preventing unbalanced proinflammatory responses. Upon Dectin-1- or RIG-I-mediated activation, Rubicon dynamically exchanges binding partners from 14-3-3β to CARD9 in a stimulation-specific and phosphorylation-dependent manner, disassembling the CBM signaling complex and ultimately terminating PRR-induced cytokine production. Remarkably, Rubicon's actions in the autophagy complex, phagocytosis complex, and CBM complex are functionally and genetically separable. Rubicon thus differentially targets signaling complexes, depending on environmental stimuli, and may function to coordinate various immune responses against microbial infection.

The Dynamic Analysis of SFD-Sliding Bearing Flexible Rotor System Based on Optimization Design

The paper establishes the mechanical model of SFD-sliding bearing flexible rotor system, adopting Runge-Kutta method to solve nonlinear differential equation, thus acquiring the unbalanced response curve and then gaining the first two critical speeds of the system. Meanwhile, the paper analyzes the sensitivity of the system on the first two critical speeds towards structural parameters, offering design variables to optimization analysis. Based on sensitivity analysis, genetic algorithm is employed to give an optimization analysis on critical speed, which aims to remove critical speed from working speed as much as possible. The critical speed ameliorates after the optimization which supplies theoretical basis as well as theoretical analysis towards the dynamic stability of high-speed rotor system and provides reference for the design of such rotor system.

New insights into hepatosplenic candidosis, a manifestation of chronic disseminated candidosis

Chronic disseminated candidosis, often referred to as hepatosplenic candidosis (HSC), is an infection due to Candida spp. that mainly involves the liver and spleen. HSC occurs mostly in patients after profound and prolonged neutropenia, which is more often seen in patients with acute haematological malignancies. The incidence of HSC ranges from 3% to 29% in patients suffering from Acute Leukaemia. However, it is now seen less frequently with the widespread use of antifungal agents as prophylaxis or as preemptive therapy. Early and adequate diagnosis and treatment of HSC are crucial, as treatment delays can negatively affect the prognosis of the underlying condition. The pathogenesis is not well understood, but it is believed that it may be due to an unbalanced adaptive immune response that leads to an exacerbated inflammatory reaction, resulting in an Immune Reconstitution Inflammatory Syndrome. In this context, new therapeutic approaches such as the use of adjuvant high-dose corticosteroids have been shown beneficial. This article will focus on the clinical, diagnostic and therapeutic aspects of HSC and provide an accurate review of recent pathophysiological data.

The Cholinergic System and Inflammation: Common Pathways in Delirium Pathophysiology

To investigate whether delirium is associated with an unbalanced inflammatory response or a dysfunctional interaction between the cholinergic and immune systems. Cohort observational study. General hospital orthopedic ward. One hundred one individuals aged 60 and older with no previous cognitive impairment undergoing elective arthroplasty. Incidence of postoperative delirium, plasma cholinesterase activity (acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)) and inflammatory mediators (C-reactive protein (CRP), interleukin (IL)-1 beta, tumor necrosis factor alpha, IL-6, IL-8, IL-10) before and after surgery. Thirty-seven participants developed postoperative delirium and had greater production of CRP and proinflammatory to anti-inflammatory ratio after surgery. In participants with delirium, but not in controls, preoperative levels of plasma cholinesterase activity correlated with ΔCRP (AChE: ρ = 0.428, P = .008 and BuChE: ρ = 0.423, P = .009), ΔIL-6 (AChE: ρ = 0.339, P = .04), and ΔP/A ratio (AChE: ρ = 0.346, P = .04). Delirium was associated not only with an unbalanced inflammatory response, but also with a dysfunctional interaction between the cholinergic and immune systems. Comprehensive understanding of the relationship between the cholinergic and immune systems is crucial to developing new insights into delirium pathophysiology and novel therapeutic interventions.

Concentric Eyewall Formation in Typhoon Sinlaku (2008). Part II: Axisymmetric Dynamical Processes

Abstract In Part I of this study, the association between the secondary eyewall formation (SEF) and the broadening of the outer swirling wind in Typhoon Sinlaku (2008) was documented. The findings from Part I help lay the groundwork for the application of a newly proposed intensification paradigm to SEF. Part II presents a new model for SEF that utilizes this new paradigm and its axisymmetric view of the dynamics. The findings point to a sequence of structure changes that occur in the vortex’s outer-core region, culminating in SEF. The sequence begins with a broadening of the tangential winds, followed by an increase of the corresponding boundary layer (BL) inflow and an enhancement of convergence in the BL where the secondary eyewall forms. The narrow region of strong BL convergence is associated with the generation of supergradient winds in and just above the BL that acts to rapidly decelerate inflow there. The progressive strengthening of BL inflow and the generation of an effective adverse radial force therein leads to an eruption of air from the BL to support convection outside the primary eyewall in a favorable thermodynamic/kinematic environment. The results suggest that the unbalanced response in the BL serves as an important mechanism for initiating and sustaining a ring of deep convection in a narrow supergradient wind zone outside the primary eyewall. This progressive BL control on SEF suggests that the BL scheme and its coupling to the interior flow need to be adequately represented in numerical models to improve the prediction of SEF timing and preferred location.