A perfect storm: examining the synergistic effects of negative and positive emotional instability on promoting weight loss activities in anorexia nervosa

PubMed Central

Selby, Edward A.; Cornelius, Talea; Fehling, Kara B.; Kranzler, Amy; Panza, Emily A.; Lavender, Jason M.; Wonderlich, Stephen A.; Crosby, Ross D.; Engel, Scott G.; Mitchell, James E.; Crow, Scott J.; Peterson, Carol B.; Grange, Daniel Le

2015-01-01

Growing evidence indicates that both positive and negative emotion potentially influence the development and maintenance of anorexia nervosa, through both positive and negative reinforcement of weight loss activities. Such reactive emotional experience may be characterized by frequent and intense fluctuations in emotion, a construct known as “emotional instability.” The purpose of this study was to investigate the association between positive emotional instability and weight loss activities in anorexia nervosa, and to investigate the synergistic effects of positive and negative emotional instability on promoting weight loss activities. Using ecological momentary assessment methods, 118 participants with anorexia nervosa reported their emotional experiences and behaviors at least six times daily over 2 weeks using a portable digital device. Using generalized linear modeling, results indicated that high levels of both positive and negative emotional instability, and the interaction between the two, were associated with more frequent weight-loss activities, beyond anorexia subtype and mean levels of emotional intensity. These findings indicate that when women with anorexia exhibit both high levels of both positive and negative emotional instability they are more prone to a variety of weight loss activities. The importance of addressing the role of both positive and negative emotion in anorexia treatment is discussed. PMID:26379588

Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer.

PubMed

Pritchard, Colin C; Morrissey, Colm; Kumar, Akash; Zhang, Xiaotun; Smith, Christina; Coleman, Ilsa; Salipante, Stephen J; Milbank, Jennifer; Yu, Ming; Grady, William M; Tait, Jonathan F; Corey, Eva; Vessella, Robert L; Walsh, Tom; Shendure, Jay; Nelson, Peter S

2014-09-25

A hypermutated subtype of advanced prostate cancer was recently described, but prevalence and mechanisms have not been well-characterized. Here we find that 12% (7 of 60) of advanced prostate cancers are hypermutated, and that all hypermutated cancers have mismatch repair gene mutations and microsatellite instability (MSI). Mutations are frequently complex MSH2 or MSH6 structural rearrangements rather than MLH1 epigenetic silencing. Our findings identify parallels and differences in the mechanisms of hypermutation in prostate cancer compared with other MSI-associated cancers.

Analysis of Affective Instability in Ecological Momentary Assessment: Indices Using Successive Difference and Group Comparison via Multilevel Modeling

ERIC Educational Resources Information Center

Jahng, Seungmin; Wood, Phillip K.; Trull, Timothy J.

2008-01-01

Temporal instability of affect is a defining characteristic of psychological disorders such as borderline personality disorder (BPD) and mood cycling disorders. Ecological momentary assessment (EMA) enables researchers to directly assess such frequent and extreme fluctuations over time. The authors examined 4 operationalizations of such temporal…

Non-contrast MR imaging of the glenohumeral joint. Part II. Glenohumeral instability and labrum tears.

PubMed

Rafii, Mahvash

2004-11-01

MR imaging of the shoulder without contrast is frequently used for evaluation of glenohumeral instability in spite of the popularity of MR arthrography. With proper imaging technique, familiarity with normal anatomy and variants as well as knowledge of the expected pathologic findings high diagnostic accuracy may be achieved.

Targetable genetic features of primary testicular and primary central nervous system lymphomas

PubMed Central

Chapuy, Bjoern; Roemer, Margaretha G. M.; Stewart, Chip; Tan, Yuxiang; Abo, Ryan P.; Zhang, Liye; Dunford, Andrew J.; Meredith, David M.; Thorner, Aaron R.; Jordanova, Ekaterina S.; Liu, Gang; Feuerhake, Friedrich; Ducar, Matthew D.; Illerhaus, Gerald; Gusenleitner, Daniel; Linden, Erica A.; Sun, Heather H.; Homer, Heather; Aono, Miyuki; Pinkus, Geraldine S.; Ligon, Azra H.; Ligon, Keith L.; Ferry, Judith A.; Freeman, Gordon J.; van Hummelen, Paul; Golub, Todd R.; Getz, Gad; Rodig, Scott J.; de Jong, Daphne; Monti, Stefano

2016-01-01

Primary central nervous system lymphomas (PCNSLs) and primary testicular lymphomas (PTLs) are extranodal large B-cell lymphomas (LBCLs) with inferior responses to current empiric treatment regimens. To identify targetable genetic features of PCNSL and PTL, we characterized their recurrent somatic mutations, chromosomal rearrangements, copy number alterations (CNAs), and associated driver genes, and compared these comprehensive genetic signatures to those of diffuse LBCL and primary mediastinal large B-cell lymphoma (PMBL). These studies identify unique combinations of genetic alterations in discrete LBCL subtypes and subtype-selective bases for targeted therapy. PCNSLs and PTLs frequently exhibit genomic instability, and near-uniform, often biallelic, CDKN2A loss with rare TP53 mutations. PCNSLs and PTLs also use multiple genetic mechanisms to target key genes and pathways and exhibit near-uniform oncogenic Toll-like receptor signaling as a result of MYD88 mutation and/or NFKBIZ amplification, frequent concurrent B-cell receptor pathway activation, and deregulation of BCL6. Of great interest, PCNSLs and PTLs also have frequent 9p24.1/PD-L1/PD-L2 CNAs and additional translocations of these loci, structural bases of immune evasion that are shared with PMBL. PMID:26702065

Prediction of slug-to-annular flow pattern transition (STA) for reducing the risk of gas-lift instabilities and effective gas/liquid transport from low-pressure reservoirs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toma, P.R.; Vargas, E.; Kuru, E.

Flow-pattern instabilities have frequently been observed in both conventional gas-lifting and unloading operations of water and oil in low-pressure gas and coalbed reservoirs. This paper identifies the slug-to-annular flow-pattern transition (STA) during upward gas/liquid transportation as a potential cause of flow instability in these operations. It is recommended that the slug-flow pattern be used mainly to minimize the pressure drop and gas compression work associated with gas-lifting large volumes of oil and water. Conversely, the annular flow pattern should be used during the unloading operation to produce gas with relatively small amounts of water and condensate. New and efficient artificialmore » lifting strategies are required to transport the liquid out of the depleted gas or coalbed reservoir level to the surface. This paper presents held data and laboratory measurements supporting the hypothesis that STA significantly contributes to flow instabilities and should therefore be avoided in upward gas/liquid transportation operations. Laboratory high-speed measurements of flow-pressure components under a broad range of gas-injection rates including STA have also been included to illustrate the onset of large STA-related flow-pressure oscillations. The latter body of data provides important insights into gas deliquification mechanisms and identifies potential solutions for improved gas-lifting and unloading procedures. A comparison of laboratory data with existing STA models was performed first. Selected models were then numerically tested in field situations. Effective field strategies for avoiding STA occurrence in marginal and new (offshore) field applications (i.e.. through the use of a slug or annular flow pattern regimen from the bottomhole to wellhead levels) are discussed.« less

Development and Reliability Testing of the FEDS System for Classifying Glenohumeral Instability

PubMed Central

Kuhn, John E.; Helmer, Tara T.; Dunn, Warren R.; Throckmorton V, Thomas W.

2010-01-01

Background Classification systems for glenohumeral instability (GHI) are opinion based, not validated, and poorly defined. This study is designed to methodologically develop and test a GHI classification system. Methods: Classification System Development A systematic literature review identified 18 systems for classifying GHI. The frequency characteristics used was recorded. Additionally 31 members of the American Shoulder and Elbow Surgeons responded to a survey to identify features important to characterize GHI. Frequency, Etiology, Direction, and Severity (FEDS), were found to be most important. Frequency was defined as solitary (one episode), occasional (2–5x/year), or frequent (>5x/year). Etiology was defined as traumatic or atraumatic. Direction referred to the primary direction of instability (anterior, posterior, or inferior). Severity was defined as either subluxation or dislocation. Methods: Reliability Testing Fifty GHI patients completed a questionnaire at their initial visit. One of six sports medicine fellowship trained physicians completed a similar questionnaire after examining the patient. Patients returned after two weeks and were examined by the original physician and two other physicians. Inter- and intra-rater agreement for the FEDS classification system was calculated. Results Agreement between patients and physicians was lowest for frequency (39%; k=0.130) and highest for direction (82%; k=0.636). Physician intra-rater agreement was 84– 97% for the individual FEDS characteristics (k=0.69 to 0.87)). Physician inter-rater agreement ranged from 82–90% (k=0.44 to 0.76). Conclusions The FEDS system has content validity and is highly reliable for classifying GHI. Physical examination using provocative testing to determine the primary direction of instability produces very high levels of inter- and intra-rater agreement. Level of evidence Level II, Development of Diagnostic Criteria with Consecutive Series of Patients, Diagnosis Study. PMID:21277809

Detection of social group instability among captive rhesus macaques using joint network modeling

PubMed Central

Beisner, Brianne A.; Jin, Jian; Fushing, Hsieh; Mccowan, Brenda

2015-01-01

Social stability in group-living animals is an emergent property which arises from the interaction amongst multiple behavioral networks. However, pinpointing when a social group is at risk of collapse is difficult. We used a joint network modeling approach to examine the interdependencies between two behavioral networks, aggression and status signaling, from four stable and three unstable groups of rhesus macaques in order to identify characteristic patterns of network interdependence in stable groups that are readily distinguishable from unstable groups. Our results showed that the most prominent source of aggression-status network interdependence in stable social groups came from more frequent dyads than expected with opposite direction status-aggression (i.e. A threatens B and B signals acceptance of subordinate status). In contrast, unstable groups showed a decrease in opposite direction aggression-status dyads (but remained higher than expected) as well as more frequent than expected dyads with bidirectional aggression. These results demonstrate that not only was the stable joint relationship between aggression and status networks readily distinguishable from unstable time points, social instability manifested in at least two different ways. In sum, our joint modeling approach may prove useful in quantifying and monitoring the complex social dynamics of any wild or captive social system, as all social systems are composed of multiple interconnected networks PMID:26052339

ULF waves and plasma stability in different regions of the magnetosheath

NASA Astrophysics Data System (ADS)

Soucek, Jan; Escoubet, C. Philippe; Grison, Benjamin

2016-04-01

We present a statistical study of the occurrence and properties of ultra low frequency waves in the magnetosheath and interpret the results in terms of the competition of mirror and Alfvén-ion-cyclotron (AIC) instabilities. Both mirror and AIC waves are generated in high beta plasma of the magnetosheath when ion temperature anisotropy exceeds the threshold of the respective instabilities. These waves are frequently observed in the terrestrial and planetary magnetosheaths, but their distribution within the magnetosheath is inhomogeneous and their character varies as a function of location, local and upstream plasma parameters. We studied the spatial distribution of the two wave modes in the magnetosheath together with the local plasma parameters important for the stability of ULF waves. This analysis was performed on a dataset of all magnetosheath crossings observed by Cluster spacecraft over two years. For each observation we used bow shock, magnetopause and magnetosheath flow models to identify the relative position of the spacecraft with respect to magnetosheath boundaries and local properties of the upstream shock crossing. A strong dependence of parameters characterizing plasma stability and mirror/AIC wave occurrence on upstream ΘBn and MA is identified. The occurrence of mirror and AIC modes was compared against the respective instability thresholds and it was observed that AIC waves occurred nearly exclusively under mirror stable conditions. This is interpreted in terms of the different character of non-linear saturation of the two modes.

The structure of lifetime manic-hypomanic spectrum.

PubMed

Cassano, G B; Mula, M; Rucci, P; Miniati, M; Frank, E; Kupfer, D J; Oppo, A; Calugi, S; Maggi, L; Gibbons, R; Fagiolini, A

2009-01-01

The observation that bipolar disorders frequently go unrecognized has prompted the development of screening instruments designed to improve the identification of bipolarity in clinical and non-clinical samples. Starting from a lifetime approach, researchers of the Spectrum Project developed the Mood Spectrum Self-Report (MOODS-SR) that assesses threshold-level manifestations of unipolar and bipolar mood psychopathology, but also atypical symptoms, behavioral traits and temperamental features. The aim of the present study is to examine the structure of mania/hypomania using 68 items of the MOODS-SR that explore cognitive, mood and energy/activity features associated with mania/hypomania. A data pool of 617 patients with bipolar disorders, recruited at Pittsburgh and Pisa, Italy was used for this purpose. Classical exploratory factor analysis, based on a tetrachoric matrix, was carried out on the 68 items, followed by an Item Response Theory (IRT)-based factor analytic approach. Nine factors were initially identified, that include Psychomotor Activation, Creativity, Mixed Instability, Sociability/Extraversion, Spirituality/Mysticism/Psychoticism, Mixed Irritability, Inflated Self-esteem, Euphoria, Wastefulness/Recklessness, and account overall for 56.4% of the variance of items. In a subsequent IRT-based bi-factor analysis, only five of them (Psychomotor Activation, Mixed Instability, Spirituality/Mysticism/Psychoticism, Mixed Irritability, Euphoria) were retained. Our data confirm the central role of Psychomotor Activation in mania/hypomania and support the definitions of pure manic (Psychomotor Activation and Euphoria) and mixed manic (Mixed Instability and Mixed Irritability) components, bearing the opportunity to identify patients with specific profiles for a better clinical and neurobiological definition.

Health coverage instability for mothers in working families.

PubMed

Anderson, Steven G; Eamon, Mary Keegan

2004-07-01

Using data from the National Longitudinal Survey of Youth, the authors examined the health insurance coverage stability of 1,667 women in working families over a three-year period (1995-1997). Findings revealed that coverage instability is common. Nearly one-half of low-income women experienced health coverage instability over the three-year study period, and low-income women with poor education, single marital status, low work hours, and frequent job changes were at even greater risk of coverage instability. The findings also imply that women affected by recent welfare reforms are likely to experience widespread health coverage problems. The implications for health care policy development, social work administration, and social work practice are discussed.

Mood instability is a common feature of mental health disorders and is associated with poor clinical outcomes

PubMed Central

Lloyd, Theodore; Jackson, Richard; Ball, Michael; Shetty, Hitesh; Broadbent, Matthew; Geddes, John R; Stewart, Robert; McGuire, Philip; Taylor, Matthew

2015-01-01

Objectives Mood instability is a clinically important phenomenon but has received relatively little research attention. The objective of this study was to assess the impact of mood instability on clinical outcomes in a large sample of people receiving secondary mental healthcare. Design Observational study using an anonymised electronic health record case register. Setting South London and Maudsley NHS Trust (SLaM), a large provider of inpatient and community mental healthcare in the UK. Participants 27 704 adults presenting to SLaM between April 2006 and March 2013 with a psychotic, affective or personality disorder. Exposure The presence of mood instability within 1 month of presentation, identified using natural language processing (NLP). Main outcome measures The number of days spent in hospital, frequency of hospital admission, compulsory hospital admission and prescription of antipsychotics or non-antipsychotic mood stabilisers over a 5-year follow-up period. Results Mood instability was documented in 12.1% of people presenting to mental healthcare services. It was most frequently documented in people with bipolar disorder (22.6%), but was common in people with personality disorder (17.8%) and schizophrenia (15.5%). It was associated with a greater number of days spent in hospital (β coefficient 18.5, 95% CI 12.1 to 24.8), greater frequency of hospitalisation (incidence rate ratio 1.95, 1.75 to 2.17), greater likelihood of compulsory admission (OR 2.73, 2.34 to 3.19) and an increased likelihood of prescription of antipsychotics (2.03, 1.75 to 2.35) or non-antipsychotic mood stabilisers (2.07, 1.77 to 2.41). Conclusions Mood instability occurs in a wide range of mental disorders and is not limited to affective disorders. It is generally associated with relatively poor clinical outcomes. These findings suggest that clinicians should screen for mood instability across all common mental health disorders. The data also suggest that targeted interventions for mood instability may be useful in patients who do not have a formal affective disorder. PMID:25998036

Theo van Rens Prize. Arthroscopic assessment of the unstable shoulder.

PubMed

Hintermann, B; Gächter, A

1994-01-01

The purpose of this study was to evaluate prospectively the findings during shoulder arthroscopy in patients with recurrent anterior instability of the glenohumeral joint. One hundred and seventy-eight patients who fulfilled the criteria of having had at least one documented shoulder dislocation were included in the study. The pathological findings most frequently noted at arthroscopy were: anterior glenoid labral tears (85%), ventral capsule insufficiency (80%), Hill-Sachs compression fractures (67%), glenohumeral ligament insufficiency (55%), rotator cuff tears (20%), posterior glenoid labral tears (8%), and SLAP lesions (5%). Abnormalities were noted more frequently than expected, and there were significant differences between preoperative and postoperative diagnoses. Our study has taught us that a multiplicity of morphological changes are associated with instability of the glenohumeral joint, and that there is no single cause. The labrum and rim of the anterior inferior glenoid, for instance, showed typical abnormalities corresponding to different entities of anterior instability. In practice, this is very important, as the abnormalities visualized by imaging methods determine the surgical treatment.

GPR applications for geotechnical stability of transportation infrastructures

NASA Astrophysics Data System (ADS)

Benedetto, A.; Benedetto, F.; Tosti, F.

2012-09-01

Nowadays, severe meteorological events are always more frequent all over the world. This causes a strong impact on the environment such as numerous landslides, especially in rural areas. Rural roads are exposed to an increased risk for geotechnical instability. In the meantime, financial resources for maintenance are certainly decreased due to the international crisis and other different domestic factors. In this context, the best allocation of funds becomes a priority: efficiency and effectiveness of plans and actions are crucially requested. For this purpose, the correct localisation of geotechnically instable domains is strategic. In this paper, the use of Ground-Penetrating Radar (GPR) for geotechnical inspection of pavement and sub-pavement layers is proposed. A three-step protocol has been calibrated and validated to allocate efficiently and effectively the maintenance funds. In the first step, the instability is localised through an inspection at traffic speed using a 1-GHz GPR horn launched antenna. The productivity is generally about or over 300 Km/day. Data are processed offline by automatic procedures. In the second step, a GPR inspection restricted to the critical road sections is carried out using two coupled antennas. One antenna is used for top pavement inspection (1.6 GHz central frequency) and a second antenna (600 MHz central frequency) is used for sub-pavement structure diagnosis. Finally, GPR data are post-processed in the time and frequency domains to identify accurately the geometry of the instability. The case study shows the potentiality of this protocol applied to the rural roads exposed to a landslide.

Chromosome 3 allelic losses and microsatellite alterations in transitional cell carcinoma of the urinary bladder.

PubMed Central

Li, M.; Zhang, Z. F.; Reuter, V. E.; Cordon-Cardo, C.

1996-01-01

A deletion analysis of chromosome 3 was conducted in 72 cases of transitional cell carcinoma of the urinary bladder using seven microsatellites spanning the 3p arm and two additional microsatellites in 3q. Results showed that 19 of 72 (26.4%) cases had deletions in one or more 3p regions. Two regions of frequent deletion were identified: 3p12-14 and 3p21-23. Less frequent deletions at 3p24.2-25 were also observed. Deletions at 3p were weakly correlated with tumor grade, but strongly with pathological stage. Among 70 cases with histological grade available, 4 of 29 (13.8%) grade 1 and 2 tumors, and 15 of 41 (36.6%) grade 3 tumors showed allelic losses in one or more of the 3p regions studied (P = 0.055). Among 69 cases with pathological stage available, none of 27 superficial carcinomas (pTa, pTis, and pT1) showed 3p deletions, whereas 18 of 42 (42.9%) muscle invasive lesions (pT2, pT3, and pT4) displayed allelic losses at 3p (P < 0.001). In addition, 12 cases showed microsatellite instability, but there was no correlation between abnormalities and tumor grade or stage. No correlation was found between deletions at 3p21-23 and microsatellite instability. In conclusion, deletions at three discrete regions of 3p were identified in bladder carcinoma, suggesting the involvement of candidate tumor suppressor genes residing in these regions. Moreover, detection of allelic losses in these regions was associated with higher tumor grade and more advanced stage, suggesting their potential involvement in bladder tumor progression. Images Figure 1 Figure 3 PMID:8686747

[Colorectal oncogenesis].

PubMed

Laurent-Puig, P; Agostini, J; Maley, K

2010-11-01

Recent progress in the field of molecular biology has allowed us to identify at least two different molecular mechanisms implicated in colorectal carcinogenesis (CRC): chromosomal instability (CIN) and genetic instability. Even though the two molecular mechanisms differ, their signalling pathways, implicated in malignant transformation of colonic epithelial cells, appear to be similar. The most frequent group of CRC, which represents 80% of sporadic CRC, is characterized by allelic losses on the short arm of chromosome 17 and 8 and on the long arm of chromosome 5, 18 and 22. These allelic losses are associated with mutations in TP53, APC, SMAD2 and SMAD4 genes. All of these alterations are grouped under the phenotype CIN. A genetic instability termed MSI (microsatellite instability), which results from a mismatch repair (MMR) deficiency, appears in 12-15% of CRC cases. The presence of MMR deficiency leads to the accumulation of mutations in genes controlling cell cycle and apoptosis (TGFBRII, BAX or CASPASE5). More recently, the existence of a third phenotype was suggested. The main alteration associated with this group of tumors is the hypermethylation of the promoter region of numerous genes, leading to their inactivation. An activating mutation of BRAF is frequently associated with this phenotype. As described above, CRC shows genetic heterogeneity, however the consequences in terms of signalling pathway alterations are similar. For example, the activation of Wnt signalling pathways can result from the inactivation of the APC gene in the CIN phenotype or from an activating mutation in the β-catenin gene in MSI tumors. The inactivation of TGFβ pathways is also present in both tumor types and is driven by SMAD4, and more rarely by a SMAD2 inactivating mutation in CIN tumors, or by the existence of a frame-shift mutation occurring in a polyG coding track of the TGFβ (transforming growth factor) receptor type II in MSI tumors. The RAS-MAP kinase pathway is activated by KRAS mutations in CIN tumors or by BRAF mutations in MSI tumors. The p53 pathway is inactivated by TP53 inactivation in CIN tumors or by BAX inactivating mutations in MSI tumors.

Soft tissue-based surgical techniques for treatment of posterior shoulder instability.

PubMed

Castagna, Alessandro; Conti, Marco; Garofalo, Raffaele

2017-01-01

Posterior shoulder instability is a rare clinical condition that encompasses different degrees of severity including various possible pathologies involving the labrum, capsule, bony lesions, and even locked posterior dislocation. When focusing on soft tissue involvement, the diagnosis of posterior instability may be difficult to make because frequently patients report vague symptoms not associated with a clear history of traumatic shoulder dislocation. Pathological soft tissue conditions associated with posterior instability in most cases are related to posterior labral tear and/or posterior capsular detensioning/tear. The diagnosis can be facilitated by physical examination using specific clinical tests (i. e., jerk test, Kim test, and reinterpreted O'Brien test) together with appropriate imaging studies (i. e., magnetic resonance arthrography). Arthroscopy may help in a complete evaluation of the joint and allows for the treatment of soft tissue lesions in posterior instability. Caution is warranted in the case of concomitant posterior glenoid chondral defect as a potential cause of poor outcome after soft tissue repair in posterior instability.

Experimental Replication of an Aeroengine Combustion Instability

NASA Technical Reports Server (NTRS)

Cohen, J. M.; Hibshman, J. R.; Proscia, W.; Rosfjord, T. J.; Wake, B. E.; McVey, J. B.; Lovett, J.; Ondas, M.; DeLaat, J.; Breisacher, K.

2000-01-01

Combustion instabilities in gas turbine engines are most frequently encountered during the late phases of engine development, at which point they are difficult and expensive to fix. The ability to replicate an engine-traceable combustion instability in a laboratory-scale experiment offers the opportunity to economically diagnose the problem (to determine the root cause), and to investigate solutions to the problem, such as active control. The development and validation of active combustion instability control requires that the causal dynamic processes be reproduced in experimental test facilities which can be used as a test bed for control system evaluation. This paper discusses the process through which a laboratory-scale experiment was designed to replicate an instability observed in a developmental engine. The scaling process used physically-based analyses to preserve the relevant geometric, acoustic and thermo-fluid features. The process increases the probability that results achieved in the single-nozzle experiment will be scalable to the engine.

Modulation Instability and Phase-Shifted Fermi-Pasta-Ulam Recurrence

PubMed Central

Kimmoun, O.; Hsu, H. C.; Branger, H.; Li, M. S.; Chen, Y. Y.; Kharif, C.; Onorato, M.; Kelleher, E. J. R.; Kibler, B.; Akhmediev, N.; Chabchoub, A.

2016-01-01

Instabilities are common phenomena frequently observed in nature, sometimes leading to unexpected catastrophes and disasters in seemingly normal conditions. One prominent form of instability in a distributed system is its response to a harmonic modulation. Such instability has special names in various branches of physics and is generally known as modulation instability (MI). The MI leads to a growth-decay cycle of unstable waves and is therefore related to Fermi-Pasta-Ulam (FPU) recurrence since breather solutions of the nonlinear Schrödinger equation (NLSE) are known to accurately describe growth and decay of modulationally unstable waves in conservative systems. Here, we report theoretical, numerical and experimental evidence of the effect of dissipation on FPU cycles in a super wave tank, namely their shift in a determined order. In showing that ideal NLSE breather solutions can describe such dissipative nonlinear dynamics, our results may impact the interpretation of a wide range of new physics scenarios. PMID:27436005

Early Life Psychosocial Stressors and Housing Instability among Young Sexual Minority Men: the P18 Cohort Study.

PubMed

Krause, Kristen D; Kapadia, Farzana; Ompad, Danielle C; D'Avanzo, Paul A; Duncan, Dustin T; Halkitis, Perry N

2016-06-01

Homelessness and housing instability is a significant public health problem among young sexual minority men. While there is a growing body of literature on correlates of homelessness among sexual minority men, there is a lack of literature parsing the different facets of housing instability. The present study examines factors associated with both living and sleeping in unstable housing among n = 600 sexual minority men (ages 18-19). Multivariate models were constructed to examine the extent to which sociodemographic, interpersonal, and behavioral factors as well as adverse childhood experiences explain housing instability. Overall, 13 % of participants reported sleeping in unstable housing and 18 % had lived in unstable housing at some point in the 6 months preceding the assessment. The odds of currently sleeping in unstable housing were greater among those who experienced more frequent lack of basic needs (food, proper hygiene, clothing) during their childhoods. More frequent experiences of childhood physical abuse and a history of arrest were associated with currently living in unstable housing. Current enrollment in school was a protective factor with both living and sleeping in unstable housing. These findings indicate that being unstably housed can be rooted in early life experiences and suggest a point of intervention that may prevent unstable housing among sexual minority men.

Bullying involvement and adolescent substance use: A multilevel investigation of individual and neighbourhood risk factors.

PubMed

Lambe, Laura J; Craig, Wendy M

2017-09-01

Youth involved with school bullying are vulnerable to many negative outcomes, including substance use. Research has yet to examine how this vulnerability operates in the context of other individual and neighbourhood differences. The current study aimed to fill this gap by using multilevel modeling to investigate both the individual and neighbourhood risk factors associated with frequent drunkenness and frequent cannabis use among adolescents. Data from the 2010 Canadian Health Behaviours in School-Aged Children (HBSC) survey were analyzed. Participants consisted of 8971 students from 173 neighbourhoods across Canada. Multilevel modeling was used to examine both individual (age, gender, bullying, victimization, peer deviancy, negative affect) and neighbourhood (socioeconomic status, crime, physical neighbourhood disorder, residential instability) risk factors. We tested whether the links between bullying involvement and frequent substance use were mediated by other risk factors. Both individual and neighbourhood risk factors were associated with an increased likelihood of frequent substance use. Specifically, bullying served as a unique risk factor for frequent substance use over and above more traditional risk factors. A cross-level interaction was observed between residential instability and peer deviancy, such that the link between peer deviancy and frequent drunkenness was stronger in more residentially-unstable neighbourhoods. Peer deviancy partially mediated the link between bullying and both types of frequent substance use, whereas both peer deviancy and negative affect mediated the link between victimization and both types of frequent substance use. Youth who bully others are vulnerable to frequent substance use across peer and neighbourhood contexts. Copyright © 2017 Elsevier B.V. All rights reserved.

Mood instability and impulsivity as trait predictors of suicidal thoughts.

PubMed

Peters, Evyn M; Balbuena, Lloyd; Marwaha, Steven; Baetz, Marilyn; Bowen, Rudy

2016-12-01

Impulsivity, the tendency to act quickly without adequate planning or concern for consequences, is a commonly cited risk factor for suicidal thoughts and behaviour. There are many definitions of impulsivity and how it relates to suicidality is not well understood. Mood instability, which describes frequent fluctuations of mood over time, is a concept related to impulsivity that may help explain this relationship. The purpose of this study was to determine whether impulsivity could predict suicidal thoughts after controlling for mood instability. This study utilized longitudinal data from the 2000 Adult Psychiatric Morbidity Survey (N = 2,406). There was a time interval of 18 months between the two waves of the study. Trait impulsivity and mood instability were measured with the Structured Clinical Interview for DSM-IV Axis II Personality Disorders. Logistic regression analyses were used to evaluate baseline impulsivity and mood instability as predictors of future suicidal thoughts. Impulsivity significantly predicted the presence of suicidal thoughts, but this effect became non-significant with mood instability included in the same model. Impulsivity may be a redundant concept when predicting future suicidal thoughts if mood instability is considered. The significance is that research and therapy focusing on mood instability along with impulsivity may be useful in treating the suicidal patient. Mood instability and impulsivity both predict future suicidal thoughts. Impulsivity does not predict suicidal thoughts after controlling for mood instability. Assessing and treating mood instability could be important aspects of suicide prevention and risk management. © 2015 The British Psychological Society.

Treatment of chronic scapholunate dissociation with tenodesis: A systematic review.

PubMed

Athlani, L; Pauchard, N; Detammaecker, R; Huguet, S; Lombard, J; Dap, F; Dautel, G

2018-04-01

Scapholunate (SL) instability is the most common dissociative carpal instability condition. It is the most frequent cause of wrist osteoarthritis, defined as scapholunate advanced collapse or SLAC wrist. Familiarity with the SL ligament complex is required to understand the various features of SL instability. Damage to the SL interosseous ligament is the main prerequisite for SL instability; however the extrinsic, palmar and dorsal ligaments of the carpus also come into play. When more than 6 weeks has passed since the initial injury event, SL instability is considered chronic because ligament healing is no longer possible. Before osteoarthritis sets in and when the SL instability is still reducible (scaphoid can be reverticalized), ligament reconstruction surgery is indicated. Since the end of the 1970s, various ligament reconstruction or tenodesis techniques have been described. These techniques are used in cases of chronic, dynamic or static reducible SL instability, when no repairable ligament stump and no chondral lesions are present. The aim is to correct the SL instability using a free or pedicled tendon graft to reduce pain while limiting the loss of mobility and protecting against osteoarthritis-related collapse in the long-term. We will perform a systematic review of the various tenodesis techniques available in the literature. Copyright © 2017 SFCM. Published by Elsevier Masson SAS. All rights reserved.

The crack effect on instability in a machine tool spindle with gas bearings

NASA Astrophysics Data System (ADS)

Huang, Bo-Wun

2005-09-01

Gas-bearing spindles are required for increased spindle speed in precise machining. Due to manufacturing flaws or cyclic loading, cracks frequently appear in a rotating spindle systems. Cracks markedly affect the dynamic characteristics of rotating machinery. Hence, in this study, high-speed spindles with gas bearings and the crack effect on the instability dynamics are considered. Most investigations on dynamic characteristics of the spindle system were confined to ball-bearing-type spindles. This work examines the dynamic instability in a cracked rotating spindle system with gas bearings. A round Euler-Bernoulli beam is used to approximate the spindle. The Hamilton principle is applied to derive the equation of motion for the spindle system. The effects of crack depth, rotation speed and provided air pressure on the dynamic instability of a rotating spindle system are studied

Claims-based proxies of patient instability among commercially insured adults with schizophrenia

PubMed Central

Ruetsch, Charles; Un, Hyong; Waters, Heidi C

2018-01-01

Objective Schizophrenia (Sz) patients are among the highest utilizers of hospital-based services. Prevention of relapse is in part a treatment goal in order to reduce hospital admissions. However, predicting relapse is a challenge, particularly for payers and disease management firms with only access to claims data. Understandably, such organizations have had little success predicting relapse. A tool that allows payers to identify patients at elevated risk of relapse could facilitate targeted interventions prior to relapse and avoid rehospitalization. In this study, a series of proxy measures of patient instability, calculated from claims data were examined for their utility in identifying Sz patients at elevated risk of relapse. Methods Aetna claims were used to assess the relationship between instability of Sz patients and valence and magnitude of antipsychotic (AP) medication change during a 2-year period. Six proxies of instability including hospital admissions, emergency department visits, medication utilization patterns, and use of outpatient services were identified. Results were replicated using claims data from Truven MarketScan®. Results Patients who switched AP ingredient had the highest overall instability at the point of switch and the second steepest decline in instability following switch. Those who changed to a long-acting injectable AP showed the second highest level of instability and the steepest decrease in instability following the change. Patients augmented with a second AP showed the smallest increase in instability, up to the switch. Results were directionally consistent between the two data sets. Conclusion Using claims-based proxy measures to estimate instability may provide a viable method to better understand Sz patient markers of change in disease severity. Also, such proxies could be used to identify those individuals with the greatest need for treatment modification preventing relapse, improving patient outcomes, and reducing the burden of illness. PMID:29765242

Genomic instability in cancer: Teetering on the limit of tolerance

PubMed Central

Andor, Noemi; Maley, Carlo C.; Ji, Hanlee P.

2017-01-01

Cancer genomic instability contributes to the phenomenon of intratumoral genetic heterogeneity, provides the genetic diversity required for natural selection and enables the extensive phenotypic diversity that is frequently observed among patients. Genomic instability has previously been associated with poor prognosis. However, we have evidence that for solid tumors of epithelial origin, extreme levels of genomic instability, where more than 75% of the genome is subject to somatic copy number alterations, are associated with a potentially better prognosis compared to intermediate levels under this threshold. This has been observed in clonal subpopulations of larger size, especially when genomic instability is shared among a limited number of clones. We hypothesize that cancers with extreme levels of genomic instability may be teetering on the brink of a threshold where so much of their genome is adversely altered that cells rarely replicate successfully. Another possibility is that tumors with high levels of genomic instability are more immunogenic than other cancers with a less extensive burden of genetic aberrations. Regardless of the exact mechanism, but hinging on our ability to quantify how a tumor’s burden of genetic aberrations is distributed among coexisting clones – genomic instability has important therapeutic implications. Herein, we explore the possibility that a high genomic instability could be the basis for a tumor’s sensitivity to DNA damaging therapies. We primarily focus on studies of epithelial-derived solid tumors. PMID:28432052

Evaluation and Management of Failed Shoulder Instability Surgery.

PubMed

Cartucho, António; Moura, Nuno; Sarmento, Marco

2017-01-01

Failed shoulder instability surgery is mostly considered to be the recurrence of shoulder dislocation but subluxation, painful or non-reliable shoulder are also reasons for patient dissatisfaction and should be considered in the notion. The authors performed a revision of the literature and online contents on evaluation and management of failed shoulder instability surgery. When we look at the reasons for failure of shoulder instability surgery we point the finger at poor patient selection, technical error and an additional traumatic event. More than 80% of surgical failures, for shoulder instability, are associated with bone loss. Quantification of glenoid bone loss and investigation of an engaging Hill-Sachs lesion are determining facts. Adequate imaging studies are determinant to assess labrum and capsular lesions and to rule out associated pathology as rotator cuff tears. CT-scan is the method of choice to diagnose and quantify bone loss. Arthroscopic soft tissue procedures are indicated in patients with minimal bone loss and no contact sports. Open soft tissue procedures should be performed in patients with small bone defects, with hiperlaxity and practicing contact sports. Soft tissue techniques, as postero-inferior capsular plication and remplissage, may be used in patients with less than 25% of glenoid bone loss and Hill-Sachs lesions. Bone block procedures should be used for glenoid larger bone defects in the presence of an engaging Hill-Sachs lesion or in the presence of poor soft tissue quality. A tricortical iliac crest graft may be used as a primary procedure or as a salvage procedure after failure of a Bristow or a Latarjet procedure. Less frequently, the surgeon has to address the Hill-Sachs lesion. When a 30% loss of humeral head circumference is present a filling graft should be used. Reasons for failure are multifactorial. In order to address this entity, surgeons must correctly identify the causes and tailor the right solution.

Resonant Drag Instabilities in protoplanetary disks: the streaming instability and new, faster-growing instabilities

NASA Astrophysics Data System (ADS)

Squire, Jonathan; Hopkins, Philip F.

2018-04-01

We identify and study a number of new, rapidly growing instabilities of dust grains in protoplanetary disks, which may be important for planetesimal formation. The study is based on the recognition that dust-gas mixtures are generically unstable to a Resonant Drag Instability (RDI), whenever the gas, absent dust, supports undamped linear modes. We show that the "streaming instability" is an RDI associated with epicyclic oscillations; this provides simple interpretations for its mechanisms and accurate analytic expressions for its growth rates and fastest-growing wavelengths. We extend this analysis to more general dust streaming motions and other waves, including buoyancy and magnetohydrodynamic oscillations, finding various new instabilities. Most importantly, we identify the disk "settling instability," which occurs as dust settles vertically into the midplane of a rotating disk. For small grains, this instability grows many orders of magnitude faster than the standard streaming instability, with a growth rate that is independent of grain size. Growth timescales for realistic dust-to-gas ratios are comparable to the disk orbital period, and the characteristic wavelengths are more than an order of magnitude larger than the streaming instability (allowing the instability to concentrate larger masses). This suggests that in the process of settling, dust will band into rings then filaments or clumps, potentially seeding dust traps, high-metallicity regions that in turn seed the streaming instability, or even overdensities that coagulate or directly collapse to planetesimals.

Glenohumeral instability: evaluation with MR arthrography.

PubMed

Beltran, J; Rosenberg, Z S; Chandnani, V P; Cuomo, F; Beltran, S; Rokito, A

1997-01-01

Magnetic resonance arthrography is superior to other imaging techniques in evaluation of the glenohumeral joint. Normal variants that can be diagnostic pitfalls include the anterosuperior sublabral foramen, the Buford complex, and hyaline cartilage under the labrum. Anteroinferior dislocation is the most frequent cause of anterior glenohumeral instability and produces a constellation of lesions (anteroinferior labral tear, classic and osseous Bankart lesions, Hill-Sachs lesion). Variants of anteroinferior labral tears include anterior labroligamentous periosteal sleeve avulsion and glenoid labral articular disruption. Anterior glenohumeral instability can also involve tears of the anterior or anterosuperior labrum or the glenohumeral ligaments. Posterior glenohumeral instability can involve a posterior labral tear, posterior capsular stripping or laxity; fracture, erosion, or sclerosis and ectopic ossification of the posterior glenoid fossa; reverse Hill-Sachs lesion; McLaughlin fracture; or posterosuperior glenoid impingement. Superior labral anterior and posterior lesions involve the superior labrum with varying degrees of biceps tendon involvement.

Simulation of magnetic holes formation in the magnetosheath

NASA Astrophysics Data System (ADS)

Ahmadi, Narges; Germaschewski, Kai; Raeder, Joachim

2017-12-01

Magnetic holes have been frequently observed in the Earth's magnetosheath and are believed to be the consequence of the nonlinear evolution of the mirror instability. Mirror mode perturbations mainly form as magnetic holes in regions where the plasma is marginally mirror stable with respect to the linear instability criterion. We present an expanding box particle-in-cell simulation to mimic the changing conditions in the magnetosheath as the plasma is convected through it that produces mirror mode magnetic holes. We show that in the initial nonlinear evolution, where the plasma conditions are mirror unstable, the magnetic peaks are dominant, while later, as the plasma relaxes toward marginal stability, the fluctuations evolve into deep magnetic holes. While the averaged plasma parameters in the simulation remain close to the mirror instability threshold, the local plasma in the magnetic holes is highly unstable to mirror instability and locally mirror stable in the magnetic peaks.

Prevalence of chronic ankle instability in high school and division I athletes.

PubMed

Tanen, Leah; Docherty, Carrie L; Van Der Pol, Barbara; Simon, Janet; Schrader, John

2014-02-01

The purpose of this study was to determine the prevalence of chronic ankle instability among high school and collegiate athletes. Descriptive epidemiological survey. Athletes from four high schools and a division I university were contacted to participate. For collegiate athletes, a questionnaire packet was distributed during preparticipation physicals. For high school athletes, parental consent was obtained and then questionnaires were distributed during preparticipation physicals, parent meetings, or individual team meetings. All athletes completed the Cumberland Ankle Instability Tool for both their left and right ankles. Subjects also provided general demographic data and completed the Ankle Instability Instrument regarding history of lateral ankle sprains and giving way. Athletes were identified as having chronic ankle instability if they scored less than 24 on the Cumberland Ankle Instability Tool. Of the 512 athletes who completed and returned surveys, 23.4% were identified as having chronic ankle instability. High school athletes were more likely to have chronic ankle instability than their collegiate counterparts (P < .001). Chronic ankle instability was more prevalent among women than among men in both high school (P = .01) and collegiate settings (P = .01). Findings of this study revealed differences in the distribution of chronic ankle instability that warrant further study.

When can efforts to control nuisance and invasive species backfire?

USGS Publications Warehouse

Zipkin, E.F.; Kraft, C.E.; Cooch, E.G.; Sullivan, P.J.

2009-01-01

Population control through harvest has the potential to reduce the abundance of nuisance and invasive species. However, demographic structure and density-dependent processes can confound removal efforts and lead to undesirable consequences, such as overcompensation (an increase in abundance in response to harvest) and instability (population cycling or chaos). Recent empirical studies have demonstrated the potential for increased mortality (such as that caused by harvest) to lead to overcompensation and instability in plant, insect, and fish populations. We developed a general population model with juvenile and adult stages to help determine the conditions under which control harvest efforts can produce unintended outcomes. Analytical and simulation analyses of the model demonstrated that the potential for overcompensation as a result of harvest was significant for species with high fecundity, even when annual stage-specific survivorship values were fairly low. Population instability as a result of harvest occurred less frequently and was only possible with harvest strategies that targeted adults when both fecundity and adult survivorship were high. We considered these results in conjunction with current literature on nuisance and invasive species to propose general guidelines for assessing the risks associated with control harvest based on life history characteristics of target populations. Our results suggest that species with high per capita fecundity (over discrete breeding periods), short juvenile stages, and fairly constant survivorship rates are most likely to respond undesirably to harvest. It is difficult to determine the extent to which overcompensation and instability could occur during real-world removal efforts, and more empirical removal studies should be undertaken to evaluate population-level responses to control harvests. Nevertheless, our results identify key issues that have been seldom acknowledged and are potentially generic across taxa. ?? 2009 by the Ecological Society ot America.

When can efforts to control nuisance and invasive species backfire?

PubMed

Zipkin, Elise F; Kraft, Clifford E; Cooch, Evan G; Sullivan, Patrick J

2009-09-01

Population control through harvest has the potential to reduce the abundance of nuisance and invasive species. However, demographic structure and density-dependent processes can confound removal efforts and lead to undesirable consequences, such as overcompensation (an increase in abundance in response to harvest) and instability (population cycling or chaos). Recent empirical studies have demonstrated the potential for increased mortality (such as that caused by harvest) to lead to overcompensation and instability in plant, insect, and fish populations. We developed a general population model with juvenile and adult stages to help determine the conditions under which control harvest efforts can produce unintended outcomes. Analytical and simulation analyses of the model demonstrated that the potential for overcompensation as a result of harvest was significant for species with high fecundity, even when annual stage-specific survivorship values were fairly low. Population instability as a result of harvest occurred less frequently and was only possible with harvest strategies that targeted adults when both fecundity and adult survivorship were high. We considered these results in conjunction with current literature on nuisance and invasive species to propose general guidelines for assessing the risks associated with control harvest based on life history characteristics of target populations. Our results suggest that species with high per capita fecundity (over discrete breeding periods), short juvenile stages, and fairly constant survivorship rates are most likely to respond undesirably to harvest. It is difficult to determine the extent to which overcompensation and instability could occur during real-world removal efforts, and more empirical removal studies should be undertaken to evaluate population-level responses to control harvests. Nevertheless, our results identify key issues that have been seldom acknowledged and are potentially generic across taxa.

Simultaneous use of camera and probe diagnostics to unambiguously identify and study the dynamics of multiple underlying instabilities during the route to plasma turbulence.

PubMed

Thakur, S C; Brandt, C; Light, A; Cui, L; Gosselin, J J; Tynan, G R

2014-11-01

We use multiple-tip Langmuir probes and fast imaging to unambiguously identify and study the dynamics of underlying instabilities during the controlled route to fully-developed plasma turbulence in a linear magnetized helicon plasma device. Langmuir probes measure radial profiles of electron temperature, plasma density and potential; from which we compute linear growth rates of instabilities, cross-phase between density and potential fluctuations, Reynold's stress, particle flux, vorticity, time-delay estimated velocity, etc. Fast imaging complements the 1D probe measurements by providing temporally and spatially resolved 2D details of plasma structures associated with the instabilities. We find that three radially separated plasma instabilities exist simultaneously. Density gradient driven resistive drift waves propagating in the electron diamagnetic drift direction separate the plasma into an edge region dominated by strong, velocity shear driven Kelvin-Helmholtz instabilities and a central core region which shows coherent Rayleigh-Taylor modes propagating in the ion diamagnetic drift direction. The simultaneous, complementary use of both probes and camera was crucial to identify the instabilities and understand the details of the very rich plasma dynamics.

Shoulder disorders in an outpatient clinic: an epidemiological study.

PubMed

Malavolta, Eduardo Angeli; Gracitelli, Mauro Emilio Conforto; Assunção, Jorge Henrique; Pinto, Gustavo de Mello Ribeiro; da Silveira, Arthur Zorzi Freire; Ferreira, Arnaldo Amado

2017-01-01

To describe shoulder disorders in patients evaluated by two shoulder and elbow surgeons. This cross-sectional study analyzed patients evaluated by two authors, excluding acute fractures and dislocations and patients with symptoms not involving the shoulder. Age and sex distribution was determined for the different diagnoses. We evaluated 1001 patients. Mean age was 51.43±15.15 years and 51.0% were female. Disorders of the rotator cuff occurred in 64.3% (41.2% tendinopathy, 11.0% partial tears and 12.2% full-thickness tears). Adhesive capsulitis occurred in 13.5% of cases and glenohumeral instability in 8.1%. Rotator cuff disorders were more common in women, with a peak between 50 and 59 years for tendinopathy and partial tears and between 60 and 69 years for full-thickness tears. Glenohumeral instability was more frequent in men, with a peak between 30 and 39 years. The most frequent diagnosis was rotator cuff tendinopathy, followed by adhesive capsulitis, full-thickness rotator cuff tears, partial rotator cuff tears and glenohumeral instability. Rotator cuff lesions were more common in women, with a peak between 60 and 69 years for full-thickness tears. Level of Evidence IV, Case Series.

Localized multi-scale energy and vorticity analysis. II. Finite-amplitude instability theory and validation

NASA Astrophysics Data System (ADS)

San Liang, X.; Robinson, Allan R.

2007-12-01

A novel localized finite-amplitude hydrodynamic stability analysis is established in a unified treatment for the study of real oceanic and atmospheric processes, which are in general highly nonlinear, and intermittent in space and time. We first re-state the classical definition using the multi-scale energy and vorticity analysis (MS-EVA) developed in Liang and Robinson [Liang, X.S., Robinson, A.R., 2005. Localized multiscale energy and vorticity analysis. I. Fundamentals. Dyn. Atmos. Oceans 38, 195-230], and then manipulate certain global operators to achieve the temporal and spatial localization. The key of the spatial localization is transfer-transport separation, which is made precise with the concept of perfect transfer, while relaxation of marginalization leads to the localization of time. In doing so the information of transfer lost in the averages is retrieved and an easy-to-use instability metric is obtained. The resulting metric is field-like (Eulerian), conceptually generalizing the classical formalism, a bulk notion over the whole system. In this framework, an instability has a structure, which is of particular use for open flow processes. We check the structure of baroclinic instability with the benchmark Eady model solution, and the Iceland-Faeroe Frontal (IFF) intrusion, a highly localized and nonlinear process occurring frequently in the region between Iceland and Faeroe Islands. A clear isolated baroclinic instability is identified around the intrusion, which is further found to be characterized by the transition from a spatially growing mode to a temporally growing mode. We also check the consistency of the MS-EVA dynamics with the barotropic Kuo model. An observation is that a local perturbation burst does not necessarily imply an instability: the perturbation energy could be transported from other processes occurring elsewhere. We find that our analysis yields a Kuo theorem-consistent mean-eddy interaction, which is not seen in a conventional Reynolds stress framework. Using the techniques of marginalization and localization, this work sets up an example for the generalization of certain geophysical fluid dynamics theories for more generic purposes.

[Capsular retensioning in anterior unidirectional glenohumeral instability].

PubMed

Benítez Pozos, Leonel; Martínez Molina, Oscar; Castañeda Landa, Ezequiel

2007-01-01

To present the experience of the Orthopedics Service PEMEX South Central Hospital in the management of anterior unidirectional shoulder instability with an arthroscopic technique consisting of capsular retensioning either combined with other anatomical repair procedures or alone. Thirty-one patients with anterior unidirectional shoulder instability operated-on between January 1999 and December 2005 were included. Fourteen patients underwent capsular retensioning and radiofrequency, and in 17 patients, capsular retensioning was combined with suture anchors. Patients with a history of relapsing glenohumeral dislocations and subluxations, with anterior instability with or without associated Bankart lesions were selected; all of them were young. The results were assessed considering basically the occurrence of instability during the postoperative follow-up. No cases of recurring instability occurred. Two cases had neuroma and one experienced irritation of the suture site. Six patients had residual limitation of combined lateral rotation and abduction movements, of a mean of 10 degrees compared with the healthy contralateral side. The most frequent incident was the leak of solutions to the soft tissues. Capsular retensioning, whether combined or not with other anatomical repair techniques, has proven to result in a highly satisfactory rate of glenohumeral stabilization in cases of anterior unidirectional instabilities. The arthroscopic approach offers the well-known advantages of causing less damage to the soft tissues, and a shorter time to starting rehabilitation therapy and exercises.

Mode Medium Interaction. A Theoretical Study.

DTIC Science & Technology

1980-09-01

Report) 10. SUPPLEMENTARY NOTES I9. KEY WORDS (Conrlfnue on reverse side II necessary mnd Identify by block rumber) CO, Laser Transfer Function...Chemical Laser Unstable Resonator Brillouin Scattering Instability Supersonic Laser Modes Acoustic Noise Acoustic Instability Perturbed Resonator Gain...end Identify by block number) An instability in the output of a high-power unstable-resonator cw CO2 laser is analyzed in terms of the perturbative

A9 region in EPHB2 mutation is frequent in tumors with microsatellite instability. Analysis of prognosis.

PubMed

Rafael, Sara; Vidaurreta, Marta; Veganzones, Silvia; De La Orden, Virgnia; Mediero, Beatriz; Gutierrez, Maria Luisa; Maestro, Maria Luisa

2013-11-01

The aim of the present study was to determine the relation of EPH tyrosine kinase receptor B2 (EPHB2) A9 region mutation and microsatellite instability (MSI); and to analyze their influence in prognosis of patients with sporadic colorectal cancer (CRC). A total of 481 patients with CRC were examined. MSI (NCI criteria) and EPHB2 were analyzed using PCR and fragment analysis software. EPHB2 mutation was detected in 3.1% of patients. Mutation of EPHB2 was associated with location and with MSI status. We considered low instability (L-MSI) when only one marker showed instability, high instability (H-MSI) when two or more markers were positive and microsatelllite stable (MSS) when no instability was detected. The stratified analysis of overall survival (OS) and disease-free survival (DFS) in MSI according to EPHB2 status revealed no statistically significant differences. However, the risk of recurrence of H-MSI tumors with EPHB2 mutation carriers was 3.6-times higher than in non-mutation carriers. The frequency of EPHB2 mutation is higher in patients with H-MSI than MSS tumors. Promising results were found regarding the prognostic influence of EPHB2 in H-MSI.

Posterior Shoulder Instability

PubMed Central

Antosh, Ivan J.; Tokish, John M.; Owens, Brett D.

2016-01-01

Context: Posterior shoulder instability has become more frequently recognized and treated as a unique subset of shoulder instability, especially in the military. Posterior shoulder pathology may be more difficult to accurately diagnose than its anterior counterpart, and commonly, patients present with complaints of pain rather than instability. “Posterior instability” may encompass both dislocation and subluxation, and the most common presentation is recurrent posterior subluxation. Arthroscopic and open treatment techniques have improved as understanding of posterior shoulder instability has evolved. Evidence Acquisition: Electronic databases including PubMed and MEDLINE were queried for articles relating to posterior shoulder instability. Study Design: Clinical review. Level of Evidence: Level 4. Results: In low-demand patients, nonoperative treatment of posterior shoulder instability should be considered a first line of treatment and is typically successful. Conservative treatment, however, is commonly unsuccessful in active patients, such as military members. Those patients with persistent shoulder pain, instability, or functional limitations after a trial of conservative treatment may be considered surgical candidates. Arthroscopic posterior shoulder stabilization has demonstrated excellent clinical outcomes, high patient satisfaction, and low complication rates. Advanced techniques may be required in select cases to address bone loss, glenoid dysplasia, or revision. Conclusion: Posterior instability represents about 10% of shoulder instability and has become increasingly recognized and treated in military members. Nonoperative treatment is commonly unsuccessful in active patients, and surgical stabilization can be considered in patients who do not respond. Isolated posterior labral repairs constitute up to 24% of operatively treated labral repairs in a military population. Arthroscopic posterior stabilization is typically considered as first-line surgical treatment, while open techniques may be required in complex or revision settings. PMID:27697889

Replication Fork Protection Factors Controlling R-Loop Bypass and Suppression.

PubMed

Chang, Emily Yun-Chia; Stirling, Peter C

2017-01-14

Replication-transcription conflicts have been a well-studied source of genome instability for many years and have frequently been linked to defects in RNA processing. However, recent characterization of replication fork-associated proteins has revealed that defects in fork protection can directly or indirectly stabilize R-loop structures in the genome and promote transcription-replication conflicts that lead to genome instability. Defects in essential DNA replication-associated activities like topoisomerase, or the minichromosome maintenance (MCM) helicase complex, as well as fork-associated protection factors like the Fanconi anemia pathway, both appear to mitigate transcription-replication conflicts. Here, we will highlight recent advances that support the concept that normal and robust replisome function itself is a key component of mitigating R-loop coupled genome instability.

Frameshift mutational target gene analysis identifies similarities and differences in constitutional mismatch repair-deficiency and Lynch syndrome.

PubMed

Maletzki, Claudia; Huehns, Maja; Bauer, Ingrid; Ripperger, Tim; Mork, Maureen M; Vilar, Eduardo; Klöcking, Sabine; Zettl, Heike; Prall, Friedrich; Linnebacher, Michael

2017-07-01

Mismatch-repair deficient (MMR-D) malignancies include Lynch Syndrome (LS), which is secondary to germline mutations in one of the MMR genes, and the rare childhood-form of constitutional mismatch repair-deficiency (CMMR-D); caused by bi-allelic MMR gene mutations. A hallmark of LS-associated cancers is microsatellite instability (MSI), characterized by coding frameshift mutations (cFSM) in target genes. By contrast, tumors arising in CMMR-D patients are thought to display a somatic mutation pattern differing from LS. This study has the main goal to identify cFSM in MSI target genes relevant in CMMR-D and to compare the spectrum of common somatic mutations, including alterations in DNA polymerases POLE and D1 between LS and CMMR-D. CMMR-D-associated tumors harbored more somatic mutations compared to LS cases, especially in the TP53 gene and in POLE and POLD1, where novel mutations were additionally identified. Strikingly, MSI in classical mononucleotide markers BAT40 and CAT25 was frequent in CMMR-D cases. MSI-target gene analysis revealed mutations in CMMR-D-associated tumors, some of them known to be frequently hit in LS, such as RNaseT2, HT001, and TGFβR2. Our results imply a general role for these cFSM as potential new drivers of MMR-D tumorigenesis. © 2017 Wiley Periodicals, Inc.

On the feeding zone of planetesimal formation by the streaming instability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Chao-Chin; Johansen, Anders, E-mail: ccyang@astro.lu.se, E-mail: anders@astro.lu.se

2014-09-10

The streaming instability is a promising mechanism to overcome the barriers in direct dust growth and lead to the formation of planetesimals. Most previous studies of the streaming instability, however, were focused on a local region of a protoplanetary disk with a limited simulation domain such that only one filamentary concentration of solids has been observed. The characteristic separation between filaments is therefore not known. To address this, we conduct the largest-scale simulations of the streaming instability to date, with computational domains up to 1.6 gas scale heights both horizontally and vertically. The large dynamical range allows the effect ofmore » vertical gas stratification to become prominent. We observe more frequent merging and splitting of filaments in simulation boxes of high vertical extent. We find multiple filamentary concentrations of solids with an average separation of about 0.2 local gas scale heights, much higher than the most unstable wavelength from linear stability analysis. This measures the characteristic separation of planetesimal forming events driven by the streaming instability and thus the initial feeding zone of planetesimals.« less

Affective instability and the course of bipolar depression: results from the STEP-BD randomised controlled trial of psychosocial treatment

PubMed Central

Stange, Jonathan P.; Sylvia, Louisa G.; da Silva Magalhães, Pedro Vieira; Miklowitz, David J.; Otto, Michael W.; Frank, Ellen; Yim, Christine; Berk, Michael; Dougherty, Darin D.; Nierenberg, Andrew A.; Deckersbach, Thilo

2016-01-01

Background Little is known about predictors of recovery from bipolar depression. Aims We investigated affective instability (a pattern of frequent and large mood shifts over time) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychosocial treatment for acute depression. Method A total of 252 out-patients with DSM-IV bipolar I or II disorder and who were depressed enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and were randomised to one of three types of intensive psychotherapy for depression (n = 141) or a brief psychoeducational intervention (n = 111). All analyses were by intention-to-treat. Results Degree of instability of symptoms of depression and mania predicted a lower likelihood of recovery and longer time until recovery, independent of the concurrent effects of symptom severity. Affective instability did not moderate the effects of psychosocial treatment on recovery from depression. Conclusions Affective instability may be a clinically relevant characteristic that influences the course of bipolar depression. PMID:26795426

Wellbore stability analysis and its application in the Fergana basin, central Asia

NASA Astrophysics Data System (ADS)

Chuanliang, Yan; Jingen, Deng; Baohua, Yu; Hailong, Liu; Fucheng, Deng; Zijian, Chen; Lianbo, Hu; Haiyan, Zhu; Qin, Han

2014-02-01

Wellbore instability is one of the major problems hampering the drilling speed in the Fergana basin. Comprehensive analysis of the geological and engineering data in this area indicates that the Fergana basin is characterized by high in situ stress and plenty of natural fractures, especially in the formations which are rich in bedding structure and have several high-pressure systems. Complex accidents such as wellbore collapse, sticking, well kick and lost circulation happen frequently. Tests and theoretical analysis reveals that the wellbore instability in the Fergana basin was influenced by multiple interactive mechanisms dominated by the instability of the bedding shale. Selecting a proper drilling fluid density and improving the sealing characteristic of the applied drilling fluid is the key to preventing wellbore instability in the Fergana basin. The mechanical mechanism of wellbore instability in the Fergana basin was analysed and a method to determine the proper drilling fluid density was proposed. The research results were successfully used to guide the drilling work of the Jida-4 well; compared with the Jida-3 well, the drilling cycle of the Jida-4 well was reduced by 32%.

Histone demethylase JARID1C inactivation triggers genomic instability in sporadic renal cancer

PubMed Central

Rondinelli, Beatrice; Rosano, Dalia; Antonini, Elena; Frenquelli, Michela; Montanini, Laura; Huang, DaChuan; Segalla, Simona; Yoshihara, Kosuke; Amin, Samir B.; Lazarevic, Dejan; The, Bin Tean; Verhaak, Roel G.W.; Futreal, P. Andrew; Di Croce, Luciano; Chin, Lynda; Cittaro, Davide; Tonon, Giovanni

2015-01-01

Mutations in genes encoding chromatin-remodeling proteins are often identified in a variety of cancers. For example, the histone demethylase JARID1C is frequently inactivated in patients with clear cell renal cell carcinoma (ccRCC); however, it is largely unknown how JARID1C dysfunction promotes cancer. Here, we determined that JARID1C binds broadly to chromatin domains characterized by the trimethylation of lysine 9 (H3K9me3), which is a histone mark enriched in heterochromatin. Moreover, we found that JARID1C localizes on heterochromatin, is required for heterochromatin replication, and forms a complex with established players of heterochromatin assembly, including SUV39H1 and HP1α, as well as with proteins not previously associated with heterochromatin assembly, such as the cullin 4 (CUL4) complex adaptor protein DDB1. Transcription on heterochromatin is tightly suppressed to safeguard the genome, and in ccRCC cells, JARID1C inactivation led to the unrestrained expression of heterochromatic noncoding RNAs (ncRNAs) that in turn triggered genomic instability. Moreover, ccRCC patients harboring JARID1C mutations exhibited aberrant ncRNA expression and increased genomic rearrangements compared with ccRCC patients with tumors endowed with other genetic lesions. Together, these data suggest that inactivation of JARID1C in renal cancer leads to heterochromatin disruption, genomic rearrangement, and aggressive ccRCCs. Moreover, our results shed light on a mechanism that underlies genomic instability in sporadic cancers. PMID:26551685

Parkinsonism in fragile X-associated tremor/ataxia syndrome (FXTAS): revisited.

PubMed

Niu, Yu-Qiong; Yang, Jin-Chen; Hall, Deborah A; Leehey, Maureen A; Tassone, Flora; Olichney, John M; Hagerman, Randi J; Zhang, Lin

2014-04-01

Parkinsonian features have been used as a minor diagnostic criterion for fragile X-associated tremor/ataxia syndrome (FXTAS). However, prior studies have examined parkinsonism (defined as having bradykinesia with at least rest tremor or postural instability) mostly in premutation carriers without a diagnosis of FXTAS. The current study was intended to elaborate this important aspect of the FXTAS spectrum, and to quantify the relationships between parkinsonism, FXTAS clinical staging and genetic/molecular measures. Thirty eight (38) FXTAS patients and 10 age-matched normal controls underwent a detailed neurological examination that included all but one item (i.e. rigidity) of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS). The FXTAS patient group displayed substantially higher prevalence of parkinsonian features including body bradykinesia (57%) and rest tremor (26%), compared to the control group. Furthermore, parkinsonism was identified in 29% of FXTAS patients. Across all patients, body bradykinesia scores significantly correlated with FXTAS clinical stage, FMR1 mRNA level, and ataxic gait of cerebellar origin, while postural instability was associated with intention tremor. Parkinsonian features in FXTAS appear to be characterized as bradykinesia concurrent with cerebellar gait ataxia, postural instability accompanied by intention tremor, and frequent rest tremor, representing distinctive patterns that highlight the need for further clinical studies including genetic testing for the FMR1 premutation. The association between FMR1 mRNA level and bradykinesia implicates pathophysiological mechanisms which may link FMR1 mRNA toxicity, dopamine deficiency and parkinsonism in FXTAS. Copyright © 2014 Elsevier Ltd. All rights reserved.

Anticipating Terrorist Safe Havens from Instability Induced Conflict

NASA Astrophysics Data System (ADS)

Shearer, Robert; Marvin, Brett

This chapter presents recent methods developed at the Center for Army Analysis to classify patterns of nation-state instability that lead to conflict. The ungoverned areas endemic to failed nation-states provide terrorist organizations with safe havens from which to plan and execute terrorist attacks. Identification of those states at risk for instability induced conflict should help to facilitate effective counter terrorism policy planning efforts. Nation-states that experience instability induced conflict are similar in that they share common instability factors that make them susceptible to experiencing conflict. We utilize standard pattern classification algorithms to identify these patterns. First, we identify features (political, military, economic and social) that capture the instability of a nation-state. Second, we forecast the future levels of these features for each nation-state. Third, we classify each future state’s conflict potential based upon the conflict level of those states in the past most similar to the future state.

The Norwegian PMS2 founder mutation c.989-1G > T shows high penetrance of microsatellite instable cancers with normal immunohistochemistry.

PubMed

Grindedal, Eli Marie; Aarset, Harald; Bjørnevoll, Inga; Røyset, Elin; Mæhle, Lovise; Stormorken, Astrid; Heramb, Cecilie; Medvik, Heidi; Møller, Pål; Sjursen, Wenche

2014-01-01

Using immunohistochemistry (IHC) to select cases for mismatch repair (MMR) genetic testing, we failed to identify a large kindred with the deleterious PMS2 mutation c.989-1G > T. The purpose of the study was to examine the sensitivity of IHC and microsatellite instability-analysis (MSI) to identify carriers of the mutation, and to estimate its penetrance and expressions. All carriers and obligate carriers of the mutation were identified. All cancer diagnoses were confirmed. IHC and MSI-analysis were performed on available tumours. Penetrances of cancers included in the Amsterdam and the Bethesda Criteria, for MSI-high tumours and MSI-high and low tumours were calculated by the Kaplan-Meier algorithm. Probability for co-segregation of the mutation and cancers by chance was 0.000004. Fifty-six carriers or obligate carriers were identified. There was normal staining for PMS2 in 15/18 (83.3%) of tumours included in the AMS1/AMS2/Bethesda criteria. MSI-analysis showed that 15/21 (71.4%) of tumours were MSI-high and 4/21 (19.0%) were MSI-low. Penetrance at 70 years was 30.6% for AMS1 cancers (colorectal cancers), 42.8% for AMS2 cancers, 47.2% for Bethesda cancers, 55.6% for MSI-high and MSI-low cancers and 52.2% for MSI-high cancers. The mutation met class 5 criteria for pathogenicity. IHC was insensitive in detecting tumours caused by the mutation. Penetrance of cancers that displayed MSI was 56% at 70 years. Besides colorectal cancers, the most frequent expressions were carcinoma of the endometrium and breast in females and stomach and prostate in males.

The Norwegian PMS2 founder mutation c.989-1G > T shows high penetrance of microsatellite instable cancers with normal immunohistochemistry

PubMed Central

2014-01-01

Background Using immunohistochemistry (IHC) to select cases for mismatch repair (MMR) genetic testing, we failed to identify a large kindred with the deleterious PMS2 mutation c.989-1G > T. The purpose of the study was to examine the sensitivity of IHC and microsatellite instability-analysis (MSI) to identify carriers of the mutation, and to estimate its penetrance and expressions. Methods All carriers and obligate carriers of the mutation were identified. All cancer diagnoses were confirmed. IHC and MSI-analysis were performed on available tumours. Penetrances of cancers included in the Amsterdam and the Bethesda Criteria, for MSI-high tumours and MSI-high and low tumours were calculated by the Kaplan-Meier algorithm. Results Probability for co-segregation of the mutation and cancers by chance was 0.000004. Fifty-six carriers or obligate carriers were identified. There was normal staining for PMS2 in 15/18 (83.3%) of tumours included in the AMS1/AMS2/Bethesda criteria. MSI-analysis showed that 15/21 (71.4%) of tumours were MSI-high and 4/21 (19.0%) were MSI-low. Penetrance at 70 years was 30.6% for AMS1 cancers (colorectal cancers), 42.8% for AMS2 cancers, 47.2% for Bethesda cancers, 55.6% for MSI-high and MSI-low cancers and 52.2% for MSI-high cancers. Conclusions The mutation met class 5 criteria for pathogenicity. IHC was insensitive in detecting tumours caused by the mutation. Penetrance of cancers that displayed MSI was 56% at 70 years. Besides colorectal cancers, the most frequent expressions were carcinoma of the endometrium and breast in females and stomach and prostate in males. PMID:24790682

Intimate partner violence and housing instability.

PubMed

Pavao, Joanne; Alvarez, Jennifer; Baumrind, Nikki; Induni, Marta; Kimerling, Rachel

2007-02-01

The mental and physical health consequences of intimate partner violence (IPV) have been well established, yet little is known about the impact of violence on a woman's ability to obtain and maintain housing. This cross-sectional study examines the relationship between recent IPV and housing instability among a representative sample of California women. It is expected that women who have experienced IPV will be at increased risk for housing instability as evidenced by: (1) late rent or mortgage, (2) frequent moves because of difficulty obtaining affordable housing, and/or (3) without their own housing. Data were taken from the 2003 California Women's Health Survey, a population-based, random-digit-dial, annual probability survey of adult California women (N=3619). Logistic regressions were used to predict housing instability in the past 12 months, adjusting for the following covariates; age, race/ethnicity, education, poverty status, marital status, children in the household, and past year IPV. In the multivariate model, age, race/ethnicity, marital status, poverty, and IPV were significant predictors of housing instability. After adjusting for all covariates, women who experienced IPV in the last year had almost four times the odds of reporting housing instability than women who did not experience IPV (adjusted odds ratio=3.98, 95% confidence interval: 2.94-5.39). This study found that IPV was associated with housing instability among California women. Future prospective studies are needed to learn more about the nature and direction of the relationship between IPV and housing instability and the possible associated negative health consequences.

Single-cell sequencing reveals karyotype heterogeneity in murine and human malignancies.

PubMed

Bakker, Bjorn; Taudt, Aaron; Belderbos, Mirjam E; Porubsky, David; Spierings, Diana C J; de Jong, Tristan V; Halsema, Nancy; Kazemier, Hinke G; Hoekstra-Wakker, Karina; Bradley, Allan; de Bont, Eveline S J M; van den Berg, Anke; Guryev, Victor; Lansdorp, Peter M; Colomé-Tatché, Maria; Foijer, Floris

2016-05-31

Chromosome instability leads to aneuploidy, a state in which cells have abnormal numbers of chromosomes, and is found in two out of three cancers. In a chromosomal instable p53 deficient mouse model with accelerated lymphomagenesis, we previously observed whole chromosome copy number changes affecting all lymphoma cells. This suggests that chromosome instability is somehow suppressed in the aneuploid lymphomas or that selection for frequently lost/gained chromosomes out-competes the CIN-imposed mis-segregation. To distinguish between these explanations and to examine karyotype dynamics in chromosome instable lymphoma, we use a newly developed single-cell whole genome sequencing (scWGS) platform that provides a complete and unbiased overview of copy number variations (CNV) in individual cells. To analyse these scWGS data, we develop AneuFinder, which allows annotation of copy number changes in a fully automated fashion and quantification of CNV heterogeneity between cells. Single-cell sequencing and AneuFinder analysis reveals high levels of copy number heterogeneity in chromosome instability-driven murine T-cell lymphoma samples, indicating ongoing chromosome instability. Application of this technology to human B cell leukaemias reveals different levels of karyotype heterogeneity in these cancers. Our data show that even though aneuploid tumours select for particular and recurring chromosome combinations, single-cell analysis using AneuFinder reveals copy number heterogeneity. This suggests ongoing chromosome instability that other platforms fail to detect. As chromosome instability might drive tumour evolution, karyotype analysis using single-cell sequencing technology could become an essential tool for cancer treatment stratification.

Landslide Susceptibility Analysis along Li-Shing Mountain Road in Nantou County, Taiwan

NASA Astrophysics Data System (ADS)

Yeh, J. H.; Chan, H. C.; Chen, B. A.

2016-12-01

Slopeland hazards are frequently occurred during typhoon periods in the mountain areas of Taiwan. The Li-Shing Mountain Road was suffered from the landslide and erosion of road foundation due to its fragile geological structure, overuse of land, and heavy rainfall. Transportation of agricultural produce in Li-Shing areas was seriously affected while the Li-Shing Mountain Road was blocked by the landslides. To evaluate the landslide susceptibilities along the Li-Shing Mountain Road, this study collected the landslide inventories from Typhoon Mindulle in July, 2004 and Typhoon Kalmaegi in July, 2008. By combining the landslide inventories with hydrological and geological factors, such as rainfall, distance to river, geology, and land slope and aspect, the Instability Index Method was used to specify the landslide susceptibilities of the slopes along the Li-Shing Mountain Road. The accuracy of the present model was evaluated by comparison of the predicted and the typhoon triggered landslides. Finally, the high landslide potential slopes along the Li-Shing Mountain Road were identified. It is expected to provide the information for landslide warning system and engineering countermeasures planning along the Li-Shing Mountain Road. Keywords: Landslide, Instability Index Method, Li-Shing Mountain Road

Cortical–Subcortical Interactions in Hypersomnia Disorders: Mechanisms Underlying Cognitive and Behavioral Aspects of the Sleep–Wake Cycle

PubMed Central

Larson-Prior, Linda J.; Ju, Yo-El; Galvin, James E.

2014-01-01

Subcortical circuits mediating sleep–wake functions have been well characterized in animal models, and corroborated by more recent human studies. Disruptions in these circuits have been identified in hypersomnia disorders (HDs) such as narcolepsy and Kleine–Levin Syndrome, as well as in neurodegenerative disorders expressing excessive daytime sleepiness. However, the behavioral expression of sleep–wake functions is not a simple on-or-off state determined by subcortical circuits, but encompasses a complex range of behaviors determined by the interaction between cortical networks and subcortical circuits. While conceived as disorders of sleep, HDs are equally disorders of wake, representing a fundamental instability in neural state characterized by lapses of alertness during wake. These episodic lapses in alertness and wakefulness are also frequently seen in neurodegenerative disorders where electroencephalogram demonstrates abnormal function in cortical regions associated with cognitive fluctuations (CFs). Moreover, functional connectivity MRI shows instability of cortical networks in individuals with CFs. We propose that the inability to stabilize neural state due to disruptions in the sleep–wake control networks is common to the sleep and cognitive dysfunctions seen in hypersomnia and neurodegenerative disorders. PMID:25309500

Instability after total hip arthroplasty

PubMed Central

Werner, Brian C; Brown, Thomas E

2012-01-01

Instability following total hip arthroplasty (THA) is an unfortunately frequent and serious problem that requires thorough evaluation and preoperative planning before surgical intervention. Prevention through optimal index surgery is of great importance, as the management of an unstable THA is challenging even for an experienced joints surgeon. However, even after well-planned surgery, a significant incidence of recurrent instability still exists. Non-operative management is often successful if the components are well-fixed and correctly positioned in the absence of neurocognitive disorders. If conservative management fails, surgical options include revision of malpositioned components; exchange of modular components such as the femoral head and acetabular liner; bipolar arthroplasty; tripolar arthroplasty; use of a larger femoral head; use of a constrained liner; soft tissue reinforcement and advancement of the greater trochanter. PMID:22919568

Genomic Instability in Human Pluripotent Stem Cells Arises from Replicative Stress and Chromosome Condensation Defects.

PubMed

Lamm, Noa; Ben-David, Uri; Golan-Lev, Tamar; Storchová, Zuzana; Benvenisty, Nissim; Kerem, Batsheva

2016-02-04

Human pluripotent stem cells (hPSCs) frequently acquire chromosomal aberrations such as aneuploidy in culture. These aberrations progressively increase over time and may compromise the properties and clinical utility of the cells. The underlying mechanisms that drive initial genomic instability and its continued progression are largely unknown. Here, we show that aneuploid hPSCs undergo DNA replication stress, resulting in defective chromosome condensation and segregation. Aneuploid hPSCs show altered levels of actin cytoskeletal genes controlled by the transcription factor SRF, and overexpression of SRF rescues impaired chromosome condensation and segregation defects in aneuploid hPSCs. Furthermore, SRF downregulation in diploid hPSCs induces replication stress and perturbed condensation similar to that seen in aneuploid cells. Together, these results suggest that decreased SRF expression induces replicative stress and chromosomal condensation defects that underlie the ongoing chromosomal instability seen in aneuploid hPSCs. A similar mechanism may also operate during initiation of instability in diploid cells. Copyright © 2016 Elsevier Inc. All rights reserved.

[Distal clavicle fractures. Classifications and management].

PubMed

Ockert, Ben; Wiedemann, E; Haasters, F

2015-05-01

Fractures of the distal third of the clavicle represent 10-30% of all clavicle fractures . Frequently, these fractures result in instability due to a combination of bony and ligamentous injury. Thus, assessment of the stability is essential for adequate treatment of these fractures. This article presents a review of the different classification systems for distal clavicle fractures with respect to anatomical and functional factors to allow for comprehensive assessment of stability. Furthermore, the different treatment options for each fracture type are analyzed. Fractures to the distal third of the clavicle without instability can be treated conservatively with satisfactory outcome. In contrast, instability may result in symptomatic non-union under conservative treatment; therefore, distal clavicle fractures with instability should be treated operatively with respect to the functional demands of the patient. Operative treatment with locked plating in combination with coracoclavicular fixation results in excellent functional results. Arthroscopically assisted fracture fixation may be beneficial in terms of a minimally invasive approach as well as assessment and treatment of associated glenohumeral lesions.

Associated lateral/medial knee instability and its relevant factors in anterior cruciate ligament-injured knees.

PubMed

Yuuki, Arata; Muneta, Takeshi; Ohara, Toshiyuki; Sekiya, Ichiro; Koga, Hideyuki

2017-03-01

Associations of lateral/medial knee instability with anterior cruciate ligament (ACL) injury have not been thoroughly investigated. The purposes of this study were to investigate whether lateral/medial knee instability is associated with ACL injury, and to clarify relevant factors for lateral/medial knee instability in ACL-injured knees. One hundred and nineteen patients with unilateral ACL-injured knees were included. Lateral/medial knee instability was assessed with varus/valgus stress X-ray examination for both injured and uninjured knees by measuring varus/valgus angle, lateral/medial joint opening, and lateral/medial joint opening index. Manual knee instability tests for ACL were evaluated to investigate associations between lateral/medial knee instability and anterior and/or rotational instabilities. Patients' backgrounds were evaluated to identify relevant factors for lateral/medial knee instability. Damage on the lateral collateral ligament (LCL) on MRI was also evaluated. All parameters regarding lateral knee instability in injured knees were significantly greater than in uninjured knees. There were significant correlations between lateral knee instability and the Lachman test as well as the pivot shift test. Patients with LCL damage had significantly greater lateral joint opening than those without LCL damage on MRI. Sensitivity of LCL damage on MRI to lateral joint opening was 100%, while its specificity was 36%. No other relevant factors were identified. In medial knee instability, there were also correlations between medial knee instability and the Lachman test/pivot shift test. However, the correlations were weak and other parameters were not significant. Lateral knee instability was greater in ACL-deficient knees than in uninjured knees. Lateral knee instability was associated with ACL-related instabilities as well as LCL damage on MRI, whereas MRI had low specificity to lateral knee instability. On the other hand, the association of medial knee instability on ACL-related instability was less than that of lateral knee instability. Level IV, case series with no comparison group. Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Neurotology symptoms at referral to vestibular evaluation

PubMed Central

2013-01-01

Background Dizziness-vertigo is common in adults, but clinical providers may rarely diagnose vestibular impairment and referral could be delayed. To assess neurotology symptoms (including triggers) reported by patients with peripheral vestibular disease, during the year just before their referral to vestibular evaluation. Methods 282 patients with peripheral vestibular disease and 282 control subjects accepted to participate. They had no middle ear, retinal, neurological, psychiatric, autoimmune or autonomic disorders. They reported their symptoms by a standardized questionnaire along with their anxiety/depression symptoms. Results Patients were referred after months or years from the onset of their symptoms, 24% of them reported frequent falls with a long clinical evolution; 10% of them reported no vertigo but instability related to specific triggers; 86% patients and 12% control subjects reported instability when moving the head rapidly and 79% patients and 6% control subjects reported instability when changing posture. Seven out of the 9 symptoms explored by the questionnaire allowed the correct classification of circa 95% of the participants (Discriminant function analysis, p < 0.001). High blood pressure, dyslipidemia and anxiety/depression symptoms showed a mild correlation with the total score of symptoms (multiple R2 =0.18, p < 0.001). Conclusions Late referral to vestibular evaluation may underlie a history of frequent falls; some patients may not report vertigo, but instability related to specific triggers, which could be useful to prompt vestibular evaluation. High blood pressure, dyslipidemia and anxiety/depression symptoms may have a mild influence on the report of symptoms of vestibular disease in both, patients and control subjects. PMID:24279682

Elimination of Intermediate-Frequency Combustion Instability in the Fastrac Engine Thrust Chamber

NASA Technical Reports Server (NTRS)

Rocker, Marvin; Nesman, Tomas E.; Turner, Jim E. (Technical Monitor)

2001-01-01

A series of tests were conducted to measure the combustion performance of the Fastrac engine thrust chamber. The thrust chamber exhibited benign, yet marginally unstable combustion. The marginally unstable combustion was characterized by chamber pressure oscillations with large amplitudes and a frequency that was too low to be identified as acoustic or high-frequency combustion instability and too high to be identified as chug or low-frequency combustion instability. The source of the buzz or intermediate-frequency combustion instability was traced to the fuel venturi whose violently noisy cavitation caused resonance in the feedline downstream. Combustion was stabilized by increasing the throat diameter of the fuel venturi such that the cavitation would occur more quietly.

GFP-based fluorescence assay for CAG repeat instability in cultured human cells.

PubMed

Santillan, Beatriz A; Moye, Christopher; Mittelman, David; Wilson, John H

2014-01-01

Trinucleotide repeats can be highly unstable, mutating far more frequently than point mutations. Repeats typically mutate by addition or loss of units of the repeat. CAG repeat expansions in humans trigger neurological diseases that include myotonic dystrophy, Huntington disease, and several spinocerebellar ataxias. In human cells, diverse mechanisms promote CAG repeat instability, and in mice, the mechanisms of instability are varied and tissue-dependent. Dissection of mechanistic complexity and discovery of potential therapeutics necessitates quantitative and scalable screens for repeat mutation. We describe a GFP-based assay for screening modifiers of CAG repeat instability in human cells. The assay exploits an engineered intronic CAG repeat tract that interferes with expression of an inducible GFP minigene. Like the phenotypes of many trinucleotide repeat disorders, we find that GFP function is impaired by repeat expansion, in a length-dependent manner. The intensity of fluorescence varies inversely with repeat length, allowing estimates of repeat tract changes in live cells. We validate the assay using transcription through the repeat and engineered CAG-specific nucleases, which have previously been reported to induce CAG repeat instability. The assay is relatively fast and should be adaptable to large-scale screens of chemical and shRNA libraries.

GFP-Based Fluorescence Assay for CAG Repeat Instability in Cultured Human Cells

PubMed Central

Santillan, Beatriz A.; Moye, Christopher; Mittelman, David; Wilson, John H.

2014-01-01

Trinucleotide repeats can be highly unstable, mutating far more frequently than point mutations. Repeats typically mutate by addition or loss of units of the repeat. CAG repeat expansions in humans trigger neurological diseases that include myotonic dystrophy, Huntington disease, and several spinocerebellar ataxias. In human cells, diverse mechanisms promote CAG repeat instability, and in mice, the mechanisms of instability are varied and tissue-dependent. Dissection of mechanistic complexity and discovery of potential therapeutics necessitates quantitative and scalable screens for repeat mutation. We describe a GFP-based assay for screening modifiers of CAG repeat instability in human cells. The assay exploits an engineered intronic CAG repeat tract that interferes with expression of an inducible GFP minigene. Like the phenotypes of many trinucleotide repeat disorders, we find that GFP function is impaired by repeat expansion, in a length-dependent manner. The intensity of fluorescence varies inversely with repeat length, allowing estimates of repeat tract changes in live cells. We validate the assay using transcription through the repeat and engineered CAG-specific nucleases, which have previously been reported to induce CAG repeat instability. The assay is relatively fast and should be adaptable to large-scale screens of chemical and shRNA libraries. PMID:25423602

Housing instability is as strong a predictor of poor health outcomes as level of danger in an abusive relationship: findings from the SHARE Study.

PubMed

Rollins, Chiquita; Glass, Nancy E; Perrin, Nancy A; Billhardt, Kris A; Clough, Amber; Barnes, Jamie; Hanson, Ginger C; Bloom, Tina L

2012-03-01

Advocates, clinicians, policy makers, and survivors frequently cite intimate partner violence (IPV) as an immediate cause of or precursor to housing problems. Research has indicated an association between homelessness and IPV, yet few studies examine IPV and housing instability. Housing instability differs from homelessness, in that someone experiencing housing instability may currently have a place to live but faces difficulties with maintaining the residence. We present baseline findings from a longitudinal cohort study of 278 female IPV survivors with housing as a primary concern. Our analysis indicates the greater the number of housing instability risk factors (e.g., eviction notice, problems with landlord, moving multiple times), the more likely the abused woman reported symptoms consistent with PTSD (p < .001), depression (p < .001), reduced quality of life (p < .001), increased work/school absence (OR = 1.28, p < .004), and increased hospital/emergency department use (OR = 1.22, p < .001). These outcomes persist even when controlling for the level of danger in the abusive relationship and for survivors' drug and alcohol use. Importantly, both housing instability and danger level had stronger associations with negative health outcomes than other factors such as age, alcohol, and drug use; both make unique contributions to negative health outcomes and could contribute in different ways. Housing instability is an important and understudied social determinant of health for IPV survivors. These findings begin to address the literature gap on the relationship between housing instability, IPV, and survivors' health, employment, and utilization of medical care services.

Online Assessment of Voltage Stability in Power Systems with PMUs

NASA Astrophysics Data System (ADS)

Chitare, Prasad Bhagwat; Murthy Balijepalli, V. S. K.; Khaparde, S. A.

2013-05-01

Abstract: For the assessment of voltage instability which comprises the detection of voltage instability and identification of critical buses, two indices namely, system wide Qtax, and bus-specific qtax, are proposed. The Qtax, based on the sensitivity of the reactive power injections to the loading in the system provides early detection of impending voltage instability. The computed qtax indices identify the critcal buses among the load buses in the system. The identified critical buses provided optimal lacations for the corrective control actions for averting voltage instability. Additionally, for voltage stability monitoring, determining the poing of exhaustion of the reactive reserves in system is also crucial. This is addressed by proposed Q-Monitoring Index (QMI), which is the ratio of the reactive component of the source current to the sink current that flows through the adjacent transmission line. These proposed indices together can provide early indication to impending voltage instability. This has been illustrated on IEEE-39 bus system. The reactive support on identified critical buses results in maximum increase in the loadability of the system.

Tissue identity testing of cancer by short tandem repeat polymorphism: pitfalls of interpretation in the presence of microsatellite instability.

PubMed

Much, Melissa; Buza, Natalia; Hui, Pei

2014-03-01

Tissue identity testing by short tandem repeat (STR) polymorphism offers discriminating power in resolving tissue mix-up or contamination. However, one caveat is the presence of microsatellite unstable tumors, in which genetic alterations may drastically change the STR wild-type polymorphism leading to unexpected allelic discordance. We examined how tissue identity testing results can be altered by the presence of microsatellite instability (MSI). Eleven cases of MSI-unstable (9 intestinal and 2 endometrial adenocarcinomas) and 10 cases of MSI-stable tumors (all colorectal adenocarcinomas) were included. All had been previously tested by polymerase chain reaction testing at 5 National Cancer Institute (NCI) recommended MSI loci and/or immunohistochemistry for DNA mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2). Tissue identity testing targeting 15 STR loci was performed using AmpF/STR Identifiler Amplification. Ten of 11 MSI-unstable tumors demonstrated novel alleles at 5 to 12 STR loci per case and frequently with 3 or more allelic peaks. However, all affected loci showed identifiable germline allele(s) in MSI-high tumors. A wild-type allelic profile was seen in 7 of 10 MSI-stable tumors. In the remaining 3 cases, isolated novel alleles were present at a unique single locus in addition to germline alleles. Loss of heterozygosity was observed frequently in both MSI-stable (6/11 cases) and MSI-unstable tumors (8/10 cases). In conclusion, MSI may significantly alter the wild-type allelic polymorphism, leading to potential interpretation errors of STR genotyping. Careful examination of the STR allelic pattern, high index of suspicion, and follow-up MSI testing are crucial to avoid erroneous conclusions and subsequent clinical and legal consequences. Copyright © 2014 Elsevier Inc. All rights reserved.

Beam measurement of the high frequency impedance sources with long bunches in the CERN Super Proton Synchrotron

NASA Astrophysics Data System (ADS)

Lasheen, A.; Argyropoulos, T.; Bohl, T.; Esteban Müller, J. F.; Timko, H.; Shaposhnikova, E.

2018-03-01

Microwave instability in the Super Proton Synchrotron (SPS) at CERN is one of the main limitations to reach the requirements for the High Luminosity-LHC project (increased beam intensity by a factor 2). To identify the impedance source responsible of the instability, beam measurements were carried out to probe the SPS impedance. The method presented in this paper relies on measurements of the unstable spectra of single bunches, injected in the SPS with the rf voltage switched off. The modulation of the bunch profile gives information about the main impedance sources driving microwave instability, and is compared to particle simulations using the SPS impedance model to identify the most important contributions. This allowed us to identify the vacuum flanges as the main impedance source for microwave instability in the SPS, and to evaluate possible missing impedance sources.

Seasonal simulations of the planetary boundary layer and boundary-layer stratocumulus clouds with a general circulation model

NASA Technical Reports Server (NTRS)

Randall, D. A.; Abeles, J. A.; Corsetti, T. G.

1985-01-01

The formulation of the planetary boundary layer (PBL) and stratocumulus parametrizations in the UCLA general circulation model (GCM) are briefly summarized, and extensive new results are presented illustrating some aspects of the simulated seasonal changes of the global distributions of PBL depth, stratocumulus cloudiness, cloud-top entrainment instability, the cumulus mass flux, and related fields. Results from three experiments designed to reveal the sensitivity of the GCM results to aspects of the PBL and stratocumulus parametrizations are presented. The GCM results show that the layer cloud instability appears to limit the extent of the marine subtropical stratocumulus regimes, and that instability frequently occurs in association with cumulus convection over land. Cumulus convection acts as a very significant sink of PBL mass throughout the tropics and over the midlatitude continents in winter.

Chemical Effect on Wellbore Instability of Nahr Umr Shale

PubMed Central

Nie, Zhen

2013-01-01

Wellbore instability is one of the major problems that hamper the drilling speed in Halfaya Oilfield. Comprehensive analysis of geological and engineering data indicates that Halfaya Oilfield features fractured shale in the Nahr Umr Formation. Complex accidents such as wellbore collapse and sticking emerged frequently in this formation. Tests and theoretical analysis revealed that wellbore instability in the Halfaya Oilfield was influenced by chemical effect of fractured shale and the formation water with high ionic concentration. The influence of three types of drilling fluids on the rock mechanical properties of Nahr Umr Shale is tested, and time-dependent collapse pressure is calculated. Finally, we put forward engineering countermeasures for safety drilling in Halfaya Oilfield and point out that increasing the ionic concentration and improving the sealing capacity of the drilling fluid are the way to keep the wellbore stable. PMID:24282391

Chemical effect on wellbore instability of Nahr Umr Shale.

PubMed

Yu, Baohua; Yan, Chuanliang; Nie, Zhen

2013-01-01

Wellbore instability is one of the major problems that hamper the drilling speed in Halfaya Oilfield. Comprehensive analysis of geological and engineering data indicates that Halfaya Oilfield features fractured shale in the Nahr Umr Formation. Complex accidents such as wellbore collapse and sticking emerged frequently in this formation. Tests and theoretical analysis revealed that wellbore instability in the Halfaya Oilfield was influenced by chemical effect of fractured shale and the formation water with high ionic concentration. The influence of three types of drilling fluids on the rock mechanical properties of Nahr Umr Shale is tested, and time-dependent collapse pressure is calculated. Finally, we put forward engineering countermeasures for safety drilling in Halfaya Oilfield and point out that increasing the ionic concentration and improving the sealing capacity of the drilling fluid are the way to keep the wellbore stable.

Work-related ladder fall fractures: identification and diagnosis validation using narrative text.

PubMed

Smith, Gordon S; Timmons, Robert A; Lombardi, David A; Mamidi, Dheeresh K; Matz, Simon; Courtney, Theodore K; Perry, Melissa J

2006-09-01

To identify ladder-related fracture injuries and determine how ladder fall fractures differ from other ladder-related injuries. Ladder-related fracture cases were identified using narrative text and coded data from workers' compensation claims. Potential cases were identified by text searches and verified with claim records. Injury characteristics were compared using proportionate injury ratios. Of 9826 ladder-related injuries, 7% resulted in fracture cases. Falls caused 89% of fractures and resulted in more medical costs and disability days than other injuries. Frequent mechanisms were ladder instability (22%) and lost footing (22%). Narrative text searches identified 17% more fractures than injury codes alone. Males were more likely to sustain a fall fracture than other injuries; construction workers were most likely, and retail workers were the least likely to sustain fractures. Fractures are an important injury from ladder falls, resulting more serious consequences than other ladder-related injuries. Text analysis can improve the quality and utility of workers compensation data by identifying and understanding injury causes. Proportionate injury ratios are also useful for making cross-group comparisons of injury experience when denominator data are not available. Greater attention to risk factors for ladder falls is needed for targeting interventions.

Experimental Evidence for the Los Alamos Proton Storage Ring Beam Instability

NASA Astrophysics Data System (ADS)

Plum, M.; Fitzgerald, D. H.; Macek, R.; Sander, O.; Thiessen, H. A.; Wang, T. S.; Wilkinson, C.

1997-05-01

Although the exact instability mechanism at the Proton Storage Ring (PSR) has not yet been conclusively identified, the evidence gathered to date is consistent with an e-p instability. We have recently acquired new data which shows that clearing electrodes significantly affect the instability threshold. A set of comprehensive measurements is also planned for the first months of 1997. In this paper we will present our latest data.

Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition

PubMed Central

Ferguson, Lynnette R.; Chen, Helen; Collins, Andrew R.; Connell, Marisa; Damia, Giovanna; Dasgupta, Santanu; Malhotra, Meenakshi; Meeker, Alan K.; Amedei, Amedeo; Amin, Amr; Ashraf, S. Salman; Aquilano, Katia; Azmi, Asfar S.; Bhakta, Dipita; Bilsland, Alan; Boosani, Chandra S.; Chen, Sophie; Ciriolo, Maria Rosa; Fujii, Hiromasa; Guha, Gunjan; Halicka, Dorota; Helferich, William G.; Keith, W. Nicol; Mohammed, Sulma I.; Niccolai, Elena; Yang, Xujuan; Honoki, Kanya; Parslow, Virginia R.; Prakash, Satya; Rezazadeh, Sarallah; Shackelford, Rodney E.; Sidransky, David; Tran, Phuoc T.; Yang, Eddy S.; Maxwell, Christopher A.

2015-01-01

Genomic instability can initiate cancer, augment progression, and influence the overall prognosis of the affected patient. Genomic instability arises from many different pathways, such as telomere damage, centrosome amplification, epigenetic modifications, and DNA damage from endogenous and exogenous sources, and can be perpetuating, or limiting, through the induction of mutations or aneuploidy, both enabling and catastrophic. Many cancer treatments induce DNA damage to impair cell division on a global scale but it is accepted that personalized treatments, those that are tailored to the particular patient and type of cancer, must also be developed. In this review, we detail the mechanisms from which genomic instability arises and can lead to cancer, as well as treatments and measures that prevent genomic instability or take advantage of the cellular defects caused by genomic instability. In particular, we identify and discuss five priority targets against genomic instability: (1) prevention of DNA damage; (2) enhancement of DNA repair; (3) targeting deficient DNA repair; (4) impairing centrosome clustering; and, (5) inhibition of telomerase activity. Moreover, we highlight vitamin D and B, selenium, carotenoids, PARP inhibitors, resveratrol, and isothiocyanates as priority approaches against genomic instability. The prioritized target sites and approaches were cross validated to identify potential synergistic effects on a number of important areas of cancer biology. PMID:25869442

A mobile threat to genome stability: The impact of non-LTR retrotransposons upon the human genome

PubMed Central

Konkel, Miriam K.; Batzer, Mark A.

2010-01-01

It is now commonly agreed that the human genome is not the stable entity originally presumed. Deletions, duplications, inversions, and insertions are common, and contribute significantly to genomic structural variations (SVs). Their collective impact generates much of the inter-individual genomic diversity observed among humans. Not only do these variations change the structure of the genome; they may also have functional implications, e.g. altered gene expression. Some SVs have been identified as the cause of genetic disorders, including cancer predisposition. Cancer cells are notorious for their genomic instability, and often show genomic rearrangements at the microscopic and submicroscopic level to which transposable elements (TEs) contribute. Here, we review the role of TEs in genome instability, with particular focus on non-LTR retrotransposons. Currently, three non-LTR retrotransposon families – long interspersed element 1 (L1), SVA (short interspersed element (SINE-R), variable number of tandem repeats (VNTR), and Alu), and Alu (a SINE) elements – mobilize in the human genome, and cause genomic instability through both insertion- and post-insertion-based mutagenesis. Due to the abundance and high sequence identity of TEs, they frequently mislead the homologous recombination repair pathway into non-allelic homologous recombination, causing deletions, duplications, and inversions. While less comprehensively studied, non-LTR retrotransposon insertions and TE-mediated rearrangements are probably more common in cancer cells than in healthy tissue. This may be at least partially attributed to the commonly seen global hypomethylation as well as general epigenetic dysfunction of cancer cells. Where possible, we provide examples that impact cancer predisposition and/or development. PMID:20307669

Coulomb Fission in Multiply-Charged Ammonia Clusters: Accurate Measurements of the Rayleigh Instability Limit from Fragmentation Patterns.

PubMed

Harris, Christopher; Stace, Anthony J

2018-03-15

A series of experiments have been undertaken on the fragmentation of multiply charged ammonia clusters, (NH 3 ) n z+ , where z ≤ 8 and n ≤ 850, to establish Rayleigh instability limits, whereby clusters at certain critical sizes become unstable due to Coulomb repulsion between the resident charges. Experimental results on size-selected clusters are found to be in excellent agreement with theoretical predictions of Rayleigh instability limits at all values of the charge. Electrostatic theory has been used to help identify fragmentation patterns on the assumption that the clusters separate into two dielectric spheres, and the predicted Coulomb repulsion energies used to establish pathways and the sizes of cluster fragments. The results show that fragmentation is very asymmetric in terms of both the numbers of molecules involved and the amount of charge each fragment accommodates. For clusters carrying a charge ≤+4, the results show that fragmentation proceeds via the loss of small, singly charged clusters. When clusters carry a charge of +5 or more, the experimental observations suggest a marked switch in behavior. Although the laboratory measurements equate to fragmentation via the loss of a large dication cluster, electrostatic theory supports an interpretation that involves the sequential loss of two smaller, singly charged clusters possibly accompanied by the extensive evaporation of neutral molecules. It is suggested that this change in fragmentation pattern is driven by the channelling of Coulomb repulsion energy into intermolecular modes within these larger clusters. Overall, the results appear to support the ion evaporation model that is frequently used to interpret electrospray experiments.

Demonstration of various rotor instabilities (exhibit of Bently Rotor Dynamics Research Corporation Laborator rigs at symposium on instability in rotaing machinery)

NASA Technical Reports Server (NTRS)

Muszynska, A.

1985-01-01

The operation of rotor rigs used to demonstrate various instability phenomena occurring in rotating machines is described. The instability phenomena demonstrated included oil whirl/whip antiswirl, rub, loose rotating parts, water-lubricated bearing instabilities, and cracked shaft. The rotor rigs were also used to show corrective measures for preventing instabilities. Vibrational response data from the rigs were taken with modern, computerized instrumentation. The rotor nonsynchronous perturbation rig demonstrated modal identification techniques for rotor/bearing systems. Computer-aided data acquisition and presentation, using the dynamic stiffness method, makes it possible to identify rotor and bearing parameters for low modes. The shaft mode demonstrator presented the amplified modal shape line of the shaft excited by inertia forces of unbalance (synchronous perturbation). The first three bending modes of the shaft can be demonstrated. The user-friendly software, Orbits, presented a simulation of rotor precessional motion that is characteristic of various instability phenomena. The data presentation demonstration used data measured on a turbine driven compressor train as an example of how computer aided data acquisition and presentation assists in identifying rotating machine malfunctions.

Adolescent patellar instability: current concepts review.

PubMed

Clark, D; Metcalfe, A; Wogan, C; Mandalia, V; Eldridge, J

2017-02-01

Patellar instability most frequently presents during adolescence. Congenital and infantile dislocation of the patella is a distinct entity from adolescent instability and measurable abnormalities may be present at birth. In the normal patellofemoral joint an increase in quadriceps angle and patellar height are matched by an increase in trochlear depth as the joint matures. Adolescent instability may herald a lifelong condition leading to chronic disability and arthritis. Restoring normal anatomy by trochleoplasty, tibial tubercle transfer or medial patellofemoral ligament (MPFL) reconstruction in the young adult prevents further instability. Although these techniques are proven in the young adult, they may cause growth arrest and deformity where the physis is open. A vigorous non-operative strategy may permit delay of surgery until growth is complete. Where non-operative treatment has failed a modified MPFL reconstruction may be performed to maintain stability until physeal closure permits anatomical reconstruction. If significant growth remains an extraosseous reconstruction of the MPFL may impart the lowest risk to the physis. If minor growth remains image intensifier guided placement of femoral intraosseous fixation may impart a small, but acceptable, risk to the physis. This paper presents and discusses the literature relating to adolescent instability and provides a framework for management of these patients. Cite this article: Bone Joint J 2017;99-B:159-70. ©2017 The British Editorial Society of Bone & Joint Surgery.

Hypermethylation of miR-203 in endometrial carcinomas.

PubMed

Huang, Yi-Wen; Kuo, Chieh-Ti; Chen, Jo-Hsin; Goodfellow, Paul J; Huang, Tim H-M; Rader, Janet S; Uyar, Denise S

2014-05-01

Aberrant expression of SOX4 in endometrial cancer has been identified and partially was contributed to hypermethylation of miR-129-2. Other miRNAs are suspected to influence SOX 4 as well. The current study seeks to identify other hypermethylated miRNAs that regulate SOX4 in endometrial carcinomas. Methylation levels of miRNA promoter regions were measured by combined bisulfite restriction analysis (COBRA) and pyrosequencing assays. Gene expression was determined by RT-qPCR. Methylation level of a miRNA locus was corrected with clinicopathologic factors for 252 gynecological specimens. In silico analysis identified 13 miRNA loci bound on the 3'-UTR of SOX4. Using COBRA assays, increased methylation of miR-203, miR-219-2, miR-596, and miR-618 was detected in endometrial cancer cells relative to those seen in a normal cell line and in normal endometrium. Transfection of a miR-203 mimic decreased SOX4 gene expression. Hypermethylation of miR-203 was detected in 52% of type I endometrioid endometrial carcinomas (n=131) but was not seen in any of 10 uninvolved normal endometria (P<0.001). Methylation status of miR-203 was significantly associated with microsatellite instability and MLH1 methylation in endometrial tumors (P<0.001). Furthermore, hypermethylation of miR-203 was found in endometrioid and clear endometrial subtype tumors, but not in cervical squamous cell and ovarian carcinomas. Hypermethylation of miR-203 is a frequent event in endometrial carcinomas and is strongly associated with microsatellite instability and MLH1 methylation status. Thus, miR-203 methylation level might represent a marker for patients with endometrioid and clear endometrial sub-cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

Theory of Collisional Two-Stream Plasma Instabilities in the Solar Chromosphere

NASA Astrophysics Data System (ADS)

Madsen, Chad Allen; Dimant, Yakov; Oppenheim, Meers; Fontenla, Juan

2014-06-01

The solar chromosphere experiences intense heating just above its temperature minimum. The heating increases the electron temperature in this region by over 2000 K. Furthermore, it exhibits little time variation and appears widespread across the solar disk. Although semi-empirical models, UV continuum observations, and line emission measurements confirm the existence of the heating, its source remains unexplained. Potential heating sources such as acoustic shocks, resistive dissipation, and magnetic reconnection via nanoflares fail to account for the intensity, persistence, and ubiquity of the heating. Fontenla (2005) suggested turbulence from a collisional two-stream plasma instability known as the Farley-Buneman instability (FBI) could contribute significantly to the heating. This instability is known to heat the plasma of the E-region ionosphere which bears many similarities to the chromospheric plasma. However, the ionospheric theory of the FBI does not account for the diverse ion species found in the solar chromosphere. This work develops a new collisional, two-stream instability theory appropriate for the chromospheric plasma environment using a linear fluid analysis to derive a new dispersion relationship and critical E x B drift velocity required to trigger the instability. Using a 1D, non-local thermodynamic equilibrium, radiative transfer model and careful estimates of collision rates and magnetic field strengths, we calculate the trigger velocities necessary to induce the instability throughout the chromosphere. Trigger velocities as low as 4 km s^-1 are found near the temperature minimum, well below the local neutral acoustic speed in that region. From this, we expect the instability to occur frequently, converting kinetic energy contained in neutral convective flows from the photosphere into thermal energy via turbulence. This could contribute significantly to chromospheric heating and explain its persistent and ubiquitous nature.

Athlete shoulder injuries: CT arthrographic findings.

PubMed

Rafii, M; Firooznia, H; Bonamo, J J; Minkoff, J; Golimbu, C

1987-02-01

Forty-three professional and amateur athletes with persistent shoulder pain that interfered with their sports activities were evaluated by computed tomographic (CT) arthrography. In 19 patients, glenohumeral instability (14 anterior, two posterior, three multidirectional) was diagnosed with CT arthrography based on the simultaneous presence of labral and capsular lesions. The findings were crucial in establishing the diagnosis of instability in six patients in whom the condition was not suggested or could not be confirmed clinically. Another significant injury consisted of labral lesions not associated with glenohumeral instability. These tears often involved the anterior and parasuperior segments of this structure. Other, less frequently detected lesions included segmental labral enlargement and several labra with abnormal orientation (everted labrum). Early onset of degenerative disease was present in many athletes, especially those with a long history of sports activity. CT arthrographic findings were correlated with arthroscopic or surgical results in 19 patients.

Expanded complexity of unstable repeat diseases

PubMed Central

Polak, Urszula; McIvor, Elizabeth; Dent, Sharon Y.R.; Wells, Robert D.; Napierala, Marek

2015-01-01

Unstable Repeat Diseases (URDs) share a common mutational phenomenon of changes in the copy number of short, tandemly repeated DNA sequences. More than 20 human neurological diseases are caused by instability, predominantly expansion, of microsatellite sequences. Changes in the repeat size initiate a cascade of pathological processes, frequently characteristic of a unique disease or a small subgroup of the URDs. Understanding of both the mechanism of repeat instability and molecular consequences of the repeat expansions is critical to developing successful therapies for these diseases. Recent technological breakthroughs in whole genome, transcriptome and proteome analyses will almost certainly lead to new discoveries regarding the mechanisms of repeat instability, the pathogenesis of URDs, and will facilitate development of novel therapeutic approaches. The aim of this review is to give a general overview of unstable repeats diseases, highlight the complexities of these diseases, and feature the emerging discoveries in the field. PMID:23233240

Management of failed instability surgery: how to get it right the next time.

PubMed

Boone, Julienne L; Arciero, Robert A

2010-07-01

Traumatic anterior shoulder dislocations are the most frequent type of joint dislocation and affect approximately 1.7% of the general population. The literature supports the consideration of primary stabilization in high-risk patients because of reported recurrences as high as 80% to 90% with nonoperative treatment regimens. Successful stabilization of anterior glenohumeral instability relies on not only good surgical techniques but also careful patient selection. Failure rates after open and arthroscopic stabilization have been reported to range from 2% to 8% and 4% to 13%, respectively. Recurrent shoulder instability leads to increased morbidity to the patient, increased pain, decreased activity level, prolonged time away from work and sports, and a general decrease in quality of life. This article reviews the potential pitfalls in anterior shoulder stabilization and discusses appropriate methods of addressing them in revision surgery. Copyright 2010 Elsevier Inc. All rights reserved.

Filamentation instability in a quantum magnetized plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bret, A.; and Instituto de Investigaciones Energeticas y Aplicaciones Industriales, Campus Universitario de Ciudad Real, 13071 Ciudad Real

2008-02-15

The filamentation instability occurring when a nonrelativistic electron beam passes through a quantum magnetized plasma is investigated by means of a cold quantum magnetohydrodynamic model. It is proved that the instability can be completely suppressed by quantum effects if and only if a finite magnetic field is present. A dimensionless parameter is identified that measures the strength of quantum effects. Strong quantum effects allow for a much smaller magnetic field to suppress the instability than in the classical regime.

A survey of deep tissue injury in elite female wheelchair basketball players.

PubMed

Shimizu, Yukiyo; Mutsuzaki, Hirotaka; Tachibana, Kaori; Tsunoda, Kenji; Hotta, Kazushi; Fukaya, Takashi; Ikeda, Eiji; Yamazaki, Masashi; Wadano, Yasuyoshi

2017-01-01

To investigate deep tissue injuries (DTIs) in elite female wheelchair basketball players and identify factors associated with their occurrence. Study participants were 22 female wheelchair basketball players on the Japanese national team. The sacral and bilateral ischial regions of each participant were examined using ultrasonography to detect DTIs. DTIs were found in 15 players (68.2%). DTIs were more frequent in players with a central nervous system disorder (CNSd) (85.7%) than in those with skeletal system disease (SSd) (37.5%, p = 0.020), and in players using a wheelchair in daily life (84.6%) than those using a wheelchair only for basketball (44.4%, p = 0.046). Players with pelvic instability were more likely to have DTIs (90.9% vs. 45.5%, p = 0.017). DTIs were deeper in the ischial region than the sacral region (p = 0.022). Players with CNSd had more DTIs in sacral regions (90% vs. 10%, p = 0.014). Players with DTIs had lower systolic blood pressure (sBP), red blood cell (RBC) count, and serum creatinine levels (sCr) (all p < 0.05). Ischial DTIs were deeper than sacral DTIs. Players with CNSd had more sacral DTIs than those with SSd. CNSd, wheelchair use in daily life, pelvic instability, and lower sBP, RBC, and sCr increased the risk of DTIs.

Electron-acoustic Instability Simulated By Modified Zakharov Equations

NASA Astrophysics Data System (ADS)

Jásenský, V.; Fiala, V.; Vána, O.; Trávnícek, P.; Hellinger, P.

We present non-linear equations describing processes in plasma when electron - acoustic waves are excited. These waves are present for instance in the vicinity of Earth's bow shock and in the polar ionosphere. Frequently they are excited by an elec- tron beam in a plasma with two electron populations, a cold and hot one. We derive modified Zakharov equations from kinetic theory for such a case together with numer- ical method for solving of this type of equations. Bispectral analysis is used to show which non-linear wave processes are of importance in course of the instability. Finally, we compare these results with similar simulations using Vlasov approach.

Trends in Ankle Arthroscopy and Its Use in the Management of Pathologic Conditions of the Lateral Ankle in the United States: A National Database Study.

PubMed

Werner, Brian C; Burrus, M Tyrrell; Park, Joseph S; Perumal, Venkat; Gwathmey, F Winston

2015-07-01

This study aimed to investigate current trends in ankle arthroscopy across time, sex, age, and region of the United States as well as the use of ankle arthroscopy in the management of lateral ankle instability. Patients who underwent ankle arthroscopy and those who underwent ankle arthroscopy and lateral ankle ligament repair or peroneal retinacular repair from 2007 through 2011 were identified using the PearlDiver national database. These searches yielded volumes of unique patients, sex and age distribution, and regional volumes of patients. Χ-square linear-by-linear association analysis was used for comparisons, with P < .05 considered significant. We identified 15,366 ankle arthroscopy procedures in the database from 2007 to 2011. Over the 5-year study period, there was a significant increase in the overall number of ankle arthroscopies being performed, from 2,814 in 2007 to 3,314 in 2011 (P < .0001). Female patients had ankle arthroscopy more frequently than did male patients (P = .027). The majority of patients who had ankle arthroscopy were between the ages of 30 and 49 years. The use of ankle arthroscopy during lateral ligament repair procedures increased from 37.2% in 2007 to 43.7% in 2011 (P < .0001). The incidence of combined ankle arthroscopy and peroneal tendon retinacular repair increased 50%, from 2.8/100 ankle arthroscopies in 2007 to 4.2/100 ankle arthroscopies in 2011 (P < .0001). The incidence of ankle arthroscopy increased significantly from 2007 to 2011, outpacing shoulder, knee, and elbow arthroscopy. Ankle arthroscopy was performed more frequently in female patients and most commonly in patients younger than 50 years. The use of ankle arthroscopy in the surgical management of lateral ankle instability also increased significantly. The incidence of concomitant ankle arthroscopy and lateral ligament repair increased significantly, as did the incidence of concomitant ankle arthroscopy and repair of peroneal tendon subluxation. Level IV, therapeutic case series. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Development of potential map for landslides by comparing instability indices of various time periods

NASA Astrophysics Data System (ADS)

Chiang, Jie-Lun; Tian, Yu-Qing; Chen, Yie-Ruey; Tsai, Kuang-Jung

2017-04-01

In recent years, extreme rainfall events occur frequently and induced serious landslides and debris flow disasters in Taiwan. The instability indices will differ when using landslide maps of different time periods. We analyzed the landslide records during the period year, 2008 2012, the landslide area contributed 0.42% 2.94% of the total watershed area, the 2.94% was caused by the typhoon Morakot in August, 2009, which brought massive rainfall in which the cumulative maximum rainfall was up to 2900 mm. We analyzed the instability factors including elevation, slope, aspect, soil, and geology. And comparing the instability indices by using individual landslide map of 2008 2012, the landslide maps of the union of the five years, and interaction of the five years. The landslide area from union of the five years contributed 3.71%,the landslide area from interaction of the five years contributed 0.14%. In this study, Kriging was used to establish the susceptibility map in selected watershed. From interaction of the five years, we found the instability index above 4.3 can correspond to those landslide records. The potential landslide area of the selected watershed, where collapses occur more likely, belongs to high level and medium-high level; the area is 13.43% and 3.04% respectively.

Suppression of the Saffman-Taylor instability through injection of a finite slug of polymer

NASA Astrophysics Data System (ADS)

Beeson-Jones, Timothy H.; Woods, Andrew W.

2014-11-01

During secondary oil recovery, relatively mobile water can channel through oil owing to the Saffman-Taylor instability. Injection of a finite slug of polymer solution from a central well prior to the water flood suppresses the growth of the instability by reducing the adverse mobility ratio at the leading interface. A linear stability analysis of an axisymmetric base state identifies how perturbations on the leading and trailing interfaces become coupled. It also reveals the dependence of the long-time algebraic growth of each mode on the mobility ratios across the two interfaces. The viscosity of the polymer solution which minimizes the growth rate of the instability is identified, and the impact of different slug sizes on this growth is described. Funded by EPSRC & BP.

Operative shoulder instability injury management in Australian Football League players: A case series.

PubMed

Bonacci, Jason; Manson, Brent; Bowe, Steven J; Gill, Stephen; Seward, Hugh; Hoy, Greg; Page, Richard

2017-11-27

The purpose of this study was to review the surgical management procedures of shoulder instability injuries in Australian Football League (AFL) players, and determine outcomes regarding return to sport and injury recurrence. Retrospective cohort study. Elite AFL players with shoulder instability resulting in surgery were assessed in a retrospective cohort design (72 players/77 shoulders). Type of initial injury, surgical management, return to sport and injury recurrence were obtained. The mean follow-up period post-surgery was 2.9 years. Return to sport outcomes were compared between arthroscopic and open surgery using a Kaplan-Meier survival analysis. Logistic regression modelling was used to determine associations between injury recurrence, type of injury, participant age and method of surgery. Shoulder instability injuries occurred most frequently during tackling (40%). Arthroscopic surgery was preferred for primary shoulder instability. Nine (16%) recurrences occurred in those who underwent arthroscopic surgery compared to two (9%) following open surgery. Return to the elite level was slightly but significantly (2 weeks, p=0.049) longer for open compared to arthroscopic surgery. Recurrence was 5 times more likely if the primary injury was a dislocation and more likely in players who were younger at the time of surgery. Tackling was the predominant mechanism for shoulder instability injuries in AFL players and arthroscopic surgery was more commonly performed for primary injuries. Sustaining a dislocation as the primary injury and younger age increased the likelihood of recurrent instability. Careful consideration should be given to the operative management of these individuals. Copyright © 2017. Published by Elsevier Ltd.

Status of NASA full-scale engine aeroelasticity research

NASA Technical Reports Server (NTRS)

Lubomski, J. F.

1980-01-01

Data relevant to several types of aeroelastic instabilities were obtained using several types of turbojet and turbofan engines. In particular, data relative to separated flow (stall) flutter, choke flutter, and system mode instabilities are presented. The unique characteristics of these instabilities are discussed, and a number of correlations are presented that help identify the nature of the phenomena.

Rotordynamic Instability Problems in High-Performance Turbomachinery

NASA Technical Reports Server (NTRS)

1980-01-01

Diagnostic and remedial methods concerning rotordynamic instability problems in high performance turbomachinery are discussed. Instabilities due to seal forces and work-fluid forces are identified along with those induced by rotor bearing systems. Several methods of rotordynamic control are described including active feedback methods, the use of elastometric elements, and the use of hydrodynamic journal bearings and supports.

Multiple sclerosis and employment: Associations of psychological factors and work instability.

PubMed

Wicks, Charlotte Rose; Ward, Karl; Stroud, Amanda; Tennant, Alan; Ford, Helen L

2016-10-12

People with multiple sclerosis often stop working earlier than expected. Psychological factors may have an impact on job retention. Investigation may inform interventions to help people stay in work. To investigate the associations between psychological factors and work instability in people with multiple sclerosis. A multi-method, 2-phased study. Focus groups were held to identify key themes. Questionnaire packs using validated scales of the key themes were completed at baseline and at 8-month follow-up. Four key psychological themes emerged. Out of 208 study subjects 57.2% reported medium/high risk of job loss, with marginal changes at 8 months. Some psychological variables fluctuated significantly, e.g. depression fell from 24.6% to 14.5%. Work instability and anxiety and depression were strongly correlated (χ2 p < 0.001). Those with probable depression at baseline had 7.1 times increased odds of medium/high work instability, and baseline depression levels also predicted later work instability (Hosmer-Lemeshow test 0.899; Nagelkerke R Square 0.579). Psychological factors fluctuated over the 8-month follow-up period. Some psychological variables, including anxiety and depression, were significantly associated with, and predictive of, work instability. Longitudinal analysis should further identify how these psychological attributes impact on work instability and potential job loss in the longer term.

Lunate fractures and associated radiocarpal and midcarpal instabilities: a systematic review.

PubMed

Shunmugam, Meenalochani; Phadnis, Joideep; Watts, Amy; Bain, Gregory I

2018-01-01

The aim of this study was to analyse lunate fractures and any associated osseo-ligamentous injuries. A systematic review identified 34 cases. We identified carpal instabilities at the radiocarpal and midcarpal joints in volar and dorsal directions. Radiocarpal instabilities (10/34) were usually dorsoradial (8/10), with a transverse lunate fracture, best seen on a coronal image. Midcarpal instabilities (24/34) were usually volar (14/18), with a volar lunate shear fracture, best seen on a sagittal image. Instabilities were sub-classified into non-displaced, subluxated and dislocated. Associated fractures of the scaphoid and the radial and ulnar styloid processes were common. Lunate fractures without subluxation or dislocation had good outcomes with cast immobilization or fixation of associated fractures. Lunate fracture-subluxations are unstable injuries that are best managed with fixation of the carpal fractures. Lunate fracture-dislocations are complex injuries, requiring stabilization of the lunate, associated fractures and ligament injuries; complications are common and acute or delayed salvage procedures may be required.

Subspine impingement: 2 case reports of a previously unreported cause of instability in total hip arthroplasty.

PubMed

Davidovitch, Roy I; DelSole, Edward M; Vigdorchik, Jonathan M

2016-03-23

Instability is a common cause of revision hip arthroplasty and is frequently due to improper component placement and subsequent component impingement. Impingement of the greater trochanter upon the anterior inferior iliac spine (AIIS) has been described as a cause of symptomatic femoroacetabular impingement (FAI), but has never been described as a cause of instability following total hip arthroplasty (THA). We present 2 cases of patients undergoing THA. Each patient was evaluated preoperatively and found to have a prominent AIIS, which was concerning due to it overhanging the anterolateral acetabular lip. Both patients had intraoperative posterior instability of their THA, the cause of which was determined to be impingement of the greater trochanter upon a prominent AIIS. Open resection of the AIIS was performed with subsequent resolution of impingement. AIIS impingement has been reported as a cause of symptomatic FAI. In these case reports, open or arthroscopic resection of the AIIS resulted in resolution of symptoms. Morphologically distinct subtypes of the AIIS have been previously described based upon computed tomography, and some subtypes are associated with a high risk of impingement in the native hip. No previous studies have described this phenomenon in the setting of THA. Instability is a common cause of revision THA. Impingement of the greater trochanter upon a prominent AIIS is a previously unreported cause of THA instability which can be addressed with intraoperative resection of the AIIS with good result.

Value of stress ultrasound for the diagnosis of chronic ankle instability compared to manual anterior drawer test, stress radiography, magnetic resonance imaging, and arthroscopy.

PubMed

Cho, Jae Ho; Lee, Doo Hyung; Song, Hyung Keun; Bang, Joon Young; Lee, Kyung Tai; Park, Young Uk

2016-04-01

Clinicians frequently diagnose chronic ankle instability using the manual anterior drawer test and stress radiography. However, both examinations can yield incorrect results and do not reveal the extent of ankle instability. Stress ultrasound has been reported to be a new diagnostic tool for the diagnosis of chronic ankle instability. The purpose of this study was to assess the diagnostic value of stress ultrasound for chronic ankle instability compared to the manual anterior drawer test, stress radiography, magnetic resonance imaging (MRI), and arthroscopy. Twenty-eight consecutive patients who underwent ankle arthroscopy and subsequent modified Broström repair for treatment of chronic ankle instability were included. The arthroscopic findings were used as the reference standard. A standardized physical examination (manual anterior drawer test), stress radiography, MRI, and stress ultrasound were performed to assess the anterior talofibular ligament (ATFL) prior to operation. Ultrasound images were taken in the resting position and the maximal anterior drawer position. Grade 3 lateral instability was verified arthroscopically in all 28 cases with a clinical diagnosis (100%). Twenty-two cases showed grade III instability on the manual anterior drawer test (78.6%). Twenty-four cases displayed anterior translation exceeding 5 mm on stress radiography (86%), and talar tilt angle exceeded 15° in three cases (11 %). Nineteen cases displayed a partial chronic tear (change in thickness or signal intensity), and nine cases displayed complete tear on MRI (100%). Lax and wavy ATFL was evident on stress ultrasound in all cases (100 %). The mean value of the ATFL length was 2.8 ± 0.3 cm for the stressed condition and 2.1 ± 0.2 cm for the resting condition (p < 0.001). Stress ultrasound may be useful for the diagnosis of chronic ankle instability in addition to the manual anterior drawer test and stress radiography. III.

Carotid interventions and blood pressure.

PubMed

Hirschl, Mirko; Kundi, Michael

2014-12-01

Arterial baroreceptors are pressure sensors found in the carotid sinus near the bifurcation of the carotid artery and in the aortic arch. Carotid interventions, whether endovascular or surgical, affect this complicated control system and the post-interventional blood pressure behavior. Comparisons between the intervention techniques, however, are challenging due to the varying measurement methods, duration of observation, and patient populations. The question as to which interventional method is preferable, if undisturbed regulation of blood pressure is concerned, still remains unanswered. The fact that blood pressure events (i.e., hemodynamic instability, hypertension, unstable blood pressure) frequently occur both immediately after intervention and in the long term, mandates a particularly careful cardiopulmonary and blood pressure monitoring. Direct and indirect measurements of baroreceptor sensitivity can be helpful in identifying high-risk patients, although the association to hard clinical endpoints is rarely documented for methodological reasons.

A giant, submarine creep zone as a precursor of large-scale slope instability offshore the Dongsha Islands (South China Sea)

NASA Astrophysics Data System (ADS)

Li, Wei; Alves, Tiago M.; Wu, Shiguo; Rebesco, Michele; Zhao, Fang; Mi, Lijun; Ma, Benjun

2016-10-01

A giant submarine creep zone exceeding 800 km2 on the continental slope offshore the Dongsha Islands, South China Sea, is investigated using bathymetric and 3D seismic data tied to borehole information. The submarine creep zone is identified as a wide area of seafloor undulations with ridges and troughs. The troughs form NW- and WNW-trending elongated depressions separating distinct seafloor ridges, which are parallel or sub-parallel to the continental slope. The troughs are 0.8-4.7 km-long and 0.4 to 2.1 km-wide. The ridges have wavelengths of 1-4 km and vertical relief of 10-30 m. Slope strata are characterised by the presence of vertically stacked ridges and troughs at different stratigraphic depths, but remaining relatively stationary in their position. The interpreted ridges and troughs are associated with large-scale submarine creep, and the troughs can be divided into three types based on their different internal characters and formation processes. The large-scale listric faults trending downslope below MTD 1 and horizon T0 may be the potential glide planes for the submarine creep movement. High sedimentation rates, local fault activity and the frequent earthquakes recorded on the margin are considered as the main factors controlling the formation of this giant submarine creep zone. Our results are important to the understanding of sediment instability on continental slopes as: a) the interpreted submarine creep is young, or even active at present, and b) areas of creeping may evolve into large-scale slope instabilities, as recorded by similar large-scale events in the past.

A mobile threat to genome stability: The impact of non-LTR retrotransposons upon the human genome.

PubMed

Konkel, Miriam K; Batzer, Mark A

2010-08-01

It is now commonly agreed that the human genome is not the stable entity originally presumed. Deletions, duplications, inversions, and insertions are common, and contribute significantly to genomic structural variations (SVs). Their collective impact generates much of the inter-individual genomic diversity observed among humans. Not only do these variations change the structure of the genome; they may also have functional implications, e.g. altered gene expression. Some SVs have been identified as the cause of genetic disorders, including cancer predisposition. Cancer cells are notorious for their genomic instability, and often show genomic rearrangements at the microscopic and submicroscopic level to which transposable elements (TEs) contribute. Here, we review the role of TEs in genome instability, with particular focus on non-LTR retrotransposons. Currently, three non-LTR retrotransposon families - long interspersed element 1 (L1), SVA (short interspersed element (SINE-R), variable number of tandem repeats (VNTR), and Alu), and Alu (a SINE) elements - mobilize in the human genome, and cause genomic instability through both insertion- and post-insertion-based mutagenesis. Due to the abundance and high sequence identity of TEs, they frequently mislead the homologous recombination repair pathway into non-allelic homologous recombination, causing deletions, duplications, and inversions. While less comprehensively studied, non-LTR retrotransposon insertions and TE-mediated rearrangements are probably more common in cancer cells than in healthy tissue. This may be at least partially attributed to the commonly seen global hypomethylation as well as general epigenetic dysfunction of cancer cells. Where possible, we provide examples that impact cancer predisposition and/or development. Copyright © 2010 Elsevier Ltd. All rights reserved.

Classification of instability after reverse shoulder arthroplasty guides surgical management and outcomes.

PubMed

Abdelfattah, Adham; Otto, Randall J; Simon, Peter; Christmas, Kaitlyn N; Tanner, Gregory; LaMartina, Joey; Levy, Jonathan C; Cuff, Derek J; Mighell, Mark A; Frankle, Mark A

2018-04-01

Revision of unstable reverse shoulder arthroplasty (RSA) remains a significant challenge. The purpose of this study was to determine the reliability of a new treatment-guiding classification for instability after RSA, to describe the clinical outcomes of patients stabilized operatively, and to identify those with higher risk of recurrence. All patients undergoing revision for instability after RSA were identified at our institution. Demographic, clinical, radiographic, and intraoperative data were collected. A classification was developed using all identified causes of instability after RSA and allocating them to 1 of 3 defined treatment-guiding categories. Eight surgeons reviewed all data and applied the classification scheme to each case. Interobserver and intraobserver reliability was used to evaluate the classification scheme. Preoperative clinical outcomes were compared with final follow-up in stabilized shoulders. Forty-three revision cases in 34 patients met the inclusion for study. Five patients remained unstable after revision. Persistent instability most commonly occurred in persistent deltoid dysfunction and postoperative acromial fractures but also in 1 case of soft tissue impingement. Twenty-one patients remained stable at minimum 2 years of follow-up and had significant improvement of clinical outcome scores and range of motion. Reliability of the classification scheme showed substantial and almost perfect interobserver and intraobserver agreement among all the participants (κ = 0.699 and κ = 0.851, respectively). Instability after RSA can be successfully treated with revision surgery using the reliable treatment-guiding classification scheme presented herein. However, more understanding is needed for patients with greater risk of recurrent instability after revision surgery. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Genome-wide analysis in UK Biobank identifies four loci associated with mood instability and genetic correlation with major depressive disorder, anxiety disorder and schizophrenia.

PubMed

Ward, Joey; Strawbridge, Rona J; Bailey, Mark E S; Graham, Nicholas; Ferguson, Amy; Lyall, Donald M; Cullen, Breda; Pidgeon, Laura M; Cavanagh, Jonathan; Mackay, Daniel F; Pell, Jill P; O'Donovan, Michael; Escott-Price, Valentina; Smith, Daniel J

2017-11-30

Mood instability is a core clinical feature of affective and psychotic disorders. In keeping with the Research Domain Criteria approach, it may be a useful construct for identifying biology that cuts across psychiatric categories. We aimed to investigate the biological validity of a simple measure of mood instability and evaluate its genetic relationship with several psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, attention deficit hyperactivity disorder (ADHD), anxiety disorder and post-traumatic stress disorder (PTSD). We conducted a genome-wide association study (GWAS) of mood instability in 53,525 cases and 60,443 controls from UK Biobank, identifying four independently associated loci (on chromosomes 8, 9, 14 and 18), and a common single-nucleotide polymorphism (SNP)-based heritability estimate of ~8%. We found a strong genetic correlation between mood instability and MDD (r g  = 0.60, SE = 0.07, p = 8.95 × 10 -17 ) and a small but significant genetic correlation with both schizophrenia (r g  = 0.11, SE = 0.04, p = 0.01) and anxiety disorders (r g  = 0.28, SE = 0.14, p = 0.04), although no genetic correlation with BD, ADHD or PTSD was observed. Several genes at the associated loci may have a role in mood instability, including the DCC netrin 1 receptor (DCC) gene, eukaryotic translation initiation factor 2B subunit beta (eIF2B2), placental growth factor (PGF) and protein tyrosine phosphatase, receptor type D (PTPRD). Strengths of this study include the very large sample size, but our measure of mood instability may be limited by the use of a single question. Overall, this work suggests a polygenic basis for mood instability. This simple measure can be obtained in very large samples; our findings suggest that doing so may offer the opportunity to illuminate the fundamental biology of mood regulation.

Family Mobility and Neighborhood Change: New Evidence and Implications for Community Initiatives

ERIC Educational Resources Information Center

Coulton, Claudia; Theodos, Brett; Turner, Margery A.

2009-01-01

Americans change residences frequently. Residential mobility can reflect positive changes in a family's circumstances or be a symptom of instability and insecurity. Mobility may also change neighborhoods as a whole. To shed light on these challenges, this report uses a unique survey conducted for the "Making Connections" initiative. The…

Post-midnight equatorial irregularity distributions and vertical drift velocity variations during solstices

NASA Astrophysics Data System (ADS)

Su, S.-Y.; Liu, C. H.; Chao, C.-K.

2018-04-01

Longitudinal distributions of post-midnight equatorial ionospheric irregularity occurrences observed by ROCSAT-1 (1st satellite of the Republic of China) during moderate to high solar activity years in two solstices are studied with respect to the vertical drift velocity and density variations. The post-midnight irregularity distributions are found to be similar to the well-documented pre-midnight ones, but are different from some published distributions taken during solar minimum years. Even though the post-midnight ionosphere is sinking in general, longitudes of frequent positive vertical drift and high density seems to coincide with the longitudes of high irregularity occurrences. Large scatters found in the vertical drift velocity and density around the dip equator in different ROCSAT-1 orbits indicate the existence of large and frequent variations in the vertical drift velocity and density that seem to be able to provide sufficient perturbations for the Rayleigh-Taylor (RT) instability to cause the irregularity occurrences. The need of seeding agents such as gravity waves from atmospheric convective clouds to initiate the Rayleigh-Taylor instability may not be necessary.

[Glenohumeral instability in patients over 40 years-old: injuries, treatment and complications].

PubMed

López-Hualda, A; Marín-Aguado, M A; Valencia-García, H; López-González, D; Gavín-González, C

2014-01-01

Recurrent shoulder dislocation is infrequent after forty years and presents different injuries than younger patients. To compare injuries and complications after surgery between one group older than forty years of age and another younger group. A review was made o all patients who had undergone arthroscopic surgery due to glenohumeral instability from 1999 until 2011. The mean follow-up was 64 months. The case group consisted of all patients older than 40 years at the time of the surgery (n=21), which was compared with a similar sized control group of randomly selected younger patients (n=27). The mean age in the older group was 54 years (SD 11.86), while it was 26 years (SD 5.80) in the younger group. No differences were founded between both groups in labrum injury, Hill-Sachs injury, and bone Bankart lesion (P>.05). Rotator cuff tears were 7.3 times (95% CI; 2.5-21.6) more frequent in the older group (81%) compared to the younger group (P<.05). However, neurological injuries after dislocation were not more frequent in this group. There was no significant difference between the complications after surgery and the age according to the design (P>.05). Anterior recurrent dislocation after forty years of age is usually associated with rotator cuff tears. Arthroscopic treatment of instability was effective with no more postoperative complications. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

Regularization of instabilities in gravity theories

NASA Astrophysics Data System (ADS)

Ramazanoǧlu, Fethi M.

2018-01-01

We investigate instabilities and their regularization in theories of gravitation. Instabilities can be beneficial since their growth often leads to prominent observable signatures, which makes them especially relevant to relatively low signal-to-noise ratio measurements such as gravitational wave detections. An indefinitely growing instability usually renders a theory unphysical; hence, a desirable instability should also come with underlying physical machinery that stops the growth at finite values, i.e., regularization mechanisms. The prototypical gravity theory that presents such an instability is the spontaneous scalarization phenomena of scalar-tensor theories, which feature a tachyonic instability. We identify the regularization mechanisms in this theory and show that they can be utilized to regularize other instabilities as well. Namely, we present theories in which spontaneous growth is triggered by a ghost rather than a tachyon and numerically calculate stationary solutions of scalarized neutron stars in these theories. We speculate on the possibility of regularizing known divergent instabilities in certain gravity theories using our findings and discuss alternative theories of gravitation in which regularized instabilities may be present. Even though we study many specific examples, our main point is the recognition of regularized instabilities as a common theme and unifying mechanism in a vast array of gravity theories.

Fast flows, ULF waves, firehose instability and their association in the Earth's mid-tail current sheet

NASA Astrophysics Data System (ADS)

Wang, C. P.; Xing, X.

2017-12-01

Ultra-Low Frequency (ULF) plasma waves with frequency range between 1 mHz to 10 Hz are widely observed in the Earth's magnetosphere and on the ground. In particular, Pi2 and Pc4 waves have been found to be closely related to many important dynamic processes in the magnetotail, e.g., fast flows (V > 300 km/s). Observations have shown Pi2 waves in association with fast flows in the near-Earth plasma sheet (X>-30 RE). However, in the mid-tail region, where fast flows are more frequently observed than those in the near-Earth magnetotail, this association has not been evaluated. Our preliminary study using ARTEMIS probes in the mid-tail region (X -60 RE) shows close association between Pi2 and Pc4 waves with the presence of fast flows. Strong connection between mid-tail Pi2 pulsations and high-latitude ground Pi2 signatures are also observed. Among many proposed theories for Pi2 wave, ballooning and firehose instabilities are plausible mechanisms in leading to the generation of plasma waves around Pi2 frequency band. Ballooning instability is widely admitted for fast flow associated Pi2 pulsations in the near-Earth region. However, firehose instability is expected to occur more easily in mid-tail and beyond due to the specific pressure anisotropy in that region. We examined the pressure anisotropy conditions and evaluated firehose instability condition for both Pi2 and Pc4 events in mid-tail. It is found that the plasma is unstable against firehose instability in association with the initiation of Pi2 and Pc4 waves. These may suggest that firehose instability can be a wave generation mechanism in the mid-tail region.

Understanding Transient Forcing with Plasma Instability Model, Ionospheric Propagation Model and GNSS Observations

NASA Astrophysics Data System (ADS)

Deshpande, K.; Zettergren, M. D.; Datta-Barua, S.

2017-12-01

Fluctuations in the Global Navigation Satellite Systems (GNSS) signals observed as amplitude and phase scintillations are produced by plasma density structures in the ionosphere. Phase scintillation events in particular occur due to structures at Fresnel scales, typically about 250 meters at ionospheric heights and GNSS frequency. Likely processes contributing to small-scale density structuring in auroral and polar regions include ionospheric gradient-drift instability (GDI) and Kelvin-Helmholtz instability (KHI), which result, generally, from magnetosphere-ionosphere interactions (e.g. reconnection) associated with cusp and auroral zone regions. Scintillation signals, ostensibly from either GDI or KHI, are frequently observed in the high latitude ionosphere and are potentially useful diagnostics of how energy from the transient forcing in the cusp or polar cap region cascades, via instabilities, to small scales. However, extracting quantitative details of instabilities leading to scintillation using GNSS data drastically benefits from both a model of the irregularities and a model of GNSS signal propagation through irregular media. This work uses a physics-based model of the generation of plasma density irregularities (GEMINI - Geospace Environment Model of Ion-Neutral Interactions) coupled to an ionospheric radio wave propagation model (SIGMA - Satellite-beacon Ionospheric-scintillation Global Model of the upper Atmosphere) to explore the cascade of density structures from medium to small (sub-kilometer) scales. Specifically, GEMINI-SIGMA is used to simulate expected scintillation from different instabilities during various stages of evolution to determine features of the scintillation that may be useful to studying ionospheric density structures. Furthermore we relate the instabilities producing GNSS scintillations to the transient space and time-dependent magnetospheric phenomena and further predict characteristics of scintillation in different geophysical situations. Finally we present initial comparison of our modeling results with GNSS scintillation observed via an array of receivers at Poker Flat.

Electromagnetic Components of Auroral Hiss and Lower Hybrid Waves in the Polar Magnetosphere

NASA Technical Reports Server (NTRS)

Wong, H. K.

1995-01-01

DE-1 has frequently observed waves in the whistler and lower hybrid frequencies range. Besides the electrostatic components, these waves also exhibit electromagnetic components. It is generally believed that these waves are excited by the electron acoustic instability and the electron-beam-driven lower hybrid instability. Because the electron acoustic and the lower hybrid waves are predominately electrostatic waves, they cannot account for the observed electromagnetic components. In this work, it is suggested that these electromagnetic components can be explained by waves that are generated near the resonance cone and that propagate away from the source. The role that these electromagnetic waves can play in particle acceleration processes at low altitude is discussed.

Importance of Resolving the Spectral Support of Beam-plasma Instabilities in Simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shalaby, Mohamad; Broderick, Avery E.; Chang, Philip

2017-10-20

Many astrophysical plasmas are prone to beam-plasma instabilities. For relativistic and dilute beams, the spectral support of the beam-plasma instabilities is narrow, i.e., the linearly unstable modes that grow with rates comparable to the maximum growth rate occupy a narrow range of wavenumbers. This places stringent requirements on the box-sizes when simulating the evolution of the instabilities. We identify the implied lower limits on the box size imposed by the longitudinal beam plasma instability, i.e., typically the most stringent condition required to correctly capture the linear evolution of the instabilities in multidimensional simulations. We find that sizes many orders ofmore » magnitude larger than the resonant wavelength are typically required. Using one-dimensional particle-in-cell simulations, we show that the failure to sufficiently resolve the spectral support of the longitudinal instability yields slower growth and lower levels of saturation, potentially leading to erroneous physical conclusion.« less

Tertiary instability of zonal flows within the Wigner-Moyal formulation of drift turbulence

NASA Astrophysics Data System (ADS)

Zhu, Hongxuan; Ruiz, D. E.; Dodin, I. Y.

2017-10-01

The stability of zonal flows (ZFs) is analyzed within the generalized-Hasegawa-Mima model. The necessary and sufficient condition for a ZF instability, which is also known as the tertiary instability, is identified. The qualitative physics behind the tertiary instability is explained using the recently developed Wigner-Moyal formulation and the corresponding wave kinetic equation (WKE) in the geometrical-optics (GO) limit. By analyzing the drifton phase space trajectories, we find that the corrections proposed in Ref. to the WKE are critical for capturing the spatial scales characteristic for the tertiary instability. That said, we also find that this instability itself cannot be adequately described within a GO formulation in principle. Using the Wigner-Moyal equations, which capture diffraction, we analytically derive the tertiary-instability growth rate and compare it with numerical simulations. The research was sponsored by the U.S. Department of Energy.

Association between genomic instability and evolutionary chromosomal rearrangements in Neotropical Primates.

PubMed

Puntieri, Fiona; Andrioli, Nancy B; Nieves, Mariela

2018-06-14

During the last decades the mammalian genome has been proposed to have regions prone to breakage and reorganization concentrated in certain chromosomal bands that seem to correspond to evolutionary breakpoints. These bands are likely to be involved in chromosome fragility or instability. In Primates, some biomarkers of genetic damage may be associated with various degrees of genomic instability. Here, we investigated the usefulness of Sister Chromatid Exchange (SCE) as a biomarker of potential sites of frequent chromosome breakage and rearrangement in Alouatta caraya, Ateles chamek, Ateles paniscus and Cebus cay. These Neotropical species have particular genomic and chromosomal features allowing the analysis of genomic instability for comparative purposes. We determined the frequency of spontaneous induction of SCEs and assessed the relationship between these and structural rearrangements implicated in the evolution of the primates of interest. Overall, A. caraya and C. cay presented a low proportion of statistically significant unstable bands, suggesting fairly stable genomes and the existence of some kind of protection against endogenous damage. In contrast, Ateles showed a highly significant proportion of unstable bands; these were mainly found in the rearranged regions, which is consistent with the numerous genomic reorganizations that might have occurred during the evolution of this genus.

Active damping of the e-p instability at the Los Alamos Proton Storage Ring

NASA Astrophysics Data System (ADS)

Macek, R. J.; Assadi, S.; Byrd, J. M.; Deibele, C. E.; Henderson, S. D.; Lee, S. Y.; McCrady, R. C.; Pivi, M. F. T.; Plum, M. A.; Walbridge, S. B.; Zaugg, T. J.

2007-12-01

A prototype of an analog, transverse (vertical) feedback system for active damping of the two-stream (e-p) instability has been developed and successfully tested at the Los Alamos Proton Storage Ring (PSR). This system was able to improve the instability threshold by approximately 30% (as measured by the change in RF buncher voltage at instability threshold). The feedback system configuration, setup procedures, and optimization of performance are described. Results of several experimental tests of system performance are presented including observations of instability threshold improvement and grow-damp experiments, which yield estimates of instability growth and damping rates. A major effort was undertaken to identify and study several factors limiting system performance. Evidence obtained from these tests suggests that performance of the prototype was limited by higher instability growth rates arising from beam leakage into the gap at lower RF buncher voltage and the onset of instability in the horizontal plane, which had no feedback.

Management and prevention of acute and chronic lateral ankle instability in athletic patient populations

PubMed Central

McCriskin, Brendan J; Cameron, Kenneth L; Orr, Justin D; Waterman, Brian R

2015-01-01

Acute and chronic lateral ankle instability are common in high-demand patient populations. If not managed appropriately, patients may experience recurrent instability, chronic pain, osteochondral lesions of the talus, premature osteoarthritis, and other significant long-term disability. Certain populations, including young athletes, military personnel and those involved in frequent running, jumping, and cutting motions, are at increased risk. Proposed risk factors include prior ankle sprain, elevated body weight or body mass index, female gender, neuromuscular deficits, postural imbalance, foot/ankle malalignment, and exposure to at-risk athletic activity. Prompt, accurate diagnosis is crucial, and evidence-based, functional rehabilitation regimens have a proven track record in returning active patients to work and sport. When patients fail to improve with physical therapy and external bracing, multiple surgical techniques have been described with reliable results, including both anatomic and non-anatomic reconstructive methods. Anatomic repair of the lateral ligamentous complex remains the gold standard for recurrent ankle instability, and it effectively restores native ankle anatomy and joint kinematics while preserving physiologic ankle and subtalar motion. Further preventative measures may minimize the risk of ankle instability in athletic cohorts, including prophylactic bracing and combined neuromuscular and proprioceptive training programs. These interventions have demonstrated benefit in patients at heightened risk for lateral ankle sprain and allow active cohorts to return to full activity without adversely affecting athletic performance. PMID:25793157

Management and prevention of acute and chronic lateral ankle instability in athletic patient populations.

PubMed

McCriskin, Brendan J; Cameron, Kenneth L; Orr, Justin D; Waterman, Brian R

2015-03-18

Acute and chronic lateral ankle instability are common in high-demand patient populations. If not managed appropriately, patients may experience recurrent instability, chronic pain, osteochondral lesions of the talus, premature osteoarthritis, and other significant long-term disability. Certain populations, including young athletes, military personnel and those involved in frequent running, jumping, and cutting motions, are at increased risk. Proposed risk factors include prior ankle sprain, elevated body weight or body mass index, female gender, neuromuscular deficits, postural imbalance, foot/ankle malalignment, and exposure to at-risk athletic activity. Prompt, accurate diagnosis is crucial, and evidence-based, functional rehabilitation regimens have a proven track record in returning active patients to work and sport. When patients fail to improve with physical therapy and external bracing, multiple surgical techniques have been described with reliable results, including both anatomic and non-anatomic reconstructive methods. Anatomic repair of the lateral ligamentous complex remains the gold standard for recurrent ankle instability, and it effectively restores native ankle anatomy and joint kinematics while preserving physiologic ankle and subtalar motion. Further preventative measures may minimize the risk of ankle instability in athletic cohorts, including prophylactic bracing and combined neuromuscular and proprioceptive training programs. These interventions have demonstrated benefit in patients at heightened risk for lateral ankle sprain and allow active cohorts to return to full activity without adversely affecting athletic performance.

The multi-species Farley-Buneman instability in the solar chromosphere

DOE Office of Scientific and Technical Information (OSTI.GOV)

Madsen, Chad A.; Dimant, Yakov S.; Oppenheim, Meers M.

2014-03-10

Empirical models of the solar chromosphere show intense electron heating immediately above its temperature minimum. Mechanisms such as resistive dissipation and shock waves appear insufficient to account for the persistence and uniformity of this heating as inferred from both UV lines and continuum measurements. This paper further develops the theory of the Farley-Buneman instability (FBI) which could contribute substantially to this heating. It expands upon the single-ion theory presented by Fontenla by developing a multiple-ion-species approach that better models the diverse, metal-dominated ion plasma of the solar chromosphere. This analysis generates a linear dispersion relationship that predicts the critical electronmore » drift velocity needed to trigger the instability. Using careful estimates of collision frequencies and a one-dimensional, semi-empirical model of the chromosphere, this new theory predicts that the instability may be triggered by velocities as low as 4 km s{sup -1}, well below the neutral acoustic speed. In the Earth's ionosphere, the FBI occurs frequently in situations where the instability trigger speed significantly exceeds the neutral acoustic speed. From this, we expect neutral flows rising from the photosphere to have enough energy to easily create electric fields and electron Hall drifts with sufficient amplitude to make the FBI common in the chromosphere. If so, this process will provide a mechanism to convert neutral flow and turbulence energy into electron thermal energy in the quiet Sun.« less

The Multi-species Farley-Buneman Instability in the Solar Chromosphere

NASA Astrophysics Data System (ADS)

Madsen, Chad A.; Dimant, Yakov S.; Oppenheim, Meers M.; Fontenla, Juan M.

2014-03-01

Empirical models of the solar chromosphere show intense electron heating immediately above its temperature minimum. Mechanisms such as resistive dissipation and shock waves appear insufficient to account for the persistence and uniformity of this heating as inferred from both UV lines and continuum measurements. This paper further develops the theory of the Farley-Buneman instability (FBI) which could contribute substantially to this heating. It expands upon the single-ion theory presented by Fontenla by developing a multiple-ion-species approach that better models the diverse, metal-dominated ion plasma of the solar chromosphere. This analysis generates a linear dispersion relationship that predicts the critical electron drift velocity needed to trigger the instability. Using careful estimates of collision frequencies and a one-dimensional, semi-empirical model of the chromosphere, this new theory predicts that the instability may be triggered by velocities as low as 4 km s-1, well below the neutral acoustic speed. In the Earth's ionosphere, the FBI occurs frequently in situations where the instability trigger speed significantly exceeds the neutral acoustic speed. From this, we expect neutral flows rising from the photosphere to have enough energy to easily create electric fields and electron Hall drifts with sufficient amplitude to make the FBI common in the chromosphere. If so, this process will provide a mechanism to convert neutral flow and turbulence energy into electron thermal energy in the quiet Sun.

Sudden onset odontoid fracture caused by cervical instability in hypotonic cerebral palsy.

PubMed

Shiohama, Tadashi; Fujii, Katsunori; Kitazawa, Katsuhiko; Takahashi, Akiko; Maemoto, Tatsuo; Honda, Akihito

2013-11-01

Fractures of the upper cervical spine rarely occur but carry a high rate of mortality and neurological disabilities in children. Although odontoid fractures are commonly caused by high-impact injuries, cerebral palsy children with cervical instability have a risk of developing spinal fractures even from mild trauma. We herein present the first case of an odontoid fracture in a 4-year-old boy with cerebral palsy. He exhibited prominent cervical instability due to hypotonic cerebral palsy from infancy. He suddenly developed acute respiratory failure, which subsequently required mechanical ventilation. Neuroimaging clearly revealed a type-III odontoid fracture accompanied by anterior displacement with compression of the cervical spinal cord. Bone mineral density was prominently decreased probably due to his long-term bedridden status and poor nutritional condition. We subsequently performed posterior internal fixation surgically using an onlay bone graft, resulting in a dramatic improvement in his respiratory failure. To our knowledge, this is the first report of an odontoid fracture caused by cervical instability in hypotonic cerebral palsy. Since cervical instability and decreased bone mineral density are frequently associated with cerebral palsy, odontoid fractures should be cautiously examined in cases of sudden onset respiratory failure and aggravated weakness, especially in hypotonic cerebral palsy patients. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Pathways and Mechanisms that Prevent Genome Instability in Saccharomyces cerevisiae

PubMed Central

Putnam, Christopher D.; Kolodner, Richard D.

2017-01-01

Genome rearrangements result in mutations that underlie many human diseases, and ongoing genome instability likely contributes to the development of many cancers. The tools for studying genome instability in mammalian cells are limited, whereas model organisms such as Saccharomyces cerevisiae are more amenable to these studies. Here, we discuss the many genetic assays developed to measure the rate of occurrence of Gross Chromosomal Rearrangements (called GCRs) in S. cerevisiae. These genetic assays have been used to identify many types of GCRs, including translocations, interstitial deletions, and broken chromosomes healed by de novo telomere addition, and have identified genes that act in the suppression and formation of GCRs. Insights from these studies have contributed to the understanding of pathways and mechanisms that suppress genome instability and how these pathways cooperate with each other. Integrated models for the formation and suppression of GCRs are discussed. PMID:28684602

Vibration analyzer

NASA Technical Reports Server (NTRS)

Bozeman, Richard J., Jr. (Inventor)

1990-01-01

The invention relates to monitoring circuitry for the real time detection of vibrations of a predetermined frequency and which are greater than a predetermined magnitude. The circuitry produces an instability signal in response to such detection. The circuitry is particularly adapted for detecting instabilities in rocket thrusters, but may find application with other machines such as expensive rotating machinery, or turbines. The monitoring circuitry identifies when vibration signals are present having a predetermined frequency of a multi-frequency vibration signal which has an RMS energy level greater than a predetermined magnitude. It generates an instability signal only if such a vibration signal is identified. The circuitry includes a delay circuit which responds with an alarm signal only if the instability signal continues for a predetermined time period. When used with a rocket thruster, the alarm signal may be used to cut off the thruster if such thruster is being used in flight. If the circuitry is monitoring tests of the thruster, it generates signals to change the thruster operation, for example, from pulse mode to continuous firing to determine if the instability of the thruster is sustained once it is detected.

Failure of operative treatment for glenohumeral instability: etiology and management.

PubMed

Shah, Apurva S; Karadsheh, Mark S; Sekiya, Jon K

2011-05-01

Failure of primary shoulder stabilization procedures is often related to uncorrected anatomic pathology. Orthopaedic surgeons must recognize excessive capsular laxity or large glenohumeral bone defects preoperatively to avoid recurrence of instability. When history, physical examination, and radiographic evaluation are used in conjunction, patients at risk for failure can be identified. The instability severity index score permits precise identification of patients at risk. When treating patients in whom prior surgical intervention has failed, the success of revision procedures correlates to the surgeon's ability to identify the essential pathology and use lesion-specific treatment strategies. Revision procedures remain technically demanding. Keen preoperative and intraoperative judgment is required to avoid additional recurrence of instability after revision procedures, particularly because results deteriorate with each successive operation. Glenoid or humeral defects with greater than 25% bone loss compromise stability provided through the mechanism of concavity compression. These defects must be specifically addressed to avoid recurrence of instability. We prefer anatomic reconstruction techniques combined with capsulolabral repair and, if bone defects are present, anatomic reconstruction with osteochondral allograft. Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Oxidation-Mediated Fingering in Liquid Metals

NASA Astrophysics Data System (ADS)

Eaker, Collin B.; Hight, David C.; O'Regan, John D.; Dickey, Michael D.; Daniels, Karen E.

2017-10-01

We identify and characterize a new class of fingering instabilities in liquid metals; these instabilities are unexpected due to the large interfacial tension of metals. Electrochemical oxidation lowers the effective interfacial tension of a gallium-based liquid metal alloy to values approaching zero, thereby inducing drastic shape changes, including the formation of fractals. The measured fractal dimension (D =1.3 ±0.05 ) places the instability in a different universality class than other fingering instabilities. By characterizing changes in morphology and dynamics as a function of droplet volume and applied electric potential, we identify the three main forces involved in this process: interfacial tension, gravity, and oxidative stress. Importantly, we find that electrochemical oxidation can generate compressive interfacial forces that oppose the tensile forces at a liquid interface. The surface oxide layer ultimately provides a physical and electrochemical barrier that halts the instabilities at larger positive potentials. Controlling the competition between interfacial tension and oxidative (compressive) stresses at the interface is important for the development of reconfigurable electronic, electromagnetic, and optical devices that take advantage of the metallic properties of liquid metals.

The universal instability in general geometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helander, P.; Plunk, G. G.

2015-09-15

The “universal” instability has recently been revived by Landreman et al. [Phys. Rev. Lett. 114, 095003 (2015)], who showed that it indeed exists in plasma geometries with straight (but sheared) magnetic field lines. Here, it is demonstrated analytically that this instability can be presented in more general sheared and toroidal geometries. In a torus, the universal instability is shown to be closely related to the trapped-electron mode, although the trapped-electron drive is usually dominant. However, this drive can be weakened or eliminated, as in the case in stellarators with the maximum-J property, leaving the parallel Landau resonance to drive amore » residual mode, which is identified as the universal instability.« less

Avalanching glacier instabilities: Review on processes and early warning perspectives

NASA Astrophysics Data System (ADS)

Faillettaz, Jérome; Funk, Martin; Vincent, Christian

2015-06-01

Avalanching glacier instabilities are gravity-driven rupture phenomena that might cause major disasters, especially when they are at the origin of a chain of processes. Reliably forecasting such events combined with a timely evacuation of endangered inhabited areas often constitute the most efficient action. Recently, considerable efforts in monitoring, analyzing, and modeling such phenomena have led to significant advances in destabilization process understanding, improving early warning perspectives. The purpose of this paper is to review the recent progress in this domain. Three different types of instabilities can be identified depending on the thermal properties of the ice/bed interface. If cold (1), the maturation of the rupture is associated with a typical time evolution of surface velocities and passive seismic activity. A prediction of the final break off is possible using these precursory signs. For the two other types, water plays a key role in the development of the instability. If the ice/bed interface is partly temperate (2), the presence of meltwater may reduce the basal resistance, which promotes the instability. No clear and easily detectable precursory signs are known in this case, and the only way to infer any potential instability is to monitor the temporal evolution of the thermal regime. The last type of instability (3) concerns steep temperate glacier tongues switching for several days/weeks during the melting season into a so-called "active phase" followed in rare cases by a major break-off event. Although the prediction of such events is still far from being achievable, critical conditions promoting the final instability can be identified.

Combustion instability investigations on the BR710 jet engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konrad, W.; Brehm, N.; Kameier, F.

1998-01-01

During the development of the BR710 jet engine, audible combustor instabilities (termed rumble) occurred. Amplitudes measured with test cell microphones were up to 130 dB at around 100 Hz. Disturbances of this amplitude are clearly undesirable, even if only present during start-up, and a research program was initiated to eliminate the problem. Presented here is the methodical and structured approach used to identify, understand, and remove the instability. Some reference is made to theory, which was used for guidance, but the focus of the work is on the research done to find the cause of the problem and to correctmore » it. The investigation followed two separate, but parallel, paths--one looking in detail at individual components of the engine to identify possible involvement in the instability and the other looking at the pressure signals from various parts of a complete engine to help pinpoint the source of the disturbance. The main cause of the BR710 combustor rumble was found to be a self-excited aerodynamic instability arising from the design of the fuel injector head. In the end, minor modifications lead to spray pattern changes, which greatly reduced the combustor noise. As a result of this work, new recommendation are made for reducing the risk of combustion instabilities in jet engines.« less

Two or more impingement and/or instability deformities are often present in patients with hip pain.

PubMed

Tibor, Lisa M; Liebert, Gunnar; Sutter, Reto; Impellizzeri, Franco M; Leunig, Michael

2013-12-01

Damage to the hip can occur due to impingement or instability caused by anatomic factors such as femoral and acetabular version, neck-shaft angle, alpha angle, and lateral center-edge angle (CEA). The associations between these anatomic factors and how often they occur in a painful hip are unclear but if unaddressed might explain failed hip preservation surgery. We determined (1) the influence of sex on the expression of impingement-related or instability-related factors, (2) the associations among these factors, and (3) how often both impingement and/or instability factors occur in the same hip. We retrospectively reviewed a cohort of 170 hips (145 patients) undergoing MR arthrography of the hip for any reason. We excluded 58 hips with high-grade dysplasia, Perthes' sequelae, previous surgery, or incomplete radiographic information, leaving 112 hips (96 patients). We measured femoral version and alpha angles on MR arthrograms. Acetabular anteversion, lateral CEA, and neck-shaft angle were measured on pelvic radiographs. We observed a correlation between sex and alpha angle. Weak or no correlations were observed between the other five parameters. In 66% of hips, two or more (of five) impingement parameters, and in 51% of hips, two or more (of five) instability parameters were found. Patients with hip pain frequently have several anatomic factors potentially contributing to chondrolabral damage. To address pathologic hip loading due to impingement and/or instability, all of the anatomic influences should be known. As we found no associations between anatomic factors, we recommend an individualized assessment of each painful hip.

Peroneus quartus and functional ankle instability.

PubMed

Lotito, G; Pruvost, J; Collado, H; Coudreuse, J-M; Bensoussan, L; Curvale, G; Viton, J-M; Delarque, A

2011-07-01

Physical and rehabilitation medicine physicians commonly see patients with chronic functional ankle instability. The main anatomical structures involved in ankle stability are the peroneus (fibularis) brevis and peroneus longus muscles. Several anatomical muscle-tendon variations have been described in the literature as being sometimes responsible for this instability, the peroneus quartus muscle being the most frequent. The objective of this clinical study is to discuss the implication of the bilateral peroneus quartus muscle in functional ankle instability. This 26-year-old patient was seen in PM&R consultation for recurrent episodes of lateral ankle sprains. The clinical examination found a moderate hyperlaxity on the right side in bilateral ankle varus. We also noted a bilateral weakness of the peroneus muscles. Additional imaging examinations showed a supernumerary bilateral peroneus quartus. The electroneuromyogram of the peroneus muscles was normal. In the literature the incidence of a supernumerary peroneus quartus muscle varies from 0 to 21.7%. Most times this muscle is asymptomatic and is only fortuitously discovered. However some cases of chronic ankle pain or instability have been reported in the literature. It seems relevant to discuss, around the clinical case of this patient, the impact of this muscle on ankle instability especially when faced with lingering weakness of the peroneus brevis and longus muscles in spite of eccentric strength training and in the absence of any neurological impairment. One of the hypotheses, previously described in the literature, would be the overcrowding effect resulting in a true conflict by reducing the available space for the peroneal muscles in the peroneal sheath. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Bridge scour and stream instability countermeasures : experience, selection, and design guidance : third edition. Volume 1

DOT National Transportation Integrated Search

2009-09-01

This document identifies and provides design guidelines for bridge scour and stream instability countermeasures that have been implemented by various State departments of transportation (DOTs) in the United States. Countermeasure experience, selectio...

Bridge scour and stream instability countermeasures : experience, selection, and design guidance : third edition. Volume 2

DOT National Transportation Integrated Search

2009-09-01

This document identifies and provides design guidelines for bridge scour and stream instability countermeasures that have been implemented by various State departments of transportation (DOTs) in the United States. Countermeasure experience, selectio...

Geographies of Social Exclusion: Education Access in the Philippines

ERIC Educational Resources Information Center

Symaco, Lorraine Pe

2013-01-01

Despite the massive education sector of the country, the Philippines--being located in the Pacific Ring of Fire and the typhoon belt--is home to a number of natural instabilities that frequently disrupt the school calendar. Conflict areas in selected parts of the island of Mindanao and the remote geographic features of the country also pose…

Friendship Conflict, Conflict Responses, and Instability: Unique Links to Anxious and Angry Forms of Rejection Sensitivity

ERIC Educational Resources Information Center

Croft, Carissa D.; Zimmer-Gembeck, Melanie J.

2014-01-01

Rejection sensitivity (RS) instigates conflict and prompts maladaptive conflict responses within romantic relationships. We tested whether RS had similar effects within friendships (N = 262, X[subscript age] = 11.7) by investigating whether (a) RS was associated with more frequent conflict, (b) two RS forms prompted different conflict responses,…

General cause of sheath instability identified for low collisionality plasmas in devices with secondary electron emission.

PubMed

Campanell, M D; Khrabrov, A V; Kaganovich, I D

2012-06-08

A condition for sheath instability due to secondary electron emission (SEE) is derived for low collisionality plasmas. When the SEE coefficient of the electrons bordering the depleted loss cone in energy space exceeds unity, the sheath potential is unstable to a negative perturbation. This result explains three different instability phenomena observed in Hall thruster simulations including a newly found state with spontaneous ∼20  MHz oscillations. When instabilities occur, the SEE propagating between the walls becomes the dominant contribution to the particle flux, energy loss and axial transport.

Collision-Driven Negative-Energy Waves and the Weibel Instability of a Relativistic Electron Beam in a Quasineutral Plasma

NASA Astrophysics Data System (ADS)

Karmakar, Anupam; Kumar, Naveen; Shvets, Gennady; Polomarov, Oleg; Pukhov, Alexander

2008-12-01

A new model describing the Weibel instability of a relativistic electron beam propagating through a resistive plasma is developed. For finite-temperature beams, a new class of negative-energy magnetosound waves is identified, whose growth due to collisional dissipation destabilizes the beam-plasma system even for high beam temperatures. We perform 2D and 3D particle-in-cell simulations and show that in 3D geometry the Weibel instability persists even for collisionless background plasma. The anomalous plasma resistivity in 3D is caused by the two-stream instability.

MESSENGER Orbital Observations of Large-Amplitude Kelvin-Helmholtz Waves at Mercury's Magnetopause

NASA Technical Reports Server (NTRS)

Sundberg, Torbjorn; Boardsen, Scott A.; Slavin, James A.; Anderson, Brian J.; Korth, Haje; Zurbuchen, Thomas H.; Raines, Jim M.; Solomon, Sean C.

2012-01-01

We present a survey of Kelvi\\ n-Helmholtz (KH) waves at Mercury's magnetopause during MESSENGER's first Mercury year in orb it. The waves were identified on the basis of the well-established sawtooth wave signatures that are associated with non-linear KH vortices at the magnetopause. MESSENGER frequently observed such KH waves in the dayside region of the magnetosphere where the magnetosheath flow velocity is still sub -sonic, which implies that instability growth rates at Mercury's magnetopau are much larger than at Earth. We attribute these greater rates to the limited wave energy dissipation in Mercury's highly resistive regolith. The wave amplitude was often on the order of ' 00 nT or more, and the wave periods were - 10- 20 s. A clear dawn-dusk asymmetry is present in the data, in that all of the observed wave events occurred in the post-noon and dusk-side sectors of the magnetopause. This asymmetry is like ly related to finite Larmor-radius effects and is in agreement with results from particle-in-cell simulations of the instability. The waves were observed almost exclusively during periods when the north-south component of the magnetosheath magnetic field was northward, a pattern similar to that for most terrestrial KH wave events. Accompanying plasma measurements show that the waves were associated with the transport of magnetosheath plasma into the magnetosphere.

Analysis of the vortices in the inner flow of reversible pump turbine with the new omega vortex identification method

NASA Astrophysics Data System (ADS)

Zhang, Yu-ning; Liu, Kai-hua; Li, Jin-wei; Xian, Hai-zhen; Du, Xiao-ze

2018-05-01

Reversible pump turbines are widely employed in the pumped hydro energy storage power plants. The frequent shifts among various operational modes for the reversible pump turbines pose various instability problems, e.g., the strong pressure fluctuation, the shaft swing, and the impeller damage. The instability is related to the vortices generated in the channels of the reversible pump turbines in the generating mode. In the present paper, a new omega vortex identification method is applied to the vortex analysis of the reversible pump turbines. The main advantage of the adopted algorithm is that it is physically independent of the selected values for the vortex identification in different working modes. Both weak and strong vortices can be identified by setting the same omega value in the whole passage of the reversible pump turbine. Five typical modes (turbine mode, runaway mode, turbine brake mode, zero-flow-rate mode and reverse pump mode) at several typical guide vane openings are selected for the analysis and comparisons. The differences between various modes and different guide vane openings are compared both qualitatively in terms of the vortex distributions and quantitatively in terms of the areas of the vortices in the reversible pump turbines. Our findings indicate that the new omega method could be successfully applied to the vortex identification in the reversible pump turbines.

Historical problem areas lessons learned

NASA Technical Reports Server (NTRS)

Sackheim, Bob; Fester, Dale A.

1991-01-01

Historical problem areas in space transportation propulsion technology are identified in viewgraph form. Problem areas discussed include materials compatibility, contamination, pneumatic/feed system flow instabilities, instabilities in rocket engine combustion and fuel sloshing, exhaust plume interference, composite rocket nozzle failure, and freeze/thaw damage.

Differences in histological features and PD-L1 expression between sporadic microsatellite instability and Lynch-syndrome-associated disease in Japanese patients with colorectal cancer.

PubMed

Yamada, Rin; Yamaguchi, Tatsuro; Iijima, Takeru; Wakaume, Rika; Takao, Misato; Koizumi, Koichi; Hishima, Tsunekazu; Horiguchi, Shin-Ichiro

2018-06-01

The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients. Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations. The following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, P = 0.0002), especially solid type (30.6 vs. 3.6%, P = 0.0061); medullary morphology (19.4 and 0%, P = 0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, P = 0.042), and PD-L1 expression (25.0 vs. 3.6%, P = 0.034). However, the groups did not differ in terms of the mean invasive front and intratumoral CD8-positive cell densities. In a logistic regression analysis, PD-L1 expression correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval: 1.55-37.7, P = 0.012), but not with the difference between sporadic MSI cancer and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval: 0.50-45.0, P = 0.176). Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.

Bone fragment union and remodeling after arthroscopic bony bankart repair for traumatic anterior shoulder instability with a glenoid defect: influence on postoperative recurrence of instability.

PubMed

Nakagawa, Shigeto; Ozaki, Ritsuro; Take, Yasuhiro; Mae, Tatsuo; Hayashida, Kenji

2015-06-01

Although good clinical outcomes have been reported after arthroscopic bony Bankart repair, the extent of bone union is still unclear. To investigate bone union after arthroscopic bony Bankart repair and its influence on postoperative recurrence of instability. Cohort study; Level of evidence, 3. Among 113 consecutive shoulders that underwent arthroscopic bony Bankart repair, postoperative evaluation of bone union by computed tomography (CT) was performed at various times in 81 shoulders. Bone union was investigated during 3 periods: 3 to 6 months postoperatively (first period), 7 to 12 months postoperatively (second period), and 13 months or more postoperatively (third period). The influence of the size of the preoperative glenoid defect and the size of the bone fragment on bone union was investigated, as well as the influence of bone union on postoperative recurrence of instability. In shoulders with bone union, bone fragment remodeling and changes in the glenoid defect size were also investigated. The bone union rate was 30.5% in the first period, 55.3% in the second period, and 84.6% in the third period. Among 53 shoulders with CT evaluation in the second period or later and follow-up for a minimum of 1 year, there was complete union in 33 shoulders (62.3%), partial union in 3 (5.7%), nonunion in 8 (15.1%), and no fragment on CT in 9 (17.0%). The complete union rate was 50% for 22 shoulders with small bone fragments (<5% of the glenoid diameter), 56.3% for 16 shoulders with medium fragments (5%-10%), and 86.7% for 15 shoulders with large fragments (>10%). The recurrence rate for postoperative instability was only 6.1% for shoulders with complete union, while it was 50% for shoulders with partial union, nonunion, no fragment, and no fragment on CT. The recurrence rate was significantly higher (36.4%) in shoulders with small fragments, but it was significantly lower in shoulders with bone union. In shoulders with bone union, the bone fragment frequently became larger over time, while the size of the glenoid defect decreased significantly from 18.6% preoperatively to 4.7% postoperatively. Bone union was not always achieved after arthroscopic bony Bankart repair, and union was often delayed. Recurrence of instability was significantly more frequent when bone union failed. The size of the glenoid defect decreased significantly in shoulders with bone union. © 2015 The Author(s).

Spindle Epithelial Tumor with Thymus-Like Differentiation (SETTLE): A Next-Generation Sequencing Study.

PubMed

Stevens, Todd M; Morlote, Diana; Swensen, Jeff; Ellis, Michelle; Harada, Shuko; Spencer, Sharon; Prieto-Granada, Carlos N; Folpe, Andrew L; Gatalica, Zoran

2018-05-07

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a malignant biphasic neoplasm of the thyroid or neck with propensity for late metastasis. Unlike synovial sarcoma, its main morphologic mimic, SETTLE lacks synovial sarcoma-associated translocations. A single case of SETTLE has shown a KRAS mutation but to date no comprehensive next generation sequencing studies of this rare neoplasm have been undertaken. Herein, we subjected 5 well defined cases of SETTLE to direct sequence analysis of 592 genes and fusion gene analysis of 52 genes frequently rearranged in human cancers. We identified one case with two pathogenic variants in the KMT2D gene, one being in an intron splice site (c.674-1A>G) and the other being a frameshift variant (p.M2829fs). This same case also had a pathogenic nonsense variant in the KMT2C gene (p.R1237*). A second case of SETTLE carried a pathogenic NRAS missense variant, Q61R. No other molecular alterations, microsatellite instability, gene fusions or amplifications were identified.

Characteristics and transport effects of the electron drift instability in Hall-effect thrusters

NASA Astrophysics Data System (ADS)

Lafleur, T.; Baalrud, S. D.; Chabert, P.

2017-02-01

The large electron {E}× {B} drift (relative to the ions) in the azimuthal direction of Hall-effect thrusters is well known to excite a strong instability. In a recent paper (Lafleur et al 2016 Phys. Plasmas 23 053503) we demonstrated that this instability leads to an enhanced electron-ion friction force that increases the electron cross-field mobility to levels similar to those seen experimentally. Here we extend this work by considering in detail the onset criteria for the formation of this instability (both in xenon, and other propellants of interest), and identify a number of important characteristics that it displays within Hall-effect thrusters (HETs): including the appearance of an additional non-dimensionalized scaling parameter (the instability growth-to-convection ratio), which controls the instability evolution and amplitude. We also investigate the effect that the instability has on electron and ion heating in HETs, and show that it leads to an ion rotation in the azimuthal direction that is in agreement with that seen experimentally.

Expression levels of DNA replication and repair genes predict regional somatic repeat instability in the brain but are not altered by polyglutamine disease protein expression or age.

PubMed

Mason, Amanda G; Tomé, Stephanie; Simard, Jodie P; Libby, Randell T; Bammler, Theodor K; Beyer, Richard P; Morton, A Jennifer; Pearson, Christopher E; La Spada, Albert R

2014-03-15

Expansion of CAG/CTG trinucleotide repeats causes numerous inherited neurological disorders, including Huntington's disease (HD), several spinocerebellar ataxias and myotonic dystrophy type 1. Expanded repeats are genetically unstable with a propensity to further expand when transmitted from parents to offspring. For many alleles with expanded repeats, extensive somatic mosaicism has been documented. For CAG repeat diseases, dramatic instability has been documented in the striatum, with larger expansions noted with advancing age. In contrast, only modest instability occurs in the cerebellum. Using microarray expression analysis, we sought to identify the genetic basis of these regional instability differences by comparing gene expression in the striatum and cerebellum of aged wild-type C57BL/6J mice. We identified eight candidate genes enriched in cerebellum, and validated four--Pcna, Rpa1, Msh6 and Fen1--along with a highly associated interactor, Lig1. We also explored whether expression levels of mismatch repair (MMR) proteins are altered in a line of HD transgenic mice, R6/2, that is known to show pronounced regional repeat instability. Compared with wild-type littermates, MMR expression levels were not significantly altered in R6/2 mice regardless of age. Interestingly, expression levels of these candidates were significantly increased in the cerebellum of control and HD human samples in comparison to striatum. Together, our data suggest that elevated expression levels of DNA replication and repair proteins in cerebellum may act as a safeguard against repeat instability, and may account for the dramatically reduced somatic instability present in this brain region, compared with the marked instability observed in the striatum.

Identifying balance impairments in people with Parkinson's disease using video and wearable sensors.

PubMed

Stack, Emma; Agarwal, Veena; King, Rachel; Burnett, Malcolm; Tahavori, Fatemeh; Janko, Balazs; Harwin, William; Ashburn, Ann; Kunkel, Dorit

2018-05-01

Falls and near falls are common among people with Parkinson's (PwP). To date, most wearable sensor research focussed on fall detection, few studies explored if wearable sensors can detect instability. Can instability (caution or near-falls) be detected using wearable sensors in comparison to video analysis? Twenty-four people (aged 60-86) with and without Parkinson's were recruited from community groups. Movements (e.g. walking, turning, transfers and reaching) were observed in the gait laboratory and/or at home; recorded using clinical measures, video and five wearable sensors (attached on the waist, ankles and wrists). After defining 'caution' and 'instability', two researchers evaluated video data and a third the raw wearable sensor data; blinded to each other's evaluations. Agreement between video and sensor data was calculated on stability, timing, step count and strategy. Data was available for 117 performances: 82 (70%) appeared stable on video. Ratings agreed in 86/117 cases (74%). Highest agreement was noted for chair transfer, timed up and go test and 3 m walks. Video analysts noted caution (slow, contained movements, safety-enhancing postures and concentration) and/or instability (saving reactions, stopping after stumbling or veering) in 40/134 performances (30%): raw wearable sensor data identified 16/35 performances rated cautious or unstable (sensitivity 46%) and 70/82 rated stable (specificity 85%). There was a 54% chance that a performance identified from wearable sensors as cautious/unstable was so; rising to 80% for stable movements. Agreement between wearable sensor and video data suggested that wearable sensors can detect subtle instability and near-falls. Caution and instability were observed in nearly a third of performances, suggesting that simple, mildly challenging actions, with clearly defined start- and end-points, may be most amenable to monitoring during free-living at home. Using the genuine near-falls recorded, work continues to automatically detect subtle instability using algorithms. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Molecular excited states from the SCAN functional

NASA Astrophysics Data System (ADS)

Tozer, David J.; Peach, Michael J. G.

2018-06-01

The performance of the strongly constrained and appropriately normed (SCAN) meta-generalised gradient approximation exchange-correlation functional is investigated for the calculation of time-dependent density-functional theory molecular excitation energies of local, charge-transfer and Rydberg character, together with the excited ? potential energy curve in H2. The SCAN results frequently resemble those obtained using a global hybrid functional, with either a standard or increased fraction of exact orbital exchange. For local excitations, SCAN can exhibit significant triplet instability problems, resulting in imaginary triplet excitation energies for a number of cases. The Tamm-Dancoff approximation offers a simple approach to improve the situation, but the excitation energies are still significantly underestimated. Understanding the origin of these (near)-triplet instabilities may provide useful insight into future functional development.

Pattern formation and mass transfer under stationary solutal Marangoni instability.

PubMed

Schwarzenberger, Karin; Köllner, Thomas; Linde, Hartmut; Boeck, Thomas; Odenbach, Stefan; Eckert, Kerstin

2014-04-01

According to the seminal theory by Sternling and Scriven, solutal Marangoni convection during mass transfer of surface-active solutes may occur as either oscillatory or stationary instability. With strong support of Manuel G. Velarde, a combined initiative of experimental works, in particular to mention those of Linde, Wierschem and coworkers, and theory has enabled a classification of dominant wave types of the oscillatory mode and their interactions. In this way a rather comprehensive understanding of the nonlinear evolution of the oscillatory instability could be achieved. A comparably advanced state-of-the-art with respect to the stationary counterpart seemed to be out of reach a short time ago. Recent developments on both the numerical and experimental side, in combination with assessing an extensive number of older experiments, now allow one to draw a more unified picture. By reviewing these works, we show that three main building blocks exist during the nonlinear evolution: roll cells, relaxation oscillations and relaxation oscillations waves. What is frequently called interfacial turbulence results from the interaction between these partly coexisting basic patterns which may additionally occur in different hierarchy levels. The second focus of this review lies on the practical importance of such convection patterns concerning their influence on mass transfer characteristics. Particular attention is paid here to the interaction between Marangoni and buoyancy effects which frequently complicates the pattern formation even more. To shed more light on these dependencies, new simulations regarding the limiting case of stabilizing density stratification and vanishing buoyancy are incorporated. Copyright © 2013 Elsevier B.V. All rights reserved.

Lynch syndrome-associated colorectal carcinoma: frequent involvement of the left colon and rectum and late-onset presentation supports a universal screening approach.

PubMed

Hartman, Douglas J; Brand, Randall E; Hu, Huankai; Bahary, Nathan; Dudley, Beth; Chiosea, Simon I; Nikiforova, Marina N; Pai, Reetesh K

2013-11-01

The optimal strategy for screening patients with colorectal carcinoma for Lynch syndrome (LS) is a subject of continued debate in the literature with some advocating universal screening while others arguing for selective screening. We evaluated 1292 colorectal carcinomas for DNA mismatch repair protein abnormalities and identified 150 (11.6%) tumors demonstrating high-levels of microsatellite instability (MSI-H). MSI-H colorectal carcinomas were divided into sporadic (112/1292, 8.7%) and LS/probable LS-associated (38/1292, 2.9%) groups based on BRAF V600E mutation, MLH1 promoter hypermethylation, cancer history, and germline mismatch repair gene mutation. All MSI-H colorectal carcinomas were analyzed for grade, location, and tumor histology. The utility of the revised Bethesda guidelines and published predictive pathology models for MSI-H colorectal carcinomas (PREDICT and MSPath) were evaluated. Left-sided MSI-H colorectal carcinomas were more frequently associated with LS compared with right-sided MSI-H colorectal carcinomas (12/21, 57% versus 26/129, 20%, P = .0008). There was no significant difference in histology between sporadic MSI-H and LS/probable LS-associated colorectal carcinomas except for a slightly higher proportion of sporadic MSI-H tumors demonstrating tumor-infiltrating lymphocytes (81% versus 61%, P = .015). Neither pathology predictive model identified all LS-associated colorectal carcinomas (PREDICT: 33/38, 87%; MSPath: 35/38, 92%). 12/117 (10%) MSI-H colorectal carcinomas identified in patients >60 years were LS/probable LS-associated. Our results demonstrate that models of predicting MSI-H fail to identify LS-associated colorectal carcinoma given their reliance on right-sided location. A significant proportion (32%) of LS-associated colorectal carcinoma is identified in patients >60 years. Finally, our results demonstrate similar morphologic features between LS-associated and sporadic MSI-H colorectal carcinomas. © 2013.

Experimental Study of Thermal Field Evolution in the Short-Impending Stage Before Earthquakes

NASA Astrophysics Data System (ADS)

Ren, Yaqiong; Ma, Jin; Liu, Peixun; Chen, Shunyun

2017-08-01

Phenomena at critical points are vital for identifying the short-impending stage prior to earthquakes. The peak stress is a critical point when stress is converted from predominantly accumulation to predominantly release. We call the duration between the peak stress and instability "the meta-instability stage", which refers to the short-impending stage of earthquakes. The meta-instability stage consists of a steady releasing quasi-static stage and an accelerated releasing quasi-dynamic stage. The turning point of the above two stages is the remaining critical point. To identify the two critical points in the field, it is necessary to study the characteristic phenomena of various physical fields in the meta-instability stage in the laboratory, and the strain and displacement variations were studied. Considering that stress and relative displacement can be detected by thermal variations and peculiarities in the full-field observations, we employed a cooled thermal infrared imaging system to record thermal variations in the meta-instability stage of stick slip events generated along a simulated, precut planer strike slip fault in a granodiorite block on a horizontally bilateral servo-controlled press machine. The experimental results demonstrate the following: (1) a large area of decreasing temperatures in wall rocks and increasing temperatures in sporadic sections of the fault indicate entrance into the meta-instability stage. (2) The rapid expansion of regions of increasing temperatures on the fault and the enhancement of temperature increase amplitude correspond to the turning point from the quasi-static stage to the quasi-dynamic stage. Our results reveal thermal indicators for the critical points prior to earthquakes that provide clues for identifying the short-impending stage of earthquakes.

The nucleus is the target for radiation-induced chromosomal instability

NASA Technical Reports Server (NTRS)

Kaplan, M. I.; Morgan, W. F.

1998-01-01

We have previously described chromosomal instability in cells of a human-hamster hybrid cell line after exposure to X rays. Chromosomal instability in these cells is characterized by the appearance of novel chromosomal rearrangements multiple generations after exposure to ionizing radiation. To identify the cellular target(s) for radiation-induced chromosomal instability, cells were treated with 125I-labeled compounds and frozen. Radioactive decays from 125I cause damage to the cell primarily at the site of their decay, and freezing the cells allows damage to accumulate in the absence of other cellular processes. We found that the decay of 125I-iododeoxyuridine, which is incorporated into the DNA, caused chromosomal instability. While cell killing and first-division chromosomal rearrangements increased with increasing numbers of 125I decays, the frequency of chromosomal instability was independent of dose. Chromosomal instability could also be induced from incorporation of 125I-iododeoxyuridine without freezing the cells for accumulation of decays. This indicates that DNA double-strand breaks in frozen cells resulting from 125I decays failed to lead to instability. Incorporation of an 125I-labeled protein (125I-succinyl-concanavalin A), which was internalized into the cell and/or bound to the plasma membrane, neither caused chromosomal instability nor potentiated chromosomal instability induced by 125I-iododeoxyuridine. These results show that the target for radiation-induced chromosomal instability in these cells is the nucleus.

High Mitochondrial DNA Stability in B-Cell Chronic Lymphocytic Leukemia

PubMed Central

Cerezo, María; Bandelt, Hans-Jürgen; Martín-Guerrero, Idoia; Ardanaz, Maite; Vega, Ana; Carracedo, Ángel; García-Orad, África; Salas, Antonio

2009-01-01

Background Chronic Lymphocytic Leukemia (CLL) leads to progressive accumulation of lymphocytes in the blood, bone marrow, and lymphatic tissues. Previous findings have suggested that the mtDNA could play an important role in CLL. Methodology/Principal Findings The mitochondrial DNA (mtDNA) control-region was analyzed in lymphocyte cell DNA extracts and compared with their granulocyte counterpart extract of 146 patients suffering from B-Cell CLL; B-CLL (all recruited from the Basque country). Major efforts were undertaken to rule out methodological artefacts that would render a high false positive rate for mtDNA instabilities and thus lead to erroneous interpretation of sequence instabilities. Only twenty instabilities were finally confirmed, most of them affecting the homopolymeric stretch located in the second hypervariable segment (HVS-II) around position 310, which is well known to constitute an extreme mutational hotspot of length polymorphism, as these mutations are frequently observed in the general human population. A critical revision of the findings in previous studies indicates a lack of proper methodological standards, which eventually led to an overinterpretation of the role of the mtDNA in CLL tumorigenesis. Conclusions/Significance Our results suggest that mtDNA instability is not the primary causal factor in B-CLL. A secondary role of mtDNA mutations cannot be fully ruled out under the hypothesis that the progressive accumulation of mtDNA instabilities could finally contribute to the tumoral process. Recommendations are given that would help to minimize erroneous interpretation of sequencing results in mtDNA studies in tumorigenesis. PMID:19924307

Cryogenic pellet launcher adapted for controlling of tokamak plasma edge instabilities.

PubMed

Lang, P T; Cierpka, P; Harhausen, J; Neuhauser, J; Wittmann, C; Gál, K; Kálvin, S; Kocsis, G; Sárközi, J; Szepesi, T; Dorner, C; Kauke, G

2007-02-01

One of the main challenges posed recently on pellet launcher systems in fusion-oriented plasma physics is the control of the plasma edge region. Strong energy bursts ejected from the plasma due to edge localized modes (ELMs) can form a severe threat for in-vessel components but can be mitigated by sufficiently frequent triggering of the underlying instabilities using hydrogen isotope pellet injection. However, pellet injection systems developed mainly for the task of ELM control, keeping the unwanted pellet fueling minimized, are still missing. Here, we report on a novel system developed under the premise of its suitability for control and mitigation of plasma edge instabilities. The system is based on the blower gun principle and is capable of combining high repetition rates up to 143 Hz with low pellet velocities. Thus, the flexibility of the accessible injection geometry can be maximized and the pellet size kept low. As a result the new system allows for an enhancement in the tokamak operation as well as for more sophisticated experiments investigating the underlying physics of the plasma edge instabilities. This article reports on the design of the new system, its main operational characteristics as determined in extensive test bed runs, and also its first test at the tokamak experiment ASDEX Upgrade.

Studies of fluid instabilities in flows of lava and debris

NASA Technical Reports Server (NTRS)

Fink, Jonathan H.

1987-01-01

At least two instabilities have been identified and utilized in lava flow studies: surface folding and gravity instability. Both lead to the development of regularly spaced structures on the surfaces of lava flows. The geometry of surface folds have been used to estimate the rheology of lava flows on other planets. One investigation's analysis assumed that lava flows have a temperature-dependent Newtonian rheology, and that the lava's viscosity decreased exponentially inward from the upper surface. The author reviews studies by other investigators on the analysis of surface folding, the analysis of Taylor instability in lava flows, and the effect of surface folding on debris flows.

Strange mode instabilities and mass loss in evolved massive primordial stars

NASA Astrophysics Data System (ADS)

Yadav, Abhay Pratap; Kühnrich Biavatti, Stefan Henrique; Glatzel, Wolfgang

2018-04-01

A linear stability analysis of models for evolved primordial stars with masses between 150 and 250 M⊙ is presented. Strange mode instabilities with growth rates in the dynamical range are identified for stellar models with effective temperatures below log Teff = 4.5. For selected models, the final fate of the instabilities is determined by numerical simulation of their evolution into the non-linear regime. As a result, the instabilities lead to finite amplitude pulsations. Associated with them are acoustic energy fluxes capable of driving stellar winds with mass-loss rates in the range between 7.7 × 10-7 and 3.5 × 10-4 M⊙ yr-1.

Assessing Spontaneous Combustion Instability with Recurrence Quantification Analysis

NASA Technical Reports Server (NTRS)

Eberhart, Chad J.; Casiano, Matthew J.

2016-01-01

Spontaneous instabilities can pose a significant challenge to verification of combustion stability, and characterizing its onset is an important avenue of improvement for stability assessments of liquid propellant rocket engines. Recurrence Quantification Analysis (RQA) is used here to explore nonlinear combustion dynamics that might give insight into instability. Multiple types of patterns representative of different dynamical states are identified within fluctuating chamber pressure data, and markers for impending instability are found. A class of metrics which describe these patterns is also calculated. RQA metrics are compared with and interpreted against another metric from nonlinear time series analysis, the Hurst exponent, to help better distinguish between stable and unstable operation.

Arthroscopic Management of Anterior, Posterior, and Multidirectional Shoulder Instabilities.

PubMed

Field, Larry D; Ryu, Richard K N; Abrams, Jeffrey S; Provencher, Matthew

2016-01-01

Arthroscopic shoulder stabilization offers several potential advantages compared with open surgery, including the opportunity to more accurately evaluate the glenohumeral joint at the time of diagnostic assessment; comprehensively address multiple pathologic lesions that may be identified; and avoid potential complications unique to open stabilization, such as postoperative subscapularis failure. A thorough understanding of normal shoulder anatomy and biomechanics, along with the pathoanatomy responsible for anterior, posterior, and multidirectional shoulder instability patterns, is very important in the management of patients who have shoulder instability. The treating physician also must be familiar with diagnostic imaging and physical examination maneuvers that are required to accurately diagnose shoulder instability.

Waves on the surface of the Orion molecular cloud.

PubMed

Berné, Olivier; Marcelino, Núria; Cernicharo, José

2010-08-19

Massive stars influence their parental molecular cloud, and it has long been suspected that the development of hydrodynamical instabilities can compress or fragment the cloud. Identifying such instabilities has proved difficult. It has been suggested that elongated structures (such as the 'pillars of creation') and other shapes arise because of instabilities, but alternative explanations are available. One key signature of an instability is a wave-like structure in the gas, which has hitherto not been seen. Here we report the presence of 'waves' at the surface of the Orion molecular cloud near where massive stars are forming. The waves seem to be a Kelvin-Helmholtz instability that arises during the expansion of the nebula as gas heated and ionized by massive stars is blown over pre-existing molecular gas.

Inactivation of parkin by promoter methylation correlated with lymph node metastasis and genomic instability in nasopharyngeal carcinoma.

PubMed

Ni, Haifeng; Zhou, Zhen; Jiang, Bo; Yuan, Xiaoyang; Cao, Xiaolin; Huang, Guangwu; Li, Yong

2017-03-01

This study aimed to investigate the inactivation of the parkin gene by promoter methylation and its relationship with genome instability in nasopharyngeal carcinoma. Parkin was considered as a tumor suppressor gene in various types of cancers. However, its role in nasopharyngeal carcinoma is unexplored. Genomic instabilities were detected in nasopharyngeal carcinoma tissues by the random amplified polymorphic DNA. The methylation-specific polymerase chain reaction, semi-quantitative reverse transcription polymerase chain reaction, and immunohistochemical analysis were used to detect methylation and mRNA and protein expression of parkin in 54 cases of nasopharyngeal carcinoma tissues and 16 cases of normal nasopharyngeal epithelia tissues, and in 5 nasopharyngeal carcinoma cell lines (CNE1, CNE2, TWO3, C666, and HONE1) and 1 normal nasopharyngeal epithelia cell line (NP69). mRNA expression of parkin in CNE1 and CNE2 was analyzed before and after methyltransferase inhibitor 5-aza-2-deoxycytidine treatment. The relationship between promoter methylation and mRNA expression, demethylation and mRNA expression, and mRNA and protein expression of the gene and clinical factors and genomic instabilities were analyzed. The mRNA and protein expression levels were significantly reduced in 54 cases of human nasopharyngeal carcinoma compared with 16 cases of normal nasopharyngeal epithelia. Parkin-methylated cases showed significantly lower mRNA and protein expression levels compared with unmethylated cases. After 5-aza-2-deoxycytidine treatment, parkin mRNA expression was restored in CNE1 and CNE2; 92.59% (50/54) of nasopharyngeal carcinoma demonstrated genomic instability. Parkin is frequently inactivated by promoter methylation, and its mRNA and protein expression correlate with lymph node metastasis and genomic instability. Parkin deficiency probably promotes tumorigenesis in nasopharyngeal carcinoma.

Neural basis of postural instability identified by VTC and EEG

PubMed Central

Cao, Cheng; Jaiswal, Niharika; Newell, Karl M.

2010-01-01

In this study, we investigated the neural basis of virtual time to contact (VTC) and the hypothesis that VTC provides predictive information for future postural instability. A novel approach to differentiate stable pre-falling and transition-to-instability stages within a single postural trial while a subject was performing a challenging single leg stance with eyes closed was developed. Specifically, we utilized wavelet transform and stage segmentation algorithms using VTC time series data set as an input. The VTC time series was time-locked with multichannel (n = 64) EEG signals to examine its underlying neural substrates. To identify the focal sources of neural substrates of VTC, a two-step approach was designed combining the independent component analysis (ICA) and low-resolution tomography (LORETA) of multichannel EEG. There were two major findings: (1) a significant increase of VTC minimal values (along with enhanced variability of VTC) was observed during the transition-to-instability stage with progression to ultimate loss of balance and falling; and (2) this VTC dynamics was associated with pronounced modulation of EEG predominantly within theta, alpha and gamma frequency bands. The sources of this EEG modulation were identified at the cingulate cortex (ACC) and the junction of precuneus and parietal lobe, as well as at the occipital cortex. The findings support the hypothesis that the systematic increase of minimal values of VTC concomitant with modulation of EEG signals at the frontal-central and parietal–occipital areas serve collectively to predict the future instability in posture. PMID:19655130

Characterization and Simulation of the Thermoacoustic Instability Behavior of an Advanced, Low Emissions Combustor Prototype

NASA Technical Reports Server (NTRS)

DeLaat, John C.; Paxson, Daniel E.

2008-01-01

Extensive research is being done toward the development of ultra-low-emissions combustors for aircraft gas turbine engines. However, these combustors have an increased susceptibility to thermoacoustic instabilities. This type of instability was recently observed in an advanced, low emissions combustor prototype installed in a NASA Glenn Research Center test stand. The instability produces pressure oscillations that grow with increasing fuel/air ratio, preventing full power operation. The instability behavior makes the combustor a potentially useful test bed for research into active control methods for combustion instability suppression. The instability behavior was characterized by operating the combustor at various pressures, temperatures, and fuel and air flows representative of operation within an aircraft gas turbine engine. Trends in instability behavior versus operating condition have been identified and documented, and possible explanations for the trends provided. A simulation developed at NASA Glenn captures the observed instability behavior. The physics-based simulation includes the relevant physical features of the combustor and test rig, employs a Sectored 1-D approach, includes simplified reaction equations, and provides time-accurate results. A computationally efficient method is used for area transitions, which decreases run times and allows the simulation to be used for parametric studies, including control method investigations. Simulation results show that the simulation exhibits a self-starting, self-sustained combustion instability and also replicates the experimentally observed instability trends versus operating condition. Future plans are to use the simulation to investigate active control strategies to suppress combustion instabilities and then to experimentally demonstrate active instability suppression with the low emissions combustor prototype, enabling full power, stable operation.

The Spinal Instability Neoplastic Score: Impact on Oncologic Decision-Making.

PubMed

Versteeg, Anne L; Verlaan, Jorrit-Jan; Sahgal, Arjun; Mendel, Ehud; Quraishi, Nasir A; Fourney, Daryl R; Fisher, Charles G

2016-10-15

Systematic literature review. To address the following questions in a systematic literature review: 1. How is spinal neoplastic instability defined or classified in the literature before and after the introduction of the Spinal Instability Neoplastic Score (SINS)? 2. How has SINS affected daily clinical practice? 3. Can SINS be used as a prognostic tool? Spinal neoplastic-related instability was defined in 2010 and simultaneously SINS was introduced as a novel tool with criteria agreed upon by expert consensus to assess the degree of spinal stability. PubMed, Embase, and clinical trial databases were searched with the key words "spinal neoplasm," "spinal instability," "spinal instability neoplastic score," and synonyms. Studies describing spinal neoplastic-related instability were eligible for inclusion. Primary outcomes included studies describing and/or defining neoplastic-related instability, SINS, and studies using SINS as a prognostic factor. The search identified 1414 articles, of which 51 met the inclusion criteria. No precise definition or validated assessment tool was used specific to spinal neoplastic-related instability prior to the introduction of SINS. Since the publication of SINS in 2010, the vast majority of the literature regarding spinal instability has used SINS to assess or describe instability. Twelve studies specifically investigated the prognostic value of SINS in patients who underwent radiotherapy or surgery. No consensus could be determined regarding the definition, assessment, or reporting of neoplastic-related instability before introduction of SINS. Defining spinal neoplastic-related instability and the introduction of SINS have led to improved uniform reporting within the spinal neoplastic literature. Currently, the prognostic value of SINS is controversial. N/A.

Characterization and Simulation of Thermoacoustic Instability in a Low Emissions Combustor Prototype

NASA Technical Reports Server (NTRS)

DeLaat, John C.; Paxson, Daniel E.

2008-01-01

Extensive research is being done toward the development of ultra-low-emissions combustors for aircraft gas turbine engines. However, these combustors have an increased susceptibility to thermoacoustic instabilities. This type of instability was recently observed in an advanced, low emissions combustor prototype installed in a NASA Glenn Research Center test stand. The instability produces pressure oscillations that grow with increasing fuel/air ratio, preventing full power operation. The instability behavior makes the combustor a potentially useful test bed for research into active control methods for combustion instability suppression. The instability behavior was characterized by operating the combustor at various pressures, temperatures, and fuel and air flows representative of operation within an aircraft gas turbine engine. Trends in instability behavior vs. operating condition have been identified and documented. A simulation developed at NASA Glenn captures the observed instability behavior. The physics-based simulation includes the relevant physical features of the combustor and test rig, employs a Sectored 1-D approach, includes simplified reaction equations, and provides time-accurate results. A computationally efficient method is used for area transitions, which decreases run times and allows the simulation to be used for parametric studies, including control method investigations. Simulation results show that the simulation exhibits a self-starting, self-sustained combustion instability and also replicates the experimentally observed instability trends vs. operating condition. Future plans are to use the simulation to investigate active control strategies to suppress combustion instabilities and then to experimentally demonstrate active instability suppression with the low emissions combustor prototype, enabling full power, stable operation.

76 FR 23171 - Electric Reliability Organization Interpretations of Interconnection Reliability Operations and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-26

... (MW and MVAR), or system configuration to maintain system stability, acceptable voltage or power flows... identified system conditions to prevent system instability or cascading outages, and protect other facilities... instability, cascading outages, and protect other facilities in response to contingencies. Therefore, a...

Research on aviation fuel instability

NASA Technical Reports Server (NTRS)

Baker, C. E.; Bittker, D. A.; Cohen, S. M.; Seng, G. T.

1984-01-01

The problems associated with aircraft fuel instability are discussed. What is currently known about the problem is reviewed and a research program to identify those areas where more research is needed is discussed. The term fuel instability generally refers to the gums, sediments, or deposits which can form as a result of a set of complex chemical reactions when a fuel is stored for a long period at ambient conditions or when the fuel is thermally stressed inside the fuel system of an aircraft.

Convective Electrokinetic Instability With Conductivity Gradients

NASA Astrophysics Data System (ADS)

Chen, Chuan-Hua; Lin, Hao; Lele, Sanjiva; Santiago, Juan

2003-11-01

Electrokinetic flow instability has been experimentally identified and quantified in a glass T-junction microchannel system with a cross section of 11 um x 155 um. In this system, buffers of different conductivities were electrokinetically driven into a common mixing channel by a DC electric field. A convective instability was observed with a threshold electric field of 0.45 kV/cm for a 10:1 conductivity ratio. A physical model has been developed which consists of a modified Ohmic model formulation for electrolyte solutions and the Navier-Stokes equations with an electric body force term. The model and experiments show that bulk charge accumulation in regions of conductivity gradients is the key mechanism of such instabilities. A linear stability analysis was performed in a convective framework, and Briggs-Bers criteria were applied to determine the nature of instability. The analysis shows the instability is governed by two key parameters: the ratio of molecular diffusion to electroviscous time scale which governs the onset of instability, and the ratio of electroviscous to electroosmotic velocity which governs whether the instability is convective or absolute. The model predicted critical electric field, growth rate, wavelength, and phase speed which were comparable to experimental data.

Experimental evidence of ion-induced instabilities in the NSLS-II storage ring

DOE PAGES

Cheng, Weixing; Li, Yongjun; Podobedov, Boris

2017-03-12

Fast ion instability has been identified as one of the most prominent instabilities in the recently constructed NSLS-II storage ring at Brookhaven National Laboratory. At a relatively low beam current (~ 25 mA) multi-bunch fills, ion-induced instabilities have already been observed during the early stages of machine commissioning. At present user operation with 250 mA in ~1000 bunches, the fast ion still remains the dominant instability, even after months of vacuum conditioning at high current. Ion-induced dipole motions of the electron beam have been suppressed using the transverse bunch-by-bunch (BxB) feedback system. However other adverse effects of this instability, suchmore » as the vertical beam size increase along the bunch train cannot be cured by the feedback system. Therefore, to achieve the NSLS-II design current of 500 mA while maintaining a small vertical beam emittance, it is important to further understand the fast ion instability and develop mitigation techniques. This paper reports on a series of ion-instability observations at various fill patterns and beam currents using start-of-art NSLS-II diagnostic tools.« less

Experimental evidence of ion-induced instabilities in the NSLS-II storage ring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Weixing; Li, Yongjun; Podobedov, Boris

Fast ion instability has been identified as one of the most prominent instabilities in the recently constructed NSLS-II storage ring at Brookhaven National Laboratory. At a relatively low beam current (~ 25 mA) multi-bunch fills, ion-induced instabilities have already been observed during the early stages of machine commissioning. At present user operation with 250 mA in ~1000 bunches, the fast ion still remains the dominant instability, even after months of vacuum conditioning at high current. Ion-induced dipole motions of the electron beam have been suppressed using the transverse bunch-by-bunch (BxB) feedback system. However other adverse effects of this instability, suchmore » as the vertical beam size increase along the bunch train cannot be cured by the feedback system. Therefore, to achieve the NSLS-II design current of 500 mA while maintaining a small vertical beam emittance, it is important to further understand the fast ion instability and develop mitigation techniques. This paper reports on a series of ion-instability observations at various fill patterns and beam currents using start-of-art NSLS-II diagnostic tools.« less

Systematic review of chronic ankle instability in children

PubMed Central

2014-01-01

Background Chronic ankle instability (CAI) is a disabling condition often encountered after ankle injury. Three main components of CAI exist; perceived instability; mechanical instability (increased ankle ligament laxity); and recurrent sprain. Literature evaluating CAI has been heavily focused on adults, with little attention to CAI in children. Hence, the objective of this study was to systematically review the prevalence of CAI in children. Methods Studies were retrieved from major databases from earliest records to March 2013. References from identified articles were also examined. Studies involving participants with CAI, classified by authors as children, were considered for inclusion. Papers investigating traumatic instability or instability arising from fractures were excluded. Two independent examiners undertook all stages of screening, data extraction and methodological quality assessments. Screening discrepancies were resolved by reaching consensus. Results Following the removal of duplicates, 14,263 papers were screened for eligibility against inclusion and exclusion criteria. Nine full papers were included in the review. Symptoms of CAI evaluated included perceived and mechanical ankle instability along with recurrent ankle sprain. In children with a history of ankle sprain, perceived instability was reported in 23-71% whilst mechanical instability was found in 18-47% of children. A history of recurrent ankle sprain was found in 22% of children. Conclusion Due to the long-lasting impacts of CAI, future research into the measurement and incidence of ankle instability in children is recommended. PMID:24641786

Genome instability in Novel Lolium multiflorum x L. arundinaceum hybrids

USDA-ARS?s Scientific Manuscript database

We have identified a method whereby Lolium multiflorum (Lm) or L. arundinaceum (Fa) genomes are preferentially eliminated through a mitotic loss behavior in interspecific Lm x Fa F1 hybrids,generating either dihaploid Lm lines or Fa lines. The genome instability has been visualized phenotypically an...

[Symptoms of DSM IV borderline personality disorder in a nonclinical population of adolescents: study of a series of 35 patients].

PubMed

Chabrol, H; Chouicha, K; Montovany, A; Callahan, S

2001-01-01

1,363 high school students were solicited to complete a personality disorder questionnaire and were encouraged to continue in the study by signing up for interviews with Master's level psychology students. 107 students (7.8%, 34 males, 73 females, mean age = 16.7 +/- 1.8) manifested themselves for the interview and were assessed by using structured diagnostic interviews for borderline personality disorder and major depressive disorder (DIB-R, Revised Diagnostic Interview for Borderlines; MINI, Mini International Neuropsychiatric Interview). The interviews were audiotaped. Interrater reliability was determined by independent ratings of 12 borderline subjects and 12 non-borderline subjects (kappa: 0.795). The distribution of the 107 subjects based on the number of DSM IV borderline personality disorder criteria indicated a gradual dispersion suggesting a continuum from normality to borderline personality disorder: 8% of the subjects met none of the criteria; 16% met one criterion; 17% met two; 12.5%, three; 13.7%, four; 8.4%, five; 5.6%, six; 9.3%, seven; 4.6%, eight; 4.6%, nine. Thirty-five of these 107 subjects (32.7%, 6 males, 29 females, mean age = 16.7 +/- 1.7) received a diagnosis of borderline personality disorder according to DSM IV criteria. The most frequent symptoms were paranoid ideation or dissociative symptoms (97.1%), affective instability (88.6%), inappropriate, intense anger (85.6%), suicidal gestures or automutilation (82.9%), followed by frantic efforts to avoid abandonment (77%), impulsivity (65.7%), unstable and intense relationships (62.9%), identity disturbance (60%), and emptiness (57.1%). The comparison between borderline and non-borderline subjects showed that all borderline personality disorder criteria discriminated significantly between the two groups. The high incidence of paranoid ideation (97.1%) and dissociative experiences (65.7%) in the borderline group suggests the pertinence of criterion 9 in the diagnosis of borderline personality disorder in adolescents. Two criteria of schizotypal personality disorder were also frequent in this group: 68.6% of the borderline group reported odd beliefs or magical thinking, in particular beliefs in clairvoyance or telepathy and 88.6% reported unusual perceptual experiences, in particular sensing the presence of a force or person and bodily illusions. Moreover, 31.4% of the borderline group reported transient "quasi" psychotic experiences, mainly "quasi" visual hallucinations. Auditory hallucinations or delusional ideas were not observed. This symptomatology suggests a "quasi" psychotic dimension of adolescent borderline personality disorder. Affective instability was the next most frequent symptom which was usually marked by a cyclothymic appearance. Comorbidity with major depressive disorder was high: 85.7% of the borderline subjects had a concurrent diagnosis of major depression versus 45.8% of the non-borderline subjects. Thus, major depression is more frequent than most of the borderline personality disorder criteria, with the exception of the already noted paranoid ideation and affective instability. Hypomanic symptoms were frequent in the borderline group (65.7%) as well as in the non-borderline group (38.8%). This symptomatology suggests that adolescent borderline personality disorder is linked to an attenuated bipolar spectrum characterised by major depressive episodes and soft signs of bipolarity. However, hypomanic symptoms, which were quite frequent in non-borderline subjects, might also be due to a mechanism of defence, i.e. the denial of depression. Comorbidity with anxiety disorders appeared also to be high: anxiety symptoms were found in 91.4% of the borderline subjects who reported symptoms of generalised anxiety disorder, panic disorder, and somatoform disorders. The overall clinical appearance of these borderline adolescents not referred for treatment seemed to be quite similar to that of borderline adolescents in clinical samples. This study shows that adolescent borderline personality disorder in non-clinical population is a serious disorder characterised by the importance of mental suffering and behavioural disturbances the disorganising power of which may fix the developmental process in a pathological pathway. Adolescent borderline personality disorder appears in this study to be strongly associated with major depressive disorder and at-risk behaviours linked to impulsivity, affective instability, and suicidal ideation. However, this study found an absence of precise cut-off between borderline and non-borderline subjects. Two factors might have contributed to the appearance of a continuum. First, some degree of impulsivity and instability in affectivity, self-images and interpersonal relationships is part of normal adolescence. (ABSTRACT TRUNCATED)

Instability mechanisms and transition scenarios of spiral turbulence in Taylor-Couette flow.

PubMed

Meseguer, Alvaro; Mellibovsky, Fernando; Avila, Marc; Marques, Francisco

2009-10-01

Alternating laminar and turbulent helical bands appearing in shear flows between counterrotating cylinders are accurately computed and the near-wall instability phenomena responsible for their generation identified. The computations show that this intermittent regime can only exist within large domains and that its spiral coherence is not dictated by endwall boundary conditions. A supercritical transition route, consisting of a progressive helical alignment of localized turbulent spots, is carefully studied. Subcritical routes disconnected from secondary laminar flows have also been identified.

High Frequency Adaptive Instability Suppression Controls in a Liquid-Fueled Combustor

NASA Technical Reports Server (NTRS)

Kopasakis, George

2003-01-01

This effort extends into high frequency (>500 Hz), an earlier developed adaptive control algorithm for the suppression of thermo-acoustic instabilities in a liquidfueled combustor. The earlier work covered the development of a controls algorithm for the suppression of a low frequency (280 Hz) combustion instability based on simulations, with no hardware testing involved. The work described here includes changes to the simulation and controller design necessary to control the high frequency instability, augmentations to the control algorithm to improve its performance, and finally hardware testing and results with an experimental combustor rig developed for the high frequency case. The Adaptive Sliding Phasor Averaged Control (ASPAC) algorithm modulates the fuel flow in the combustor with a control phase that continuously slides back and forth within the phase region that reduces the amplitude of the instability. The results demonstrate the power of the method - that it can identify and suppress the instability even when the instability amplitude is buried in the noise of the combustor pressure. The successful testing of the ASPAC approach helped complete an important NASA milestone to demonstrate advanced technologies for low-emission combustors.

SPIRAL INSTABILITY CAN DRIVE THERMONUCLEAR EXPLOSIONS IN BINARY WHITE DWARF MERGERS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kashyap, Rahul; Fisher, Robert; García-Berro, Enrique

2015-02-10

Thermonuclear, or Type Ia supernovae (SNe Ia), originate from the explosion of carbon–oxygen white dwarfs, and serve as standardizable cosmological candles. However, despite their importance, the nature of the progenitor systems that give rise to SNe Ia has not been hitherto elucidated. Observational evidence favors the double-degenerate channel in which merging white dwarf binaries lead to SNe Ia. Furthermore, significant discrepancies exist between observations and theory, and to date, there has been no self-consistent merger model that yields a SNe Ia. Here we show that a spiral mode instability in the accretion disk formed during a binary white dwarf mergermore » leads to a detonation on a dynamical timescale. This mechanism sheds light on how white dwarf mergers may frequently yield SNe Ia.« less

Association between Recurrent Metastasis from Stage II and III Primary Colorectal Tumors and Moderate Microsatellite Instability

PubMed Central

Garcia, Melissa; Choi, Chan; Kim, Hyeong-Rok; Daoud, Yahya; Toiyama, Yuji; Takahashi, Masanobu; Goel, Ajay; Boland, C Richard; Koi, Minoru

2012-01-01

Colorectal cancer (CRC) cells frequently have low levels of microsatellite instability (MSI-L) and elevated microsatellite alterations at tetranucleotide repeats (EMAST), but little is known about the clinicopathological significance of these features. We observed that patients with stage II or III CRC with MSI-L and/or EMAST had a shorter times of recurrence-free survival than patients with high levels of MSI (MSI-H) (P=.0084) or with highly stable microsatellites (H-MSS) (P=.0415), based on Kaplan-Meier analysis. MSI-L and/or EMAST were independent predictors of recurrent distant metastasis from primary stage II or III colorectal tumors (Cox proportional hazard analysis hazard ratio, 1.83; 95% confidence interval, 1.06–3.15; P=.0301). PMID:22465427

Chromosomal instability mediated by non-B DNA: cruciform conformation and not DNA sequence is responsible for recurrent translocation in humans.

PubMed

Inagaki, Hidehito; Ohye, Tamae; Kogo, Hiroshi; Kato, Takema; Bolor, Hasbaira; Taniguchi, Mariko; Shaikh, Tamim H; Emanuel, Beverly S; Kurahashi, Hiroki

2009-02-01

Chromosomal aberrations have been thought to be random events. However, recent findings introduce a new paradigm in which certain DNA segments have the potential to adopt unusual conformations that lead to genomic instability and nonrandom chromosomal rearrangement. One of the best-studied examples is the palindromic AT-rich repeat (PATRR), which induces recurrent constitutional translocations in humans. Here, we established a plasmid-based model that promotes frequent intermolecular rearrangements between two PATRRs in HEK293 cells. In this model system, the proportion of PATRR plasmid that extrudes a cruciform structure correlates to the levels of rearrangement. Our data suggest that PATRR-mediated translocations are attributable to unusual DNA conformations that confer a common pathway for chromosomal rearrangements in humans.

Theoretical and experimental design studies for the Atmospheric General Circulation Experiment

NASA Technical Reports Server (NTRS)

Fowlis, W. W.; Hathaway, D. H.; Miller, T. L.; Roberts, G. O.; Kopecky, K. J.

1985-01-01

The major criterion for the Atmospheric General Circulation Experiment (AGCE) design is that it be possible to realize strong baroclinic instability in the spherical configuration chosen. A configuration was selected in which a hemispherical shell of fluid is subjected to latitudinal temperature gradients on its spherical boundaries and the latitudinal boundaries are insulators. Work in the laboratory with a cylindrical version of this configuration revealed more instabilities than baroclinic instability. Since researchers fully expect these additional instabilities to appear in the spherical configuration also, they decided to continue the laboratory cylindrical annulus studies. Four flow regimes were identified: an axisymmetric Hadley circulation, boundary layer convection, baroclinic waves and deep thermal convection. Regime diagrams were prepared.

Instabilities in a staircase stratified shear flow

NASA Astrophysics Data System (ADS)

Ponetti, G.; Balmforth, N. J.; Eaves, T. S.

2018-01-01

We study stratified shear flow instability where the density profile takes the form of a staircase of interfaces separating uniform layers. Internal gravity waves riding on density interfaces can resonantly interact due to a background shear flow, resulting in the Taylor-Caulfield instability. The many steps of the density profile permit a multitude of interactions between different interfaces, and a rich variety of Taylor-Caulfield instabilities. We analyse the linear instability of a staircase with piecewise-constant density profile embedded in a background linear shear flow, locating all the unstable modes and identifying the strongest. The interaction between nearest-neighbour interfaces leads to the most unstable modes. The nonlinear dynamics of the instabilities are explored in the long-wavelength, weakly stratified limit (the defect approximation). Unstable modes on adjacent interfaces saturate by rolling up the intervening layer into a distinctive billow. These nonlinear structures coexist when stacked vertically and are bordered by the sharp density gradients that are the remnants of the steps of the original staircase. Horizontal averages remain layer-like.

Systematic review of postural control and lateral ankle instability, part I: can deficits be detected with instrumented testing.

PubMed

McKeon, Patrick O; Hertel, Jay

2008-01-01

To answer the following clinical questions: (1) Is poor postural control associated with increased risk of a lateral ankle sprain? (2) Is postural control adversely affected after acute lateral ankle sprain? (3) Is postural control adversely affected in those with chronic ankle instability? PubMed and CINAHL entries from 1966 through October 2006 were searched using the terms ankle sprain, ankle instability, balance, chronic ankle instability, functional ankle instability, postural control, and postural sway. Only studies assessing postural control measures in participants on a stable force plate performing the modified Romberg test were included. To be included, a study had to address at least 1 of the 3 clinical questions stated above and provide adequate results for calculation of effect sizes or odds ratios where applicable. We calculated odds ratios with 95% confidence intervals for studies assessing postural control as a risk factor for lateral ankle sprains. Effect sizes were estimated with the Cohen d and associated 95% confidence intervals for comparisons of postural control performance between healthy and injured groups, or healthy and injured limbs, respectively. Poor postural control is most likely associated with an increased risk of sustaining an acute ankle sprain. Postural control is impaired after acute lateral ankle sprain, with deficits identified in both the injured and uninjured sides compared with controls. Although chronic ankle instability has been purported to be associated with altered postural control, these impairments have not been detected consistently with the use of traditional instrumented measures. Instrumented postural control testing on stable force plates is better at identifying deficits that are associated with an increased risk of ankle sprain and that occur after acute ankle sprains than at detecting deficits related to chronic ankle instability.

Hepatic Differentiation and Maturation of Human Embryonic Stem Cells Cultured in a Perfused Three-Dimensional Bioreactor

PubMed Central

Synnergren, Jane; Jensen, Janne; Björquist, Petter; Ingelman-Sundberg, Magnus

2013-01-01

Drug-induced liver injury is a serious and frequently occurring adverse drug reaction in the clinics and is hard to predict during preclinical studies. Today, primary hepatocytes are the most frequently used cell model for drug discovery and prediction of toxicity. However, their use is marred by high donor variability regarding drug metabolism and toxicity, and instable expression levels of liver-specific genes such as cytochromes P450. An in vitro model system based on human embryonic stem cells (hESC), with their unique properties of pluripotency and self-renewal, has potential to provide a stable and unlimited supply of human hepatocytes. Much effort has been made to direct hESC toward the hepatic lineage, mostly using 2-dimensional (2D) cultures. Although the results are encouraging, these cells lack important functionality. Here, we investigate if hepatic differentiation of hESC can be improved by using a 3-dimensional (3D) bioreactor system. Human ESCs were differentiated toward the hepatic lineage using the same cells in either the 3D or 2D system. A global transcriptional analysis identified important differences between the 2 differentiation regimes, and we identified 10 pathways, highly related to liver functions, which were significantly upregulated in cells differentiated in the bioreactor compared to 2D control cultures. The enhanced hepatic differentiation observed in the bioreactor system was also supported by immunocytochemistry. Taken together, our results suggest that hepatic differentiation of hESC is improved when using this 3D bioreactor technology as compared to 2D culture systems. PMID:22970843

Hepatic differentiation and maturation of human embryonic stem cells cultured in a perfused three-dimensional bioreactor.

PubMed

Sivertsson, Louise; Synnergren, Jane; Jensen, Janne; Björquist, Petter; Ingelman-Sundberg, Magnus

2013-02-15

Drug-induced liver injury is a serious and frequently occurring adverse drug reaction in the clinics and is hard to predict during preclinical studies. Today, primary hepatocytes are the most frequently used cell model for drug discovery and prediction of toxicity. However, their use is marred by high donor variability regarding drug metabolism and toxicity, and instable expression levels of liver-specific genes such as cytochromes P450. An in vitro model system based on human embryonic stem cells (hESC), with their unique properties of pluripotency and self-renewal, has potential to provide a stable and unlimited supply of human hepatocytes. Much effort has been made to direct hESC toward the hepatic lineage, mostly using 2-dimensional (2D) cultures. Although the results are encouraging, these cells lack important functionality. Here, we investigate if hepatic differentiation of hESC can be improved by using a 3-dimensional (3D) bioreactor system. Human ESCs were differentiated toward the hepatic lineage using the same cells in either the 3D or 2D system. A global transcriptional analysis identified important differences between the 2 differentiation regimes, and we identified 10 pathways, highly related to liver functions, which were significantly upregulated in cells differentiated in the bioreactor compared to 2D control cultures. The enhanced hepatic differentiation observed in the bioreactor system was also supported by immunocytochemistry. Taken together, our results suggest that hepatic differentiation of hESC is improved when using this 3D bioreactor technology as compared to 2D culture systems.

The Frequency of Autoimmune N-Methyl-D-Aspartate Receptor Encephalitis Surpasses That of Individual Viral Etiologies in Young Individuals Enrolled in the California Encephalitis Project

PubMed Central

Sheriff, Heather; Dalmau, Josep; Tilley, Drake H.; Glaser, Carol A.

2012-01-01

Background. In 2007, the California Encephalitis Project (CEP), which was established to study the epidemiology of encephalitis, began identifying cases of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Increasing numbers of anti-NMDAR encephalitis cases have been identified at the CEP, and this form rivals commonly known viral etiologies as a causal agent. We report here the relative frequency and differences among encephalitides caused by anti-NMDAR and viral etiologies within the CEP experience. Methods. Demographic, frequency, and clinical data from patients with anti-NMDAR encephalitis are compared with those with viral encephalitic agents: enterovirus, herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), and West Nile virus (WNV). All examined cases presented to the CEP between September 2007 and February 2011 and are limited to individuals aged ≤30 years because of the predominance of anti-NMDAR encephalitis in this group. The diagnostic costs incurred in a single case are also included. Results. Anti-NMDAR encephalitis was identified >4 times as frequently as HSV-1, WNV, or VZV and was the leading entity identified in our cohort. We found that 65% of anti-NMDAR encephalitis occurred in patients aged ≤18 years. This disorder demonstrated a predilection, which was not observed with viral etiologies, for females (P < .01). Seizures, language dysfunction, psychosis, and electroencephalographic abnormalities were significantly more frequent in patients with anti-NMDAR encephalitis (P < .05), and autonomic instability occurred exclusively in this group. Discussion. Anti-NMDAR encephalitis rivals viral etiologies as a cause of encephalitis within the CEP cohort. This entity deserves a prominent place on the encephalitic differential diagnosis to avoid unnecessary diagnostic and treatment costs, and to permit a more timely treatment. PMID:22281844

Landscape of Microsatellite Instability Across 39 Cancer Types.

PubMed

Bonneville, Russell; Krook, Melanie A; Kautto, Esko A; Miya, Jharna; Wing, Michele R; Chen, Hui-Zi; Reeser, Julie W; Yu, Lianbo; Roychowdhury, Sameek

2017-01-01

Microsatellite instability (MSI) is a pattern of hypermutation that occurs at genomic microsatellites and is caused by defects in the mismatch repair system. Mismatch repair deficiency that leads to MSI has been well described in several types of human cancer, most frequently in colorectal, endometrial, and gastric adenocarcinomas. MSI is known to be both predictive and prognostic, especially in colorectal cancer; however, current clinical guidelines only recommend MSI testing for colorectal and endometrial cancers. Therefore, less is known about the prevalence and extent of MSI among other types of cancer. Using our recently published MSI-calling software, MANTIS, we analyzed whole-exome data from 11,139 tumor-normal pairs from The Cancer Genome Atlas and Therapeutically Applicable Research to Generate Effective Treatments projects and external data sources across 39 cancer types. Within a subset of these cancer types, we assessed mutation burden, mutational signatures, and somatic variants associated with MSI. We identified MSI in 3.8% of all cancers assessed-present in 27 of tumor types-most notably adrenocortical carcinoma (ACC), cervical cancer (CESC), and mesothelioma, in which MSI has not yet been well described. In addition, MSI-high ACC and CESC tumors were observed to have a higher average mutational burden than microsatellite-stable ACC and CESC tumors. We provide evidence of as-yet-unappreciated MSI in several types of cancer. These findings support an expanded role for clinical MSI testing across multiple cancer types as patients with MSI-positive tumors are predicted to benefit from novel immunotherapies in clinical trials.

Long-term Outcome of Unconstrained Primary Total Hip Arthroplasty in Ipsilateral Residual Poliomyelitis.

PubMed

Buttaro, Martín A; Slullitel, Pablo A; García Mansilla, Agustín M; Carlucci, Sofía; Comba, Fernando M; Zanotti, Gerardo; Piccaluga, Francisco

2017-03-01

Incapacitating articular sequelae in the hip joint have been described for patients with late effects of poliomyelitis. In these patients, total hip arthroplasty (THA) has been associated with a substantial rate of dislocation. This study was conducted to evaluate the long-term clinical and radiologic outcomes of unconstrained THA in this specific group of patients. The study included 6 patients with ipsilateral polio who underwent primary THA between 1985 and 2006. Patients with polio who underwent THA on the nonparalytic limb were excluded. Mean follow-up was 119.5 months (minimum, 84 months). Clinical outcomes were evaluated with the modified Harris Hip Score (mHHS) and the visual analog scale (VAS) pain score. Radiographs were examined to identify the cause of complications and determine the need for revision surgery. All patients showed significantly better functional results when preoperative and postoperative mHHS (67.58 vs 87.33, respectively; P=.002) and VAS pain score (7.66 vs 2, respectively; P=.0003) were compared. Although 2 cases of instability were diagnosed, only 1 patient needed acetabular revision as a result of component malpositioning. None of the patients had component loosening, osteolysis, or infection. Unconstrained THA in the affected limb of patients with poliomyelitis showed favorable long-term clinical results, with improved function and pain relief. Nevertheless, instability may be a more frequent complication in this group of patients compared with the general population. [Orthopedics. 2017; 40(2):e255-e261.]. Copyright 2016, SLACK Incorporated.

Supersonic Coaxial Jets: Noise Predictions and Measurements

NASA Technical Reports Server (NTRS)

Dahl, Milo D.; Papamoschou, Dimitri; Hixon, Ray

1998-01-01

The noise from perfectly expanded coaxial jets was measured in an anechoic chamber for different operating conditions with the same total thrust, mass flow, and exit area. The shape of the measured noise spectrum at different angles to the jet axis was found to agree with spectral shapes for single, axisymmetric jets. Based on these spectra, the sound was characterized as being generated by large turbulent structures or fine-scale turbulence. Modeling the large scale structures as instability waves, a stability analysis was conducted for the coaxial jets to identify the growing and decaying instability waves in each shear layer and predict their noise radiation pattern outside the jet. When compared to measured directivity, the analysis identified the region downstream of the outer potential core, where the two shear layers were merging, as the source of the peak radiated noise where instability waves, with their origin in the inner shear layer, reach their maximum amplitude. Numerical computations were also performed using a linearized Euler equation solver. Those results were compared to both the results from the instability wave analysis and to measured data.

Dynamic stability of electrodynamic maglev systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai, Y.; Chen, S.S.; Mulcahy, T.M.

1997-01-01

Because dynamic instabilities are not acceptable in any commercial maglev system, it is important to consider dynamic instability in the development of all maglev systems. This study considers the stability of maglev systems based on mathematical models and experimental data. Divergence and flutter are obtained for coupled vibration of a three-degree-of-freedom maglev vehicle on a guideway consisting of double L-shaped aluminum segments. The theory and analysis for motion-dependent magnetic-force-induced instability developed in this study provides basic stability characteristics and identifies future research needs for maglev systems.

End Point of Black Ring Instabilities and the Weak Cosmic Censorship Conjecture.

PubMed

Figueras, Pau; Kunesch, Markus; Tunyasuvunakool, Saran

2016-02-19

We produce the first concrete evidence that violation of the weak cosmic censorship conjecture can occur in asymptotically flat spaces of five dimensions by numerically evolving perturbed black rings. For certain thin rings, we identify a new, elastic-type instability dominating the evolution, causing the system to settle to a spherical black hole. However, for sufficiently thin rings the Gregory-Laflamme mode is dominant, and the instability unfolds similarly to that of black strings, where the horizon develops a structure of bulges connected by necks which become ever thinner over time.

Consensus in chronic ankle instability: aetiology, assessment, surgical indications and place for arthroscopy.

PubMed

Guillo, S; Bauer, T; Lee, J W; Takao, M; Kong, S W; Stone, J W; Mangone, P G; Molloy, A; Perera, A; Pearce, C J; Michels, F; Tourné, Y; Ghorbani, A; Calder, J

2013-12-01

Ankle sprains are the most common injuries sustained during sports activities. Most ankle sprains recover fully with non-operative treatment but 20-30% develop chronic ankle instability. Predicting which patients who sustain an ankle sprain will develop instability is difficult. This paper summarises a consensus on identifying which patients may require surgery, the optimal surgical intervention along with treatment of concomitant pathology given the evidence available today. It also discusses the role of arthroscopic treatment and the anatomical basis for individual procedures. Copyright © 2013. Published by Elsevier Masson SAS.

Interplay between electric fields generated by reconnection and by secondary processes

NASA Astrophysics Data System (ADS)

Lapenta, G.; Innocenti, M. E.; Pucci, F.; Cazzola, E.; Berchem, J.; Newman, D. L.; El-Alaoui, M.; Walker, R. J.; Goldman, M. V.; Ergun, R.

2017-12-01

Reconnection regions are surrounded by several sources of free energy that push reconnection towards a turbulent regime: beams can drive streaming instabilities, currents can drive tearing like secondary instabilities, velocity and density shears can drive Kelvin-Helmholtz or Rayleigh-Taylor type of instabilities. The interaction between these instabilities can be very complex. For instance, from a kinetic point of view, instabilities resulting from shears are intermixed with drift-type instabilities, such as drift-kink, kink driven by relative species drift, lower hybrid modes of the electrostatic or electromagnetic type. In addition, the interaction with reconnection is two ways: reconnection causes the conditions for those instabilities to develop while the instabilities alter the progress of reconnection. Although MMS has observed features that can be associated with such instabilities: strong localized parallel electric fields (monopolar and bipolar), fluctuations in the drift range (lower hybrid, whistler), it has been difficult to determine which ones operate and how they differ depending on the symmetric and asymmetric reconnection configurations observed in the magnetotail and at the magnetopause, respectively. We present a comparison between the results of kinetic simulations obtained for typical magnetotail and the magnetopause configurations, using for each of them both analytical equilibria and results of global MHD simulations to initialize the iPIC3D simulations. By selecting what drivers (e.g. shear/no shear) are present, we can identify what instabilities develop and determine their effects on the progression of reconnection in the magnetotail and at the magnetopause. We focus especially on the role of drift waves and whistler instabilities, and discuss our results by comparing them with MMS observations.

Non-linear tides in a homogeneous rotating planet or star: global modes and elliptical instability

NASA Astrophysics Data System (ADS)

Barker, Adrian J.; Braviner, Harry J.; Ogilvie, Gordon I.

2016-06-01

We revisit the global modes and instabilities of homogeneous rotating ellipsoidal fluid masses, which are the simplest global models of rotationally and tidally deformed gaseous planets or stars. The tidal flow in a short-period planet may be unstable to the elliptical instability, a hydrodynamic instability that can drive tidal evolution. We perform a global (and local WKB) analysis to study this instability using the elegant formalism of Lebovitz & Lifschitz. We survey the parameter space of global instabilities with harmonic orders ℓ ≤ 5, for planets with spins that are purely aligned (prograde) or anti-aligned (retrograde) with their orbits. In general, the instability has a much larger growth rate if the planetary spin and orbit are anti-aligned rather than aligned. We have identified a violent instability for anti-aligned spins outside of the usual frequency range for the elliptical instability (when n/Ω ≲ -1, where n and Ω are the orbital and spin angular frequencies, respectively) if the tidal amplitude is sufficiently large. We also explore the instability in a rigid ellipsoidal container, which is found to be quantitatively similar to that with a realistic free surface. Finally, we study the effect of rotation and tidal deformation on mode frequencies. We find that larger rotation rates and larger tidal deformations both decrease the frequencies of the prograde sectoral surface gravity modes. This increases the prospect of their tidal excitation, potentially enhancing the tidal response over expectations from linear theory. In a companion paper, we use our results to interpret global simulations of the elliptical instability.

Investigation on thermo-acoustic instability dynamic characteristics of hydrocarbon fuel flowing in scramjet cooling channel based on wavelet entropy method

NASA Astrophysics Data System (ADS)

Zan, Hao; Li, Haowei; Jiang, Yuguang; Wu, Meng; Zhou, Weixing; Bao, Wen

2018-06-01

As part of our efforts to find ways and means to further improve the regenerative cooling technology in scramjet, the experiments of thermo-acoustic instability dynamic characteristics of hydrocarbon fuel flowing have been conducted in horizontal circular tubes at different conditions. The experimental results indicate that there is a developing process from thermo-acoustic stability to instability. In order to have a deep understanding on the developing process of thermo-acoustic instability, the method of Multi-scale Shannon Wavelet Entropy (MSWE) based on Wavelet Transform Correlation Filter (WTCF) and Multi-Scale Shannon Entropy (MSE) is adopted in this paper. The results demonstrate that the developing process of thermo-acoustic instability from noise and weak signals is well detected by MSWE method and the differences among the stability, the developing process and the instability can be identified. These properties render the method particularly powerful for warning thermo-acoustic instability of hydrocarbon fuel flowing in scramjet cooling channels. The mass flow rate and the inlet pressure will make an influence on the developing process of the thermo-acoustic instability. The investigation on thermo-acoustic instability dynamic characteristics at supercritical pressure based on wavelet entropy method offers guidance on the control of scramjet fuel supply, which can secure stable fuel flowing in regenerative cooling system.

[Instability of the distal radioulnar joint: Treatment options for ulnar lesions of the triangular fibrocartilage complex].

PubMed

Spies, C K; Prommersberger, K J; Langer, M; Müller, L P; Hahn, P; Unglaub, F

2015-08-01

Injuries of the triangular fibrocartilage complex (TFCC) may be fatal to the distal radioulnar joint (DRUJ). This structure is one of the crucial stabilizers and guarantees unrestricted pronosupination of the forearm. A systematic examination is mandatory to diagnose DRUJ instability reliably. A clinical examination in comparison to the contralateral side is obligatory. Plain radiographs are required to exclude osseous lesions or deformities. Computed tomography of both wrists in neutral, pronation and supination is necessary to verify DRUJ instability in ambiguous situations. Based on a systematic examination wrist and DRUJ arthroscopy identify lesions clearly. Injuries of the radioulnar ligaments which entail DRUJ instability, should be reconstructed preferably anatomically. Ulnar-sided TFCC lesions may often cause DRUJ instability. Osseous ligament avulsions are mostly treated osteosynthetically. Ligament tears may be refixated using anchor or transosseous sutures. Tendon transplants are necessary for an anatomical reconstruction in cases of irreparable ruptures.

Assessment of anterior shoulder instability by CT arthrography.

PubMed

Yang, S O; Cho, K J; Kim, M J; Ro, I W

1987-09-01

Computed tomography (CT) immediately after double-contrast shoulder arthrography was taken in twenty-two young male patients with anterior shoulder instability including recurrent dislocation and subluxation. This recently developed technique called CT arthrography can provide significant information about patients with glenohumeral instability which is difficult to obtain by conventional arthrography. Information about glenoid labrum pathology is useful for proper management of the shoulder with instability. Lesions identified in this study include anterior labral defects (attenuation, tear, displacement), anterior capsular distension and/or detachment, Hill-Sachs lesion, anterior glenoid rim compression fracture, and fracture of scapula. This article describes the method used in CT arthrography of the glenohumeral joint, reviews the normal cross-sectional anatomy, and emphasizes the importance of the application of CT arthrography in the shoulder disorder with instability. CT arthrography of the glenohumeral joint is easy to perform, is accurate, and has lower radiation dose than arthrotomography.

Active Combustion Control for Aircraft Gas-Turbine Engines-Experimental Results for an Advanced, Low-Emissions Combustor Prototype

NASA Technical Reports Server (NTRS)

DeLaat, John C.; Kopasakis, George; Saus, Joseph R.; Chang, Clarence T.; Wey, Changlie

2012-01-01

Lean combustion concepts for aircraft engine combustors are prone to combustion instabilities. Mitigation of instabilities is an enabling technology for these low-emissions combustors. NASA Glenn Research Center s prior activity has demonstrated active control to suppress a high-frequency combustion instability in a combustor rig designed to emulate an actual aircraft engine instability experience with a conventional, rich-front-end combustor. The current effort is developing further understanding of the problem specifically as applied to future lean-burning, very low-emissions combustors. A prototype advanced, low-emissions aircraft engine combustor with a combustion instability has been identified and previous work has characterized the dynamic behavior of that combustor prototype. The combustor exhibits thermoacoustic instabilities that are related to increasing fuel flow and that potentially prevent full-power operation. A simplified, non-linear oscillator model and a more physics-based sectored 1-D dynamic model have been developed to capture the combustor prototype s instability behavior. Utilizing these models, the NASA Adaptive Sliding Phasor Average Control (ASPAC) instability control method has been updated for the low-emissions combustor prototype. Active combustion instability suppression using the ASPAC control method has been demonstrated experimentally with this combustor prototype in a NASA combustion test cell operating at engine pressures, temperatures, and flows. A high-frequency fuel valve was utilized to perturb the combustor fuel flow. Successful instability suppression was shown using a dynamic pressure sensor in the combustor for controller feedback. Instability control was also shown with a pressure feedback sensor in the lower temperature region upstream of the combustor. It was also demonstrated that the controller can prevent the instability from occurring while combustor operation was transitioning from a stable, low-power condition to a normally unstable high-power condition, thus enabling the high-power condition.

Tibiofemoral Instability After Primary Total Knee Arthroplasty: Posterior-Stabilized Implants for Obese Patients.

PubMed

Can, Ata; Erdogan, Fahri; Erdogan, Ayse Ovul

2017-09-01

Tibiofemoral instability is a common complication after total knee arthroplasty (TKA), accounting for up to 22% of all revision procedures. Instability is the second most common cause of revision in the first 5 years after primary TKA. In this study, 13 knees with tibiofemoral instability after TKA were identified among 693 consecutive primary TKA procedures. Patient demographics, body mass index, clinical symptoms, previous deformity, previous knee surgery, complications, interval between index TKA and first tibiofemoral instability, causes of instability, and interval between index TKA and revision TKA were retrospectively reviewed. Clinical outcomes were assessed with the Lysholm Knee Scoring Scale. All patients were women, and mean body mass index was 37.7 kg/m 2 (range, 27.2-52.6 kg/m 2 ). Mean interval between index TKA and first tibiofemoral instability was 23.4 months (range, 9-45 months), and mean interval between index TKA and revision TKA was 25.6 months (range, 14-48 months). All patients had posterior cruciate ligament-retaining implants. Of the 13 knees, 11 had flexion instability and 2 had global instability. In all patients, instability was caused by incompetence of the posterior cruciate ligament; additionally, 1 patient had undersized and malpositioned implants. In 4 knees, the polyethylene insert was broken as well. All patients underwent revision TKA. Lysholm Knee Scoring Scale score had improved from a mean of 35.8 (range, 30-46) to a mean of 68.3 (range, 66-76). All patients included in this study were female and obese. The main cause of instability was secondary posterior cruciate ligament rupture and incompetence. The use of posterior-stabilized implants for primary TKA may prevent secondary instability in obese patients. [Orthopedics. 2017; 40(5):e812-e819.]. Copyright 2017, SLACK Incorporated.

Convective instabilities in a ternary alloy mushy layer

NASA Astrophysics Data System (ADS)

Anderson, Daniel; Guba, Peter

2014-11-01

We investigate a mathematical model of convection, thermal and solutal diffusion in a primary mushy layer during the solidification of a ternary alloy. In particular, we explore the influence of phase-change effects, such as solute rejection, latent heat and background solidification, in a linear stability analysis of a non-convecting base state solution. We identify how different rates of diffusion (e.g. double diffusion) as well as how different rates of solute rejection (double solute rejection) play a role in this system. Novel modes of instability that can be present under statically stable conditions are identified. Parcel arguments are proposed to explain the physical mechanisms that give rise to the instabilities. This work was supported in part by the U.S. National Science Foundation, DMS-1107848 (D.M.A.) and by the Slovak Scientific Grant Agency, VEGA 1/0711/12 (P.G.).

Fluctuations and correlations in modulation instability

NASA Astrophysics Data System (ADS)

Solli, D. R.; Herink, G.; Jalali, B.; Ropers, C.

2012-07-01

Stochastically driven nonlinear processes are responsible for spontaneous pattern formation and instabilities in numerous natural and artificial systems, including well-known examples such as sand ripples, cloud formations, water waves, animal pigmentation and heart rhythms. Technologically, a type of such self-amplification drives free-electron lasers and optical supercontinuum sources whose radiation qualities, however, suffer from the stochastic origins. Through time-resolved observations, we identify intrinsic properties of these fluctuations that are hidden in ensemble measurements. We acquire single-shot spectra of modulation instability produced by laser pulses in glass fibre at megahertz real-time capture rates. The temporally confined nature of the gain physically limits the number of amplified modes, which form an antibunched arrangement as identified from a statistical analysis of the data. These dynamics provide an example of pattern competition and interaction in confined nonlinear systems.

Somatic frameshift mutations in the Bloom syndrome BLM gene are frequent in sporadic gastric carcinomas with microsatellite mutator phenotype

PubMed Central

Calin, George; Ranzani, Guglielmina N; Amadori, Dino; Herlea, Vlad; Matei, Irina; Barbanti-Brodano, Giuseppe; Negrini, Massimo

2001-01-01

Background Genomic instability has been reported at microsatellite tracts in few coding sequences. We have shown that the Bloom syndrome BLM gene may be a target of microsatelliteinstability (MSI) in a short poly-adenine repeat located in its coding region. To further characterize the involvement of BLM in tumorigenesis, we have investigated mutations in nine genes containing coding microsatellites in microsatellite mutator phenotype (MMP) positive and negative gastric carcinomas (GCs). Methods We analyzed 50 gastric carcinomas (GCs) for mutations in the BLM poly(A) tract aswell as in the coding microsatellites of the TGFβ1-RII, IGFIIR, hMSH3, hMSH6, BAX, WRN, RECQL and CBL genes. Results BLM mutations were found in 27% of MMP+ GCs (4/15 cases) but not in any of the MMP negative GCs (0/35 cases). The frequency of mutations in the other eight coding regions microsatellite was the following: TGFβ1-RII (60 %), BAX (27%), hMSH6 (20%),hMSH3 (13%), CBL (13%), IGFIIR (7%), RECQL (0%) and WRN (0%). Mutations in BLM appear to be more frequently associated with frameshifts in BAX and in hMSH6and/or hMSH3. Tumors with BLM alterations present a higher frequency of unstable mono- and trinucleotide repeats located in coding regions as compared with mutator phenotype tumors without BLM frameshifts. Conclusions BLM frameshifts are frequent alterations in GCs specifically associated with MMP+tumors. We suggest that BLM loss of function by MSI may increase the genetic instability of a pre-existent unstable genotype in gastric tumors. PMID:11532193

Ion-driven instabilities in the solar wind: Wind observations of 19 March 2005

DOE PAGES

Gary, S. Peter; Jian, Lan K.; Broiles, Thomas W.; ...

2016-01-16

Intervals of enhanced magnetic fluctuations have been frequently observed in the solar wind. However, it remains an open question as to whether these waves are generated at the Sun and then transported outward by the solar wind or generated locally in the interplanetary medium. Magnetic field and plasma measurements from the Wind spacecraft under slow solar wind conditions on 19 March 2005 demonstrate seven events of enhanced magnetic fluctuations at spacecraft-frame frequencies somewhat above the proton cyclotron frequency and propagation approximately parallel or antiparallel to the background magnetic field B o. The proton velocity distributions during these events are characterizedmore » by two components: a more dense, slower core and a less dense, faster beam. In conclusion, observed plasma parameters are used in a kinetic linear dispersion equation analysis for electromagnetic fluctuations at k x B o = 0; for two events the most unstable mode is the Alfvén-cyclotron instability driven by a proton component temperature anisotropy T ⊥/T || > 1 (where the subscripts denote directions relative to B o), and for three events the most unstable mode is the right-hand polarized magnetosonic instability driven primarily by ion component relative flows. Thus, both types of ion anisotropies and both types of instabilities are likely to be local sources of these enhanced fluctuation events in the solar wind.« less

Ion-driven instabilities in the solar wind: Wind observations of 19 March 2005

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gary, S. Peter; Jian, Lan K.; Broiles, Thomas W.

Intervals of enhanced magnetic fluctuations have been frequently observed in the solar wind. However, it remains an open question as to whether these waves are generated at the Sun and then transported outward by the solar wind or generated locally in the interplanetary medium. Magnetic field and plasma measurements from the Wind spacecraft under slow solar wind conditions on 19 March 2005 demonstrate seven events of enhanced magnetic fluctuations at spacecraft-frame frequencies somewhat above the proton cyclotron frequency and propagation approximately parallel or antiparallel to the background magnetic field B o. The proton velocity distributions during these events are characterizedmore » by two components: a more dense, slower core and a less dense, faster beam. In conclusion, observed plasma parameters are used in a kinetic linear dispersion equation analysis for electromagnetic fluctuations at k x B o = 0; for two events the most unstable mode is the Alfvén-cyclotron instability driven by a proton component temperature anisotropy T ⊥/T || > 1 (where the subscripts denote directions relative to B o), and for three events the most unstable mode is the right-hand polarized magnetosonic instability driven primarily by ion component relative flows. Thus, both types of ion anisotropies and both types of instabilities are likely to be local sources of these enhanced fluctuation events in the solar wind.« less

Intrastrand triplex DNA repeats in bacteria: a source of genomic instability

PubMed Central

Holder, Isabelle T.; Wagner, Stefanie; Xiong, Peiwen; Sinn, Malte; Frickey, Tancred; Meyer, Axel; Hartig, Jörg S.

2015-01-01

Repetitive nucleic acid sequences are often prone to form secondary structures distinct from B-DNA. Prominent examples of such structures are DNA triplexes. We observed that certain intrastrand triplex motifs are highly conserved and abundant in prokaryotic genomes. A systematic search of 5246 different prokaryotic plasmids and genomes for intrastrand triplex motifs was conducted and the results summarized in the ITxF database available online at http://bioinformatics.uni-konstanz.de/utils/ITxF/. Next we investigated biophysical and biochemical properties of a particular G/C-rich triplex motif (TM) that occurs in many copies in more than 260 bacterial genomes by CD and nuclear magnetic resonance spectroscopy as well as in vivo footprinting techniques. A characterization of putative properties and functions of these unusually frequent nucleic acid motifs demonstrated that the occurrence of the TM is associated with a high degree of genomic instability. TM-containing genomic loci are significantly more rearranged among closely related Escherichia coli strains compared to control sites. In addition, we found very high frequencies of TM motifs in certain Enterobacteria and Cyanobacteria that were previously described as genetically highly diverse. In conclusion we link intrastrand triplex motifs with the induction of genomic instability. We speculate that the observed instability might be an adaptive feature of these genomes that creates variation for natural selection to act upon. PMID:26450966

Ion-driven instabilities in the solar wind: Wind observations of 19 March 2005.

PubMed

Gary, S Peter; Jian, Lan K; Broiles, Thomas W; Stevens, Michael L; Podesta, John J; Kasper, Justin C

2016-01-01

Intervals of enhanced magnetic fluctuations have been frequently observed in the solar wind. But it remains an open question as to whether these waves are generated at the Sun and then transported outward by the solar wind or generated locally in the interplanetary medium. Magnetic field and plasma measurements from the Wind spacecraft under slow solar wind conditions on 19 March 2005 demonstrate seven events of enhanced magnetic fluctuations at spacecraft-frame frequencies somewhat above the proton cyclotron frequency and propagation approximately parallel or antiparallel to the background magnetic field B o . The proton velocity distributions during these events are characterized by two components: a more dense, slower core and a less dense, faster beam. Observed plasma parameters are used in a kinetic linear dispersion equation analysis for electromagnetic fluctuations at k x B o  = 0; for two events the most unstable mode is the Alfvén-cyclotron instability driven by a proton component temperature anisotropy T ⊥ /T ||  > 1 (where the subscripts denote directions relative to B o ), and for three events the most unstable mode is the right-hand polarized magnetosonic instability driven primarily by ion component relative flows. Thus, both types of ion anisotropies and both types of instabilities are likely to be local sources of these enhanced fluctuation events in the solar wind.

Ion‐driven instabilities in the solar wind: Wind observations of 19 March 2005

PubMed Central

Jian, Lan K.; Broiles, Thomas W.; Stevens, Michael L.; Podesta, John J.; Kasper, Justin C.

2016-01-01

Abstract Intervals of enhanced magnetic fluctuations have been frequently observed in the solar wind. But it remains an open question as to whether these waves are generated at the Sun and then transported outward by the solar wind or generated locally in the interplanetary medium. Magnetic field and plasma measurements from the Wind spacecraft under slow solar wind conditions on 19 March 2005 demonstrate seven events of enhanced magnetic fluctuations at spacecraft‐frame frequencies somewhat above the proton cyclotron frequency and propagation approximately parallel or antiparallel to the background magnetic field B o. The proton velocity distributions during these events are characterized by two components: a more dense, slower core and a less dense, faster beam. Observed plasma parameters are used in a kinetic linear dispersion equation analysis for electromagnetic fluctuations at k x B o = 0; for two events the most unstable mode is the Alfvén‐cyclotron instability driven by a proton component temperature anisotropy T⊥/T|| > 1 (where the subscripts denote directions relative to B o), and for three events the most unstable mode is the right‐hand polarized magnetosonic instability driven primarily by ion component relative flows. Thus, both types of ion anisotropies and both types of instabilities are likely to be local sources of these enhanced fluctuation events in the solar wind. PMID:27818854

Self-reported knee joint instability is related to passive mechanical stiffness in medial knee osteoarthritis.

PubMed

Creaby, Mark W; Wrigley, Tim V; Lim, Boon-Whatt; Hinman, Rana S; Bryant, Adam L; Bennell, Kim L

2013-11-20

Self-reported knee joint instability compromises function in individuals with medial knee osteoarthritis and may be related to impaired joint mechanics. The purpose of this study was to evaluate the relationship between self-reported instability and the passive varus-valgus mechanical behaviour of the medial osteoarthritis knee. Passive varus-valgus angular laxity and stiffness were assessed using a modified isokinetic dynamometer in 73 participants with medial tibiofemoral osteoarthritis. All participants self-reported the absence or presence of knee instability symptoms and the degree to which instability affected daily activity on a 6-point likert scale. Forward linear regression modelling identified a significant inverse relationship between passive mid-range knee stiffness and symptoms of knee instability (r = 0.27; P < 0.05): reduced stiffness was indicative of more severe instability symptoms. Angular laxity and end-range stiffness were not related to instability symptoms (P > 0.05). Conceivably, a stiffer passive system may contribute toward greater joint stability during functional activities. Importantly however, net joint stiffness is influenced by both active and passive stiffness, and thus the active neuromuscular system may compensate for reduced passive stiffness in order to maintain joint stability. Future work is merited to examine the role of active stiffness in symptomatic joint stability.

Self-reported knee joint instability is related to passive mechanical stiffness in medial knee osteoarthritis

PubMed Central

2013-01-01

Background Self-reported knee joint instability compromises function in individuals with medial knee osteoarthritis and may be related to impaired joint mechanics. The purpose of this study was to evaluate the relationship between self-reported instability and the passive varus-valgus mechanical behaviour of the medial osteoarthritis knee. Methods Passive varus-valgus angular laxity and stiffness were assessed using a modified isokinetic dynamometer in 73 participants with medial tibiofemoral osteoarthritis. All participants self-reported the absence or presence of knee instability symptoms and the degree to which instability affected daily activity on a 6-point likert scale. Results Forward linear regression modelling identified a significant inverse relationship between passive mid-range knee stiffness and symptoms of knee instability (r = 0.27; P < 0.05): reduced stiffness was indicative of more severe instability symptoms. Angular laxity and end-range stiffness were not related to instability symptoms (P > 0.05). Conclusions Conceivably, a stiffer passive system may contribute toward greater joint stability during functional activities. Importantly however, net joint stiffness is influenced by both active and passive stiffness, and thus the active neuromuscular system may compensate for reduced passive stiffness in order to maintain joint stability. Future work is merited to examine the role of active stiffness in symptomatic joint stability. PMID:24252592

Anterior Shoulder Instability in the Military Athlete.

PubMed

Waterman, Brian; Owens, Brett D; Tokish, John M

Given its young, predominately male demographics and intense physical demands, the US military remains an ideal cohort for the study of anterior shoulder instability. A literature search of PubMed, MEDLINE, and the Cochrane Database was performed to identify all peer-reviewed publications from 1950 to 2016 from US military orthopaedic surgeons focusing on the management of anterior shoulder instability. Clinical review. Level 4. The incidence of anterior shoulder instability events in the military occurs at an order of magnitude greater than in civilian populations, with rates as high as 3% per year among high-risk groups. With more than 90% risk of a Bankart lesion and high risk for instability recurrence, the military has advocated for early intervention of first-time shoulder instability while documenting up to 76% relative risk reduction versus nonoperative treatment. Preoperative evaluation with advanced radiographic imaging should be used to evaluate for attritional bone loss or "off-track" engaging defects to guide comprehensive surgical management. With complex recurrent shoulder instability and/or cases of clinically significant osseous lesions, potential options such as remplissage, anterior open capsular procedures, or bone augmentation procedures may be preferentially considered. Careful risk stratification, clinical evaluation, and selective surgical management for at-risk military patients with anterior shoulder instability can optimize the recurrence risk and functional outcome in this population.

Microstructure Instability of Candidate Fuel Cladding Alloys: Corrosion and Stress Corrosion Cracking Implications

NASA Astrophysics Data System (ADS)

Jiao, Yinan; Zheng, Wenyue; Guzonas, David; Kish, Joseph

2016-02-01

This paper addresses some of the overarching aspects of microstructure instability expected from both high temperature and radiation exposure that could affect the corrosion and stress corrosion cracking (SCC) resistance of the candidate austenitic Fe-Cr-Ni alloys being considered for the fuel cladding of the Canadian supercritical water-cooled reactor (SCWR) concept. An overview of the microstructure instability expected by both exposures is presented prior to turning the focus onto the implications of such instability on the corrosion and SCC resistance. Results from testing conducted using pre-treated (thermally-aged) Type 310S stainless steel to shed some light on this important issue are included to help identify the outstanding corrosion resistance assessment needs.

On the ejection-induced instability in Navier-Stokes solutions of unsteady separation.

PubMed

Obabko, Aleksandr V; Cassel, Kevin W

2005-05-15

Numerical solutions of the flow induced by a thick-core vortex have been obtained using the unsteady, two-dimensional Navier-Stokes equations. The presence of the vortex causes an adverse pressure gradient along the surface, which leads to unsteady separation. The calculations by Brinckman and Walker for a similar flow identify a possible instability, purported to be an inviscid Rayleigh instability, in the region where ejection of near-wall vorticity occurs during the unsteady separation process. In results for a range of Reynolds numbers in the present investigation, the oscillations are also found to occur. However, they can be eliminated with increased grid resolution. Despite this behaviour, the instability may be physical but requires a sufficient amplitude of disturbances to be realized.

Radiation-induced instability and its relation to radiation carcinogenesis

NASA Technical Reports Server (NTRS)

Ullrich, R. L.; Ponnaiya, B.

1998-01-01

PURPOSE: A model that identifies radiation-induced genetic instability as the earliest cellular event in the multi-step sequence leading to radiation-induced cancer was previously proposed. In this paper ongoing experiments are discussed which are designed to test this model and its predictions in mouse mammary epithelial cells. RESULTS: Several lines of evidence are presented that appear to support this model: first, the development of delayed mutations in p53 following irradiation in altered growth variants; secondly, the high frequencies for the induction of both instability and transformation following irradiation in mammary epithelial cells; and finally, the demonstration that susceptibility to the induction of cytogenetic instability is a heritable trait that correlates with susceptibility to transformation and radiation-induced mammary cancer. Mice resistant to transformation and mammary cancer development are also resistant to the development of instability after irradiation. In contrast, mice sensitive to transformation and cancer are also sensitive to the development of cytogenetic instability. CONCLUSIONS: Data from this laboratory and from the studies cited above suggest a specific, and perhaps unique, role for radiation-induced instability as a critical early event associated with initiation of the carcinogenic process.

Parametric Instability Rates in Periodically Driven Band Systems

NASA Astrophysics Data System (ADS)

Lellouch, S.; Bukov, M.; Demler, E.; Goldman, N.

2017-04-01

In this work, we analyze the dynamical properties of periodically driven band models. Focusing on the case of Bose-Einstein condensates, and using a mean-field approach to treat interparticle collisions, we identify the origin of dynamical instabilities arising from the interplay between the external drive and interactions. We present a widely applicable generic numerical method to extract instability rates and link parametric instabilities to uncontrolled energy absorption at short times. Based on the existence of parametric resonances, we then develop an analytical approach within Bogoliubov theory, which quantitatively captures the instability rates of the system and provides an intuitive picture of the relevant physical processes, including an understanding of how transverse modes affect the formation of parametric instabilities. Importantly, our calculations demonstrate an agreement between the instability rates determined from numerical simulations and those predicted by theory. To determine the validity regime of the mean-field analysis, we compare the latter to the weakly coupled conserving approximation. The tools developed and the results obtained in this work are directly relevant to present-day ultracold-atom experiments based on shaken optical lattices and are expected to provide an insightful guidance in the quest for Floquet engineering.

Predicting balance improvements following STARS treatments in chronic ankle instability participants.

PubMed

Wikstrom, Erik A; McKeon, Patrick O

2017-04-01

Sensory Targeted Ankle Rehabilitation Strategies that stimulate sensory receptors improve postural control in chronic ankle instability participants. However, not all participants have equal responses. Therefore, identifying predictors of treatment success is needed to improve clinician efficiency when treating chronic ankle instability. Therefore, the purpose was to identify predictors of successfully improving postural control in chronic ankle instability participants. Secondary data analysis. Fifty-nine participants with self-reported chronic ankle instability participated. The condition was defined as a history of at least two episodes of "giving way" within the past 6 months; and limitations in self-reported function as measured by the Foot and Ankle Ability Measure. Participants were randomized into three treatment groups (plantar massage, ankle joint mobilization, calf stretching) that received 6, 5-min treatment sessions over a 2-week period. The main outcome measure was treatment success, defined as a participant exceeding the minimal detectable change score for a clinician-oriented single limb balance test. Participants with ≥3 balance test errors had a 73% probability of treatment success following ankle joint mobilizations. Participants with a self-reported function between limb difference <16.07% and who made >2.5 errors had a 99% probability of treatment success following plantar massage. Those who sustained ≥11 ankle sprains had a 94% treatment success probability following calf stretching. Self-reported functional deficits, worse single limb balance, and number of previous ankle sprains are important characteristics when determining if chronic ankle instability participants will have an increased probability of treatment success. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

[Latest progress on diagnosis and treatment of glenohumeral instability].

PubMed

Zhao, Gang; Liu, Yu-Jie

2014-02-01

As a common and frequently-occurring disease,glenohumeral instability is become one of disease which restrict upper limb activity. The diagnosis of this disease is easy, but it is very difficult to assess the degree of periarticular soft tissue injuries. With the development of magnetic resonance imaging and arthroscopy, MRA become the gold standard for evaluation of glenoid labrum, joint capsule and ligaments injury. The traditional manual reduction is a fast, simple method, but often can cause adverse consequences,such as rotator cuff tear,ligament relaxation,and habitual dislocation. Open operation can rebuild stability of joint,but with many new treatment methods,especially the arthroscopic reconstruction has gradually replaced the open operation, and become the mainstream trend, but for the long-term effect of capsular tightening surgery, rotator cuff gap closure is not clear,it is need further follow-up observation.

Narratives of Self-Neglect: Patterns of Traumatic Personal Experiences and Maladaptive Behaviors in Cognitively Intact Older Adults.

PubMed

Lien, Cynthia; Rosen, Tony; Bloemen, Elizabeth M; Abrams, Robert C; Pavlou, Maria; Lachs, Mark S

2016-11-01

To identify patterns of personal experience or behavior in self-neglect by exploring narratives of cognitively intact older adults. Descriptive study involving semistructured interviews and unstructured narratives. A parent study of self-neglect characteristics. Cognitively intact, self-neglecting older adults referred from 11 community-based senior services agencies (N = 69). Interviews included a comprehensive psychiatric assessment using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis-I and II Disorders and an unstructured interview that allowed subjects to describe important elements of their life stories. Content analysis was used to identify personal experiences and behavior patterns in each subject's narrative. Four types of traumatic personal experiences (psychologically traumatic loss, separation or abandonment (29%); violent victimization, physical trauma, or sexual abuse (19%); exposure to war or political violence (9%); prolonged mourning (7%)) and five behavior patterns (significant financial instability (23%), severe lifelong mental illness (16%), mistrust of people or paranoia (13%), distrust and avoidance of the medical establishment (13%), substance abuse or dependence (13%)) were identified in the life stories. Patterns of traumatic personal experiences and maladaptive behaviors that self-neglecters frequently report were identified. Experiences, perceptions, and behaviors developed over a lifetime may contribute to elder self-neglect. Further exploration and better understanding of these patterns may identify potential risk factors and areas for future targeted screening, intervention, and prevention. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Prevalence of chronic ankle instability and associated symptoms in university dance majors: an exploratory study.

PubMed

Simon, Janet; Hall, Emily; Docherty, Carrie

2014-01-01

Previous investigations have established that dancers suffer a large number of injuries to the lower leg, foot, and ankle, with a portion of these being significant time loss injuries or in some cases career ending. Lateral ankle sprain is a common injury in dancers and can often lead to recurrent instability and repetitive injuries. Research in other active populations has linked ankle sprains to the development of chronic ankle instability (CAI). Therefore, the purpose of this study was to identify the prevalence of CAI and related symptoms of ankle sprain in a student dance population. Individuals were included if they were currently a modern or ballet dance major at the investigators' university (exclusion criterion: a history of fracture or surgery in the lower extremities). A self-reported demographic questionnaire and the Identification of Functional Ankle Instability survey were used to identify the presence and characteristics of CAI. A total of 83 questionnaires were collected, and after exclusions, 77 participants remained: 43 modern dancers and 34 ballet dancers (10 males and 67 females, mean age 19.61 ± 2.53 years, mean dance experience 13.61 ± 3.16 years). Of all dancers surveyed, 41 (53.2%) had CAI, and of those 24 (58.5%) were modern dancers, and 17 (41.5%) were ballet dancers. When looking only at those dancers who had a previous lateral ankle sprain, 75.9% were identified as having CAI. Chronic Ankle Instability can create long-term problems for anyone but especially female dancers, who place extreme stress on their feet and ankles from being en pointe or demi-pointe. It is important to educate dancers, instructors, and medical staff of the importance of recognizing CAI and seeking medical care for ankle sprains and their residual symptoms.

Marangoni instability in a thin film heated from below: Effect of nonmonotonic dependence of surface tension on temperature

NASA Astrophysics Data System (ADS)

Sarma, Rajkumar; Mondal, Pranab Kumar

2018-04-01

We investigate Marangoni instability in a thin liquid film resting on a substrate of low thermal conductivity and separated from the surrounding gas phase by a deformable free surface. Considering a nonmonotonic variation of surface tension with temperature, here we analytically derive the neutral stability curve for the monotonic and oscillatory modes of instability (for both the long-wave and short-wave perturbations) under the framework of linear stability analysis. For the long-wave instability, we derive a set of amplitude equations using the scaling k ˜(Bi) 1 /2 , where k is the wave number and Bi is the Biot number. Through this investigation, we demonstrate that for such a fluid layer upon heating from below, both monotonic and oscillatory instability can appear for a certain range of the dimensionless parameters, viz., Biot number (Bi ) , Galileo number (Ga ) , and inverse capillary number (Σ ) . Moreover, we unveil, through this study, the influential role of the above-mentioned parameters on the stability of the system and identify the critical values of these parameters above which instability initiates in the liquid layer.

Modulational instability and discrete breathers in a nonlinear helicoidal lattice model

NASA Astrophysics Data System (ADS)

Ding, Jinmin; Wu, Tianle; Chang, Xia; Tang, Bing

2018-06-01

We investigate the problem on the discrete modulation instability of plane waves and discrete breather modes in a nonlinear helicoidal lattice model, which is described by a discrete nonlinear Schrödinger equation with the first-, second-, and third-neighbor coupling. By means of the linear stability analysis, we present an analytical expression of the instability growth rate and identify the regions of modulational instability of plane waves. It is shown that the introduction of the third-neighbor coupling will affect the shape of the areas of modulational instability significantly. Based on the results obtained by the modulational instability analysis, we predict the existence conditions for the stationary breather modes. Otherwise, by making use of the semidiscrete multiple-scale method, we obtain analytical solutions of discrete breather modes and analyze their properties for different types of nonlinearities. Our results show that the discrete breathers obtained are stable for a long time only when the system exhibits the repulsive nonlinearity. In addition, it is found that the existence of the stable bright discrete breather closely relates to the presence of the third-neighbor coupling.

On the nonlinear stability of a high-speed, axisymmetric boundary layer

NASA Technical Reports Server (NTRS)

Pruett, C. David; Ng, Lian L.; Erlebacher, Gordon

1991-01-01

The stability of a high-speed, axisymmetric boundary layer is investigated using secondary instability theory and direct numerical simulation. Parametric studies based on the temporal secondary instability theory identify subharmonic secondary instability as a likely path to transition on a cylinder at Mach 4.5. The theoretical predictions are validated by direct numerical simulation at temporally-evolving primary and secondary disturbances in an axisymmetric boundary-layer flow. At small amplitudes of the secondary disturbance, predicted growth rates agree to several significant digits with values obtained from the spectrally-accurate solution of the compressible Navier-Stokes equations. Qualitative agreement persists to large amplitudes of the secondary disturbance. Moderate transverse curvature is shown to significantly affect the growth rate of axisymmetric second mode disturbances, the likely candidates of primary instability. The influence of curvature on secondary instability is largely indirect but most probably significant, through modulation of the primary disturbance amplitude. Subharmonic secondary instability is shown to be predominantly inviscid in nature, and to account for spikes in the Reynolds stress components at or near the critical layer.

Glenohumeral Instability Related to Special Conditions: SLAP Tears, Pan-labral Tears, and Multidirectional Instability.

PubMed

Van Blarcum, Gregory S; Svoboda, Steven J

2017-09-01

Glenohumeral instability is one of the more common conditions seen by sports medicine physicians, especially in young, active athletes. The associated anatomy of the glenohumeral joint (the shallow nature of the glenoid and the increased motion it allows) make the shoulder more prone to instability events as compared with other joints. Although traumatic dislocations or instability events associated with acute labral tears (ie, Bankart lesions) are well described in the literature, there exists other special shoulder conditions that are also associated with shoulder instability: superior labrum anterior/posterior (SLAP) tears, pan-labral tears, and multidirectional instability. SLAP tears can be difficult to diagnose and arthroscopic diagnosis remains the gold standard. Surgical treatment as ranged from repair to biceps tenodesis with varying reports of success. Along the spectrum of SLAP tears, pan-labral tears consist of 360-degree injuries to the labrum. Patients can present complaining of either anterior or posterior instability alone, making the physical examination and advanced imaging a crucial component of the work up of the patients. Arthroscopic labral repair remains a good initial option for surgical treatment of these conditions. Multidirectional instability remains one of the more difficult conditions for the sports medicine physician to diagnose and treat. Symptoms may only be reported as vague pain versus frank instability making the diagnoses particularly challenging, especially in a patient with overall joint laxity. Conservative management to include physical therapy is the mainstay initial treatment in patients without an identifiable structural abnormality. Surgical management of this condition has evolved from open to arthroscopic capsular shifts with comparable results.

Late Holocene flood probabilities in the Black Hills, South Dakota with emphasis on the Medieval Climate Anomaly

USGS Publications Warehouse

Harden, Tessa M.; O'Connor, James E.; Driscoll, Daniel G.

2015-01-01

A stratigraphic record of 35 large paleofloods and four large historical floods during the last 2000 years for four basins in the Black Hills of South Dakota reveals three long-term flooding episodes, identified using probability distributions, at A.D.: 120–395, 900–1290, and 1410 to present. During the Medieval Climate Anomaly (~ A.D. 900–1300) the four basins collectively experienced 13 large floods compared to nine large floods in the previous 800 years, including the largest floods of the last 2000 years for two of the four basins. This high concentration of extreme floods is likely caused by one or more of the following: 1) instability of air masses caused by stronger than normal westerlies; 2) larger or more frequent hurricanes in the Gulf of Mexico and Atlantic Ocean; and/or 3) reduced land covering vegetation or increased forest fires caused by persistent regional drought.

Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors.

PubMed

Yamamoto, Kenta; Wang, Jiguang; Sprinzen, Lisa; Xu, Jun; Haddock, Christopher J; Li, Chen; Lee, Brian J; Loredan, Denis G; Jiang, Wenxia; Vindigni, Alessandro; Wang, Dong; Rabadan, Raul; Zha, Shan

2016-06-15

Missense mutations in ATM kinase, a master regulator of DNA damage responses, are found in many cancers, but their impact on ATM function and implications for cancer therapy are largely unknown. Here we report that 72% of cancer-associated ATM mutations are missense mutations that are enriched around the kinase domain. Expression of kinase-dead ATM (Atm(KD/-)) is more oncogenic than loss of ATM (Atm(-/-)) in mouse models, leading to earlier and more frequent lymphomas with Pten deletions. Kinase-dead ATM protein (Atm-KD), but not loss of ATM (Atm-null), prevents replication-dependent removal of Topo-isomerase I-DNA adducts at the step of strand cleavage, leading to severe genomic instability and hypersensitivity to Topo-isomerase I inhibitors. Correspondingly, Topo-isomerase I inhibitors effectively and preferentially eliminate Atm(KD/-), but not Atm-proficientor Atm(-/-) leukemia in animal models. These findings identify ATM kinase-domain missense mutations as a potent oncogenic event and a biomarker for Topo-isomerase I inhibitor based therapy.

Beam-plasma instabilities and the beam-plasma discharge

NASA Technical Reports Server (NTRS)

Kellogg, P. J.; Boswell, R. W.

1986-01-01

Using a new waves on magnetized beams and turbulence (WOMBAT) 0-450 eV electron gun, measurements bearing on the generation of beam-plasma discharge (BPD) are made. The new gun has a narrower divergence angle than the old, and the BPD ignition current is found to be proportional to the cross-sectional area of the plasma. The high-frequency instabilities are identified with the two Trivelpiece-Gould modes, (1959). The upper frequency is identified as a Cerenkov resonance with the upper Trivelpiece-Gould mode, and the lower frequency with a cyclotron resonance with the lower mode, in agreement with theoretical expectations. Convective growth rates are found to be small. A mechanism involving the conversion of a convective instability to an absolute one by trapping of the unstable waves in the density perturbations of the low-frequency waves, is suggested for the low-frequency wave control of the onset of the high frequency precursors to the BPD.

Field experiences with rotordynamic instability in high-performance turbomachinery. [oil and natural gas recovery

NASA Technical Reports Server (NTRS)

Doyle, H. E.

1980-01-01

Two field situations illustrate the consequences of rotordynamic instability in centrifugal compressors. One involves the reinjection of produced gas into a North Sea oil formation for the temporary extraction of crude. The other describes on-shore compressors used to deliver natural gas from off-shore wells. The problems which developed and the remedies attempted in each case are discussed. Instability problems resulted in lost production, extended construction periods and costs, and heavy maintenance expenditures. The need for effective methods to properly identify the problem in the field and in the compressor design stage is emphasized.

Many-body instabilities and mass generation in slow Dirac materials

NASA Astrophysics Data System (ADS)

Triola, Christopher; Zhu, Jianxin; Migliori, Albert; Balatsky, Alexander

2015-03-01

Some Kondo insulators are expected to possess topologically protected surface states with linear Dirac spectrum, the topological Kondo insulators. Because the bulk states of these systems typically have heavy effective electron masses, the surface states may exhibit extraordinarily small Fermi velocities that could force the effective fine structure constant of the surface states into the strong coupling regime. Using a tight-binding model we study the many-body instabilities of these systems and identify regions of parameter space for which antiferromagnetic, ferromagnetic and charge density wave instabilities occur. Work Supported by USDOE BES E304.

Simulations of Instabilities in Complex Valve and Feed Systems

NASA Technical Reports Server (NTRS)

Ahuja, Vineet; Hosangadi, Ashvin; Shipman, Jeremy; Cavallo, Peter A.

2006-01-01

CFD analyses are playing an increasingly important role in identifying and characterizing flow induced instabilities in rocket engine test facilities and flight systems. In this paper, we analyze instability mechanisms that range from turbulent pressure fluctuations due to vortex shedding in structurally complex valve systems to flow resonance in plug cavities to large scale pressure fluctuations due to collapse of cavitation induced vapor clouds. Furthermore, we discuss simulations of transient behavior related to valve motion that can serve as guidelines for valve scheduling. Such predictions of valve response to varying flow conditions is of crucial importance to engine operation and testing.

Generation of capillary instabilities by external disturbances in a liquid jet. Ph.D. Thesis - State Univ. of N.Y.

NASA Technical Reports Server (NTRS)

Leib, S. J.

1985-01-01

The receptivity problem in a circular liquid jet is considered. A time harmonic axial pressure gradient is imposed on the steady, parallel flow of a jet of liquid emerging from a circular duct. Using a technique developed in plasma physics a casual solution to the forced problem is obtained over certain ranges of Weber number for a number of mean velocity profiles. This solution contains a term which grows exponentially in the downstream direction and can be identified with a capillary instability wave. Hence, it is found that the externally imposed disturbances can indeed trigger instability waves in a liquid jet. The amplitude of the instability wave generated relative to the amplitude of the forcing is computed numerically for a number of cases.

On the 'flip-flop' instability of Bondi-Hoyle accretion flows

NASA Technical Reports Server (NTRS)

Livio, Mario; Soker, Noam; Matsuda, Takuya; Anzer, Ulrich

1991-01-01

A simple physical interpretation is advanced by means of an analysis of the shock cone in the accretion flows past a compact object and with an examination of the accretion-line stability analyses. The stability of the conical shock is examined against small angular deflections with attention given to several simplifying assumptions. A line instability is identified in the Bondi-Hoyle accretion flows that leads to the formation of a large opening-angle shock. When the opening angle becomes large the instability becomes irregular oscillation. The analytical methodology is compared to previous numerical configurations that demonstrate different shock morphologies. The Bondi-Hoyle accretion onto a compact object is concluded to generate a range of nonlinear instabilities in both homogeneous and inhomogeneous cases with a quasiperiodic oscillation in the linear regime.

Localized instabilities and spinodal decomposition in driven systems in the presence of elasticity

NASA Astrophysics Data System (ADS)

Meca, Esteban; Münch, Andreas; Wagner, Barbara

2018-01-01

We study numerically and analytically the instabilities associated with phase separation in a solid layer on which an external material flux is imposed. The first instability is localized within a boundary layer at the exposed free surface by a process akin to spinodal decomposition. In the limiting static case, when there is no material flux, the coherent spinodal decomposition is recovered. In the present problem, stability analysis of the time-dependent and nonuniform base states as well as numerical simulations of the full governing equations are used to establish the dependence of the wavelength and onset of the instability on parameter settings and its transient nature as the patterns eventually coarsen into a flat moving front. The second instability is related to the Mullins-Sekerka instability in the presence of elasticity and arises at the moving front between the two phases when the flux is reversed. Stability analyses of the full model and the corresponding sharp-interface model are carried out and compared. Our results demonstrate how interface and bulk instabilities can be analyzed within the same framework which allows us to identify and distinguish each of them clearly. The relevance for a detailed understanding of both instabilities and their interconnections in a realistic setting is demonstrated for a system of equations modeling the lithiation and delithiation processes within the context of lithium ion batteries.

Electrophysiological predictors of sudden cardiac death on physical exercise test in young athletes

NASA Astrophysics Data System (ADS)

Balykova, L. A.; Kotlyarov, A. A.; Ivyanskiy, S. A.; Shirokova, A. A.; Miheeva, K. A.; Makarov, L. M.

2017-01-01

The problem of sudden death of young athletes continues to be actual. Among its reasons, primary electric myocardium diseases along with organic heart troubles (cardiomyopathies, cordites, anomalies of coronary arteries) take an important place. The most frequent variant of channelopathesis long QT syndrome (LQTS). Both inherited and acquired LQTS may be the reason of sudden cardiac death during physical activity and have to be revealed prior to sports admission. LQTS diagnostics in young athletes become problematic due to secondary exercise-related QT prolongation. Physical load test may reveal myocardium electric instability and enhance LQTS diagnostics accuracy without genetic testing. The aim was to study electrophysiological parameters of myocardium repolarization and reveal the signs of electrical instability as predictors of the life-threatening arrhythmias in young athletes during physical exercise test. In conclusion, electrophysiological myocardium parameters during physical exercise test noted to be markers of electrical myocardial instability and in combination with the other Schwartz criteria, was evidenced the inherited or acquired LQTS. QTc prolongation in athletes at the peak of exercise as well as in early recovery period were noted to be additional predictor life-threatening arrhythmias and sudden cardiac death in young athletes

Pediatric and adolescent anterior shoulder instability: clinical management of first-time dislocators.

PubMed

Lin, Kenneth M; James, Evan W; Spitzer, Elad; Fabricant, Peter D

2018-02-01

The purpose of this review is to discuss the epidemiology, pathoanatomy, diagnosis, and clinical management of pediatric and adolescent patients following a first-time shoulder dislocation. Shoulder instability is becoming increasingly common as pediatric and adolescent patients engage in earlier organized sports competition. Recommended treatment following a first-time glenohumeral dislocation event in adolescents depends on several factors, but surgical stabilization is becoming more frequently performed. Surgical indications include bony Bankart lesion, ALPSA lesion, bipolar injury (e.g. Hill-Sachs humeral head depression fracture) or off-season injury in an overhead or throwing athlete. Complications following surgical treatment are rare but most commonly are associated with recurrent instability. Young children (eg. open proximal humerus growth plate), individuals averse to surgery, or in-season athletes who accept the risk of redislocation may complete an accelerated rehabilitation program for expedited return to play in the absence of the structural abnormalities listed above. Following a first-time dislocation event in pediatric and adolescent patients, a detailed discussion of the risks and benefits of nonoperative versus operative management is critical to match the recommended treatment with the patient's injury pattern, risk factors, and activity goals.

Examining Factors Associated with (In)Stability in Social Information Processing among Urban School Children: A Latent Transition Analytic Approach

ERIC Educational Resources Information Center

Goldweber, Asha; Bradshaw, Catherine P.; Goodman, Kimberly; Monahan, Kathryn; Cooley-Strickland, Michele

2011-01-01

There is compelling evidence for the role of social information processing (SIP) in aggressive behavior. However, less is known about factors that influence stability versus instability in patterns of SIP over time. Latent transition analysis was used to identify SIP patterns over one year and examine how community violence exposure, aggressive…

Primary versus revision arthroscopic reconstruction with remplissage for shoulder instability with moderate bone loss.

PubMed

McCabe, Michael P; Weinberg, Douglas; Field, Larry D; O'Brien, Michael J; Hobgood, E Rhett; Savoie, Felix H

2014-04-01

This study aims to evaluate our outcomes of arthroscopic remplissage in this setting. A retrospective review was performed to identify patients who underwent arthroscopic remplissage of an engaging Hill-Sachs lesion along with anterior capsulolabral reconstruction for anterior glenohumeral instability with moderate glenohumeral bone loss at our institution. Thirty-five patients, with a minimum of 2 years' follow-up, were identified. We assessed the American Shoulder and Elbow Surgeons score, incidence of recurrent instability, and postoperative Rowe instability score. Follow-up was available for 30 patients (31 shoulders). The mean age was 24.6 years, with a mean follow-up period of 41 months. Prior instability surgery had failed in 11 patients, and they underwent capsulolabral reconstruction and remplissage ("revision surgery"). The failure rate in revision cases (36%) was significantly higher than the failure rate in primary surgery cases (0%) (P = .01). Failure resulted from trauma in all 4 patients, and none required further surgery. The mean American Shoulder and Elbow Surgeons score for all patients improved from 50 preoperatively to 91 postoperatively (P < .001), with no significant postoperative difference between primary and revision patients (P = .13). The patients with clinical failure showed nonsignificant improvement from 41 preoperatively to 72 postoperatively (P = .08). The mean postoperative Rowe score for the entire cohort was 90. The Rowe score was significantly lower in the 4 cases of failure than in the 27 non-failure cases (51 v 96, P < .001). In our experience, aggressive capsulolabral reconstruction with remplissage in traumatic instability patients with moderate bone loss and engaging humeral Hill-Sachs lesions yields acceptable outcomes for primary instability surgery. However, a significantly higher failure rate occurred when arthroscopic reconstruction with remplissage was performed in the revision setting. Level IV, therapeutic case series. Copyright © 2014 Arthroscopy Association of North America. All rights reserved.

Systematic Review of Postural Control and Lateral Ankle Instability, Part I: Can Deficits Be Detected With Instrumented Testing

PubMed Central

McKeon, Patrick O; Hertel, Jay

2008-01-01

Objective: To answer the following clinical questions: (1) Is poor postural control associated with increased risk of a lateral ankle sprain? (2) Is postural control adversely affected after acute lateral ankle sprain? (3) Is postural control adversely affected in those with chronic ankle instability? Data Sources: PubMed and CINAHL entries from 1966 through October 2006 were searched using the terms ankle sprain, ankle instability, balance, chronic ankle instability, functional ankle instability, postural control, and postural sway. Study Selection: Only studies assessing postural control measures in participants on a stable force plate performing the modified Romberg test were included. To be included, a study had to address at least 1 of the 3 clinical questions stated above and provide adequate results for calculation of effect sizes or odds ratios where applicable. Data Extraction: We calculated odds ratios with 95% confidence intervals for studies assessing postural control as a risk factor for lateral ankle sprains. Effect sizes were estimated with the Cohen d and associated 95% confidence intervals for comparisons of postural control performance between healthy and injured groups, or healthy and injured limbs, respectively. Data Synthesis: Poor postural control is most likely associated with an increased risk of sustaining an acute ankle sprain. Postural control is impaired after acute lateral ankle sprain, with deficits identified in both the injured and uninjured sides compared with controls. Although chronic ankle instability has been purported to be associated with altered postural control, these impairments have not been detected consistently with the use of traditional instrumented measures. Conclusions: Instrumented postural control testing on stable force plates is better at identifying deficits that are associated with an increased risk of ankle sprain and that occur after acute ankle sprains than at detecting deficits related to chronic ankle instability. PMID:18523566

Risk and Protective Processes Predicting Rural African American Young Men's Substance Abuse.

PubMed

Cho, Junhan; Kogan, Steven M

2016-12-01

Informed by a life course perspective, this study tested a cascade model linking harsh, unresponsive parenting during childhood to young African American men's substance abuse via precocious transitions, economic instability, and future orientation. The moderating influence of community disadvantage and romantic partner support on the hypothesized pathways was also examined. At the baseline, the sample included 505 African American men between ages 19 and 22 years from high-poverty rural communities. Follow-up data were collected 18 months after baseline. Using structural equation modeling, we identified harsh, unresponsive parenting influenced precocious transitions in adolescence, which in turn increased economic instability during young adulthood. Economic instability was associated with a reduction in future orientation, a proximal influence on increases in substance abuse. Also, residence in a disadvantaged community amplified the influence of precocious transitions on economic instability and the influence of economic instability on future orientation. Involvement with supportive romantic partnership evinced a protective effect, attenuating the influence of precocious transitions on economic instability and the influence of economic instability on a future orientation. This study expands understanding of young adults' substance abuse by demonstrating the risk and protective processes linking substance abuse to developmental factors across childhood, adolescence, and young adulthood. © Society for Community Research and Action 2016.

Active Control of High Frequency Combustion Instability in Aircraft Gas-Turbine Engines

NASA Technical Reports Server (NTRS)

Corrigan, Bob (Technical Monitor); DeLaat, John C.; Chang, Clarence T.

2003-01-01

Active control of high-frequency (greater than 500 Hz) combustion instability has been demonstrated in the NASA single-nozzle combustor rig at United Technologies Research Center. The combustor rig emulates an actual engine instability and has many of the complexities of a real engine combustor (i.e. actual fuel nozzle and swirler, dilution cooling, etc.) In order to demonstrate control, a high-frequency fuel valve capable of modulating the fuel flow at up to 1kHz was developed. Characterization of the fuel delivery system was accomplished in a custom dynamic flow rig developed for that purpose. Two instability control methods, one model-based and one based on adaptive phase-shifting, were developed and evaluated against reduced order models and a Sectored-1-dimensional model of the combustor rig. Open-loop fuel modulation testing in the rig demonstrated sufficient fuel modulation authority to proceed with closed-loop testing. During closed-loop testing, both control methods were able to identify the instability from the background noise and were shown to reduce the pressure oscillations at the instability frequency by 30%. This is the first known successful demonstration of high-frequency combustion instability suppression in a realistic aero-engine environment. Future plans are to carry these technologies forward to demonstration on an advanced low-emission combustor.

Majority of Solar Wind Intervals Support Ion-Driven Instabilities

NASA Astrophysics Data System (ADS)

Klein, K. G.; Alterman, B. L.; Stevens, M. L.; Vech, D.; Kasper, J. C.

2018-05-01

We perform a statistical assessment of solar wind stability at 1 AU against ion sources of free energy using Nyquist's instability criterion. In contrast to typically employed threshold models which consider a single free-energy source, this method includes the effects of proton and He2 + temperature anisotropy with respect to the background magnetic field as well as relative drifts between the proton core, proton beam, and He2 + components on stability. Of 309 randomly selected spectra from the Wind spacecraft, 53.7% are unstable when the ion components are modeled as drifting bi-Maxwellians; only 4.5% of the spectra are unstable to long-wavelength instabilities. A majority of the instabilities occur for spectra where a proton beam is resolved. Nearly all observed instabilities have growth rates γ slower than instrumental and ion-kinetic-scale timescales. Unstable spectra are associated with relatively large He2 + drift speeds and/or a departure of the core proton temperature from isotropy; other parametric dependencies of unstable spectra are also identified.

Radiographic signs of static carpal instability with distal end radius fractures: is current treatment adequate?

PubMed

Bunker, D L J; Pappas, G; Moradi, P; Dowd, M B

2012-01-01

Patients presenting with distal end radius fractures may have concomitant carpal instability due to disruption of the scapholunate ligament. This study examined the incidence of static radiographic signs of carpal instability in patients with distal radial fractures before and after fracture treatment. We performed a retrospective radiographic study of 141 patients presenting to Central Middlesex Hospital, London between January 2002-May 2004 with distal end radius fractures. We used abnormal scapholunate angle as the primary indicator of possible carpal dissociation. Abnormal scapholunate angles were noted in 39% of patients at presentation and 35% of patients after treatment with no statistically significant intra-patient variability. Persistent static radiographic signs of carpal instability are high in this subset of patients. The long-term morbidity of persistent wrist instability may be avoided by early radiological diagnosis with clinical correlation to identify carpal ligament injuries and initiate treatment that addresses both the bony and ligamentous components of the injury.

Majority of Solar Wind Intervals Support Ion-Driven Instabilities.

PubMed

Klein, K G; Alterman, B L; Stevens, M L; Vech, D; Kasper, J C

2018-05-18

We perform a statistical assessment of solar wind stability at 1 AU against ion sources of free energy using Nyquist's instability criterion. In contrast to typically employed threshold models which consider a single free-energy source, this method includes the effects of proton and He^{2+} temperature anisotropy with respect to the background magnetic field as well as relative drifts between the proton core, proton beam, and He^{2+} components on stability. Of 309 randomly selected spectra from the Wind spacecraft, 53.7% are unstable when the ion components are modeled as drifting bi-Maxwellians; only 4.5% of the spectra are unstable to long-wavelength instabilities. A majority of the instabilities occur for spectra where a proton beam is resolved. Nearly all observed instabilities have growth rates γ slower than instrumental and ion-kinetic-scale timescales. Unstable spectra are associated with relatively large He^{2+} drift speeds and/or a departure of the core proton temperature from isotropy; other parametric dependencies of unstable spectra are also identified.

Introduction to section 2. Climax-stage magmatism: Growth history Of Kilauea Volcano and its instability

NASA Astrophysics Data System (ADS)

Lipman, Peter W.

On the south flank of Hawai'i Island, frequent eruptions, abundant earthquakes, and rapid ground deformation mark the current locus of volcanism along the Hawaiian Ridge. Kïlauea and Mauna Loa volcanoes are in a tholeiitic shield-building stage, erupting mainly on land. South of Kïlauea, Lö'ihi Seamount has erupted alkalic and transitional basalts that mark the growth of Hawai`i's youngest volcano. Kïlauea is the most active volcano on Earth, and its summit caldera and two rift zones characterize the typical shield stage of Hawaiian volcanoes. Kïlauea's south flank, between the rift zones, is subject to sustained and episodic seaward displacements associated with frequent earthquakes and expressed on land by the Hilina fault system.

Clonal evolution in paired endometrial intraepithelial neoplasia/atypical hyperplasia and endometrioid adenocarcinoma.

PubMed

Russo, Mariano; Broach, James; Sheldon, Kathryn; Houser, Kenneth R; Liu, Dajiang J; Kesterson, Joshua; Phaeton, Rebecca; Hossler, Carrie; Hempel, Nadine; Baker, Maria; Newell, Jordan M; Zaino, Richard; Warrick, Joshua I

2017-09-01

Endometrial intraepithelial neoplasia (EIN) and atypical endometrial hyperplasia (AH) are histomorphologically defined precursors to endometrioid adenocarcinoma, which are unified as EIN/AH by the World Health Organization. EIN/AH harbors a constellation of molecular alterations similar to those found in endometrioid adenocarcinoma. However, the process of clonal evolution from EIN/AH to carcinoma is poorly characterized. To investigate, we performed next-generation sequencing, copy number alteration (CNA) analysis, and immunohistochemistry for mismatch repair protein expression on EIN/AH and endometrioid adenocarcinoma samples from 6 hysterectomy cases with spatially distinct EIN/AH and carcinoma. In evaluating all samples, EIN/AH and carcinoma did not differ in mutational burden, CNA burden, or specific genes mutated (all P>.1). All paired EIN/AH and carcinoma samples shared at least one identical somatic mutation, frequently in PI(3)K pathway members. Large CNAs (>10 genes in length) were identified in 83% of cases; paired EIN/AH and carcinoma samples shared at least one identical CNA in these cases. Mismatch repair protein expression matched in all paired EIN/AH and carcinoma samples. All paired EIN/AH and carcinoma samples had identical The Cancer Genome Atlas subtype, with 3 classified as "copy number low endometrioid" and 3 classified as "microsatellite instability hypermutated." Although paired EIN/AH and carcinoma samples were clonal, private mutations (ie, present in only one sample) were identified in EIN/AH and carcinoma in all cases, frequently in established cancer-driving genes. These findings indicate that EIN/AH gives rise to endometrioid adenocarcinoma by a complex process of subclone evolution, not a linear accumulation of molecular events. Copyright © 2017 Elsevier Inc. All rights reserved.

Migration of mitochondrial DNA in the nuclear genome of colorectal adenocarcinoma.

PubMed

Srinivasainagendra, Vinodh; Sandel, Michael W; Singh, Bhupendra; Sundaresan, Aishwarya; Mooga, Ved P; Bajpai, Prachi; Tiwari, Hemant K; Singh, Keshav K

2017-03-29

Colorectal adenocarcinomas are characterized by abnormal mitochondrial DNA (mtDNA) copy number and genomic instability, but a molecular interaction between mitochondrial and nuclear genome remains unknown. Here we report the discovery of increased copies of nuclear mtDNA (NUMT) in colorectal adenocarcinomas, which supports link between mtDNA and genomic instability in the nucleus. We name this phenomenon of nuclear occurrence of mitochondrial component as numtogenesis. We provide a description of NUMT abundance and distribution in tumor versus matched blood-derived normal genomes. Whole-genome sequence data were obtained for colon adenocarcinoma and rectum adenocarcinoma patients participating in The Cancer Genome Atlas, via the Cancer Genomics Hub, using the GeneTorrent file acquisition tool. Data were analyzed to determine NUMT proportion and distribution on a genome-wide scale. A NUMT suppressor gene was identified by comparing numtogenesis in other organisms. Our study reveals that colorectal adenocarcinoma genomes, on average, contains up to 4.2-fold more somatic NUMTs than matched normal genomes. Women colorectal tumors contained more NUMT than men. NUMT abundance in tumor predicted parallel abundance in blood. NUMT abundance positively correlated with GC content and gene density. Increased numtogenesis was observed with higher mortality. We identified YME1L1, a human homolog of yeast YME1 (yeast mitochondrial DNA escape 1) to be frequently mutated in colorectal tumors. YME1L1 was also mutated in tumors derived from other tissues. We show that inactivation of YME1L1 results in increased transfer of mtDNA in the nuclear genome. Our study demonstrates increased somatic transfer of mtDNA in colorectal tumors. Our study also reveals sex-based differences in frequency of NUMT occurrence and that NUMT in blood reflects NUMT in tumors, suggesting NUMT may be used as a biomarker for tumorigenesis. We identify YME1L1 as the first NUMT suppressor gene in human and demonstrate that inactivation of YME1L1 induces migration of mtDNA to the nuclear genome. Our study reveals that numtogenesis plays an important role in the development of cancer.

Micro-Scale Genomic DNA Copy Number Aberrations as Another Means of Mutagenesis in Breast Cancer

PubMed Central

Chao, Hann-Hsiang; He, Xiaping; Parker, Joel S.; Zhao, Wei; Perou, Charles M.

2012-01-01

Introduction In breast cancer, the basal-like subtype has high levels of genomic instability relative to other breast cancer subtypes with many basal-like-specific regions of aberration. There is evidence that this genomic instability extends to smaller scale genomic aberrations, as shown by a previously described micro-deletion event in the PTEN gene in the Basal-like SUM149 breast cancer cell line. Methods We sought to identify if small regions of genomic DNA copy number changes exist by using a high density, gene-centric Comparative Genomic Hybridizations (CGH) array on cell lines and primary tumors. A custom tiling array for CGH (244,000 probes, 200 bp tiling resolution) was created to identify small regions of genomic change, which was focused on previously identified basal-like-specific, and general cancer genes. Tumor genomic DNA from 94 patients and 2 breast cancer cell lines was labeled and hybridized to these arrays. Aberrations were called using SWITCHdna and the smallest 25% of SWITCHdna-defined genomic segments were called micro-aberrations (<64 contiguous probes, ∼ 15 kb). Results Our data showed that primary tumor breast cancer genomes frequently contained many small-scale copy number gains and losses, termed micro-aberrations, most of which are undetectable using typical-density genome-wide aCGH arrays. The basal-like subtype exhibited the highest incidence of these events. These micro-aberrations sometimes altered expression of the involved gene. We confirmed the presence of the PTEN micro-amplification in SUM149 and by mRNA-seq showed that this resulted in loss of expression of all exons downstream of this event. Micro-aberrations disproportionately affected the 5′ regions of the affected genes, including the promoter region, and high frequency of micro-aberrations was associated with poor survival. Conclusion Using a high-probe-density, gene-centric aCGH microarray, we present evidence of small-scale genomic aberrations that can contribute to gene inactivation. These events may contribute to tumor formation through mechanisms not detected using conventional DNA copy number analyses. PMID:23284754

Predicting Depression From Language-Based Emotion Dynamics: Longitudinal Analysis of Facebook and Twitter Status Updates

PubMed Central

Kern, Margaret L; Fulcher, Ben D; Rickard, Nikki S

2018-01-01

Background Frequent expression of negative emotion words on social media has been linked to depression. However, metrics have relied on average values, not dynamic measures of emotional volatility. Objective The aim of this study was to report on the associations between depression severity and the variability (time-unstructured) and instability (time-structured) in emotion word expression on Facebook and Twitter across status updates. Methods Status updates and depression severity ratings of 29 Facebook users and 49 Twitter users were collected through the app MoodPrism. The average proportion of positive and negative emotion words used, within-person variability, and instability were computed. Results Negative emotion word instability was a significant predictor of greater depression severity on Facebook (rs(29)=.44, P=.02, 95% CI 0.09-0.69), even after controlling for the average proportion of negative emotion words used (partial rs(26)=.51, P=.006) and within-person variability (partial rs(26)=.49, P=.009). A different pattern emerged on Twitter where greater negative emotion word variability indicated lower depression severity (rs(49)=−.34, P=.01, 95% CI −0.58 to 0.09). Differences between Facebook and Twitter users in their emotion word patterns and psychological characteristics were also explored. Conclusions The findings suggest that negative emotion word instability may be a simple yet sensitive measure of time-structured variability, useful when screening for depression through social media, though its usefulness may depend on the social media platform. PMID:29739736

Black Hole Accretion and Feedback Driven by Thermal Instability

NASA Astrophysics Data System (ADS)

Gaspari, M.; Ruszkowski, M.; Oh, S. P.; Churazov, E.; Brighenti, F.; Ettori, S.; Sharma, P.; Temi, P.

2013-03-01

Multiwavelength data indicate that the cores of several galaxy clusters are moderately cooling, though not catastrophically, showing signs of filamentary extended multiphase gas. Through 3D AMR hydrodynamic simulations, we study the impact of thermal instability in the evolution of the intracluster medium. Common moderate turbulence of just over 100 km/s leads to the growth of nonlinear thermal instability within the central few tens kpc. In the presence of a global counterbalancing heating, the condensation of extended filamentary cold gas is violent, occurring when the cooling time falls below 10 times the free-fall time. The frequent stochastic collisions, fragmentations and shearing motions between the cold clouds, filaments and the central torus, efficiently reduce angular momentum. Tracking the accreting gas with a dynamical range of 10 million, we find that the accretion rate is boosted up to 100 times with respect to the Bondi rate. In a commonly turbulent and quasi-stable atmosphere, the mode of black accretion is cold and chaotic, substantially different from the classic idealized scenario. Only in the transonic regime, turbulent dissipation starts to inhibit thermal instability. On sub-parsec scales the cold phase is channeled via a funnel, triggering the black hole feedback likely linked to mechanical jets/outflows. As shown by long-term self-regulated simulations, the interplay of chaotic cold accretion and AGN feedback is crucial in order to avoid the cooling catastrophe and to reproduce the key thermodynamical features of observed clusters.

Sustainable land cover and terrain modification to enhance convection and precipitation in the arid region of the United Arab Emirates

NASA Astrophysics Data System (ADS)

Wulfmeyer, V.; Branch, O.; Adebabseh, A.; Temimi, M.

2017-12-01

Irrigated plantations and modified terrain can provide a sustainable means of enhancing convective rainfall in arid regions like the United Arab Emirates, or UAE, and can be used to aid ongoing cloud seeding operations through the geographic-localization of seedable cloud formation. The first method, the planting of vast irrigated plantations of hardy desert shrubs, can lead to wind convergence and vertical mixing through increased roughness and modified radiative balances. When upper-air atmospheric instability is present, these phenomena can initiate convection. The second method, increasing the elevation of moderate-sized mountains, is based on the correlation between elevation and the number of summertime convection initiation events observed in the mountains of the UAE and Oman. This augmentation of existing orographic features should therefore increase the likelihood and geographic range of convection initiation events. High-resolution simulations provide a powerful means of assessing the likely impacts of land surface modifications. Previous convection-permitting simulations have yielded some evidential support for these hypotheses, but higher resolutions down to 1 km provide more detail regarding convective processes and land surface representation. Using seasonal simulations with the WRF-NOAHMP land-atmosphere model at a 2.5 km resolution, we identify frequent zones of convergence and atmospheric instability in the UAE and select interesting cases. Using these results, as well as an agricultural feasibility study, we identify optimal plantation positions within the UAE. We then run realistic plantation scenarios for single case studies at 1 km resolution. Using the same cases, we simulate the impact of augmenting mountain elevations on convective processes, with the augmentation being achieved through GIS-based modification of the terrain data. For both methods, we assess the impacts quantitatively and qualitatively, and assess key processes and dependencies. If we can demonstrate that convective rainfall would be enhanced through feasible agricultural and engineering methods, then land surface-based weather modification deserves serious consideration as a solution for water scarcity and anthropogenic climate change.

Stability of Molasse: TLS for structural analysis in the valley of Gotteron-Fribourg, Switzerland

NASA Astrophysics Data System (ADS)

Ben Hammouda, Mariam; Jaboyedoff, Michel; Derron, Marc Henri; Bouaziz, Samir; Mazotti, Benoit

2016-04-01

The marine molasses of Fribourg (Switzerland) is an area where the cliff collapses and rockfalls are quite frequent and difficult to predict due to this particular lithology, a poorly consolidated greywacke. Because of some recent rockfall events, the situation became critical especially in the valley of Gotteron where a big block has slightly moved down and might destroy a house in case of rupture. The cliff made of jointed sandstone and thin layers of clay and siltstone presents many fractures, joints and massive cross bedding surfaces which increases the possibility of slab failure. This paper presents a detailed structural analysis of the cliff and the identification of the potential failure mechanisms. The methodology is about combining field observation and terrestrial LiDAR scanning point cloud in order to assess the stability of potential slope instabilities of molasses. Three LiDAR scans were done i) to extract discontinuity families depending to the dip and the dip direction of joints and ii) to run kinematic tests in order to identify responsible sets for each potential failure mechanisms. Raw point clouds were processed using IMAlign module of Polyworks and CloudCompare software. The structural analysis based on COLTOP 3D (Jaboyedoff et al. 2007) allowed the identification of four discontinuity sets that were not measured in the field. Two different failure mechanisms have been identified as critical: i) planar sliding which is the main responsible mechanism of the present fallen block and ii) wedge sliding. The planar sliding is defined by the discontinuity sets J1 and J5 with a direction parallel to the slope and with a steep dip angle. The wedges, defined by couples of discontinuity sets, contribute to increase cracks' opening and to the detachment of slabs. The use of TLS combined with field survey provides us a first interpretation of instabilities and a very promising structural analysis.

Ca2+ Overload and Sarcoplasmic Reticulum Instability in tric-a Null Skeletal Muscle*

PubMed Central

Zhao, Xiaoli; Yamazaki, Daiju; Park, Ki Ho; Komazaki, Shinji; Tjondrokoesoemo, Andoria; Nishi, Miyuki; Lin, Peihui; Hirata, Yutaka; Brotto, Marco; Takeshima, Hiroshi; Ma, Jianjie

2010-01-01

The sarcoplasmic reticulum (SR) of skeletal muscle contains K+, Cl−, and H+ channels may facilitate charge neutralization during Ca2+ release. Our recent studies have identified trimeric intracellular cation (TRIC) channels on SR as an essential counter-ion permeability pathway associated with rapid Ca2+ release from intracellular stores. Skeletal muscle contains TRIC-A and TRIC-B isoforms as predominant and minor components, respectively. Here we test the physiological function of TRIC-A in skeletal muscle. Biochemical assay revealed abundant expression of TRIC-A relative to the skeletal muscle ryanodine receptor with a molar ratio of TRIC-A/ryanodine receptor ∼5:1. Electron microscopy with the tric-a−/− skeletal muscle showed Ca2+ overload inside the SR with frequent formation of Ca2+ deposits compared with the wild type muscle. This elevated SR Ca2+ pool in the tric-a−/− muscle could be released by caffeine, whereas the elemental Ca2+ release events, e.g. osmotic stress-induced Ca2+ spark activities, were significantly reduced likely reflecting compromised counter-ion movement across the SR. Ex vivo physiological test identified the appearance of “alternan” behavior with isolated tric-a−/− skeletal muscle, i.e. transient and drastic increase in contractile force appeared within the decreasing force profile during repetitive fatigue stimulation. Inhibition of SR/endoplasmic reticulum Ca2+ ATPase function could lead to aggravation of the stress-induced alternans in the tric-a−/− muscle. Our data suggests that absence of TRIC-A may lead to Ca2+ overload in SR, which in combination with the reduced counter-ion movement may lead to instability of Ca2+ movement across the SR membrane. The observed alternan behavior with the tric-a−/− muscle may reflect a skeletal muscle version of store overload-induced Ca2+ release that has been reported in the cardiac muscle under stress conditions. PMID:20858894

Type IV collagen is a novel DEJ biomarker that is reduced by radiotherapy.

PubMed

McGuire, J D; Gorski, J P; Dusevich, V; Wang, Y; Walker, M P

2014-10-01

The dental basement membrane (BM) is composed of collagen types IV, VI, VII, and XVII, fibronectin, and laminin and plays an inductive role in epithelial-mesenchymal interactions during tooth development. The BM is degraded and removed during later-stage tooth morphogenesis; however, its original position defines the location of the dentin-enamel junction (DEJ) in mature teeth. We recently demonstrated that type VII collagen is a novel component of the inner enamel organic matrix layer contiguous with the DEJ. Since it is frequently co-expressed with and forms functional complexes with type VII collagen, we hypothesized that type IV collagen should also be localized to the DEJ in mature human teeth. To identify collagen IV, we first evaluated defect-free erupted teeth from various donors. To investigate a possible stabilizing role, we also evaluated extracted teeth exposed to high-dose radiotherapy--teeth that manifest post-radiotherapy DEJ instability. We now show that type IV collagen is a component within the morphological DEJ of posterior and anterior teeth from individuals aged 18 to 80 yr. Confocal microscopy revealed that immunostained type IV collagen was restricted to the 5- to 10-µm-wide optical DEJ, while collagenase treatment or previous in vivo tooth-level exposure to > 60 Gray irradiation severely reduced immunoreactivity. This assignment was confirmed by Western blotting with whole-tooth crown and enamel extracts. Without reduction, type IV collagen contained macromolecular α-chains of 225 and 250 kDa. Compositionally, our results identify type IV collagen as the first macromolecular biomarker of the morphological DEJ of mature teeth. Given its network structure and propensity to stabilize the dermal-epidermal junction, we propose that a collagen-IV-enriched DEJ may, in part, explain its well-known fracture toughness, crack propagation resistance, and stability. In contrast, loss of type IV collagen may represent a biochemical rationale for the DEJ instability observed following oral cancer radiotherapy. © International & American Associations for Dental Research.

Type IV Collagen is a Novel DEJ Biomarker that is Reduced by Radiotherapy

PubMed Central

McGuire, J.D.; Gorski, J.P.; Dusevich, V.; Wang, Y.; Walker, M.P.

2014-01-01

The dental basement membrane (BM) is composed of collagen types IV, VI, VII, and XVII, fibronectin, and laminin and plays an inductive role in epithelial-mesenchymal interactions during tooth development. The BM is degraded and removed during later-stage tooth morphogenesis; however, its original position defines the location of the dentin-enamel junction (DEJ) in mature teeth. We recently demonstrated that type VII collagen is a novel component of the inner enamel organic matrix layer contiguous with the DEJ. Since it is frequently co-expressed with and forms functional complexes with type VII collagen, we hypothesized that type IV collagen should also be localized to the DEJ in mature human teeth. To identify collagen IV, we first evaluated defect-free erupted teeth from various donors. To investigate a possible stabilizing role, we also evaluated extracted teeth exposed to high-dose radiotherapy – teeth that manifest post-radiotherapy DEJ instability. We now show that type IV collagen is a component within the morphological DEJ of posterior and anterior teeth from individuals aged 18 to 80 yr. Confocal microscopy revealed that immunostained type IV collagen was restricted to the 5- to 10-µm-wide optical DEJ, while collagenase treatment or previous in vivo tooth-level exposure to > 60 Gray irradiation severely reduced immunoreactivity. This assignment was confirmed by Western blotting with whole-tooth crown and enamel extracts. Without reduction, type IV collagen contained macromolecular α-chains of 225 and 250 kDa. Compositionally, our results identify type IV collagen as the first macromolecular biomarker of the morphological DEJ of mature teeth. Given its network structure and propensity to stabilize the dermal-epidermal junction, we propose that a collagen-IV-enriched DEJ may, in part, explain its well-known fracture toughness, crack propagation resistance, and stability. In contrast, loss of type IV collagen may represent a biochemical rationale for the DEJ instability observed following oral cancer radiotherapy. PMID:25146181

No associations between self-reported knee joint instability and radiographic features in knee osteoarthritis patients prior to Total Knee Arthroplasty: A cross-sectional analysis of the Longitudinal Leiden Orthopaedics Outcomes of Osteo-Arthritis study (LOAS) data.

PubMed

Leichtenberg, Claudia S; Meesters, Jorit J L; Kroon, Herman M; Verdegaal, Suzan H M; Tilbury, Claire; Dekker, Joost; Nelissen, Rob G H H; Vliet Vlieland, Thea P M; van der Esch, Martin

2017-08-01

To describe the prevalence of self-reported knee joint instability in patients with pre-surgery knee osteoarthritis (OA) and to explore the associations between self-reported knee joint instability and radiological features. A cross-sectional study including patients scheduled for primary Total Knee Arthroplasty (TKA). Self-reported knee instability was examined by questionnaire. Radiological features consisted of osteophyte formation and joint space narrowing (JSN), both scored on a 0 to three scale. Scores >1 are defined as substantial JSN or osteophyte formation. Regression analyses were provided to identify associations of radiological features with self-reported knee joint instability. Two hundred and sixty-five patients (mean age 69years and 170 females) were included. Knee instability was reported by 192 patients (72%). Substantial osteophyte formation was present in 78 patients (41%) reporting and 33 patients (46%) not reporting knee joint instability. Substantial JSN was present in 137 (71%) and 53 patients (73%), respectively. Self-reported knee instability was not associated with JSN (relative to score 0, odds ratios (95% CI) of score 1, 2 and 3 were 0.87 (0.30-2.54), 0.98 (0.38-2.52), 0.68 (0.25-1.86), respectively) or osteophyte formation (relative to score 0, odds ratios (95% CI) of score 1, 2 and 3 were 0.77 (0.36-1.64), 0.69 (0.23-1.45), 0.89 (0.16-4.93), respectively). Stratified analysis for pain, age and BMI showed no associations between self-reported knee joint instability and radiological features. Self-reported knee joint instability is not associated with JSN or osteophyte formation. Copyright © 2017 Elsevier B.V. All rights reserved.

Active control: an investigation method for combustion instabilities

NASA Astrophysics Data System (ADS)

Poinsot, T.; Yip, B.; Veynante, D.; Trouvé, A.; Samaniego, J. M.; Candel, S.

1992-07-01

Closed-loop active control methods and their application to combustion instabilities are discussed. In these methods the instability development is impeded with a feedback control loop: the signal provided by a sensor monitoring the flame or pressure oscillations is processed and sent back to actuators mounted on the combustor or on the feeding system. Different active control systems tested on a non-premixed multiple-flame turbulent combustor are described. These systems can suppress all unstable plane modes of oscillation (i.e. low frequency modes). The active instability control (AIC) also constitutes an original and powerful technique for studies of mechanisms leading to instability or resulting from the instability. Two basic applications of this kind are described. In the first case the flame is initially controlled with AIC, the feedback loop is then switched off and the growth of the instability is analysed through high speed Schlieren cinematography and simultaneous sound pressure and reaction rate measurements. Three phases are identified during th growth of the oscillations: (1) a linear phase where acoustic waves induce a flapping motion of the flame sheets without interaction between sheets, (2) a modulation phase, where flame sheets interact randomly and (3) a nonlinear phase where the flame sheets are broken and a limit cycle is reached. In the second case we investigate different types of flame extinctions associated with combustion instability. It is shown that pressure oscillations may lead to partial or total extinctions. Extinctions occur in various forms but usually follow a rapid growth of pressure oscillations. The flame is extinguished during the modulation phase observed in the initiation experiments. In these studies devoted to transient instability phenomena, the control system constitutes a unique investigation tool because it is difficult to obtain the same information by other means. Implications for modelling and prediction of combustion instabilities are discussed.

CLINICAL COMMENTARY ON MIDFOOT AND FOREFOOT INVOLVEMENT IN LATERAL ANKLE SPRAINS AND CHRONIC ANKLE INSTABILITY. PART 2: CLINICAL CONSIDERATIONS

PubMed Central

Feger, Mark A.; Hertel, Jay

2016-01-01

Lateral ankle sprains (LAS) and chronic ankle instability (CAI) are common musculoskeletal injuries that are a result of inversion injury during sport. The midfoot and forefoot is frequently injured during a LAS, is often overlooked during clinical examination, and maybe contributory to the development of CAI. The purpose of part two of this clinical commentary and current concept review is to increase clinician's awareness of the contribution of midfoot and forefoot impairment to functional limitation and disability of individuals who experience LAS and CAI and to facilitate future research in this area. The importance of multisegmented foot and ankle assessment from a clinical and research perspective is stressed. Select physical assessment and manual therapeutic techniques are presented to assist the clinician in examination and treatment of the ankle-foot complex in patients with LAS and CAI. PMID:27999731

PTEN in the maintenance of genome integrity: From DNA replication to chromosome segregation.

PubMed

Hou, Sheng-Qi; Ouyang, Meng; Brandmaier, Andrew; Hao, Hongbo; Shen, Wen H

2017-10-01

Faithful DNA replication and accurate chromosome segregation are the key machineries of genetic transmission. Disruption of these processes represents a hallmark of cancer and often results from loss of tumor suppressors. PTEN is an important tumor suppressor that is frequently mutated or deleted in human cancer. Loss of PTEN has been associated with aneuploidy and poor prognosis in cancer patients. In mice, Pten deletion or mutation drives genomic instability and tumor development. PTEN deficiency induces DNA replication stress, confers stress tolerance, and disrupts mitotic spindle architecture, leading to accumulation of structural and numerical chromosome instability. Therefore, PTEN guards the genome by controlling multiple processes of chromosome inheritance. Here, we summarize current understanding of the PTEN function in promoting high-fidelity transmission of genetic information. We also discuss the PTEN pathways of genome maintenance and highlight potential targets for cancer treatment. © 2017 WILEY Periodicals, Inc.

High levels of histones promote whole-genome-duplications and trigger a Swe1WEE1-dependent phosphorylation of Cdc28CDK1.

PubMed

Maya Miles, Douglas; Peñate, Xenia; Sanmartín Olmo, Trinidad; Jourquin, Frederic; Muñoz Centeno, Maria Cruz; Mendoza, Manuel; Simon, Marie-Noelle; Chavez, Sebastian; Geli, Vincent

2018-03-27

Whole-genome duplications (WGDs) have played a central role in the evolution of genomes and constitute an important source of genome instability in cancer. Here, we show in Saccharomyces cerevisiae that abnormal accumulations of histones are sufficient to induce WGDs. Our results link these WGDs to a reduced incorporation of the histone variant H2A.Z to chromatin. Moreover, we show that high levels of histones promote Swe1 WEE1 stabilisation thereby triggering the phosphorylation and inhibition of Cdc28 CDK1 through a mechanism different of the canonical DNA damage response. Our results link high levels of histones to a specific type of genome instability that is quite frequently observed in cancer and uncovers a new mechanism that might be able to respond to high levels of histones. © 2018, Maya Miles et al.

High levels of histones promote whole-genome-duplications and trigger a Swe1WEE1-dependent phosphorylation of Cdc28CDK1

PubMed Central

Peñate, Xenia; Sanmartín Olmo, Trinidad; Jourquin, Frederic; Muñoz Centeno, Maria Cruz; Mendoza, Manuel; Simon, Marie-Noelle; Chavez, Sebastian

2018-01-01

Whole-genome duplications (WGDs) have played a central role in the evolution of genomes and constitute an important source of genome instability in cancer. Here, we show in Saccharomyces cerevisiae that abnormal accumulations of histones are sufficient to induce WGDs. Our results link these WGDs to a reduced incorporation of the histone variant H2A.Z to chromatin. Moreover, we show that high levels of histones promote Swe1WEE1 stabilisation thereby triggering the phosphorylation and inhibition of Cdc28CDK1 through a mechanism different of the canonical DNA damage response. Our results link high levels of histones to a specific type of genome instability that is quite frequently observed in cancer and uncovers a new mechanism that might be able to respond to high levels of histones. PMID:29580382

Hamiltonian bifurcation perspective on two interacting vortex pairs: From symmetric to asymmetric leapfrogging, period doubling, and chaos

NASA Astrophysics Data System (ADS)

Whitchurch, Brandon; Kevrekidis, Panayotis G.; Koukouloyannis, Vassilis

2018-01-01

In this work we study the dynamical behavior of two interacting vortex pairs, each one of them consisting of two point vortices with opposite circulation in the two-dimensional plane. The vortices are considered as effective particles and their interaction can be described in classical mechanics terms. We first construct a Poincaré section, for a typical value of the energy, in order to acquire a picture of the structure of the phase space of the system. We divide the phase space in different regions which correspond to qualitatively distinct motions and we demonstrate its different temporal evolution in the "real" vortex space. Our main emphasis is on the leapfrogging periodic orbit, around which we identify a region that we term the "leapfrogging envelope" which involves mostly regular motions, such as higher order periodic and quasiperiodic solutions. We also identify the chaotic region of the phase plane surrounding the leapfrogging envelope as well as the so-called walkabout and braiding motions. Varying the energy as our control parameter, we construct a bifurcation tree of the main leapfrogging solution and its instabilities, as well as the instabilities of its daughter branches. We identify the symmetry-breaking instability of the leapfrogging solution (in line with earlier works), and also obtain the corresponding asymmetric branches of periodic solutions. We then characterize their own instabilities (including period doubling ones) and bifurcations in an effort to provide a more systematic perspective towards the types of motions available to this dynamical system.

Comparative Study Between Cobalt Chrome and Titanium Alloy Rods for Multilevel Spinal Fusion: Proximal Junctional Kyphosis More Frequently Occurred in Patients Having Cobalt Chrome Rods.

PubMed

Han, Sanghyun; Hyun, Seung-Jae; Kim, Ki-Jeong; Jahng, Tae-Ahn; Kim, Hyun-Jib

2017-07-01

The use of titanium alloy (Ti) rods is frequently associated with rod fracture after spinal fixation. To address this issue, cobalt chrome (CoCr) rods, which are advantageous because of their greater strength and resistance to fatigue relative to Ti rods, have been introduced. The purpose of the present study was to compare radiographic outcomes after the use of Ti versus CoCr rods in a matched cohort of patients undergoing posterior spinal fusion for treatment of spinal instability. We retrospectively reviewed data from patients who had undergone spinal fusion involving more than 3 levels at a single institution between 2004 and 2015. Patients were matched for age, diagnosis, 3-column osteotomy, levels fused, and T score. Fifty patients with Ti rods were identified and appropriately matched to 50 consecutive patients with CoCr rods. The distributions of age at surgery, sex, diagnosis, 3-column osteotomy, levels fused, number of patients with previous surgical procedures, and T score did not significantly differ between the 2 groups. However, there were significant differences in length of follow-up (CoCr, 25.0 vs. Ti, 28.5 months; P < 0.001), fusion rate (CoCr, 45 [90%] vs. Ti, 33 [66%]; P = 0.004), occurrence of rod breakage (CoCr, 0 vs. T, 8 [16%]; P = 0.006), and junctional kyphosis (CoCr, 24 [46%] vs. Ti, 9 [18%]; P = 0.003). Our findings indicate that the use of CoCr rods is effective in ensuring stability of the posterior spinal construct and accomplishment of spinal fusion. Furthermore, our results indicate that junctional kyphosis may occur more frequently in CoCr systems than in Ti systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Anti–N-Methyl-D-Aspartate Receptor (NMDAR) Encephalitis in Children and Adolescents

PubMed Central

Florance, Nicole R.; Davis, Rebecca L.; Lam, Christopher; Szperka, Christina; Zhou, Lei; Ahmad, Saba; Campen, Cynthia J.; Moss, Heather; Peter, Nadja; Gleichman, Amy J.; Glaser, Carol A.; Lynch, David R.; Rosenfeld, Myrna R.; Dalmau, Josep

2010-01-01

Objective To report the clinical features of anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis in patients ≤ 18 years old. Methods Information was obtained by the authors or referring physicians. Antibodies were determined by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA) using HEK293 cells ectopically expressing NR1. Results Over an 8-month period, 81 patients (12 male) with anti-NMDAR encephalitis were identified. Thirty-two (40%) were ≤18 years old (youngest 23 months, median 14 years); 6 were male. The frequency of ovarian teratomas was 56% in women >18 years old, 31% in girls ≤18 years old (p = 0.05), and 9% in girls ≤14 years old ( p = 0.008). None of the male patients had tumors. Of 32 patients ≤18 years old, 87.5% presented with behavioral or personality change, sometimes associated with seizures and frequent sleep dysfunction; 9.5% with dyskinesias or dystonia; and 3% with speech reduction. On admission, 53% had severe speech deficits. Eventually, 77% developed seizures, 84% stereotyped movements, 86% autonomic instability, and 23% hypoventilation. Responses to immunotherapy were slow and variable. Overall, 74% had full or substantial recovery after immunotherapy or tumor removal. Neurological relapses occurred in 25%. At the last follow-up, full recovery occurred more frequently in patients who had a teratoma that was removed (5/8) than in those without a teratoma (4/23; p = 0.03). Interpretation Anti-NMDAR encephalitis is increasingly recognized in children, comprising 40% of all cases. Younger patients are less likely to have tumors. Behavioral and speech problems, seizures, and abnormal movements are common early symptoms. The phenotype resembles that of the adults, although dysautonomia and hypoventilation are less frequent or severe in children. PMID:19670433

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents.

PubMed

Florance, Nicole R; Davis, Rebecca L; Lam, Christopher; Szperka, Christina; Zhou, Lei; Ahmad, Saba; Campen, Cynthia J; Moss, Heather; Peter, Nadja; Gleichman, Amy J; Glaser, Carol A; Lynch, David R; Rosenfeld, Myrna R; Dalmau, Josep

2009-07-01

To report the clinical features of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in patients < or = 18 years old. Information was obtained by the authors or referring physicians. Antibodies were determined by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA) using HEK293 cells ectopically expressing NR1. Over an 8-month period, 81 patients (12 male) with anti-NMDAR encephalitis were identified. Thirty-two (40%) were < or =18 years old (youngest 23 months, median 14 years); 6 were male. The frequency of ovarian teratomas was 56% in women >18 years old, 31% in girls < or =18 years old (p = 0.05), and 9% in girls < or =14 years old (p = 0.008). None of the male patients had tumors. Of 32 patients < or =18 years old, 87.5% presented with behavioral or personality change, sometimes associated with seizures and frequent sleep dysfunction; 9.5% with dyskinesias or dystonia; and 3% with speech reduction. On admission, 53% had severe speech deficits. Eventually, 77% developed seizures, 84% stereotyped movements, 86% autonomic instability, and 23% hypoventilation. Responses to immunotherapy were slow and variable. Overall, 74% had full or substantial recovery after immunotherapy or tumor removal. Neurological relapses occurred in 25%. At the last follow-up, full recovery occurred more frequently in patients who had a teratoma that was removed (5/8) than in those without a teratoma (4/23; p = 0.03). Anti-NMDAR encephalitis is increasingly recognized in children, comprising 40% of all cases. Younger patients are less likely to have tumors. Behavioral and speech problems, seizures, and abnormal movements are common early symptoms. The phenotype resembles that of the adults, although dysautonomia and hypoventilation are less frequent or severe in children. Ann Neurol 2009;66:11-18.

Aberrant protein expression and frequent allelic loss of MSH3 in colorectal cancer with low-level microsatellite instability.

PubMed

Plaschke, Jens; Preußler, Mark; Ziegler, Andreas; Schackert, Hans K

2012-07-01

High level of microsatellite instability (MSI-H) in colorectal cancer (CRC) is caused by the inactivation of mismatch repair (MMR) genes; however, it is unknown for tumors with low level MSI (MSI-L). The protein complex involving MSH3 preferentially recognizes insertion/deletion loops (IDLs) of two to eight bases and di- and tetranucleotide repeats are affected in the majority of MSI-L CRC. We selected 10 and eight MSI-L CRCs from 228 and 204 patients with sporadic and hereditary disease, respectively. The tumors were analyzed for protein expression of MSH3, MSH2, MSH6, MLH1, and PMS2, and for mutations and loss of heterozygosity (LOH) in MSH3. Four tumors showed a markedly reduced MSH3 expression, whereas all 18 tumors had normal expression of the remaining MMR proteins. Twenty-five different sequence variants were identified. None of these results in a truncated protein, though L902W represents the first constitutional missense mutation in MSH3 predicted to be functional based on conservation among mutS homologues. All variants have also been found in normal DNA of the patients and in controls. LOH intragenic to MSH3 was evident for 12 of 16 (75%) informative tumors. Occurrence of sequence variants in normal DNA of the patients and in controls excludes somatic mutations and mutations specific to the CRC patient population, respectively. In contrast, the high frequency of LOH as well as the aberrant protein expression in some tumors indicates an involvement of MSH3 impairment in MSI-L CRC.

The Hierarchical Taxonomy of Psychopathology (HiTOP): A dimensional alternative to traditional nosologies.

PubMed

Kotov, Roman; Krueger, Robert F; Watson, David; Achenbach, Thomas M; Althoff, Robert R; Bagby, R Michael; Brown, Timothy A; Carpenter, William T; Caspi, Avshalom; Clark, Lee Anna; Eaton, Nicholas R; Forbes, Miriam K; Forbush, Kelsie T; Goldberg, David; Hasin, Deborah; Hyman, Steven E; Ivanova, Masha Y; Lynam, Donald R; Markon, Kristian; Miller, Joshua D; Moffitt, Terrie E; Morey, Leslie C; Mullins-Sweatt, Stephanie N; Ormel, Johan; Patrick, Christopher J; Regier, Darrel A; Rescorla, Leslie; Ruggero, Camilo J; Samuel, Douglas B; Sellbom, Martin; Simms, Leonard J; Skodol, Andrew E; Slade, Tim; South, Susan C; Tackett, Jennifer L; Waldman, Irwin D; Waszczuk, Monika A; Widiger, Thomas A; Wright, Aidan G C; Zimmerman, Mark

2017-05-01

The reliability and validity of traditional taxonomies are limited by arbitrary boundaries between psychopathology and normality, often unclear boundaries between disorders, frequent disorder co-occurrence, heterogeneity within disorders, and diagnostic instability. These taxonomies went beyond evidence available on the structure of psychopathology and were shaped by a variety of other considerations, which may explain the aforementioned shortcomings. The Hierarchical Taxonomy Of Psychopathology (HiTOP) model has emerged as a research effort to address these problems. It constructs psychopathological syndromes and their components/subtypes based on the observed covariation of symptoms, grouping related symptoms together and thus reducing heterogeneity. It also combines co-occurring syndromes into spectra, thereby mapping out comorbidity. Moreover, it characterizes these phenomena dimensionally, which addresses boundary problems and diagnostic instability. Here, we review the development of the HiTOP and the relevant evidence. The new classification already covers most forms of psychopathology. Dimensional measures have been developed to assess many of the identified components, syndromes, and spectra. Several domains of this model are ready for clinical and research applications. The HiTOP promises to improve research and clinical practice by addressing the aforementioned shortcomings of traditional nosologies. It also provides an effective way to summarize and convey information on risk factors, etiology, pathophysiology, phenomenology, illness course, and treatment response. This can greatly improve the utility of the diagnosis of mental disorders. The new classification remains a work in progress. However, it is developing rapidly and is poised to advance mental health research and care significantly as the relevant science matures. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Instability of monoclonal myeloma protein may be identified as susceptibility to penetration and binding by newly synthesized Congo red derivatives.

PubMed

Spólnik, Paweł; Konieczny, Leszek; Piekarska, Barbara; Rybarska, Janina; Stopa, Barbara; Zemanek, Grzegorz; Król, Marcin; Roterman, Irena

2004-06-01

Monoclonal myeloma proteins often have an abnormal, unstable structure, and tend to aggregate with fatal clinical consequences. A method for early clinical identification of this aggregation tendency is impatiently awaited. This work proposes the use of supramolecular dyes as specific ligands to reveal protein instability. Disclosure of excessive polypeptide chain flexibility in unstable monoclonal proteins, leading to increased susceptibility to penetration by foreign compounds, appeared possible when new supramolecular Congo red-derived dyes with different protein-binding capabilities were used for complexation. Two basic protein instability levels, local and global, were differentiated by comparing the extent of protein loading with dye and the subsequent electrophoretic migration rate of the complexes. A simple electrophoretic test is proposed for assessment of the instability of monoclonal proteins in clinical conditions.

Applying Nyquist's method for stability determination to solar wind observations

NASA Astrophysics Data System (ADS)

Klein, Kristopher G.; Kasper, Justin C.; Korreck, K. E.; Stevens, Michael L.

2017-10-01

The role instabilities play in governing the evolution of solar and astrophysical plasmas is a matter of considerable scientific interest. The large number of sources of free energy accessible to such nearly collisionless plasmas makes general modeling of unstable behavior, accounting for the temperatures, densities, anisotropies, and relative drifts of a large number of populations, analytically difficult. We therefore seek a general method of stability determination that may be automated for future analysis of solar wind observations. This work describes an efficient application of the Nyquist instability method to the Vlasov dispersion relation appropriate for hot, collisionless, magnetized plasmas, including the solar wind. The algorithm recovers the familiar proton temperature anisotropy instabilities, as well as instabilities that had been previously identified using fits extracted from in situ observations in Gary et al. (2016). Future proposed applications of this method are discussed.

Thermal relaxation and critical instability of near-critical fluid microchannel flow.

PubMed

Chen, Lin; Zhang, Xin-Rong; Okajima, Junnosuke; Maruyama, Shigenao

2013-04-01

We present two-dimensional numerical investigations of the temperature and velocity evolution of a pure near-critical fluid confined in microchannels. The fluid is subjected to two sides heating after it reached isothermal steady state. We focus on the abnormal behaviors of the near-critical fluid in response to the sudden imposed heat flux. New thermal-mechanical effects dominated by fluid instability originating from the boundary and local equilibrium process are reported. Near the microchannel boundaries, the instability grows very quickly and an unexpected vortex formation mode is identified when near-critical thermal-mechanical effect is interacting with the microchannel shear flow. The mechanism of the new kind of Kelvin-Helmholtz instability induced by boundary expansion and density stratification processes is also discussed in detail. This mechanism may bring about innovations in the field of microengineering.

Thermal relaxation and critical instability of near-critical fluid microchannel flow

NASA Astrophysics Data System (ADS)

Chen, Lin; Zhang, Xin-Rong; Okajima, Junnosuke; Maruyama, Shigenao

2013-04-01

We present two-dimensional numerical investigations of the temperature and velocity evolution of a pure near-critical fluid confined in microchannels. The fluid is subjected to two sides heating after it reached isothermal steady state. We focus on the abnormal behaviors of the near-critical fluid in response to the sudden imposed heat flux. New thermal-mechanical effects dominated by fluid instability originating from the boundary and local equilibrium process are reported. Near the microchannel boundaries, the instability grows very quickly and an unexpected vortex formation mode is identified when near-critical thermal-mechanical effect is interacting with the microchannel shear flow. The mechanism of the new kind of Kelvin-Helmholtz instability induced by boundary expansion and density stratification processes is also discussed in detail. This mechanism may bring about innovations in the field of microengineering.

Management of acute and chronic ankle instability.

PubMed

Maffulli, Nicola; Ferran, Nicholas A

2008-10-01

Acute lateral ankle ligament injuries are common. If left untreated, they can result in chronic instability. Nonsurgical measures, including functional rehabilitation, are the management methods of choice for acute injuries, with surgical intervention reserved for high-demand athletes. Chronic lateral ankle instability is multifactorial. Failed nonsurgical management after appropriate rehabilitation is an indication for surgery. Of the many surgical options available, anatomic repair of the anterior talofibular and calcaneofibular ligaments is recommended when the quality of the ruptured ligaments permits. Anatomic reconstruction with autograft or allograft should be performed when the ruptured ligaments are attenuated. Ankle arthroscopy is an important adjunct to ligamentous repair and should be performed at the time of repair to identify and address intra-articular conditions associated with chronic ankle instability. Tenodesis procedures are not recommended because they may disturb ankle and hindfoot biomechanics.

Dorsal surgical stabilisation using tension bands for treatment of traumatic atlanto-occipital instability in a cat.

PubMed

Vedrine, B; Maurin, M P

2017-12-01

An atlanto-occipital instability secondary to a dog bite was diagnosed in a 4-year-old Persian cat. Dorsal stabilisation of the instability was made with two OrthoFiber prostheses (Securos), which were used as tension bands between the nuchal crests of the occipital bone and the spinous process of the axis. Total recovery was achieved 4 days after surgery. Normal alignment of the atlanto-occipital joint was observed on survey radiographs taken 6 weeks post-surgery. Although the right loop had failed, the alignment was still normal and no neurological after-effects could be identified. Dorsal divergent tension bands between the nuchal crests of the occipital bone and the spinous process of the axis can be used to stabilise traumatic atlanto-occipital instability. © 2017 Australian Veterinary Association.

FU Orionis Outbursts in the Triangulum Galaxy (M33)

NASA Astrophysics Data System (ADS)

Zawadzki, Nicole; Moe, Maxwell

2018-01-01

FU Orionis systems (FUors) are young T-Tauri stars that brighten upwards of 6 magnitudes due to an instability in their disk. It is unclear whether all T-Tauri stars experience this period of disk instability to create FUor outbursts, or if a binary companion is required to trigger these instabilities. To date, there have been around 20 known FUors detected in the Milky Way. To better understand the occurrence rate of these instabilities more observations are needed. By using observations of M33 from the Canada-France-Hawaii telescope, SDSS, and an ongoing survey at the Bok 90” telescope, a 15+ year baseline can be established to identify FUor outbursts in M33. By measuring the occurrence rate of FUors in M33 from these observations, the question of whether a binary companion is required can be answered.

Observation of astrophysical Weibel instability in counterstreaming laser-produced plasmas

NASA Astrophysics Data System (ADS)

Fox, W.; Fiksel, G.; Bhattacharjee, A.; Germaschewski, K.; Chang, P.-Y.; Hu, S. X.; Nilson, P. M.

2013-10-01

Astrophysical shocks are typically collisionless and require collective electromagnetic fields to couple the upstream and downstream plasmas. The Weibel instability has been proposed to be one of such collective mechanism. Here we present laboratory tests of this process through observations of the Weibel instability generated between two counterstreaming, supersonic plasma flows, generated on the OMEGA EP laser facility by irradiating of a pair of opposing parallel CH targets by UV laser pulses (0.351 μm, 1.8 kJ, 2 ns). The Weibel-generated electromagnetic fields were probed with an ultrafast proton beam, generated with a high-intensity laser pulse (1.053 μm, 800 J, 10 ps) focused to >1018 W/cm2 onto a thin Cu disk. Growth of a striated, transverse instability is observed at the midplane as the two plasmas interpenetrate, which is identified as the Weibel instability through agreement with analytic theory and particle-in-cell simulations. These laboratory observations directly demonstrate the existence of this astrophysical process, and pave the way for further detailed laboratory study of this instability and its consequences for particle energization and shock formation. This work was supported by DOE grant DE-SC0007168.

Development and Breakdown of Goertler Vortices in High Speed Boundary Layers

NASA Technical Reports Server (NTRS)

Li, Fei; Choudhari, Meelan; Chang, Chau-Lyan; Wu, Minwei; Greene, Ptrick T.

2010-01-01

The nonlinear development of G rtler instability over a concave surface gives rise to a highly distorted stationary flow in the boundary layer that has strong velocity gradients in both spanwise and wall-normal directions. This distorted flow is susceptible to strong, high frequency secondary instability that leads to the onset of transition. For high Mach number flows, the boundary layer is also subject to the second mode instability. The nonlinear development of G rtler vortices and the ensuing growth and breakdown of secondary instability, the G rtler vortex interactions with second mode instabilities as well as oblique second mode interactions are examined in the context of both internal and external hypersonic configurations using nonlinear parabolized stability equations, 2-D eigenvalue analysis and direct numerical simulation. For G rtler vortex development inside the Purdue Mach 6 Ludwieg tube wind tunnel, multiple families of unstable secondary eigenmodes are identified and their linear and nonlinear evolution is examined. The computation of secondary instability is continued past the onset of transition to elucidate the physical mechanisms underlying the laminar breakdown process. Nonlinear breakdown scenarios associated with transition over a Mach 6 compression cone configuration are also explored.

Extended mimetic gravity: Hamiltonian analysis and gradient instabilities

NASA Astrophysics Data System (ADS)

Takahashi, Kazufumi; Kobayashi, Tsutomu

2017-11-01

We propose a novel class of degenerate higher-order scalar-tensor theories as an extension of mimetic gravity. By performing a noninvertible conformal transformation on "seed" scalar-tensor theories which may be nondegenerate, we can generate a large class of theories with at most three physical degrees of freedom. We identify a general seed theory for which this is possible. Cosmological perturbations in these extended mimetic theories are also studied. It is shown that either of tensor or scalar perturbations is plagued with gradient instabilities, except for a special case where the scalar perturbations are presumably strongly coupled, or otherwise there appear ghost instabilities.

[Microsatellite instability and human papilloma virus genotypes in preneoplastic and neoplastic uterine cervix lesions].

PubMed

Roa S, Juan Carlos; Martínez S, Ricardo; Montenegro, Sonia; Roa E, Iván; Capurro V, Italo; Ibacache S, Gilda; Melo A, Angélica

2007-01-01

The association between some specific human papilloma virus (HPV) types and cervix cancer is well known. However, the genetic conditions that favor the development of cervical cancer are less well known. To determine the presence of satellite instability (MSI) in preneoplastic and neoplastic lesions of the cervix and correlate these findings with HPV genotypes. Biopsy samples of cervical lesions were studied. Sixteen had low grade lesions, 22 had high grade lesions and 28 had an epidermoid cancer. Viral types were identified with polymerase chain reaction, dot-blot hybridization and restriction fragment length polymorphism. MSI was determined using a panel of eight highly informative microsatellites. Microsatellite instability in at least one locus was observed in 91, 56 and 69% of low grade lesions, high grade lesions and epidermoid carcinomas, respectively. MSI-High grade, MSI-Low grade instability and microsatellite stability were observed in 5, 60 and 46% of samples, respectively. Two of three samples with high grade instability had HPV 52 genotype. Other viral subtypes had frequencies that ranged from 78% to 100%, with the exception of HPV16 that was present in only 53% of samples with low grade instability. Two thirds of biopsy samples from cervical lesions had MSI, mechanism that can be involved in the first stages of cervical carcinogenesis. The low frequency of high grade instability, its association with HPV52 and the low frequency of HPV16 in samples with low grade instability, suggest different coadjutant mechanisms in cervical carcinogenesis.

Numerical Simulations of Instabilities in Single-Hole Office Elements

NASA Technical Reports Server (NTRS)

Ahuja, Vineet; Hosangadi, Ashvin; Hitt, Matthew A.; Lineberry, David M.

2013-01-01

An orifice element is commonly used in liquid rocket engine test facilities either as a flow metering device, a damper for acoustic resonance or to provide a large reduction in pressure over a very small distance in the piping system. While the orifice as a device is largely effective in stepping down pressure, it is also susceptible to a wake-vortex type instability that generates pressure fluctuations that propagate downstream and interact with other elements of the test facility resulting in structural vibrations. Furthermore in piping systems an unstable feedback loop can exist between the vortex shedding and acoustic perturbations from upstream components resulting in an amplification of the modes convecting downstream. Such was the case in several tests conducted at NASA as well as in the Ariane 5 strap-on P230 engine in a static firing test where pressure oscillations of 0.5% resulted in 5% thrust oscillations. Exacerbating the situation in cryogenic test facilities, is the possibility of the formation of vapor clouds when the pressure in the wake falls below the vapor pressure leading to a cavitation instability that has a lower frequency than the primary wake-vortex instability. The cavitation instability has the potential for high amplitude fluctuations that can cause catastrophic damage in the facility. In this paper high-fidelity multi-phase numerical simulations of an orifice element are used to characterize the different instabilities, understand the dominant instability mechanisms and identify the tonal content of the instabilities.

State dependence of climatic instability over the past 720,000 years from Antarctic ice cores and climate modeling.

PubMed

Kawamura, Kenji; Abe-Ouchi, Ayako; Motoyama, Hideaki; Ageta, Yutaka; Aoki, Shuji; Azuma, Nobuhiko; Fujii, Yoshiyuki; Fujita, Koji; Fujita, Shuji; Fukui, Kotaro; Furukawa, Teruo; Furusaki, Atsushi; Goto-Azuma, Kumiko; Greve, Ralf; Hirabayashi, Motohiro; Hondoh, Takeo; Hori, Akira; Horikawa, Shinichiro; Horiuchi, Kazuho; Igarashi, Makoto; Iizuka, Yoshinori; Kameda, Takao; Kanda, Hiroshi; Kohno, Mika; Kuramoto, Takayuki; Matsushi, Yuki; Miyahara, Morihiro; Miyake, Takayuki; Miyamoto, Atsushi; Nagashima, Yasuo; Nakayama, Yoshiki; Nakazawa, Takakiyo; Nakazawa, Fumio; Nishio, Fumihiko; Obinata, Ichio; Ohgaito, Rumi; Oka, Akira; Okuno, Jun'ichi; Okuyama, Junichi; Oyabu, Ikumi; Parrenin, Frédéric; Pattyn, Frank; Saito, Fuyuki; Saito, Takashi; Saito, Takeshi; Sakurai, Toshimitsu; Sasa, Kimikazu; Seddik, Hakime; Shibata, Yasuyuki; Shinbori, Kunio; Suzuki, Keisuke; Suzuki, Toshitaka; Takahashi, Akiyoshi; Takahashi, Kunio; Takahashi, Shuhei; Takata, Morimasa; Tanaka, Yoichi; Uemura, Ryu; Watanabe, Genta; Watanabe, Okitsugu; Yamasaki, Tetsuhide; Yokoyama, Kotaro; Yoshimori, Masakazu; Yoshimoto, Takayasu

2017-02-01

Climatic variabilities on millennial and longer time scales with a bipolar seesaw pattern have been documented in paleoclimatic records, but their frequencies, relationships with mean climatic state, and mechanisms remain unclear. Understanding the processes and sensitivities that underlie these changes will underpin better understanding of the climate system and projections of its future change. We investigate the long-term characteristics of climatic variability using a new ice-core record from Dome Fuji, East Antarctica, combined with an existing long record from the Dome C ice core. Antarctic warming events over the past 720,000 years are most frequent when the Antarctic temperature is slightly below average on orbital time scales, equivalent to an intermediate climate during glacial periods, whereas interglacial and fully glaciated climates are unfavourable for a millennial-scale bipolar seesaw. Numerical experiments using a fully coupled atmosphere-ocean general circulation model with freshwater hosing in the northern North Atlantic showed that climate becomes most unstable in intermediate glacial conditions associated with large changes in sea ice and the Atlantic Meridional Overturning Circulation. Model sensitivity experiments suggest that the prerequisite for the most frequent climate instability with bipolar seesaw pattern during the late Pleistocene era is associated with reduced atmospheric CO 2 concentration via global cooling and sea ice formation in the North Atlantic, in addition to extended Northern Hemisphere ice sheets.

State dependence of climatic instability over the past 720,000 years from Antarctic ice cores and climate modeling

PubMed Central

Kawamura, Kenji; Abe-Ouchi, Ayako; Motoyama, Hideaki; Ageta, Yutaka; Aoki, Shuji; Azuma, Nobuhiko; Fujii, Yoshiyuki; Fujita, Koji; Fujita, Shuji; Fukui, Kotaro; Furukawa, Teruo; Furusaki, Atsushi; Goto-Azuma, Kumiko; Greve, Ralf; Hirabayashi, Motohiro; Hondoh, Takeo; Hori, Akira; Horikawa, Shinichiro; Horiuchi, Kazuho; Igarashi, Makoto; Iizuka, Yoshinori; Kameda, Takao; Kanda, Hiroshi; Kohno, Mika; Kuramoto, Takayuki; Matsushi, Yuki; Miyahara, Morihiro; Miyake, Takayuki; Miyamoto, Atsushi; Nagashima, Yasuo; Nakayama, Yoshiki; Nakazawa, Takakiyo; Nakazawa, Fumio; Nishio, Fumihiko; Obinata, Ichio; Ohgaito, Rumi; Oka, Akira; Okuno, Jun’ichi; Okuyama, Junichi; Oyabu, Ikumi; Parrenin, Frédéric; Pattyn, Frank; Saito, Fuyuki; Saito, Takashi; Saito, Takeshi; Sakurai, Toshimitsu; Sasa, Kimikazu; Seddik, Hakime; Shibata, Yasuyuki; Shinbori, Kunio; Suzuki, Keisuke; Suzuki, Toshitaka; Takahashi, Akiyoshi; Takahashi, Kunio; Takahashi, Shuhei; Takata, Morimasa; Tanaka, Yoichi; Uemura, Ryu; Watanabe, Genta; Watanabe, Okitsugu; Yamasaki, Tetsuhide; Yokoyama, Kotaro; Yoshimori, Masakazu; Yoshimoto, Takayasu

2017-01-01

Climatic variabilities on millennial and longer time scales with a bipolar seesaw pattern have been documented in paleoclimatic records, but their frequencies, relationships with mean climatic state, and mechanisms remain unclear. Understanding the processes and sensitivities that underlie these changes will underpin better understanding of the climate system and projections of its future change. We investigate the long-term characteristics of climatic variability using a new ice-core record from Dome Fuji, East Antarctica, combined with an existing long record from the Dome C ice core. Antarctic warming events over the past 720,000 years are most frequent when the Antarctic temperature is slightly below average on orbital time scales, equivalent to an intermediate climate during glacial periods, whereas interglacial and fully glaciated climates are unfavourable for a millennial-scale bipolar seesaw. Numerical experiments using a fully coupled atmosphere-ocean general circulation model with freshwater hosing in the northern North Atlantic showed that climate becomes most unstable in intermediate glacial conditions associated with large changes in sea ice and the Atlantic Meridional Overturning Circulation. Model sensitivity experiments suggest that the prerequisite for the most frequent climate instability with bipolar seesaw pattern during the late Pleistocene era is associated with reduced atmospheric CO2 concentration via global cooling and sea ice formation in the North Atlantic, in addition to extended Northern Hemisphere ice sheets. PMID:28246631

Prognostic significance of cell cycle proteins and genomic instability in borderline, early and advanced stage ovarian carcinomas.

PubMed

Blegen, H.; Einhorn, N.; Sjövall, K.; Roschke, A.; Ghadimi, B. M.; McShane, L. M.; Nilsson, B.; Shah, K.; Ried, T.; Auer, G.

2000-11-01

Disturbed cell cycle-regulating checkpoints and impairment of genomic stability are key events during the genesis and progression of malignant tumors. We analyzed 80 epithelial ovarian tumors of benign (n = 10) and borderline type (n = 18) in addition to carcinomas of early (n = 26) and advanced (n = 26) stages for the expression of Ki67, cyclin A and cyclin E, p21WAF-1, p27KIP-1 and p53 and correlated the results with the clinical course. Genomic instability was assessed by DNA ploidy measurements and, in 35 cases, by comparative genomic hybridization. Overexpression of cyclin A and cyclin E was observed in the majority of invasive carcinomas, only rarely in borderline tumors and in none of the benign tumors. Similarly, high expression of p53 together with undetectable p21 or loss of chromosome arm 17p were frequent events only in adenocarcinomas. Both borderline tumors and adenocarcinomas revealed a high number of chromosomal gains and losses. However, regional chromosomal amplifications were found to occur 13 times more frequently in the adenocarcinomas than in the borderline tumors. The expression pattern of low p27 together with high Ki67 was found to be an independent predictor of poor outcome in invasive carcinomas. The results provide a link between disturbed cell cycle regulatory proteins, chromosomal aberrations and survival in ovarian carcinomas.

Self-Reported Knee Instability Before and After Total Knee Replacement Surgery.

PubMed

Fleeton, Genevieve; Harmer, Alison R; Nairn, Lillias; Crosbie, Jack; March, Lyn; Crawford, Ross; van der Esch, Martin; Fransen, Marlene

2016-04-01

To determine the prevalence and burden of pain and activity limitations associated with retaining presurgery self-reported knee instability 6 months after total knee replacement (TKR) surgery and to identify early potentially modifiable risk factors for retaining knee instability in the operated knee after TKR surgery. A secondary analysis was performed using measures obtained from 390 participants undergoing primary unilateral TKR and participating in a randomized clinical trial. Self-reported knee instability was measured using 2 items from the Activities of Daily Living Scale of the Knee Outcome Survey. Outcome measures were knee pain (range 0-20) and physical function (range 0-68) on the Western Ontario and McMaster Universities Arthritis Index (WOMAC), stair-climb power, 50-foot walk time, knee range of motion, and isometric knee flexion and extension strength. In this study, 72% of participants reported knee instability just prior to surgery, with 32% retaining instability in the operated knee 6 months after surgery. Participants retaining operated knee instability had significantly more knee pain and activity limitations 6 months after surgery, with mean ± SD WOMAC scores of 4.8 ± 3.7 and 17.5 ± 11.1, respectively, compared to participants without knee instability, with 2.9 ± 3.1 and 9.8 ± 9.2. The multivariable predictor model for retained knee instability included a high comorbidity score (>6), low stair-climb power (<150 watts), more pain in the operated knee (>7 of 20), and younger age (<60 years). Self-reported knee instability is highly prevalent before and after TKR surgery and is associated with a considerable burden of pain and activity limitation in the operated knee. Increasing lower extremity muscle power may reduce the risk of retaining knee instability after TKR surgery. © 2016, American College of Rheumatology.

Loss of heterozygosity and microsatellite instability are rare in sporadic dedifferentiated liposarcoma: a study of 43 well-characterized cases.

PubMed

Davis, Jessica L; Grenert, James P; Horvai, Andrew E

2014-06-01

Defects in mismatch repair proteins have been identified in Lynch syndrome-associated liposarcomas, as well as in rare sporadic sarcomas. However, it is unclear if mismatch repair defects have a role in sarcoma tumorigenesis. Microsatellite instability is a surrogate marker of mismatch repair defects. To determine whether sporadic dedifferentiated liposarcomas display microsatellite instability and, if so, to evaluate whether such instability differs between the lipogenic and nonlipogenic components of these tumors. The diagnoses of conventional dedifferentiated liposarcoma were confirmed by a combination of morphologic, immunophenotypic, and molecular studies. Standard fluorescence-based polymerase chain reaction, including 5 mononucleotide microsatellite markers (BAT25, BAT26, NR21, NR24, and MONO27), as well as 2 pentanucleotide repeat markers (Penta C and Penta D), was used to test for instability and loss of heterozygosity. We demonstrated only a single case (1 of 43) with microsatellite instability at one mononucleotide marker. No sarcomas showed high-level microsatellite instability. However, loss of heterozygosity at the pentanucleotide markers was observed in 8 of 43 cases. The presence of loss of heterozygosity was overrepresented in the nonlipogenic (dedifferentiated) components compared with the paired lipogenic (well differentiated) components. Mismatch repair defects do not contribute to sporadic dedifferentiated liposarcoma tumorigenesis. Whether the observed loss of heterozygosity drives tumorigenesis in liposarcoma, for example by affecting tumor suppressor or cell cycle regulator genes, remains to be determined.

A framework to quantify karyotype variation associated with CHO cell line instability at a single-cell level.

PubMed

Baik, Jong Youn; Lee, Kelvin H

2017-05-01

Chinese hamster ovary (CHO) cells, the major mammalian host cells for biomanufacturing of therapeutic proteins, have been extensively investigated to enhance productivity and product quality. However, cell line instability resulting in unexpected changes in productivity or product quality continues to be a challenge. Based on previous reports about causes and characteristics of production instability, we hypothesized that chromosomal rearrangements due to genomic instability are associated with production instability and that these events can be characterized. We developed a production instability model using secreted alkaline phosphatase (SEAP)-expressing CHO cells (CHO-SEAP) as well as a framework to quantify chromosomal rearrangements by karyotyping. In the absence of methotrexate (MTX), CHO-SEAP cells exhibited a slightly increased growth rate, a significantly decreased specific productivity, and changes in the chromosomal rearrangement ratio of seven chromosomes. In contrast, when MTX was re-introduced, the growth rate and SEAP productivity reversed to the initial values, demonstrating the reversibility of production instability in CHO-SEAP cells. Fluorescence in situ hybridization analysis identified that the SEAP genes were incorporated in the chromosomal rearrangement (insertion) part of the der(Z9) chromosome. Karyotype analysis indicated that the insertion ratio of the der(Z9) chromosome decreased in the CHO-SEAP cells grown without MTX, demonstrating a correlation between chromosomal rearrangement and production instability. Our results support a mechanism for production instability, wherein a randomly generated chromosomal rearrangement (or genotype) results in cells with a growth advantage that is also associated with non (or low)-producing traits. As a result, the non-producing cells grow faster and thereby outgrow the producing population. Biotechnol. Bioeng. 2017;114: 1045-1053. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The role of arthroscopy in chronic elbow instability.

PubMed

Goodwin, David; Dynin, Maria; Macdonnell, J Ryan; Kessler, Michael W

2013-12-01

Elbow arthroscopy has had an emerging role in the management of many disorders of the elbow. In patients with chronic elbow instability, several arthroscopic techniques have been described in the diagnosis and management of posterolateral rotatory instability and valgus instability. We performed a systematic review investigating the role of arthroscopy in posterolateral rotatory instability and valgus instability in the elbow using the PubMed and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases, and the Cochrane Database of Systematic Reviews, consisting of articles from peer-reviewed journals published in the English language after January 1, 1991. Search criteria initially identified 249 articles. Twenty-five articles met criteria for inclusion. This included 17 review articles, 4 cadaveric studies, 3 retrospective studies, and 1 prospective study. Two of the retrospective studies compared arthroscopic and open techniques. Articles included in this systematic review concluded that arthroscopy is an accurate adjunct to physical examination and imaging in the diagnosis of chronic elbow instability and affords an exceptional view of the joint with the ability to address intra-articular pathologic conditions. Arthroscopic surgical techniques have shown equivalent clinical outcomes in a comparison of arthroscopic and open techniques. Elbow arthroscopy is a valuable tool in the diagnosis and management of chronic elbow instability. Patients treated arthroscopically benefit from additional diagnostic techniques, improved visualization of the elbow joint, the ability to address coexisting intra-articular pathologic conditions, and minimal soft tissue injury with no clinical consequences in outcomes. With such significant advantages, the use of elbow arthroscopy is likely to expand in the management of chronic elbow instability. Level IV, systematic review. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Gross Instability After Hip Arthroscopy: An Analysis of Case Reports Evaluating Surgical and Patient Factors.

PubMed

Yeung, Marco; Memon, Muzammil; Simunovic, Nicole; Belzile, Etienne; Philippon, Marc J; Ayeni, Olufemi R

2016-06-01

Gross hip instability is a rare complication after hip arthroscopy, and there is limited literature surrounding this topic. This systematic review investigates cases of gross hip instability after arthroscopy and discusses the risk factors associated with this complication. A systematic search was performed in duplicate for studies investigating gross hip instability after hip arthroscopy up to October 2015. Study parameters including sample size, mechanism and type of dislocation, surgical procedure details, patient characteristics, postoperative rehabilitation protocol, and level of evidence were analyzed. The systematic review identified 9 case reports investigating gross hip instability after hip arthroscopy (10 patients). Anterior dislocation occurred in 66.7% of patients, and most injuries occurred with a low-energy mechanism. Common surgical factors cited included unrepaired capsulotomy (77.8%) and iliopsoas release (33.3%), whereas patient factors included female gender (77.8%), acetabular dysplasia (22.2%), and general ligamentous laxity (11.1%). Postoperative restrictions and protocols were variable and inconsistently reported, and their relation to post-arthroscopy instability was difficult to ascertain. This systematic review discussed various patient, surgical, and postoperative risk factors of gross hip instability after arthroscopy. Patient characteristics such as female gender, hip dysplasia, and ligamentous laxity may be risk factors for post-arthroscopy dislocation. Similarly, surgical risk factors for iatrogenic hip instability may include unrepaired capsulotomies and iliopsoas debridement, although the role of capsular closure in iatrogenic instability is not clear. The influences of postoperative restrictions and protocols on dislocation are also unclear in the current literature. Surgeons should be cognizant of these risk factors when performing hip arthroscopy and be mindful that these factors appear to occur in combination. Level IV, systematic review of Level IV studies. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Transient disturbance growth in flows over convex surfaces

NASA Astrophysics Data System (ADS)

Karp, Michael; Hack, M. J. Philipp

2017-11-01

Flows over curved surfaces occur in a wide range of applications including airfoils, compressor and turbine vanes as well as aerial, naval and ground vehicles. In most of these applications the surface has convex curvature, while concave surfaces are less common. Since monotonic boundary-layer flows over convex surfaces are exponentially stable, they have received considerably less attention than flows over concave walls which are destabilized by centrifugal forces. Non-modal mechanisms may nonetheless enable significant disturbance growth which can make the flow susceptible to secondary instabilities. A parametric investigation of the transient growth and secondary instability of flows over convex surfaces is performed. The specific conditions yielding the maximal transient growth and strongest instability are identified. The effect of wall-normal and spanwise inflection points on the instability process is discussed. Finally, the role and significance of additional parameters, such as the geometry and pressure gradient, is analyzed.

Instabilities in wormlike micelle systems. From shear-banding to elastic turbulence.

PubMed

Fardin, M-A; Lerouge, S

2012-09-01

Shear-banding is ubiquitous in complex fluids. It is related to the organization of the flow into macroscopic bands bearing different viscosities and local shear rates and stacked along the velocity gradient direction. This flow-induced transition towards a heterogeneous flow state has been reported in a variety of systems, including wormlike micellar solutions, telechelic polymers, emulsions, clay suspensions, colloidal gels, star polymers, granular materials, or foams. In the past twenty years, shear-banding flows have been probed by various techniques, such as rheometry, velocimetry and flow birefringence. In wormlike micelle solutions, many of the data collected exhibit unexplained spatio-temporal fluctuations. Different candidates have been identified, the main ones being wall slip, interfacial instability between bands or bulk instability of one of the bands. In this review, we present experimental evidence for a purely elastic instability of the high shear rate band as the main origin for fluctuating shear-banding flows.

Modulated electron cyclotron drift instability in a high-power pulsed magnetron discharge.

PubMed

Tsikata, Sedina; Minea, Tiberiu

2015-05-08

The electron cyclotron drift instability, implicated in electron heating and anomalous transport, is detected in the plasma of a planar magnetron. Electron density fluctuations associated with the mode are identified via an adapted coherent Thomson scattering diagnostic, under direct current and high-power pulsed magnetron operation. Time-resolved analysis of the mode amplitude reveals that the instability, found at MHz frequencies and millimeter scales, also exhibits a kHz-scale modulation consistent with the observation of larger-scale plasma density nonuniformities, such as the rotating spoke. Sharply collimated axial fluctuations observed at the magnetron axis are consistent with the presence of escaping electrons in a region where the magnetic and electric fields are antiparallel. These results distinguish aspects of magnetron physics from other plasma sources of similar geometry, such as the Hall thruster, and broaden the scope of instabilities which may be considered to dictate magnetron plasma features.

Spatiotemporal chaos in the dynamics of buoyantly and diffusively unstable chemical fronts

NASA Astrophysics Data System (ADS)

Baroni, M. P. M. A.; Guéron, E.; De Wit, A.

2012-03-01

Nonlinear dynamics resulting from the interplay between diffusive and buoyancy-driven Rayleigh-Taylor (RT) instabilities of autocatalytic traveling fronts are analyzed numerically for various values of the relevant parameters. These are the Rayleigh numbers of the reactant A and autocatalytic product B solutions as well as the ratio D =DB/DA between the diffusion coefficients of the two key chemical species. The interplay between the coarsening dynamics characteristic of the RT instability and the constant short wavelength modulation of the diffusive instability can lead in some regimes to complex dynamics dominated by irregular succession of birth and death of fingers. By using spectral entropy measurements, we characterize the transition between order and spatial disorder in this system. The analysis of the power spectrum and autocorrelation function, moreover, identifies similarities between the various spatial patterns. The contribution of the diffusive instability to the complex dynamics is discussed.

Instability, finite amplitude pulsation and mass-loss in models of massive OB-type stars

NASA Astrophysics Data System (ADS)

Yadav, Abhay Pratap; Glatzel, Wolfgang

2017-11-01

Variability and mass-loss are common phenomena in massive OB-type stars. It is argued that they are caused by violent strange mode instabilities identified in corresponding stellar models. We present a systematic linear stability analysis with respect to radial perturbations of massive OB-type stars with solar chemical composition and masses between 23 and 100 M⊙. For selected unstable stellar models, we perform non-linear simulations of the evolution of the instabilities into the non-linear regime. Finite amplitude pulsations with periods in the range between hours and 100 d are found to be the final result of the instabilities. The pulsations are associated with a mean acoustic luminosity which can be the origin of a pulsationally driven wind. Corresponding mass-loss rates lie in the range between 10-9 and 10-4 M⊙ yr-1 and may thus affect the evolution of massive stars.

Effects of ridge cracking and interface sliding on morphological symmetry breaking in straight-sided blisters

NASA Astrophysics Data System (ADS)

Li, Shi-Chen; Yu, Sen-Jiang; He, Linghui; Ni, Yong

2018-03-01

Complex surface patterns generated by nonlinear buckling originate from various symmetry-breaking instabilities. Identifying possible key factors that regulate the instability modes is critical to reveal the mechanism of the surface pattern selection. In this paper, how another two factors (ridge cracking and interface sliding) including Poisson's ratio influence the morphological symmetry breaking in straight-sided blisters are systematically studied. Morphology diagrams from stability analysis show that ridge cracking and low Poisson's ratio promote symmetric instability mode and favor bubble-like blisters while interface sliding and high Poisson's ratio facilitate antisymmetric instability mode and result in telephone cord buckles. The analytical predictions are evidenced by experimental observations on annealed silicon nitride films on glass substrates and confirmed by nonlinear numerical simulations. This study explains how and why the rarely observed bubble-like blisters in accompany with ridge crack can appear in brittle thin films in comparison with the ubiquitously observed telephone cord buckles that usually form as the development of an antisymmetric instability mode when straight-sided blisters undergo the super-critical isotropic compression.

Simulations of Large-Area Electron Beam Diodes

NASA Astrophysics Data System (ADS)

Swanekamp, S. B.; Friedman, M.; Ludeking, L.; Smithe, D.; Obenschain, S. P.

1999-11-01

Large area electron beam diodes are typically used to pump the amplifiers of KrF lasers. Simulations of large-area electron beam diodes using the particle-in-cell code MAGIC3D have shown the electron flow in the diode to be unstable. Since this instability can potentially produce a non-uniform current and energy distribution in the hibachi structure and lasing medium it can be detrimental to laser efficiency. These results are similar to simulations performed using the ISIS code.(M.E. Jones and V.A. Thomas, Proceedings of the 8^th) International Conference on High-Power Particle Beams, 665 (1990). We have identified the instability as the so called ``transit-time" instability(C.K. Birdsall and W.B. Bridges, Electrodynamics of Diode Regions), (Academic Press, New York, 1966).^,(T.M. Antonsen, W.H. Miner, E. Ott, and A.T. Drobot, Phys. Fluids 27), 1257 (1984). and have investigated the role of the applied magnetic field and diode geometry. Experiments are underway to characterize the instability on the Nike KrF laser system and will be compared to simulation. Also some possible ways to mitigate the instability will be presented.

Simulations of Instabilities in Tidal Tails

NASA Astrophysics Data System (ADS)

Comparetta, Justin N.; Quillen, A. C.

2010-05-01

We use graphics cards to run a hybrid test particle/N-body simulation to integrate 4 million massless particle trajectories within fully self-consistent N-body simulations of 128,000 - 256,000 particles. The number of massless particles allows us to resolve fine structure in the spatial distribution and phase space of a dwarf galaxy that is disrupted in the tidal field of a Milky Way type galaxy. The tidal tails exhibit clumping or a smoke-like appearance. By running simulations with different satellite particle mass, number of massive vs massless particles and with and without a galaxy disk, we have determined that the instabilities are not due to numerical noise or shocking as the satellite passes through the disk of the Galaxy. The instability is possibly a result of self-gravity which indicates it may be due to Jeans instabilities. Simulations involving different halo particle mass may suggest limitations on dark matter halo substructure. We find that the instabilities are visible in velocity space as well as real space and thus could be identified from velocity surveys as well as number counts.

Refinement of 1p36 alterations not involving PRDM16 in myeloid and lymphoid malignancies.

PubMed

Duhoux, Francois P; Ameye, Geneviève; Lambot, Virginie; Herens, Christian; Lambert, Frédéric; Raynaud, Sophie; Wlodarska, Iwona; Michaux, Lucienne; Roche-Lestienne, Catherine; Labis, Elise; Taviaux, Sylvie; Chapiro, Elise; Nguyen-Khac, Florence; Khac, Florence Nguyen; Struski, Stéphanie; Dobbelstein, Sophie; Dastugue, Nicole; Lippert, Eric; Speleman, Frank; Van Roy, Nadine; De Weer, An; Rack, Katrina; Talmant, Pascaline; Richebourg, Steven; Mugneret, Francine; Tigaud, Isabelle; Mozziconacci, Marie-Joëlle; Laibe, Sophy; Nadal, Nathalie; Terré, Christine; Libouton, Jeanne-Marie; Decottignies, Anabelle; Vikkula, Miikka; Poirel, Hélène A

2011-01-01

Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis.

Refinement of 1p36 Alterations Not Involving PRDM16 in Myeloid and Lymphoid Malignancies

PubMed Central

Duhoux, Francois P.; Ameye, Geneviève; Lambot, Virginie; Herens, Christian; Lambert, Frédéric; Raynaud, Sophie; Wlodarska, Iwona; Michaux, Lucienne; Roche-Lestienne, Catherine; Labis, Elise; Taviaux, Sylvie; Chapiro, Elise; Khac, Florence Nguyen; Struski, Stéphanie; Dobbelstein, Sophie; Dastugue, Nicole; Lippert, Eric; Speleman, Frank; Van Roy, Nadine; De Weer, An; Rack, Katrina; Talmant, Pascaline; Richebourg, Steven; Mugneret, Francine; Tigaud, Isabelle; Mozziconacci, Marie-Joëlle; Laibe, Sophy; Nadal, Nathalie; Terré, Christine; Libouton, Jeanne-Marie; Decottignies, Anabelle; Vikkula, Miikka; Poirel, Hélène A.

2011-01-01

Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis. PMID:22039459

Patterns of Welfare Attitudes in the Australian Population.

PubMed

Schofield, Timothy P; Butterworth, Peter

2015-01-01

The study of community attitudes toward welfare and welfare recipients is an area of increasing interest. This is not only because negative attitudes can lead to stigmatization and discrimination, but because of the relevance of social attitudes to policy decisions. We quantify the attitudes toward welfare in the Australian population using attitude data from a nationally representative survey (N = 3243). Although there was broad support for the social welfare system, negative attitudes are held toward those who receive welfare benefits. Using canonical correlation analysis we identify multivariate associations between welfare attitudes and respondent demographic characteristics. A primary attitudinal dimension of welfare positivity was found amongst those with higher levels of education, life instability, and personal exposure to the welfare system. Other patterns of negative welfare attitudes appeared to be motivated by beliefs that the respondent's personal circumstances indicate their deservingness. Moreover, a previously unidentified and unconsidered subset of respondents was identified. This group had positive attitudes toward receiving government benefits despite having no recent experience of welfare. They did, however, possess many of the characteristics that frequently lead to welfare receipt. These results provide insights into not only how attitudinal patterns segment across the population, but are of relevance to policy makers considering how to align welfare reform with community attitudes.

Patterns of Welfare Attitudes in the Australian Population

PubMed Central

Schofield, Timothy P.; Butterworth, Peter

2015-01-01

The study of community attitudes toward welfare and welfare recipients is an area of increasing interest. This is not only because negative attitudes can lead to stigmatization and discrimination, but because of the relevance of social attitudes to policy decisions. We quantify the attitudes toward welfare in the Australian population using attitude data from a nationally representative survey (N = 3243). Although there was broad support for the social welfare system, negative attitudes are held toward those who receive welfare benefits. Using canonical correlation analysis we identify multivariate associations between welfare attitudes and respondent demographic characteristics. A primary attitudinal dimension of welfare positivity was found amongst those with higher levels of education, life instability, and personal exposure to the welfare system. Other patterns of negative welfare attitudes appeared to be motivated by beliefs that the respondent’s personal circumstances indicate their deservingness. Moreover, a previously unidentified and unconsidered subset of respondents was identified. This group had positive attitudes toward receiving government benefits despite having no recent experience of welfare. They did, however, possess many of the characteristics that frequently lead to welfare receipt. These results provide insights into not only how attitudinal patterns segment across the population, but are of relevance to policy makers considering how to align welfare reform with community attitudes. PMID:26554361

Frequent Users of Hospital Emergency Departments in Korea Characterized by Claims Data from the National Health Insurance: A Cross Sectional Study

PubMed Central

Woo, Jung Hoon; Grinspan, Zachary; Shapiro, Jason; Rhee, Sang Youl

2016-01-01

The Korean National Health Insurance, which provides universal coverage for the entire Korean population, is now facing financial instability. Frequent emergency department (ED) users may represent a medically vulnerable population who could benefit from interventions that both improve care and lower costs. To understand the nature of frequent ED users in Korea, we analyzed claims data from a population-based national representative sample. We performed both bivariate and multivariable analyses to investigate the association between patient characteristics and frequent ED use (4+ ED visits in a year) using claims data of a 1% random sample of the Korean population, collected in 2009. Among 156,246 total ED users, 4,835 (3.1%) were frequent ED users. These patients accounted for 14% of 209,326 total ED visits and 17.2% of $76,253,784 total medical expenses generated from all ED visits in the 1% data sample. Frequent ED users tended to be older, male, and of lower socio-economic status compared with occasional ED users (p < 0.001 for each). Moreover, frequent ED users had longer stays in the hospital when admitted, higher probability of undergoing an operative procedure, and increased mortality. Among 8,425 primary diagnoses, alcohol-related complaints and schizophrenia showed the strongest positive correlation with the number of ED visits. Among the frequent ED users, mortality and annual outpatient department visits were significantly lower in the alcohol-related patient subgroup compared with other frequent ED users; furthermore, the rate was even lower than that for non-frequent ED users. Our findings suggest that expanding mental health and alcohol treatment programs may be a reasonable strategy to decrease the dependence of these patients on the ED. PMID:26809051

Numerical results on noise-induced dynamics in the subthreshold regime for thermoacoustic systems

NASA Astrophysics Data System (ADS)

Gupta, Vikrant; Saurabh, Aditya; Paschereit, Christian Oliver; Kabiraj, Lipika

2017-03-01

Thermoacoustic instability is a serious issue in practical combustion systems. Such systems are inherently noisy, and hence the influence of noise on the dynamics of thermoacoustic instability is an aspect of practical importance. The present work is motivated by a recent report on the experimental observation of coherence resonance, or noise-induced coherence with a resonance-like dependence on the noise intensity as the system approaches the stability margin, for a prototypical premixed laminar flame combustor (Kabiraj et al., Phys. Rev. E, 4 (2015)). We numerically investigate representative thermoacoustic models for such noise-induced dynamics. Similar to the experiments, we study variation in system dynamics in response to variations in the noise intensity and in a critical control parameter as the systems approach their stability margins. The qualitative match identified between experimental results and observations in the representative models investigated here confirms that coherence resonance is a feature of thermoacoustic systems. We also extend the experimental results, which were limited to the case of subcritical Hopf bifurcation, to the case of supercritical Hopf bifurcation. We identify that the phenomenon has qualitative differences for the systems undergoing transition via subcritical and supercritical Hopf bifurcations. Two important practical implications are associated with the findings. Firstly, the increase in noise-induced coherence as the system approaches the onset of thermoacoustic instability can be considered as a precursor to the instability. Secondly, the dependence of noise-induced dynamics on the bifurcation type can be utilised to distinguish between subcritical and supercritical bifurcation prior to the onset of the instability.

Roles of human POLD1 and POLD3 in genome stability

PubMed Central

Tumini, Emanuela; Barroso, Sonia; -Calero, Carmen Pérez; Aguilera, Andrés

2016-01-01

DNA replication is essential for cellular proliferation. If improperly controlled it can constitute a major source of genome instability, frequently associated with cancer and aging. POLD1 is the catalytic subunit and POLD3 is an accessory subunit of the replicative Pol δ polymerase, which also functions in DNA repair, as well as the translesion synthesis polymerase Pol ζ, whose catalytic subunit is REV3L. In cells depleted of POLD1 or POLD3 we found a differential but general increase in genome instability as manifested by DNA breaks, S-phase progression impairment and chromosome abnormalities. Importantly, we showed that both proteins are needed to maintain the proper amount of active replication origins and that POLD3-depletion causes anaphase bridges accumulation. In addition, POLD3-associated DNA damage showed to be dependent on RNA-DNA hybrids pointing toward an additional and specific role of this subunit in genome stability. Interestingly, a similar increase in RNA-DNA hybrids-dependent genome instability was observed in REV3L-depleted cells. Our findings demonstrate a key role of POLD1 and POLD3 in genome stability and S-phase progression revealing RNA-DNA hybrids-dependent effects for POLD3 that might be partly due to its Pol ζ interaction. PMID:27974823

Learning from the Past, Looking to the Future: Modeling Social Unrest in Karachi, Pakistan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olson, Jarrod; Kurzrok, Andrew J.; Hund, Gretchen

Social unrest represents a major challenge for policy makers around the globe, as it can quickly escalate from small scale disturbances to highly public protests, riots and even civil war. This research was motivated by a need to understand social instability and to unpack the comments made during a spring 2013 conference hosted by Pacific Northwest National Laboratory’s Center for Global Security and the U.S. Institute for Peace, where policymakers noted that models considering social instability are often not suitable for decision-making. This analysis shows that existing state level models of instability could be improved in spatial scale to themore » city level, even without significantly improved data access. Better data would make this analysis more complete and likely improve the quality of the model. Another challenge with incorporating modeling into decision-making is the need to understand uncertainty in a model. Policy makers are frequently tasked with making decisions without a clear outcome, so characterization of uncertainty is critical. This report describes the work and findings of the project. It took place in three phases: a literature review of social stability research, a “hindsight scan” that looked at historical data, and a “foresight scan” looking at future scenarios.« less

Fibular lengthening for the management of translational talus instability in hereditary multiple exostoses patients.

PubMed

Lee, Dong Yeon; Kim, Joong Il; Song, Mi Hyun; Choi, Eun Seok; Park, Moon Seok; Yoo, Won Joon; Chung, Chin Youb; Choi, In Ho; Cho, Tae-Joon

2014-01-01

Hereditary multiple exostoses (HME) patients frequently present with ankle valgus deformity and marked fibular shortening. Loss of the lateral buttress may cause translational talus instability (TTI) that manifests as ankle pain after physical exercise, medial clear space widening on plain radiographs, and gross translational movement of the talus within the mortise. Among 123 HME patients examined and/or surgically treated, 10 patients (14 ankles) with symptomatic TTI underwent fibular lengthening with osteochondroma excision. Twelve ankles of 9 patients were followed for >1 year after surgery. Total fibular length gain averaged 15.3 mm and distal migration of the distal fibular fragment averaged 5.5 mm. The mean medial clear space decreased from preoperative 6.7 mm to postlengthening 3.5 mm. Gross instability of the talus within the ankle mortise disappeared in all cases. AOFAS ankle-hindfoot score improved from preoperative 80.3 to 97.3 at the latest follow-up. The current study showed the fibular lengthening improved lateral ankle stability by providing lateral buttress on the talus and providing favorable short-term result by ameliorating exercise-induced ankle pain in TTI of HME. The authors carefully conclude that TTI is a rare but potentially disabling condition in HME patients, requiring special attention during follow-up of HME patients. Level IV.

Cytokinesis Failure Leading to Chromosome Instability in v-Src-Induced Oncogenesis.

PubMed

Nakayama, Yuji; Soeda, Shuhei; Ikeuchi, Masayoshi; Kakae, Keiko; Yamaguchi, Naoto

2017-04-12

v-Src, an oncogene found in Rous sarcoma virus, is a constitutively active variant of c-Src. Activation of Src is observed frequently in colorectal and breast cancers, and is critical in tumor progression through multiple processes. However, in some experimental conditions, v-Src causes growth suppression and apoptosis. In this review, we highlight recent progress in our understanding of cytokinesis failure and the attenuation of the tetraploidy checkpoint in v-Src-expressing cells. v-Src induces cell cycle changes-such as the accumulation of the 4N cell population-and increases the number of binucleated cells, which is accompanied by an excess number of centrosomes. Time-lapse analysis of v-Src-expressing cells showed that cytokinesis failure is caused by cleavage furrow regression. Microscopic analysis revealed that v-Src induces delocalization of cytokinesis regulators including Aurora B and Mklp1. Tetraploid cell formation is one of the causes of chromosome instability; however, tetraploid cells can be eliminated at the tetraploidy checkpoint. Interestingly, v-Src weakens the tetraploidy checkpoint by inhibiting the nuclear exclusion of the transcription coactivator YAP, which is downstream of the Hippo pathway and its nuclear exclusion is critical in the tetraploidy checkpoint. We also discuss the relationship between v-Src-induced chromosome instability and growth suppression in v-Src-induced oncogenesis.

Formal Solutions for Polarized Radiative Transfer. III. Stiffness and Instability

NASA Astrophysics Data System (ADS)

Janett, Gioele; Paganini, Alberto

2018-04-01

Efficient numerical approximation of the polarized radiative transfer equation is challenging because this system of ordinary differential equations exhibits stiff behavior, which potentially results in numerical instability. This negatively impacts the accuracy of formal solvers, and small step-sizes are often necessary to retrieve physical solutions. This work presents stability analyses of formal solvers for the radiative transfer equation of polarized light, identifies instability issues, and suggests practical remedies. In particular, the assumptions and the limitations of the stability analysis of Runge–Kutta methods play a crucial role. On this basis, a suitable and pragmatic formal solver is outlined and tested. An insightful comparison to the scalar radiative transfer equation is also presented.

Antisocial personality disorder--stable and unstable subtypes.

PubMed

Ullrich, Simone; Coid, Jeremy

2010-04-01

There have been criticisms that the criteria for antisocial personality disorder (ASPD) are over-dependent on criminal behavior. This study aimed to identify unrelated criteria of social and behavioral problems and instability, and to investigate their associations in a representative household sample of adults in the UK. Approximately one third of adults with ASPD did not fulfill any of the criteria for instability. They were less aggressive and involved in illegal activities but expressed less remorse for their behaviors. Instability in ASPD was mediated primarily through comorbid anxiety disorders and borderline personality disorder. The concept of Secondary Psychopathy, which has not generally been applied to ASPD, demonstrated many similarities to the unstable subtype.

Comprehensive experimental and numerical analysis of instability phenomena in pump turbines

NASA Astrophysics Data System (ADS)

Gentner, Ch; Sallaberger, M.; Widmer, Ch; Bobach, B.-J.; Jaberg, H.; Schiffer, J.; Senn, F.; Guggenberger, M.

2014-03-01

The changes in the electricity market have led to changed requirements for the operation of pump turbines. Utilities need to change fast and frequently between pumping and generating modes and increasingly want to operate at off-design conditions for extended periods. Operation of the units in instable areas of the machine characteristic is not acceptable and may lead to self-excited vibration of the hydraulic system. In turbine operation of pump turbines unstable behaviour can occur at low load off-design operation close to runaway conditions (S-shape of the turbine characteristic). This type of instability may impede the synchronization of the machine in turbine mode and thus increase start-up and switch over times. A pronounced S-shaped instability can also lead to significant drop of discharge in the event of load rejection. Low pressure on the suction side and in the tail-race tunnel could cause dangerous separation of the water column. Understanding the flow features that lead to the instable behaviour of pump turbines is a prerequisite to the design of machines that can fulfil the growing requirements relating to operational flexibility. Flow simulation in these instability zones is demanding due to the complex and highly unsteady flow patterns. Only unsteady simulation methods are able to reproduce the governing physical effects in these operating regions. ANDRITZ HYDRO has been investigating the stability behaviour of pump turbines in turbine operation in cooperation with several universities using simulation and measurements. In order to validate the results of flow simulation of unstable operating points, the Graz University of Technology (Austria) performed detailed experimental investigations. Within the scope of a long term research project, the operating characteristics of several pump turbine runners have been measured and flow patterns in the pump turbine at speed no load and runaway have been examined by 2D Laser particle image velocimetry (PIV). For several wicket gate positions, the flow fields in the vane-less space at runner inlet observed in the experiment are compared with the results of unsteady CFD flow simulations. Physical phenomena are visualized and insight to flow phenomena is given. Analyses using both results of simulation and measurement allow deriving a consistent explanation of the fluid mechanical mechanisms leading to the S-shaped instability of pump turbines.

Experiments and theory on parametric instabilities excited in HF heating experiments at HAARP

NASA Astrophysics Data System (ADS)

Kuo, Spencer; Snyder, Arnold; Lee, M. C.

2014-06-01

Parametric instabilities excited by O-mode HF heater and the induced ionospheric modification were explored via HAARP digisonde operated in a fast mode. The impact of excited Langmuir waves and upper hybrid waves on the ionosphere are manifested by bumps in the virtual spread, which expand the ionogram echoes upward as much as 140 km and the downward range spread of the sounding echoes, which exceeds 50 km over a significant frequency range. The theory of parametric instabilities is presented. The theory identifies the ionogram bump located between the 3.2 MHz heater frequency and the upper hybrid resonance frequency and the bump below the upper hybrid resonance frequency to be associated with the Langmuir and upper hybrid instabilities, respectively. The Langmuir bump is located close to the upper hybrid resonance frequency, rather than to the heater frequency, consistent with the theory. Each bump in the virtual height spread of the ionogram is similar to the cusp occurring in daytime ionograms at the E-F2 layer transition, indicating that there is a small ledge in the density profile similar to E-F2 layer transitions. The experimental results also show that the strong impact of the upper hybrid instability on the ionosphere can suppress the Langmuir instability.

Experiments and theory on parametric instabilities excited in HF heating experiments at HAARP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuo, Spencer; Snyder, Arnold; Lee, M. C.

2014-06-15

Parametric instabilities excited by O-mode HF heater and the induced ionospheric modification were explored via HAARP digisonde operated in a fast mode. The impact of excited Langmuir waves and upper hybrid waves on the ionosphere are manifested by bumps in the virtual spread, which expand the ionogram echoes upward as much as 140 km and the downward range spread of the sounding echoes, which exceeds 50 km over a significant frequency range. The theory of parametric instabilities is presented. The theory identifies the ionogram bump located between the 3.2 MHz heater frequency and the upper hybrid resonance frequency and the bump below themore » upper hybrid resonance frequency to be associated with the Langmuir and upper hybrid instabilities, respectively. The Langmuir bump is located close to the upper hybrid resonance frequency, rather than to the heater frequency, consistent with the theory. Each bump in the virtual height spread of the ionogram is similar to the cusp occurring in daytime ionograms at the E-F2 layer transition, indicating that there is a small ledge in the density profile similar to E-F2 layer transitions. The experimental results also show that the strong impact of the upper hybrid instability on the ionosphere can suppress the Langmuir instability.« less

POD analysis of the instability mode of a low-speed streak in a laminar boundary layer

NASA Astrophysics Data System (ADS)

Deng, Si-Chao; Pan, Chong; Wang, Jin-Jun; Rinoshika, Akira

2017-12-01

The instability of one single low-speed streak in a zero-pressure-gradient laminar boundary layer is investigated experimentally via both hydrogen bubble visualization and planar particle image velocimetry (PIV) measurement. A single low-speed streak is generated and destabilized by the wake of an interference wire positioned normal to the wall and in the upstream. The downstream development of the streak includes secondary instability and self-reproduction process, which leads to the generation of two additional streaks appearing on either side of the primary one. A proper orthogonal decomposition (POD) analysis of PIV measured velocity field is used to identify the components of the streak instability in the POD mode space: for a sinuous/varicose type of POD mode, its basis functions present anti-symmetric/symmetric distributions about the streak centerline in the streamwise component, and the symmetry condition reverses in the spanwise component. It is further shown that sinuous mode dominates the turbulent kinematic energy (TKE) through the whole streak evolution process, the TKE content first increases along the streamwise direction to a saturation value and then decays slowly. In contrast, varicose mode exhibits a sustained growth of the TKE content, suggesting an increasing competition of varicose instability against sinuous instability.

Transverse instabilities of stripe domains in magnetic thin films with perpendicular magnetic anisotropy

NASA Astrophysics Data System (ADS)

Ruth, Max E.; Iacocca, Ezio; Kevrekidis, Panayotis G.; Hoefer, Mark A.

2018-03-01

Stripe domains are narrow, elongated, reversed regions that exist in magnetic materials with perpendicular magnetic anisotropy. They appear as a pair of domain walls that can exhibit topology with a nonzero chirality. Recent experimental and numerical investigations identify an instability of stripe domains along the long direction as a means of nucleating isolated magnetic skyrmions. Here, the onset and nonlinear evolution of transverse instabilities for a dynamic stripe domain known as the bion stripe are investigated. Both nontopological and topological variants of the bion stripe are shown to exhibit a long-wavelength transverse instability with different characteristic features. In the former, small transverse variations in the stripe's width lead to a neck instability that eventually pinches the nontopological stripe into a chain of two-dimensional breathers composed of droplet soliton pairs. In the latter case, small variations in the stripe's center result in a snake instability whose topological structure leads to the nucleation of dynamic magnetic skyrmions and antiskyrmions as well as perimeter-modulated droplets. Quantitative, analytical predictions for both the early, linear evolution and the long-time, nonlinear evolution are achieved using an averaged Lagrangian approach that incorporates both exchange (dispersion) and anisotropy (nonlinearity). The method of analysis is general and can be applied to other filamentary structures.

Competition between Langmuir and upper-hybrid turbulence in a high-frequency-pumped ionosphere.

PubMed

Thidé, B; Sergeev, E N; Grach, S M; Leyser, T B; Carozzi, T D

2005-12-16

We show how the secondary escaping radiation, also known as stimulated electromagnetic emission (SEE), from the ionosphere irradiated by a high-intensity radio beam, can be used to study both reflection altitude ponderomotive parametric instabilities and upper-hybrid altitude thermal parametric instabilities. This has allowed us to observe the transfer of energy from smaller to higher sideband frequency offsets and to identify a new transient SEE feature.

Modeling, Modal Properties, and Mesh Stiffness Variation Instabilities of Planetary Gears

NASA Technical Reports Server (NTRS)

Parker, Robert G.; Lin, Jian; Krantz, Timothy L. (Technical Monitor)

2001-01-01

Planetary gear noise and vibration are primary concerns in their applications in helicopters, automobiles, aircraft engines, heavy machinery and marine vehicles. Dynamic analysis is essential to the noise and vibration reduction. This work analytically investigates some critical issues and advances the understanding of planetary gear dynamics. A lumped-parameter model is built for the dynamic analysis of general planetary gears. The unique properties of the natural frequency spectra and vibration modes are rigorously characterized. These special structures apply for general planetary gears with cyclic symmetry and, in practically important case, systems with diametrically opposed planets. The special vibration properties are useful for subsequent research. Taking advantage of the derived modal properties, the natural frequency and vibration mode sensitivities to design parameters are investigated. The key parameters include mesh stiffnesses, support/bearing stiffnesses, component masses, moments of inertia, and operating speed. The eigen-sensitivities are expressed in simple, closed-form formulae associated with modal strain and kinetic energies. As disorders (e.g., mesh stiffness variation. manufacturing and assembling errors) disturb the cyclic symmetry of planetary gears, their effects on the free vibration properties are quantitatively examined. Well-defined veering rules are derived to identify dramatic changes of natural frequencies and vibration modes under parameter variations. The knowledge of free vibration properties, eigen-sensitivities, and veering rules provide important information to effectively tune the natural frequencies and optimize structural design to minimize noise and vibration. Parametric instabilities excited by mesh stiffness variations are analytically studied for multi-mesh gear systems. The discrepancies of previous studies on parametric instability of two-stage gear chains are clarified using perturbation and numerical methods. The operating conditions causing parametric instabilities are expressed in closed-form suitable for design guidance. Using the well-defined modal properties of planetary gears, the effects of mesh parameters on parametric instability are analytically identified. Simple formulae are obtained to suppress particular instabilities by adjusting contact ratios and mesh phasing.

Genetic and Epigenetic Changes in Chromosomally Stable and Unstable Progeny of Irradiated Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baulch, Janet E.; Aypar, Umut; Waters, Katrina M.

2014-09-24

Radiation induced genomic instability is a well-studied phenomenon, the underlying mechanisms of which are poorly understood. Persistent oxidative stress, mitochondrial dysfunction, elevated cytokine levels and epigenetic changes are among the mechanisms invoked in the perpetuation of the phenotype. To determine whether epigenetic aberrations affect genomic instability we measured DNA methylation, mRNA and microRNA (miR) levels in well characterized chromosomally stable and unstable clonally expanded single cell survivors of irradiation. While no changes in DNA methylation were observed for the gene promoters evaluated, increased LINE-1 methylation was observed for two unstable clones (LS12, CS9) and decreased Alu element methylation was observedmore » for the other two unstable clones (115, Fe5.0-8). These relationships also manifested for mRNA and miR expression. mRNA identified for the LS12 and CS9 clones were most similar to each other (261 mRNA), while the 115 and Fe5.0-8 clones were more similar to each other, and surprisingly also similar to the two stable clones, 114 and 118 (286 mRNA among these four clones). Pathway analysis showed enrichment for pathways involved in mitochondrial function and cellular redox, themes routinely invoked in genomic instability. The commonalities between the two subgroups of clones were also observed for miR. The number of miR for which anti-correlated mRNA were identified suggests that these miR exert functional effects in each clone. The results of this study demonstrate significant genetic and epigenetic changes in unstable cells, but similar changes almost equally common in chromosomally stable cells. Possible conclusions might be that the chromosomally stable clones have some other form of instability, or that some of the observed changes represent a sort of radiation signature for and that other changes are related to genomic instability. Irrespective, these findings again suggest that a spectrum of changes both drive genomic instability and permit unstable cells to persist and proliferate.« less

Intra-articular findings in symptomatic minor instability of the lateral elbow (SMILE).

PubMed

Arrigoni, Paolo; Cucchi, Davide; D'Ambrosi, Riccardo; Butt, Usman; Safran, Marc R; Denard, Patrick; Randelli, Pietro

2017-07-01

Lateral epicondylitis is generally considered an extra-articular condition. The role of minor instability in the aetiology of lateral elbow pain has rarely been considered. The aim of this study was to evaluate the correlation of lateral ligamentous laxity with aspects of intra-articular lateral elbow pathology and investigate the role of minor instability in lateral elbow pain. Thirty-five consecutive patients aged between 20 and 60 years with recalcitrant lateral epicondylitis who had failed conservative therapy and had no previous trauma or overt instability, were included. The presence of three signs of lateral ligamentous patholaxity and five intra-articular findings were documented during arthroscopy. The relative incidence of each of these was calculated, and the correlation between patholaxity and intra-articular pathology was evaluated. At least one sign of lateral ligamentous laxity was observed in 48.6% of the studied cohort, and 85.7% demonstrated at least one intra-articular abnormal finding. Radial head ballottement was the most common sign of patholaxity (42.9%). Synovitis was the most common intra-articular aspect of pathology (77.1%), followed by lateral capitellar chondropathy (40.0%). A significant correlation was found between the presence of lateral ligamentous patholaxity signs and capitellar chondropathy (p = 0.0409), as well as anteromedial synovitis (p = 0.0408). Almost one half of patients suffering from recalcitrant lateral epicondylitis display signs of lateral ligamentous patholaxity, and over 85% demonstrate at least one intra-articular abnormality. The most frequent intra-articular findings are synovitis and lateral capitellar chondropathy, which correlate significantly with the presence of lateral ligamentous patholaxity. The fact that several patients demonstrated multiple intra-articular findings in relation to laxity provides support to a sequence of pathologic changes that may result from a symptomatic minor instability of the lateral elbow (SMILE) condition. III.

Along - Strike Analysis of Contemporary Ocean Temperature Change on the Cascadia Margin and Implications to Upper Slope Hydrate Instability

NASA Astrophysics Data System (ADS)

Phrampus, B.; Harris, R. N.; Trehu, A. M.; Embley, R. W.; Merle, S. G.

2017-12-01

Gas hydrates are found globally on continental margins and due to the large amount of sequestered carbon in hydrate reservoirs, whether these deposits are dynamic or stable has significant implications for slope stability, ocean/atmosphere carbon budget, and deep-water energy exploration. Recent studies indicate that upper slope hydrate degradation may be relatively widespread on passive margins due to recent ocean temperature warming between 0.012 and 0.033 °C/yr (e.g. Svalbard, North Alaska, and US Atlantic margin). However, the potential and breadth of warming induced hydrate instability remains contentious based on multiple observations including: 1) seep locations not consistent with locations of hydrate dissociation, 2) a lack of hydrate in regions of warming, and 3) evidence for long-lived seepage in regions associated with contemporary warming-induced hydrate dissociation. At the Cascadia margin, a recent study suggests that contemporary warming of intermediate water intersects the hydrate stability zone leading to hydrate dissociation that feeds upper slope seeps. Here, we provide a systematic analysis of along-strike variations in hydrate distribution along the Cascadia margin combined with a multivariable regression of ocean temperatures to characterize the potential of upper slope hydrate instability. Preliminary seep locations reveal upper slope seeps and observed regions of hydrate are correlated spatially between 42.5 and 48.0 °N, outside this region there is a dearth of identified upper slope hydrate and seeps. Between 44.5 and 48.0 °N a contemporary warming trend is as large as 0.006 °C/yr and is collocated with upper slope hydrate and gas seepage. This warming rate is relatively small, 2-5x smaller than warming trends identified in the Arctic where temperature induced hydrate instability remains uncertain. Additionally, we identify a region between 42.5 and 44.5 °N with collocated upper slope seepage and hydrate but no evidence of ocean warming, suggesting upper slope seepage is not driven by temperature induced hydrate instability, but maybe driven by tectonic uplift. These results highlight the absence of temperature driven seepage and slope instability on the Cascadia margin and deemphasize the impact of lower latitude warming on global hydrate dynamics and carbon budget.

In vivo magnetic resonance microscopy of brain structure in unanesthetized flies

NASA Astrophysics Data System (ADS)

Jasanoff, Alan; Sun, Phillip Z.

2002-09-01

We present near-cellular-resolution magnetic resonance (MR) images of an unanesthetized animal, the blowfly Sarcophaga bullata. Immobilized flies were inserted into a home-built gradient probe in a 14.1-T magnet, and images of voxel size (20-40 μm) 3—comparable to the diameter of many neuronal cell bodies in the fly's brain—were obtained in several hours. Use of applied field gradients on the order of 60 G/cm allowed minimally distorted images to be produced, despite significant susceptibility differences across the specimen. The images we obtained have exceptional contrast-to-noise levels; comparison with histology-based anatomical information shows that the MR microscopy faithfully represents patterns of nervous tissue and allows distinct brain regions to be clearly identified. Even at the highest resolutions we explored, morphological detail was pronounced in the apparent absence of instabilities or movement-related artifacts frequently observed during imaging of live animal specimens. This work demonstrates that the challenges of noninvasive in vivo MR microscopy can be overcome in a system amenable to studies of brain structure and physiology.

Characteristics and development of European cyclones with tropical origin in reanalysis data

NASA Astrophysics Data System (ADS)

Dekker, Mark M.; Haarsma, Reindert J.; Vries, Hylke de; Baatsen, Michiel; Delden, Aarnout J. van

2018-01-01

Major storm systems over Europe frequently have a tropical origin. This paper analyses the characteristics and dynamics of such cyclones in the observational record, using MERRA reanalysis data for the period 1979-2013. By stratifying the cyclones along three key phases of their development (tropical phase, extratropical transition and final re-intensification), we identify four radically different life cycles: the tropical cyclone and extratropical cyclone life cycles, the classic extratropical transition and the warm seclusion life cycle. More than 50% of the storms reaching Europe from low latitudes follow the warm seclusion life cycle. It also contains the strongest cyclones. They are characterized by a warm core and a frontal T-bone structure, with a northwestward warm conveyor belt and the effects of dry intrusion. Rapid deepening occurs in the latest phase, around their arrival in Europe. Both baroclinic instability and release of latent heat contribute to the strong intensification. The pressure minimum occurs often a day after entering Europe, which enhances the potential threat of warm seclusion storms for Europe. The impact of a future warmer climate on the development of these storms is discussed.

Functional imaging of photovoltaic materials

NASA Astrophysics Data System (ADS)

Leite, Marina

For the past two decades, extensive efforts have been made to increase the short-circuit current (Jsc) of non-epitaxial solar cells to achieve higher efficiency devices. Yet, improvements in the overall device performance are still limited by the open-circuit voltage (Voc). We address this critical limiting factor of all promising materials for photovoltaics by realizing a novel nanoscale imaging platform with unprecedented spatial resolution (<100 nm), based on a variant of Kelvin-probe force microscopy. We mapped the local Voc of a variety of inorganic materials, and measured local changes >150 mV in CIGS, not resolved by conventional electrical measurements. To identify the origin of the instability frequently observed in perovskite solar cells, we leveraged our recently developed method to scan one frame in 16 seconds to spatially and temporally resolve their photo-voltage. Surprisingly, we observed local and reversible changes in the Voc of the devices upon post-illumination treatments. Our innovative functional imaging is non destructive and can be applied to other optoelectronic devices, such as LEDs and photodetectors. The author acknowledge APS and NSF (Award # 16-10833) for funding.

A novel mutation in ETFDH manifesting as severe neonatal-onset multiple acyl-CoA dehydrogenase deficiency.

PubMed

van der Westhuizen, Francois H; Smuts, Izelle; Honey, Engela; Louw, Roan; Schoonen, Maryke; Jonck, Lindi-Maryn; Dercksen, Marli

2018-01-15

Neonatal-onset multiple acyl-CoA dehydrogenase deficiency (MADD type I) is an autosomal recessive disorder of the electron transfer flavoprotein function characterized by a severe clinical and biochemical phenotype, including congenital abnormalities with unresponsiveness to riboflavin treatment as distinguishing features. From a retrospective study, relying mainly on metabolic data, we have identified a novel mutation, c.1067G>A (p.Gly356Glu) in exon 8 of ETFDH, in three South African Caucasian MADD patients with the index patient presenting the hallmark features of type I MADD and two patients with compound heterozygous (c.1067G>A+c.1448C>T) mutations presenting with MADD type III. SDS-PAGE western blot confirmed the significant effect of this mutation on ETFDH structural instability. The identification of this novel mutation in three families originating from the South African Afrikaner population is significant to direct screening and strategies for this disease, which amongst the organic acidemias routinely screened for, is relatively frequently observed in this population group. Copyright © 2017 Elsevier B.V. All rights reserved.

Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors

PubMed Central

Yamamoto, Kenta; Wang, Jiguang; Sprinzen, Lisa; Xu, Jun; Haddock, Christopher J; Li, Chen; Lee, Brian J; Loredan, Denis G; Jiang, Wenxia; Vindigni, Alessandro; Wang, Dong; Rabadan, Raul; Zha, Shan

2016-01-01

Missense mutations in ATM kinase, a master regulator of DNA damage responses, are found in many cancers, but their impact on ATM function and implications for cancer therapy are largely unknown. Here we report that 72% of cancer-associated ATM mutations are missense mutations that are enriched around the kinase domain. Expression of kinase-dead ATM (AtmKD/-) is more oncogenic than loss of ATM (Atm-/-) in mouse models, leading to earlier and more frequent lymphomas with Pten deletions. Kinase-dead ATM protein (Atm-KD), but not loss of ATM (Atm-null), prevents replication-dependent removal of Topo-isomerase I-DNA adducts at the step of strand cleavage, leading to severe genomic instability and hypersensitivity to Topo-isomerase I inhibitors. Correspondingly, Topo-isomerase I inhibitors effectively and preferentially eliminate AtmKD/-, but not Atm-proficientor Atm-/- leukemia in animal models. These findings identify ATM kinase-domain missense mutations as a potent oncogenic event and a biomarker for Topo-isomerase I inhibitor based therapy. DOI: http://dx.doi.org/10.7554/eLife.14709.001 PMID:27304073

Active suppression of vortex-driven combustion instability using controlled liquid-fuel injection

NASA Astrophysics Data System (ADS)

Pang, Bin

Combustion instabilities remain one of the most challenging problems encountered in developing propulsion and power systems. Large amplitude pressure oscillations, driven by unsteady heat release, can produce numerous detrimental effects. Most previous active control studies utilized gaseous fuels to suppress combustion instabilities. However, using liquid fuel to suppress combustion instabilities is more realistic for propulsion applications. Active instability suppression in vortex-driven combustors using a direct liquid fuel injection strategy was theoretically established and experimentally demonstrated in this dissertation work. Droplet size measurements revealed that with pulsed fuel injection management, fuel droplet size could be modulated periodically. Consequently, desired heat release fluctuation could be created. If this oscillatory heat release is coupled with the natural pressure oscillation in an out of phase manner, combustion instabilities can be suppressed. To identify proper locations of supplying additional liquid fuel for the purpose of achieving control, the natural heat release pattern in a vortex-driven combustor was characterized in this study. It was found that at high Damkohler number oscillatory heat release pattern closely followed the evolving vortex front. However, when Damkohler number became close to unity, heat release fluctuation wave no longer coincided with the coherent structures. A heat release deficit area was found near the dump plane when combustor was operated in lean premixed conditions. Active combustion instability suppression experiments were performed in a dump combustor using a controlled liquid fuel injection strategy. High-speed Schlieren results illustrated that vortex shedding plays an important role in maintaining self-sustained combustion instabilities. Complete combustion instability control requires total suppression of these large-scale coherent structures. The sound pressure level at the excited dominant frequency was reduced by more than 20 dB with controlled liquid fuel injection method. Scaling issues were also investigated in this dump combustor to test the effectiveness of using pulsed liquid fuel injection strategies to suppress instabilities at higher power output conditions. With the liquid fuel injection control method, it was possible to suppress strong instabilities with initial amplitude of +/-5 psi down to the background noise level. The stable combustor operating range was also expanded from equivalence ratio of 0.75 to beyond 0.9.

Differentially Private Frequent Subgraph Mining

PubMed Central

Xu, Shengzhi; Xiong, Li; Cheng, Xiang; Xiao, Ke

2016-01-01

Mining frequent subgraphs from a collection of input graphs is an important topic in data mining research. However, if the input graphs contain sensitive information, releasing frequent subgraphs may pose considerable threats to individual's privacy. In this paper, we study the problem of frequent subgraph mining (FGM) under the rigorous differential privacy model. We introduce a novel differentially private FGM algorithm, which is referred to as DFG. In this algorithm, we first privately identify frequent subgraphs from input graphs, and then compute the noisy support of each identified frequent subgraph. In particular, to privately identify frequent subgraphs, we present a frequent subgraph identification approach which can improve the utility of frequent subgraph identifications through candidates pruning. Moreover, to compute the noisy support of each identified frequent subgraph, we devise a lattice-based noisy support derivation approach, where a series of methods has been proposed to improve the accuracy of the noisy supports. Through formal privacy analysis, we prove that our DFG algorithm satisfies ε-differential privacy. Extensive experimental results on real datasets show that the DFG algorithm can privately find frequent subgraphs with high data utility. PMID:27616876

System Detects Vibrational Instabilities

NASA Technical Reports Server (NTRS)

Bozeman, Richard J., Jr.

1990-01-01

Sustained vibrations at two critical frequencies trigger diagnostic response or shutdown. Vibration-analyzing electronic system detects instabilities of combustion in rocket engine. Controls pulse-mode firing of engine and identifies vibrations above threshold amplitude at 5.9 and/or 12kHz. Adapted to other detection and/or control schemes involving simultaneous real-time detection of signals above or below preset amplitudes at two or more specified frequencies. Potential applications include rotating machinery and encoders and decoders in security systems.

A Study of Baroclinic Instability Induced Convergence Near the Bottom Using Water Age Simulations

NASA Astrophysics Data System (ADS)

Zhang, Wenxia; Hetland, Robert D.

2018-03-01

Baroclinic instability of lateral density gradients gives way to lateral buoyancy transport, which often results in convergence of buoyancy transport. Along a sloping bottom, the induced convergence can force upward extension of bottom water. Eddy transport induced convergence at the bottom and the consequent suspended layers of bottom properties are investigated using a three-dimensional idealized model. Motivated by the distinct characteristics of intrusions over the Texas-Louisiana shelf, a series of configurations are performed with the purpose of identifying parameter impacts on the intensity of eddy transport. This study uses the "horizontal slope Burger number" as the predominant parameter; the parameter is functioned with SH=SRi-1/2=δ/Ri to identify formation of baroclinic instability, where S is the slope Burger number, δ is the slope parameter, and Ri is the Richardson number, previously shown to be the parameter that predicts the intensity of baroclinic instability on the shelf. Intrusion spreads into the interior abutting a layer that is characterized by degraded vertical stratification; a thickening in the bottom boundary layer colocates with the intrusion, which usually thins at either edge of the intrusion because of a density barrier in association with concentrated isopycnals. The intensity of convergence degrades and bottom tracer fluxes reduce linearly with increased SH on logarithmic scales, and the characteristics of bottom boundary layer behavior and the reversal in alongshore current tend to vanish.

Everyday resilience in district health systems: emerging insights from the front lines in Kenya and South Africa

PubMed Central

Gilson, Lucy; Barasa, Edwine; Nxumalo, Nonhlanhla; Cleary, Susan; Goudge, Jane; Molyneux, Sassy; Tsofa, Benjamin; Lehmann, Uta

2017-01-01

Recent global crises have brought into sharp relief the absolute necessity of resilient health systems that can recognise and react to societal crises. While such crises focus the global mind, the real work lies, however, in being resilient in the face of routine, multiple challenges. But what are these challenges and what is the work of nurturing everyday resilience in health systems? This paper considers these questions, drawing on long-term, primarily qualitative research conducted in three different district health system settings in Kenya and South Africa, and adopting principles from case study research methodology and meta-synthesis in its analytic approach. The paper presents evidence of the instability and daily disruptions managed at the front lines of the district health system. These include patient complaints, unpredictable staff, compliance demands, organisational instability linked to decentralisation processes and frequently changing, and sometimes unclear, policy imperatives. The paper also identifies managerial responses to these challenges and assesses whether or not they indicate everyday resilience, using two conceptual lenses. From this analysis, we suggest that such resilience seems to arise from the leadership offered by multiple managers, through a combination of strategies that become embedded in relationships and managerial routines, drawing on wider organisational capacities and resources. While stable governance structures and adequate resources do influence everyday resilience, they are not enough to sustain it. Instead, it appears important to nurture the power of leaders across every system to reframe challenges, strengthen their routine practices in ways that encourage mindful staff engagement, and develop social networks within and outside organisations. Further research can build on these insights to deepen understanding. PMID:29081995

Everyday resilience in district health systems: emerging insights from the front lines in Kenya and South Africa.

PubMed

Gilson, Lucy; Barasa, Edwine; Nxumalo, Nonhlanhla; Cleary, Susan; Goudge, Jane; Molyneux, Sassy; Tsofa, Benjamin; Lehmann, Uta

2017-01-01

Recent global crises have brought into sharp relief the absolute necessity of resilient health systems that can recognise and react to societal crises. While such crises focus the global mind, the real work lies, however, in being resilient in the face of routine, multiple challenges. But what are these challenges and what is the work of nurturing everyday resilience in health systems? This paper considers these questions, drawing on long-term, primarily qualitative research conducted in three different district health system settings in Kenya and South Africa, and adopting principles from case study research methodology and meta-synthesis in its analytic approach. The paper presents evidence of the instability and daily disruptions managed at the front lines of the district health system. These include patient complaints, unpredictable staff, compliance demands, organisational instability linked to decentralisation processes and frequently changing, and sometimes unclear, policy imperatives. The paper also identifies managerial responses to these challenges and assesses whether or not they indicate everyday resilience, using two conceptual lenses. From this analysis, we suggest that such resilience seems to arise from the leadership offered by multiple managers, through a combination of strategies that become embedded in relationships and managerial routines, drawing on wider organisational capacities and resources. While stable governance structures and adequate resources do influence everyday resilience, they are not enough to sustain it. Instead, it appears important to nurture the power of leaders across every system to reframe challenges, strengthen their routine practices in ways that encourage mindful staff engagement, and develop social networks within and outside organisations. Further research can build on these insights to deepen understanding.

Frequent Truncating Mutation of TFAM Induces Mitochondrial DNA Depletion and Apoptotic Resistance in Microsatellite-Unstable Colorectal Cancer

PubMed Central

Guo, Jianhui; Zheng, Li; Liu, Wenyong; Wang, Xianshu; Wang, Zemin; Wang, Zehua; French, Amy J.; Kang, Dongchon; Chen, Lin; Thibodeau, Stephen N.; Liu, Wanguo

2013-01-01

The mitochondrial transcription factor A (TFAM) is required for mitochondrial DNA (mtDNA) replication and transcription. Disruption of TFAM results in heart failure and premature aging in mice. But very little is known about the role of TFAM in cancer development. Here, we report the identification of frequent frameshift mutations in the coding mononucleotide repeat of TFAM in sporadic colorectal cancer (CRC) cell lines and in primary tumors with microsatellite instability (MSI), but not in microsatellite stable (MSS) CRC cell lines and tumors. The presence of the TFAM truncating mutation, in CRC cells with MSI, reduced the TFAM protein level in vivo and in vitro and correlated with mtDNA depletion. Furthermore, forced overexpression of wild-type TFAM in RKO cells carrying a TFAM truncating mutation suppressed cell proliferation and inhibited RKO cell-induced xenograft tumor growth. Moreover, these cells showed more susceptibility to cisplatin-induced apoptosis due to an increase of cytochrome b (Cyt b) expression and its release from mitochondria. An interaction assay between TFAM and the heavy-strand promoter (HSP) of mitochondria revealed that mutant TFAM exhibited reduced binding to HSP, leading to reduction in Cyt b transcription. Collectively, these data provide evidence that a high incidence of TFAM truncating mutations leads to mitochondrial copy number reduction and mitochondrial instability, distinguishing most CRC with MSI from MSS CRC. These mutations may play an important role in tumorigenesis and cisplatin-induced apoptotic resistance of most microsatellite-unstable CRCs. PMID:21467167

Self-organized kilometer-scale shoreline sand wave generation: Sensitivity to model and physical parameters

NASA Astrophysics Data System (ADS)

Idier, Déborah; Falqués, Albert; Rohmer, Jérémy; Arriaga, Jaime

2017-09-01

The instability mechanisms for self-organized kilometer-scale shoreline sand waves have been extensively explored by modeling. However, while the assumed bathymetric perturbation associated with the sand wave controls the feedback between morphology and waves, its effect on the instability onset has not been explored. In addition, no systematic investigation of the effect of the physical parameters has been done yet. Using a linear stability model, we investigate the effect of wave conditions, cross-shore profile, closure depth, and two perturbation shapes (P1: cross-shore bathymetric profile shift, and P2: bed level perturbation linearly decreasing offshore). For a P1 perturbation, no instability occurs below an absolute critical angle θc0≈ 40-50°. For a P2 perturbation, there is no absolute critical angle: sand waves can develop also for low-angle waves. In fact, the bathymetric perturbation shape plays a key role in low-angle wave instability: such instability only develops if the curvature of the depth contours offshore the breaking zone is larger than the shoreline one. This can occur for the P2 perturbation but not for P1. The analysis of bathymetric data suggests that both curvature configurations could exist in nature. For both perturbation types, large wave angle, small wave period, and large closure depth strongly favor instability. The cross-shore profile has almost no effect with a P1 perturbation, whereas large surf zone slope and gently sloping shoreface strongly enhance instability under low-angle waves for a P2 perturbation. Finally, predictive statistical models are set up to identify sites prone to exhibit either a critical angle close to θc0 or low-angle wave instability.

Neutrino signal from pair-instability supernovae

NASA Astrophysics Data System (ADS)

Wright, Warren P.; Gilmer, Matthew S.; Fröhlich, Carla; Kneller, James P.

2017-11-01

A very massive star with a carbon-oxygen core in the range of 64M ⊙

Engine-Scale Combustor Rig Designed, Fabricated, and Tested for Combustion Instability Control Research

NASA Technical Reports Server (NTRS)

DeLaat, John C.; Breisacher, Kevin J.

2000-01-01

Low-emission combustor designs are prone to combustor instabilities. Because active control of these instabilities may allow future combustors to meet both stringent emissions and performance requirements, an experimental combustor rig was developed for investigating methods of actively suppressing combustion instabilities. The experimental rig has features similar to a real engine combustor and exhibits instabilities representative of those in aircraft gas turbine engines. Experimental testing in the spring of 1999 demonstrated that the rig can be tuned to closely represent an instability observed in engine tests. Future plans are to develop and demonstrate combustion instability control using this experimental combustor rig. The NASA Glenn Research Center at Lewis Field is leading the Combustion Instability Control program to investigate methods for actively suppressing combustion instabilities. Under this program, a single-nozzle, liquid-fueled research combustor rig was designed, fabricated, and tested. The rig has many of the complexities of a real engine combustor, including an actual fuel nozzle and swirler, dilution cooling, and an effusion-cooled liner. Prior to designing the experimental rig, a survey of aircraft engine combustion instability experience identified an instability observed in a prototype engine as a suitable candidate for replication. The frequency of the instability was 525 Hz, with an amplitude of approximately 1.5-psi peak-to-peak at a burner pressure of 200 psia. The single-nozzle experimental combustor rig was designed to preserve subcomponent lengths, cross sectional area distribution, flow distribution, pressure-drop distribution, temperature distribution, and other factors previously found to be determinants of burner acoustic frequencies, mode shapes, gain, and damping. Analytical models were used to predict the acoustic resonances of both the engine combustor and proposed experiment. The analysis confirmed that the test rig configuration and engine configuration had similar longitudinal acoustic characteristics, increasing the likelihood that the engine instability would be replicated in the rig. Parametric analytical studies were performed to understand the influence of geometry and condition variations and to establish a combustion test plan. Cold-flow experiments verified that the design values of area and flow distributions were obtained. Combustion test results established the existence of a longitudinal combustion instability in the 500-Hz range with a measured amplitude approximating that observed in the engine. Modifications to the rig configuration during testing also showed the potential for injector independence. The research combustor rig was developed in partnership with Pratt & Whitney of West Palm Beach, Florida, and United Technologies Research Center of East Hartford, Connecticut. Experimental testing of the combustor rig took place at United Technologies Research Center.

Canonical DNA Repair Pathways Influence R-Loop-Driven Genome Instability.

PubMed

Stirling, Peter C; Hieter, Philip

2017-10-27

DNA repair defects create cancer predisposition in humans by fostering a higher rate of mutations. While DNA repair is quite well characterized, recent studies have identified previously unrecognized relationships between DNA repair and R-loop-mediated genome instability. R-loops are three-stranded nucleic acid structures in which RNA binds to genomic DNA to displace a loop of single-stranded DNA. Mutations in homologous recombination, nucleotide excision repair, crosslink repair, and DNA damage checkpoints have all now been linked to formation and function of transcription-coupled R-loops. This perspective will summarize recent literature linking DNA repair to R-loop-mediated genomic instability and discuss how R-loops may contribute to mutagenesis in DNA-repair-deficient cancers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dynamics of flows, fluctuations, and global instability under electrode biasing in a linear plasma device

NASA Astrophysics Data System (ADS)

Desjardins, T. R.; Gilmore, M.

2016-05-01

Grid biasing is utilized in a large-scale helicon plasma to modify an existing instability. It is shown both experimentally and with a linear stability analysis to be a hybrid drift-Kelvin-Helmholtz mode. At low magnetic field strengths, coherent fluctuations are present, while at high magnetic field strengths, the plasma is broad-band turbulent. Grid biasing is used to drive the once-coherent fluctuations to a broad-band turbulent state, as well as to suppress them. There is a corresponding change in the flow shear. When a high positive bias (10Te) is applied to the grid electrode, a large-scale ( n ˜/n ≈50 % ) is excited. This mode has been identified as the potential relaxation instability.

Basic theory for polarized, astrophysical maser radiation in a magnetic field

NASA Technical Reports Server (NTRS)

Watson, William D.

1994-01-01

Fundamental alterations in the theory and resulting behavior of polarized, astrophysical maser radiation in the presence of a magnetic field have been asserted based on a calculation of instabilities in the radiative transfer. I reconsider the radiative transfer and find that the relevant instabilities do not occur. Calculational errors in the previous investigation are identified. In addition, such instabilities would have appeared -- but did not -- in the numerous numerical solutions to the same radiative transfer equations that have been presented in the literature. As a result, all modifications that have been presented in a recent series of papers (Elitzur 1991, 1993) to the theory for polarized maser radiation in the presence of a magnetic field are invalid. The basic theory is thus clarified.

Pad-mode-induced instantaneous mode instability for simple models of brake systems

NASA Astrophysics Data System (ADS)

Oberst, S.; Lai, J. C. S.

2015-10-01

Automotive disc brake squeal is fugitive, transient and remains difficult to predict. In particular, instantaneous mode squeal observed experimentally does not seem to be associated with mode coupling and its mechanism is not clear. The effects of contact pressures, friction coefficients as well as material properties (pressure and temperature dependency and anisotropy) for brake squeal propensity have not been systematically explored. By analysing a finite element model of an isotropic pad sliding on a plate similar to that of a previously reported experimental study, pad modes have been identified and found to be stable using conventional complex eigenvalue analysis. However, by subjecting the model to contact pressure harmonic excitation for a range of pressures and friction coefficients, a forced response analysis reveals that the dissipated energy for pad modes is negative and becomes more negative with increasing contact pressures and friction coefficients, indicating the potential for instabilities. The frequency of the pad mode in the sliding direction is within the range of squeal frequencies observed experimentally. Nonlinear time series analysis of the vibration velocity also confirms the evolution of instabilities induced by pad modes as the friction coefficient increases. By extending this analysis to a more realistic but simple brake model in the form of a pad-on-disc system, in-plane pad-modes, which a complex eigenvalue analysis predicts to be stable, have also been identified by negative dissipated energy for both isotropic and anisotropic pad material properties. The influence of contact pressures on potential instabilities has been found to be more dominant than changes in material properties owing to changes in pressure or temperature. Results here suggest that instantaneous mode squeal is likely caused by in-plane pad-mode instabilities.

Predictors of respiratory instability in neonates undergoing patient ductus arteriosus ligation after the introduction of targeted milrinone treatment.

PubMed

Ting, Joseph Y; Resende, Maura; More, Kiran; Nicholls, Donna; Weisz, Dany E; El-Khuffash, Afif; Jain, Amish; McNamara, Patrick J

2016-08-01

The postoperative course of preterm babies undergoing surgical closure of a patent ductus arteriosus (PDA) is often complicated by postligation cardiac syndrome (PLCS). Despite targeted milrinone prophylaxis, some infants continue to experience postoperative respiratory deterioration. Our objective is to describe the immediate postoperative course and identify risk factors for respiratory instability when preterm infants undergoing PDA ligation are managed with targeted milrinone treatment. A retrospective review of a cohort of infants undergoing PDA ligation between January, 2010 and August, 2013 was conducted. All infants had a targeted neonatal echocardiogram performed 1 hour after surgery. Infants received prophylactic milrinone treatment if the left ventricular output was <200 mL/kg/min. The primary outcome measure was the development of respiratory instability within 24 hours of surgery. Multivariable logistic regression was performed to identify predictors of respiratory instability. Eighty-six infants with a median gestational age of 25 weeks (interquartile range [IQR], 24-26) and a birth weight of 740 g (IQR, 640-853) were included in this study. Forty-nine (57.0%) received milrinone prophylaxis. There were 44 (51.2%) infants who developed oxygenation or ventilation failure, and 7 (8.1%) neonates developed PLCS. Infants with longer isovolumic relaxation time (IVRT ≥30 milliseconds) were more likely to develop either oxygenation or ventilation failure. Although the incidence of PLCS has declined after the introduction of targeted milrinone prophylaxis, many preterm infants continue to develop respiratory instability after surgical ligation. In this population, diastolic dysfunction manifested by prolonged IVRT could be associated with an adverse postoperative respiratory course. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Smoking Patterns and Their Relationship to Drinking Among First-Year College Students

PubMed Central

2014-01-01

Introduction: Unlike older smokers, young adult smokers frequently engage in light and intermittent smoking. It remains unclear how stable such smoking patterns are over time, as substantial variability exists between these smokers. This study identified subgroups of college student smokers based on the trajectory of their smoking frequency during the first year of college, thereby examining stability versus instability over time. We then tested if the interplay between drinking and smoking differed in the identified groups to determine the relative role drinking may play in intermittent versus more regular smoking. Methods: Incoming college students at 3 institutions completed online biweekly surveys of their daily substance use throughout the first year of college. Students who reported smoking at least 1 cigarette during this year (n = 266) were included in analyses (70% female, 74% White). Results: Group-based trajectory modeling identified 5 groups of smokers, 3 of which maintained their smoking frequency throughout the year (77%), and 2 groups of infrequent smokers showed significant trends (11% increasing, 12% decreasing). Notably, nondaily smoking was maintained at different specific frequencies (e.g., 1 vs. 3 days per week). Identified groups differed in the relationship between drinking and smoking, where cooccurrence was particularly strong among infrequent smokers, and trends in smoking quantity differed between groups. Conclusions: While there was a diversity of smoking patterns in the sample, patterns of intermittent smoking remain relatively stable for a majority of students throughout the year. Intervention messages targeting drinking and smoking should be tailored on the basis of smoking frequency. PMID:24415586

A review of educational strategies to improve nurses' roles in recognizing and responding to deteriorating patients.

PubMed

Liaw, S Y; Scherpbier, A; Klainin-Yobas, P; Rethans, J-J

2011-09-01

Physiological instability leading to clinical deterioration often precedes cardiopulmonary arrest. Nurses, who have the most frequent patient contact and responsibility for ongoing monitoring of patients, play a crucial role in recognizing and responding to clinical deterioration. The importance of education in supporting such a role has been addressed in numerous studies. This study aimed to identify nurses' educational needs and explore educational strategies to enhance their ability in recognizing and managing wards with deteriorating patients. A literature search from databases (2000-2010) was undertaken to include papers that identified the educational needs of ward nurses and existing educational programmes related to the care of deteriorating patients. Twenty-six papers were included in this review. Findings identified the educational need to empower nurses with the appropriate knowledge and skills in recognizing, reporting and responding to patient deterioration. The review of existing educational programmes and their outcomes identified valuable teaching information and strategies, and areas that could be improved in meeting nurses' educational needs. The review has highlighted important aspects of patient safety in clinical deterioration that could be further addressed by educational strategies targeting the role of ward nurses. These strategies include: utilizing clinical decision-making models to develop nurses' decision making skills; developing a standardized tool for systematic nursing assessment and management of clinical deterioration; incorporating training in clinical deterioration as a core competence of pre-registered nursing education; providing vital signs training to nursing assistants; and conducting more rigorous studies to evaluate the effectiveness of the educational programmes. © 2011 The Authors. International Nursing Review © 2011 International Council of Nurses.

The serrated neoplasia pathway of colorectal tumors: Identification of MUC5AC hypomethylation as an early marker of polyps with malignant potential.

PubMed

Renaud, Florence; Mariette, Christophe; Vincent, Audrey; Wacrenier, Agnès; Maunoury, Vincent; Leclerc, Julie; Coppin, Lucie; Crépin, Michel; Van Seuningen, Isabelle; Leteurtre, Emmanuelle; Buisine, Marie-Pierre

2016-03-15

The serrated neoplasia pathway accounts for 20-30% of colorectal cancers (CRC), which are characterized by extensive methylation (CpG island methylation phenotype, CIMP), frequent BRAF mutation and high microsatellite instability (MSI). We recently identified MUC5AC mucin gene hypomethylation as a specific marker of MSI CRC. The early identification of preneoplastic lesions among serrated polyps is currently challenging. Here, we performed a detailed pathological and molecular analysis of a large series of colorectal serrated polyps and evaluated the usefulness of mucin genes MUC2 and MUC5AC to differentiate serrated polyps and to identify lesions with malignant potential. A series of 330 colorectal polyps including 218 serrated polyps [42 goblet cell-rich hyperplastic polyps (GCHP), 68 microvesicular hyperplastic polyps (MVHP), 100 sessile serrated adenoma (SSA) and eight traditional serrated adenoma (TSA)] and 112 conventional adenomas was analyzed for BRAF/KRAS mutations, MSI, CIMP, MLH1 and MGMT methylation, and MUC2 and MUC5AC expression and methylation. We show that MUC5AC hypomethylation is an early event in the serrated neoplasia pathway, and specifically detects MVHP and SSA, arguing for a filiation between MVHP, SSA and CIMP-H/MSI CRC, whereas GCHP and TSA arise from a distinct pathway. Moreover, MUC5AC hypomethylation specifically identified serrated lesions with BRAF mutation, CIMP-H or MSI, suggesting that it may be useful to identify serrated neoplasia pathway-related precursor lesions. Our data suggest that MVHP should be recognized among HP and require particular attention. © 2015 UICC.

Breast Tumors with Elevated Expression of 1q Candidate Genes Confer Poor Clinical Outcome and Sensitivity to Ras/PI3K Inhibition

PubMed Central

Viveka Thangaraj, Soundara; Periasamy, Jayaprakash; Bhaskar Rao, Divya; Barnabas, Georgina D.; Raghavan, Swetha; Ganesan, Kumaresan

2013-01-01

Genomic aberrations are common in cancers and the long arm of chromosome 1 is known for its frequent amplifications in breast cancer. However, the key candidate genes of 1q, and their contribution in breast cancer pathogenesis remain unexplored. We have analyzed the gene expression profiles of 1635 breast tumor samples using meta-analysis based approach and identified clinically significant candidates from chromosome 1q. Seven candidate genes including exonuclease 1 (EXO1) are consistently over expressed in breast tumors, specifically in high grade and aggressive breast tumors with poor clinical outcome. We derived a EXO1 co-expression module from the mRNA profiles of breast tumors which comprises 1q candidate genes and their co-expressed genes. By integrative functional genomics investigation, we identified the involvement of EGFR, RAS, PI3K / AKT, MYC, E2F signaling in the regulation of these selected 1q genes in breast tumors and breast cancer cell lines. Expression of EXO1 module was found as indicative of elevated cell proliferation, genomic instability, activated RAS/AKT/MYC/E2F1 signaling pathways and loss of p53 activity in breast tumors. mRNA–drug connectivity analysis indicates inhibition of RAS/PI3K as a possible targeted therapeutic approach for the patients with activated EXO1 module in breast tumors. Thus, we identified seven 1q candidate genes strongly associated with the poor survival of breast cancer patients and identified the possibility of targeting them with EGFR/RAS/PI3K inhibitors. PMID:24147022

High-resolution copy number variation analysis of schizophrenia in Japan.

PubMed

Kushima, I; Aleksic, B; Nakatochi, M; Shimamura, T; Shiino, T; Yoshimi, A; Kimura, H; Takasaki, Y; Wang, C; Xing, J; Ishizuka, K; Oya-Ito, T; Nakamura, Y; Arioka, Y; Maeda, T; Yamamoto, M; Yoshida, M; Noma, H; Hamada, S; Morikawa, M; Uno, Y; Okada, T; Iidaka, T; Iritani, S; Yamamoto, T; Miyashita, M; Kobori, A; Arai, M; Itokawa, M; Cheng, M-C; Chuang, Y-A; Chen, C-H; Suzuki, M; Takahashi, T; Hashimoto, R; Yamamori, H; Yasuda, Y; Watanabe, Y; Nunokawa, A; Someya, T; Ikeda, M; Toyota, T; Yoshikawa, T; Numata, S; Ohmori, T; Kunimoto, S; Mori, D; Iwata, N; Ozaki, N

2017-03-01

Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10 -9 , 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e.g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.

Evolutionary interaction between W/Y chromosome and transposable elements.

PubMed

Śliwińska, Ewa B; Martyka, Rafał; Tryjanowski, Piotr

2016-06-01

The W/Y chromosome is unique among chromosomes as it does not recombine in its mature form. The main side effect of cessation of recombination is evolutionary instability and degeneration of the W/Y chromosome, or frequent W/Y chromosome turnovers. Another important feature of W/Y chromosome degeneration is transposable element (TEs) accumulation. Transposon accumulation has been confirmed for all W/Y chromosomes that have been sequenced so far. Models of W/Y chromosome instability include the assemblage of deleterious mutations in protein coding genes, but do not include the influence of transposable elements that are accumulated gradually in the non-recombining genome. The multiple roles of genomic TEs, and the interactions between retrotransposons and genome defense proteins are currently being studied intensively. Small RNAs originating from retrotransposon transcripts appear to be, in some cases, the only mediators of W/Y chromosome function. Based on the review of the most recent publications, we present knowledge on W/Y evolution in relation to retrotransposable element accumulation.

Growth, progression and chromosome instability of Neuroblastoma: a new scenario of tumorigenesis?

PubMed

Tonini, Gian Paolo

2017-01-05

Neuroblastoma is a pediatric cancer with a low survival rate of patients with metastatic stage 4 disease. Tumor aggressiveness and progression have been associated with structural copy number variations (CNVs) that are observed in malignant cells. In contrast, localized Neuroblastomas, which are associated with a low number of structural CNVs but frequent numerical CNVs, are less aggressive, and patients have good outcomes. Finally, whole-genome and whole-exome sequencing of Neuroblastoma tissues have shown few damaging mutations in these tumors. In the present report it is proposed that chromosome instability (CIN) plays a major role in Neuroblastoma tumorigenesis and that CIN is already present in the early phases of tumor development. High CIN can promote several types of chromosomal damage including chromothripsis, gene deletion, amplification and rearrangements, which deregulate gene expression. Indeed, gene rearrangements have been reported as a new scenario in the development of Neuroblastoma, which supports the hypothesis that CIN is an early step preliminary to the late catastrophic events leading to tumor development.

Subtalar dislocation without associated fractures: Case report and review of literature

PubMed Central

Giannoulis, Dionisios; Papadopoulos, Dimitrios V; Lykissas, Marios G; Koulouvaris, Panagiotis; Gkiatas, Ioannis; Mavrodontidis, Alexandros

2015-01-01

Isolated subtalar dislocations are unusual injuries due to the inherent instability of the talus. Subtalar dislocations are frequently associated with fractures of the malleoli, the talus, the calcaneus or the fifth metatarsal. Four types of subtalar dislocation have been described according to the direction of the foot in relation to the talus: medial, lateral posterior and anterior. It has been shown that some of these dislocations may spontaneously reduce. A rare case of a 36-year-old male patient who sustained a closed medial subtalar dislocation without any associated fractures of the ankle is reported. The patient suffered a pure closed medial subtalar dislocation that is hardly reported in the literature. Six months after injury the patient did not report any pain, had a satisfactory range of motion, and no signs of residual instability or early posttraumatic osteoarthritis. The traumatic mechanism, the treatment options, and the importance of a stable and prompt closed reduction and early mobilization are discussed. PMID:25893182

QUASI-BIENNIAL OSCILLATIONS IN THE SOLAR TACHOCLINE CAUSED BY MAGNETIC ROSSBY WAVE INSTABILITIES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zaqarashvili, Teimuraz V.; Carbonell, Marc; Oliver, Ramon

2010-11-20

Quasi-biennial oscillations (QBOs) are frequently observed in solar activity indices. However, no clear physical mechanism for the observed variations has been suggested so far. Here, we study the stability of magnetic Rossby waves in the solar tachocline using the shallow water magnetohydrodynamic approximation. Our analysis shows that the combination of typical differential rotation and a toroidal magnetic field with a strength of {>=}10{sup 5} G triggers the instability of the m = 1 magnetic Rossby wave harmonic with a period of {approx}2 years. This harmonic is antisymmetric with respect to the equator and its period (and growth rate) depends onmore » the differential rotation parameters and magnetic field strength. The oscillations may cause a periodic magnetic flux emergence at the solar surface and consequently may lead to the observed QBO in solar activity features. The period of QBOs may change throughout a cycle, and from cycle to cycle, due to variations of the mean magnetic field and differential rotation in the tachocline.« less

Human papillomavirus type 16 E7 oncoprotein engages but does not abrogate the mitotic spindle assembly checkpoint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Yueyang; Munger, Karl, E-mail: kmunger@rics.bwh.harvard.edu

2012-10-10

The mitotic spindle assembly checkpoint (SAC) ensures faithful chromosome segregation during mitosis by censoring kinetochore-microtubule interactions. It is frequently rendered dysfunctional during carcinogenesis causing chromosome missegregation and genomic instability. There are conflicting reports whether the HPV16 E7 oncoprotein drives chromosomal instability by abolishing the SAC. Here we report that degradation of mitotic cyclins is impaired in cells with HPV16 E7 expression. RNAi-mediated depletion of Mad2 or BubR1 indicated the involvement of the SAC, suggesting that HPV16 E7 expression causes sustained SAC engagement. Mutational analyses revealed that HPV16 E7 sequences that are necessary for retinoblastoma tumor suppressor protein binding as wellmore » as sequences previously implicated in binding the nuclear and mitotic apparatus (NuMA) protein and in delocalizing dynein from the mitotic spindle contribute to SAC engagement. Importantly, however, HPV16 E7 does not markedly compromise the SAC response to microtubule poisons.« less

A framework for list representation, enabling list stabilization through incorporation of gene exchangeabilities.

PubMed

Soneson, Charlotte; Fontes, Magnus

2012-01-01

Analysis of multivariate data sets from, for example, microarray studies frequently results in lists of genes which are associated with some response of interest. The biological interpretation is often complicated by the statistical instability of the obtained gene lists, which may partly be due to the functional redundancy among genes, implying that multiple genes can play exchangeable roles in the cell. In this paper, we use the concept of exchangeability of random variables to model this functional redundancy and thereby account for the instability. We present a flexible framework to incorporate the exchangeability into the representation of lists. The proposed framework supports straightforward comparison between any 2 lists. It can also be used to generate new more stable gene rankings incorporating more information from the experimental data. Using 2 microarray data sets, we show that the proposed method provides more robust gene rankings than existing methods with respect to sampling variations, without compromising the biological significance of the rankings.

Determination of billows and other turbulent structures, part 4.1A

NASA Technical Reports Server (NTRS)

Rastogi, P. K.

1984-01-01

Billows are regular, wave-like arrays of cross-flow vortices that develop in stratified oceanic or atmospheric flows with large shear. Atmospheric billows can become manifest through condensation. Billows are frequently seen in their characteristic cloud forms in the lower atmosphere. Under suitable viewing conditions, billows can also be seen in noctilucent clouds that form near the polar mesosphere during the summer months. Other turbulent structures -- related to billows -- are the Kelvin-Helmholtz instability (KHI) and cat's eye structures that occur in fully developed turbulent shear flows. Shear flows may contain perturbations at many different horizontal wavelengths and vertical scales. Realistic theoretical models have been constructed to study the stability and growth of these perturbations. The extent to which billows and Kelvin-Helmholtz instability have been observed in the atmosphere with the use of radars is outlined. Most of these observations are confined to the troposphere. Suggestions are made for improved radar experiments that are required to detect these structures at higher altitudes.

Investigation of MHD Instabilities in Jets and Bubbles Using a Compact Coaxial Plasma Gun in a Background Magnetized Plasma

NASA Astrophysics Data System (ADS)

Zhang, Y.; Fisher, D. M.; Wallace, B.; Gilmore, M.; Hsu, S. C.

2016-10-01

A compact coaxial plasma gun is employed for experimental investigation of launching plasma into a lower density background magnetized plasma. Experiments are being conducted in the linear device HelCat at UNM. Four distinct operational regimes with qualitatively different dynamics are identified by fast CCD camera images. For regime I plasma jet formation, a global helical magnetic configuration is determined by a B-dot probe array data. Also the m =1 kink instability is observed and verified. Furthermore, when the jet is propagating into background magnetic field, a longer length and lifetime jet is formed. Axial shear flow caused by the background magnetic tension force contributes to the increased stability of the jet body. In regime II, a spheromak-like plasma bubble formation is identified when the gun plasma is injected into vacuum. In contrast, when the bubble propagates into a background magnetic field, the closed magnetic field configuration does not hold anymore and a lateral side, Reilgh-Taylor instability develops. Detailed experimental data and analysis will be presented for these cases.

A Genome-Wide Association Study for Regulators of Micronucleus Formation in Mice.

PubMed

McIntyre, Rebecca E; Nicod, Jérôme; Robles-Espinoza, Carla Daniela; Maciejowski, John; Cai, Na; Hill, Jennifer; Verstraten, Ruth; Iyer, Vivek; Rust, Alistair G; Balmus, Gabriel; Mott, Richard; Flint, Jonathan; Adams, David J

2016-08-09

In mammals the regulation of genomic instability plays a key role in tumor suppression and also controls genome plasticity, which is important for recombination during the processes of immunity and meiosis. Most studies to identify regulators of genomic instability have been performed in cells in culture or in systems that report on gross rearrangements of the genome, yet subtle differences in the level of genomic instability can contribute to whole organism phenotypes such as tumor predisposition. Here we performed a genome-wide association study in a population of 1379 outbred Crl:CFW(SW)-US_P08 mice to dissect the genetic landscape of micronucleus formation, a biomarker of chromosomal breaks, whole chromosome loss, and extranuclear DNA. Variation in micronucleus levels is a complex trait with a genome-wide heritability of 53.1%. We identify seven loci influencing micronucleus formation (false discovery rate <5%), and define candidate genes at each locus. Intriguingly at several loci we find evidence for sexual dimorphism in micronucleus formation, with a locus on chromosome 11 being specific to males. Copyright © 2016 McIntyre et al.

Strain-induced shear instability in Liverpool Bay

NASA Astrophysics Data System (ADS)

Wihsgott, Juliane; Palmer, Matthew R.

2013-04-01

Liverpool Bay is a shallow subsection of the eastern Irish Sea with large tides (10 m), which drive strong tidal currents (1 ms-1). The Bay is heavily influenced by large freshwater inputs from several Welsh and English rivers that maintain a strong and persistent horizontal density gradient. This gradient interacts with the sheared tidal currents to strain freshwater over denser pelagic water on a semi-diurnal frequency. This Strain-Induced-Periodic-Stratification (SIPS) has important implications on vertical and horizontal mixing. The subtle interaction between stratification and turbulence in this complex environment is shown to be of critical importance to freshwater transport, and subsequently the fate of associated biogeochemical and pollutant pathways. Recent work identified an asymmetry of current ellipses due to SIPS that increases shear instability in the halocline with the potential to enhance diapycnal mixing. Here, we use data from a short, high intensity process study which reveals this mid-water mechanism maintains prolonged periods of sub-critical gradient Richardson number (Ri ≤ ¼) that suggests shear instability is likely. A time series of measurements from a microstructure profiler identifies the associated increase in turbulence is short lived and 'patchy' but sufficient to promote diapycnal mixing. The significance of this mixing process is further investigated by comparing our findings with long-term observations from the Liverpool Bay Coastal Observatory. We identify that the conditions for shear instability during SIPS are regularly met and suggest that this process contributes to the current underestimates of near coastal mixing observed in regional models. To assist our understanding of the observed processes and to test the current capability of turbulence 'closure schemes' we employ a one-dimensional numerical model to investigate the physical mechanisms driving diapycnal mixing in Liverpool Bay.

Wrinkling instabilities in soft bilayered systems

PubMed Central

Budday, Silvia; Andres, Sebastian; Walter, Bastian

2017-01-01

Wrinkling phenomena control the surface morphology of many technical and biological systems. While primary wrinkling has been extensively studied, experimentally, analytically and computationally, higher-order instabilities remain insufficiently understood, especially in systems with stiffness contrasts well below 100. Here, we use the model system of an elastomeric bilayer to experimentally characterize primary and secondary wrinkling at moderate stiffness contrasts. We systematically vary the film thickness and substrate prestretch to explore which parameters modulate the emergence of secondary instabilities, including period-doubling, period-tripling and wrinkle-to-fold transitions. Our experiments suggest that period-doubling is the favourable secondary instability mode and that period-tripling can emerge under disturbed boundary conditions. High substrate prestretch can suppress period-doubling and primary wrinkles immediately transform into folds. We combine analytical models with computational simulations to predict the onset of primary wrinkling, the post-buckling behaviour, secondary bifurcations and the wrinkle-to-fold transition. Understanding the mechanisms of pattern selection and identifying the critical control parameters of wrinkling will allow us to fabricate smart surfaces with tunable properties and to control undesired surface patterns like in the asthmatic airway. This article is part of the themed issue ‘Patterning through instabilities in complex media: theory and applications.’ PMID:28373385

Spatial Linear Instability of Confluent Wake/Boundary Layers

NASA Technical Reports Server (NTRS)

Liou, William W.; Liu, Feng-Jun; Rumsey, C. L. (Technical Monitor)

2001-01-01

The spatial linear instability of incompressible confluent wake/boundary layers is analyzed. The flow model adopted is a superposition of the Blasius boundary layer and a wake located above the boundary layer. The Orr-Sommerfeld equation is solved using a global numerical method for the resulting eigenvalue problem. The numerical procedure is validated by comparing the present solutions for the instability of the Blasius boundary layer and for the instability of a wake with published results. For the confluent wake/boundary layers, modes associated with the boundary layer and the wake, respectively, are identified. The boundary layer mode is found amplified as the wake approaches the wall. On the other hand, the modes associated with the wake, including a symmetric mode and an antisymmetric mode, are stabilized by the reduced distance between the wall and the wake. An unstable mode switching at low frequency is observed where the antisymmetric mode becomes more unstable than the symmetric mode when the wake velocity defect is high.

Perinatal substance use, residential instability, and negative behavioral outcomes among adolescents: Lessons from the maternal lifestyle study.

PubMed

Cotton, Brandi P; Lohman, Matthew C; Brooks, Jessica M; LaGasse, Linda L

2017-08-01

Both housing instability and prenatal substance use are known risk factors for behavioral problems among adolescents. The purpose of this study was to investigate the association between residential instability (residential mobility and homelessness) and delinquent behaviors among adolescents enrolled in the maternal lifestyle study (MLS), a 16-year research study that explored short-term and long-term effects of in-utero exposure to cocaine and/or opiates (N = 736). Logistic regression was used to measure the association between housing problems with youth crimes, school delinquency, and substance use at 11, 15, and 16 years of age. Both high-frequency residential mobility and homelessness were associated with deviant behaviors across the entire sample of children born with in-utero cocaine/opiate exposure and those without. Psychiatric nursing care of youth should include a comprehensive assessment of residential instability to identify risk and target potential interventions. © 2018 Wiley Periodicals, Inc.

SDO/AIA Observation of Kelvin-Helmholtz Instability in the Solar Corona

NASA Technical Reports Server (NTRS)

Ofman, L.; Thompson, B. J.

2011-01-01

We present observations of the formation, propagation and decay of vortex-shaped features in coronal images from the Solar Dynamics Observatory (SDO) associated with an eruption starting at about 2:30UT on Apr 8, 2010. The series of vortices formed along the interface between an erupting (dimming) region and the surrounding corona. They ranged in size from several to ten arcseconds, and traveled along the interface at 6-14 km s-1. The features were clearly visible in six out of the seven different EUV wavebands of the Atmospheric Imaging Assembly (AIA). Based on the structure, formation, propagation and decay of these features, we identified these features as the first observations of the Kelvin- Helmholtz (KH) instability in the corona in EUV. The interpretation is supported by linear analysis and by MHD model of KH instability. We conclude that the instability is driven by the velocity shear between the erupting and closed magnetic field of the Coronal Mass Ejection (CME).

Demonstration of repeatability in a high-energy-density planar shear mixing layer experiment

DOE PAGES

Merritt, Elizabeth Catherine; Doss, Forrest William; Di Stefano, Carlos A.; ...

2017-03-11

On laser-driven platforms the assumption of experiment repeatability is particularly important due to a typically low data acquisition rate that doesn’t often allow for data redundancy. If the platform is repeatable, then measurements of the repeatable dynamics from multiple experiments can be treated as measurements of the same system. In high-energy-density hydrodynamic instability experiments the interface growth is assumed to be one of the repeatable aspects of the system. In this paper we demonstrate the repeatability of the instability growth in the counter-propagating shear experiment at the OMEGA laser facility, where the instability growth is characterized by the tracer layermore » thickness or mix-width evolution. Furthermore, in our previous experiment campaigns we have assumed the instability growth was repeatable enough to identify trends, but in this work we explicitly show that the mix-width measurements for nominally identical experiments are repeatable within the measurement error bars.« less

Flux tube gyrokinetic simulations of the edge pedestal

NASA Astrophysics Data System (ADS)

Parker, Scott; Wan, Weigang; Chen, Yang

2011-10-01

The linear instabilities of DIII-D H-mode pedestal are studied with gyrokinetic micro-turbulence simulations. The simulation code GEM is an electromagnetic δf code with global tokamak geometry in the form of Miller equilibrium. Local flux tube simulations are carried out for multiple positions of two DIII-D profiles: shot #98889 and shot #131997. Near the top of the pedestal, the instability is clearly ITG. The dominant instability of the pedestal appears at the steep gradient region, and it is identified as a low frequency mode mostly driven by electron temperature gradient. The mode propagates along the electron diamagnetic direction for low n and may propagate along the ion direction for high n. At some positions near the steep gradient region, an ion instability is found which shows some characteristics of kinetic ballooning mode (KBM). These results will be compared to the results of E. Wang et al. and D. Fulton et al. in the same session. We thank R. Groebner and P. Snyder for providing experimental profiles and helpful discussions.

The formation of co-orbital planets and their resulting transit signatures

NASA Astrophysics Data System (ADS)

Granados Contreras, Agueda Paula; Boley, Aaron

2018-04-01

Systems with Tightly-packed Inner Planets (STIPs) are metastable, exhibiting sudden transitions to an unstable state that can potentially lead to planet consolidation. When these systems are embedded in a gaseous disc, planet-disc interactions can significantly reduce the frequency of instabilities, and if they do occur, disc torques alter the dynamical outcomes. We ran a suite of N-body simulations of synthetic 6-planet STIPs using an independent implementation of IAS15 that includes a prescription for gaseous tidal damping. The algorithm is based on the results of disc simulations that self-consistently evolve gas and planets. Even for very compact configurations, the STIPS are resistant to instability when gas is present. However, instability can still occur, and in some cases, the combination of system instability and gaseous damping leads to the formation of co-orbiting planets that are stable even when gas damping is removed. While rare, such systems should be detectable in transit surveys, although the dynamics of the system can make the transit signature difficult to identify.

Amplification due to two-stream instability of self-electric and magnetic fields of an ion beam propagating in background plasma

NASA Astrophysics Data System (ADS)

Tokluoglu, Erinc K.; Kaganovich, Igor D.; Carlsson, Johan A.; Hara, Kentaro; Startsev, Edward A.

2018-05-01

Propagation of charged particle beams in background plasma as a method of space charge neutralization has been shown to achieve a high degree of charge and current neutralization and therefore enables nearly ballistic propagation and focusing of charged particle beams. Correspondingly, the use of plasmas for propagation of charged particle beams has important applications for transport and focusing of intense particle beams in inertial fusion and high energy density laboratory plasma physics. However, the streaming of beam ions through a background plasma can lead to the development of two-stream instability between the beam ions and the plasma electrons. The beam electric and magnetic fields enhanced by the two-stream instability can lead to defocusing of the ion beam. Using particle-in-cell simulations, we study the scaling of the instability-driven self-electromagnetic fields and consequent defocusing forces with the background plasma density and beam ion mass. We identify plasma parameters where the defocusing forces can be reduced.

Natural History of Anterior Shoulder Instability.

PubMed

Carpinteiro, Eduardo Palma; Barros, Andre Aires

2017-01-01

The shoulder is the most complex joint in the body. The large freedom of motion in this joint is the main cause of instability. Instability varies in its degree, direction, etiology and volition and there is a large spectrum of conditions. Based on literature research and also in our own experience, we propose to elucidate the reader about the natural history of instability and its importance for the appropriate management of this pathology, by answering the following questions: What happens in the shoulder after the first dislocation? Which structures suffer damage? Who are the patients at higher risk of recurrence? How does the disease evolve without treatment? Will surgical treatment avoid future negative outcomes and prevent degenerative joint disease? Who should we treat and when? 80% of anterior-inferior dislocations occur in young patients. Recurrent instability is common and multiple dislocations are the rule. Instability is influenced by a large number of variables, including age of onset, activity profile, number of episodes,delay between first episode and surgical treatment. Understanding the disease and its natural evolution is determinant to decide the treatment in order to obtain the best outcome. It is crucial to identify the risk factors for recurrence. Delay in surgical treatment, when indicated, leads to worse results. Surgical technique should address the type and severity of both soft tissue and bone lesions, when present.

Shock-Induced Disappearance and Subsequent Recovery of Plasmaspheric Hiss: Coordinated Observations of RBSP, THEMIS, and POES Satellite

DOE PAGES

Liu, Nigang; Su, Zhenpeng; Gao, Zhonglei; ...

2017-10-04

Here, plasmaspheric hiss is an extremely low frequency whistler–mode emission contributing significantly to the loss of radiation belt electrons. There are two main competing mechanisms for the generation of plasmaspheric hiss: excitation by local instability in the outer plasmasphere and origination from chorus outside the plasmasphere. Here on the basis of the analysis of an event of shock–induced disappearance and subsequent recovery of plasmaspheric hiss observed by RBSP, THEMIS, and POES missions, we attempt to identify its dominant generation mechanism. In the preshock plasmasphere, the local electron instability was relatively weak and the hiss waves with bidirectional Poynting fluxes mainlymore » originated from the dayside chorus waves. On arrival of the shock, the removal of preexisting dayside chorus and the insignificant variation of low–frequency wave instability caused the prompt disappearance of hiss waves. In the next few hours, the local instability in the plasmasphere was greatly enhanced due to the substorm injection of hot electrons. The enhancement of local instability likely played a dominant role in the temporary recovery of hiss with unidirectional Poynting fluxes. These temporarily recovered hiss waves were generated near the equator and then propagated toward higher latitudes. In contrast, both the enhancement of local instability and the recurrence of prenoon chorus contributed to the substantial recovery of hiss with bidirectional Poynting fluxes.« less

Shock-Induced Disappearance and Subsequent Recovery of Plasmaspheric Hiss: Coordinated Observations of RBSP, THEMIS, and POES Satellite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Nigang; Su, Zhenpeng; Gao, Zhonglei

Here, plasmaspheric hiss is an extremely low frequency whistler–mode emission contributing significantly to the loss of radiation belt electrons. There are two main competing mechanisms for the generation of plasmaspheric hiss: excitation by local instability in the outer plasmasphere and origination from chorus outside the plasmasphere. Here on the basis of the analysis of an event of shock–induced disappearance and subsequent recovery of plasmaspheric hiss observed by RBSP, THEMIS, and POES missions, we attempt to identify its dominant generation mechanism. In the preshock plasmasphere, the local electron instability was relatively weak and the hiss waves with bidirectional Poynting fluxes mainlymore » originated from the dayside chorus waves. On arrival of the shock, the removal of preexisting dayside chorus and the insignificant variation of low–frequency wave instability caused the prompt disappearance of hiss waves. In the next few hours, the local instability in the plasmasphere was greatly enhanced due to the substorm injection of hot electrons. The enhancement of local instability likely played a dominant role in the temporary recovery of hiss with unidirectional Poynting fluxes. These temporarily recovered hiss waves were generated near the equator and then propagated toward higher latitudes. In contrast, both the enhancement of local instability and the recurrence of prenoon chorus contributed to the substantial recovery of hiss with bidirectional Poynting fluxes.« less

Fluid aspects of electron streaming instability in electron-ion plasmas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jao, C.-S.; Hau, L.-N.; Department of Physics, National Central University, Jhongli, Taiwan

2014-02-15

Electrons streaming in a background electron and ion plasma may lead to the formation of electrostatic solitary wave (ESW) and hole structure which have been observed in various space plasma environments. Past studies on the formation of ESW are mostly based on the particle simulations due to the necessity of incorporating particle's trapping effects. In this study, the fluid aspects and thermodynamics of streaming instabilities in electron-ion plasmas including bi-streaming and bump-on-tail instabilities are addressed based on the comparison between fluid theory and the results from particle-in-cell simulations. The energy closure adopted in the fluid model is the polytropic lawmore » of d(pρ{sup −γ})/dt=0 with γ being a free parameter. Two unstable modes are identified for the bump-on-tail instability and the growth rates as well as the dispersion relation of the streaming instabilities derived from the linear theory are found to be in good agreement with the particle simulations for both bi-streaming and bump-on-tail instabilities. At the nonlinear saturation, 70% of the electrons are trapped inside the potential well for the drift velocity being 20 times of the thermal velocity and the pρ{sup −γ} value is significantly increased. Effects of ion to electron mass ratio on the linear fluid theory and nonlinear simulations are also examined.« less

Causes of genome instability: the effect of low dose chemical exposures in modern society

PubMed Central

Langie, Sabine A.S.; Koppen, Gudrun; Desaulniers, Daniel; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Azqueta, Amaya; Bisson, William H.; Brown, Dustin; Brunborg, Gunnar; Charles, Amelia K.; Chen, Tao; Colacci, Annamaria; Darroudi, Firouz; Forte, Stefano; Gonzalez, Laetitia; Hamid, Roslida A.; Knudsen, Lisbeth E.; Leyns, Luc; Lopez de Cerain Salsamendi, Adela; Memeo, Lorenzo; Mondello, Chiara; Mothersill, Carmel; Olsen, Ann-Karin; Pavanello, Sofia; Raju, Jayadev; Rojas, Emilio; Roy, Rabindra; Ryan, Elizabeth; Ostrosky-Wegman, Patricia; Salem, Hosni K.; Scovassi, Ivana; Singh, Neetu; Vaccari, Monica; Van Schooten, Frederik J.; Valverde, Mahara; Woodrick, Jordan; Zhang, Luoping; van Larebeke, Nik; Kirsch-Volders, Micheline; Collins, Andrew R.

2015-01-01

Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome’s integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis. PMID:26106144

R-loops: targets for nuclease cleavage and repeat instability.

PubMed

Freudenreich, Catherine H

2018-01-11

R-loops form when transcribed RNA remains bound to its DNA template to form a stable RNA:DNA hybrid. Stable R-loops form when the RNA is purine-rich, and are further stabilized by DNA secondary structures on the non-template strand. Interestingly, many expandable and disease-causing repeat sequences form stable R-loops, and R-loops can contribute to repeat instability. Repeat expansions are responsible for multiple neurodegenerative diseases, including Huntington's disease, myotonic dystrophy, and several types of ataxias. Recently, it was found that R-loops at an expanded CAG/CTG repeat tract cause DNA breaks as well as repeat instability (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Two factors were identified as causing R-loop-dependent breaks at CAG/CTG tracts: deamination of cytosines and the MutLγ (Mlh1-Mlh3) endonuclease, defining two new mechanisms for how R-loops can generate DNA breaks (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Following R-loop-dependent nicking, base excision repair resulted in repeat instability. These results have implications for human repeat expansion diseases and provide a paradigm for how RNA:DNA hybrids can cause genome instability at structure-forming DNA sequences. This perspective summarizes mechanisms of R-loop-induced fragility at G-rich repeats and new links between DNA breaks and repeat instability.

Unilateral fixation for treatment of occipitocervical instability in children with congenital vertebral anomalies of the craniocervical junction.

PubMed

Mazur, Marcus D; Ravindra, Vijay M; Brockmeyer, Douglas L

2015-04-01

OBJECT Patients with occipitocervical (OC) instability from congenital vertebral anomalies (CVAs) of the craniocervical junction (CCJ) often have bony abnormalities that make instrumentation placement difficult. Within this patient population, some bilateral instrumentation constructs either fail or are not feasible, and a unilateral construct must be used. The authors describe the surgical management and outcomes of this disorder in patients in whom unilateral fixation constructs were used to treat OC instability. METHODS From a database of OC fusion procedures, the authors identified patients who underwent unilateral fixation for the management of OC instability. Patient characteristics, surgical details, and radiographic outcomes were reviewed. In each patient, CT scans were performed at least 4 months after surgery to evaluate for fusion. RESULTS Eight patients with CVAs of the CCJ underwent unilateral fixation for the treatment of OC instability. For 4 patients, the procedure occurred after a bilateral OC construct failed or infection forced hardware removal. For the remainder, it was the primary procedure. Two patients required reoperation for hardware revision and 1 developed nonunion requiring revision of the bone graft. Ultimately, 7 patients demonstrated osseous fusion on CT scans and 1 had a stable fibrous union. CONCLUSIONS These findings demonstrate that a unilateral OC fixation is effective for the treatment of OC instability in children with CVAs of the CCJ in whom bilateral screw placement fails or is not feasible.

Cross-cultural adaptation, reliability, and validation of the Korean version of the identification functional ankle instability (IdFAI).

PubMed

Ko, Jupil; Rosen, Adam B; Brown, Cathleen N

2017-09-12

To cross-culturally adapt the Identification Functional Ankle Instability for use with Korean-speaking participants. The English version of the IdFAI was cross-culturally adapted into Korean based on the guidelines. The psychometric properties in the Korean version of the IdFAI were measured for test-retest reliability, internal consistency, criterion-related validity, discriminative validity, and measurement error 181 native Korean-speakers. Intra-class correlation coefficients (ICC 2,1 ) between the English and Korean versions of the IdFAI for test-retest reliability was 0.98 (standard error of measurement = 1.41). The Cronbach's alpha coefficient was 0.89 for the Korean versions of IdFAI. The Korean versions of the IdFAI had a strong correlation with the SF-36 (r s  = -0.69, p < .001) and the Korean version of the Cumberland Ankle Instability Tool (r s  = -0.65, p < .001). The cutoff score of >10 was the optimal cutoff score to distinguish between the group memberships. The minimally detectable change of the Korean versions of the IdFAI score was 3.91. The Korean versions of the IdFAI have shown to be an excellent, reliable, and valid instrument. The Korean versions of the IdFAI can be utilized to assess the presence of Chronic Ankle Instability by researchers and clinicians working among Korean-speaking populations. Implications for rehabilitation The high recurrence rate of sprains may result into Chronic Ankle Instability (CAI). The Identification of Functional Ankle Instability Tool (IdFAI) has been validated and recommended to identify patients with Chronic Ankle Instability (CAI). The Korean version of the Identification of Functional Ankle Instability Tool (IdFAI) may be also recommend to researchers and clinicians for assessing the presence of Chronic Ankle Instability (CAI) in Korean-speaking population.

FANCD2 limits replication stress and genome instability in cells lacking BRCA2

PubMed Central

Buffa, Francesca M.; McDermott, Ultan; Tarsounas, Madalena

2016-01-01

The tumor suppressor BRCA2 plays a key role in genome integrity by promoting replication fork stability and homologous recombination (HR) DNA repair. Here we report that human cancer cells lacking BRCA2 rely on the Fanconi anemia protein FANCD2 to limit replication fork progression and genomic instability. Our results identify a novel role for FANCD2 in limiting constitutive replication stress in BRCA2-deficient cells, which impacts on cell survival and treatment responses. PMID:27322732

Cross-phase-modulation-induced instability in photonic-crystal fibers.

PubMed

Serebryannikov, E E; Konorov, S O; Ivanov, A A; Alfimov, M V; Scalora, M; Zheltikov, A M

2005-08-01

Cross-phase-modulation-induced instability is identified as a significant mechanism for efficient parametric four-wave-mixing frequency conversion in photonic-crystal fibers. Fundamental-wavelength femtosecond pulses of a Cr, forsterite laser are used in our experiments to transform the spectrum of copropagating second-harmonic pulses of the same laser in a photonic-crystal fiber. Efficient generation of sidebands shifted by more than 80 THz with respect to the central frequency of the second harmonic is observed in the output spectrum of the probe field.

Dynamic stability of maglev systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai, Y.; Chen, S.S.; Mulcahy, T.M.

1994-05-01

Because dynamic instabilities are not acceptable in any commercial maglev system, it is important to consider dynamic instability in the development of all maglev systems. This study considers the stability of maglev systems based on experimental data, scoping calculations, and simple mathematical models. Divergence and flutter are obtained for coupled vibration of a three-degree-of-freedom maglev vehicle on a guideway consisting of double L-shaped aluminum segments. The theory and analysis developed in this study provides basic stability characteristics and identifies future research needs for maglev systems.

The role of emotions in depression and aggression

PubMed Central

Malonda, Elisabeth; Samper, Paula

2016-01-01

Background Depression is a broad and heterogeneous diagnostic grouping, central to which is depressed mood or inability to enjoy most activities. Depressive symptoms are frequently accompanied by conduct problems stemming from anger. It is very important to know the interrelation of these emotions very well to be able to help adolescents to manage them more easily. The main aim of this article is to present the problem of interaction between negative affects (emotional instability, anger state and trait, physical and verbal aggression and depression) analyzing the different relationship through the time in spanish sample. Material and Methods The sample included 470 adolescents (192 boys and 225 girls) in a three-wave longitudinal study in Valencia (Spain). The mean age was 14.70 in the first wave. Structural equations modelling was employed to explore two longitudinal models. Results The results show differences based on sex, and that an internalised variable, like emotional instability, is relevant to prevent the appearance of depression directly in girls and also the later appearance of aggression as long as anger mediates, in both boys and girls, so the control of anger becomes an important goal to control the rest of the negative affects. Conclusions This results has consequences in the preparation of all programmes that try to establish an emotional control on adolescents, as not only has to be taken into account as a direct goal the control of externalised emotions like anger, but internalised emotions like emotional instability have to be taken into account also. Furthermore, it is also made apparent that not only the punctual explosions and externalisation of anger have to be worked on, but the temperamental aspects which are the base of anger trait have to be worked on too. Key words:Emotional instability, anger, depression, aggression, negative emotions, adolescence. PMID:27545395

Predicting Depression From Language-Based Emotion Dynamics: Longitudinal Analysis of Facebook and Twitter Status Updates.

PubMed

Seabrook, Elizabeth M; Kern, Margaret L; Fulcher, Ben D; Rickard, Nikki S

2018-05-08

Frequent expression of negative emotion words on social media has been linked to depression. However, metrics have relied on average values, not dynamic measures of emotional volatility. The aim of this study was to report on the associations between depression severity and the variability (time-unstructured) and instability (time-structured) in emotion word expression on Facebook and Twitter across status updates. Status updates and depression severity ratings of 29 Facebook users and 49 Twitter users were collected through the app MoodPrism. The average proportion of positive and negative emotion words used, within-person variability, and instability were computed. Negative emotion word instability was a significant predictor of greater depression severity on Facebook (r s (29)=.44, P=.02, 95% CI 0.09-0.69), even after controlling for the average proportion of negative emotion words used (partial r s (26)=.51, P=.006) and within-person variability (partial r s (26)=.49, P=.009). A different pattern emerged on Twitter where greater negative emotion word variability indicated lower depression severity (r s (49)=-.34, P=.01, 95% CI -0.58 to 0.09). Differences between Facebook and Twitter users in their emotion word patterns and psychological characteristics were also explored. The findings suggest that negative emotion word instability may be a simple yet sensitive measure of time-structured variability, useful when screening for depression through social media, though its usefulness may depend on the social media platform. ©Elizabeth M Seabrook, Margaret L Kern, Ben D Fulcher, Nikki S Rickard. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 08.05.2018.

Telomere dysfunction and chromosome structure modulate the contribution of individual chromosomes in abnormal nuclear morphologies.

PubMed

Pampalona, J; Soler, D; Genescà, A; Tusell, L

2010-01-05

The cytokinesis-block micronucleus assay has emerged as a biomarker of chromosome damage relevant to cancer. Although it was initially developed to measure micronuclei, it is also useful for measuring nucleoplasmic bridges and nuclear buds. Abnormal nuclear morphologies are frequently observed in malignant tissues and short-term tumour cell cultures. Changes in chromosome structure and number resulting from chromosome instability are important factors in oncogenesis. Telomeres have become key players in the initiation of chromosome instability related to carcinogenesis by means of breakage-fusion-bridge cycles. To better understand the connection between telomere dysfunction and the appearance of abnormal nuclear morphologies, we have characterised the presence of micronuclei, nucleoplasmic bridges and nuclear buds in human mammary primary epithelial cells. These cells can proliferate beyond the Hayflick limit by spontaneously losing expression of the p16(INK4a) protein. Progressive telomere shortening leads to the loss of the capping function, and the appearance of end-to-end chromosome fusions that can enter into breakage-fusion-bridge cycles generating massive chromosomal instability. In human mammary epithelial cells, different types of abnormal nuclear morphologies were observed, however only nucleoplasmatic bridges and buds increased significantly with population doublings. Fluorescent in situ hybridisation using centromeric and painting specific probes for chromosomes with eroded telomeres has revealed that these chromosomes are preferentially included in the different types of abnormal nuclear morphologies observed, thus reflecting their common origin. Accordingly, real-time imaging of cell divisions enabled us to determine that anaphase bridge resolution was mainly through chromatin breakage and the formation of symmetric buds in daughter nuclei. Few micronuclei emerged in this cell system thus validating the scoring of nucleoplasmic bridges and nuclear buds for measuring chromosome instability in telomere-dysfunction cell environments.

Long-lived Min mice develop advanced intestinal cancers through a genetically conservative pathway.

PubMed

Halberg, Richard B; Waggoner, Jesse; Rasmussen, Kristen; White, Alanna; Clipson, Linda; Prunuske, Amy J; Bacher, Jeffery W; Sullivan, Ruth; Washington, Mary Kay; Pitot, Henry C; Petrini, John H J; Albertson, Donna G; Dove, William F

2009-07-15

C57BL/6J mice carrying the Min allele of Adenomatous polyposis coli (Apc) develop numerous adenomas along the entire length of the intestine and consequently die at an early age. This short lifespan would prevent the accumulation of somatic genetic mutations or epigenetic alterations necessary for tumor progression. To overcome this limitation, we generated F(1) Apc(Min/+) hybrids by crossing C57BR/cdcJ and SWR/J females to C57BL/6J Apc(Min/+) males. These hybrids developed few intestinal tumors and often lived longer than 1 year. Many of the tumors (24-87%) were invasive adenocarcinomas, in which neoplastic tissue penetrated through the muscle wall into the mesentery. In a few cases (3%), lesions metastasized by extension to regional lymph nodes. The development of these familial cancers does not require chromosomal gains or losses, a high level of microsatellite instability, or the presence of Helicobacter. To test whether genetic instability might accelerate tumor progression, we generated Apc(Min/+) mice homozygous for the hypomorphic allele of the Nijmegen breakage syndrome gene (Nbs1(DeltaB)) and also treated Apc(Min/+) mice with a strong somatic mutagen. These imposed genetic instabilities did not reduce the time required for cancers to form nor increase the percentage of cancers nor drive progression to the point of distant metastasis. In summary, we have found that the Apc(Min/+) mouse model for familial intestinal cancer can develop frequent invasive cancers in the absence of overt genomic instability. Possible factors that promote invasion include age-dependent epigenetic changes, conservative somatic recombination, or direct effects of alleles in the F(1) hybrid genetic background.

Experimental investigation of large-scale vortices in a freely spreading gravity current

NASA Astrophysics Data System (ADS)

Yuan, Yeping; Horner-Devine, Alexander R.

2017-10-01

A series of laboratory experiments are presented to compare the dynamics of constant-source buoyant gravity currents propagating into laterally confined (channelized) and unconfined (spreading) environments. The plan-form structure of the spreading current and the vertical density and velocity structures on the interface are quantified using the optical thickness method and a combined particle image velocimetry and planar laser-induced fluorescence method, respectively. With lateral boundaries, the buoyant current thickness is approximately constant and Kelvin-Helmholtz instabilities are generated within the shear layer. The buoyant current structure is significantly different in the spreading case. As the current spreads laterally, nonlinear large-scale vortex structures are observed at the interface, which maintain a coherent shape as they propagate away from the source. These structures are continuously generated near the river mouth, have amplitudes close to the buoyant layer thickness, and propagate offshore at speeds approximately equal to the internal wave speed. The observed depth and propagation speed of the instabilities match well with the fastest growing mode predicted by linear stability analysis, but with a shorter wavelength. The spreading flows have much higher vorticity, which is aggregated within the large-scale structures. Secondary instabilities are generated on the leading edge of the braids between the large-scale vortex structures and ultimately break and mix on the lee side of the structures. Analysis of the vortex dynamics shows that lateral stretching intensifies the vorticity in the spreading currents, contributing to higher vorticity within the large-scale structures in the buoyant plume. The large-scale instabilities and vortex structures observed in the present study provide new insights into the origin of internal frontal structures frequently observed in coastal river plumes.

Minor shoulder instability.

PubMed

Castagna, Alessandro; Nordenson, Ulf; Garofalo, Raffaele; Karlsson, Jon

2007-02-01

The wide spectrum of shoulder instability is difficult to include in 1 classification. The distinction between traumatic, unidirectional, and atraumatic multidirectional instability is still widely used, even though this classification is not sufficiently precise to include all the different pathological findings of shoulder instability. We present "minor instability," which is a pathological condition causing a dysfunction of the glenohumeral articulation, especially in combination with microtrauma, repetitive or not, or after a period of immobilization or inactivity. When "minor shoulder instability" is suspected, the patient's history and detailed clinical examination represent the most important factors when establishing the diagnosis. In particular, the apprehension test stressing the middle glenohumeral ligament (MGHL)/labral complex in the position of midabduction and external rotation may be painful and may even reveal anterior instability or subluxation. Conventional radiographs are negative in most cases, as is magnetic resonance imaging arthrography. It is only after an accurate arthroscopic assessment that the pathological lesion can be found. The major pathological process can be identified at the level of the anterior superior labrum, in particular the MGHL complex, and appears as hyperemia, fraying, stretching, loosening, thinning, hypoplasia, or even absence. It may, however, be difficult to distinguish between a normal variant and a pathological lesion. Clinical symptoms and examination should always be correlated with arthroscopic findings. Recommended treatment is to restore shoulder stability and thereby prevent shoulder pain secondary to the increase in laxity. A reduction in range of motion should be expected during the postoperative phase, at least up to six to nine months. External rotation is usually permanently reduced by a few degrees.

Outcomes and complications following graft reconstruction for anterior sternoclavicular joint instability.

PubMed

Willinger, Lukas; Schanda, Jakob; Herbst, Elmar; Imhoff, Andreas B; Martetschläger, Frank

2016-12-01

Publications describing tendon graft reconstruction for anterior sternoclavicular joint (SCJ) instability are rare and usually refer to small patient numbers. The aim of this study was to systematically review the literature regarding outcomes and complications following tendon graft reconstruction techniques for anterior SCJ instability. An online database was systematically searched to identify studies on graft reconstruction for anterior SCJ instability. Reported outcome scores were graded as excellent, good, fair and poor to summarize the study results. All reported complications were recorded. Five articles with a total of 80 patients met the inclusion criteria. Reported outcomes were excellent in 10 %, good in 89 % and fair in 1 %. Recurrent instability was found in 10 % of the patients, and 5 % underwent revision surgery due to persistent impairment of shoulder function related to SCJ instability or osteoarthritis. Surgical stabilization techniques for the SCJ using autologous tendon grafts have shown to be safe and reliable and make better patients' pain situation and shoulder function. However, a certain amount of impairment might persist, which needs to be discussed with patients. Severe complications were rare and revision rates were as low as 5 %. Therefore, graft reconstruction techniques should be considered for patients with chronic anterior SCJ instability after a course of failed conservative treatment. This study is valuable for clinicians in daily clinical practice when dealing with this difficult-to-treat pathology and can help surgeons to better predict the clinical outcomes and complications following SCJ graft reconstruction. It should, however, not lead to underestimation of the potential risks of the procedure. Systematic review, Level IV.

Developmental instability analysis of BKD-infected spring Chinook salmon (Onchorhynchus tshawytscha) prior to seawater exposure

USGS Publications Warehouse

Campbell, W.B.; Emlen, J.M.

1997-01-01

Stress in organisms results in energy dissipation, making developmental pathways less stable. Effects of chronic stress, manifested as small random departures from phenotypic symmetry, reflect developmental instability, are considered to be epigenetic and an effect produced by compromised fitness. Instability is detectable and effectively interpreted among sites or populations if samples are collected randomly, the stressor is present throughout character development, characters are identified accurately and excessive mortality does not erase the existence of developmental instability. Bacterial kidney disease (BKD) is a chronic systemic disease in salmonids that, after vertical transmission from parent to egg, persists and spreads throughout ontogeny, potentially affecting developmental processes. Because levels of progeny infection reflect parental infection levels, groups of offspring from parents with high and low levels of BKD infection can be compared to assess the effects of disease-mediated developmental stress. Analyses of fluctuating asymmetry in five bilateral characters were inconclusive, but significant reductions in the proportion of unusable scales, in the number of circulus errors, and in the directional asymmetry of branchiostegal rays were observed in fish from the high-BKD group. This group also contained individuals of significantly larger size. These results are opposite to those expected from traditional developmental instability theory in suggesting that surviving high-BKD fish have greater developmental stability. This reversal appears to be produced by selective mortality having a greater effect than sublethal stress in altering developmental instability patterns. These results are discussed with respect to size selectivity, heterosis and the assumptions supporting developmental instability as a tool for detecting chronic sublethal stress.

Disturbed Dreaming and the Instability of Sleep: Altered Nonrapid Eye Movement Sleep Microstructure in Individuals with Frequent Nightmares as Revealed by the Cyclic Alternating Pattern

PubMed Central

Simor, Péter; Bódizs, Róbert; Horváth, Klára; Ferri, Raffaele

2013-01-01

Study Objectives: Nightmares are disturbing mental experiences during sleep that usually result in abrupt awakenings. Frequent nightmares are associated with poor subjective sleep quality, and recent polysomnographic data suggest that nightmare sufferers exhibit impaired sleep continuity during nonrapid eye movement (NREM) sleep. Because disrupted sleep might be related to abnormal arousal processes, the goal of this study was to examine polysomnographic arousal-related activities in a group of nightmare sufferers and a healthy control group. Design: Sleep microstructure analysis was carried out by scoring the cyclic alternating pattern (CAP) in NREM sleep and the arousal index in rapid eye movement (REM) sleep on the second night of the polysomnographic examination. Setting: Hospital-based sleep research laboratory. Participants: There were 17 in the nightmare (NMs) group and 23 in the healthy control (CTLs) group. Interventions: N/A. Measurements and Results: The NMs group exhibited reduced amounts of CAP A1 subtype and increased CAP A2 and A3 subtypes, as well as longer duration of CAP A phases in comparison with CTLs. Moreover, these differences remained significant after controlling for the confounding factors of anxious and depressive symptoms. The absolute number and frequency of REM arousals did not differ significantly between the two groups. Conclusions: The results of our study indicate that NREM sleep microstructure is altered during nonsymptomatic nights of nightmares. Disrupted sleep in the NMs group seems to be related to abnormal arousal processes, specifically an imbalance in sleep-promoting and arousing mechanisms during sleep. Citation: Simor P; Bódizs R; Horváth K; Ferri R. Disturbed dreaming and the instability of sleep: altered nonrapid eye movement sleep microstructure in individuals with frequent nightmares as revealed by the cyclic alternating pattern. SLEEP 2013;36(3):413-419. PMID:23449753

HIV risk, health, and social characteristics of sexual minority female injection drug users in Baltimore

PubMed Central

German, Danielle; Latkin, Carl A.

2015-01-01

Female injection drug users {IDU} who report sex with women are at increased risk for HIV and social instability, but it is important to assess whether these disparities also exist according to sexual minority identity rather than behaviorally defined categories. Within a sample of current IDU in Baltimore, about 17% of female study participants (n=307) identified as gay/lesbian/bisexual. In controlled models, sexual minorities were three times as likely to report sex exchange behavior and four times as likely to report a recent STI. Injection risk did not differ significantly, but sexual minority women reported higher prevalence of socio-economic instability, negative health indicators, and fewer network financial, material, and health support resources. There is a need to identify and address socio-economic marginalization, social support, and health issues among female IDUs who identify as lesbian or bisexual. PMID:25504312

"Talk with me": perspectives on services for men with problem gambling and housing instability.

PubMed

Guilcher, Sara J T; Hamilton-Wright, Sarah; Skinner, Wayne; Woodhall-Melnik, Julia; Ferentzy, Peter; Wendaferew, Aklilu; Hwang, Stephen W; Matheson, Flora I

2016-08-02

Problem gambling and homelessness are recognized as important public health concerns that significantly impact individuals, their friends and families, communities and broader society. We aimed to explore the experiences with health and social services of men who had histories of problem gambling and housing instability in Toronto, Ontario. We used a community-based participatory approach with a multi-service agency serving low-income individuals. We conducted qualitative interviews with men (n = 30) who had experienced problem gambling and housing instability. Our interviews employed open-ended questions to elicit men's perceptions of services related to housing instability, problem gambling and other comorbid conditions (e.g., mental illness, substance use). We reviewed relevant themes related to experiences with services (e.g., Use of and feedback on: health and social services, housing services, justice/legal aid services, substance use services, gambling services; stigma; goals; triggers; physical health; coping strategies; finances; relationships; barriers to services and recommendations for services). The concept of person-centred engagement was identified as a main overarching theme, and seemed to be lacking in most of the men's experiences of services. Person-centred engagement for these men entailed empowerment and autonomy; empathy, compassion and sincerity; respectful communication; and tailored and holistic life plans. While there was a strong emphasis placed on independence, the men identified the importance of positive therapeutic relationships as being critical aspects of the recovery process. Based on our analyses, several recommendations were identified: 1) Increasing general awareness of services for problem gambling; 2) Delivering integrated services in a one-stop-shop; 3) Addressing mental health with psychotherapy and pharmacotherapy; 4) Providing timely access to prevention and recovery services; and 5) Enhancing life skills with peer support. Our study highlighted that most of the men we interviewed were not having their health and social needs met. Services need to address the intersection of problem gambling, housing instability, and other comorbidities. Ensuring services are grounded in person-centred engagement appears to be critical for optimal service delivery.

An integrated genomics analysis of epigenetic subtypes in human breast tumors links DNA methylation patterns to chromatin states in normal mammary cells.

PubMed

Holm, Karolina; Staaf, Johan; Lauss, Martin; Aine, Mattias; Lindgren, David; Bendahl, Pär-Ola; Vallon-Christersson, Johan; Barkardottir, Rosa Bjork; Höglund, Mattias; Borg, Åke; Jönsson, Göran; Ringnér, Markus

2016-02-29

Aberrant DNA methylation is frequently observed in breast cancer. However, the relationship between methylation patterns and the heterogeneity of breast cancer has not been comprehensively characterized. Whole-genome DNA methylation analysis using Illumina Infinium HumanMethylation450 BeadChip arrays was performed on 188 human breast tumors. Unsupervised bootstrap consensus clustering was performed to identify DNA methylation epigenetic subgroups (epitypes). The Cancer Genome Atlas data, including methylation profiles of 669 human breast tumors, was used for validation. The identified epitypes were characterized by integration with publicly available genome-wide data, including gene expression levels, DNA copy numbers, whole-exome sequencing data, and chromatin states. We identified seven breast cancer epitypes. One epitype was distinctly associated with basal-like tumors and with BRCA1 mutations, one epitype contained a subset of ERBB2-amplified tumors characterized by multiple additional amplifications and the most complex genomes, and one epitype displayed a methylation profile similar to normal epithelial cells. Luminal tumors were stratified into the remaining four epitypes, with differences in promoter hypermethylation, global hypomethylation, proliferative rates, and genomic instability. Specific hyper- and hypomethylation across the basal-like epitype was rare. However, we observed that the candidate genomic instability drivers BRCA1 and HORMAD1 displayed aberrant methylation linked to gene expression levels in some basal-like tumors. Hypomethylation in luminal tumors was associated with DNA repeats and subtelomeric regions. We observed two dominant patterns of aberrant methylation in breast cancer. One pattern, constitutively methylated in both basal-like and luminal breast cancer, was linked to genes with promoters in a Polycomb-repressed state in normal epithelial cells and displayed no correlation with gene expression levels. The second pattern correlated with gene expression levels and was associated with methylation in luminal tumors and genes with active promoters in normal epithelial cells. Our results suggest that hypermethylation patterns across basal-like breast cancer may have limited influence on tumor progression and instead reflect the repressed chromatin state of the tissue of origin. On the contrary, hypermethylation patterns specific to luminal breast cancer influence gene expression, may contribute to tumor progression, and may present an actionable epigenetic alteration in a subset of luminal breast cancers.

Inefficient differentiation response to cell cycle stress leads to genomic instability and malignant progression of squamous carcinoma cells

PubMed Central

Alonso-Lecue, Pilar; de Pedro, Isabel; Coulon, Vincent; Molinuevo, Rut; Lorz, Corina; Segrelles, Carmen; Ceballos, Laura; López-Aventín, Daniel; García-Valtuille, Ana; Bernal, José M; Mazorra, Francisco; Pujol, Ramón M; Paramio, Jesús; Ramón Sanz, J; Freije, Ana; Toll, Agustí; Gandarillas, Alberto

2017-01-01

Squamous cell carcinoma (SCC) or epidermoid cancer is a frequent and aggressive malignancy. However in apparent paradox it retains the squamous differentiation phenotype except for very dysplastic lesions. We have shown that cell cycle stress in normal epidermal keratinocytes triggers a squamous differentiation response involving irreversible mitosis block and polyploidisation. Here we show that cutaneous SCC cells conserve a partial squamous DNA damage-induced differentiation response that allows them to overcome the cell division block. The capacity to divide in spite of drug-induced mitotic stress and DNA damage made well-differentiated SCC cells more genomically instable and more malignant in vivo. Consistently, in a series of human biopsies, non-metastatic SCCs displayed a higher degree of chromosomal alterations and higher expression of the S phase regulator Cyclin E and the DNA damage signal γH2AX than the less aggressive, non-squamous, basal cell carcinomas. However, metastatic SCCs lost the γH2AX signal and Cyclin E, or accumulated cytoplasmic Cyclin E. Conversely, inhibition of endogenous Cyclin E in well-differentiated SCC cells interfered with the squamous phenotype. The results suggest a dual role of cell cycle stress-induced differentiation in squamous cancer: the resulting mitotic blocks would impose, when irreversible, a proliferative barrier, when reversible, a source of genomic instability, thus contributing to malignancy. PMID:28661481

Abnormal RNA splicing and genomic instability after induction of DNMT3A mutations by CRISPR/Cas9 gene editing.

PubMed

Banaszak, Lauren G; Giudice, Valentina; Zhao, Xin; Wu, Zhijie; Gao, Shouguo; Hosokawa, Kohei; Keyvanfar, Keyvan; Townsley, Danielle M; Gutierrez-Rodrigues, Fernanda; Fernandez Ibanez, Maria Del Pilar; Kajigaya, Sachiko; Young, Neal S

2018-03-01

DNA methyltransferase 3A (DNMT3A) mediates de novo DNA methylation. Mutations in DNMT3A are associated with hematological malignancies, most frequently acute myeloid leukemia. DNMT3A mutations are hypothesized to establish a pre-leukemic state, rendering cells vulnerable to secondary oncogenic mutations and malignant transformation. However, the mechanisms by which DNMT3A mutations contribute to leukemogenesis are not well-defined. Here, we successfully created four DNMT3A-mutated K562 cell lines with frameshift mutations resulting in truncated DNMT3A proteins. DNMT3A-mutated cell lines exhibited significantly impaired growth and increased apoptotic activity compared to wild-type (WT) cells. Consistent with previous studies, DNMT3A-mutated cells displayed impaired differentiation capacity. RNA-seq was used to compare transcriptomes of DNMT3A-mutated and WT cells; DNMT3A ablation resulted in downregulation of genes involved in spliceosome function, causing dysfunction of RNA splicing. Unexpectedly, we observed DNMT3A-mutated cells to exhibit marked genomic instability and an impaired DNA damage response compared to WT. CRISPR/Cas9-mediated DNMT3A-mutated K562 cells may be used to model effects of DNMT3A mutations in human cells. Our findings implicate aberrant splicing and induction of genomic instability as potential mechanisms by which DNMT3A mutations might predispose to malignancy. Published by Elsevier Inc.

WD-repeat instability and diversification of the Podospora anserina hnwd non-self recognition gene family.

PubMed

Chevanne, Damien; Saupe, Sven J; Clavé, Corinne; Paoletti, Mathieu

2010-05-06

Genes involved in non-self recognition and host defence are typically capable of rapid diversification and exploit specialized genetic mechanism to that end. Fungi display a non-self recognition phenomenon termed heterokaryon incompatibility that operates when cells of unlike genotype fuse and leads to the cell death of the fusion cell. In the fungus Podospora anserina, three genes controlling this allorecognition process het-d, het-e and het-r are paralogs belonging to the same hnwd gene family. HNWD proteins are STAND proteins (signal transduction NTPase with multiple domains) that display a WD-repeat domain controlling recognition specificity. Based on genomic sequence analysis of different P. anserina isolates, it was established that repeat regions of all members of the gene family are extremely polymorphic and undergoing concerted evolution arguing for frequent recombination within and between family members. Herein, we directly analyzed the genetic instability and diversification of this allorecognition gene family. We have constituted a collection of 143 spontaneous mutants of the het-R (HNWD2) and het-E (hnwd5) genes with altered recognition specificities. The vast majority of the mutants present rearrangements in the repeat arrays with deletions, duplications and other modifications as well as creation of novel repeat unit variants. We investigate the extreme genetic instability of these genes and provide a direct illustration of the diversification strategy of this eukaryotic allorecognition gene family.

The inactive X chromosome is epigenetically unstable and transcriptionally labile in breast cancer.

PubMed

Chaligné, Ronan; Popova, Tatiana; Mendoza-Parra, Marco-Antonio; Saleem, Mohamed-Ashick M; Gentien, David; Ban, Kristen; Piolot, Tristan; Leroy, Olivier; Mariani, Odette; Gronemeyer, Hinrich; Vincent-Salomon, Anne; Stern, Marc-Henri; Heard, Edith

2015-04-01

Disappearance of the Barr body is considered a hallmark of cancer, although whether this corresponds to genetic loss or to epigenetic instability and transcriptional reactivation is unclear. Here we show that breast tumors and cell lines frequently display major epigenetic instability of the inactive X chromosome, with highly abnormal 3D nuclear organization and global perturbations of heterochromatin, including gain of euchromatic marks and aberrant distributions of repressive marks such as H3K27me3 and promoter DNA methylation. Genome-wide profiling of chromatin and transcription reveal modified epigenomic landscapes in cancer cells and a significant degree of aberrant gene activity from the inactive X chromosome, including several genes involved in cancer promotion. We demonstrate that many of these genes are aberrantly reactivated in primary breast tumors, and we further demonstrate that epigenetic instability of the inactive X can lead to perturbed dosage of X-linked factors. Taken together, our study provides the first integrated analysis of the inactive X chromosome in the context of breast cancer and establishes that epigenetic erosion of the inactive X can lead to the disappearance of the Barr body in breast cancer cells. This work offers new insights and opens up the possibility of exploiting the inactive X chromosome as an epigenetic biomarker at the molecular and cytological levels in cancer. © 2015 Chaligné et al.; Published by Cold Spring Harbor Laboratory Press.

The use of ultrasound in the assessment of the glenoid labrum of the glenohumeral joint. Part II: Examples of labral pathologies.

PubMed

Krzyżanowski, Wojciech; Tarczyńska, Marta

2012-09-01

Labral pathologies of the glenohumeral joint are most commonly caused by trauma. The majority of lesions affect the anterior part of labrum, resulting from much higher frequency of anterior shoulder dislocations over posterior ones. Another subgroup of labral lesions, not directly related to joint instability, are SLAP tears. Other findings include degenerative changes of labrum and paralabral cysts. Diagnostic imaging is crucial for making a decision regarding operative treatment. Apart from a standard X-ray examination, the imaging mainly relies on magnetic resonance or computed tomography arthrography. Based on their own experience, the authors propose the use of ultrasound in the assessment of labral tears of the glenohumeral joint. Different signs indicating labral pathology may be discovered and assessed during ultrasound examination. They include permanent displacement of the labrum onto the glenoid, labral instability during dynamic examination, lack of the labrum in the anatomical position, hypoechoic zone at the base of the labrum >2 mm in width, residual or swollen labrum as well as paralabral cyst(s). The most frequent appearance of labral pathology is displacement of the anteroinferior labrum onto the external aspect of the glenoid typically seen after anterior shoulder dislocation. The another most important US feature is labral instability while dynamically examined. The swelling or reduced size of the labrum usually indicates degeneration. This article presents sonographic images of selected labral pathologies.

Collective Temperature Anisotropy Instabilities in Intense Charged Particle Beams

NASA Astrophysics Data System (ADS)

Startsev, Edward

2006-10-01

Periodic focusing accelerators, transport systems and storage rings have a wide range of applications ranging from basic scientific research in high energy and nuclear physics, to applications such as ion-beam-driven high energy density physics and fusion, and spallation neutron sources. Of particular importance at the high beam currents and charge densities of practical interest, are the effects of the intense self fields produced by the beam space charge and current on determining the detailed equilibrium, stability and transport properties. Charged particle beams confined by external focusing fields represent an example of nonneutral plasma. A characteristic feature of such plasmas is the non-uniformity of the equilibrium density profiles and the nonlinearity of the self fields, which makes detailed analytical investigation very difficult. The development and application of advanced numerical tools such as eigenmode codes [1] and Monte-Carlo particle simulation methods [2] are often the only tractable approach to understand the underlying physics of different instabilities familiar in electrically neutral plasmas which may cause a degradation in beam quality. Two such instabilities are the electrostatic Harris instability [2] and the electromagnetic Weibel instability [1], both driven by a large temperature anisotropy which develops naturally in accelerators. The beam acceleration causes a large reduction in the longitudinal temperature and provides the free energy to drive collective temperature anisotropy instabilities. Such instabilities may lead to an increase in the longitudinal velocity spread, which will make focusing the beam difficult, and may impose a limit on the beam luminosity and the minimum spot size achievable in focusing experiments. This paper reviews recent advances in the theory and simulation of collective instabilities in intense charged particle beams caused by temperature anisotropy. We also describe new simulation tools that have been developed to study these instabilities. The results of the investigations that identify the instability growth rates, levels of saturations, and conditions for quiescent beam propagation will also be discussed. [1] E.A. Startsev and R.C. Davidson, Phys.Plasmas 10, 4829 (2003). [2] E.A. Startsev, R.C. Davidson and H. Qin, Phys.Rev. ST Accel. Beams 8,124201 (2005).

Development of solar wind shock models with tensor plasma pressure for data analysis

NASA Technical Reports Server (NTRS)

Abraham-Shrauner, B.

1975-01-01

The development of solar wind shock models with tensor plasma pressure and the comparison of some of the shock models with the satellite data from Pioneer 6 through Pioneer 9 are reported. Theoretically, difficulties were found in non-turbulent fluid shock models for tensor pressure plasmas. For microscopic shock theories nonlinear growth caused by plasma instabilities was frequently not clearly demonstrated to lead to the formation of a shock. As a result no clear choice for a shock model for the bow shock or interplanetary tensor pressure shocks emerged.

Theory of cosmological perturbations with cuscuton

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boruah, Supranta S.; Kim, Hyung J.; Geshnizjani, Ghazal, E-mail: ssarmabo@uwaterloo.ca, E-mail: h268kim@uwaterloo.ca, E-mail: ggeshniz@uwaterloo.ca

2017-07-01

This paper presents the first derivation of the quadratic action for curvature perturbations, ζ, within the framework of cuscuton gravity. We study the scalar cosmological perturbations sourced by a canonical single scalar field in the presence of cuscuton field. We identify ζ as comoving curvature with respect to the source field and we show that it retains its conservation characteristic on super horizon scales. The result provides an explicit proof that cuscuton modification of gravity around Friedmann-Lemaitre-Robertson-Walker (FLRW) metric is ghost free. We also investigate the potential development of other instabilities in cuscuton models. We find that in a largemore » class of these models, there is no generic instability problem. However, depending on the details of slow-roll parameters, specific models may display gradient instabilities.« less

Patterns, Instabilities, Colors, and Flows in Vertical Foam Films

NASA Astrophysics Data System (ADS)

Yilixiati, Subinuer; Wojcik, Ewelina; Zhang, Yiran; Pearsall, Collin; Sharma, Vivek

2015-03-01

Foams find use in many applications in daily life, industry and biology. Examples include beverages, firefighting foam, cosmetics, foams for oil recovery and foams formed by pollutants. Foams are collection of bubbles separated by thin liquid films that are stabilized against drainage by the presence of surfactant molecules. Drainage kinetics and stability of the foam are strongly influenced by surfactant type, addition of particles, proteins and polymers. In this study, we utilize the thin film interference colors as markers for identifying patterns, instabilities and flows within vertical foam films. We experimentally study the emergence of thickness fluctuations near the borders and within thinning films, and study how buoyancy, capillarity and gravity driven instabilities and flows, are affected by variation in bulk and interfacial physicochemical properties dependent on the choice of constituents.

Correlated network of networks enhances robustness against catastrophic failures.

PubMed

Min, Byungjoon; Zheng, Muhua

2018-01-01

Networks in nature rarely function in isolation but instead interact with one another with a form of a network of networks (NoN). A network of networks with interdependency between distinct networks contains instability of abrupt collapse related to the global rule of activation. As a remedy of the collapse instability, here we investigate a model of correlated NoN. We find that the collapse instability can be removed when hubs provide the majority of interconnections and interconnections are convergent between hubs. Thus, our study identifies a stable structure of correlated NoN against catastrophic failures. Our result further suggests a plausible way to enhance network robustness by manipulating connection patterns, along with other methods such as controlling the state of node based on a local rule.

Correlated network of networks enhances robustness against catastrophic failures

PubMed Central

Zheng, Muhua

2018-01-01

Networks in nature rarely function in isolation but instead interact with one another with a form of a network of networks (NoN). A network of networks with interdependency between distinct networks contains instability of abrupt collapse related to the global rule of activation. As a remedy of the collapse instability, here we investigate a model of correlated NoN. We find that the collapse instability can be removed when hubs provide the majority of interconnections and interconnections are convergent between hubs. Thus, our study identifies a stable structure of correlated NoN against catastrophic failures. Our result further suggests a plausible way to enhance network robustness by manipulating connection patterns, along with other methods such as controlling the state of node based on a local rule. PMID:29668730

Arthroscopic Bankart repair and capsular shift for recurrent anterior shoulder instability: functional outcomes and identification of risk factors for recurrence.

PubMed

Ahmed, Issaq; Ashton, Fiona; Robinson, Christopher Michael

2012-07-18

Arthroscopic Bankart repair and capsular shift is a well-established technique for the treatment of anterior shoulder instability. The purpose of this study was to evaluate the outcomes following arthroscopic Bankart repair and capsular shift and to identify risk factors that are predictive of recurrence of glenohumeral instability. We performed a retrospective review of a prospectively collected database consisting of 302 patients who had undergone arthroscopic Bankart repair and capsular shift for the treatment of recurrent anterior glenohumeral instability. The prevalence of patient and injury-related risk factors for recurrence was assessed. Cox proportional hazards models were used to estimate the predicted probability of recurrence within two years. The chief outcome measures were the risk of recurrence and the two-year functional outcomes assessed with the Western Ontario shoulder instability index (WOSI) and disabilities of the arm, shoulder and hand (DASH) scores. The rate of recurrent glenohumeral instability after arthroscopic Bankart repair and capsular shift was 13.2%. The median time to recurrence was twelve months, and this complication developed within one year in 55% of these patients. The risk of recurrence was independently predicted by the patient's age at surgery, the severity of glenoid bone loss, and the presence of an engaging Hill-Sachs lesion (all p < 0.001). These variables were incorporated into a model to provide an estimate of the risk of recurrence after surgery. Varying the cutoff level for the predicted probability of recurrence in the model from 50% to lower values increased the sensitivity of the model to detect recurrences but decreased the positive predictive value of the model to correctly predict failed repairs. There was a significant improvement in the mean WOSI and DASH scores at two years postoperatively (both p < 0.001), but the mean scores in the group with recurrence were significantly lower than those in the group without recurrence (both p < 0.001). Our study identified factors that are independently associated with a higher risk of recurrence following arthroscopic Bankart repair and capsular shift. These data can be useful for counseling patients undergoing this procedure for the treatment of recurrent glenohumeral instability and individualizing treatment options for particular groups of patients. Prognostic level I. See Instructions for authors for a complete description of levels of evidence.

Chromosomal instability in enterohaemorrhagic Escherichia coli O157:H7: impact on adherence, tellurite resistance and colony phenotype

PubMed Central

Bielaszewska, Martina; Middendorf, Barbara; Tarr, Phillip I; Zhang, Wenlan; Prager, Rita; Aldick, Thomas; Dobrindt, Ulrich; Karch, Helge; Mellmann, Alexander

2011-01-01

Tellurite (Tel) resistant enterohaemorrhagic Escherichia coli (EHEC) O157:H7 is a global pathogen. In strain EDL933 Tel resistance (TelR) is encoded by duplicate ter cluster in O islands (OI) 43 and 48, which also harbour iha, encoding the adhesin and siderophore receptor Iha. We identified five EHEC O157:H7 strains that differentiate into large (L) colonies and small (S) colonies with high and low Tel minimal inhibitory concentrations (MICs) respectively. S colonies (Tel-MICs ≤ 4 µg ml−1) sustained large internal deletions within the TelR OIs via homologous recombination between IS elements and lost ter and iha. Moreover, complete excision of the islands occurred by site-specific recombination between flanking direct repeats. Complete excision of OI 43 and OI 48 occurred in 1.81 × 10−3 and 1.97 × 10−4 cells in culture, respectively; internal deletion of OI 48 was more frequent (9.7 × 10−1 cells). Under iron limitation that promotes iha transcription, iha-negative derivatives adhered less well to human intestinal epithelial cells and grew slower than did their iha-positive counterparts. Experiments utilizing iha deletion and complementation mutants identified Iha as the major factor responsible for these phenotypic differences. Spontaneous deletions affecting TelR OIs contribute to EHEC O157 genome plasticity and might impair virulence and/or fitness. PMID:21299654

Distinctions of bipolar disorder symptoms in adolescence.

PubMed

Gudiene, Devika; Leskauskas, Darius; Markeviciūte, Aurelija; Klimavicius, Dalius; Adomaitiene, Virginija

2008-01-01

Bipolar disorder in adolescents is a serious mental illness with problematic diagnosis that adversely affects social, academic, emotional, and family functioning. The objective of this study was to analyze features of premorbid and clinical symptoms, comorbidity, and course of bipolar disorder in adolescence. Data for analysis were collected from all case histories (N=6) of 14-18-year-old patients, hospitalized with diagnosis of bipolar disorder in the Unit of Children's and Adolescents' Psychiatry, Department of Psychiatry, Hospital of Kaunas University of Medicine, during the period from 2000 to 2005. Analysis of bipolar disorder course showed that five patients previously had been diagnosed with an episode of depression. The most frequent symptoms typical to bipolar disorder were disobedience and impulsive behavior, rapid changes of mood. The most common premorbid features were frequent changes of mood, being active in communication, hyperactive behavior. Adolescence-onset bipolar disorder was frequently comorbid with emotionally instable personality disorder, borderline type. Findings of the study confirm the notion that oppositional or impulsive behavior, rapid changes of mood without any reason, dysphoric mood and euphoric mood episodes with increased energy were cardinal symptoms of bipolar disorder with mania in adolescents. Most frequent premorbid features of these patients were quite similar to attention-deficit/hyperactivity disorder making differential diagnosis problematic.

Evolution of Tumor Clones in Adult Acute Lymphoblastic Leukemia.

PubMed

Smirnova, S Yu; Sidorova, Yu V; Ryzhikova, N V; Sychevskaya, K A; Parovichnikova, E N; Sudarikov, A B

2016-01-01

Clonal instability of a tumor cell population in acute lymphoblastic leukemia (ALL) may complicate the monitoring of a minimal residual disease (MRD) by means of patient-specific targets identified at the disease onset. Most of the data concerning the possible instability of rearranged clonal TCR and IG genes during disease recurrence were obtained for ALL in children. The appropriate features of adult ALL, which are known to differ from those of childhood ALL in certain biological characteristics and prognosis, remain insufficiently studied. The aim of this study was to assess the stability of IG and TCR gene rearrangements in adult ALL. Rearrangements were identified according to the BIOMED-2 protocol (PCR followed by fragment analysis). Mismatch in clonal rearrangements at onset and relapse was identified in 83% of patients, indicating clonal instability during treatment. Clonal evolution and diversity of IG and TCR gene rearrangements may be one of the tumor progression mechanisms. New rearrangements may emerge due to residual VDJ-recombinase activity in tumor cells. Also, many clonal IG and TCR gene rearrangements may be present at different levels at a diagnosis, but less abundant clones may be "invisible" due to limited detection sensitivity. Later, major clones may disappear in the course of chemotherapy, while others may proliferate. Investigation of clonal evolution and heterogeneity in ALL and their impact on the treatment efficacy will contribute to the identification of new prognostic factors and the development of therapeutic approaches.

Loss of heterozygosity and microsatellite instability in chromosomal segments commonly deleted in squamous cell carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Dyke, D.L.; Worsham, M.J.; Zarbo, R.J.

1994-09-01

To evaluate genetic loss in an unselected series of squamous cell carcinoma (SCC) of the head and neck region (SCCHN), including early stage tumors that do not proliferate aggressively in vitro, we have compared microsatellite repeat polymorphisms (MSRP) in normal blood DNA and tumor DNA from 44 patients with SCCHN, using nine MSRPs from 5q15-q21, proximal 8p, 9p21-p23, 18q21-qter, and 21q21. In previous cytogenetic studies, these chromosome segments were deleted in 40-60% of SCCHN and SCC of the female genital tract. Loss of heterozygosity (LOH) was observed from the ANK1 locus (8p21.1-p11.2) in 2/29 informative tumors. LOH was observed atmore » D5S98 (5q15-5q21) in 5/19, and at D21S11 (21q21) in 5/33 informative tumors. These LOH frequencies were lower than expected, which suggests that the critical region of deletion from these chromosome regions exludes the MSRPs studied here, especially for the 8p MSRP, which may reside in proximal 8p. Alternatively, the observed LOH rates may be appropriate for earlier pathologic stage tumors: total genetic loss increases with tumor stage, and the present study included more stage I and II tumors than did the cytogenetic studies. LOH was observed at D9S126, 1FN, and/or D9S199 (at 9p21, 9p22, & 9p23) in 16/38 informative tumors, and at D18S34 and/or MBP (at 18q21 & 18q22-qter) in 17/39 informative tumors. In addition, three tumors demonstrated microsatellite instability at the MBP locus, and one of these had an expansion at D9S199 as well. This tumor, HFH-SCC-20, also demonstrated microsatellite instability at many other MSRP loci. These results confirm that genetic loss from 9p and 18q is frequent in SCCHN, and demonstrate that microsatellite instability also occurs. Of 66 MSRP changes, 62 were LOH and 4 were microsatellite instabilities. These results also show the usefulness of analyses of MSRP LOH and microsatellite instability in squamous cell carcinoma.« less

Vestibular rehabilitation: clinical benefits to patients with Parkinson's disease.

PubMed

Zeigelboim, Bianca Simone; Klagenberg, Karlin Fabianne; Teive, Hélio A Ghizoni; Munhoz, Renato Puppi; Martins-Bassetto, Jackeline

2009-06-01

To evaluate the effectiveness of the vestibular rehabilitation (VR) exercises by means of an assessment before and after the application of the Brazilian version of the Dizziness Handicap Inventory (DHI) questionnaire. Twelve patients were studied, the following procedures were carried out: anamnesis, otorhinolaryngological and vestibular evaluation, and the application of the DHI before and after the VR. Clinically resting tremors and subjective postural instability were the motor complaints most frequently associated with complaints of vertigo in 12 cases (100%); in the vestibular exam, all the patients presented abnormalities, frequently from the uni and bilateral peripheral vestibular deficiency syndromes in 10 cases (83.3%); there was significant improvement in the physical, functional and emotional aspects of the DHI after the completion of the VR. The VR following the Cawthorne and Cooksey protocol were shown to be useful in managing subjective complaints of several aspects evaluated in this protocol.

Identifying and Characterizing Kinetic Instabilities using Solar Wind Observations of Non-Maxwellian Plasmas

NASA Astrophysics Data System (ADS)

Klein, K. G.

2016-12-01

Weakly collisional plasmas, of the type typically observed in the solar wind, are commonly in a state other than local thermodynamic equilibrium. This deviation from a Maxwellian velocity distribution can be characterized by pressure anisotropies, disjoint beams streaming at differing speeds, leptokurtic distributions at large energies, and other non-thermal features. As these features may be artifacts of dynamic processes, including the the acceleration and expansion of the solar wind, and as the free energy contained in these features can drive kinetic micro-instabilities, accurate measurement and modeling of these features is essential for characterizing the solar wind. After a review of these features, a technique is presented for the efficient calculation of kinetic instabilities associated with a general, non-Maxwellian plasma. As a proof of principle, this technique is applied to bi-Maxwellian systems for which kinetic instability thresholds are known, focusing on parameter scans including beams and drifting heavy minor ions. The application of this technique to fits of velocity distribution functions from current, forthcoming, and proposed missions including WIND, DSCOVR, Solar Probe Plus, and THOR, as well as the underlying measured distribution functions, is discussed. Particular attention is paid to the effects of instrument pointing and integration time, as well as potential deviation between instabilities associated with the Maxwellian fits and those associated with the observed, potentially non-Maxwellian, velocity distribution. Such application may further illuminate the role instabilities play in the evolution of the solar wind.

Direct experimental evidence of ion-ion co-stream instability excited in the sheath-presheath of Ar +He two-ion species plasma

NASA Astrophysics Data System (ADS)

Kella, Vara Prasad; Ghosh, Joydeep; Chattopadhyay, Prabal; Sharma, Devendra; Saxena, Yogesh

2017-10-01

Recent experimental measurements of ion flow speeds near the sheath edge of two-ion species plasma shows that, the ions reach the sheath edge with common sound speed other than their individual Bohm speeds at nearly equal ion concentrations. Baalrud et al., explain these results on the basis of ion-ion two-stream instability enhanced collisional friction between the ions. Some authors stipulate the existence of the instability indirectly, by measuring the ion flow speeds near the sheath edge. In these experiments, the instability is directly observed from the floating potential fluctuations from Langmuir probe placed near the sheath edge and from grid in Ar +He plasma. The frequency spectra shows broad band peaks with central frequency in the range 150-200 kHz. The intensity of the instability maximizes in the plasma produced with approximately equal ion concentrations of both the ion species. The frequency and amplitude of the peak decreases as the He+ to Ar+ concentration ratio decreases from unity. The phase velocity of the wave is measured as 11 +/-2 km/s and identified to be twice the ion-sound speed in the bulk ( 6.3 km/s), which is good agreement with earlier results of IAWs. The measured wave number and frequencies are compared with the theoretical dispersion relations. These observations confirm the existence of ion-ion co-stream instability in sheath-presheath of two-ion species plasma.

Mutational signatures reveal the role of RAD52 in p53-independent p21-driven genomic instability.

PubMed

Galanos, Panagiotis; Pappas, George; Polyzos, Alexander; Kotsinas, Athanassios; Svolaki, Ioanna; Giakoumakis, Nickolaos N; Glytsou, Christina; Pateras, Ioannis S; Swain, Umakanta; Souliotis, Vassilis L; Georgakilas, Alexandros G; Geacintov, Nicholas; Scorrano, Luca; Lukas, Claudia; Lukas, Jiri; Livneh, Zvi; Lygerou, Zoi; Chowdhury, Dipanjan; Sørensen, Claus Storgaard; Bartek, Jiri; Gorgoulis, Vassilis G

2018-03-16

Genomic instability promotes evolution and heterogeneity of tumors. Unraveling its mechanistic basis is essential for the design of appropriate therapeutic strategies. In a previous study, we reported an unexpected oncogenic property of p21 WAF1/Cip1 , showing that its chronic expression in a p53-deficient environment causes genomic instability by deregulation of the replication licensing machinery. We now demonstrate that p21 WAF1/Cip1 can further fuel genomic instability by suppressing the repair capacity of low- and high-fidelity pathways that deal with nucleotide abnormalities. Consequently, fewer single nucleotide substitutions (SNSs) occur, while formation of highly deleterious DNA double-strand breaks (DSBs) is enhanced, crafting a characteristic mutational signature landscape. Guided by the mutational signatures formed, we find that the DSBs are repaired by Rad52-dependent break-induced replication (BIR) and single-strand annealing (SSA) repair pathways. Conversely, the error-free synthesis-dependent strand annealing (SDSA) repair route is deficient. Surprisingly, Rad52 is activated transcriptionally in an E2F1-dependent manner, rather than post-translationally as is common for DNA repair factor activation. Our results signify the importance of mutational signatures as guides to disclose the repair history leading to genomic instability. We unveil how chronic p21 WAF1/Cip1 expression rewires the repair process and identifies Rad52 as a source of genomic instability and a candidate therapeutic target.

Instability waves and low-frequency noise radiation in the subsonic chevron jet

NASA Astrophysics Data System (ADS)

Ran, Lingke; Ye, Chuangchao; Wan, Zhenhua; Yang, Haihua; Sun, Dejun

2017-11-01

Spatial instability waves associated with low-frequency noise radiation at shallow polar angles in the chevron jet are investigated and are compared to the round counterpart. The Reynolds-averaged Navier-Stokes equations are solved to obtain the mean flow fields, which serve as the baseflow for linear stability analysis. The chevron jet has more complicated instability waves than the round jet, where three types of instability modes are identified in the vicinity of the nozzle, corresponding to radial shear, azimuthal shear, and their integrated effect of the baseflow, respectively. The most unstable frequency of all chevron modes and round modes in both jets decrease as the axial location moves downstream. Besides, the azimuthal shear effect related modes are more unstable than radial shear effect related modes at low frequencies. Compared to a round jet, a chevron jet reduces the growth rate of the most unstable modes at downstream locations. Moreover, linearized Euler equations are employed to obtain the beam pattern of pressure generated by spatially evolving instability waves at a dominant low frequency St=0.3 , and the acoustic efficiencies of these linear wavepackets are evaluated for both jets. It is found that the acoustic efficiency of linear wavepacket is able to be reduced greatly in the chevron jet, compared to the round jet.

Sites of instability in the human TCF3 (E2A) gene adopt G-quadruplex DNA structures in vitro

PubMed Central

Williams, Jonathan D.; Fleetwood, Sara; Berroyer, Alexandra; Kim, Nayun; Larson, Erik D.

2015-01-01

The formation of highly stable four-stranded DNA, called G-quadruplex (G4), promotes site-specific genome instability. G4 DNA structures fold from repetitive guanine sequences, and increasing experimental evidence connects G4 sequence motifs with specific gene rearrangements. The human transcription factor 3 (TCF3) gene (also termed E2A) is subject to genetic instability associated with severe disease, most notably a common translocation event t(1;19) associated with acute lymphoblastic leukemia. The sites of instability in TCF3 are not randomly distributed, but focused to certain sequences. We asked if G4 DNA formation could explain why TCF3 is prone to recombination and mutagenesis. Here we demonstrate that sequences surrounding the major t(1;19) break site and a region associated with copy number variations both contain G4 sequence motifs. The motifs identified readily adopt G4 DNA structures that are stable enough to interfere with DNA synthesis in physiological salt conditions in vitro. When introduced into the yeast genome, TCF3 G4 motifs promoted gross chromosomal rearrangements in a transcription-dependent manner. Our results provide a molecular rationale for the site-specific instability of human TCF3, suggesting that G4 DNA structures contribute to oncogenic DNA breaks and recombination. PMID:26029241

Instability waves and low-frequency noise radiation in the subsonic chevron jet

NASA Astrophysics Data System (ADS)

Ran, Lingke; Ye, Chuangchao; Wan, Zhenhua; Yang, Haihua; Sun, Dejun

2018-06-01

Spatial instability waves associated with low-frequency noise radiation at shallow polar angles in the chevron jet are investigated and are compared to the round counterpart. The Reynolds-averaged Navier-Stokes equations are solved to obtain the mean flow fields, which serve as the baseflow for linear stability analysis. The chevron jet has more complicated instability waves than the round jet, where three types of instability modes are identified in the vicinity of the nozzle, corresponding to radial shear, azimuthal shear, and their integrated effect of the baseflow, respectively. The most unstable frequency of all chevron modes and round modes in both jets decrease as the axial location moves downstream. Besides, the azimuthal shear effect related modes are more unstable than radial shear effect related modes at low frequencies. Compared to a round jet, a chevron jet reduces the growth rate of the most unstable modes at downstream locations. Moreover, linearized Euler equations are employed to obtain the beam pattern of pressure generated by spatially evolving instability waves at a dominant low frequency St=0.3, and the acoustic efficiencies of these linear wavepackets are evaluated for both jets. It is found that the acoustic efficiency of linear wavepacket is able to be reduced greatly in the chevron jet, compared to the round jet.

The initial instability and finite-amplitude stability of alternate bars in straight channels

USGS Publications Warehouse

Nelson, J.M.

1990-01-01

The initial instability and fully developed stability of alternate bars in straight channels are investigated using linearized and nonlinear analyses. The fundamental instability leading to these features is identified through a linear stability analysis of the equations governing the flow and sediment transport fields. This instability is explained in terms of topographically induced steering of the flow and the associated pattern of erosion and deposition on the bed. While the linear theory is useful for examining the instability mechanism, this approach is shown to yield relatively little information about well-developed alternate bars and, specifically, the linear analysis is shown to yield poor predictions of the fully developed bar wavelength. A fully nonlinear approach is presented that permits computation of the evolution of these bed features from an initial perturbation to their fully developed morphology. This analysis indicates that there is typically substantial elongation of the bar wavelength during the evolution process, a result that is consistent with observations of bar development in flumes and natural channels. The nonlinear approach demonstrates that the eventual stability of these features is a result of the interplay between topographic steering effects, secondary flow production as a result of streamline curvature, and gravitationally induced modifications of sediment fluxes over a sloping bed. ?? 1990.

Assessment of postural instability in patients with Parkinson's disease.

PubMed

Błaszczyk, J W; Orawiec, R; Duda-Kłodowska, D; Opala, G

2007-10-01

Postural instability is one of the most disabling features of idiopathic Parkinson's disease (PD). In this study, we focused on postural instability as the main factor predisposing parkinsonians to falls. For this purpose, changes in sway characteristics during quiet stance due to visual feedback exclusion were studied. We searched for postural sway measures that could be potential discriminators for an increased fall risk. A group of 110 subjects: 55 parkinsonians (Hoehn and Yahr: 1-3), and 55 age-matched healthy volunteers participated in the experiment. Their spontaneous sway characteristics while standing quiet with eyes open and eyes closed were analyzed. We found that an increased mediolateral sway and sway area while standing with eyes closed are characteristic of parkinsonian postural instability and may serve to quantify well a tendency to fall. These sway indices significantly correlated with disease severity rated both by the Hoehn and Yahr scale as well as by the Motor Section of the UPDRS. A forward shift of a mean COP position in parkinsonians which reflects their flexed posture was also significantly greater to compare with the elderly subjects and exhibited a high sensitivity to visual conditions. Both groups of postural sway abnormalities identified here may be used as accessible and reliable measures which allow for quantitative assessment of postural instability in Parkinson's disease.

Effective stability against superradiance of Kerr black holes with synchronised hair

NASA Astrophysics Data System (ADS)

Degollado, Juan Carlos; Herdeiro, Carlos A. R.; Radu, Eugen

2018-06-01

Kerr black holes with synchronised hair [1,2] are a counter example to the no hair conjecture, in General Relativity minimally coupled to simple matter fields (with mass μ) obeying all energy conditions. Since these solutions have, like Kerr, an ergoregion it has been a lingering possibility that they are afflicted by the superradiant instability, the same process that leads to their dynamical formation from Kerr. A recent breakthrough [3] confirmed this instability and computed the corresponding timescales for a sample of solutions. We discuss how these results and other observations support two conclusions: 1) starting from the Kerr limit, the increase of hair for fixed coupling μM (where M is the BH mass) increases the timescale of the instability; 2) there are hairy solutions for which this timescale, for astrophysical black hole masses, is larger than the age of the Universe. The latter conclusion introduces the limited, but physically relevant concept of effective stability. The former conclusion, allows us to identify an astrophysically viable domain of such effectively stable hairy black holes, occurring, conservatively, for Mμ ≲ 0.25. These are hairy BHs that form dynamically, from the superradiant instability of Kerr, within an astrophysical timescale, but whose own superradiant instability occurs only in a cosmological timescale.

Distinguishing the Magnetorotational Instability (MRI) from Magnetized Ekman Flows in the PPPL MRI Experiment

NASA Astrophysics Data System (ADS)

Gilson, Erik; Caspary, Kyle; Goodman, Jeremy; Ji, Hantao; Schartman, Ethan; Wei, Xing

2015-11-01

Results are presented from initial experiments on the upgraded Magnetorotational Instability (MRI) experiment that uses GaInSn as the working fluid and now operates with conductive end caps to improve the coupling of angular momentum to the fluid to increase the saturation amplitude of the MRI signal. Measurements of the fluid velocity field and perturbed magnetic field over a range of magnetic Reynolds numbers, Rm , and Lundquist numbers, S, are compared with results from the SFEMaNS code in order to separate the effects of MRI on the system from effects such as Ekman flows and Shercliff layer instabilities. The MRI can be identified by observing its growth rate, noting the relative magnitudes and spatial distributions of the perturbed radial flow velocity ur and radial magnetic field Br, and measuring the scaling of ur and Br with Rm . The clear identification of the onset of MRI in the apparatus is complicated by the geometry and boundary conditions creating an imperfect supercritical pitchfork bifurcation. Nevertheless, a stability diagram can be created that shows that MRI is a weak-field instability that occurs only below a certain value of the normalized magnetic field S / Rm but above a threshold where viscous effects damps the growth of the instability.

Confronting stillbirths and newborn deaths in areas of conflict and political instability: a neglected global imperative.

PubMed

Wise, Paul H; Darmstadt, Gary L

2015-08-01

Despite considerable improvements in reproductive and newborn health throughout the world, relatively poor outcomes persist in areas plagued by conflict or political instability. To assess the contribution of areas of conflict and instability to global patterns of stillbirths and newborn deaths and to identify opportunities for effective intervention in these areas. Analysis of the available data on stillbirths and neonatal mortality in association with conflict and governance indicators, and review of epidemiological and political literature pertaining to the provision of health and public services in areas of conflict and instability. Of the 15 countries with the highest neonatal mortality rates in the world, 14 are characterized by chronic conflict or political instability. If India and China are excluded, countries experiencing chronic conflict or political instability account for approximately 42% of all neonatal deaths worldwide. Efforts to address adverse reproductive and newborn outcomes in these areas must adapt recommended intervention protocols to the special security and governance conditions associated with unstable political environment. Despite troubling relative and absolute indicators, the special requirements of improving reproductive and neonatal outcomes in areas affected by conflict and political instability have not received adequate attention. New integrated political and technical strategies will be required. This should include moving beyond traditional approaches concerned with complex humanitarian emergencies. Rather, global efforts must be based on a deeper understanding of the specific governance requirements associated with protracted and widespread health requirements. A focus on women's roles, regional strategies which take advantage of relative stability and governance capacity in neighbouring states, virtual infrastructure, and assistance regimens directed specifically to unstable areas may prove useful.

Arthroscopic Findings in Anterior Shoulder Instability

PubMed Central

Hantes, Michael; Raoulis, Vasilios

2017-01-01

Background: In the last years, basic research and arthroscopic surgery, have improved our understanding of shoulder anatomy and pathology. It is a fact that arthroscopic treatment of shoulder instability has evolved considerably over the past decades. The aim of this paper is to present the variety of pathologies that should be identified and treated during shoulder arthroscopy when dealing with anterior shoulder instability cases. Methods: A review of the current literature regarding arthroscopic shoulder anatomy, anatomic variants, and arthroscopic findings in anterior shoulder instability, is presented. In addition, correlation of arthroscopic findings with physical examination and advanced imaging (CT and MRI) in order to improve our understanding in anterior shoulder instability pathology is discussed. Results: Shoulder instability represents a broad spectrum of disease and a thorough understanding of the pathoanatomy is the key for a successful treatment of the unstable shoulder. Patients can have a variety of pathologies concomitant with a traditional Bankart lesion, such as injuries of the glenoid (bony Bankart), injuries of the glenoid labrum, superiorly (SLAP) or anteroinferiorly (e.g. anterior labroligamentous periosteal sleeve avulsion, and Perthes), capsular lesions (humeral avulsion of the glenohumeral ligament), and accompanying osseous-cartilage lesions (Hill-Sachs, glenolabral articular disruption). Shoulder arthroscopy allows for a detailed visualization and a dynamic examination of all anatomic structures, identification of pathologic findings, and treatment of all concomitant lesions. Conclusion: Surgeons must be well prepared and understanding the normal anatomy of the glenohumeral joint, including its anatomic variants to seek for the possible pathologic lesions in anterior shoulder instability during shoulder arthroscopy. Patient selection criteria, improved surgical techniques, and implants available have contributed to the enhancement of clinical and functional outcomes to the point that arthroscopic treatment is considered nowadays the standard of care. PMID:28400880

Constrained fixed-fulcrum reverse shoulder arthroplasty improves functional outcome in epileptic patients with recurrent shoulder instability

PubMed Central

Thangarajah, Tanujan; Higgs, Deborah; Bayley, J I L; Lambert, Simon M

2016-01-01

AIM: To report the results of fixed-fulcrum fully constrained reverse shoulder arthroplasty for the treatment of recurrent shoulder instability in patients with epilepsy. METHODS: A retrospective review was conducted at a single facility. Cases were identified using a computerized database and all clinic notes and operative reports were reviewed. All patients with epilepsy and recurrent shoulder instability were included for study. Between July 2003 and August 2011 five shoulders in five consecutive patients with epilepsy underwent fixed-fulcrum fully constrained reverse shoulder arthroplasty for recurrent anterior shoulder instability. The mean duration of epilepsy in the cohort was 21 years (range, 5-51) and all patients suffered from grand mal seizures. RESULTS: Mean age at the time of surgery was 47 years (range, 32-64). The cohort consisted of four males and one female. Mean follow-up was 4.7 years (range, 4.3-5 years). There were no further episodes of instability, and no further stabilisation or revision procedures were performed. The mean Oxford shoulder instability score improved from 8 preoperatively (range, 5-15) to 30 postoperatively (range, 16-37) (P = 0.015) and the mean subjective shoulder value improved from 20 (range, 0-50) preoperatively to 60 (range, 50-70) postoperatively (P = 0.016). Mean active forward elevation improved from 71° preoperatively (range, 45°-130°) to 100° postoperatively (range, 80°-90°) and mean active external rotation improved from 15° preoperatively (range, 0°-30°) to 40° (20°-70°) postoperatively. No cases of scapular notching or loosening were noted. CONCLUSION: Fixed-fulcrum fully constrained reverse shoulder arthroplasty should be considered for the treatment of recurrent shoulder instability in patients with epilepsy. PMID:27458554

Energy dynamics in a simulation of LAPD turbulence

NASA Astrophysics Data System (ADS)

Friedman, Brett

2012-10-01

It is often assumed that linear instabilities maintain turbulence in plasmas and some fluids, but this is not always the case. It is well known that many fluids display subcritical turbulence at a Reynolds number well below the threashold of linear instability. Certain plasma models such as drift waves in a sheared slab also exhibit subcritical turbulence [1]. In other instances such as drift-ballooning turbulence in tokamak edge plasmas, linear instabilities exist in a system, but they become subdominant to more robust nonlinear mechanisms that sustain a turbulent state [2, 3]. In our simulation of LAPD turbulence, which was previously analyzed in [4], we diagnose the results using an energy dynamics analysis [5]. This allows us to track energy input into turbulent fluctuations and energy dissipation out of them. We also track conservative energy transfer between different energy types (e.g. from potential to kinetic energy) and between different Fourier waves of the system. The result is that a nonlinear instability drives and maintains the turbulence in the steady state saturated phase of the simulation. While a linear restistive drift wave instability resides in the system, the nonlinear drift wave instability dominates when the fluctuation amplitude becomes large enough. The nonlinear instability is identified by its energy growth rate spectrum, which varies significantly from the linear growth rate spectrum. The main differences are the presence of positive growth rates when k|| = 0 and negative growth rates for nonzero k||, which is opposite that of the linear growth rate spectrum.[4pt] [1] B. D. Scott, Phys. Rev. Lett., 65, 3289 (1990).[0pt] [2] A. Zeiler et al, Phys. Plasmas, 3, 2951 (1996).[0pt] [3] B. D. Scott, Phys. Plasmas, 12, 062314 (2005).[0pt] [4] P. Popovich et al, Phys. Plasmas, 17, 122312 (2010).[0pt] [5] [physics.plasm-ph].

[The molecular biology of epithelial ovarian cancer].

PubMed

Leary, Alexandra; Pautier, Patricia; Tazi, Youssef; Morice, Philippe; Duvillard, Pierre; Gouy, Sébastien; Uzan, Catherine; Gauthier, Hélène; Balleyguier, Corinne; Lhommé, Catherine

2012-12-01

Epithelial ovarian cancer frequently presents at an advanced stage where the cornerstone of management remains surgery and platinum-based chemotherapy. Unfortunately, despite sometimes dramatic initial responses, advanced ovarian cancer almost invariably relapses. Little progress has been made in the identification of effective targeted-therapies for ovarian cancer. The majority of clinical trials investigating novel agents have been negative and the only approved targeted-therapy is bevacizumab, for which reliable predictive biomarkers still elude us. Ovarian cancer is treated as a uniform disease. Yet, biological studies have highlighted the heterogeneity of this malignancy with marked differences in histology, oncogenesis, prognosis, chemo-responsiveness, and molecular profile. Recent high throughput molecular analyses have identified a huge number of genomic/phenotypic alterations. Broadly speaking, high grade serous carcinomas (type II) display significant genomic instability and numerous amplifications and losses; low grade (type I) tumors are genomically stable but display frequent mutations. Importantly, many of these genomic alterations relate to known oncogenes for which targeted-therapies are available or in development. There is today a real potential for personalized medicine in ovarian cancer. We will review the current literature regarding the molecular characterization of epithelial ovarian cancer and discuss the biological rationale for a number of targeted strategies. In order to translate these biological advances into meaningful clinical improvements for our patients, it is imperative to incorporate translational research in ovarian cancer trials, a number of strategies will be proposed such as the acquisition of quality tumor samples, including sequential pre- and post-treatment biopsies, the potential of liquid biopsies, and novel trial designs more adapted to the molecular era of ovarian cancer research.

Defects in the Fanconi Anemia Pathway and Chromatid Cohesion in Head and Neck Cancer.

PubMed

Stoepker, Chantal; Ameziane, Najim; van der Lelij, Petra; Kooi, Irsan E; Oostra, Anneke B; Rooimans, Martin A; van Mil, Saskia E; Brink, Arjen; Dietrich, Ralf; Balk, Jesper A; Ylstra, Bauke; Joenje, Hans; Feller, Stephan M; Brakenhoff, Ruud H

2015-09-01

Failure to repair DNA damage or defective sister chromatid cohesion, a process essential for correct chromosome segregation, can be causative of chromosomal instability (CIN), which is a hallmark of many types of cancers. We investigated how frequent this occurs in head and neck squamous cell carcinoma (HNSCC) and whether specific mechanisms or genes could be linked to these phenotypes. The genomic instability syndrome Fanconi anemia is caused by mutations in any of at least 16 genes regulating DNA interstrand crosslink (ICL) repair. Since patients with Fanconi anemia have a high risk to develop HNSCC, we investigated whether and to which extent Fanconi anemia pathway inactivation underlies CIN in HNSCC of non-Fanconi anemia individuals. We observed ICL-induced chromosomal breakage in 9 of 17 (53%) HNSCC cell lines derived from patients without Fanconi anemia. In addition, defective sister chromatid cohesion was observed in five HNSCC cell lines. Inactivation of FANCM was responsible for chromosomal breakage in one cell line, whereas in two other cell lines, somatic mutations in PDS5A or STAG2 resulted in inadequate sister chromatid cohesion. In addition, FANCF methylation was found in one cell line by screening an additional panel of 39 HNSCC cell lines. Our data demonstrate that CIN in terms of ICL-induced chromosomal breakage and defective chromatid cohesion is frequently observed in HNSCC. Inactivation of known Fanconi anemia and chromatid cohesion genes does explain CIN in the minority of cases. These findings point to phenotypes that may be highly relevant in treatment response of HNSCC. ©2015 American Association for Cancer Research.

Midcarpal instability: a diagnostic role for dynamic ultrasound?

PubMed

Toms, A; Chojnowski, A; Cahir, J

2009-06-01

The aim of this study was to describe the technique of dynamic ultrasound (US) examination of the triquetral clunk, and to illustrate the range of findings in four patients with midcarpal instability (MCI). Four patients were identified (3 men, 1 woman). The case notes, plain radiographs, MRI and dynamic US for each patient were reviewed. Digital video files recording the dynamic US of the triquetral clunks were analysed for the following features of abnormal triquetral mobility: direction and speed of triquetral snap, amount of anteroposterior translocation, and flexion or extension during the snap. Five different triquetral clunks were recorded in 4 patients. In four out of five cases the clunk occurred during ulnar translocation of the wrist, and in one during radial translocation. Anteroposterior translocation was anterior (3.4 - 4.7 mm) in three of the clunks and posterior (1 - 10 mm) in two. The degree of flexion or extension varied between 1 and 16 degrees . The snapping phase of the clunk lasted between 0.17 and 0.25 seconds. Dynamic US can be used to confirm the diagnosis of midcarpal instability by identifying a triquetral catch-up clunk. Quantification of carpal mobility with US may lead to further insights into the mechanics of MCI.

Screening for Homelessness in the Veterans Health Administration: Monitoring Housing Stability through Repeat Screening.

PubMed

Byrne, Thomas; Fargo, Jamison D; Montgomery, Ann Elizabeth; Roberts, Christopher B; Culhane, Dennis P; Kane, Vincent

2015-01-01

This study examined veterans' responses to the Veterans Health Administration's (VHA's) universal screen for homelessness and risk of homelessness during the first 12 months of implementation. We calculated the baseline annual frequency of homelessness and risk of homelessness among all veterans who completed an initial screen during the study period. We measured changes in housing status among veterans who initially screened positive and then completed a follow-up screen, assessed factors associated with such changes, and identified distinct risk profiles of veterans who completed a follow-up screen. More than 4 million veterans completed an initial screen; 1.8% (n=77,621) screened positive for homelessness or risk of homelessness. Of those who initially screened positive for either homelessness or risk of homelessness and who completed a second screen during the study period, 85.0% (n=15,060) resolved their housing instability prior to their second screen. Age, sex, race, VHA eligibility, and screening location were all associated with changes in housing stability. We identified four distinct risk profiles for veterans with ongoing housing instability. To address homelessness among veterans, efforts should include increased and targeted engagement of veterans experiencing persistent housing instability.

Excitonic gap formation in pumped Dirac materials

NASA Astrophysics Data System (ADS)

Triola, Christopher; Pertsova, Anna; Markiewicz, Robert S.; Balatsky, Alexander V.

2017-05-01

Recent pump-probe experiments demonstrate the possibility that Dirac materials may be driven into transient excited states describable by two chemical potentials, one for the electrons and one for the holes. Given the Dirac nature of the spectrum, such an inverted population allows the optical tunability of the density of states of the electrons and holes, effectively offering control of the strength of the Coulomb interaction. Here we discuss the feasibility of realizing transient excitonic instabilities in optically pumped Dirac materials. We demonstrate, theoretically, the reduction of the critical coupling leading to the formation of a transient condensate of electron-hole pairs and identify signatures of this state. Furthermore, we provide guidelines for experiments by both identifying the regimes in which such exotic many-body states are more likely to be observed and estimating the magnitude of the excitonic gap for a few important examples of existing Dirac materials. We find a set of material parameters for which our theory predicts large gaps and high critical temperatures and which could be realized in future Dirac materials. We also comment on transient excitonic instabilities in three-dimensional Dirac and Weyl semimetals. This study provides an example of a transient collective instability in driven Dirac materials.

Analysis of Pull-In Instability of Geometrically Nonlinear Microbeam Using Radial Basis Artificial Neural Network Based on Couple Stress Theory

PubMed Central

Heidari, Mohammad; Heidari, Ali; Homaei, Hadi

2014-01-01

The static pull-in instability of beam-type microelectromechanical systems (MEMS) is theoretically investigated. Two engineering cases including cantilever and double cantilever microbeam are considered. Considering the midplane stretching as the source of the nonlinearity in the beam behavior, a nonlinear size-dependent Euler-Bernoulli beam model is used based on a modified couple stress theory, capable of capturing the size effect. By selecting a range of geometric parameters such as beam lengths, width, thickness, gaps, and size effect, we identify the static pull-in instability voltage. A MAPLE package is employed to solve the nonlinear differential governing equations to obtain the static pull-in instability voltage of microbeams. Radial basis function artificial neural network with two functions has been used for modeling the static pull-in instability of microcantilever beam. The network has four inputs of length, width, gap, and the ratio of height to scale parameter of beam as the independent process variables, and the output is static pull-in voltage of microbeam. Numerical data, employed for training the network, and capabilities of the model have been verified in predicting the pull-in instability behavior. The output obtained from neural network model is compared with numerical results, and the amount of relative error has been calculated. Based on this verification error, it is shown that the radial basis function of neural network has the average error of 4.55% in predicting pull-in voltage of cantilever microbeam. Further analysis of pull-in instability of beam under different input conditions has been investigated and comparison results of modeling with numerical considerations shows a good agreement, which also proves the feasibility and effectiveness of the adopted approach. The results reveal significant influences of size effect and geometric parameters on the static pull-in instability voltage of MEMS. PMID:24860602

Soliton instabilities and vortex street formation in a polariton quantum fluid.

PubMed

Grosso, G; Nardin, G; Morier-Genoud, F; Léger, Y; Deveaud-Plédran, B

2011-12-09

Exciton polaritons have been shown to be an optimal system in order to investigate the properties of bosonic quantum fluids. We report here on the observation of dark solitons in the wake of engineered circular obstacles and their decay into streets of quantized vortices. Our experiments provide a time-resolved access to the polariton phase and density, which allows for a quantitative study of instabilities of freely evolving polaritons. The decay of solitons is quantified and identified as an effect of disorder-induced transverse perturbations in the dissipative polariton gas.

Collegiate contingencies

PubMed Central

Lamal, P. A.; Rakos, Richard F.; Greenspoon, Joel

2000-01-01

We discuss contemporary trends and developments that affect colleges and universities and describe several central contingencies that have given rise to, maintain, and operate in response to these trends and developments. We identify the differential impacts of these contingencies on faculty, students, and administrators in various types of higher education institutions. These contingencies are sources of conflict between and among these three groups within the academy that, we argue, cause significant instability in contemporary academe. We discuss prominent domains of this dis-equilibrium and propose several general interventions to address the sources of the instability. PMID:22478348

Many-body instabilities and mass generation in slow Dirac materials

NASA Astrophysics Data System (ADS)

Triola, Christopher; Zhu, Jian-Xin; Migliori, Albert; Balatsky, Alexander V.

2015-07-01

Some Kondo insulators are expected to possess topologically protected surface states with linear Dirac spectrum: the topological Kondo insulators. Because the bulk states of these systems typically have heavy effective electron masses, the surface states may exhibit extraordinarily small Fermi velocities that could force the effective fine structure constant of the surface states into the strong coupling regime. Using a tight-binding model, we study the many-body instabilities of these systems and identify regions of parameter space in which the system exhibits spin density wave and charge density wave order.

Analysis and control of hourglass instabilities in underintegrated linear and nonlinear elasticity

NASA Technical Reports Server (NTRS)

Jacquotte, Olivier P.; Oden, J. Tinsley

1994-01-01

Methods are described to identify and correct a bad finite element approximation of the governing operator obtained when under-integration is used in numerical code for several model problems: the Poisson problem, the linear elasticity problem, and for problems in the nonlinear theory of elasticity. For each of these problems, the reason for the occurrence of instabilities is given, a way to control or eliminate them is presented, and theorems of existence, uniqueness, and convergence for the given methods are established. Finally, numerical results are included which illustrate the theory.

Long-wave theory for a new convective instability with exponential growth normal to the wall.

PubMed

Healey, J J

2005-05-15

A linear stability theory is presented for the boundary-layer flow produced by an infinite disc rotating at constant angular velocity in otherwise undisturbed fluid. The theory is developed in the limit of long waves and when the effects of viscosity on the waves can be neglected. This is the parameter regime recently identified by the author in a numerical stability investigation where a curious new type of instability was found in which disturbances propagate and grow exponentially in the direction normal to the disc, (i.e. the growth takes place in a region of zero mean shear). The theory describes the mechanisms controlling the instability, the role and location of critical points, and presents a saddle-point analysis describing the large-time evolution of a wave packet in frames of reference moving normal to the disc. The theory also shows that the previously obtained numerical solutions for numerically large wavelengths do indeed lie in the asymptotic long-wave regime, and so the behaviour and mechanisms described here may apply to a number of cross-flow instability problems.

Aeroservoelastic Stability Analysis of the X-43A Stack

NASA Technical Reports Server (NTRS)

Pak, Chan-gi

2008-01-01

The first air launch attempt of an X-43A stack, consisting of the booster, adapter and Hyper-X research vehicle, ended in failure shortly after the successful drop from the National Aeronautics and Space Administration Dryden Flight Research Center (Edwards, California) B-52B airplane and ignition of the booster. The stack was observed to begin rolling and yawing violently upon reaching transonic speeds, and the grossly oscillating fins of the booster separated shortly thereafter. The flight then had to be terminated with the stack out of control. Very careful linear flutter and aeroservoelastic analyses were subsequently performed as reported herein to numerically duplicate the observed instability. These analyses properly identified the instability mechanism and demonstrated the importance of including the flight control laws, rigid-body modes, structural flexible modes and control surface flexible modes. In spite of these efforts, however, the predicted instability speed remained more than 25 percent higher than that observed in flight. It is concluded that transonic shock phenomena, which linear analyses cannot take into account, are also important for accurate prediction of this mishap instability.

Wing Wake Vortices and Temporal Vortex Pair Instabilities

NASA Astrophysics Data System (ADS)

Williamson, C. H. K.; Leweke, T.; Miller, G. D.

In this presentation we include selected results which have originated from vortex dynamics studies conducted at Cornell, in collaboration with IRPHE, Marseille. These studies concern, in particular, the spatial development of delta wing trailing vortices, and the temporal development of counter-rotating vortex pairs. There are, as might be expected, similarities in the instabilities of both of these basic flows, as shown in our laboratory-scale studies. In the case of the spatial development of vortex pairs in the wake of a delta wing, either in free flight or towed from an XY carriage system in a towing tank, we have found three distinct instability length scales as the trailing vortex pair travels downstream. The first (smallest-scale) instability is found immediately behind the delta wing, and this scales on the thickness of the two shear layers separating from the wing trailing edge. The second (short-wave) instability, at an intermediate distance downstream, scales on the primary vortex core dimensions. The third (long-wave) instability far downstream represents the classical "Crow" instability (Crow, 1970), scaling on the distance between the two primary vortices. By imposing disturbances on the delta wing incident velocity, we find that the long-wave instability is receptive to a range of wavelengths. Our experimental measurements of instability growth rates are compared with theoretical predictions, which are based on the theory of Widnall et al. (1971), and which require, as input, DPIV measurements of axial and circumferential velocity profiles. This represents the first time that theoretical and experimental growth rates have been compared, without the imposition of ad-hoc assumptions regarding the vorticity distribution. The agreement with theory appears to be good. The ease with which a Delta wing may be flown in free flight was demonstrated at the Symposium, using a giant polystyrene triangular wing, launched from the back of the auditorium, and ably caught by Professor Sid Leibovich, in whose honour the Symposium was held. In the case of the temporal growth of vortex pairs, formed by the closing of a pair of long flaps underwater, we find two principal instabilities; namely, a longwavelength Crow instability, and a short-wavelength "elliptic" instability. Comparisons between experiment and theory for the growth rates of the long-wave instability, over a range of perturbed wavelengths, appears to be very good. The vortex pair "pinches off", or reconnects, to form vortex rings in the manner assumed to occur in contrails behind jet aircraft. We discover a symmetry-breaking phase relationship for the short wave disturbances growing in the two vortices, which we 380 C.H.K. Williamson et al. show to be consistent with a kinematic matching condition between the two disturbances. Further results demonstrate that this instability is a manifestation of an elliptic instability, which is here identified for the first time in a real open flow. We therefore refer to this flow as a "cooperative elliptic" instability. The long-term evolution of the flow involves the inception of secondary miniscule vortex pairs, which are perpendicular to the primary vortex pair.

Instability and dynamics of volatile thin films

NASA Astrophysics Data System (ADS)

Ji, Hangjie; Witelski, Thomas P.

2018-02-01

Volatile viscous fluids on partially wetting solid substrates can exhibit interesting interfacial instabilities and pattern formation. We study the dynamics of vapor condensation and fluid evaporation governed by a one-sided model in a low-Reynolds-number lubrication approximation incorporating surface tension, intermolecular effects, and evaporative fluxes. Parameter ranges for evaporation-dominated and condensation-dominated regimes and a critical case are identified. Interfacial instabilities driven by the competition between the disjoining pressure and evaporative effects are studied via linear stability analysis. Transient pattern formation in nearly flat evolving films in the critical case is investigated. In the weak evaporation limit unstable modes of finite-amplitude nonuniform steady states lead to rich droplet dynamics, including flattening, symmetry breaking, and droplet merging. Numerical simulations show that long-time behaviors leading to evaporation or condensation are sensitive to transitions between filmwise and dropwise dynamics.

Fault stability under conditions of variable normal stress

USGS Publications Warehouse

Dieterich, J.H.; Linker, M.F.

1992-01-01

The stability of fault slip under conditions of varying normal stress is modelled as a spring and slider system with rate- and state-dependent friction. Coupling of normal stress to shear stress is achieved by inclining the spring at an angle, ??, to the sliding surface. Linear analysis yields two conditions for unstable slip. The first, of a type previously identified for constant normal stress systems, results in instability if stiffness is below a critical value. Critical stiffness depends on normal stress, constitutive parameters, characteristic sliding distance and the spring angle. Instability of the first type is possible only for velocity-weakening friction. The second condition yields instability if spring angle ?? <-cot-1??ss, where ??ss is steady-state sliding friction. The second condition can arise under conditions of velocity strengthening or weakening. Stability fields for finite perturbations are investigated by numerical simulation. -Authors

Degenerate higher derivative theories beyond Horndeski: evading the Ostrogradski instability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Langlois, David; Noui, Karim, E-mail: langlois@apc.univ-paris7.fr, E-mail: karim.noui@lmpt.univ-tours.fr

2016-02-01

Theories with higher order time derivatives generically suffer from ghost-like instabilities, known as Ostrogradski instabilities. This fate can be avoided by considering ''degenerate'' Lagrangians, whose kinetic matrix cannot be inverted, thus leading to constraints between canonical variables and a reduced number of physical degrees of freedom. In this work, we derive in a systematic way the degeneracy conditions for scalar-tensor theories that depend quadratically on second order derivatives of a scalar field. We thus obtain a classification of all degenerate theories within this class of scalar-tensor theories. The quartic Horndeski Lagrangian and its extension beyond Horndeski belong to these degeneratemore » cases. We also identify new families of scalar-tensor theories with the property that they are degenerate despite the nondegeneracy of the purely scalar part of their Lagrangian.« less

Nonlinear modulation near the Lighthill instability threshold in 2+1 Whitham theory

NASA Astrophysics Data System (ADS)

Bridges, Thomas J.; Ratliff, Daniel J.

2018-04-01

The dispersionless Whitham modulation equations in 2+1 (two space dimensions and time) are reviewed and the instabilities identified. The modulation theory is then reformulated, near the Lighthill instability threshold, with a slow phase, moving frame and different scalings. The resulting nonlinear phase modulation equation near the Lighthill surfaces is a geometric form of the 2+1 two-way Boussinesq equation. This equation is universal in the same sense as Whitham theory. Moreover, it is dispersive, and it has a wide range of interesting multi-periodic, quasi-periodic and multi-pulse localized solutions. For illustration the theory is applied to a complex nonlinear 2+1 Klein-Gordon equation which has two Lighthill surfaces in the manifold of periodic travelling waves. This article is part of the theme issue `Stability of nonlinear waves and patterns and related topics'.

A predictive model to allocate frequent service users of community-based mental health services to different packages of care.

PubMed

Grigoletti, Laura; Amaddeo, Francesco; Grassi, Aldrigo; Boldrini, Massimo; Chiappelli, Marco; Percudani, Mauro; Catapano, Francesco; Fiorillo, Andrea; Perris, Francesco; Bacigalupi, Maurizio; Albanese, Paolo; Simonetti, Simona; De Agostini, Paola; Tansella, Michele

2010-01-01

To develop predictive models to allocate patients into frequent and low service users groups within the Italian Community-based Mental Health Services (CMHSs). To allocate frequent users to different packages of care, identifying the costs of these packages. Socio-demographic and clinical data and GAF scores at baseline were collected for 1250 users attending five CMHSs. All psychiatric contacts made by these patients during six months were recorded. A logistic regression identified frequent service users predictive variables. Multinomial logistic regression identified variables able to predict the most appropriate package of care. A cost function was utilised to estimate costs. Frequent service users were 49%, using nearly 90% of all contacts. The model classified correctly 80% of users in the frequent and low users groups. Three packages of care were identified: Basic Community Treatment (4,133 Euro per six months); Intensive Community Treatment (6,180 Euro) and Rehabilitative Community Treatment (11,984 Euro) for 83%, 6% and 11% of frequent service users respectively. The model was found to be accurate for 85% of users. It is possible to develop predictive models to identify frequent service users and to assign them to pre-defined packages of care, and to use these models to inform the funding of psychiatric care.

The Shoulder Instability-Return to Sport after Injury (SIRSI): a valid and reproducible scale to quantify psychological readiness to return to sport after traumatic shoulder instability.

PubMed

Gerometta, Antoine; Klouche, Shahnaz; Herman, Serge; Lefevre, Nicolas; Bohu, Yoann

2018-01-01

The main goal of this study was to propose and validate a tool to quantify the psychological readiness of athletes to return to sport following traumatic shoulder instability and conservative or surgical management. «Knee» was replaced by the term «shoulder» in the Anterior Cruciate Ligament-Return to Sport after Injury scale. This pilot test of the Shoulder Instability-Return to Sport after Injury scale (SIRSI) was performed in a group of athletes who underwent surgery for post-traumatic chronic anterior shoulder instability. The final version was then validated according to the international COSMIN methodology. A retrospective study was performed including all rugby players who had reported an episode of instability between 2012 and 2013. The WOSI and the Walch-Duplay scales were used as reference questionnaires. Sixty-two patients were included, mean age 26 ± 5.2 years old, 5 women/57 men. Patients were professional or competitive athletes (70.9%) and followed-up for 4.6 ± 1.6 years after the first episode of shoulder instability. Shoulder surgery was performed in 30/62 (48.4%) patients, a mean 1.6 ± 1.2 years after the first episode of instability. The SIRSI was strongly correlated with the reference questionnaires (r = 0.80, p < 10 -5 ). The mean SIRSI score was significantly higher in patients who returned to play rugby (60.9 ± 26.6% vs 38.1 ± 25.6%, p = 0.001). The internal consistency of the scale was high (α = 0.96). Reproducibility of the test-retest was excellent (ρ = 0.93, 95% CI [0.89-0.96], p < 10 -5 ). No ceiling/floor effects were found. The SIRSI is a valid, reproducible scale that identifies patients who are ready to return to the same sport after an episode of shoulder instability, whether they undergo surgery or not. III.

Paths and wakes of deformable nearly spheroidal rising bubbles close to the transition to path instability

NASA Astrophysics Data System (ADS)

Cano-Lozano, José Carlos; Martínez-Bazán, Carlos; Magnaudet, Jacques; Tchoufag, Joël

2016-09-01

We report on a series of results provided by three-dimensional numerical simulations of nearly spheroidal bubbles freely rising and deforming in a still liquid in the regime close to the transition to path instability. These results improve upon those of recent computational studies [Cano-Lozano et al., Int. J. Multiphase Flow 51, 11 (2013), 10.1016/j.ijmultiphaseflow.2012.11.005; Phys. Fluids 28, 014102 (2016), 10.1063/1.4939703] in which the neutral curve associated with this transition was obtained by considering realistic but frozen bubble shapes. Depending on the dimensionless parameters that characterize the system, various paths geometries are observed by letting an initially spherical bubble starting from rest rise under the effect of buoyancy and adjust its shape to the surrounding flow. These include the well-documented rectilinear axisymmetric, planar zigzagging, and spiraling (or helical) regimes. A flattened spiraling regime that most often eventually turns into either a planar zigzagging or a helical regime is also frequently observed. Finally, a chaotic regime in which the bubble experiences small horizontal displacements (typically one order of magnitude smaller than in the other regimes) is found to take place in a region of the parameter space where no standing eddy exists at the back of the bubble. The discovery of this regime provides evidence that path instability does not always result from a wake instability as previously believed. In each regime, we examine the characteristics of the path, bubble shape, and vortical structure in the wake, as well as their couplings. In particular, we observe that, depending on the fluctuations of the rise velocity, two different vortex shedding modes exist in the zigzagging regime, confirming earlier findings with falling spheres. The simulations also reveal that significant bubble deformations may take place along zigzagging or spiraling paths and that, under certain circumstances, they dramatically alter the wake structure. The instability thresholds that can be inferred from the computations compare favorably with experimental data provided by various sets of recent experiments guaranteeing that the bubble surface is free of surfactants.

Transition on Hypersonic Vehicles with Crossflow

DTIC Science & Technology

2017-11-01

for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing...modes, attachment-line and centerline traveling instabilities were identified. These transition mechanisms were identified by their peculiar transition...58 5.2.2. Effect of Stationary Crossflow on Traveling Vortices ........................................... 64 5.3. Angle of Attack

Emotional hyper-reactivity and cardiometabolic risk in remitted bipolar patients: a machine learning approach.

PubMed

Dargél, A A; Roussel, F; Volant, S; Etain, B; Grant, R; Azorin, J-M; M'Bailara, K; Bellivier, F; Bougerol, T; Kahn, J-P; Roux, P; Aubin, V; Courtet, P; Leboyer, M; Kapczinski, F; Henry, C

2018-05-15

Remitted bipolar disorder (BD) patients frequently present with chronic mood instability and emotional hyper-reactivity, associated with poor psychosocial functioning and low-grade inflammation. We investigated emotional hyper-reactivity as a dimension for characterization of remitted BD patients, and clinical and biological factors for identifying those with and without emotional hyper-reactivity. A total of 635 adult remitted BD patients, evaluated in the French Network of Bipolar Expert Centers from 2010-2015, were assessed for emotional reactivity using the Multidimensional Assessment of Thymic States. Machine learning algorithms were used on clinical and biological variables to enhance characterization of patients. After adjustment, patients with emotional hyper-reactivity (n = 306) had significantly higher levels of systolic and diastolic blood pressure (P < 1.0 × 10 -8 ), high-sensitivity C-reactive protein (P < 1.0 × 10 -8 ), fasting glucose (P < 2.23 × 10 -6 ), glycated hemoglobin (P = 0.0008) and suicide attempts (P = 1.4 × 10 -8 ). Using models of combined clinical and biological factors for distinguishing BD patients with and without emotional hyper-reactivity, the strongest predictors were: systolic and diastolic blood pressure, fasting glucose, C-reactive protein and number of suicide attempts. This predictive model identified patients with emotional hyper-reactivity with 84.9% accuracy. The assessment of emotional hyper-reactivity in remitted BD patients is clinically relevant, particularly for identifying those at higher risk of cardiometabolic dysfunction, chronic inflammation, and suicide. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High-frequency electrostatic waves in the magnetosphere.

NASA Technical Reports Server (NTRS)

Young, T. S. T.

1973-01-01

High-frequency electrostatic microinstabilities in magnetospheric plasmas are considered in detail. Rather special plasma parameters are found to be required to match the theoretical wave spectrum with satellite observations in the magnetosphere. In particular, it is necessary to have a cold and a warm species of electrons such that (1) the warm component has an anomalous velocity distribution function that is nonmonotonic in the perpendicular component of velocity and is the source of free energy driving the instabilities, (2) the density ratio of the cold component to the hot component is greater than about 0.01, and (3) the temperature ratio of the two components for cases of high particle density is no less than 0.1. These requirements and the corresponding instability criteria are satisfied only in the trapping region; this is also the region in which the waves are most frequently observed. The range of unstable wavelengths and an estimate of the diffusion coefficient are also obtained. The wave are found to induce strong diffusion in velocity space for low-energy electrons during periods of moderate wave amplitude.

Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis.

PubMed

Wassef, Michel; Rodilla, Veronica; Teissandier, Aurélie; Zeitouni, Bruno; Gruel, Nadege; Sadacca, Benjamin; Irondelle, Marie; Charruel, Margaux; Ducos, Bertrand; Michaud, Audrey; Caron, Matthieu; Marangoni, Elisabetta; Chavrier, Philippe; Le Tourneau, Christophe; Kamal, Maud; Pasmant, Eric; Vidaud, Michel; Servant, Nicolas; Reyal, Fabien; Meseure, Dider; Vincent-Salomon, Anne; Fre, Silvia; Margueron, Raphaël

2015-12-15

Alterations of chromatin modifiers are frequent in cancer, but their functional consequences often remain unclear. Focusing on the Polycomb protein EZH2 that deposits the H3K27me3 (trimethylation of Lys27 of histone H3) mark, we showed that its high expression in solid tumors is a consequence, not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis. High EZH2 expression in tumors results from a tight coupling to proliferation to ensure H3K27me3 homeostasis. However, this process malfunctions in breast cancer. Low EZH2 expression relative to proliferation and mutations in Polycomb genes actually indicate poor prognosis and occur in metastases. We show that while altered EZH2 activity consistently modulates a subset of its target genes, it promotes a wider transcriptional instability. Importantly, transcriptional changes that are consequences of EZH2 loss are predominantly irreversible. Our study provides an unexpected understanding of EZH2's contribution to solid tumors with important therapeutic implications. © 2015 Wassef et al.; Published by Cold Spring Harbor Laboratory Press.

Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis

PubMed Central

Wassef, Michel; Rodilla, Veronica; Teissandier, Aurélie; Zeitouni, Bruno; Gruel, Nadege; Sadacca, Benjamin; Irondelle, Marie; Charruel, Margaux; Ducos, Bertrand; Michaud, Audrey; Caron, Matthieu; Marangoni, Elisabetta; Chavrier, Philippe; Le Tourneau, Christophe; Kamal, Maud; Pasmant, Eric; Vidaud, Michel; Servant, Nicolas; Reyal, Fabien; Meseure, Dider; Vincent-Salomon, Anne; Fre, Silvia; Margueron, Raphaël

2015-01-01

Alterations of chromatin modifiers are frequent in cancer, but their functional consequences often remain unclear. Focusing on the Polycomb protein EZH2 that deposits the H3K27me3 (trimethylation of Lys27 of histone H3) mark, we showed that its high expression in solid tumors is a consequence, not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis. High EZH2 expression in tumors results from a tight coupling to proliferation to ensure H3K27me3 homeostasis. However, this process malfunctions in breast cancer. Low EZH2 expression relative to proliferation and mutations in Polycomb genes actually indicate poor prognosis and occur in metastases. We show that while altered EZH2 activity consistently modulates a subset of its target genes, it promotes a wider transcriptional instability. Importantly, transcriptional changes that are consequences of EZH2 loss are predominantly irreversible. Our study provides an unexpected understanding of EZH2's contribution to solid tumors with important therapeutic implications. PMID:26637281

Mechanisms of arrhythmogenesis related to calcium-driven alternans in a model of human atrial fibrillation

NASA Astrophysics Data System (ADS)

Chang, Kelly C.; Trayanova, Natalia A.

2016-11-01

The occurrence of atrial fibrillation (AF) is associated with progressive changes in the calcium handling system of atrial myocytes. Calcium cycling instability has been implicated as an underlying mechanism of electrical alternans observed in patients who experience AF. However, the extent to which calcium-induced alternation of electrical activity in the atria contributes to arrhythmogenesis is unknown. In this study, we investigated the effects of calcium-driven alternans (CDA) on arrhythmia susceptibility in a biophysically detailed, 3D computer model of the human atria representing electrical and structural remodeling secondary to chronic AF. We found that elevated propensity to CDA rendered the atria vulnerable to ectopy-induced arrhythmia. It also increased the complexity and persistence of arrhythmias induced by fast pacing, with unstable scroll waves meandering and frequently breaking up to produce multiple wavelets. Our results suggest that calcium-induced electrical instability may increase arrhythmia vulnerability and promote increasing disorganization of arrhythmias in the chronic AF-remodeled atria, thus playing an important role in the progression of the disease.

Stream stability at highway structures.

DOT National Transportation Integrated Search

1995-11-01

This document provides guidelines for identifying stream instability problems at highway stream crossings and for the selection and design of appropriate countermeasures to mitigate potential damages to bridges and other highway components at stream ...

Serrated Colon Polyps as Precursors to Colorectal Cancer

PubMed Central

Sweetser, Seth; Smyrk, Thomas C.; Sinicrope, Frank A.

2013-01-01

Identification of the serrated neoplasia pathway has improved our understanding of the pathogenesis of colorectal cancer (CRC). Insights have included an increased recognition of the malignant potential of different types of serrated polyps, such as sessile and traditional serrated adenomas. Sessile serrated adenomas share molecular features with colon tumors, such as microsatellite instability and a methylator phenotype, indicating that these lesions are precursors that progress via the serrated neoplasia pathway. There is evidence that the serrated pathway contributes to interval or missed cancers. These data have important implications for clinical practice and CRC prevention, since hyperplastic polyps were previously regarded as having no malignant potential. Endoscopic detection of serrated polyps is a challenge because they are often inconspicuous with indistinct margins, and are frequently covered by adherent mucus. It is important for gastroenterologists to recognize the subtle endoscopic features of serrated polyps, which would facilitate their detection and removal, to ensure a high-quality colonoscopy examination. Recognition of the role of serrated polyps in colon carcinogenesis has led to the inclusion of these lesions in post-polypectomy surveillance guidelines. However, an enhanced effort is needed to identify and completely remove serrated adenomas, with the goal of increasing the effectiveness of colonoscopy to reduce CRC incidence. PMID:23267866

New target genes in endometrial tumors show a role for the estrogen-receptor pathway in microsatellite-unstable cancers.

PubMed

Ferreira, Ana M; Tuominen, Iina; Sousa, Sónia; Gerbens, Frans; van Dijk-Bos, Krista; Osinga, Jan; Kooi, Krista A; Sanjabi, Bahram; Esendam, Chris; Oliveira, Carla; Terpstra, Peter; Hardonk, Menno; van der Sluis, Tineke; Zazula, Monika; Stachura, Jerzy; van der Zee, Ate G; Hollema, Harry; Sijmons, Rolf H; Aaltonen, Lauri A; Seruca, Raquel; Hofstra, Robert M W; Westers, Helga

2014-12-01

Microsatellite instability (MSI) in tumors results in an accumulation of mutations in (target) genes. Previous studies suggest that the profile of target genes differs according to tumor type. This paper describes the first genome-wide search for target genes for mismatch repair-deficient endometrial cancers. Genes expressed in normal endometrium containing coding repeats were analyzed for mutations in tumors. We identified 44 possible genes of which seven are highly mutated (>15%). Some candidates were also found mutated in colorectal and gastric tumors. The most frequently mutated gene, NRIP1 encoding nuclear receptor-interacting protein 1, was silenced in an endometrial tumor cell line and expression microarray experiments were performed. Silencing of NRIP1 was associated with differences in the expression of several genes in the estrogen-receptor network. Furthermore, an enrichment of genes related to cell cycle (regulation) and replication was observed. We present a new profile of target genes, some of them tissue specific, whereas others seem to play a more general role in MSI tumors. The high-mutation frequency combined with the expression data suggest, for the first time, an involvement of NRIP1 in endometrial cancer development. © 2014 WILEY PERIODICALS, INC.

Fra-1 promotes growth and survival in RAS-transformed thyroid cells by controlling cyclin A transcription

PubMed Central

Casalino, Laura; Bakiri, Latifa; Talotta, Francesco; Weitzman, Jonathan B; Fusco, Alfredo; Yaniv, Moshe; Verde, Pasquale

2007-01-01

Fra-1 is frequently overexpressed in epithelial cancers and implicated in invasiveness. We previously showed that Fra-1 plays crucial roles in RAS transformation in rat thyroid cells and mouse fibroblasts. Here, we report a novel role for Fra-1 as a regulator of mitotic progression in RAS-transformed thyroid cells. Fra-1 expression and phosphorylation are regulated during the cell cycle, peaking at G2/M. Knockdown of Fra-1 caused a proliferative block and apoptosis. Although most Fra-1-knockdown cells accumulated in G2, a fraction of cells entering M-phase underwent abortive cell division and exhibited hallmarks of genomic instability (micronuclei, lagging chromosomes and anaphase bridges). Furthermore, we established a link between Fra-1 and the cell-cycle machinery by identifying cyclin A as a novel transcriptional target of Fra-1. During the cell cycle, Fra-1 was recruited to the cyclin A gene (ccna2) promoter, binding to previously unidentified AP-1 sites and the CRE. Fra-1 also induced the expression of JunB, which in turn interacts with the cyclin A promoter. Hence, Fra-1 induction is important in thyroid tumorigenesis, critically regulating cyclin expression and cell-cycle progression. PMID:17347653

Molecular changes in thyroid neoplasia.

PubMed

Jarzab, B; Włoch, J; Wiench, M

2001-01-01

All authors integrating the known facts into a model of thyroid carcinogenesis concur that two main histotypes of thyroid cancer exhibit different routes of molecular development. RET rearrangements are an initiating event in papillary carcinoma, and simultaneously the most characteristic mutation for this type of cancer. They are followed by further, not well recognized, mutations. RAS mutations are regarded as a crucial event in the development of follicular tumors already at the adenoma step, while in papillary cancer they belong to the spectrum of secondary mutations, enabling tumor progression. Aberrant DNA methylation, causing loss of P16 tumor supressor gene, may be a common event in both types of cancer. Aneuploidy is seen much more frequently in follicular than in papillary cancer, which also exhibits a low rate for loss of heterozygosity and microsatellite instability. Mutations of the P53 tumor supressor gene are a common feature of undifferentiated thyroid cancers and could be responsible for their aggressive phenotype. RET rearrangements have been proposed as identifying fingerprints for irradiation induced thyroid cancer in children. Our own data speak against this hypothesis. We noted a high frequency of RET/PTC3 mutations in a group of Polish children with papillary thyroid carcinoma, regarded as sporadic cancer.

The use of ultrasound in the assessment of the glenoid labrum of the glenohumeral joint. Part II: Examples of labral pathologies

PubMed Central

Tarczyńska, Marta

2012-01-01

Labral pathologies of the glenohumeral joint are most commonly caused by trauma. The majority of lesions affect the anterior part of labrum, resulting from much higher frequency of anterior shoulder dislocations over posterior ones. Another subgroup of labral lesions, not directly related to joint instability, are SLAP tears. Other findings include degenerative changes of labrum and paralabral cysts. Diagnostic imaging is crucial for making a decision regarding operative treatment. Apart from a standard X-ray examination, the imaging mainly relies on magnetic resonance or computed tomography arthrography. Based on their own experience, the authors propose the use of ultrasound in the assessment of labral tears of the glenohumeral joint. Different signs indicating labral pathology may be discovered and assessed during ultrasound examination. They include permanent displacement of the labrum onto the glenoid, labral instability during dynamic examination, lack of the labrum in the anatomical position, hypoechoic zone at the base of the labrum >2 mm in width, residual or swollen labrum as well as paralabral cyst(s). The most frequent appearance of labral pathology is displacement of the anteroinferior labrum onto the external aspect of the glenoid typically seen after anterior shoulder dislocation. The another most important US feature is labral instability while dynamically examined. The swelling or reduced size of the labrum usually indicates degeneration. This article presents sonographic images of selected labral pathologies. PMID:26672471

The Relationship between the (In-)Stability of NORs and Their Chromosomal Location: The Example of Cercopithecidae and a Short Review of Other Primates.

PubMed

Gerbault-Seureau, Michèle; Cacheux, Lauriane; Dutrillaux, Bernard

2017-01-01

Amongst Cercopithecidae, the species of the Cercopithecini tribe underwent a very active chromosome evolution, principally by fissions, which increased their chromosome number up to 72. In contrast, all the species of Papionini have fairly similar karyotypes with 42 chromosomes. In animals, nucleolus organizer regions (NORs) are generally considered as instable structures, which frequently vary in size, number, and location at both infra- and interspecific levels. Although in Cercopithecinae the NORs, involved in breaks, exchanges, and translocations, behave like fragile sites in somatic cells, their number and location appear to be very stable between species. Fluorescence in situ hybridization of a 28S rDNA probe on metaphase chromosomes displayed a unique interstitial location in either an acrocentric pair (in 12 species of Cercopithecini) or a metacentric pair (in 6 species of Papionini). A non-exhaustive survey of literature data on NOR location in other primates shows that numerical variations of the NORs principally depend on their location: most multiple NORs are in terminal positions, while almost all unique NORs are in interstitial positions. We propose that this correlation is the consequence of the selection against gametic imbalances involving the chromosomal material distal to the NORs, which is effective when they are interstitially, but not terminally, located. Thus, the consequences of the interstitial NOR instability for reproduction are essentially limited to their size variations, as observed in Cercopithecidae. © 2018 S. Karger AG, Basel.

Effects of camptothecin or TOP1 overexpression on genetic stability in Saccharomyces cerevisiae.

PubMed

Sloan, Roketa; Huang, Shar-Yin Naomi; Pommier, Yves; Jinks-Robertson, Sue

2017-11-01

Topoisomerase I (Top1) removes DNA torsional stress by nicking and resealing one strand of DNA, and is essential in higher eukaryotes. The enzyme is frequently overproduced in tumors and is the sole target of the chemotherapeutic drug camptothecin (CPT) and its clinical derivatives. CPT stabilizes the covalent Top1-DNA cleavage intermediate, which leads to toxic double-strand breaks (DSBs) when encountered by a replication fork. In the current study, we examined genetic instability associated with CPT treatment or with Top1 overexpression in the yeast Saccharomyces cerevisiae. Two types of instability were monitored: Top1-dependent deletions in haploid strains, which do not require processing into a DSB, and instability at the repetitive ribosomal DNA (rDNA) locus in diploid strains, which reflects DSB formation. Three 2-bp deletion hotspots were examined and mutations at each were elevated either when a wild-type strain was treated with CPT or when TOP1 was overexpressed, with the mutation frequency correlating with the level of TOP1 overexpression. Under both conditions, deletions at novel positions were enriched. rDNA stability was examined by measuring loss-of-heterozygosity and as was observed previously upon CPT treatment of a wild-type strain, Top1 overexpression destabilized rDNA. We conclude that too much, as well as too little of Top1 is detrimental to eukaryotic genomes, and that CPT has destabilizing effects that extend beyond those associated with DSB formation. Copyright © 2017 Elsevier B.V. All rights reserved.

A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers

PubMed Central

Putnam, Christopher D.; Srivatsan, Anjana; Nene, Rahul V.; Martinez, Sandra L.; Clotfelter, Sarah P.; Bell, Sara N.; Somach, Steven B.; E.S. de Souza, Jorge; Fonseca, André F.; de Souza, Sandro J.; Kolodner, Richard D.

2016-01-01

Gross chromosomal rearrangements (GCRs) play an important role in human diseases, including cancer. The identity of all Genome Instability Suppressing (GIS) genes is not currently known. Here multiple Saccharomyces cerevisiae GCR assays and query mutations were crossed into arrays of mutants to identify progeny with increased GCR rates. One hundred eighty two GIS genes were identified that suppressed GCR formation. Another 438 cooperatively acting GIS genes were identified that were not GIS genes, but suppressed the increased genome instability caused by individual query mutations. Analysis of TCGA data using the human genes predicted to act in GIS pathways revealed that a minimum of 93% of ovarian and 66% of colorectal cancer cases had defects affecting one or more predicted GIS gene. These defects included loss-of-function mutations, copy-number changes associated with reduced expression, and silencing. In contrast, acute myeloid leukaemia cases did not appear to have defects affecting the predicted GIS genes. PMID:27071721

Risk factors for acute kidney injury after partial hepatectomy

PubMed Central

Bredt, Luis Cesar; Peres, Luis Alberto Batista

2017-01-01

AIM To identify risk factors for the occurrence of acute kidney injury (AKI) in the postoperative period of partial hepatectomies. METHODS Retrospective analysis of 446 consecutive resections in 405 patients, analyzing clinical characteristics, preoperative laboratory data, intraoperative data, and postoperative laboratory data and clinical evolution. Adopting the International Club of Ascites criteria for the definition of AKI, potential predictors of AKI by logistic regression were identified. RESULTS Of the total 446 partial liver resections, postoperative AKI occurred in 80 cases (17.9%). Identified predictors of AKI were: Non-dialytic chronic kidney injury (CKI), biliary obstruction, the Model for End-Stage Liver Disease (MELD) score, the extent of hepatic resection, the occurrence of intraoperative hemodynamic instability, post-hepatectomy haemorrhage, and postoperative sepsis. CONCLUSION The MELD score, the presence of non-dialytic CKI and biliary obstruction in the preoperative period, and perioperative hemodynamics instability, bleeding, and sepsis are risk factors for the occurrence of AKI in patients that underwent partial hepatectomy. PMID:28706580

Advice for Travellers to Tropical and Subtropical Countries

PubMed Central

Lawee, David; Scapattura, Philip

1985-01-01

Travellers to areas where political instability, poverty or inadequate public health measures render them at risk of exposure to infections and diseases they are unlikely to meet at home should seek prophylaxis and protection before departure. Inoculation is the best form of protection for certain diseases; since protocols change frequently, a reliable local source of current information should be found. Prophylaxis against malaria involves both mechanical protection against mosquito bites, and appropriate chemoprophylaxis. Water safety must be considered where chlorinated water is not available; a protocol for decontamination is presented, and guidelines for avoiding gastrointestinal disorders are listed. PMID:21274125

Studies of longitudinal instability with an electron beam

NASA Astrophysics Data System (ADS)

This progress report covers the research on the 'Study of Longitudinal Instability with an Electron Beam' performed at the University of Maryland during the period from September 1, 1993 to February 28, 1994 of the two-year grant sponsored by the Department of Energy, under Grant No. DEFG02-92ER54178. This research is motivated by the issue of longitudinal instability in induction linacs as drivers for heavy ion inertial fusion. The Fusion Policy Advisory Committee (FPAC) in its final report to DOE (September 1990) identified longitudinal instability as a key physics problem that needs to be solved if an induction linac is to be developed into a successful HIF driver. The FPAC report also stated that 'in parallel' to the design and construction of ILSE 'enhanced theoretical and experimental efforts are required for an improved understanding of potentially serious longitudinal beam instability issues'. The experiment with electron beams in this area is a low-cost way to gain a thorough understanding of the instability and to test computer codes in collaboration with LBL, LLNL, and I. Haber at NRL. The last six months saw the transition of the research activities from phase 1 to phase 2. By the end of last September, the experiments on space-charge waves had been completed. This had fulfilled the first year's goal of this two-year grant. Though the completion of the experiments was one month later than that scheduled and the data analysis still continues up to now, the authors have done much more than was originally proposed.

What I always wanted to know about instability training.

PubMed

Fowles, Jonathon R

2010-02-01

A very popular mode of training in recent years has been the use of instability devices and exercises to train the core musculature. Instability training is viewed by many as the most effective way to train the core; however, evidence on this topic paints a slightly different picture. An extensive review of the literature by Behm et al. 2010 (Appl. Physiol. Metab. Nutr. 35(1): 91-108) identified the fact that instability training can increase core muscle activation, but it may not be the best choice in all situations. Unstable training can reduce overall muscular power output, which may have important implications if the goal of a given training program is to maximize the output or physiological stress on a given muscle, as is the case in certain types of athletic training or in certain clinical exercise situations. Nevertheless, the balance of this evidence leads to the recommendations in the position stand (Behm et al. 2010, Appl. Physiol. Metab. Nutr. 35(1): 109-112) that instability training can play an important role as part of an overall periodized program for an athlete, as part of a rehabilitation program in recovery from injury, or as an interesting and novel training mode for the general population in pursuit of musculoskeletal health benefits who may not have access to or want to complete more intensive free-weight training programs. More research is needed to establish the effectiveness of instability training in preventing injury in sports, enhancing on-field sport performance, or for use in various clinical situations outside of rehabilitation for low back pain.

Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair.

PubMed

Risinger, J I; Umar, A; Boyd, J; Berchuck, A; Kunkel, T A; Barrett, J C

1996-09-01

Many human tumours have length alterations in repetitive sequence elements. Although this microsatellite instability has been attributed to mutations in four DNA mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) kindreds, many sporadic tumours exhibit instability but no detectable mutations in these genes. It is therefore of interest to identify other genes that contribute to this instability. In yeast, mutations in several genes, including RTH and MSH3, cause microsatellite instability. Thus, we screened 16 endometrial carcinomas with microsatellite instability for alterations in FEN1 (the human homolog of RTH) and in MSH3 (refs 12-14). Although we found no FEN1 mutations, a frameshift mutation in MSH3 was observed in an endometrial carcinoma and in an endometrial carcinoma cell line. Extracts of the cell line were deficient in repair of DNA substrates containing mismatches or extra nucleotides. Introducing chromosome 5, encoding the MSH3 gene, into the mutant cell line increased the stability of some but not all microsatellites. Extracts of these cells repaired certain substrates containing extra nucleotides, but were deficient in repair of those containing mismatches or other extra nucleotides. A subsequent search revealed a second gene mutation in HHUA cells, a missense mutation in the MSH6 gene. Together the data suggest that the MSH3 gene encodes a product that functions in repair of some but not all pre-mutational intermediates, its mutation in tumours can result in genomic instability and, as in yeast, MSH3 and MSH6 are partially redundant for mismatch repair.

Causes of genome instability: the effect of low dose chemical exposures in modern society.

PubMed

Langie, Sabine A S; Koppen, Gudrun; Desaulniers, Daniel; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Azqueta, Amaya; Bisson, William H; Brown, Dustin G; Brunborg, Gunnar; Charles, Amelia K; Chen, Tao; Colacci, Annamaria; Darroudi, Firouz; Forte, Stefano; Gonzalez, Laetitia; Hamid, Roslida A; Knudsen, Lisbeth E; Leyns, Luc; Lopez de Cerain Salsamendi, Adela; Memeo, Lorenzo; Mondello, Chiara; Mothersill, Carmel; Olsen, Ann-Karin; Pavanello, Sofia; Raju, Jayadev; Rojas, Emilio; Roy, Rabindra; Ryan, Elizabeth P; Ostrosky-Wegman, Patricia; Salem, Hosni K; Scovassi, A Ivana; Singh, Neetu; Vaccari, Monica; Van Schooten, Frederik J; Valverde, Mahara; Woodrick, Jordan; Zhang, Luoping; van Larebeke, Nik; Kirsch-Volders, Micheline; Collins, Andrew R

2015-06-01

Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Identifying Frequent Users of an Urban Emergency Medical Service Using Descriptive Statistics and Regression Analyses.

PubMed

Norman, Chenelle; Mello, Michael; Choi, Bryan

2016-01-01

This retrospective cohort study provides a descriptive analysis of a population that frequently uses an urban emergency medical service (EMS) and identifies factors that contribute to use among all frequent users. For purposes of this study we divided frequent users into the following groups: low- frequent users (4 EMS transports in 2012), medium-frequent users (5 to 6 EMS transports in 2012), high-frequent users (7 to 10 EMS transports in 2012) and super-frequent users (11 or more EMS transports in 2012). Overall, we identified 539 individuals as frequent users. For all groups of EMS frequent users (i.e. low, medium, high and super) one or more hospital admissions, receiving a referral for follow-up care upon discharge, and having no insurance were found to be statistically significant with frequent EMS use (P<0.05). Within the diagnostic categories, 41.61% of super-frequent users had a diagnosis of "primarily substance abuse/misuse" and among low-frequent users a majority, 53.33%, were identified as having a "reoccurring (medical) diagnosis." Lastly, relative risk ratios for the highest group of users, super-frequent users, were 3.34 (95% CI [1.90-5.87]) for obtaining at least one referral for follow-up care, 13.67 (95% CI [5.60-33.34]) for having four or more hospital admissions and 5.95 (95% CI [1.80-19.63]) for having a diagnoses of primarily substance abuse/misuse. Findings from this study demonstrate that among low- and medium-frequent users a majority of patients are using EMS for reoccurring medical conditions. This could potentially be avoided with better care management. In addition, this study adds to the current literature that illustrates a strong correlation between substance abuse/misuse and high/super-frequent EMS use. For the subgroup analysis among individuals 65 years of age and older, we did not find any of the independent variables included in our model to be statistically significant with frequent EMS use.

Destabilization of counter-propagating TAEs by off-axis, co-current Neutral Beam Injection

NASA Astrophysics Data System (ADS)

Podesta', M.; Fredrickson, E.; Gorelenkova, M.

2017-10-01

Neutral Beam injection (NBI) is a common tool to heat the plasma and drive current non-inductively in fusion devices. Energetic particles (EP) resulting from NBI can drive instabilities that are detrimental for the performance and the predictability of plasma discharges. A broad NBI deposition profile, e.g. by off-axis injection aiming near the plasma mid-radius, is often assumed to limit those undesired effects by reducing the radial gradient of the EP density, thus reducing the ``universal'' drive for instabilities. However, this work presents new evidence that off-axis NBI can also lead to undesired effects such as the destabilization of Alfvénic instabilities, as observed in NSTX-U plasmas. Experimental observations indicate that counter propagating toroidal AEs are destabilized as the radial EP density profile becomes hollow as a result of off-axis NBI. Time-dependent analysis with the TRANSP code, augmented by a reduced fast ion transport model (known as kick model), indicates that instabilities are driven by a combination of radial and energy gradients in the EP distribution. Understanding the mechanisms for wave-particle interaction, revealed by the phase space resolved analysis, is the basis to identify strategies to mitigate or suppress the observed instabilities. Work supported by the U.S. Department of Energy, Office of Science, Office of Fusion Energy Sciences under Contract Number DE-AC02-09CH11466.

Novel ZBTB24 Mutation Associated with Immunodeficiency, Centromere Instability, and Facial Anomalies Type-2 Syndrome Identified in a Patient with Very Early Onset Inflammatory Bowel Disease.

PubMed

Conrad, Máire A; Dawany, Noor; Sullivan, Kathleen E; Devoto, Marcella; Kelsen, Judith R

2017-12-01

Very early onset inflammatory bowel disease, diagnosed in children ≤5 years old, can be the initial presentation of some primary immunodeficiencies. In this study, we describe a 17-month-old boy with recurrent infections, growth failure, facial anomalies, and inflammatory bowel disease. Immune evaluation, whole-exome sequencing, karyotyping, and methylation array were performed to evaluate the child's constellation of symptoms and examination findings. Whole-exome sequencing revealed that the child was homozygous for a novel variant in ZBTB24, the gene associated with immunodeficiency, centromere instability, and facial anomalies type-2 syndrome. This describes the first case of inflammatory bowel disease associated with immunodeficiency, centromere instability, and facial anomalies type-2 syndrome in a child with a novel disease-causing mutation in ZBTB24 found on whole-exome sequencing.

Unraveling the mechanisms underlying postural instability in Parkinson's disease using dynamic posturography.

PubMed

Nonnekes, Jorik; de Kam, Digna; Geurts, Alexander C H; Weerdesteyn, Vivian; Bloem, Bastiaan R

2013-12-01

Postural instability, one of the cardinal symptoms of Parkinson's disease (PD), has devastating consequences for affected patients. Better strategies to prevent falls are needed, but this calls for an improved understanding of the complex mechanisms underlying postural instability. We must also improve our ability to timely identify patients at risk of falling. Dynamic posturography is a promising avenue to achieve these goals. The latest moveable platforms can deliver 'real-life' balance perturbations, permitting study of everyday fall circumstances. Dynamic posturography studies have shown that PD patients have fundamental problems in scaling their postural responses in accordance with the need of the actual balance task at hand. On-going studies evaluate the predictive ability of impaired posturography performance for daily life falls. We also review recent work aimed at exploring balance correcting steps in PD, and the presumed interaction between startle pathways and postural responses.

The effectiveness of arthroscopic stabilisation for failed open shoulder instability surgery.

PubMed

Millar, N L; Murrell, G A C

2008-06-01

We identified ten patients who underwent arthroscopic revision of anterior shoulder stabilisation between 1999 and 2005. Their results were compared with 15 patients, matched for age and gender, who had a primary arthroscopic stabilisation during the same period. At a mean follow-up of 37 and 36 months, respectively, the scores for pain and shoulder function improved significantly between the pre-operative and follow-up visits in both groups (p = 0.002), with no significant difference between them (p = 0.4). The UCLA and Rowe shoulder scores improved significantly (p = 0.004 and p = 0.002, respectively), with no statistically significant differences between groups (p = 0.6). Kaplan-Meier analysis for time to recurrent instability showed no differences between the groups (p = 0.2). These results suggest that arthroscopic revision anterior shoulder stabilisation is as reliable as primary arthroscopic stabilisation for patients who have had previous open surgery for recurrent anterior instability.

Neuroendocrine-type prostatic adenocarcinoma with microsatellite instability in a patient with lynch syndrome.

PubMed

Wagner, David G; Gatalica, Zoran; Lynch, Henry T; Kohl, Shane; Johansson, Sonny L; Lele, Subodh M

2010-12-01

Lynch syndrome is an autosomal-dominant cancer syndrome that can be identified with microsatellite instability molecular tests or immunohistochemical stains on pathologic material from patients who meet the Amsterdam Criteria II. The development of prostatic carcinoma in situ or invasive small cell carcinoma (SCC) of the prostate has not been previously reported in a patient with this syndrome. In this report, an 87-year-old White man with the Lynch syndrome had a prostate biopsy that revealed a mixed high-grade conventional adenocarcinoma and SCC of the prostate with high-grade prostatic intraepithelial neoplasia of the small cell neuroendocrine-type (HGPIN-NE), all showing MSH2 microsatellite instability and loss of MSH2 expression, a finding not previously published. These findings suggest that HGPIN-NE is a precursor of invasive SCC and also that prostatic SCC can develop in a patient with the Lynch syndrome.

Caspase 3 promotes genetic instability and carcinogenesis

PubMed Central

Liu, Xinjian; He, Yujun; Li, Fang; Huang, Qian; Kato, Takamitsu A.; Hall, Russell P; Li, Chuan-Yuan

2015-01-01

Summary Apoptosis is typically considered an anti-oncogenic process since caspase activation can promote the elimination of genetically unstable or damaged cells. We report that a central effector of apoptosis, caspase 3, facilitates, rather than suppresses, chemical and radiation-induced genetic instability and carcinogenesis. We found that a significant fraction of mammalian cells treated with ionizing radiation can survive, despite caspase 3 activation. Moreover, this sublethal activation of caspase 3 promoted persistent DNA damage and oncogenic transformation. In addition, chemically-induced skin carcinogenesis was significantly reduced in mice genetically deficient in caspase 3. Furthermore, attenuation of Endo G activity significantly reduced radiation-induced DNA damage and oncogenic transformation, identifying Endo G as a downstream effector of caspase 3 in this pathway. Our findings suggest that rather than acting as a broad inhibitor of carcinogenesis, caspase 3 activation may contribute to genome instability and play a pivotal role in tumor formation following damage. PMID:25866249

A cosmic double helix in the archetypical quasar 3C273.

PubMed

Lobanov, A P; Zensus, J A

2001-10-05

Finding direct evidence for plasma instability in extragalactic jets is crucial for understanding the nature of relativistic outflows from active galactic nuclei. Our radio interferometric observations of the quasar 3C273 made with the orbiting radio telescope, HALCA, and an array of ground telescopes have yielded an image in which the emission across the jet is resolved, revealing two threadlike patterns that form a double helix inside the jet. This double helical structure is consistent with a Kelvin-Helmholtz instability, and at least five different instability modes can be identified and modeled by a light jet with a Lorentz factor of 2 and Mach number of 3.5. The model reproduces in detail the internal structure of the jet on scales of up to 30 milli-arc seconds ( approximately 300 parsecs) and is consistent with the general morphology of the jet on scales of up to 1 kiloparsec.

Reply to comment on: Lawrence, J.A., Mortimore, R.N., Stone, K.J., and Busby, J.P., 2013. Sea saltwater weakening of chalk and the impact on cliff instability. Geomorphology 191, 14-22

NASA Astrophysics Data System (ADS)

Lawrence, James A.; Mortimore, Rory N.

2015-02-01

We are grateful to Dornbusch (2014) for the opportunity to clarify the role we propose for salt water weakening of the chalk and its potential importance as a mechanism contributing to cliff instability. Dornbusch's argument is based largely on a single comment "This work challenges the established view by identifying the role of salt from seawater in the degradation of porous rocks in coastal environments as a third and potentially the most important mechanism leading to chalk cliff collapse" (Lawrence et al., 2013: 15). This was not intended as a "conclusion" as suggested by Dornbusch (2014) but is rather a qualitative introductory statement highlighting the potential importance of the salt water weakening process in coastal cliff instability. The actual conclusions of the work are not challenged by Dornbusch (2014).

Prediction of nonlinear evolution character of energetic-particle-driven instabilities

DOE PAGES

Duarte, Vinicius N.; Berk, H. L.; Gorelenkov, N. N.; ...

2017-03-17

A general criterion is proposed and found to successfully predict the emergence of chirping oscillations of unstable Alfvénic eigenmodes in tokamak plasma experiments. The model includes realistic eigenfunction structure, detailed phase-space dependences of the instability drive, stochastic scattering and the Coulomb drag. The stochastic scattering combines the effects of collisional pitch angle scattering and micro-turbulence spatial diffusion. Furthermore, the latter mechanism is essential to accurately identify the transition between the fixed-frequency mode behavior and rapid chirping in tokamaks and to resolve the disparity with respect to chirping observation in spherical and conventional tokamaks.

Dynamics and Instabilities of the Shastry-Sutherland Model

NASA Astrophysics Data System (ADS)

Wang, Zhentao; Batista, Cristian D.

2018-06-01

We study the excitation spectrum in the dimer phase of the Shastry-Sutherland model by using an unbiased variational method that works in the thermodynamic limit. The method outputs dynamical correlation functions in all possible channels. This output is exploited to identify the order parameters with the highest susceptibility (single or multitriplon condensation in a specific channel) upon approaching a quantum phase transition in the magnetic field versus the J'/J phase diagram. We find four different instabilities: antiferro spin nematic, plaquette spin nematic, stripe magnetic order, and plaquette order, two of which have been reported in previous studies.

PC3 (BTG2/TIS21) possible role in chromosome instability syndromes.

PubMed

Conti, Filippo; Ghigo, Eric

2013-07-01

Chromosome instability syndromes (CIS) are autosomal recessive genetic disorders associated with defects in cell cycle regulation following DNA damage. Although most of the proteins involved in these syndromes have been identified as part of the MRN complex, little is known about their physiological functions and their interactions with other molecules that might explain the wide clinical presentation found in CIS patients. Here we discuss several observations suggesting that PC3 (BTG2/TIS21) - a protein involved in G1-S checkpoint progression control - might play a role in these pathologies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Prediction of nonlinear evolution character of energetic-particle-driven instabilities

NASA Astrophysics Data System (ADS)

Duarte, V. N.; Berk, H. L.; Gorelenkov, N. N.; Heidbrink, W. W.; Kramer, G. J.; Nazikian, R.; Pace, D. C.; Podestà, M.; Tobias, B. J.; Van Zeeland, M. A.

2017-05-01

A general criterion is proposed and found to successfully predict the emergence of chirping oscillations of unstable Alfvénic eigenmodes in tokamak plasma experiments. The model includes realistic eigenfunction structure, detailed phase-space dependences of the instability drive, stochastic scattering and the Coulomb drag. The stochastic scattering combines the effects of collisional pitch angle scattering and micro-turbulence spatial diffusion. The latter mechanism is essential to accurately identify the transition between the fixed-frequency mode behavior and rapid chirping in tokamaks and to resolve the disparity with respect to chirping observation in spherical and conventional tokamaks.

Dynamic stability of maglev systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai, Y.; Chen, S.S.; Mulcahy, T.M.

1992-09-01

Since the occurrence of dynamic instabilities is not acceptable for any commercial maglev systems, it is important to consider the dynamic instability in the development of all maglev systems. This study is to consider the stability of maglev systems based on experimental data, scoping calculations and simple mathematical models. Divergence and flutter are obtained for coupled vibration of a three-degree-of-freedom maglev vehicle on the guideway which consists of double L-shaped aluminum segments attached to a rotating wheel. The theory and analysis developed in this study provides basic stability characteristics and identifies future research needs for maglev system.

Towards multi-field D-brane inflation in a warped throat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Heng-Yu; Gong, Jinn-Ouk; Koyama, Kazuya

2010-11-01

We study the inflationary dynamics in a model of slow-roll inflation in warped throat. Inflation is realized by the motion of a D-brane along the radial direction of the throat, and at later stages instabilities develop in the angular directions. We closely investigate both the single field potential relevant for the slow-roll phase, and the full multi-field one including the angular modes which becomes important at later stages. We study the main features of the instability process, discussing its possible consequences and identifying the vacua towards which the angular modes are driven.

High-Speed Imaging of Dusty Plasma Instabilities

NASA Astrophysics Data System (ADS)

Tawidian, H.; Couëdel, L.; Mikikian, M.; Lecas, T.; Boufendi, L.; Vallée, O.

2011-11-01

Dust particles in a plasma acquire negative charges by capturing electrons. If the dust particle density is high, a huge loss of free electrons can trigger unstable behaviors in the plasma. Several types of plasma behaviors are analyzed thanks to a high-speed camera like dust particle growth instabilities (DPGI) and a new phenomenon called plasma spheroids. These small plasma spheroids are about a few mm, have a slightly enhanced luminosity, and are observed in the vicinity of the electrodes. Different behaviors are identified for these spheroids like a rotational motion, or a chaotic regime (fast appearance and disappearance).

Identification of Instability Modes of Transition in Underexpanded Jets

NASA Technical Reports Server (NTRS)

Inman, Jennifer A.; Danehy, Paul M.; Nowak, Robert J.; Alderfer, David W.

2008-01-01

A series of experiments into the behavior of underexpanded jet flows has been conducted at NASA Langley Research Center. Two nozzles supplied with high-pressure gas were used to generate axisymmetric underexpanded jets exhausting into a low-pressure chamber. These nozzles had exit Mach numbers of 1 and 2.6, though this paper will present cases involving only the supersonic nozzle. Reynolds numbers based on nozzle exit conditions ranged from about 300 to 22,000, and nozzle exit-to-ambient jet pressure ratios ranged from about 1 to 25. For the majority of cases, the jet fluid was a mixture of 99.5% nitrogen seeded with 0.5% nitric oxide (NO). Planar laser-induced fluorescence (PLIF) of NO is used to visualize the flow, visualizing planar slices of the flow rather than path integrated measurements. In addition to revealing the size and location of flow structures, PLIF images were also used to identify unsteady jet behavior in order to quantify the conditions governing the transition to turbulent flow. Flow structures that contribute to the growth of flow instabilities have been identified, and relationships between Reynolds number and transition location are presented. By highlighting deviations from mean flow properties, PLIF images are shown to aide in the identification and characterization of flow instabilities and the resulting process of transition to turbulence.

Hypersonic Boundary-Layer Stability Experiments on a Flared-Cone Model at Angle of Attack in a Quiet Wind Tunnel

NASA Technical Reports Server (NTRS)

Doggett, Glen P.; Chokani, Ndaona

1996-01-01

An experimental investigation of the effects of angle of attack on hypersonic boundary-layer stability on a flared-cone model was conducted in the low-disturbance Mach-6 Nozzle-Test Chamber Facility at NASA Langley Research Center. This unique facility provided a 'quiet' flow test environment which is well suited for stability experiments because the low levels of freestream 'noise' minimize artificial stimulation of flow-disturbance growth. Surface pressure and temperature measurements documented the adverse-pressure gradient and transition-onset location. Hot-wire anemometry diagnostics were applied to identify the instability mechanisms which lead to transition. In addition, the mean flow over the flared-cone geometry was modeled by laminar Navier-Stokes computations. Results show that the boundary layer becomes more stable on the windward ray and less stable on the leeward ray relative to the zero-degree angle-of-attack case. The second-mode instability dominates the transition process at a zero-degree angle of attack, however, on the windward ray at an angle of attack this mode was completely stabilized. The less-dominant first-mode instability was slightly destabilized on the windward ray. Non-linear mechanisms such as saturation and harmonic generation are identified from the flow-disturbance bispectra.

Modulational instability in a PT-symmetric vector nonlinear Schrödinger system

NASA Astrophysics Data System (ADS)

Cole, J. T.; Makris, K. G.; Musslimani, Z. H.; Christodoulides, D. N.; Rotter, S.

2016-12-01

A class of exact multi-component constant intensity solutions to a vector nonlinear Schrödinger (NLS) system in the presence of an external PT-symmetric complex potential is constructed. This type of uniform wave pattern displays a non-trivial phase whose spatial dependence is induced by the lattice structure. In this regard, light can propagate without scattering while retaining its original form despite the presence of inhomogeneous gain and loss. These constant-intensity continuous waves are then used to perform a modulational instability analysis in the presence of both non-hermitian media and cubic nonlinearity. A linear stability eigenvalue problem is formulated that governs the dynamical evolution of the periodic perturbation and its spectrum is numerically determined using Fourier-Floquet-Bloch theory. In the self-focusing case, we identify an intensity threshold above which the constant-intensity modes are modulationally unstable for any Floquet-Bloch momentum belonging to the first Brillouin zone. The picture in the self-defocusing case is different. Contrary to the bulk vector case, where instability develops only when the waves are strongly coupled, here an instability occurs in the strong and weak coupling regimes. The linear stability results are supplemented with direct (nonlinear) numerical simulations.

Methods to Monitor DNA Repair Defects and Genomic Instability in the Context of a Disrupted Nuclear Lamina.

PubMed

Gonzalo, Susana; Kreienkamp, Ray

2016-01-01

The organization of the genome within the nuclear space is viewed as an additional level of regulation of genome function, as well as a means to ensure genome integrity. Structural proteins associated with the nuclear envelope, in particular lamins (A- and B-type) and lamin-associated proteins, play an important role in genome organization. Interestingly, there is a whole body of evidence that links disruptions of the nuclear lamina with DNA repair defects and genomic instability. Here, we describe a few standard techniques that have been successfully utilized to identify mechanisms behind DNA repair defects and genomic instability in cells with an altered nuclear lamina. In particular, we describe protocols to monitor changes in the expression of DNA repair factors (Western blot) and their recruitment to sites of DNA damage (immunofluorescence); kinetics of DNA double-strand break repair after ionizing radiation (neutral comet assays); frequency of chromosomal aberrations (FISH, fluorescence in situ hybridization); and alterations in telomere homeostasis (Quantitative-FISH). These techniques have allowed us to shed some light onto molecular mechanisms by which alterations in A-type lamins induce genomic instability, which could contribute to the pathophysiology of aging and aging-related diseases.

Influences of the Darrieus-Landau instability on premixed turbulent flames

NASA Astrophysics Data System (ADS)

Patyal, Advitya; Matalon, Moshe

2017-11-01

The propagation of turbulent flames in three-dimensional turbulent flows is studied within the context of the hydrodynamic theory. The flame is treated as a surface of density discontinuity with the flow modified by gas expansion resulting from heat released during combustion. The flame is tracked using a level-set method with a propagation speed that depends on the local flame stretch, modulated by a Markstein length. Impact of the Darrieus-Landau instability on the topology of the flame surface is studied. It is shown that similar to passive interfaces, flames under the influence of the hydrodynamic instability resort to cylindrical structures with increasing turbulence intensity, even in 3D. The mechanism of modification of vortical structures in the burned gas is identified in terms of the alignments between the vorticity vector, flame surface normal and eigenvectors of the strain rate tensor. The results indicate that the strain rate tensor is intricately coupled with the normal to the flame surface and creates anisotropy in the orientation of vortical structures, which begins to weaken as the turbulent intensity increases. Furthermore, vorticity budgets are used to highlight the relative importance of baroclinic torque due to Darrieus-Landau instability.

Influence of watershed topographic and socio-economic attributes on the climate sensitivity of global river water quality

NASA Astrophysics Data System (ADS)

Khan, Afed U.; Jiang, Jiping; Wang, Peng; Zheng, Yi

2017-10-01

Surface waters exhibit regionalization due to various climatic conditions and anthropogenic activities. Here we assess the impact of topographic and socio-economic factors on the climate sensitivity of surface water quality, estimated using an elasticity approach (climate elasticity of water quality (CEWQ)), and identify potential risks of instability in different regions and climatic conditions. Large global datasets were used for 12 main water quality parameters from 43 water quality monitoring stations located at large major rivers. The results demonstrated that precipitation elasticity shows higher sensitivity to topographic and socio-economic determinants as compared to temperature elasticity. In tropical climate class (A), gross domestic product (GDP) played an important role in stabilizing the CEWQ. In temperate climate class (C), GDP played the same role in stability, while the runoff coefficient, slope, and population density fuelled the risk of instability. The results implied that watersheds with lower runoff coefficient, thick population density, over fertilization and manure application face a higher risk of instability. We discuss the socio-economic and topographic factors that cause instability of CEWQ parameters and conclude with some suggestions for watershed managers to bring sustainability in freshwater bodies.

Activation of Dun1 in response to nuclear DNA instability accounts for the increase in mitochondrial point mutations in Rad27/FEN1 deficient S. cerevisiae.

PubMed

Kaniak-Golik, Aneta; Kuberska, Renata; Dzierzbicki, Piotr; Sledziewska-Gojska, Ewa

2017-01-01

Rad27/FEN1 nuclease that plays important roles in the maintenance of DNA stability in the nucleus has recently been shown to reside in mitochondria. Accordingly, it has been established that Rad27 deficiency causes increased mutagenesis, but decreased microsatellite instability and homologous recombination in mitochondria. Our current analysis of mutations leading to erythromycin resistance indicates that only some of them arise in mitochondrial DNA and that the GC→AT transition is a hallmark of the mitochondrial mutagenesis in rad27 null background. We also show that the mitochondrial mutator phenotype resulting from Rad27 deficiency entirely depends on the DNA damage checkpoint kinase Dun1. DUN1 inactivation suppresses the mitochondrial mutator phenotype caused by Rad27 deficiency and this suppression is eliminated at least in part by subsequent deletion of SML1 encoding a repressor of ribonucleotide reductase. We conclude that Rad27 deficiency causes a mitochondrial mutator phenotype via activation of DNA damage checkpoint kinase Dun1 and that a Dun1-mediated increase of dNTP pools contributes to this phenomenon. These results point to the nuclear DNA instability as the source of mitochondrial mutagenesis. Consistently, we show that mitochondrial mutations occurring more frequently in yeast devoid of Rrm3, a DNA helicase involved in rDNA replication, are also dependent on Dun1. In addition, we have established that overproduction of Exo1, which suppresses DNA damage sensitivity and replication stress in nuclei of Rad27 deficient cells, but does not enter mitochondria, suppresses the mitochondrial mutagenesis. Exo1 overproduction restores also a great part of allelic recombination and microsatellite instability in mitochondria of Rad27 deficient cells. In contrast, the overproduction of Exo1 does not influence mitochondrial direct-repeat mediated deletions in rad27 null background, pointing to this homologous recombination pathway as the direct target of Rad27 activity in mitochondria.

Activation of Dun1 in response to nuclear DNA instability accounts for the increase in mitochondrial point mutations in Rad27/FEN1 deficient S. cerevisiae

PubMed Central

Dzierzbicki, Piotr

2017-01-01

Rad27/FEN1 nuclease that plays important roles in the maintenance of DNA stability in the nucleus has recently been shown to reside in mitochondria. Accordingly, it has been established that Rad27 deficiency causes increased mutagenesis, but decreased microsatellite instability and homologous recombination in mitochondria. Our current analysis of mutations leading to erythromycin resistance indicates that only some of them arise in mitochondrial DNA and that the GC→AT transition is a hallmark of the mitochondrial mutagenesis in rad27 null background. We also show that the mitochondrial mutator phenotype resulting from Rad27 deficiency entirely depends on the DNA damage checkpoint kinase Dun1. DUN1 inactivation suppresses the mitochondrial mutator phenotype caused by Rad27 deficiency and this suppression is eliminated at least in part by subsequent deletion of SML1 encoding a repressor of ribonucleotide reductase. We conclude that Rad27 deficiency causes a mitochondrial mutator phenotype via activation of DNA damage checkpoint kinase Dun1 and that a Dun1-mediated increase of dNTP pools contributes to this phenomenon. These results point to the nuclear DNA instability as the source of mitochondrial mutagenesis. Consistently, we show that mitochondrial mutations occurring more frequently in yeast devoid of Rrm3, a DNA helicase involved in rDNA replication, are also dependent on Dun1. In addition, we have established that overproduction of Exo1, which suppresses DNA damage sensitivity and replication stress in nuclei of Rad27 deficient cells, but does not enter mitochondria, suppresses the mitochondrial mutagenesis. Exo1 overproduction restores also a great part of allelic recombination and microsatellite instability in mitochondria of Rad27 deficient cells. In contrast, the overproduction of Exo1 does not influence mitochondrial direct-repeat mediated deletions in rad27 null background, pointing to this homologous recombination pathway as the direct target of Rad27 activity in mitochondria. PMID:28678842

Control of Viscous Fingering in Miscible Displacements in Porous Media with a Periodic Change of Injection Rate

NASA Astrophysics Data System (ADS)

Yuan, Q.; Zeng, F.; Knorr, K. D.; Imran, M.

2017-12-01

Context/PurposeThe viscous fingering (VF) is widely encountered in a series of miscible displacements such as CO2 sequestration and solvent-based enhanced oil recovery (EOR). Accurate prediction and effective control of its development are significant. Commercial simulators cannot capture VF because of large numerical diffusion. Moreover, previous measures for controlling VF using polymer are very expensive. In the present study, a periodic change of injection rate involving injection and extraction is used to control and reduce VF instabilities at zero cost. MethodsHighly accurate spectral method and fully implicit alternating direction implicit method are used to simulate VF with concentration-dependent diffusion (CDD) and velocity-induced dispersion (VID), although the consideration of CDD and VID may result in strong nonlinearity and stiff problem under unfavourable viscosity ratio. In-house code is developed. The VF is reduced by optimizing period and amplitude of injection rate. ResultsThe results show that the periodic change of injection rates can strongly affect VF and sweep efficiency. In particular, a period-stabilizing range is found in which the VF is reduced compared with widely used constant injection with the same amount of fluid injected. The frequent change of rate results in high sweep efficiency. The optimal injection scheme, when compared with constant injection, can improve sweep efficiency by 20-35%. InterpretationDispersion plays a key role in the mitigation of VF in periodic displacement rates. It enhances the uniform mixing of two fluids in injection stage in any period, while it can more effectively attenuate VF instabilities through the following extraction stage. Fast switch of injection and extraction can mitigate flow instability once it develops. ConclusionThis finding is very novel and significant as it is the first time to control VF instability in porous media without any additional cost. It shows great potential for EOR at zero cost.

Segmental duplications and evolutionary plasticity at tumor chromosome break-prone regions

PubMed Central

Darai-Ramqvist, Eva; Sandlund, Agneta; Müller, Stefan; Klein, George; Imreh, Stefan; Kost-Alimova, Maria

2008-01-01

We have previously found that the borders of evolutionarily conserved chromosomal regions often coincide with tumor-associated deletion breakpoints within human 3p12-p22. Moreover, a detailed analysis of a frequently deleted region at 3p21.3 (CER1) showed associations between tumor breaks and gene duplications. We now report on the analysis of 54 chromosome 3 breaks by multipoint FISH (mpFISH) in 10 carcinoma-derived cell lines. The centromeric region was broken in five lines. In lines with highly complex karyotypes, breaks were clustered near known fragile sites, FRA3B, FRA3C, and FRA3D (three lines), and in two other regions: 3p12.3-p13 (∼75 Mb position) and 3q21.3-q22.1 (∼130 Mb position) (six lines). All locations are shown based on NCBI Build 36.1 human genome sequence. The last two regions participated in three of four chromosome 3 inversions during primate evolution. Regions at 75, 127, and 131 Mb positions carry a large (∼250 kb) segmental duplication (tumor break-prone segmental duplication [TBSD]). TBSD homologous sequences were found at 15 sites on different chromosomes. They were located within bands frequently involved in carcinoma-associated breaks. Thirteen of them have been involved in inversions during primate evolution; 10 were reused by breaks during mammalian evolution; 14 showed copy number polymorphism in man. TBSD sites showed an increase in satellite repeats, retrotransposed sequences, and other segmental duplications. We propose that the instability of these sites stems from specific organization of the chromosomal region, associated with location at a boundary between different CG-content isochores and with the presence of TBSDs and “instability elements,” including satellite repeats and retroviral sequences. PMID:18230801

Segmental duplications and evolutionary plasticity at tumor chromosome break-prone regions.

PubMed

Darai-Ramqvist, Eva; Sandlund, Agneta; Müller, Stefan; Klein, George; Imreh, Stefan; Kost-Alimova, Maria

2008-03-01

We have previously found that the borders of evolutionarily conserved chromosomal regions often coincide with tumor-associated deletion breakpoints within human 3p12-p22. Moreover, a detailed analysis of a frequently deleted region at 3p21.3 (CER1) showed associations between tumor breaks and gene duplications. We now report on the analysis of 54 chromosome 3 breaks by multipoint FISH (mpFISH) in 10 carcinoma-derived cell lines. The centromeric region was broken in five lines. In lines with highly complex karyotypes, breaks were clustered near known fragile sites, FRA3B, FRA3C, and FRA3D (three lines), and in two other regions: 3p12.3-p13 ( approximately 75 Mb position) and 3q21.3-q22.1 ( approximately 130 Mb position) (six lines). All locations are shown based on NCBI Build 36.1 human genome sequence. The last two regions participated in three of four chromosome 3 inversions during primate evolution. Regions at 75, 127, and 131 Mb positions carry a large ( approximately 250 kb) segmental duplication (tumor break-prone segmental duplication [TBSD]). TBSD homologous sequences were found at 15 sites on different chromosomes. They were located within bands frequently involved in carcinoma-associated breaks. Thirteen of them have been involved in inversions during primate evolution; 10 were reused by breaks during mammalian evolution; 14 showed copy number polymorphism in man. TBSD sites showed an increase in satellite repeats, retrotransposed sequences, and other segmental duplications. We propose that the instability of these sites stems from specific organization of the chromosomal region, associated with location at a boundary between different CG-content isochores and with the presence of TBSDs and "instability elements," including satellite repeats and retroviral sequences.

Psychodynamic therapy from the perspective of self-organization. a concept of change and a methodological approach for empirical examination.

PubMed

Gumz, Antje; Geyer, Michael; Brähler, Elmar

2014-01-01

Observations from therapeutic practice and a series of empirical findings, for example, those on discontinuous change in psychotherapeutic processes, suggest modelling the therapeutic process as a self-organizing system with stable and critical instable phases and abrupt transitions. Here, a concept of psychotherapeutic change is presented that applies self-organization theory to psychodynamic principles. The authors explain the observations and considerations that form the basis of the concept and present some connections with existing findings and concepts. On the basis of this model, they generated two hypotheses regarding the co-occurrence of instability and discontinuous change and the degree of synchrony between the therapist and patient. A study design to test these hypotheses was developed and applied to a single case (psychodynamic therapy). After each session, patient and therapist rated their interaction. A measure of instability was calculated across the resulting time series. Sequences of destabilization were observed. On the basis of points of extreme instability, the process was divided into phases. Local instability maxima were accompanied by significant discontinuous change. Destabilization was highly synchronous in therapist and patient ratings. The authors discussed the concept and the methodological procedure. The approach enables the operationalization of crises and to empirically assess the significance of critical phases and developments within the therapeutic relationship. We present a concept of change that applies self-organization theory to psychodynamic therapy. We empirically tested the hypotheses formulated in the concept based on an extract of 125 long-term psychodynamic therapy sessions. We continuously monitored the therapeutic interaction and calculated a measure of the instability of the assessments. We identified several sequences of stable and unstable episodes. Episodes of high instability were accompanied by discontinuous change. On the basis of these episodes of high instability, we divided the process into four phases. Mean values of variables differed across these phases. Destabilization proved to be highly synchronous in therapist and patient ratings. The approach allows to empirically assess critical phases and developments within the therapeutic relationship. Copyright © 2013 John Wiley & Sons, Ltd.

Operative Management of Patellar Instability in the United States: An Evaluation of National Practice Patterns, Surgical Trends, and Complications.

PubMed

Arshi, Armin; Cohen, Jeremiah R; Wang, Jeffrey C; Hame, Sharon L; McAllister, David R; Jones, Kristofer J

2016-08-01

Treatment of patellofemoral instability has evolved as our understanding of the relevant pathoanatomy has improved. In light of these developments, current practice patterns and management trends have likely changed to reflect these advancements; however, this has not been evaluated in a formal study. To determine nationwide patient demographics, surgical trends, and postoperative complications associated with the operative management of patellar instability surgery. Descriptive epidemiological study. A large private-payer database (PearlDiver) comprising patients covered by Humana and United Healthcare insurance policies was retrospectively reviewed using Current Procedural Terminology (CPT) codes to identify patients who underwent surgery for patellar instability. The study cohort was established by querying for patients billed under CPT codes 27420, 27422, or 27427 while satisfying the diagnostic requirement of patellar instability (International Classification of Diseases-9th Revision codes 718.36, 718.86, or 836.3). Patient demographics, surgical trends, concomitant procedures, and postoperative complications were determined. A total of 6190 patients underwent surgical management for patellar instability. Adolescents (age range, 10-19 years) represented 51.5% of cases, and 59.6% were female. The number of patellar instability procedures increased annually over the study period in both the Humana (P = .004, R (2) = 0.76) and United Healthcare (P = .097, R (2) = 0.54) cohorts. The most common concomitant procedures were lateral retinacular release (43.7%), chondroplasty (31.1%), tibial tubercle osteotomy (13.1%), removal of loose bodies (10.5%), osteochondral grafting (9.5%), and microfracture surgery (9.5%). Manipulation under anesthesia was required in 4.6% of patients within 1 year. Patellar fracture within 1 year and infection within 30 days occurred in 2.1% and 1.2% of patients, respectively. Patellar instability surgery has increased over the past decade. This finding may be attributed to growing clinical evidence to support these procedures as well as increased surgeon familiarity and comfort with these specific techniques. We observed an unexpectedly high rate of concomitant lateral retinacular release. Overall, the rates of commonly recognized complications (stiffness, patellar fracture, and postoperative infection) were similar to those observed in smaller case series.

MSH3 polymorphisms and protein levels affect CAG repeat instability in Huntington's disease mice.

PubMed

Tomé, Stéphanie; Manley, Kevin; Simard, Jodie P; Clark, Greg W; Slean, Meghan M; Swami, Meera; Shelbourne, Peggy F; Tillier, Elisabeth R M; Monckton, Darren G; Messer, Anne; Pearson, Christopher E

2013-01-01

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)∼100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases.

MSH3 Polymorphisms and Protein Levels Affect CAG Repeat Instability in Huntington's Disease Mice

PubMed Central

Simard, Jodie P.; Clark, Greg W.; Slean, Meghan M.; Swami, Meera; Shelbourne, Peggy F.; Tillier, Elisabeth R. M.; Monckton, Darren G.; Messer, Anne; Pearson, Christopher E.

2013-01-01

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)∼100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases. PMID:23468640

Community-based approaches and partnerships: innovations in health-service delivery in Bangladesh.

PubMed

El Arifeen, Shams; Christou, Aliki; Reichenbach, Laura; Osman, Ferdous Arfina; Azad, Kishwar; Islam, Khaled Shamsul; Ahmed, Faruque; Perry, Henry B; Peters, David H

2013-12-14

In Bangladesh, rapid advancements in coverage of many health interventions have coincided with impressive reductions in fertility and rates of maternal, infant, and childhood mortality. These advances, which have taken place despite such challenges as widespread poverty, political instability, and frequent natural disasters, warrant careful analysis of Bangladesh's approach to health-service delivery in the past four decades. With reference to success stories, we explore strategies in health-service delivery that have maximised reach and improved health outcomes. We identify three distinctive features that have enabled Bangladesh to improve health-service coverage and health outcomes: (1) experimentation with, and widespread application of, large-scale community-based approaches, especially investment in community health workers using a doorstep delivery approach; (2) experimentation with informal and contractual partnership arrangements that capitalise on the ability of non-governmental organisations to generate community trust, reach the most deprived populations, and address service gaps; and (3) rapid adoption of context-specific innovative technologies and policies that identify country-specific systems and mechanisms. Continued development of innovative, community-based strategies of health-service delivery, and adaptation of new technologies, are needed to address neglected and emerging health challenges, such as increasing access to skilled birth attendance, improvement of coverage of antenatal care and of nutritional status, the effects of climate change, and chronic disease. Past experience should guide future efforts to address rising public health concerns for Bangladesh and other underdeveloped countries. Copyright © 2013 Elsevier Ltd. All rights reserved.

Subduction Thermal Regime, Slab Dehydration, and Seismicity Distribution Beneath Hikurangi Based on 3-D Simulations

NASA Astrophysics Data System (ADS)

Suenaga, Nobuaki; Ji, Yingfeng; Yoshioka, Shoichi; Feng, Deshan

2018-04-01

The downdip limit of seismogenic interfaces inferred from the subduction thermal regime by thermal models has been suggested to relate to the faulting instability caused by the brittle failure regime in various plate convergent systems. However, the featured three-dimensional thermal state, especially along the horizontal (trench-parallel) direction of a subducted oceanic plate, remains poorly constrained. To robustly investigate and further map the horizontal (trench-parallel) distribution of the subduction regime and subsequently induced slab dewatering in a descending plate beneath a convergent margin, we construct a regional thermal model that incorporates an up-to-date three-dimensional slab geometry and the MORVEL plate velocity to simulate the plate subduction history in Hikurangi. Our calculations suggest an identified thrust zone featuring remarkable slab dehydration near the Taupo volcanic arc in the North Island distributed in the Kapiti, Manawatu, and Raukumara region. The calculated average subduction-associated slab dehydration of 0.09 to 0.12 wt%/km is greater than the dehydration in other portions of the descending slab and possibly contributes to an along-arc variation in the interplate pore fluid pressure. A large-scale slab dehydration (>0.05 wt%/km) and a high thermal gradient (>4 °C/km) are also identified in the Kapiti, Manawatu, and Raukumara region and are associated with frequent deep slow slip events. An intraslab dehydration that exceeds 0.2 wt%/km beneath Manawatu near the source region of tectonic tremors suggests an unknown relationship in the genesis of slow earthquakes.

rDNA Copy Number Variants Are Frequent Passenger Mutations in Saccharomyces cerevisiae Deletion Collections and de Novo Transformants

PubMed Central

Kwan, Elizabeth X.; Wang, Xiaobin S.; Amemiya, Haley M.; Brewer, Bonita J.; Raghuraman, M. K.

2016-01-01

The Saccharomyces cerevisiae ribosomal DNA (rDNA) locus is known to exhibit greater instability relative to the rest of the genome. However, wild-type cells preferentially maintain a stable number of rDNA copies, suggesting underlying genetic control of the size of this locus. We performed a screen of a subset of the Yeast Knock-Out (YKO) single gene deletion collection to identify genetic regulators of this locus and to determine if rDNA copy number correlates with yeast replicative lifespan. While we found no correlation between replicative lifespan and rDNA size, we identified 64 candidate strains with significant rDNA copy number differences. However, in the process of validating candidate rDNA variants, we observed that independent isolates of our de novo gene deletion strains had unsolicited but significant changes in rDNA copy number. Moreover, we were not able to recapitulate rDNA phenotypes from the YKO yeast deletion collection. Instead, we found that the standard lithium acetate transformation protocol is a significant source of rDNA copy number variation, with lithium acetate exposure being the treatment causing variable rDNA copy number events after transformation. As the effects of variable rDNA copy number are being increasingly reported, our finding that rDNA is affected by lithium acetate exposure suggested that rDNA copy number variants may be influential passenger mutations in standard strain construction in S. cerevisiae. PMID:27449518

rDNA Copy Number Variants Are Frequent Passenger Mutations in Saccharomyces cerevisiae Deletion Collections and de Novo Transformants.

PubMed

Kwan, Elizabeth X; Wang, Xiaobin S; Amemiya, Haley M; Brewer, Bonita J; Raghuraman, M K

2016-09-08

The Saccharomyces cerevisiae ribosomal DNA (rDNA) locus is known to exhibit greater instability relative to the rest of the genome. However, wild-type cells preferentially maintain a stable number of rDNA copies, suggesting underlying genetic control of the size of this locus. We performed a screen of a subset of the Yeast Knock-Out (YKO) single gene deletion collection to identify genetic regulators of this locus and to determine if rDNA copy number correlates with yeast replicative lifespan. While we found no correlation between replicative lifespan and rDNA size, we identified 64 candidate strains with significant rDNA copy number differences. However, in the process of validating candidate rDNA variants, we observed that independent isolates of our de novo gene deletion strains had unsolicited but significant changes in rDNA copy number. Moreover, we were not able to recapitulate rDNA phenotypes from the YKO yeast deletion collection. Instead, we found that the standard lithium acetate transformation protocol is a significant source of rDNA copy number variation, with lithium acetate exposure being the treatment causing variable rDNA copy number events after transformation. As the effects of variable rDNA copy number are being increasingly reported, our finding that rDNA is affected by lithium acetate exposure suggested that rDNA copy number variants may be influential passenger mutations in standard strain construction in S. cerevisiae. Copyright © 2016 Kwan et al.

Sleep-wake patterns, non-rapid eye movement, and rapid eye movement sleep cycles in teenage narcolepsy.

PubMed

Xu, Xing; Wu, Huijuan; Zhuang, Jianhua; Chen, Kun; Huang, Bei; Zhao, Zhengqing; Zhao, Zhongxin

2017-05-01

To further characterize sleep disorders associated with narcolepsy, we assessed the sleep-wake patterns, rapid eye movement (REM), and non-REM (NREM) sleep cycles in Chinese teenagers with narcolepsy. A total of 14 Chinese type 1 narcoleptic patients (13.4 ± 2.6 years of age) and 14 healthy age- and sex-matched control subjects (13.6 ± 1.8 years of age) were recruited. Ambulatory 24-h polysomnography was recorded for two days, with test subjects adapting to the instruments on day one and the study data collection performed on day two. Compared with the controls, the narcoleptic patients showed a 1.5-fold increase in total sleep time over 24 h, characterized by enhanced slow-wave sleep and REM sleep. Frequent sleep-wake transitions were identified in nocturnal sleep with all sleep stages switching to wakefulness, with more awakenings and time spent in wakefulness after sleep onset. Despite eight cases of narcolepsy with sleep onset REM periods at night, the mean duration of NREM-REM sleep cycle episode and the ratio of REM/NREM sleep between patients and controls were not significantly different. Our study identified hypersomnia in teenage narcolepsy despite excessive daytime sleepiness. Sleep fragmentation extended to all sleep stages, indicating impaired sleep-wake cycles and instability of sleep stages. The limited effects on NREM-REM sleep cycles suggest the relative conservation of ultradian regulation of sleep. Copyright © 2016 Elsevier B.V. All rights reserved.

Recurrent instability after revision anterior shoulder stabilization surgery.

PubMed

Friedman, Lisa Genevra Mandeville; Griesser, Michael J; Miniaci, Anthony A; Jones, Morgan H

2014-03-01

The purpose of this study was to perform a systematic review of the literature to compare outcomes of revision anterior stabilization surgeries based on technique. This study also sought to compare the impact of bone defects on outcomes. A systematic review of the electronic databases PubMed, Cochrane Central Register of Controlled Trials, and Scopus was performed in July 2012 and March 2013. Of 345 articles identified in the search, 17 studies with Level I to IV Evidence satisfied the inclusion criteria and were analyzed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Recurrent instability was defined as redislocation, resubluxation, or a positive apprehensive test after revision surgery. Procedures were categorized as arthroscopic Bankart repair, open Bankart repair, Bristow-Latarjet procedure, and other open procedures. In total, 388 shoulders were studied. Male patients comprised 74.1% of patients, 66.7% of cases involved the dominant shoulder, the mean age was 28.2 years, and the mean follow-up period was 44.2 months. The surgical procedures classified as "other open procedures" had the highest rate of recurrent instability (42.7%), followed by arthroscopic Bankart repair (14.7%), the Bristow-Latarjet procedure (14.3%), and open Bankart repair (5.5%). Inconsistent reporting of bone defects precluded drawing significant conclusions. A number of different procedures are used to address recurrent instability after a primary operation for anterior shoulder instability has failed. There is significant variability in the rate of recurrent instability after revision anterior shoulder stabilization surgery. Level IV, systematic review of Level I to IV studies. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Unscrambling the genomic chaos of osteosarcoma reveals extensive transcript fusion, recurrent rearrangements and frequent novel TP53 aberrations

PubMed Central

Lorenz, Susanne; Barøy, Tale; Sun, Jinchang; Nome, Torfinn; Vodák, Daniel; Bryne, Jan-Christian; Håkelien, Anne-Mari; Fernandez-Cuesta, Lynnette; Möhlendick, Birte; Rieder, Harald; Szuhai, Karoly; Zaikova, Olga; Ahlquist, Terje C.; Thomassen, Gard O. S.; Skotheim, Rolf I.; Lothe, Ragnhild A.; Tarpey, Patrick S.; Campbell, Peter; Flanagan, Adrienne

2016-01-01

In contrast to many other sarcoma subtypes, the chaotic karyotypes of osteosarcoma have precluded the identification of pathognomonic translocations. We here report hundreds of genomic rearrangements in osteosarcoma cell lines, showing clear characteristics of microhomology-mediated break-induced replication (MMBIR) and end-joining repair (MMEJ) mechanisms. However, at RNA level, the majority of the fused transcripts did not correspond to genomic rearrangements, suggesting the involvement of trans-splicing, which was further supported by typical trans-splicing characteristics. By combining genomic and transcriptomic analysis, certain recurrent rearrangements were identified and further validated in patient biopsies, including a PMP22-ELOVL5 gene fusion, genomic structural variations affecting RB1, MTAP/CDKN2A and MDM2, and, most frequently, rearrangements involving TP53. Most cell lines (7/11) and a large fraction of tumor samples (10/25) showed TP53 rearrangements, in addition to somatic point mutations (6 patient samples, 1 cell line) and MDM2 amplifications (2 patient samples, 2 cell lines). The resulting inactivation of p53 was demonstrated by a deficiency of the radiation-induced DNA damage response. Thus, TP53 rearrangements are the major mechanism of p53 inactivation in osteosarcoma. Together with active MMBIR and MMEJ, this inactivation probably contributes to the exceptional chromosomal instability in these tumors. Although rampant rearrangements appear to be a phenotype of osteosarcomas, we demonstrate that among the huge number of probable passenger rearrangements, specific recurrent, possibly oncogenic, events are present. For the first time the genomic chaos of osteosarcoma is characterized so thoroughly and delivered new insights in mechanisms involved in osteosarcoma development and may contribute to new diagnostic and therapeutic strategies. PMID:26672768

[Critically ill pediatric hemato-oncology patient: What we do is what we should do?].

PubMed

García-Salido, Alberto; Nieto-Moro, Montserrat; Iglesias-Bouzas, María Isabel; González-Vicent, Marta; Serrano-González, Ana; Casado-Flores, Juan

2016-08-01

Primary objective, to describe the management and monitorization of critically ill pediatric hemato-oncology patient (CIPHO) in the Spanish pediatric intensive care units (PICU). Secondary objective, through a literature review, to identify possible areas of improvement. Observational transversal descriptive study. An anonymous web-based survey was sent to 324 Spanish pediatric intensivists from April 2011 to May 2011. None of them were pediatric residents. The survey was answered by 105 intensivists, 59/105 always agreed their treatment with the oncologist. In case of hemodynamic instability, non-invasive blood pressure monitoring is always done by 85/105 and almost always optimized by intra-arterial measuring (85/105) and central venous pressure (70/105). If respiratory failure the use of non-invasive ventilation (NIPPV) is always (36/105) or frequently (60/105) established prior to conventional mechanical ventilation. To replace or withdraw non-invasive ventilation only 44/96 of the respondents to this question use a clinical protocol. Before the instauration of conventional mechanical ventilation the oncological prognosis is considered by 72/105. In case of acute oliguric renal failure the renal replacement techniques are widely used (74/105). The withdrawal of sustaining life support is frequently discussed (75/103) and agreed with the oncologist (91/103) and caregivers (81/103). In our study, despite there is not a defined standard-of-care, the respondents showed similar therapeutics and monitorization choices. The use of NIPPV as first respiratory assistance is extended. Prospective, observational and multicenter studies should be developed to establish the results of this management in this population. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.