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Search Results: 1 - 10 of 302358 matches for " Kevin J. Sonnemann "
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β-Actin and γ-Actin Are Each Dispensable for Auditory Hair Cell Development But Required for Stereocilia Maintenance
Benjamin J. Perrin,Kevin J. Sonnemann,James M. Ervasti
PLOS Genetics , 2010, DOI: 10.1371/journal.pgen.1001158
Abstract: Hair cell stereocilia structure depends on actin filaments composed of cytoplasmic β-actin and γ-actin isoforms. Mutations in either gene can lead to progressive hearing loss in humans. Since β-actin and γ-actin isoforms are 99% identical at the protein level, it is unclear whether each isoform has distinct cellular roles. Here, we compared the functions of β-actin and γ-actin in stereocilia formation and maintenance by generating mice conditionally knocked out for Actb or Actg1 in hair cells. We found that, although cytoplasmic actin is necessary, neither β-actin nor γ-actin is required for normal stereocilia development or auditory function in young animals. However, aging mice with β-actin– or γ-actin–deficient hair cells develop different patterns of progressive hearing loss and distinct pathogenic changes in stereocilia morphology, despite colocalization of the actin isoforms. These results demonstrate overlapping developmental roles but unique post-developmental functions for β-actin and γ-actin in maintaining hair cell stereocilia.
Functional Substitution by TAT-Utrophin in Dystrophin-Deficient Mice
Kevin J. Sonnemann,Hanke Heun-Johnson,Amy J. Turner,Kristen A. Baltgalvis,Dawn A. Lowe,James M. Ervasti
PLOS Medicine , 2009, DOI: 10.1371/journal.pmed.1000083
Abstract: Background The loss of dystrophin compromises muscle cell membrane stability and causes Duchenne muscular dystrophy and/or various forms of cardiomyopathy. Increased expression of the dystrophin homolog utrophin by gene delivery or pharmacologic up-regulation has been demonstrated to restore membrane integrity and improve the phenotype in the dystrophin-deficient mdx mouse. However, the lack of a viable therapy in humans predicates the need to explore alternative methods to combat dystrophin deficiency. We investigated whether systemic administration of recombinant full-length utrophin (Utr) or ΔR4-21 “micro” utrophin (μUtr) protein modified with the cell-penetrating TAT protein transduction domain could attenuate the phenotype of mdx mice. Methods and Findings Recombinant TAT-Utr and TAT-μUtr proteins were expressed using the baculovirus system and purified using FLAG-affinity chromatography. Age-matched mdx mice received six twice-weekly intraperitoneal injections of either recombinant protein or PBS. Three days after the final injection, mice were analyzed for several phenotypic parameters of dystrophin deficiency. Injected TAT-μUtr transduced all tissues examined, integrated with members of the dystrophin complex, reduced serum levels of creatine kinase (11,290±920 U versus 5,950±1,120 U; PBS versus TAT), the prevalence of muscle degeneration/regeneration (54%±5% versus 37%±4% of centrally nucleated fibers; PBS versus TAT), the susceptibility to eccentric contraction-induced force drop (72%±5% versus 40%±8% drop; PBS versus TAT), and increased specific force production (9.7±1.1 N/cm2 versus 12.8±0.9 N/cm2; PBS versus TAT). Conclusions These results are, to our knowledge, the first to establish the efficacy and feasibility of TAT-utrophin-based constructs as a novel direct protein-replacement therapy for the treatment of skeletal and cardiac muscle diseases caused by loss of dystrophin.
Experimental and numerical analysis on PCB coupling in non uniform field environment
F. Sonnemann
Advances in Radio Science : Kleinheubacher Berichte , 2004,
Abstract: HPM and UWB pulses are capable of disrupting signal processing or even destroying semiconductor structures. Hence, it is useful to estimate the induced voltage levels on printed circuit boards (PCB) in response to different excitation signals. The considered PCB is integrated within a missile-like cylindrical structure, called GENEC, and is equipped with differential sensors to measure the E- and Hfield above the PCB. Standard transmission line theory is applied to develop a SPICE model that calculates the terminal voltages at the transmission line loads.
Cancer and pH—A Prospective  [PDF]
Kevin J. Carlin
Open Journal of Internal Medicine (OJIM) , 2014, DOI: 10.4236/ojim.2014.43011
Abstract: How can cancer develop in so many different organs in so many different ways, but the outcome is similar enough to all be under the same title—cancer? There are so many causes of cancer—viruses, genetic defects, sunburn, gastroesophageal reflux, smoking, alcohol, radiation, chemicals, etc. The above variable well known etiologies of cancer could all induce a need for repair which involves alkalinizing the cells involved. Thus the commonality for cancers could be a pH change. If true, this could give the field of cancer prevention and therapy new avenues of pursuit.
Blindly inserted nasogastric feeding tubes and thoracic complications in intensive care  [PDF]
Elpis Giantsou, Kevin J. Gunning
Health (Health) , 2010, DOI: 10.4236/health.2010.210166
Abstract: Purpose of review: This article reviews the thoracic complications from malpositioned blindly inserted nasogastric feeding tubes in mechanically ventilated patients in intensive care and the methods to check the position and promote safe placement of the feeding tubes. Recent findings: Malpositioned feeding tubes are not included in risk management databases. The reported incidence is 1-3% and more than half occur in mechanically ventilated patients. Eighty three mechanically ventilated patients were reported with malpositioned nasogastric tubes and 66% of them developed serious thoracic complications. Pneumothoraces accounted for 80% of thoracic complications that were evenly distributed between tubes with and without stylet. Repeated misplacements appear to increase the risk. Non-radiological confirmation of the position of the tube has suboptimal performance. Protocols to place feeding tubes and new technology are promising candidates. Summary: Malpositioned nasogastric feeding tubes are underreported and associated with serious thoracic complications in mechanically ventilated patients. We need more data to answer whether we can afford to prevent them.
Increasing the Pensionable Age: What Changes Are OECD Countries Making? What Considerations Are Driving Policy?  [PDF]
Hila Axelrad, Kevin J. Mahoney
Open Journal of Social Sciences (JSS) , 2017, DOI: 10.4236/jss.2017.57005
Abstract: The average age of retirement used to be low in most countries due to numerous policies introduced 30 to 40 years ago which encouraged lower retirement ages. However, in response to the growth of the older segment of the population, increased life expectancy, the need for skilled workers, and the precarious financial state of public pension systems, pension reforms have been implemented in the U.S. and Europe, and are now geared towards improving employment rates for older workers, increasing retirement ages and pension eligibility. This paper surveys recent changes in retirement age and maps the changes that have occurred in the last decades using data from 34 OECD (The Organization for Economic Cooperation and Development) countries. This paper then reviews the arguments for and against these changes, the criteria for setting a certain retirement age, and the differences in statutory retirement age by gender, occupation, employment status, and other factors unique to particular countries. The purpose of this paper is to analyze current trends in terms of raising the pensionable age.
Comparative evaluation of the treatment efficacy of suberoylanilide hydroxamic acid (SAHA) and paclitaxel in ovarian cancer cell lines and primary ovarian cancer cells from patients
Jürgen Sonnemann, Jennifer G?nge, Sabine Pilz, Christine St?tzer, Ralf Ohlinger, Antje Belau, Gerd Lorenz, James F Beck
BMC Cancer , 2006, DOI: 10.1186/1471-2407-6-183
Abstract: We compared a prototypic histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), and paclitaxel for their treatment efficacy in ovarian cancer cell lines and in primary patient-derived ovarian cancer cells. The primary cancer cells were isolated from malignant ascites collected from five patients with stage III ovarian carcinomas. Cytotoxic activities were evaluated by Alamar Blue assay and by caspase-3 activation. The ability of SAHA to kill drug-resistant 2780AD cells was also assessed.By employing the cell lines OVCAR-3, SK-OV-3, and A2780, we established SAHA at concentrations of 1 to 20 μM to be as efficient in inducing cell death as paclitaxel at concentrations of 3 to 300 nM. Consequently, we treated the patient-derived cancer cells with these doses of the drugs. All five isolates were sensitive to SAHA, with cell killing ranging from 21% to 63% after a 72-h exposure to 20 μM SAHA, while four of them were resistant to paclitaxel (i.e., <10% cell death at 300 nM paclitaxel for 72 hours). Likewise, treatment with SAHA led to an increase in caspase-3 activity in all five isolates, whereas treatment with paclitaxel had no effect on caspase-3 activity in three of them. 2780AD cells were responsive to SAHA but resistant to paclitaxel.These ex vivo findings raise the possibility that SAHA may prove effective in the treatment of paclitaxel-resistant ovarian cancer in vivo.Ovarian cancer is the most lethal gynaecological neoplasm, accounting for over 6% of deaths from cancer in women [1]. The standard treatment is a combination of surgery and chemotherapy, the latter usually consisting of a taxane/platinum combination. By this regimen, initial response rates of more than 80% are achieved [2]. Unfortunately, in the vast majority of women, diagnosis occurs after the disease has already disseminated beyond the ovaries. These patients typically relapse and eventually die as the tumours become refractory to treatment. Actually, drug resistance is supposed to
Self-Regulation of Goals and Performance: Effects of Discrepancy Feedback, Regulatory Focus, and Self-Efficacy  [PDF]
Jessica M. Nicklin, Kevin J. Williams
Psychology (PSYCH) , 2011, DOI: 10.4236/psych.2011.23030
Abstract: We adopted a social cognitive approach of motivation (Bandura, 1986, 1989, 2002) to examine the influence of normative feedback and self-set goals on positive discrepancy creation and goal revision in the face of a novel task. The moderating effects of self-efficacy and regulatory focus were also examined. A laboratory study in-cluding 297 undergraduate students demonstrated that feedback, whether based on normative standards of performance or goal-performance discrepancies was a strong predictor of positive discrepancy creation and goal revision. Self-efficacy was also an independent predictor of goal revision, but regulatory focus was not. These findings have important practical implications for a variety of performance contexts (e.g., work, school, sports). Individuals will modify their goals based largely on feedback received (goal-performance discrepancies and normative standards); however, self-efficacy independently influences goal revision beyond the effects of feed-back. Other implications for research and practice are discussed.
Reduction of pro-inflammatory cytokines in rats following 7-day oral supplementation with a proprietary eggshell membrane-derived product  [PDF]
Kevin J. Ruff, Dale P. DeVore
Modern Research in Inflammation (MRI) , 2014, DOI: 10.4236/mri.2014.31003
Abstract: NEM® brand eggshell membrane is a novel dietary supplement that has been clinically shown to alleviate arthritis joint pain and stiffness; however the mechanism of action is not well understood. Preliminary evidence from an in vitro study of NEM® indicated that the mechanism of action may be based on the reduction of pro-inflammatory cytokines. In vivo studies were therefore initiated to evaluate the effects of NEM® on pro-inflammatory and anti-inflammatory cytokines following oral administration in rats. NEM® was administered daily at doses of 6.13 mg/kg bw/day (Study 1), 10.0 mg/kg bw/day (Study 2), or at doses of 0 (control), 26.0 or 52.0 mg/kg bw/day (Study 3) by oral gavage for 7 consecutive days. Inflammation was induced in the Study 3 rats by intraperitoneal injection of lipopolysaccharide. Changes in plasma cytokine levels from baseline following 7 days of oral supplementation with NEM® at 6.13 mg/kg bw/ day (Study 1) were statistically significant at Day 8 for IL-2, TIMP-1 and VEGF, at Day 21 for IL-10, and at Day 35 for MCP-1, MCP-3 and TIMP-1, and at 10.0 mg/kg
Upper stratospheric ozone decrease events due to a positive feedback between ozone and the ozone dissociation rate
G. R. Sonnemann,P. Hartogh
Nonlinear Processes in Geophysics (NPG) , 2009,
Abstract: Ozone measurements taken with a ground based microwave instrument at Lindau (51.66° N, 10.13° E) over some years showed strong ozone decrease events within the stratopause region, particularly during the winter half-year. These events are characterized by a marked drop of the ozone mixing ratio from two to three ppmv to less than half a ppmv in extreme cases. Simultaneous water vapor measurements at the same place, also carried out by a microwave instrument, showed a strong increase of its mixing ratio and the temperature was also enhanced during these episodes. The theoretical analysis brought evidence that these events result from a positive feedback in the complex radiatively-chemical system between the ozone column density and the ozone dissociation rate.
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