Growth of Desulfovibrio on the surface of agar media.

PubMed

Iverson, W P

1966-07-01

Growth of Desulfovibrio desulfuricans (API strain) was found to take place in an atmosphere of hydrogen on the agar surface of complex media, including yeast extract (Difco), and Trypticase Soy Agar (BBL) without any added reducing agents. For growth on a 2% yeast extract-agar surface in the absence of hydrogen (nitrogen atmosphere), sodium lactate was required in the medium. Growth on the surface of Trypticase Soy Agar (TSA) under nitrogen took place readily in the absence of an added hydrogen donor. A medium (TSA plus salts) is described based upon the addition of sodium lactate (4 ml per liter), magnesium sulfate (2 g per liter), and ferrous ammonium sulfate (0.05%) to TSA, which appears suitable for the isolation and growth of Desulfovibrio on the surface of agar plates in an atmosphere of hydrogen. Sodium lactate does not appear to be essential in this medium for good growth and sulfate reduction in a hydrogen atmosphere, but is essential in a nitrogen atmosphere. Growth of Desulfovibrio (hydrogen atmosphere) on the agar surface of media commonly used for its cultivation as well as on an inorganic medium containing bicarbonate as a source of carbon is poor and erratic unless inoculated (Desulfovibrio) plates of TSA plus salts are incubated in the same container with plates of these media. This stimulatory effect of incubation with inoculated plates of TSA plus salts medium appears to be due to as yet unidentified volatile material produced by D. desulfuricans when growing on this medium. Another volatile material, or possibly the identical material, appears to act similarly to a hydrogen donor.

Strengths and weaknesses of temporal stability analysis for monitoring and estimating grid-mean soil moisture in a high-intensity irrigated agricultural landscape

NASA Astrophysics Data System (ADS)

Ran, Youhua; Li, Xin; Jin, Rui; Kang, Jian; Cosh, Michael H.

2017-01-01

Monitoring and estimating grid-mean soil moisture is very important for assessing many hydrological, biological, and biogeochemical processes and for validating remotely sensed surface soil moisture products. Temporal stability analysis (TSA) is a valuable tool for identifying a small number of representative sampling points to estimate the grid-mean soil moisture content. This analysis was evaluated and improved using high-quality surface soil moisture data that were acquired by a wireless sensor network in a high-intensity irrigated agricultural landscape in an arid region of northwestern China. The performance of the TSA was limited in areas where the representative error was dominated by random events, such as irrigation events. This shortcoming can be effectively mitigated by using a stratified TSA (STSA) method, proposed in this paper. In addition, the following methods were proposed for rapidly and efficiently identifying representative sampling points when using TSA. (1) Instantaneous measurements can be used to identify representative sampling points to some extent; however, the error resulting from this method is significant when validating remotely sensed soil moisture products. Thus, additional representative sampling points should be considered to reduce this error. (2) The calibration period can be determined from the time span of the full range of the grid-mean soil moisture content during the monitoring period. (3) The representative error is sensitive to the number of calibration sampling points, especially when only a few representative sampling points are used. Multiple sampling points are recommended to reduce data loss and improve the likelihood of representativeness at two scales.

Second-stage transsphenoidal approach (TSA) for highly vascular pituicytomas in children.

PubMed

Kim, Young Gyu; Park, Young Seok

2015-06-01

A pituicytoma in the sellar area is extremely rare in children and, due to its highly vascularized nature, can be difficult to address using the transsphenoid approach (TSA) to surgery. Here, we report a rare case of a pituicytoma that was completely removed from a child through a staged operation using the TSA. A 13-year-old girl was admitted with a 1-year history of visual disturbance and amenorrhea. Visual field examination showed left total blindness and right temporal hemianopsia. Laboratory results revealed hormonal levels all within normal ranges. Brain magnetic resonance imaging (MRI) showed a homogeneous, highly enhancing sellar and suprasellar mass, typically suggestive of a pituitary adenoma. TSA surgery revealed the tumor had a rubbery-firm consistency, hypervascularity, and profuse bleeding. We removed the tumor partially and planned a second-stage operation. Gross total removal is the treatment of choice for this type of tumor. Attempted resection of these presumed adenomas or meningiomas using the TSA often results in unexpectedly heavy intraoperative bleeding due to the high vascularity of this rare tumor, making surgery challenging, especially in children where the tumor is within a relatively narrow corridor. While pituicytomas are a rare differential diagnosis for sellar or parasellar tumors in children, total removal by second-stage TSA surgery is indicated in the case of profuse bleeding or uncertainty of biopsy. Following first-stage TSA surgery and pathologic confirmation of pituicytoma, the strategy is typically gross total removal during second-stage TSA surgery. Although very rare in children, a pituicytoma should be included in the differential diagnosis of a mass in the sellar area if the tumor is highly enhancing or very vascular. Second-stage TSA surgery is another strategy when the pathology is not clear during the first-stage TSA surgery.

Transcortical sensory aphasia: revisited and revised.

PubMed

Boatman, D; Gordon, B; Hart, J; Selnes, O; Miglioretti, D; Lenz, F

2000-08-01

Transcortical sensory aphasia (TSA) is characterized by impaired auditory comprehension with intact repetition and fluent speech. We induced TSA transiently by electrical interference during routine cortical function mapping in six adult seizure patients. For each patient, TSA was associated with multiple posterior cortical sites, including the posterior superior and middle temporal gyri, in classical Wernicke's area. A number of TSA sites were immediately adjacent to sites where Wernicke's aphasia was elicited in the same patients. Phonological decoding of speech sounds was assessed by auditory syllable discrimination and found to be intact at all sites where TSA was induced. At a subset of electrode sites where the pattern of language deficits otherwise resembled TSA, naming and word reading remained intact. Language lateralization testing by intracarotid amobarbital injection showed no evidence of independent right hemisphere language. These results suggest that TSA may result from a one-way disruption between left hemisphere phonology and lexical-semantic processing.

Growth of Desulfovibrio on the Surface of Agar Media

PubMed Central

Iverson, Warren P.

1966-01-01

Growth of Desulfovibrio desulfuricans (API strain) was found to take place in an atmosphere of hydrogen on the agar surface of complex media, including yeast extract (Difco), and Trypticase Soy Agar (BBL) without any added reducing agents. For growth on a 2% yeast extract-agar surface in the absence of hydrogen (nitrogen atmosphere), sodium lactate was required in the medium. Growth on the surface of Trypticase Soy Agar (TSA) under nitrogen took place readily in the absence of an added hydrogen donor. A medium (TSA plus salts) is described based upon the addition of sodium lactate (4 ml per liter), magnesium sulfate (2 g per liter), and ferrous ammonium sulfate (0.05%) to TSA, which appears suitable for the isolation and growth of Desulfovibrio on the surface of agar plates in an atmosphere of hydrogen. Sodium lactate does not appear to be essential in this medium for good growth and sulfate reduction in a hydrogen atmosphere, but is essential in a nitrogen atmosphere. Growth of Desulfovibrio (hydrogen atmosphere) on the agar surface of media commonly used for its cultivation as well as on an inorganic medium containing bicarbonate as a source of carbon is poor and erratic unless inoculated (Desulfovibrio) plates of TSA plus salts are incubated in the same container with plates of these media. This stimulatory effect of incubation with inoculated plates of TSA plus salts medium appears to be due to as yet unidentified volatile material produced by D. desulfuricans when growing on this medium. Another volatile material, or possibly the identical material, appears to act similarly to a hydrogen donor. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:5955798

Thermographic Analysis of Stress Distribution in Welded Joints

NASA Astrophysics Data System (ADS)

Piršić, T.; Krstulović Opara, L.; Domazet, Ž.

2010-06-01

The fatigue life prediction of welded joints based on S-N curves in conjunction with nominal stresses generally is not reliable. Stress distribution in welded area affected by geometrical inhomogeneity, irregular welded surface and weld toe radius is quite complex, so the local (structural) stress concept is accepted in recent papers. The aim of this paper is to determine the stress distribution in plate type aluminum welded joints, to analyze the reliability of TSA (Thermal Stress Analysis) in this kind of investigations, and to obtain numerical values for stress concentration factors for practical use. Stress distribution in aluminum butt and fillet welded joints is determined by using the three different methods: strain gauges measurement, thermal stress analysis and FEM. Obtained results show good agreement - the TSA mutually confirmed the FEM model and stresses measured by strain gauges. According to obtained results, it may be stated that TSA, as a relatively new measurement technique may in the future become a standard tool for the experimental investigation of stress concentration and fatigue in welded joints that can help to develop more accurate numerical tools for fatigue life prediction.

HCMM/soil moisture experiment. [relationship between surface minus air temperature differential and available water according to crop type in Canada

NASA Technical Reports Server (NTRS)

Cihlar, J. (Principal Investigator)

1980-01-01

Progress in the compilation and analysis of airborne and ground data to determine the relationship between the maximum surface minus maximum air temperature differential (delta Tsa) and available water (PAW) is reported. Also, results of an analysis of HCMM images to determine the effect of cloud cover on the availability of HCMM-type data are presented. An inverse relationship between delta Tsa and PAW is indicated along with stable delta Tsa vs. PAW distributions for fully developed canopies. Large variations, both geographical and diurnal, in the cloud cover images are reported. The average monthly daytime cloud cover fluctuated between 40 and 60 percent.

Quantifying Residual Stresses by Means of Thermoelastic Stress Analysis

NASA Technical Reports Server (NTRS)

Gyekenyesi, Andrew L.; Baaklini, George Y.

2001-01-01

This study focused on the application of the Thermoelastic Stress Analysis (TSA) technique as a tool for assessing the residual stress state of structures. TSA is based on the fact that materials experience small temperature changes when compressed or expanded. When a structure is cyclically loaded, a surface temperature profile results which correlates to the surface stresses. The cyclic surface temperature is measured with an infrared camera. Traditionally, the amplitude of a TSA signal was theoretically defined to be linearly dependent on the cyclic stress amplitude. Recent studies have established that the temperature response is also dependent on the cyclic mean stress (i.e., the static stress state of the structure). In a previous study by the authors, it was shown that mean stresses significantly influenced the TSA results for titanium- and nickel-based alloys. This study continued the effort of accurate direct measurements of the mean stress effect by implementing various experimental modifications. In addition, a more in-depth analysis was conducted which involved analyzing the second harmonic of the temperature response. By obtaining the amplitudes of the first and second harmonics, the stress amplitude and the mean stress at a given point on a structure subjected to a cyclic load can be simultaneously obtained. The experimental results showed good agreement with the theoretical predictions for both the first and second harmonics of the temperature response. As a result, confidence was achieved concerning the ability to simultaneously obtain values for the static stress state as well as the cyclic stress amplitude of structures subjected to cyclic loads using the TSA technique. With continued research, it is now feasible to establish a protocol that would enable the monitoring of residual stresses in structures utilizing TSA.

Limited antigenic variation in the Trypanosoma cruzi candidate vaccine antigen TSA-1.

PubMed

Knight, J M; Zingales, B; Bottazzi, M E; Hotez, P; Zhan, B

2014-12-01

Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi) is one of the most important neglected tropical diseases in the Western Hemisphere. The toxicities and limited efficacies of current antitrypanosomal drugs have prompted a search for alternative technologies such as a therapeutic vaccine comprised of T. cruzi antigens, including a recombinant antigen encoding the N-terminal 65 kDa portion of Trypomastigote surface antigen-1 (TSA-1). With at least six known genetically distinct T. cruzi lineages, variability between the different lineages poses a unique challenge for the development of broadly effective therapeutic vaccine. The variability across the major lineages in the current vaccine candidate antigen TSA-1 has not previously been addressed. To assess the variation in TSA-1, we cloned and sequenced TSA-1 from several different T. cruzi strains representing three of the most clinically relevant lineages. Analysis of the different alleles showed limited variation in TSA-1 across the different strains and fit with the current theory for the evolution of the different lineages. Additionally, minimal variation in known antigenic epitopes for the HLA-A 02 allele suggests that interlineage variation in TSA-1 would not impair the range and efficacy of a vaccine containing TSA-1. © 2014 John Wiley & Sons Ltd.

Protein-ligand interactions investigated by thermal shift assays (TSA) and dual polarization interferometry (DPI).

PubMed

Grøftehauge, Morten K; Hajizadeh, Nelly R; Swann, Marcus J; Pohl, Ehmke

2015-01-01

Over the last decades, a wide range of biophysical techniques investigating protein-ligand interactions have become indispensable tools to complement high-resolution crystal structure determinations. Current approaches in solution range from high-throughput-capable methods such as thermal shift assays (TSA) to highly accurate techniques including microscale thermophoresis (MST) and isothermal titration calorimetry (ITC) that can provide a full thermodynamic description of binding events. Surface-based methods such as surface plasmon resonance (SPR) and dual polarization interferometry (DPI) allow real-time measurements and can provide kinetic parameters as well as binding constants. DPI provides additional spatial information about the binding event. Here, an account is presented of new developments and recent applications of TSA and DPI connected to crystallography.

Protein–ligand interactions investigated by thermal shift assays (TSA) and dual polarization interferometry (DPI)

PubMed Central

Grøftehauge, Morten K.; Hajizadeh, Nelly R.; Swann, Marcus J.; Pohl, Ehmke

2015-01-01

Over the last decades, a wide range of biophysical techniques investigating protein–ligand interactions have become indispensable tools to complement high-resolution crystal structure determinations. Current approaches in solution range from high-throughput-capable methods such as thermal shift assays (TSA) to highly accurate techniques including microscale thermophoresis (MST) and isothermal titration calorimetry (ITC) that can provide a full thermodynamic description of binding events. Surface-based methods such as surface plasmon resonance (SPR) and dual polarization interferometry (DPI) allow real-time measurements and can provide kinetic parameters as well as binding constants. DPI provides additional spatial information about the binding event. Here, an account is presented of new developments and recent applications of TSA and DPI connected to crystallography. PMID:25615858

Effects of organoclay to miscibility, mechanical and thermal properties of poly(lactic acid) and propylene-ethylene copolymer blends

NASA Astrophysics Data System (ADS)

Wacharawichanant, S.; Ounyai, C.; Rassamee, P.

2017-07-01

The effects of propylene-ethylene copolymer (PEC or PEC3300) and clay surface modified with 25-30 wt% of trimethylstearyl ammonium (Clay-TSA) on morphology, thermal and mechanical properties of poly(lactic acid) (PLA) were investigated. The morphology analysis showed PLA/PEC3300 blends clearly demonstrated a two-phase separation of dispersed phase and the matrix phase and the addition of Clay-TSA could improve the miscibility of PLA and PEC3300 blends due to the decreased of the domain sizes of dispersed PEC3300 phase in the polymer matrix. From X-ray diffraction analysis showed the intercalation of PLA chains inside the Clay-TSA and this result implied that Clay-TSA platelets acted as an effective compatibilizer. The tensile properties showed the strain at break of PLA was improved after adding PEC3300 while Young’s modulus, tensile strength and storage modulus decreased. The addition of Clay-TSA could improve Young’s modulus of PLA/PEC3300 blends. The addition of Clay-TSA 7 phr showed the maximum of Young’s modulus of PLA/PEC3300/Clay-TSA composites. The thermal properties found that the addition of PEC3300 and Clay-TSA did not change significantly on the glass transition temperature and melting point temperature of PLA. The percent of crystallinity of PLA decreased with increasing PEC content. The thermal stability of PLA improved after adding PEC3300.

Fate of para-toluenesulfonamide (p-TSA) in groundwater under anoxic conditions: modelling results from a field site in Berlin (Germany).

PubMed

Meffe, Raffaella; Kohfahl, Claus; Hamann, Enrico; Greskowiak, Janek; Massmann, Gudrun; Dünnbier, Uwe; Pekdeger, Asaf

2014-01-01

This article reports on a field modelling study to investigate the processes controlling the plume evolution of para-toluenesulfonamide (p-TSA) in anoxic groundwater in Berlin, Germany. The organic contaminant p-TSA originates from the industrial production process of plasticisers, pesticides, antiseptics and drugs and is of general environmental concern for urban water management. Previous laboratory studies revealed that p-TSA is degradable under oxic conditions, whereas it appears to behave conservatively in the absence of oxygen (O2). p-TSA is ubiquitous in the aquatic environment of Berlin and present in high concentrations (up to 38 μg L(-1)) in an anoxic aquifer downgradient of a former sewage farm, where groundwater is partly used for drinking water production. To obtain refined knowledge of p-TSA transport and degradation in an aquifer at field scale, measurements of p-TSA were carried out at 11 locations (at different depths) between 2005 and 2010. Comparison of chloride (Cl(-)) and p-TSA field data showed that p-TSA has been retarded in the same manner as Cl(-). To verify the transport behaviour under field conditions, a two-dimensional transport model was setup, applying the dual-domain mass transfer approach in the model sector corresponding to an area of high aquifer heterogeneity. The distribution of Cl(-) and p-TSA concentrations from the site was reproduced well, confirming that both compounds behave conservatively and are subjected to retardation due to back diffusion from water stagnant zones. Predictive simulations showed that without any remediation measures, the groundwater quality near the drinking water well galleries will be affected by high p-TSA loads for about a hundred years.

Summary of Tiger Team Assessment and Technical Safety Appraisal recurring concerns in the Maintenance Area

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

Not Available

1993-01-01

Tiger Team Assessments and Technical Safety Appraisals (TSA) were reviewed and evaluated for concerns in the Maintenance Area (MA). Two hundred and thirty one (231) maintenance concerns were identified by the Tiger Team Assessments and TSA reports. These recurring concerns appear below. A summary of the Noteworthy Practices that were identified and a compilation of the maintenance concerns for each performance objective that were not considered as recurring are also included. Where the Tiger Team Assessment and TSA identified the operating contractor or facility by name, the concern has been modified to remove the name while retaining the intent ofmore » the comment.« less

Protein–ligand interactions investigated by thermal shift assays (TSA) and dual polarization interferometry (DPI)

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

Grøftehauge, Morten K., E-mail: m.k.groftehauge@durham.ac.uk; Hajizadeh, Nelly R.; Swann, Marcus J.

2015-01-01

The biophysical characterization of protein–ligand interactions in solution using techniques such as thermal shift assay, or on surfaces using, for example, dual polarization interferometry, plays an increasingly important role in complementing crystal structure determinations. Over the last decades, a wide range of biophysical techniques investigating protein–ligand interactions have become indispensable tools to complement high-resolution crystal structure determinations. Current approaches in solution range from high-throughput-capable methods such as thermal shift assays (TSA) to highly accurate techniques including microscale thermophoresis (MST) and isothermal titration calorimetry (ITC) that can provide a full thermodynamic description of binding events. Surface-based methods such as surface plasmonmore » resonance (SPR) and dual polarization interferometry (DPI) allow real-time measurements and can provide kinetic parameters as well as binding constants. DPI provides additional spatial information about the binding event. Here, an account is presented of new developments and recent applications of TSA and DPI connected to crystallography.« less

77 FR 30542 - Air Cargo Screening Fees

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-23

... Security Identification Display Area (SIDA) IDs. Another commenter requested that if TSA intends to limit... obtain SIDA IDs were not included in the fee models for this rulemaking because STAs for holders of SIDA... FR 51854. Comment: One commenter appreciated TSA's recognition that the STAs performed under the SIDA...

Indian TSA's: A Force for Community Service

ERIC Educational Resources Information Center

American Indian Journal, 1978

1978-01-01

Assisting tribal governments in meeting the needs of their members, the Kiowa Tribe, the Institute for the Development of Indian Law, and the National Paralegal Institute sponsored the first Tribal Service Advisor training event this year (TSA's can represent clients at the administrative level in many legal and social welfare areas). (JC)

[Tricostantin A inhibits self-renewal of breast cancer stem cells in vitro].

PubMed

Peng, Li; Li, Fu-Xi; Shao, Wen-Feng; Xiong, Jing-Bo

2013-10-01

To investigate the effect of tricostantin A (TSA) on self-renewal of breast cancer stem cells and explore the mechanisms. Breast cancer cell lines MDA-MB-468, MDA-MB-231, MCF-7 and SKBR3 were cultured in suspension and treated with different concentrations of TSA for 7 days, using 0.1% DMSO as the control. Secondary mammosphere formation efficiency and percentage of CD44(+)/CD24(-) sub-population in the primary mammospheres were used to evaluate the effects of TSA on self-renewal of breast cancer stem cells. The breast cancer stem cell surface marker CD44(+)/CD24(-) and the percentage of apoptosis in the primary mammospheres were assayed using flow cytometry. The mRNA expressions of Nanog, Sox2 and Oct4 in the primary mammospheres were assayed with quantitative PCR. TSA at both 100 and 500 nmol/L, but not at 10 nmol/L, partially inhibited the self-renewal of breast cancer stem cells from the 4 cell lines. TSA at 500 nmol/L induced cell apoptosis in the primary mammospheres. TSA down-regulated the mRNA expression of Nanog and Sox2 in the primary mammospheres. TSA can partially inhibit the self-renewal of breast cancer stem cells through a mechanism involving the down-regulation of Nanog and Sox2 expression, indicating the value of combined treatments with low-dose TSA and other anticancer drugs to achieve maximum inhibition of breast cancer stem cell self-renewal. The core transcriptional factor of embryonic stem cells Nanog and Sox2 can be potential targets of anticancer therapy.

A Novel Compact Wideband TSA Array for Near-Surface Ice Sheet Penetrating Radar Applications

NASA Astrophysics Data System (ADS)

Zhang, Feng; Liu, Xiaojun; Fang, Guangyou

2014-03-01

A novel compact tapered slot antenna (TSA) array for near-surface ice sheet penetrating radar applications is presented. This TSA array is composed of eight compact antenna elements which are etched on two 480mm × 283mm FR4 substrates. Each antenna element is fed by a wideband coplanar waveguide (CPW) to coupled strip-line (CPS) balun. The two antenna substrates are connected together with a metallic baffle. To obtain wideband properties, another two metallic baffles are used along broadsides of the array. This array is fed by a 1 × 8 wideband power divider. The measured S11 of the array is less than -10dB in the band of 500MHz-2GHz, and the measured gain is more than 6dBi in the whole band which agrees well with the simulated results.

Determination of retinal surface area.

PubMed

Nagra, Manbir; Gilmartin, Bernard; Thai, Ngoc Jade; Logan, Nicola S

2017-09-01

Previous attempts at determining retinal surface area and surface area of the whole eye have been based upon mathematical calculations derived from retinal photographs, schematic eyes and retinal biopsies of donor eyes. 3-dimensional (3-D) ocular magnetic resonance imaging (MRI) allows a more direct measurement, it can be used to image the eye in vivo, and there is no risk of tissue shrinkage. The primary purpose of this study is to compare, using T2-weighted 3D MRI, retinal surface areas for superior-temporal (ST), inferior-temporal (IT), superior-nasal (SN) and inferior-nasal (IN) retinal quadrants. An ancillary aim is to examine whether inter-quadrant variations in area are concordant with reported inter-quadrant patterns of susceptibility to retinal breaks associated with posterior vitreous detachment (PVD). Seventy-three adult participants presenting without retinal pathology (mean age 26.25 ± 6.06 years) were scanned using a Siemens 3-Tesla MRI scanner to provide T2-weighted MR images that demarcate fluid-filled internal structures for the whole eye and provide high-contrast delineation of the vitreous-retina interface. Integrated MRI software generated total internal ocular surface area (TSA). The second nodal point was used to demarcate the origin of the peripheral retina in order to calculate total retinal surface area (RSA) and quadrant retinal surface areas (QRSA) for ST, IT, SN, and IN quadrants. Mean spherical error (MSE) was -2.50 ± 4.03D and mean axial length (AL) 24.51 ± 1.57 mm. Mean TSA and RSA for the RE were 2058 ± 189 and 1363 ± 160 mm 2 , respectively. Repeated measures anova for QRSA data indicated a significant difference within-quadrants (P < 0.01) which, contrasted with ST (365 ± 43 mm 2 ), was significant for IT (340 ± 40 mm 2 P < 0.01), SN (337 ± 40 mm 2 P < 0.01) and IN (321 ± 39 mm 2 P < 0.01) quadrants. For all quadrants, QRSA was significantly correlated with AL (P < 0.01) and exhibited equivalent increases in retinal area/mm increase in AL. Although the differences between QRSAs are relatively small, there was evidence of concordance with reported inter-quadrant patterns of susceptibility to retinal breaks associated with PVD. The data allow AL to be converted to QRSAs, which will assist further work on inter-quadrant structural variation. © 2017 Anatomical Society.

Development of real-time and quantitative monitoring of thrombus formation in an extracorporeal centrifugal blood pump

NASA Astrophysics Data System (ADS)

Sakota, Daisuke; Fujiwara, Tatsuki; Ohuchi, Katsuhiro; Kuwana, Katsuyuki; Yamazaki, Hiroyuki; Kosaka, Ryo; Maruyama, Osamu

2018-02-01

We developed an optical detector of thrombus formed on the pivot bearing of an extracorporeal centrifugal blood pump (MERA HCF-MP23; Senko Medical Instrument Mfg. Co., Ltd., Tokyo, Japan) which is frequently used for long-term extracorporeal circulation support to bridge to an implantable artificial heart, which in turn is used for bridge to heart transplantation in Japan. In this study, we investigated the quantitative performance of the thrombus formation in acute animal experiments. A total of three experiments of extracorporeal left ventricular assist using Japanese specific pathogen-free pigs were conducted. The optical fibers were set in the pump driver unit. The incident light at nearinfrared wavelength aiming at the pivot bearing and the resulting scattered light were guided to respective fibers. The detected signal was analyzed to obtain thrombus formation level (TFL) calculated by a specially developed software. When the increase in TFL was confirmed, the pump was exchanged and the extracorporeal circulation was restarted. The number of pump exchanges were four times at each experiment so a total of twelve pumps were evaluated. 3-dimentional data surrounding the pivot bearing and the adhered thrombus was captured by a 3-dimantional surface measurement system to calculate the thrombus surface area (TSA) formed on the pivot bearing. As a result, the correlation coefficient between TFL and TSA was 0.878. The accuracy of TSA estimated by the optical detector was 3.6+/-2.3 mm2. This was small enough to not have the pump exchanged in clinical judgement. The developed detector would be useful for optimal anti-coagulation management.

49 CFR 1542.5 - Inspection authority.

Code of Federal Regulations, 2010 CFR

2010-10-01

... areas, AOA's, and SIDA's without access media or identification media issued or approved by an airport... may direct. (d) At the request of TSA and upon the completion of SIDA training as required in a... SIDA's. (e) TSA may enter and be present at an airport that does not have a security program under this...

49 CFR 1542.5 - Inspection authority.

Code of Federal Regulations, 2011 CFR

2011-10-01

... areas, AOA's, and SIDA's without access media or identification media issued or approved by an airport... may direct. (d) At the request of TSA and upon the completion of SIDA training as required in a... SIDA's. (e) TSA may enter and be present at an airport that does not have a security program under this...

49 CFR 1542.5 - Inspection authority.

Code of Federal Regulations, 2014 CFR

2014-10-01

... areas, AOA's, and SIDA's without access media or identification media issued or approved by an airport... may direct. (d) At the request of TSA and upon the completion of SIDA training as required in a... SIDA's. (e) TSA may enter and be present at an airport that does not have a security program under this...

49 CFR 1542.5 - Inspection authority.

Code of Federal Regulations, 2013 CFR

2013-10-01

... areas, AOA's, and SIDA's without access media or identification media issued or approved by an airport... may direct. (d) At the request of TSA and upon the completion of SIDA training as required in a... SIDA's. (e) TSA may enter and be present at an airport that does not have a security program under this...

49 CFR 1542.5 - Inspection authority.

Code of Federal Regulations, 2012 CFR

2012-10-01

... areas, AOA's, and SIDA's without access media or identification media issued or approved by an airport... may direct. (d) At the request of TSA and upon the completion of SIDA training as required in a... SIDA's. (e) TSA may enter and be present at an airport that does not have a security program under this...

Investigation of the fate of sulfonamides downgradient of a decommissioned sewage farm near Berlin, Germany

NASA Astrophysics Data System (ADS)

Richter, Doreen; Massmann, Gudrun; Taute, Thomas; Duennbier, Uwe

2009-05-01

The drinking water production of a drinking water treatment plant in Berlin is affected by ambient contaminated groundwater. The three organic compounds para-toluenesulfonamide (p-TSA), ortho-toluenesulfonamide (o-TSA) and benzenesulfonamide (BSA) were identified in the catchment area of this plant. The groundwater pollution is a result of former sewage farm irrigation in the area, operating for almost 70 years until the 1980s. The distribution of the sulfonamides in the anoxic groundwater was investigated, and a large number of observation and production wells were sampled for this purpose. The contaminant plume is 25 m * 3000 m * 2000 m (depth, length, width) in size. The high concentrations of p-TSA, o-TSA and BSA in the groundwater show that the sulfonamides persist over decades in an anoxic aquifer environment. Groundwater quality assessment revealed that elevated concentrations of the analytes can be expected in the abstraction well galleries in the future. Therefore, sulfonamides should periodically be monitored in the drinking water (maximum allowed concentration of 0.30 µg/L of p-TSA and for o-TSA and BSA, a limit of 0.10 µg/L for unknown substances applies). Because of the widespread application and the persistence of the sulfonamides under anoxic conditions, our local investigations suggest that the substances may generally be present in groundwater under the influence of sewage irrigation. Incubation experiments were conducted under in situ hydrostatic pressure to study the behaviour of these trace organic compounds under different redox conditions (oxic and anoxic). Groundwater sampling equipment was either sterilised or not sterilised in order to distinguish between microbiological processes occurring in the aquifer and those representing sampling and storage artefacts (incubation experiments). Results showed that the addition of oxygen to the anoxic groundwater facilitates p-TSA and o-TSA degradation. Hence, while the substances are persistent under anoxic conditions, they are more degradable in the presence of oxygen. Results also illustrate that maintaining anoxic conditions or applying appropriate preservation techniques is necessary to ensure accurate analysis.

Evaluation of mortality factors using life table analysis of Gratiana boliviana, a biological control agent of tropical soda apple in Florida

USDA-ARS?s Scientific Manuscript database

Tropical soda apple (TSA), Solanum viarum Dunal (Solanaceae), has invaded many pastures and natural areas in Florida. The biological control agent Gratiana boliviana Spaeth (Coleoptera: Chrysomelidae) is providing adequate control of TSA stands in South and Central Florida. However, poor or no es...

Aviation security : TSA is increasing procurement and deployment of the advanced imaging technology, but challenges to this effort and other areas of aviation security remain : testimony before the Subcommittee on Transportation Security and Infrastructur

DOT National Transportation Integrated Search

2010-03-17

The attempted bombing of Northwest flight 253 highlighted the importance of detecting improvised explosive devices on passengers. This testimony focuses on (1) the Transportation Security Administrations (TSA) efforts to procure and deploy advance...

C-terminal cleavage of DeltaNp63alpha is associated with TSA-induced apoptosis in immortalized corneal epithelial cells.

PubMed

Robertson, Danielle M; Ho, Su-Inn; Cavanagh, H Dwight

2010-08-01

In the central human corneal epithelium, loss of DeltaNp63 occurs in all surface epithelial cells preparing to undergo desquamation, suggesting a potential role for DeltaNp63 isoforms in mediating surface cell apoptotic shedding. In this study, the authors investigated a role for DeltaNp63 isoforms in caspase-mediated apoptosis in a telomerase-immortalized corneal epithelial cell line. For in vitro studies, hTCEpi cells were cultured in KGM-2 serum-free culture media containing 0.15 mM calcium. To assess dynamic protein interactions among individual DeltaNp63 isoforms, DeltaNp63-EGFP expression plasmids were transiently expressed in hTCEpi cells and evaluated by FRAP. Trichostatin-A (TSA; 3.31 muM) was used to induce cell death as measured by caspase activity. Cleavage and loss of endogenous DeltaNp63alpha, DeltaNp63-EGFP expression plasmids, and p53 were assessed after treatment with TSA and siRNA. Transient expression of DeltaNp63-EGFP alpha and beta isoforms resulted in the formation of a smaller isoform similar in size to DeltaNp63gamma-EGFP. FRAP demonstrated that DeltaNp63alpha-EGFP has greater immobile fraction than beta or gamma. TSA induced caspase-mediated apoptotic pathways; caspase induction was accompanied by a decrease in endogenous DeltaNp63alpha and p53. TSA upregulated DeltaNp63-EGFP plasmid expression; this was accompanied by a selective increase in cleavage of DeltaNp63alpha-EGFP. siRNA knockdown of DeltaNp63alpha correlated with a reduction in p53 independently of TSA. DeltaNp63alpha is the dominant active isoform in corneal epithelial cell nuclei. Loss of DeltaNp63alpha occurs during apoptotic signaling by cleavage at the C terminus. The corresponding loss of p53 suggests that a significant relationship appears to exist between these two regulatory proteins.

Histone deacetylases inhibitor Trichostatin A ameliorates DNFB-induced allergic contact dermatitis and reduces epidermal Langerhans cells in mice

PubMed Central

Shi, Yu-Ling; Gu, Jun; Park, Jun-Yang; Xu, Ying-Ping; Yu, Fu-Shin; Zhou, Li; Mi, Qing-Sheng

2012-01-01

Background Histone deacetylases (HDACs) influence chromatin organization, representing a key epigenetic regulatory mechanism in cells. Trichostatin A (TSA), a potent HDAC inhibitor, has anti-tumor and anti-inflammatory effects. Allergic contact dermatitis (ACD) is a T-cell-mediated inflammatory reaction in skin and is regulated by epidermal Langerhans cells (LCs). Objective The aim of this study was to investigate if TSA treatment prevents 2,4-dinitrofluorobenzene (DNFB)-induced ACD in mice and regulates epidermal LCs and other immune cells during ACD development. Methods ACD was induced by sensitizing and challenging with DNFB topically. Mice were treated intraperitoneally with TSA or vehicle DMSO as a control every other day before and during induction of ACD. The ear swelling response was measured and skin biopsies from sensitized skin areas were obtained for histology. Epidermal cells, thymus, spleens and skin draining lymph nodes were collected for immune staining. Results TSA treatment ameliorated skin lesion severity of DNFB-induced ACD. The percentages of epidermal LCs and splenic DCs as well as LC maturation were significantly reduced in TSA-treated mice. However, TSA treatment did not significantly affect the homeostasis of conventional CD4+ and CD8+ T cells, Foxp3+CD4+ regulatory T cells, iNKT cells, and γδ T cells in thymus, spleen and draining lymph nodes (dLNs). Furthermore, there were no significant differences in IL-4 and IFN-γ-producing T cells and iNKT cells between TSA- and DMSO-treated mice. Conclusion Our findings suggest that TSA may ameliorate ACD through the regulation of epidermal LCs and HDACs could serve as potential therapeutic targets for ACD and other LCs-related skin diseases. PMID:22999682

Thermoelastic Stress Analysis: An NDE Tool for the Residual Stress Assessment of Metallic Alloys

NASA Technical Reports Server (NTRS)

Gyekenyesi, Andrew L.; Baaklini, George Y.

2000-01-01

During manufacturing, certain propulsion components that will be used in a cyclic fatigue environment are fabricated to contain compressive residual stresses on their surfaces because these stresses inhibit the nucleation of cracks. Overloads and elevated temperature excursions cause the induced residual stresses to dissipate while the component is still in service, lowering its resistance to crack initiation. Research at the NASA Glenn Research Center at Lewis Field has focused on employing the Thermoelastic Stress Analysis technique (TSA, also recognized as SPATE: Stress Pattern Analysis by Thermal Emission) as a tool for monitoring the residual stress state of propulsion components. TSA is based on the fact that materials experience small temperature changes when they are compressed or expanded. When a structure is cyclically loaded (i.e., cyclically compressed and expanded), the resulting surface-temperature profile correlates to the stress state of the structure s surface. The surface-temperature variations resulting from a cyclic load are measured with an infrared camera. Traditionally, the temperature amplitude of a TSA signal has been theoretically defined to be linearly dependent on the cyclic stress amplitude. As a result, the temperature amplitude resulting from an applied cyclic stress was assumed to be independent of the cyclic mean stress.

The structure of the TsaB/TsaD/TsaE complex reveals an unexpected mechanism for the bacterial t6A tRNA-modification.

PubMed

Missoury, Sophia; Plancqueel, Stéphane; Li de la Sierra-Gallay, Ines; Zhang, Wenhua; Liger, Dominique; Durand, Dominique; Dammak, Raoudha; Collinet, Bruno; van Tilbeurgh, Herman

2018-05-08

The universal N6-threonylcarbamoyladenosine (t6A) modification at position A37 of ANN-decoding tRNAs is essential for translational fidelity. In bacteria the TsaC enzyme first synthesizes an l-threonylcarbamoyladenylate (TC-AMP) intermediate. In cooperation with TsaB and TsaE, TsaD then transfers the l-threonylcarbamoyl-moiety from TC-AMP onto tRNA. We determined the crystal structure of the TsaB-TsaE-TsaD (TsaBDE) complex of Thermotoga maritima in presence of a non-hydrolysable AMPCPP. TsaE is positioned at the entrance of the active site pocket of TsaD, contacting both the TsaB and TsaD subunits and prohibiting simultaneous tRNA binding. AMPCPP occupies the ATP binding site of TsaE and is sandwiched between TsaE and TsaD. Unexpectedly, the binding of TsaE partially denatures the active site of TsaD causing loss of its essential metal binding sites. TsaE interferes in a pre- or post-catalytic step and its binding to TsaBD is regulated by ATP hydrolysis. This novel binding mode and activation mechanism of TsaE offers good opportunities for antimicrobial drug development.

Sessile serrated adenoma (SSA) vs. traditional serrated adenoma (TSA).

PubMed

Torlakovic, Emina Emilia; Gomez, Jose D; Driman, David K; Parfitt, Jeremy R; Wang, Chang; Benerjee, Tama; Snover, Dale C

2008-01-01

The morphologic distinction between various serrated polyps of the colorectum may be challenging. The distinction between sessile serrated adenoma (SSA) and traditional serrated adenoma (TSA) may be difficult using currently available criteria mostly based on cytologic characteristics. We have evaluated 66 serrated polyps including 29 SSA, 18 TSA, and 19 hyperplastic polyps for overall shape of the polyps, architectural features of individual crypts, the presence of eosinophilic cytoplasm, size and distribution of the proliferation and maturation zones, as well as Ki-67 and CK20 expression. The extent of the expression of CK20 and Ki-67 could not distinguish between the 3 types of serrated polyps, but the distribution of their expression was very helpful and differences were statistically significant. The distribution of Ki-67+ cells was the single most helpful distinguishing feature of the serrated polyp type (P<0.0001, chi test). Hyperplastic polyps had regular, symmetric, and increased Ki-67 expression. SSA had irregular, asymmetric, and highly variable expression of Ki-67. TSA had low Ki-67 expression, which was limited to "ectopic crypts" and admixed tubular adenomalike areas. In serrated polyps, ectopic crypt formation (ECF) defined by the presence of ectopic crypts with their bases not seated adjacent to the muscularis mucosae was nearly exclusive to TSA and was found in all cases, while the presence of cytologic atypia and eosinophilia of the cytoplasm were characteristic, but not limited to TSA. No evidence of ECF, but nevertheless abnormal distribution of proliferation zone was characteristic of SSA, whereas HP had neither. The presence of the ECF defines TSA in a more rigorous fashion than previous diagnostic criteria and also explains the biologic basis of exuberant protuberant growth associated with TSA and the lack of such growth in SSA. Recognition of this phenomenon may also help in exploring the genetic and molecular basis for differences between SSA and TSA, because these architectural abnormalities may well be a reflection of abnormalities in genetically programmed mucosal development.

Spray method for recovery of heat-injured Salmonella Typhimurium and Listeria monocytogenes.

PubMed

Back, Kyeong-Hwan; Kim, Sang-Oh; Park, Ki-Hwan; Chung, Myung-Sub; Kang, Dong-Hyun

2012-10-01

Selective agar is inadequate for supporting recovery of injured cells. During risk assessment of certain foods, both injured and noninjured cells must be enumerated. In this study, a new method (agar spray method) for recovering sublethally heat-injured microorganisms was developed and used for recovery of heat-injured Salmonella Typhimurium and Listeria monocytogenes. Molten selective agar was applied as an overlay to presolidified nonselective tryptic soy agar (TSA) by spray application. Heat-injured cells (55°C for 10 min in 0.1% peptone water or 55°C for 15 min in sterilized skim milk) were inoculated directly onto solidified TSA. After a 2-h incubation period for cell repair, selective agar was applied to the TSA surface with a sprayer, and the plates were incubated. The recovery rate for heat-injured Salmonella Typhimurium and L. monocytogenes with the spray method was compared with the corresponding rates associated with TSA alone, selective media alone, and the conventional overlay method (selective agar poured on top of resuscitated cells grown on TSA and incubated for 2 h). No significant differences (P > 0.05) were found in pathogen recovery obtained with TSA, the overlay method, and the spray method. However, a lower recovery rate (P < 0.05) was obtained for isolation of injured cells on selective media. Overall, these results indicate that the agar spray method is an acceptable alternative to the conventional overlay method and is a simpler and more convenient approach to recovery and detection of injured cells.

Resonant loading of aircraft secondary structure panels for use with thermoelastic stress analysis and digital image correlation

NASA Astrophysics Data System (ADS)

Waugh, Rachael C.; Dulieu-Barton, Janice M.; Quinn, S.

2015-03-01

Thermoelastic stress analysis (TSA) is an established active thermographic approach which uses the thermoelastic effect to correlate the temperature change that occurs as a material is subjected to elastic cyclic loading to the sum of the principal stresses on the surface of the component. Digital image correlation (DIC) tracks features on the surface of a material to establish a displacement field of a component subjected to load, which can then be used to calculate the strain field. The application of both DIC and TSA on a composite plate representative of aircraft secondary structure subject to resonant frequency loading using a portable loading device, i.e. `remote loading' is described. Laboratory based loading for TSA and DIC is typically imparted using a test machine, however in the current work a vibration loading system is used which is able to excite the component of interest at resonant frequency which enables TSA and DIC to be carried out. The accuracy of the measurements made under remote loading of both of the optical techniques applied is discussed. The data are compared to extract complimentary information from the two techniques. This work forms a step towards a combined strain based non-destructive evaluation procedure able to identify and quantify the effect of defects more fully, particularly when examining component performance in service applications.

Mitigating Localized Corrosion Using Thermally Sprayed Aluminum (TSA) Coatings on Welded 25% Cr Superduplex Stainless Steel

NASA Astrophysics Data System (ADS)

Paul, S.; Lu, Q.; Harvey, M. D. F.

2015-04-01

Thermally sprayed aluminum (TSA) coating has been increasingly used for the protection of carbon steel offshore structures, topside equipment, and flowlines/pipelines exposed to both marine atmospheres and seawater immersion conditions. In this paper, the effectiveness of TSA coatings in preventing localized corrosion, such as pitting and crevice corrosion of 25% Cr superduplex stainless steel (SDSS) in subsea applications, has been investigated. Welded 25% Cr SDSS (coated and uncoated) with and without defects, and surfaces coated with epoxy paint were also examined. Pitting and crevice corrosion tests, on welded 25% Cr SDSS specimens with and without TSA/epoxy coatings, were conducted in recirculated, aerated, and synthetic seawater at 90 °C for 90 days. The tests were carried out at both the free corrosion potentials and an applied cathodic potential of -1100 mV saturated calomel electrode. The acidity (pH) of the test solution was monitored daily and adjusted to between pH 7.5 and 8.1, using dilute HCl solution or dilute NaOH, depending on the pH of the solution measured during the test. The test results demonstrated that TSA prevented pitting and crevice corrosion of 25% Cr SDSS in artificial seawater at 90 °C, even when 10-mm-diameter coating defect exposing the underlying steel was present.

Validation of FMTV Modular VHP/mVHP System and Fumigation Decontamination Process in a C-141B Starlifter Aircraft

DTIC Science & Technology

2007-08-01

each location was aseptically transferred to 5 mL Tryptic Soy Broth (TSB) and incubated at 55 ’C. Coupons were observed the following day. If...Samples were then serially diluted in buffered peptone water and pour plated (1 mL per plate) using Tryptic Soy Agar (TSA). Plates were gently swirled in...1260 area. aft surface inside of hydraulic oil box 19 39 Starboard - 750. 59 On V2 79 On platform, 99 Aft, overhead in on oxygen box overhead, forward

Topical Ophthalmic Formulation of Trichostatin A and SurR9-C84A for Quick Recovery Post-alkali Burn of Corneal Haze

PubMed Central

Roy, Kislay; Cheung, Chun Hei Antonio; Kanwar, Rupinder K.; Sandhir, Rajat; Kanwar, Jagat R.

2017-01-01

Alkali burn injury is a true ocular emergency of the conjunctiva and cornea that requires immediate precision. Lack of an immediate therapy can lead to a substantial damage in the ocular surface and anterior segment further causing visual impairment and disfigurement. We explored the regenerative capability of dominant negative survivin protein (SurR9-C84A) and histone deacetylase inhibitor trichostatin-A (TSA) in vivo, in a rat alkali burn model. A topical insult in rat eyes with NaOH led to degradation of the conjunctival and corneal epithelium. The integrity of the conjunctival and corneal tissue was increased by TSA and SurR9-C84A by improving the clathrin and claudin expressions. Wound healing was initiated by an increase in TGF-beta-1 and, increased endogenous survivin which inhibited apoptosis post-TSA and SurR9-C84A treatments. Protein expressions of fibronectin and alpha-integrin 5 were found to increase promoting corneal integrity. The cytokine analysis confirmed increased expressions of IL-1beta, IL-6, IL-12, IL-13, IFN-gamma, TNF-alpha, GMCSF, Rantes, and MMP-2 in injured cornea, which were found to be significantly downregulated by the combined treatment of SurR9-C84A and TSA. The ocular and systemic pharmacokinetic (PK) parameters were measured post-topical ocular administration of TSA and SurR9-C84A. The SurR9-C84A and TSA sustained relatively longer in the cornea, conjunctiva, and aqueous humor than in the tear fluid and plasma. Our results confirmed that a combination of TSA with SurR9-C8A worked in synergy and showed a promising healing and anti-inflammatory effect in a very short time against alkali burn. Therefore, a combination of TSA and SurR9-C84A can fulfill the need for an immediate response to wound healing in alkali burnt cornea. We also synthesized ultra-small chitosan nanoparticles (USC-NPs) targeted with alpha-SMA antibodies that can be used for delivery of TSA and SurR9-C84A specifically to the ocular burn site. PMID:28529481

A hybrid predictive model for acoustic noise in urban areas based on time series analysis and artificial neural network

NASA Astrophysics Data System (ADS)

Guarnaccia, Claudio; Quartieri, Joseph; Tepedino, Carmine

2017-06-01

The dangerous effect of noise on human health is well known. Both the auditory and non-auditory effects are largely documented in literature, and represent an important hazard in human activities. Particular care is devoted to road traffic noise, since it is growing according to the growth of residential, industrial and commercial areas. For these reasons, it is important to develop effective models able to predict the noise in a certain area. In this paper, a hybrid predictive model is presented. The model is based on the mixing of two different approach: the Time Series Analysis (TSA) and the Artificial Neural Network (ANN). The TSA model is based on the evaluation of trend and seasonality in the data, while the ANN model is based on the capacity of the network to "learn" the behavior of the data. The mixed approach will consist in the evaluation of noise levels by means of TSA and, once the differences (residuals) between TSA estimations and observed data have been calculated, in the training of a ANN on the residuals. This hybrid model will exploit interesting features and results, with a significant variation related to the number of steps forward in the prediction. It will be shown that the best results, in terms of prediction, are achieved predicting one step ahead in the future. Anyway, a 7 days prediction can be performed, with a slightly greater error, but offering a larger range of prediction, with respect to the single day ahead predictive model.

Novel biomolecule lycopene-reduced graphene oxide-silver nanoparticle enhances apoptotic potential of trichostatin A in human ovarian cancer cells (SKOV3)

PubMed Central

Zhang, Xi-Feng; Huang, Feng-Hua; Zhang, Guo-Liang; Bai, Ding-Ping; Massimo, De Felici; Huang, Yi-Fan; Gurunathan, Sangiliyandi

2017-01-01

Background Recently, there has been much interest in the field of nanomedicine to improve prevention, diagnosis, and treatment. Combination therapy seems to be most effective when two different molecules that work by different mechanisms are combined at low dose, thereby decreasing the possibility of drug resistance and occurrence of unbearable side effects. Based on this consideration, the study was designed to investigate the combination effect of reduced graphene oxide-silver nanoparticles (rGO-AgNPs) and trichostatin A (TSA) in human ovarian cancer cells (SKOV3). Methods The rGO-AgNPs were synthesized using a biomolecule called lycopene, and the resultant product was characterized by various analytical techniques. The combination effect of rGO-Ag and TSA was investigated in SKOV3 cells using various cellular assays such as cell viability, cytotoxicity, and immunofluorescence analysis. Results AgNPs were uniformly distributed on the surface of graphene sheet with an average size between 10 and 50 nm. rGO-Ag and TSA were found to inhibit cell viability in a dose-dependent manner. The combination of rGO-Ag and TSA at low concentration showed a significant effect on cell viability, and increased cytotoxicity by increasing the level of malondialdehyde and decreasing the level of glutathione, and also causing mitochondrial dysfunction. Furthermore, the combination of rGO-Ag and TSA had a more pronounced effect on DNA fragmentation and double-strand breaks, and eventually induced apoptosis. Conclusion This study is the first to report that the combination of rGO-Ag and TSA can cause potential cytotoxicity and also induce significantly greater cell death compared to either rGO-Ag alone or TSA alone in SKOV3 cells by various mechanisms including reactive oxygen species generation, mitochondrial dysfunction, and DNA damage. Therefore, this combination chemotherapy could be possibly used in advanced cancers that are not suitable for radiation therapy or surgical treatment and facilitate overcoming tumor resistance and disease progression. PMID:29075115

Statistical downscaling forecast of Chinese winter temperature based on the autumn SST anomalies

NASA Astrophysics Data System (ADS)

Lu, J.

2017-12-01

This study investigates the impacts of the autumn sea surface temperature anomalies (SSTA) on interannual variations of Chinese winter temperature, and discusses the potential predictability of December-January-February (DJF) 2-m air temperature anomalies (TSA) over China based on the intimate linkage between the DJF TSA and autumn SSTA. According to the Empirical Orthogonal Function (EOF) analysis, three leading EOF modes jointly account for 80% of the total TSA variances and are characterized by a homogeneous spatial pattern, a north-south seesaw and a cross structure. The first three EOFs exhibit a stable feature revealed by cross-validation, suggesting the potential predictability of the DJF TSA. The EOF1 mode is influenced by changes in the intensities of the Siberian High (SH), East Asian winter monsoon (EAWM) and East Asian Trough related to an Eurasian pattern teleconnection, which can be tracked back to September-October-November (SON) SSTA associated with two SSTA tripole patterns in the North Pacific and North Atlantic, a dipole mode in the Indian Ocean and an ENSO-like mode in the equatorial and subtropical Pacific. However, the Arctic Oscillation plays an important role in the second mode. The teleconnection connecting the atmospheric circulation anomalies in two hemispheres indicates that the configuration of global SON SSTA induces the two annular modes and causes a TSA oscillation between the northern and southern parts of China. The third mode is related to the westward shift of the SH and western pathway EAWM, which are attributed to two dipole modes in the North Pacific and South Pacific, Atlantic Multidecadal Oscillation and Indian Ocean Basin Mode. Therefore a physically-based statistical model is established based on autumn SSTA indices. Cross-validation suggests that this statistical downscaling forecast model shows a good performance in predicting the DJF TSA.

Diversification of Orientia tsutsugamushi genotypes by intragenic recombination and their potential expansion in endemic areas

PubMed Central

Kim, Gwanghun; Ha, Na-Young; Min, Chan-Ki; Kim, Hong-Il; Yen, Nguyen Thi Hai; Lee, Keun-Hwa; Oh, Inbo; Kang, Jae-Seung; Choi, Myung-Sik; Kim, Ik-Sang

2017-01-01

Background Scrub typhus is a mite-borne febrile disease caused by O. tsutsugamushi infection. Recently, emergence of scrub typhus has attracted considerable attention in several endemic countries in Asia and the western Pacific. In addition, the antigenic diversity of the intracellular pathogen has been a serious obstacle for developing effective diagnostics and vaccine. Methodology/Principal findings To understand the evolutionary pathway of genotypic diversification of O. tsutsugamushi and the environmental factors associated with the epidemiological features of scrub typhus, we analyzed sequence data, including spatiotemporal information, of the tsa56 gene encoding a major outer membrane protein responsible for antigenic variation. A total of 324 tsa56 sequences covering more than 85% of its open reading frame were analyzed and classified into 17 genotypes based on phylogenetic relationship. Extensive sequence analysis of tsa56 genes using diverse informatics tools revealed multiple intragenic recombination events, as well as a substantially higher mutation rate than other house-keeping genes. This suggests that genetic diversification occurred via frequent point mutations and subsequent genetic recombination. Interestingly, more diverse bacterial genotypes and dominant vector species prevail in Taiwan compared to other endemic regions. Furthermore, the co-presence of identical and sub-identical clones of tsa56 gene in geographically distant areas implies potential spread of O. tsutsugamushi genotypes. Conclusions/Significance Fluctuation and diversification of vector species harboring O. tsutsugamushi in local endemic areas may facilitate genetic recombination among diverse genotypes. Therefore, careful monitoring of dominant vector species, as well as the prevalence of O. tsutsugamushi genotypes may be advisable to enable proper anticipation of epidemiological changes of scrub typhus. PMID:28248956

Effects of Histone Deacetylase Inhibitor (HDACi); Trichostatin-A (TSA) on the expression of housekeeping genes.

PubMed

Mogal, Ashish; Abdulkadir, Sarki A

2006-04-01

In quantitative RT-PCR (qRT-PCR), analysis of gene expression is dependent on normalization using housekeeping genes such as 18S rRNA, GAPDH and beta actin. However, variability in their expression has been reported to be caused by factors like drug treatment, pathological states and cell-cycle phase. An emerging area of cancer research focuses on identifying the role of epigenetic alterations such as histone modifications and DNA methylation in the initiation and progression of cancer. Histone acetylation is the best studied modification so far and has been probed through the use of histone deacetylase inhibitors (HDACi). Further, modulation of histone acetylation is currently being explored as a therapeutic strategy in the treatment of cancer and HDACis have shown promise in inhibiting tumorigenesis and metastasis. Trichostatin-A (TSA) is the most widely used HDACi. Therefore, we were driven to identify a suitable internal control for RT-PCR following TSA treatment. We performed quantitative RT-PCR analysis using mouse prostate tissue explants, human prostate cancer (LNCaP) cells and human breast cancer (T-47D and ZR-75-1) cells following TSA treatment. Expression of housekeeping genes including 18S rRNA, beta actin, GAPDH and ribosomal highly-basic 23-kDa protein (rb 23-kDa, RPL13A) were compared in vehicle versus TSA treated samples. Our results showed marked variations in 18S rRNA, beta actin mRNA and GAPDH mRNA levels in mouse prostate explants and a human prostate cancer (LNCaP) cell line following TSA treatment. Furthermore, in two human breast cancer cell lines (T-47D and ZR-75-1) 18S rRNA, beta actin mRNA and GAPDH mRNA levels varied significantly. However, RPL13A mRNA levels remained constant in all the conditions tested. Therefore, we recommend use of RPL13A as a standard for normalization during TSA treatment.

Serrated polyps of the colon and rectum: Endoscopic features including image enhanced endoscopy

PubMed Central

Saito, Shoichi; Tajiri, Hisao; Ikegami, Masahiro

2015-01-01

In this review, I outline the characteristic endoscopic findings of serrated lesions of the colorectum based on image enhanced endoscopy (IEE). Histopathologically, lesions with serrated structures are typically classified into the following three types based: hyperplastic polyps (HPs), traditional serrated adenomas (TSAs), and sessile serrated adenoma/polyps (SSA/Ps). Both HP and SSA/P often present as dark-green colors on auto fluorescence imaging (AFI) colonoscopy that are similar to the normal surrounding mucosa. In contrast, TSAs often have elevated shapes and present as magenta colors that are similar to the tubular adenomas. The superficial type of TSA also includes many lesions that present as magenta colors. When SSA/Ps are associated with cytological dysplasia, many lesions present with magenta colors, whereas lesions that are not associated with cytological dysplasia present with dark-green colors. When observed via narrow band imaging (NBI), many SSA/P include lesions with strong mucous adhesions. Because these lesions are observed with reddish mucous adhesions, we refer to them as “red cap sign” and place such signs among the typical findings of SSA/P. Because the dilatation of the pit in SSA/P is observed as a round/oval black dot on magnified observations, we refer to this finding as II-dilatation pit (II-D pit) and also positioned it as a characteristic finding of SSA/P. In contrast, dilatations of the capillary vessels surrounding the glands, such as those that occur in tubular adenoma, are not considered to be useful for differentiating HPs from SSA/Ps. However, in cases in which SSA/P is associated with cytological dysplasia, the dilatation of capillary vessels is observed in the same area. When submucosal layer invasion occurs in the same area, the blood flow presents with irregularities that are similar to those of common colorectal cancer at an early stage and disappears as the invasion proceeds deeply. The surface pattern of invasive cancer that is observed at the tumor surface is also likely to disappear. Based on the above results, we considered that the differentiations between HP and TSA, between TSA and SSA/P, and between HP and SSA/P might become easier due to the concomitant use of white light observation and IEE. We also concluded that AFI and NBI can be useful modalities for SSA/P lesions associated with cytological dysplasia. PMID:26240687

49 CFR 1503.101 - TSA requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false TSA requirements. 1503.101 Section 1503.101... Scope of Investigative and Enforcement Procedures § 1503.101 TSA requirements. (a) The investigative and enforcement procedures in this part apply to TSA's investigation and enforcement of violations of TSA...

Analyzing commercial flight crewmember perceptions' regarding airline security effectiveness, morale, and professionalism

NASA Astrophysics Data System (ADS)

Belanger, James Durham

Since the formation of the Transportation Security Administration (TSA) following the September 11, 2001 terrorist's attacks few studies involving commercial flight crewmember perceptions' of the organization's efficacy have been conducted, nor has there been any research into the effects on crewmember morale and professionalism resulting from their interactions with the TSA. This researcher surveyed 624 flight crewmembers, using a multiple-choice instrument to ascertain both their perceptions of TSA effectiveness involving an array of security issues, in addition to how crewmember interactions with the TSA may have affected their morale and professionalism. A 2-sample t-test measured the difference in the means of pilots and flight attendants regarding the study's scope, as did 2-way ANOVA and Tukey HSD comparisons, which factored in gender. The study found that crewmembers indicated some confidence in the areas of passenger and baggage screening and the Armed Pilot Program, with less confidence regarding ancillary personnel screening, airport perimeter security, and in both crewmember anti-terrorist training and human error issues. Statistical testing indicated varying differences in sample means concerning all study related issues. Finally, crewmembers indicated some effects on morale and professionalism, with a majority indicating a negative effect on both.

7 CFR 1944.540 - Requesting TSA checks.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 13 2010-01-01 2009-01-01 true Requesting TSA checks. 1944.540 Section 1944.540... TSA checks. (a) The initial TSA check may cover the applicant's needs for the first calendar month. If... the next whole month. (b) The initial advance of TSA grant funds may not be requested simultaneously...

Design and commission of an experimental test rig to apply a full-scale pressure load on composite sandwich panels representative of an aircraft secondary structure

NASA Astrophysics Data System (ADS)

Crump, D. A.; Dulieu-Barton, J. M.; Savage, J.

2010-01-01

This paper describes the design of a test rig, which is used to apply a representative pressure load to a full-scale composite sandwich secondary aircraft structure. A generic panel was designed with features to represent those in the composite sandwich secondary aircraft structure. To provide full-field strain data from the panels, the test rig was designed for use with optical measurement techniques such as thermoelastic stress analysis (TSA) and digital image correlation (DIC). TSA requires a cyclic load to be applied to a structure for the measurement of the strain state; therefore, the test rig has been designed to be mounted on a standard servo-hydraulic test machine. As both TSA and DIC require an uninterrupted view of the surface of the test panel, an important consideration in the design is facilitating the optical access for the two techniques. To aid the test rig design a finite element (FE) model was produced. The model provides information on the deflections that must be accommodated by the test rig, and ensures that the stress and strain levels developed in the panel when loaded in the test rig would be sufficient for measurement using TSA and DIC. Finally, initial tests using the test rig have shown it to be capable of achieving the required pressure and maintaining a cyclic load. It was also demonstrated that both TSA and DIC data can be collected from the panels under load, which are used to validate the stress and deflection derived from the FE model.

Trichostatin A suppresses lung adenocarcinoma development in Grg1 overexpressing transgenic mice

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

Liu, Ju, E-mail: ju.liu@sdu.edu.cn; Molecular and Cellular Biology Division, Sunnybrook Health Science Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5; Li, Yan

Trichostatin A (TSA) is a histone deacetylase inhibitor and a potential therapeutic for various malignancies. The in vivo effect of TSA, however, has not been investigated in a transgenic lung cancer model. Previously, we generated transgenic mice with overexpression of Groucho-related-gene 1 (Grg1) and these mice all developed mucinous lung adenocarcinoma. Grg1 is a transcriptional co-repressor protein, the function of which is thought to depend on HDAC activity. However, functions outside the nucleus have also been proposed. We tested the supposition that Grg1-induced tumorigenesis is HDAC-dependent by assaying the therapeutic effect of TSA in the Grg1 transgenic mouse model. We foundmore » that TSA significantly inhibited lung tumorigenesis in Grg1 transgenic mice (p < 0.01). TSA did not affect overall Grg1 protein levels, but instead reduced ErbB1 and ErbB2 expression, which are upregulated by Grg1 in the absence of TSA. We confirmed this effect in A549 cells. Furthermore, lapatinib, an inhibitor of both ErbB1 and ErbB2, effectively masked the effect of TSA on the inhibition of A549 cell proliferation and migration, suggesting TSA does work, at least in part, by downregulating ErbB receptors. We additionally found that TSA reduced the expression of VEGF and VEGFR2, but not basic FGF and FGFR1. Our findings indicate that TSA effectively inhibits Grg1-induced lung tumorigenesis through the down-regulation of ErbB1 and ErbB2, as well as reduced VEGF signaling. This suggests TSA and other HDAC inhibitors could have therapeutic value in the treatment of lung cancers with Grg1 overexpression. - Highlights: • TSA suppresses lung tumorigenesis in Grg1 overexpressing transgenic mice. • TSA does not affect overall Grg1 protein levels in the mice and in A549 cells. • TSA reduces ErbB1 and ErbB2 expression in the mice and in A549 cells. • Lapatinib masks TSA-induced inhibition of A549 cell proliferation and migration. • TSA inhibits VEGF signaling, but not basic FGF signaling.« less

49 CFR 1550.3 - TSA inspection authority.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false TSA inspection authority. 1550.3 Section 1550.3... RULES § 1550.3 TSA inspection authority. (a) Each aircraft operator subject to this part must allow TSA..., and part 1520 of this chapter; and (2) 49 U.S.C. Subtitle VII, as amended. (b) At the request of TSA...

Estimating front-wave velocity of infectious diseases: a simple, efficient method applied to bluetongue.

PubMed

Pioz, Maryline; Guis, Hélène; Calavas, Didier; Durand, Benoît; Abrial, David; Ducrot, Christian

2011-04-20

Understanding the spatial dynamics of an infectious disease is critical when attempting to predict where and how fast the disease will spread. We illustrate an approach using a trend-surface analysis (TSA) model combined with a spatial error simultaneous autoregressive model (SAR(err) model) to estimate the speed of diffusion of bluetongue (BT), an infectious disease of ruminants caused by bluetongue virus (BTV) and transmitted by Culicoides. In a first step to gain further insight into the spatial transmission characteristics of BTV serotype 8, we used 2007-2008 clinical case reports in France and TSA modelling to identify the major directions and speed of disease diffusion. We accounted for spatial autocorrelation by combining TSA with a SAR(err) model, which led to a trend SAR(err) model. Overall, BT spread from north-eastern to south-western France. The average trend SAR(err)-estimated velocity across the country was 5.6 km/day. However, velocities differed between areas and time periods, varying between 2.1 and 9.3 km/day. For more than 83% of the contaminated municipalities, the trend SAR(err)-estimated velocity was less than 7 km/day. Our study was a first step in describing the diffusion process for BT in France. To our knowledge, it is the first to show that BT spread in France was primarily local and consistent with the active flight of Culicoides and local movements of farm animals. Models such as the trend SAR(err) models are powerful tools to provide information on direction and speed of disease diffusion when the only data available are date and location of cases.

Patterns of interannual climate variability in large marine ecosystems

NASA Astrophysics Data System (ADS)

Soares, Helena Cachanhuk; Gherardi, Douglas Francisco Marcolino; Pezzi, Luciano Ponzi; Kayano, Mary Toshie; Paes, Eduardo Tavares

2014-06-01

The purpose of this study is to investigate the vulnerability of the Brazilian and western African Large Marine Ecosystems (LMEs) to local and remote forcing, including the Pacific Decadal Oscillation (PDO) regime shift. The analyses are based on the total and partial correlation between climate indices (Niño3, tropical South Atlantic (TSA), tropical North Atlantic (TNA) and Antarctic oscillation (AAO) and oceanic and atmospheric variables (sea surface temperature (SST), wind stress, Ekman transport, sea level pressure and outgoing longwave radiation). Differences in the correlation fields between the cold and warm PDO indicate that this mode exerts a significant impact on the thermodynamic balance of the ocean-atmosphere system on the South Atlantic ocean, mainly in the South Brazil and Benguela LMEs. The PDO regime shift also resulted in an increase in the spatial variability of SST and wind stress anomalies, mainly along the western African LMEs. Another important finding is the strong AAO influence on the SST anomalies (SSTA) in the South Brazil LME. It is also striking that TSA modulates the relation between El Niño-Southern Oscillation (ENSO) and SSTA, by reducing the influence of ENSO on SSTA during the warm PDO period in the North and East Brazil LMEs and in the Guinea Current LME. The relation between AAO and SSTA on the tropical area is also influenced by the TSA. The results shown here give a clear indication that future ecosystem-based management actions aimed at the conservation of marine resources under climate change need to consider the high complexity of basin-scale interactions between local and remote climate forcings, including their effects on the ocean-atmosphere system of the South Atlantic ocean.

KSHV cell attachment sites revealed by ultra sensitive tyramide signal amplification (TSA) localize to membrane microdomains that are up-regulated on mitotic cells.

PubMed

Garrigues, H Jacques; Rubinchikova, Yelena E; Rose, Timothy M

2014-03-01

Cell surface structures initiating attachment of Kaposi's sarcoma-associated herpesvirus (KSHV) were characterized using purified hapten-labeled virions visualized by confocal microscopy with a sensitive fluorescent enhancement using tyramide signal amplification (TSA). KSHV attachment sites were present in specific cellular domains, including actin-based filopodia, lamellipodia, ruffled membranes, microvilli and intercellular junctions. Isolated microdomains were identified on the dorsal surface, which were heterogeneous in size with a variable distribution that depended on cellular confluence and cell cycle stage. KSHV binding domains ranged from scarce on interphase cells to dense and continuous on mitotic cells, and quantitation of bound virus revealed a significant increase on mitotic compared to interphase cells. KSHV also bound to a supranuclear domain that was distinct from microdomains in confluent and interphase cells. These results suggest that rearrangement of the cellular membrane during mitosis induces changes in cell surface receptors implicated in the initial attachment stage of KSHV entry. Copyright © 2014 Elsevier Inc. All rights reserved.

Endoscopic analysis of colorectal serrated lesions with cancer.

PubMed

Nagata, Shuichiro; Mitsuyama, Keiichi; Kawano, Hiroshi; Noda, Tetsuhiro; Maeyama, Yasuhiko; Mukasa, Michita; Takedatsu, Hidetoshi; Yoshioka, Shinichiro; Kuwaki, Kotaro; Akiba, Jun; Tsuruta, Osamu; Torimura, Takuji

2018-06-01

Serrated lesions, including hyperplastic polyps (HPs), traditional serrated adenomas (TSAs) and sessile serrated adenomas/polyps (SSA/Ps), are important contributors to colorectal carcinogenesis. The aim of the present study was to analyze the potential of conventional endoscopy and advanced endoscopic imaging techniques to delineate the characteristic features of serrated lesions with cancer. The present study was a retrospective analysis of the data of 168 patients who had undergone colonoscopy, and a total of 228 serrated lesions (77 HPs, 58 TSAs, 84 SSA/Ps, 9 SSA/P plus TSAs) have been identified in these patients. A cancer component was identified in 2.6% of HPs, 13.8% of TSAs and 10.7% of SSA/Ps, but none of SSA/P plus TSAs. Compared with the lesions without cancer, the lesions with cancer exhibited a larger size (HP, TSA and SSA/P), a reddish appearance (SSA/P), a two-tier raised appearance (HP and SSA/P), a central depression (HP, TSA and SSA/P), the type V pit pattern (HP, TSA and SSA/P), and/or the type III capillary pattern (TSA and SSA/P). Deep invasion was identified in 50.0% of HPs, 12.5% of TSAs and 55.6% of SSA/Ps with cancer. The Ki-67 proliferative zone was distributed diffusely within the area of the cancer, but partially within the non-cancer area of HPs, TSAs and SSA/Ps. The lesion types were also analyzed on the basis of mucin phenotype. The present study suggested that a detailed endoscopic analysis of serrated lesions with cancer is useful for delineating characteristic features, and the analysis aids treatment selection.

Alpha-tryptophan synthase of Isatis tinctoria: gene cloning and expression.

PubMed

Salvini, M; Boccardi, T M; Sani, E; Bernardi, R; Tozzi, S; Pugliesi, C; Durante, M

2008-07-01

Indole producing reaction is a crux in the regulation of metabolite flow through the pathways and the coordination of primary and secondary product biosynthesis in plants. Indole is yielded transiently from indole-3-glycerol phosphate and immediately condensed with serine to give tryptophan, by the enzyme tryptophan synthase (TS). There is evidence that plant TS, like the bacterial complex, functions as an alpha beta heteromer. In few species, e.g. maize, are known enzymes, related with the TS alpha-subunit (TSA), able to catalyse reaction producing indole, which is free to enter the secondary metabolite pathways. In this contest, we searched for TSA and TSA related genes in Isatis tinctoria, a species producing the natural blue dye indigo. The It-TSA cDNA and the full-length exons/introns genomic region were isolated. The phylogenetic analysis indicates that It-TSA is more closely related to Arabidopsis thaliana At-T14E10.210 TSA (95.7% identity at the amino acid level) with respect to A. thaliana At-T10P11.11 TSA1-like (63%), Zea mays indole-3-glycerol phosphate lyase (54%), Z. mays TSA (53%), and Z. mays indole synthase (50%). The It-TSA cDNA was also able to complement an Escherichia coli trpA mutant. To examine the involvement of It-TSA in the biosynthesis of secondary metabolism compounds, It-TSA expression was tested in seedling grown under different light conditions. Semi-quantitative RT-PCR showed an increase in the steady-state level of It-TSA mRNA, paralleled by an increase of indigo and its precursor isatan B. Our results appear to indicate an involvement for It-TSA in indigo precursor synthesis and/or tryptophan biosynthesis.

High incidence of hemiarthroplasty for shoulder osteoarthritis among recently graduated orthopaedic surgeons.

PubMed

Mann, Tobias; Baumhauer, Judith F; O'Keefe, Regis J; Harrast, John; Hurwitz, Shepard R; Voloshin, Ilya

2014-11-01

Primary glenohumeral osteoarthritis is a common indication for shoulder arthroplasty. Historically, both total shoulder arthroplasty (TSA) and hemi-shoulder arthroplasty (HSA) have been used to treat primary glenohumeral osteoarthritis. The choice between procedures is a topic of debate, with HSA proponents arguing that it is less invasive, faster, less expensive, and technically less demanding, with quality of life outcomes equivalent to those of TSA. More recent evidence suggests TSA is superior in terms of pain relief, function, ROM, strength, and patient satisfaction. We therefore investigated the practice of recently graduated orthopaedic surgeons pertaining to the surgical treatment of this disease. We hypothesized that (1) recently graduated, board eligible, orthopaedic surgeons with fellowship training in shoulder surgery are more likely to perform TSA than surgeons without this training; (2) younger patients are more likely to receive HSA than TSA; (3) patient sex affects the choice of surgery; (4) US geographic region affects practice patterns; and (5) complication rates for HSA and TSA are not different. We queried the American Board of Orthopaedic Surgery's database to identify practice patterns of orthopaedic surgeons taking their board examination. We identified 771 patients with primary glenohumeral osteoarthritis treated with TSA or HSA from 2006 to 2011. The rates of TSA and HSA were compared based on the treating surgeon's fellowship training, patient age and sex, US geographic region, and reported surgical complications. Surgeons with fellowship training in shoulder surgery were more likely (86% versus 72%; OR 2.32; 95% CI, 1.56-3.45, p<0.001) than surgeons without this training to perform TSA rather than HSA. The mean age for patients receiving HSA was not different from that for patients receiving TSA (66 versus 68, years, p=0.057). Men were more likely to receive HSA than TSA when compared to women (RR 1.54; 95% CI, 1.19-2.00, p=0.0012). The proportions of TSA and HSA were similar regardless of US geographic region (Midwest HSA 21%, TSA 79%; Northeast HSA 25%, TSA 75%; Northwest HSA 16%, TSA 84%; South HSA 27%, TSA 73%; Southeast HSA 24%, TSA 76%; Southwest HSA 23%, TSA 77%; overall p=0.708). The overall complication rates were not different with the numbers available: 8.4% (15/179) for HSA and 8.1% (48/592) for TSA (p=0.7555). The findings of this study are at odds with the recommendations in the current clinical practice guidelines for the treatment of glenohumeral osteoarthritis published by the American Academy of Orthopaedic Surgeons. These guidelines favor using TSA over HSA in the treatment of shoulder arthritis. Further investigation is needed to clarify if these practice patterns are isolated to recently graduated board eligible orthopaedic surgeons or if the use of HSA continues with orthopaedic surgeons applying for recertification. Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

49 CFR 1503.659 - Petition to reconsider or modify a final decision and order of the TSA decision maker on appeal.

Code of Federal Regulations, 2010 CFR

2010-10-01

... and order of the TSA decision maker on appeal. 1503.659 Section 1503.659 Transportation Other... Practice in TSA Civil Penalty Actions § 1503.659 Petition to reconsider or modify a final decision and order of the TSA decision maker on appeal. (a) General. Any party may petition the TSA decision maker to...

Shoulder Arthroplasty for Humeral Head Avascular Necrosis Is Associated With Increased Postoperative Complications.

PubMed

Burrus, M Tyrrell; Cancienne, Jourdan M; Boatright, Jeffrey D; Yang, Scott; Brockmeier, Stephen F; Werner, Brian C

2018-02-01

Humeral head avascular necrosis (AVN) of differing etiologies may lead to shoulder arthroplasty due to subchondral bone collapse and deformity of the articular surface. There have been no large studies evaluating the complications for these patients after they undergo total shoulder arthroplasty (TSA). The first objective of this study is to evaluate the complication rate after TSA in patients with humeral head AVN. The secondary objective is to compare the complication rates among the different etiologies of the AVN. Patients who underwent TSA were identified in the PearlDiver database using ICD-9 codes. Patients who underwent shoulder arthroplasty for humeral head AVN were identified using ICD-9 codes and were subclassified according to AVN etiology (posttraumatic, alcohol use, chronic steroid use, and idiopathic). Complications evaluated included postoperative infection within 6 months, dislocation within 1 year, revision shoulder arthroplasty up to 8 years postoperatively, shoulder stiffness within 1 year, and periprosthetic fracture within 1 year and systemic complications within 3 months. Postoperative complication rates were compared to controls. The study cohorts included 4129 TSA patients with AVN with 141,778 control TSA patients. Patients with posttraumatic AVN were significantly more likely to have a postoperative infection (OR 2.47, P  < 0.001), dislocation (OR 1.45, P  = 0.029), revision surgery (OR 1.53, P  = 0.001), stiffness (OR 1.24, P  = 0.042), and systemic complication (OR 1.49, P  < 0.001). Steroid-associated AVN was associated with a significantly increased risk for a postoperative infection (OR 1.72, P  = 0.004), revision surgery (OR 1.33, P  = 0.040), fracture (OR 2.76, P  = 0.002), and systemic complication (OR 1.59, P  < 0.001). Idiopathic and alcohol-associated AVN were not significantly associated with any of the postoperative evaluated complications. TSA in patients with humeral head AVN is associated with significantly increased rates of numerous postoperative complications compared to patients without a diagnosis of AVN, including infection, dislocation, revision arthroplasty, stiffness, periprosthetic fracture, and medical complications. Specifically, AVN due to steroid use or from a posttraumatic cause appears to be associated with the statistically highest rates of postoperative TSA complications. Given these findings, orthopedic surgeons should be increasingly aware of this association, which should influence the shared decision-making process of undergoing TSA in patients with humeral head AVN.

Efficacy of the thin agar layer method for the recovery of stressed Cronobacter spp. (Enterobacter sakazakii).

PubMed

Osaili, Tareq M; Al-Nabulsi, Anas A; Shaker, Reyad R; Al-Holy, Murad M; Al-Haddaq, Mohammed S; Olaimat, Amin N; Ayyash, Mutamed M; Al Ta'ani, Mahmoud K; Forsythe, Stephen J

2010-10-01

Cronobacter spp. (Enterobacter sakazakii) are emerging opportunistic pathogens for all age groups, and are of particular concern when it comes to infants. Prior to contaminating food, the organism may be exposed to a variety of stresses, leading to a generation of sublethally injured cells that may not be detected by selective media unless a protracted recovery period is included in the isolation procedure. This study evaluated the efficacy of the thin agar layer (TAL) method for the recovery of Cronobacter cells that had been exposed to various stress conditions. Five strains of C. sakazakii and C. muytjensii were exposed to starvation, heat, cold, acid, alkaline, chlorine, or ethanol, with or without further exposure to desiccation stress. The recovery of the stressed cells was determined on tryptone soy agar (TSA; nonselective control medium), violet red bile glucose agar (VRBGA; selective agar), Druggan-Forsythe-Iversen (DFI; selective agar), and TAL media (viz., VRBGA overlaid with TSA, and DFI overlaid with TSA). Regardless of stress type, there were no significant differences among the recoveries of stressed desiccated Cronobacter spp. cultures on TSA, DFI+TSA, and VRBGA+TSA, but there was significantly less recovery on VRBGA. The recovery of prestressed desiccated Cronobacter spp. on DFI+TSA was similar to that on TSA, whereas the recovery on VRBGA+TSA was lower. DFI+TSA performed better than VRBGA+TSA did in differentiating Cronobacter spp. within mixed bacterial cultures. The results of this study suggest the use of the TAL method DFI+TSA as an improved method for the direct recovery of stressed Cronobacter spp.

TSA-induced cell death in prostate cancer cell lines is caspase-2 dependent and involves the PIDDosome.

PubMed

Taghiyev, Agshin F; Guseva, Natalya V; Glover, Rebecca A; Rokhlin, Oskar W; Cohen, Michael B

2006-09-01

The histone deacetylase inhibitor Trichostatin A (TSA) has previously been found to induce caspase activity in the human prostate cancer cell lines DU145 and LNCaP. TSA treatment resulted in the release of cytochrome c and Smac/DIABLO from mitochondria in DU145, and activation of caspase-9 in both cell lines. We concluded that TSA mediated its effect via the mitochondrial pathway. The aim of the current study was to determine how TSA initiated the caspase cascade. The results revealed that caspase-2 plays an important role in TSA-induced apoptosis. Inhibition of caspase-2 by siRNA or expression of caspase-2dn substantially decreased caspase activity after TSA treatment in both cell lines, siRNA caspase-2 also inhibited TSA-induced cell death. Caspase-2 acts upstream of caspase-8 and -9 and mediates mitochondrial cytochrome c release. Coimmunoprecipitation experiments show that caspase-2 formed protein complexes with RADD/RAIDD and PIDD. Together, these data indicate that caspase-2 initiates caspase cascade after TSA treatment and involves the formation of the PIDDosome.

49 CFR 1542.111 - Exclusive area agreements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY Airport Security Program § 1542.111 Exclusive area agreements. (a) TSA may approve an amendment to an airport security program... aircraft operator or foreign air carrier, and maintained in the airport security program. This agreement...

49 CFR 1542.111 - Exclusive area agreements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY Airport Security Program § 1542.111 Exclusive area agreements. (a) TSA may approve an amendment to an airport security program... aircraft operator or foreign air carrier, and maintained in the airport security program. This agreement...

49 CFR 1542.111 - Exclusive area agreements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY Airport Security Program § 1542.111 Exclusive area agreements. (a) TSA may approve an amendment to an airport security program... aircraft operator or foreign air carrier, and maintained in the airport security program. This agreement...

49 CFR 1542.111 - Exclusive area agreements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY Airport Security Program § 1542.111 Exclusive area agreements. (a) TSA may approve an amendment to an airport security program... aircraft operator or foreign air carrier, and maintained in the airport security program. This agreement...

49 CFR 1542.111 - Exclusive area agreements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY Airport Security Program § 1542.111 Exclusive area agreements. (a) TSA may approve an amendment to an airport security program... aircraft operator or foreign air carrier, and maintained in the airport security program. This agreement...

Use of micro-computed tomography to evaluate the effects of exercise on preventing the degeneration of articular cartilage in tail-suspended rats

NASA Astrophysics Data System (ADS)

Luan, Hui-Qin; Sun, Lian-Wen; Huang, Yun-Fei; Wu, Xin-tong; Niu, Haijun; Liu, Hong; Fan, Yu-Bo

2015-07-01

Space flight has been shown to induce bone loss and muscle atrophy, which could initiate the degeneration of articular cartilage. Countermeasures to prevent bone loss and muscle atrophy have been explored, but few spaceflight or ground-based studies have focused on the effects on cartilage degeneration. In this study, we investigated the effects of exercise on articular cartilage deterioration in tail-suspended rats. Thirty-two female Sprague-Dawley rats were randomly divided into four groups (n = 8 in each): tail suspension (TS), tail suspension plus passive motion (TSP), tail suspension plus active exercise (TSA), and control (CON) groups. In the TS, TSP, and TSA groups, the rat hindlimbs were unloaded for 21 days by tail suspension. Next, the cartilage thickness and volume, and the attenuation coefficient of the distal femur were evaluated by micro-computed tomography (μCT). Histological analysis was used to assess the surface integrity of the cartilage, cartilage thickness, and chondrocytes. The results showed that: (1) the cartilage thickness on the distal femur was significantly lower in the TS and TSP groups compared with the CON and TSA groups; (2) the cartilage volume in the TS group was significantly lower compared with the CON, TSA, and TSP groups; and (3) histomorphology showed that the chondrocytes formed clusters where the degree of matrix staining was lower in the TS and TSP groups. There were no significant differences between any of these parameters in the CON and TSA groups. The cartilage thickness measurements obtained by μCT and histomorphology correlated well. In general, tail suspension could induce articular cartilage degeneration, but active exercise was effective in preventing this degeneration in tail-suspended rats.

Growth of Serratia liquefaciens under 7 mbar, 0°C, and CO2-Enriched Anoxic Atmospheres

PubMed Central

Ulrich, Richard; Berry, Bonnie J.; Nicholson, Wayne L.

2013-01-01

Abstract Twenty-six strains of 22 bacterial species were tested for growth on trypticase soy agar (TSA) or sea-salt agar (SSA) under hypobaric, psychrophilic, and anoxic conditions applied singly or in combination. As each factor was added to multi-parameter assays, the interactive stresses decreased the numbers of strains capable of growth and, in general, reduced the vigor of the strains observed to grow. Only Serratia liquefaciens strain ATCC 27592 exhibited growth at 7 mbar, 0°C, and CO2-enriched anoxic atmospheres. To discriminate between the effects of desiccation and hypobaria, vegetative cells of Bacillus subtilis strain 168 and Escherichia coli strain K12 were grown on TSA surfaces and simultaneously in liquid Luria-Bertani (LB) broth media. Inhibition of growth under hypobaria for 168 and K12 decreased in similar ways for both TSA and LB assays as pressures were reduced from 100 to 25 mbar. Results for 168 and K12 on TSA and LB are interpreted to indicate a direct low-pressure effect on microbial growth with both species and do not support the hypothesis that desiccation alone on TSA was the cause of reduced growth at low pressures. The growth of S. liquefaciens at 7 mbar, 0°C, and CO2-enriched anoxic atmospheres was surprising since S. liquefaciens is ecologically a generalist that occurs in terrestrial plant, fish, animal, and food niches. In contrast, two extremophiles tested in the assays, Deinococcus radiodurans strain R1 and Psychrobacter cryohalolentis strain K5, failed to grow under hypobaric (25 mbar; R1 only), psychrophilic (0°C; R1 only), or anoxic (<0.1% ppO2; both species) conditions. Key Words: Habitable zone—Hypobaria—Extremophiles—Special regions—Planetary protection. Astrobiology 13, 115–131. PMID:23289858

7 CFR 1944.514 - Comprehensive TSA grant projects.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., RURAL BUSINESS-COOPERATIVE SERVICE, RURAL UTILITIES SERVICE, AND FARM SERVICE AGENCY, DEPARTMENT OF... growth or decline, the amount of inadequate housing, economic conditions, and trends of the rural areas...

7 CFR 1944.514 - Comprehensive TSA grant projects.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., RURAL BUSINESS-COOPERATIVE SERVICE, RURAL UTILITIES SERVICE, AND FARM SERVICE AGENCY, DEPARTMENT OF... growth or decline, the amount of inadequate housing, economic conditions, and trends of the rural areas...

Visualization of mcr mRNA in a methanogen by fluorescence in situ hybridization with an oligonucleotide probe and two-pass tyramide signal amplification (two-pass TSA-FISH).

PubMed

Kubota, Kengo; Ohashi, Akiyoshi; Imachi, Hiroyuki; Harada, Hideki

2006-09-01

Two-pass tyramide signal amplification-fluorescence in situ hybridization (two-pass TSA-FISH) with a horseradish peroxidase (HRP)-labeled oligonucleotide probe was applied to detect prokaryotic mRNA. In this study, mRNA of a key enzyme for methanogenesis, methyl coenzyme M reductase (mcr), in Methanococcus vannielii was targeted. Applicability of mRNA-targeted probes to in situ hybridization was verified by Clone-FISH. It was observed that sensitivity of two-pass TSA-FISH was significantly higher than that of TSA-FISH, which was further increased by the addition of dextran sulphate in TSA working solution. Signals from two-pass TSA-FISH were more reliable compared to the weak, spotty signals yielded by TSA-FISH.

49 CFR 1507.3 - Exemptions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... exempt from the access provisions of subsection (d). (c) Personnel Background Investigation File System (DHS/TSA 004). The Personnel Background Investigation File System (PBIFS) (DHS/TSA 004) enables TSA to... Traveler Operations Files (DHS/TSA 015). The purpose of this system is to pre-screen and positively...

49 CFR 1507.3 - Exemptions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... exempt from the access provisions of subsection (d). (c) Personnel Background Investigation File System (DHS/TSA 004). The Personnel Background Investigation File System (PBIFS) (DHS/TSA 004) enables TSA to... Traveler Operations Files (DHS/TSA 015). The purpose of this system is to pre-screen and positively...

49 CFR 1507.3 - Exemptions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... exempt from the access provisions of subsection (d). (c) Personnel Background Investigation File System (DHS/TSA 004). The Personnel Background Investigation File System (PBIFS) (DHS/TSA 004) enables TSA to... Traveler Operations Files (DHS/TSA 015). The purpose of this system is to pre-screen and positively...

49 CFR 1507.3 - Exemptions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... exempt from the access provisions of subsection (d). (c) Personnel Background Investigation File System (DHS/TSA 004). The Personnel Background Investigation File System (PBIFS) (DHS/TSA 004) enables TSA to... Traveler Operations Files (DHS/TSA 015). The purpose of this system is to pre-screen and positively...

Noviherbaspirillum denitrificans sp. nov., a denitrifying bacterium isolated from rice paddy soil and Noviherbaspirillum autotrophicum sp. nov., a denitrifying, facultatively autotrophic bacterium isolated from rice paddy soil and proposal to reclassify Herbaspirillum massiliense as Noviherbaspirillum massiliense comb. nov.

PubMed

Ishii, Satoshi; Ashida, Naoaki; Ohno, Hiroki; Segawa, Takahiro; Yabe, Shuhei; Otsuka, Shigeto; Yokota, Akira; Senoo, Keishi

2017-06-01

Thirty-nine denitrifying bacterial strains closely related to one another, represented by strains TSA40T and TSA66T, were isolated from rice paddy soils. Strains TSA40T and TSA66T were Gram-stain-negative, slightly curved rod-shaped, and motile by means of polar flagella. They were able to reduce nitrate, nitrite and nitrous oxide, but unable to fix atmospheric N2. While strain TSA66T was able to grow autotrophically by H2-dependent denitrification, strain TSA40T could not. Phylogenetic analysis suggested that they belong to the family Oxalobacteraceae, the order Burkholderiales in the class Betaproteobacteria. Major components in the fatty acids (C16 : 0, C17 : 0 cyclo, C18 : 1ω7c and summed feature 3) and quinone (Q-8) also supported the affiliation of strains TSA40T and TSA66T to the family Oxalobacteraceae. Based on 16S rRNA gene sequence comparisons, strains TSA40T and TSA66T showed the greatest degree of similarity to Herbaspirillum massiliense JC206T, Noviherbaspirillum malthae CC-AFH3T, Noviherbaspirillum humi U15T, Herbaspirillum seropedicae Z67T and Paucimonas lemoignei LMG 2207T, and lower similarities to the members of other genera. Average nucleotide identity values between the genomes of strain TSA40T, TSA66T and H. massiliense JC206T were 75-77 %, which was lower than the threshold value for species discrimination (95-96 %). Based on the 16S rRNA gene sequence analysis in combination with physiological, chemotaxonomic and genomic properties, strains TSA40T (=JCM 17722T=ATCC TSD-69T) and TSA66T (=JCM 17723T=DSM 25787T) are the type strains of two novel species within the genus Noviherbaspirillum, for which the names Noviherbaspirillum denitrificans sp. nov. and Noviherbaspirillum autotrophicum sp. nov. are proposed, respectively. We also propose the reclassification of Herbaspirillum massiliense as Noviherbaspirillum massiliense comb. nov.

77 FR 4054 - Extension of Agency Information Collection Activity Under OMB Review: TSA Customer Comment Card

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-26

... Information Collection Activity Under OMB Review: TSA Customer Comment Card AGENCY: Transportation Security...). TSA uses a customer comment card to collect passenger comments at airports, including complaints... other forms of information technology. Information Collection Requirement Title: TSA Customer Comment...

49 CFR 1507.3 - Exemptions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... exempt from the access provisions of subsection (d). (e) Correspondence and Matters Tracking Records (DHS/TSA 006). The Correspondence and Matters Tracking Records (CMTR) (DHS/TSA 006) system allows TSA to... is not always possible for TSA or other agencies to know in advance what information is both relevant...

The influence of TSA and VPA on the in vitro differentiation of bone marrow mesenchymal stem cells into neuronal lineage cells: Gene expression studies.

PubMed

Fila-Danilow, Anna; Borkowska, Paulina; Paul-Samojedny, Monika; Kowalczyk, Malgorzata; Kowalski, Jan

2017-03-27

Epigenetic mechanisms regulate the transcription of genes, which can affect the differentiation of MSCs. The aim of the current work is to determine how the histone deacetylase inhibitors TSA and VPA affect the expression of neuronal lineage genes in a culture of rat MSCs (rMSCs). We analyzed the expression of early neuron marker gene (Tubb3), mature neuron markers genes (Vacht, Th, Htr2a) and the oligodendrocyte progenitor marker gene (GalC). Moreover, changes in the gene expression after three different periods of exposure to TSA and VPA were investigated for the first time. After six days of exposition to TSA and VPA, the expression of Tubb3 and GalC decreased, while the expression of Th increased. The highest increase of VAChT expression was observed after three days of TSA and VPA treatment. A decrease in Htr2a gene expression was observed after TSA treatment and an increase was observed after VPA treatment. We also observed that TSA and VPA inhibited cell proliferation and the formation of neurospheres in the rMSCs culture. The central findings of our study are that TSA and VPA affect the expression of neuronal lineage genes in an rMSCs culture. After exposure to TSA or VPA, the expression of early neuronal gene decreases but equally the expression of mature neuron genes increases. After TSA and VPA treatment ER of the oligodendrocyte progenitor marker decreased. TSA and VPA inhibit cell proliferation and the formation of neurospheres in rMSCs culture.

Pitfalls using tyramide signal amplification (TSA) in the mouse gastrointestinal tract: endogenous streptavidin-binding sites lead to false positive staining.

PubMed

Horling, L; Neuhuber, W L; Raab, M

2012-02-15

Highly sensitive immunohistochemical detection systems such as tyramide signal amplification (TSA) are widely used, since they allow using two primary antibodies raised in the same species. Most of them are based on the streptavidin-biotin-peroxidase system and include streptavidin-coupled secondary antibodies. Using TSA in cryostat-sectioned tissues of mouse esophagus, we were puzzled by negative controls with unexpected staining mostly in the ganglionic areas. This prompted us to search for the causing agent and to include also other parts of the mouse gastrointestinal tract for comparison. Streptavidin-coupled antibodies bound to endogenous binding sites yet to be characterized, which are present throughout the mouse intestines. Staining was mainly localized around neuronal cell bodies of enteric ganglia. Thus, caution is warranted when applying streptavidin-coupled antibodies in the mouse gastrointestinal tract. The use of endogenous biotin-blocking kits combined with a prolonged post-fixation time could significantly reduce unintentional staining. Copyright © 2011 Elsevier B.V. All rights reserved.

76 FR 71993 - Extension of Agency Information Collection Activity Under OMB Review: TSA Claims Management Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-21

... Information Collection Activity Under OMB Review: TSA Claims Management Program AGENCY: Transportation... Security Administration (TSA) has forwarded the Information Collection Request (ICR), Office of Management... the nature of the information collection and its expected burden. TSA published a Federal Register...

49 CFR 1522.121 - Security threat assessments for personnel of TSA-approved validation firms.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-approved validation firms. 1522.121 Section 1522.121 Transportation Other Regulations Relating to... FOR ALL MODES OF TRANSPORTATION TSA-APPROVED VALIDATION FIRMS AND VALIDATORS TSA-Approved Validation... for personnel of TSA-approved validation firms. Each of the following must successfully complete a...

Teacher Shortage Areas Nationwide Listing: 1990-91 thru 2005-06

ERIC Educational Resources Information Center

US Department of Education, 2006

2006-01-01

The nationwide Teacher Shortage Area (TSA) lists for the 2004-05 and 2005-06 school years have been completed and are listed by state in this document. A state that desires to propose teacher shortage areas for designation must submit the information required under the program regulations for the following programs: (1) Targeted teacher deferment…

7 CFR 1944.514 - Comprehensive TSA grant projects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... financial and social condition of the individuals within the community; the needs of areas with a... conflict with or duplicate housing studies, plans, projects, or any other housing related activities in a...

7 CFR 1944.514 - Comprehensive TSA grant projects.

Code of Federal Regulations, 2014 CFR

2014-01-01

... financial and social condition of the individuals within the community; the needs of areas with a... conflict with or duplicate housing studies, plans, projects, or any other housing related activities in a...

[TSA improve transgenic porcine cloned embryo development and transgene expression].

PubMed

Kong, Qing-Ran; Zhu, Jiang; Huang, Bo; Huan, Yan-Jun; Wang, Feng; Shi, Yong-Qian; Liu, Zhong-Feng; Wu, Mei-Ling; Liu, Zhong-Hua

2011-07-01

Uncompleted epigenetic reprogramming is attributed to the low efficiency of producing transgenic cloned animals. Histone modification associated with epigenetics can directly influence the embryo development and transgene expression. Trichostatin A (TSA), as an inhibitor of histone deacetylase, can change the status of histone acetylation, improve somatic cell reprogramming, and enhance cloning efficiency. TSA prevents the chromatin structure from being condensed, so that transcription factor could binds to DNA sequence easily and enhance transgene expression. Our study established the optimal TSA treatment on porcine donor cells and cloned embryos, 250 nmol/L, 24 h and 40 nmol/L, 24 h, respectively. Furthermore, we found that both the cloned embryo and the donor cell treated by TSA resulted in the highest development efficiency. Meanwhile, TSA can improve transgene expression in donor cell and cloned embryo. In summary, TSA can significantly improve porcine reconstructed embryo development and transgene expression.

7 CFR 1944.525 - Targeting of TSA funds to States.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 13 2010-01-01 2009-01-01 true Targeting of TSA funds to States. 1944.525 Section... § 1944.525 Targeting of TSA funds to States. (a) The Administrator will determine, based on the most... portion of the available funds for TSA to these States, leaving the balance available for national...

49 CFR 1503.657 - Appeal from initial decision.

Code of Federal Regulations, 2010 CFR

2010-10-01

... AND ENFORCEMENT PROCEDURES Rules of Practice in TSA Civil Penalty Actions § 1503.657 Appeal from... order of the TSA decision maker have been entered on the record. (b) Issues on appeal. A party may... appeal with the consent of the TSA decision maker. If the TSA decision maker grants an extension of time...

49 CFR 1503.201 - Reports of violations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Investigative Procedures § 1503.201 Reports of violations. (a) Any person who knows of a violation of a TSA requirement should report it to appropriate personnel of any TSA office. (b) TSA will review each report made under this section, together with any other information TSA may have that is relevant to the matter...

49 CFR 1503.413 - Notice of Proposed Civil Penalty.

Code of Federal Regulations, 2010 CFR

2010-10-01

... AND ENFORCEMENT PROCEDURES Assessment of Civil Penalties by TSA § 1503.413 Notice of Proposed Civil Penalty. (a) Issuance. TSA may initiate a civil penalty action under this section by serving a Notice of Proposed Civil Penalty on the person charged with a violation of a TSA requirement. TSA will serve the...

Differential effects of trichostatin A on gelatinase A expression in 3T3 fibroblasts and HT-1080 fibrosarcoma cells: implications for use of TSA in cancer therapy.

PubMed

Ailenberg, Menachem; Silverman, Mel

2003-03-07

Trichostatin A (TSA) is a histone deacetylase (HDAC) inhibitor with potential in cancer therapeutics. In a recent communication, we demonstrated that TSA is a selective, potent inhibitor of gelatinase A in 3T3 fibroblasts. In the present study, we extend these observations and examine the effects of TSA in 3T3 fibroblasts compared to HT-1080 fibrosarcoma cells with respect to gelatinase A expression, cell viability, and apoptosis. We find that while expression of gelatinase A in 3T3 fibroblasts is exquisitely sensitive to inhibition by TSA, expression of this enzyme in HT-1080 cells is minimally affected by this compound. Moreover, we show that TSA is pro-apoptotic in HT-1080 cells, but is anti-apoptotic in 3T3 cells. We propose a two-pronged model for the therapeutic action of TSA. On the one hand TSA selectively decreases cancer cell viability, while enhancing the viability of stromal cells. On the other hand, by selectively decreasing gelatinase A expression in stromal but not cancer cells, TSA acts to control metastatic potential by reducing the ability of metastatic cells to recruit stromal cells to secrete gelatinase A.

NMR-based Structural Analysis of Threonylcarbamoyl-AMP Synthase and Its Substrate Interactions.

PubMed

Harris, Kimberly A; Bobay, Benjamin G; Sarachan, Kathryn L; Sims, Alexis F; Bilbille, Yann; Deutsch, Christopher; Iwata-Reuyl, Dirk; Agris, Paul F

2015-08-14

The hypermodified nucleoside N(6)-threonylcarbamoyladenosine (t(6)A37) is present in many distinct tRNA species and has been found in organisms in all domains of life. This post-transcriptional modification enhances translation fidelity by stabilizing the anticodon/codon interaction in the ribosomal decoding site. The biosynthetic pathway of t(6)A37 is complex and not well understood. In bacteria, the following four proteins have been discovered to be both required and sufficient for t(6)A37 modification: TsaC, TsaD, TsaB, and TsaE. Of these, TsaC and TsaD are members of universally conserved protein families. Although TsaC has been shown to catalyze the formation of L-threonylcarbamoyl-AMP, a key intermediate in the biosynthesis of t(6)A37, the details of the enzymatic mechanism remain unsolved. Therefore, the solution structure of Escherichia coli TsaC was characterized by NMR to further study the interactions with ATP and L-threonine, both substrates of TsaC in the biosynthesis of L-threonylcarbamoyl-AMP. Several conserved amino acids were identified that create a hydrophobic binding pocket for the adenine of ATP. Additionally, two residues were found to interact with L-threonine. Both binding sites are located in a deep cavity at the center of the protein. Models derived from the NMR data and molecular modeling reveal several sites with considerable conformational flexibility in TsaC that may be important for L-threonine recognition, ATP activation, and/or protein/protein interactions. These observations further the understanding of the enzymatic reaction catalyzed by TsaC, a threonylcarbamoyl-AMP synthase, and provide structure-based insight into the mechanism of t(6)A37 biosynthesis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Trichostatin A (TSA) sensitizes the human prostatic cancer cell line DU145 to death receptor ligands treatment.

PubMed

Taghiyev, Agshin F; Guseva, Natalya V; Sturm, Mary T; Rokhlin, Oskar W; Cohen, Michael B

2005-04-01

The human prostatic carcinoma cell line DU145 has previously been found to be resistant to treatment with TNF-family ligands. However, TRAIL, TNF-alpha and anti-Fas antibodies (Ab) treatment in combination with the histone deacetylase inhibitor Trichostatin A (TSA) converted the phenotype of DU145 from resistant to sensitive. TSA induced 15% cell death but simultaneous treatment with TRAIL, TNF-alpha and anti-Fas Ab resulted in 55%, 70% and 40% cell death, respectively. Simultaneous treatment did not increase the level of TSA-induced histone acetylation, but induced the release of acetylated histones from chromatin into the cytosol. This release was caspase dependent since it was abrogated by Z-VAD-fmk. In addition, treatment with TSA induced caspase-9 activation and resulted in the release of cytochrome c and Smac/DIABLO from mitochondria. To further investigate the role of caspase-9 in TSA-mediated apoptosis we used two different approaches: (1) cells were pretreated with the caspase-9 inhibitor Z-LEHD-fmk, and (2) cells were transfected with a dominant-negative form of caspase-9. Both approaches gave similar results: cells became resistant to treatment with TSA. These data indicate that TSA mediates its effect via the mitochondrial pathway. This was confirmed by examining DU145 overexpressing Bcl-2. These transfectants were resistant to TSA treatment. Taken together, our data shows that only simultaneous treatment with TNF-family ligands and TSA in DU145 resulted in caspase activity sufficient to induce apoptosis. The combination of TSA and TNF-family ligands could potentially be the basis for the treatment of prostate cancer.

Empirical mono- versus combination antibiotic therapy in adult intensive care patients with severe sepsis - A systematic review with meta-analysis and trial sequential analysis.

PubMed

Sjövall, Fredrik; Perner, Anders; Hylander Møller, Morten

2017-04-01

To assess benefits and harms of empirical mono- vs. combination antibiotic therapy in adult patients with severe sepsis in the intensive care unit (ICU). We performed a systematic review according to the Cochrane Collaboration methodology, including meta-analysis, risk of bias assessment and trial sequential analysis (TSA). We included randomised clinical trials (RCT) assessing empirical mono-antibiotic therapy versus a combination of two or more antibiotics in adult ICU patients with severe sepsis. We exclusively assessed patient-important outcomes, including mortality. Two reviewers independently evaluated studies for inclusion, extracted data, and assessed risk of bias. Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated and the risk of random errors was assessed by TSA. Thirteen RCTs (n = 2633) were included; all were judged as having high risk of bias. Carbapenems were the most frequently used mono-antibiotic (8 of 13 trials). There was no difference in mortality (RR 1.11, 95% CI 0.95-1.29; p = 0.19) or in any other patient-important outcomes between mono- vs. combination therapy. In TSA of mortality, the Z-curve reached the futility area, indicating that a 20% relative risk difference in mortality may be excluded between the two groups. For the other outcomes, TSA indicated lack of data and high risk of random errors. This systematic review of RCTs with meta-analysis and TSA demonstrated no differences in mortality or other patient-important outcomes between empirical mono- vs. combination antibiotic therapy in adult ICU patients with severe sepsis. The quantity and quality of data was low without firm evidence for benefit or harm of combination therapy. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Transcortical Sensory Aphasia after Left Frontal Lobe Infarction: Loss of Functional Connectivity.

PubMed

Kwon, Miseon; Shim, Woo Hyun; Kim, Sang-Joon; Kim, Jong S

2017-01-01

The underlying mechanism of transcortical sensory aphasia (TSA) caused by lesions occurring in the left frontal lobe remains unclear. We attempted to investigate the mechanism with the use of functional MRI (fMRI). We studied 2 patients with TSA after a left frontal infarction identified by diffusion-weighted MRI. As control subjects, a patient with transcortical motor aphasia and a healthy normal adult were chosen. The Korean version of Western Aphasia Battery was performed initially and at 3 months post stroke. We performed fMRI using verb generation and sentence completion tasks. Resting-state fMRI (rs-fMRI) was also obtained for network-level analysis initially and at 3 months post stroke. The results of diffusion- and perfusion-weighted MRI revealed no diffusion-perfusion mismatch. Initial fMRI in patients with TSA showed no reversed inter-/intrahemispheric activation patterns. rs-fMRI showed significantly decreased resting-state functional connectivity in the language network in patients with TSA compared with the control subjects. Follow-up rs-fMRI studies showed improvement in functional connectivity along with the recovery of patients' language function. Our data showed that the auditory comprehension deficits in patients with frontal lobe infarcts is attributed to difficulty accessing the posterior language area due to functional disconnection between language centers in the acute stage of stroke. © 2017 S. Karger AG, Basel.

A Study of the Utility of Results from the 1992 Trial State Assessment (TSA) in Reading for State-Level Administrators of Assessment.

ERIC Educational Resources Information Center

Bullock, Cheryl Davis; DeStefano, Lizanne

1998-01-01

The usefulness of the 1992 TSA in reading was studied using interviews from 26 state directors of assessment. Perceptions about TSA credibility and orientation of test components and current use of TSA results were examined. The directors suggested involving more teachers in assessment, modifying descriptors, disseminating results quicker, and…

Cloning of a Recombinant Plasmid Encoding Thiol-Specific Antioxidant Antigen (TSA) Gene of Leishmania majorand Expression in the Chinese Hamster Ovary Cell Line.

PubMed

Fatemeh, Ghaffarifar; Fatemeh, Tabatabaie; Zohreh, Sharifi; Abdolhosein, Dalimiasl; Mohammad Zahir, Hassan; Mehdi, Mahdavi

2012-01-01

TSA (thiol-specific antioxidant antigen) is the immune-dominant antigen of Leishmania major and is considered to be the most promising candidate molecule for a recombinant or DNA vaccine against leishmaniasis. The aim of the present work was to express a plasmid containing the TSA gene in eukaryotic cells. Genomic DNA was extracted, and the TSA gene was amplified by polymerase chain reaction (PCR). The PCR product was cloned into the pTZ57R/T vector, followed by subcloning into the eukaryotic expression vector pcDNA3 (EcoRI and HindIII sites). The recombinant plasmid was characterised by restriction digest and PCR. Eukaryotic Chinese hamster ovary cells were transfected with the plasmid containing the TSA gene. Expression of the L. major TSA gene was confirmed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blotting. The plasmid containing the TSA gene was successfully expressed, as demonstrated by a band of 22.1 kDa on Western blots. The plasmid containing the TSA gene can be expressed in a eukaryotic cell line. Thus, the recombinant plasmid may potentially be used as a DNA vaccine in animal models.

Neuroprotective capabilities of TSA against cerebral ischemia/reperfusion injury via PI3K/Akt signaling pathway in rats.

PubMed

Ma, Xiao-Hui; Gao, Qiang; Jia, Zhen; Zhang, Ze-Wei

2015-02-01

Hundreds of previous studies demonstrated the cytoprotective effect of trichostatin-A (TSA), a kind of histone deacetylases inhibitors (HDACIs), against cerebral ischemia/reperfusion insult. Meanwhile, phosphatidylinositol-3 kinase/Akt (PI3K/Akt) is a well-known, important signaling pathway that mediates neuroprotection. However, it should be remains unclear whether the neuroprotective capabilities of TSA against cerebral ischemia/reperfusion is mediated by activation of the PI3K/Akt signaling pathway. Five groups rats (n = 12 each), with middle cerebral artery occlusion (MCAO) except sham group, were used to investigate the neuroprotective effect of certain concentration (0.05 mg/kg) of TSA, and whether the neuroprotective effect of TSA is associated with activation of the PI3K/Akt signaling pathway through using of wortmannin (0.25 mg/kg). TSA significantly increased the expression of p-Akt protein, reduced infarct volume, and attenuated neurological deficit in rats with transient MCAO, wortmannin weakened such effect of TSA dramatically. TSA could significantly decrease the neurological deficit scores and reduce the cerebral infarct volume during cerebral ischemia/reperfusion injury, which was achieved partly by activation of the PI3K/Akt signaling pathway via upgrading of p-Akt protein.

Epstein-Barr virus-infected Akata cells are sensitive to histone deacetylase inhibitor TSA-provoked apoptosis.

PubMed

Kook, Sung-Ho; Son, Young-Ok; Han, Seong-Kyu; Lee, Hyung-Soon; Kim, Beom-Tae; Jang, Yong-Suk; Choi, Ki-Choon; Lee, Keun-Soo; Kim, So-Soon; Lim, Ji-Young; Jeon, Young-Mi; Kim, Jong-Ghee; Lee, Jeong-Chae

2005-11-30

Epstein-Barr virus (EBV) infects more than 90 % of the world's population and has a potential oncogenic nature. A histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), has shown potential ability in cancer chemoprevention and treatment, but its effect on EBV-infected Akata cells has not been examined. This study investigated the effect of TSA on the proliferation and apoptosis of the cells. TSA inhibited cell growth and induced cytotoxicity in the EBV-infected Akata cells. TSA treatment sensitively induced apoptosis in the cell, which was demonstrated by the increased number of positively stained cells in the TUNEL assay, the migration of many cells to the sub-G0/G1 phase in flow cytometric analysis, and the ladder formation of genomic DNA. Western blot analysis showed that caspase-dependent pathways are involved in the TSA-induced apoptosis of EBV-infected Akata cells. Overall, this study shows that EBV-infected B lymphomas are quite sensitive to TSA-provoked apoptosis.

The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase

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

Wu, Tzu-Chin; Lin, Yi-Chin; Chen, Hsiao-Ling

Genistein has been shown to enhance the antitumor activity of trichostatin A (TSA) in human lung carcinoma A549 cells. However, whether the combined treatment exerts the same effect in other lung cancer cells is unclear. In the present study we first compared the enhancing effect of genistein on the antitumor effect of TSA in ABC-1, NCI-H460 (H460) and A549 cells. Second, we investigated whether the effects of genistein are associated with increased histone/non-histone protein acetylation. We found that the enhancing effect of genistein on cell-growth-arrest in ABC-1 cells (p53 mutant) was less than in A549 and H460 cells. Genistein enhancedmore » TSA induced apoptosis in A549 and H460 cells rather than in ABC-1 cells. After silencing p53 expression in A549 and H460 cells, the enhancing effect of genistein was diminished. In addition, genistein increased TSA-induced histone H3/H4 acetylation in A549 and H460 cells. Genistein also increased p53 acetylation in H460 cells. The inhibitor of acetyltransferase, anacardic acid, diminished the enhancing effect of genistein on all TSA-induced histone/p53 acetylation and apoptosis. Genistein in combination with TSA increased the expression of p300 protein, an acetyltransferase, in A549 and NCI-H460 cells. Furthermore, we demonstrated that genistein also enhanced the antitumor effect of genistein in A549-tumor-bearing mice. Taken together, these results suggest that the enhancing effects of genistein on TSA-induced apoptosis in lung cancer cells were p53-dependent and were associated with histone/non-histone protein acetylation. - Highlights: • Genistein enhances the antitumor effect of TSA through p53-associated pathways. • Genistein enhances TSA-induced histone acetylation commonly. • An acetyltransferase inhibitor diminishes the antitumor effect of genistein + TSA. • TSA in combination with genistein increases the expression of p300. • Genistein given by i.p. injection increases the antitumor effect of TSA in vivo.« less

UDP-Glucuronosyltransferase 1A Compromises Intracellular Accumulation and Anti-Cancer Effect of Tanshinone IIA in Human Colon Cancer Cells

PubMed Central

Liu, Miao; Wang, Qiong; Liu, Fang; Cheng, Xuefang; Wu, Xiaolan; Wang, Hong; Wu, Mengqiu; Ma, Ying; Wang, Guangji; Hao, Haiping

2013-01-01

Background and Purpose NAD(P)H: quinone oxidoreductase 1 (NQO1) mediated quinone reduction and subsequent UDP-glucuronosyltransferases (UGTs) catalyzed glucuronidation is the dominant metabolic pathway of tanshinone IIA (TSA), a promising anti-cancer agent. UGTs are positively expressed in various tumor tissues and play an important role in the metabolic elimination of TSA. This study aims to explore the role of UGT1A in determining the intracellular accumulation and the resultant apoptotic effect of TSA. Experimental Approach We examined TSA intracellular accumulation and glucuronidation in HT29 (UGT1A positive) and HCT116 (UGT1A negative) human colon cancer cell lines. We also examined TSA-mediated reactive oxygen species (ROS) production, cytotoxicity and apoptotic effect in HT29 and HCT116 cells to investigate whether UGT1A levels are directly associated with TSA anti-cancer effect. UGT1A siRNA or propofol, a UGT1A9 competitive inhibitor, was used to inhibit UGT1A expression or UGT1A9 activity. Key Results Multiple UGT1A isoforms are positively expressed in HT29 but not in HCT116 cells. Cellular S9 fractions prepared from HT29 cells exhibit strong glucuronidation activity towards TSA, which can be inhibited by propofol or UGT1A siRNA interference. TSA intracellular accumulation in HT29 cells is much lower than that in HCT116 cells, which correlates with high expression levels of UGT1A in HT29 cells. Consistently, TSA induces less intracellular ROS, cytotoxicity, and apoptotic effect in HT29 cells than those in HCT116 cells. Pretreatment of HT29 cells with UGT1A siRNA or propofol can decrease TSA glucuronidation and simultaneously improve its intracellular accumulation, as well as enhance TSA anti-cancer effect. Conclusions and Implications UGT1A can compromise TSA cytotoxicity via reducing its intracellular exposure and switching the NQO1-triggered redox cycle to metabolic elimination. Our study may shed a light in understanding the cellular pharmacokinetic and molecular mechanism by which UGTs determine the chemotherapy effects of drugs that are UGTs’ substrates. PMID:24244442

Quercetin Enhances the Antitumor Activity of Trichostatin A through Upregulation of p53 Protein Expression In Vitro and In Vivo

PubMed Central

Chan, Shu-Ting; Yang, Nae-Cherng; Huang, Chin-Shiu; Liao, Jiunn-Wang; Yeh, Shu-Lan

2013-01-01

This study investigated the effects of quercetin on the anti-tumor effect of trichostatin A (TSA), a novel anticancer drug, in vitro and in vivo and the possible mechanisms of these effects in human lung cancer cells. We first showed that quercetin (5 µM) significantly increased the growth arrest and apoptosis in A549 cells (expressing wild-type p53) induced by 25 ng/mL of (82.5 nM) TSA at 48 h by about 25% and 101%, respectively. However, such enhancing effects of quercetin (5 µM) were not significant in TSA-exposed H1299 cells (a p53 null mutant) or were much lower than in A549 cells. In addition, quercetin significantly increased TSA-induced p53 expression in A549 cells. Transfection of p53 siRNA into A549 cells significantly but not completely diminished the enhancing effects of quercetin on TSA-induced apoptosis. Furthermore, we demonstrated that quercetin enhanced TSA-induced apoptosis through the mitochondrial pathway. Transfection of p53 siRNA abolished such enhancing effects of quercetin. However, quercetin increased the acetylation of histones H3 and H4 induced by TSA in A549 cells, even with p53 siRNA transfection as well as in H1299 cells. In a xenograft mouse model of lung cancer, quercetin enhanced the antitumor effect of TSA. Tumors from mice treated with TSA in combination with quercetin had higher p53 and apoptosis levels than did those from control and TSA-treated mice. These data indicate that regulation of the expression of p53 by quercetin plays an important role in enhancing TSA-induced apoptosis in A549 cells. However, p53-independent mechanisms may also contribute to the enhancing effect of quercetin. PMID:23342112

The Smn-Independent Beneficial Effects of Trichostatin A on an Intermediate Mouse Model of Spinal Muscular Atrophy

PubMed Central

Murray, Lyndsay M.; Beauvais, Ariane; Kothary, Rashmi

2014-01-01

Spinal muscular atrophy is an autosomal recessive neuromuscular disease characterized by the progressive loss of alpha motor neurons in the spinal cord. Trichostatin A (TSA) is a histone deacetylase inhibitor with beneficial effects in spinal muscular atrophy mouse models that carry the human SMN2 transgene. It is currently unclear whether TSA specifically targets the SMN2 gene or whether other genes respond to TSA and in turn provide neuroprotection in SMA mice. We have taken advantage of the Smn2B/- mouse model that does not harbor the human SMN2 transgene, to test the hypothesis that TSA has its beneficial effects through a non-SMN mediated pathway. TSA increased the median lifespan of Smn2B/- mice from twenty days to eight weeks. As well, there was a significant attenuation of weight loss and improved motor behavior. Pen test and righting reflex both showed significant improvement, and motor neurons in the spinal cord of Smn2B/- mice were protected from degeneration. Both the size and maturity of neuromuscular junctions were significantly improved in TSA treated Smn2B/- mice. Of interest, TSA treatment did not increase the levels of Smn protein in mouse embryonic fibroblasts or myoblasts obtained from the Smn2B/- mice. In addition, no change in the level of Smn transcripts or protein in the brain or spinal cord of TSA-treated SMA model mice was observed. Furthermore, TSA did not increase Smn protein levels in the hind limb muscle, heart, or liver of Smn2B/- mice. We therefore conclude that TSA likely exerts its effects independent of the endogenous mouse Smn gene. As such, identification of the pathways regulated by TSA in the Smn2B/- mice could lead to the development of novel therapeutics for treating SMA. PMID:24984019

Promotion of Metastasis-associated Gene Expression in Survived PANC-1 Cells Following Trichostatin A Treatment.

PubMed

Chen, Zongjing; Yang, Yunxiu; Liu, Biao; Wang, Benquan; Sun, Meng; Zhang, Ling; Chen, Bicheng; You, Heyi; Zhou, Mengtao

2015-01-01

Histone deacetylase inhibitors represent a promising class of potential anticancer agents for the treatment of human malignancies. In this study, the effects of trichostatin A (TSA) on apoptosis, metastasis-associated gene expression, and activation of the Notch pathway in human pancreatic cancer cell lines were investigated. After treatment with TSA, cell viability and apoptosis were evaluated using the MTT [3-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyltetrazolium bromide] assay, Hoechst 33258 staining, and flow cytometry. Moreover, RT-PCR and western blot analyses were performed to measure the expression levels of apoptosis-associated genes (Bcl-2, Bax, and caspase-3), metastasis-associated genes (E-cadherin, vimentin, and matrix metalloproteinases), and Notch pathway activation (Notch intracellular domain, NICD). The levels of matrix metalloproteinase 2 and NICD were also semi-quantified by immunoassay. Following treatment with TSA for 24 h, PANC-1, SW1990, and MIATACA-2 cells exhibited cell death. The MTT assay revealed that TSA significantly decreased cell viability in a dose-dependent manner in PANC-1 cells. The Hoechst 33258 staining and flow cytometry results evidenced a significant increase in PANC-1 cell apoptosis following TSA treatment. The expression levels of Bax and caspase-3 were increased significantly, whereas Bcl-2 was down-regulated after TSA treatment. In the PANC-1 cells that survived after TSA treatment, the expression levels of vimentin, E-cadherin, and MMP genes were altered by the promotion of potential metastasis and increased expression of NICD. TSA can induce apoptosis of pancreatic cancer cells. In addition, the up-regulation of metastasis-related genes and the activation of the Notch pathway in the survived PANC-1 cells may be associated with a too-low level of TSA or resistance to TSA.

Speed of recovery after shoulder arthroplasty: a comparison of reverse and anatomic total shoulder arthroplasty.

PubMed

Levy, Jonathan C; Everding, Nathan G; Gil, Carlos C; Stephens, Scott; Giveans, M Russell

2014-12-01

Whereas patient expectations after anatomic total shoulder arthroplasty (TSA) and reverse shoulder arthroplasty (RSA) relate to sustained improvements in pain, function, and motion, the time necessary to reach these goals is unclear. Our purpose was to investigate the speed of recovery and to compare the effectiveness of primary TSA and RSA. We analyzed (preoperative, 3 month, 6 month, 1-year, and 2-year scores) pain scores, functional scores, and motion for 122 patients treated with primary RSA and 166 patients treated with primary TSA with a minimum of 1 year of follow-up. Comparisons were made to determine the effectiveness of treatment, time required to reach a plateau in improvement, and percentage of overall improvement at 3 and 6 months. Significant improvements were observed for both TSA and RSA at all intervals (P < .001), except with internal rotation for RSA. Pain relief was rapid after both TSA and RSA. TSA patients reached a consistent plateau for pain and function by 6 months and for shoulder elevation by 1 year. RSA patients demonstrated variability with multiple false plateau points. By 6 months, TSA patients had achieved 90% to 100% of functional improvement, whereas RSA patients reached 72% to 91%. The effectiveness of TSA was greater than that of RSA for all measures with the exception of elevation and abduction. Whereas patients treated with primary TSA and RSA can expect rapid improvements in pain, those treated with TSA can anticipate a more consistent and effective recovery of pain, function, and shoulder rotation. Patients receiving RSA can expect a variable length of recovery with greater improvements in forward elevation and abduction. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Trichostatin A Sensitizes Hepatocellular Carcinoma Cells to Enhanced NK Cell-mediated Killing by Regulating Immune-related Genes.

PubMed

Shin, Sangsu; Kim, Miok; Lee, Seon-Jin; Park, Kang-Seo; Lee, Chang Hoon

2017-01-01

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. The ability of HCC to avoid immune detection is considered one of the main factors making it difficult to cure. Abnormal histone deacetylation is thought to be one of the mechanisms for HCC immune escape, making histone deacetylases (HDACs) attractive targets for HCC treatment. Here, we investigated the effect of trichostatin A (TSA), a highly potent HDAC inhibitor, on HCC (HepG2) gene expression and function. A genome wide-transcriptional microarray was used to identify genes regulated by TSA in HepG2 cells. Gene Ontology was used to identify pathways regulated by TSA, and these changes were confirmed by qPCR. The effect of TSA on natural killer (NK) cell-mediated killing of HCC cell lines were analyzed by both flow cytometry and LDH cytotoxicity assay. A study was also conducted in a Balb/c nude mice xenograft model to assess the anti-tumor activity of TSA. TSA regulated the transcription of numerous innate immunity & tumor antigen recognition-associated genes, such as ULBP1 and RAET1G, in HCC cells. In vivo, TSA reduced tumor cell growth in an NK cell-dependent manner. In vitro, TSA treatment of HepG2 cells rendered them more susceptible to NK cell-mediated killing while increasing the expression of NKGD2 ligands, including ULBP1/2/3 and MICA/B. TSA also induced direct killing of HCC cells by stimulating apoptosis. TSA likely increases killing of HCC cells indirectly by increasing NK cell-directed killing and directly by increasing apoptosis. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Trichostatin A resistance is facilitated by HIF-1α acetylation in HeLa human cervical cancer cells under normoxic conditions

PubMed Central

Lee, Jae-Wook; Yang, Dong Hee; Park, Sojin; Han, Hae-Kyoung; Park, Jong-Wan; Kim, Bo Yeon; Um, Sung Hee; Moon, Eun-Yi

2018-01-01

Trichostatin A (TSA) is an anticancer drug that inhibits histone deacetylases (HDACs). Hypoxia-inducible factor 1 (HIF-1) participates in tumor angiogenesis by upregulating target genes, such as vascular endothelial growth factor (VEGF). In the present study, we investigated whether TSA treatment increases HIF-1α stabilization via acetylation under normoxic conditions, which would lead to VEGF upregulation and resistance to anticancer drugs. TSA enhanced total HIF-1α and VEGF-HRE reporter activity under normoxic conditions. When cells were transfected with GFP-HIF-1α, treatment with TSA increased the number of green fluorescence protein (GFP)-positive cells. TSA also enhanced the nuclear translocation of HIF-1α protein, as assessed by immunoblotting and as evidenced by increased nuclear localization of GFP-HIF-1α. An increase in the interaction between HIF-1α and the VEGF promoter, which was assessed by a chromatin immunoprecipitation (ChIP) assay, led to activation of the VEGF promoter. TSA acetylated HIF-1α at lysine (K) 674, which led to an increase in TSA-induced VEGF-HRE reporter activity. In addition, TSA-mediated cell death was reduced by the overexpression of HIF-1α but it was rescued by transfection with a HIF-1α mutant (K674R). These data demonstrate that HIF-1α may be stabilized and translocated into the nucleus for the activation of VEGF promoter by TSA-mediated acetylation at K674 under normoxic conditions. These findings suggest that HIF-1α acetylation may lead to resistance to anticancer therapeutics, such as HDAC inhibitors, including TSA. PMID:29416751

ERK inhibition enhances TSA-induced gastric cancer cell apoptosis via NF-κB-dependent and Notch-independent mechanism.

PubMed

Yao, Jun; Qian, Cui-Juan; Ye, Bei; Zhang, Xin; Liang, Yong

2012-09-04

To analyze the combined impact of the histone deacetylase inhibitor (HDACI) Trichostatin A (TSA) and the extracellular-signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 on gastric cancer (GC) cell line SGC7901 growth. SGC7901 cells were treated with TSA, PD98059 or with a TSA-PD98059 combination. Effects of drug treatment on tumor cell proliferation, apoptosis, cell cycle progression, and cell signaling pathways were investigated by MTS assay, flow cytometry, Western blotting, chromatin immunoprecipitation (ChIP) assay, electrophoretic mobility shift assay (EMSA), and luciferase reporter assay, respectively. PD98059 enhanced TSA-induced cell growth arrest, apoptosis and activation of p21(WAF1/CIP1), but reversed TSA-induced activation of ERK1/2 and nuclear factor-κB (NF-κB). TSA alone up-regulated Notch1 and Hes1, and down-regulated Notch2, but PD98059 did not affect the trends of Notch1 and Notch2 induced by TSA. Particularly, PD98059 did potentiate the ability of TSA to down-regulate phospho-histone H3 protein, but increased levels of the acetylated forms of histone H3 bound to the p21(WAF1/CIP1) promoter, leading to enhanced expression of p21(WAF1/CIP1) in SGC7901 cells. PD98059 synergistically potentiates TSA-induced GC growth arrest and apoptosis by manipulating NF-κB and p21(WAF1/CIP1) independent of Notch. Therefore, concomitant administration of HDACIs and ERK1/2 inhibitors may be a promising treatment strategy for individuals with GC. Copyright © 2012 Elsevier Inc. All rights reserved.

Trichostatin A Sensitizes Hepatocellular Carcinoma Cells to Enhanced NK Cell-mediated Killing by Regulating Immune-related Genes

PubMed Central

SHIN, SANGSU; KIM, MIOK; LEE, SEON-JIN; PARK, KANG-SEO

2017-01-01

Background/Aim: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. The ability of HCC to avoid immune detection is considered one of the main factors making it difficult to cure. Abnormal histone deacetylation is thought to be one of the mechanisms for HCC immune escape, making histone deacetylases (HDACs) attractive targets for HCC treatment. Here, we investigated the effect of trichostatin A (TSA), a highly potent HDAC inhibitor, on HCC (HepG2) gene expression and function. Materials and Methods: A genome wide-transcriptional microarray was used to identify genes regulated by TSA in HepG2 cells. Gene Ontology was used to identify pathways regulated by TSA, and these changes were confirmed by qPCR. The effect of TSA on natural killer (NK) cell-mediated killing of HCC cell lines were analyzed by both flow cytometry and LDH cytotoxicity assay. A study was also conducted in a Balb/c nude mice xenograft model to assess the anti-tumor activity of TSA. Results: TSA regulated the transcription of numerous innate immunity & tumor antigen recognition-associated genes, such as ULBP1 and RAET1G, in HCC cells. In vivo, TSA reduced tumor cell growth in an NK cell-dependent manner. In vitro, TSA treatment of HepG2 cells rendered them more susceptible to NK cell-mediated killing while increasing the expression of NKGD2 ligands, including ULBP1/2/3 and MICA/B. TSA also induced direct killing of HCC cells by stimulating apoptosis. Conclusion: TSA likely increases killing of HCC cells indirectly by increasing NK cell-directed killing and directly by increasing apoptosis. PMID:28871002

Trichostatin A Abrogates Airway Constriction, but Not Inflammation, in Murine and Human Asthma Models

PubMed Central

Trivedi, Chinmay M.; Damera, Gautam; Jiang, Meiqi; Jester, William; Hoshi, Toshinori; Epstein, Jonathan A.; Panettieri, Reynold A.

2012-01-01

Histone deacetylase (HDAC) inhibitors may offer novel approaches in the treatment of asthma. We postulate that trichostatin A (TSA), a Class 1 and 2 inhibitor of HDAC, inhibits airway hyperresponsiveness in antigen-challenged mice. Mice were sensitized and challenged with Aspergillus fumigatus antigen (AF) and treated with TSA, dexamethasone, or vehicle. Lung resistance (RL) and dynamic compliance were measured, and bronchial alveolar lavage fluid (BALF) was analyzed for numbers of leukocytes and concentrations of cytokines. Human precision-cut lung slices (PCLS) were treated with TSA and their agonist-induced bronchoconstriction was measured, and TSA-treated human airway smooth muscle (ASM) cells were evaluated for the agonist-induced activation of Rho and intracellular release of Ca2+. The activity of HDAC in murine lungs was enhanced by antigen and abrogated by TSA. TSA also inhibited methacholine (Mch)-induced increases in RL and decreases in dynamic compliance in naive control mice and in AF-sensitized and -challenged mice. Total cell counts, concentrations of IL-4, and numbers of eosinophils in BALF were unchanged in mice treated with TSA or vehicle, whereas dexamethasone inhibited the numbers of eosinophils in BALF and concentrations of IL-4. TSA inhibited the carbachol-induced contraction of PCLS. Treatment with TSA inhibited the intracellular release of Ca2+ in ASM cells in response to histamine, without affecting the activation of Rho. The inhibition of HDAC abrogates airway hyperresponsiveness to Mch in both naive and antigen-challenged mice. TSA inhibits the agonist-induced contraction of PCLS and mobilization of Ca2+ in ASM cells. Thus, HDAC inhibitors demonstrate a mechanism of action distinct from that of anti-inflammatory agents such as steroids, and represent a promising therapeutic agent for airway disease. PMID:22298527

Histone deacetylase 6 controls Notch3 trafficking and degradation in T-cell acute lymphoblastic leukemia cells.

PubMed

Pinazza, Marica; Ghisi, Margherita; Minuzzo, Sonia; Agnusdei, Valentina; Fossati, Gianluca; Ciminale, Vincenzo; Pezzè, Laura; Ciribilli, Yari; Pilotto, Giorgia; Venturoli, Carolina; Amadori, Alberto; Indraccolo, Stefano

2018-04-12

Several studies have revealed that endosomal sorting controls the steady-state levels of Notch at the cell surface in normal cells and prevents its inappropriate activation in the absence of ligands. However, whether this highly dynamic physiologic process can be exploited to counteract dysregulated Notch signaling in cancer cells remains unknown. T-ALL is a malignancy characterized by aberrant Notch signaling, sustained by activating mutations in Notch1 as well as overexpression of Notch3, a Notch paralog physiologically subjected to lysosome-dependent degradation in human cancer cells. Here we show that treatment with the pan-HDAC inhibitor Trichostatin A (TSA) strongly decreases Notch3 full-length protein levels in T-ALL cell lines and primary human T-ALL cells xenografted in mice without substantially reducing NOTCH3 mRNA levels. Moreover, TSA markedly reduced the levels of Notch target genes, including pTα, CR2, and DTX-1, and induced apoptosis of T-ALL cells. We further observed that Notch3 was post-translationally regulated following TSA treatment, with reduced Notch3 surface levels and increased accumulation of Notch3 protein in the lysosomal compartment. Surface Notch3 levels were rescued by inhibition of dynein with ciliobrevin D. Pharmacologic studies with HDAC1, 6, and 8-specific inhibitors disclosed that these effects were largely due to inhibition of HDAC6 in T-ALL cells. HDAC6 silencing by specific shRNA was followed by reduced Notch3 expression and increased apoptosis of T-ALL cells. Finally, HDAC6 silencing impaired leukemia outgrowth in mice, associated with reduction of Notch3 full-length protein in vivo. These results connect HDAC6 activity to regulation of total and surface Notch3 levels and suggest HDAC6 as a potential novel therapeutic target to lower Notch signaling in T-ALL and other Notch3-addicted tumors.

49 CFR 1542.303 - Security Directives and Information Circulars.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Contingency Measures § 1542.303 Security Directives and Information Circulars. (a) TSA may issue an... Security Directive by submitting data, views, or arguments in writing to TSA. TSA may amend the Security...

[The mechanisms of p21WAF1/Cip-1 expression in MOLT-4 cell line induced by TSA].

PubMed

Song, Yi; Liu, Mei-Ju; Zhao, Guo-Wei; Qian, Jun-Jie; Dong, Yan; Liu, Hua; Sun, Guo-Jing; Mei, Zhu-Zhong; Liu, Bin; Tian, Bao-Lei; Sun, Zhi-Xian

2005-04-01

To investigate the function and molecular mechanism of p21(WAF1/Cip-1) expression in MOLT-4 cells induced by HDAC inhibitor TSA, the expression pattern of p21(WAF1/Cip-1) and the distribution of cell cycle in TSA treated cells were analyzed. The results showed that TSA could effectively induce G(2)/M arrest and apoptosis of MOLT-4 cells. Kinetic experiments demonstrated that p21(WAF1/Cip-1) were upregulated quickly before cell arrested in G(2)/M and began decreasing at the early stage of apoptosis. Meanwhile, the proteasome inhibitor MG-132 could inhibit the decrease of p21(WAF1/Cip-1) at the early stage of apoptosis, which showed that proteasome pathway involved in p21(WAF1/Cip-1) degradation during the TSA induced G(2)/M arrest and apoptosis responses. This study also identified that the protein level of p21(WAF1/Cip-1) was highly associated with the cell cycle change induced by TSA. Compared to cells treated by TSA only, exposure MOLT-4 cells to TSA meanwhile treatment with MG-132 increased the protein level of p21(WAF1/Cip-1) and increased the numbers of cell in G(2)/M-phase, whereas the cell apoptosis were delayed. It is concluded that p21(WAF1/Cip-1) plays a significant role in G(2)/M arrest and apoptosis signaling induced by TSA in MOLT-4 cells.

Effect of trichostatin A on Burkitt's lymphoma cells: Inhibition of EPS8 activity through Phospho-Erk1/2 pathway.

PubMed

Sun, Peipei; Zhou, Xin; He, Yingzhi; Liu, Huimin; Wang, Yuxin; Chen, Yiran; Li, Meifang; He, Yanjie; Li, Guowei; Li, Yuhua

2018-03-18

Histone deacetylase inhibitors (HDACi) manifest great potential for treatment of Burkitt's lymphoma (BL), an aggressive B-cell lymphoma. Epidermal growth factor receptor pathway substrate 8 (EPS8) is confirmed overexpressed and associated with poor prognosis in solid tumors and leukemia. However, EPS8 expression and the relationship between EPS8 and HDACi on BL remains obscure. Here, we hypothesized that trichostatin A (TSA), a pan-HDACi, could inhibit BL cells by downregulating EPS8. We demonstrated that TSA reduced cell viability, induced apoptosis and cell arrest at G0/G1. Mechanismly, TSA attenuated EPS8 and downstream Phospho-Erk1/2 pathway. Knockdown of EPS8 resulted in a significant reduction in cellular proliferation and suppressed Phospho-Erk1/2 pathway activity, particularly when combined with TSA. Conversely, overexpression of EPS8 rescued this phenomenon. Then we showed that the combination of TSA and Epirubicin had a more significant effect when compared with TSA or Epirubicin alone. Finally, knockdown of EPS8 and TSA had a synergistic suppression effect on BALB/c nude mice. In conclusion, this study reveals that TSA affects BL cells by suppressing Phospho-Erk1/2 pathway through downregulating EPS8. Copyright © 2018 Elsevier Inc. All rights reserved.

Notch Antennas

NASA Technical Reports Server (NTRS)

Lee, Richard Q.

2004-01-01

Notch antennas, also known as the tapered slot antenna (TSA), have been the topics of research for decades. TSA has demonstrated multi-octave bandwidth, moderate gain (7 to 10 dB), and symmetric E- and H- plane beam patterns and can be used for many different applications. This chapter summarizes the research activities on notch antennas over the past decade with emphasis on their most recent advances and applications. This chapter begins with some discussions on the designs of single TSA; then follows with detailed discussions of issues associated with TSA designs and performance characteristics. To conclude the chapter, some recent developments in TSA arrays and their applications are highlighted.

Histone deacetylase inhibitors protect against cisplatin-induced acute kidney injury by activating autophagy in proximal tubular cells.

PubMed

Liu, Jing; Livingston, Man J; Dong, Guie; Tang, Chengyuan; Su, Yunchao; Wu, Guangyu; Yin, Xiao-Ming; Dong, Zheng

2018-02-23

Histone deacetylase inhibitors (HDACi) have therapeutic effects in models of various renal diseases including acute kidney injury (AKI); however, the underlying mechanism remains unclear. Here we demonstrate that two widely tested HDACi (suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA)) protect the kidneys in cisplatin-induced AKI by enhancing autophagy. In cultured renal proximal tubular cells, SAHA and TSA enhanced autophagy during cisplatin treatment. We further verified the protective effect of TSA against cisplatin-induced apoptosis in these cells. Notably, inhibition of autophagy by chloroquine or by autophagy gene 7 (Atg7) ablation diminished the protective effect of TSA. In mice, TSA increased autophagy in renal proximal tubules and protected against cisplatin-induced AKI. The in vivo effect of TSA was also abolished by chloroquine and by Atg7 knockout specifically from renal proximal tubules. Mechanistically, TSA stimulated AMPK and inactivated mTOR during cisplatin treatment of proximal tubule cells and kidneys in mice. Together, these results suggest that HDACi may protect kidneys by activating autophagy in proximal tubular cells.

Draft genome sequence of multidrug-resistant Staphylococcus haemolyticus IPK_TSA25 harbouring a Staphylococcus aureus plasmid, pS0385-1.

PubMed

Kim, Hyung Jun; Jang, Soojin

2017-12-01

Staphylococcus haemolyticus is the second most frequently isolated coagulase-negative staphylococci from blood cultures. Moreover, multidrug resistance associated with the genome flexibility of S. haemolyticus has been increasingly reported worldwide. Here we report the draft genome sequence of multidrug-resistant S. haemolyticus IPK_TSA25 isolated from a building surface in South Korea. Genomic DNA of S. haemolyticus IPK_TSA25 was sequenced using the PacBio RS II sequencing platform. Generated reads were assembled using PacBio SMRT Analysis 2.3.0. The draft genome was annotated and antibiotic resistance genes were identified. The genome of 2517398bp contains various antibiotic resistance genes associated with resistance to β-lactams, aminoglycosides and macrolides. Genome analysis also revealed chromosomal integration of the full-length Staphylococcus aureus plasmid pS0385-1 containing a tetracycline resistance gene. The genome sequence reported in this study will provide valuable information to understand the flexibility of the S. haemolyticus genome, which facilitates acquisition of antibiotic resistance genes and contributes to the dissemination of antibiotic resistance by this emerging pathogen. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Malaria epidemics and the influence of the tropical South Atlantic on the Indian monsoon

NASA Astrophysics Data System (ADS)

Cash, B. A.; Rodó, X.; Ballester, J.; Bouma, M. J.; Baeza, A.; Dhiman, R.; Pascual, M.

2013-05-01

The existence of predictability in the climate system beyond the relatively short timescales of synoptic weather has provided significant impetus to investigate climate variability and its consequences for society. In particular, relationships between the relatively slow changes in sea surface temperature (SST) and climate variability at widely removed points across the globe provide a basis for statistical and dynamical efforts to predict numerous phenomena, from rainfall to disease incidence, at seasonal to decadal timescales. We describe here a remote influence, identified through observational analysis and supported through numerical experiments with a coupled atmosphere-ocean model, of the tropical South Atlantic (TSA) on both monsoon rainfall and malaria epidemics in arid northwest India. Moreover, SST in the TSA is shown to provide the basis for an early warning of anomalous hydrological conditions conducive to malaria epidemics four months later, therefore at longer lead times than those afforded by rainfall. We find that the TSA is not only significant as a modulator of the relationship between the monsoon and the El Niño/Southern Oscillation, as has been suggested by previous work, but for certain regions and temporal lags is in fact a dominant driver of rainfall variability and hence malaria outbreaks.

High performance polypyrrole coating for corrosion protection and biocidal applications

NASA Astrophysics Data System (ADS)

Nautiyal, Amit; Qiao, Mingyu; Cook, Jonathan Edwin; Zhang, Xinyu; Huang, Tung-Shi

2018-01-01

Polypyrrole (PPy) coating was electrochemically synthesized on carbon steel using sulfonic acids as dopants: p-toluene sulfonic acid (p-TSA), sulfuric acid (SA), (±) camphor sulfonic acid (CSA), sodium dodecyl sulfate (SDS), and sodium dodecylbenzene sulfonate (SDBS). The effect of acidic dopants (p-TSA, SA, CSA) on passivation of carbon steel was investigated by linear potentiodynamic and compared with morphology and corrosion protection performance of the coating produced. The types of the dopants used were significantly affecting the protection efficiency of the coating against chloride ion attack on the metal surface. The corrosion performance depends on size and alignment of dopant in the polymer backbone. Both p-TSA and SDBS have extra benzene ring that stack together to form a lamellar sheet like barrier to chloride ions thus making them appropriate dopants for PPy coating in suppressing the corrosion at significant level. Further, adhesion performance was enhanced by adding long chain carboxylic acid (decanoic acid) directly in the monomer solution. In addition, PPy coating doped with SDBS displayed excellent biocidal abilities against Staphylococcus aureus. The polypyrrole coatings on carbon steels with dual function of anti-corrosion and excellent biocidal properties shows great potential application in the industry for anti-corrosion/antimicrobial purposes.

49 CFR 1544.228 - Access to cargo and cargo screening: Security threat assessments for cargo personnel in the...

Code of Federal Regulations, 2012 CFR

2012-10-01

... cargo enters an airport Security Identification Display Area or is transferred to another TSA-regulated... program accepts the cargo until the cargo— (A) Enters an airport Security Identification Display Area; (B... 49 Transportation 9 2012-10-01 2012-10-01 false Access to cargo and cargo screening: Security...

49 CFR 1544.228 - Access to cargo and cargo screening: Security threat assessments for cargo personnel in the...

Code of Federal Regulations, 2014 CFR

2014-10-01

... cargo enters an airport Security Identification Display Area or is transferred to another TSA-regulated... program accepts the cargo until the cargo— (A) Enters an airport Security Identification Display Area; (B... 49 Transportation 9 2014-10-01 2014-10-01 false Access to cargo and cargo screening: Security...

49 CFR 1544.228 - Access to cargo and cargo screening: Security threat assessments for cargo personnel in the...

Code of Federal Regulations, 2013 CFR

2013-10-01

... cargo enters an airport Security Identification Display Area or is transferred to another TSA-regulated... program accepts the cargo until the cargo— (A) Enters an airport Security Identification Display Area; (B... 49 Transportation 9 2013-10-01 2013-10-01 false Access to cargo and cargo screening: Security...

49 CFR 1544.228 - Access to cargo and cargo screening: Security threat assessments for cargo personnel in the...

Code of Federal Regulations, 2011 CFR

2011-10-01

... cargo enters an airport Security Identification Display Area or is transferred to another TSA-regulated... program accepts the cargo until the cargo— (A) Enters an airport Security Identification Display Area; (B... 49 Transportation 9 2011-10-01 2011-10-01 false Access to cargo and cargo screening: Security...

Bacteria and fungi in aerosols generated by two different types of wastewater treatment plants.

PubMed

Bauer, H; Fuerhacker, M; Zibuschka, F; Schmid, H; Puxbaum, H

2002-09-01

Raw wastewater is a potential carrier of pathogenic microorganisms and may pose a health risk when pathogenic microorganisms become aerosolized during aeration. Two different types of wastewater treatment plants were investigated, and the amounts of cultivable bacteria and fungi were measured in the emitted aerosols. Average concentrations of 17,000 CFU m(-3) of mesophilic, 2,100 CFU m(-3) of TSA-SB bacteria (bacteria associated with certain waterborne virulence factors), 1700 CFU m(-3) of mesophilic and 45 CFU m(-3) of thermotolerant fungi, were found in the aerosol emitted by the aeration tank of the activated sludge plant. In the aerosol of the fixed-film reactor 3000 CFU m(-3) mesophilic and 730CFUm(-3) TSA-SB bacteria, and 180 CFUm(-3) mesophilic and 14 CFU m(-3) thermotolerant fungi were measured. The specific emissions per population equivalent between the two types of treatment plants differed by two orders of magnitude. The microbial flux based on the open water surface area of the two treatment plants was similar. The aerosolization ratios of cultivable bacteria (expressed as CFU m(-3) aerosol/m(-3) wastewater) ranged between 8.4 x 10(-11) and 4.9 x 10(-9). The aerosolization ratio of fungi was one to three orders of magnitude higher and a significant difference between the two types of treatment plants could be observed.

Quantitative structure-retention relationship studies with immobilized artificial membrane chromatography II: partial least squares regression.

PubMed

Li, Jie; Sun, Jin; He, Zhonggui

2007-01-26

We aimed to establish quantitative structure-retention relationship (QSRR) with immobilized artificial membrane (IAM) chromatography using easily understood and obtained physicochemical molecular descriptors and to elucidate which descriptors are critical to affect the interaction process between solutes and immobilized phospholipid membranes. The retention indices (logk(IAM)) of 55 structurally diverse drugs were determined on an immobilized artificial membrane column (IAM.PC.DD2) directly or obtained by extrapolation method for highly hydrophobic compounds. Ten simple physicochemical property descriptors (clogP, rings, rotatory bond, hydro-bond counting, etc.) of these drugs were collected and used to establish QSRR and predict the retention data by partial least squares regression (PLSR). Five descriptors, clogP, rotatory bond (RotB), rings, molecular weight (MW) and total surface area (TSA), were reserved by using the Variable Importance for Projection (VIP) values as criterion to build the final PLSR model. An external test set was employed to verify the QSRR based on the training set with the five variables, and QSRR by PLSR exhibited a satisfying predictive ability with R(p)=0.902 and RMSE(p)=0.400. Comparison of coefficients of centered and scaled variables by PLSR demonstrated that, for the descriptors studied, clogP and TSA have the most significant positive effect but the rotatable bond has significant negative effect on drug IAM chromatographic retention.

An NQO1-Initiated and p53-Independent Apoptotic Pathway Determines the Anti-Tumor Effect of Tanshinone IIA against Non-Small Cell Lung Cancer

PubMed Central

Wang, Guangji; Liu, Huiying; Wu, Xiaolan; Wang, Qiong; Liu, Miao; Liao, Ke; Wu, Mengqiu; Cheng, Xuefang; Hao, Haiping

2012-01-01

NQO1 is an emerging and promising therapeutic target in cancer therapy. This study was to determine whether the anti-tumor effect of tanshinone IIA (TSA) is NQO1 dependent and to elucidate the underlying apoptotic cell death pathways. NQO1+ A549 cells and isogenically matched NQO1 transfected and negative H596 cells were used to test the properties and mechanisms of TSA induced cell death. The in vivo anti-tumor efficacy and the tissue distribution properties of TSA were tested in tumor xenografted nude mice. We observed that TSA induced an excessive generation of ROS, DNA damage, and dramatic apoptotic cell death in NQO1+ A549 cells and H596-NQO1 cells, but not in NQO1− H596 cells. Inhibition or silence of NQO1 as well as the antioxidant NAC markedly reversed TSA induced apoptotic effects. TSA treatment significantly retarded the tumor growth of A549 tumor xenografts, which was significantly antagonized by dicoumarol co-treatment in spite of the increased and prolonged TSA accumulations in tumor tissues. TSA activated a ROS triggered, p53 independent and caspase dependent mitochondria apoptotic cell death pathway that is characterized with increased ratio of Bax to Bcl-xl, mitochondrial membrane potential disruption, cytochrome c release, and subsequent caspase activation and PARP-1 cleavage. The results of these findings suggest that TSA is a highly specific NQO1 target agent and is promising in developing as an effective drug in the therapy of NQO1 positive NSCLC. PMID:22848731

A New Opportunity: Loans from Annuities.

ERIC Educational Resources Information Center

Salzarulo, W. Peter

1984-01-01

Many faculty members have tax sheltered annuities (TSA). One method of obtaining the use of the funds in a TSA involves treating the amount received from the TSA as a loan rather than as a taxable withdrawal or distribution. (MLW)

78 FR 37561 - Extension of Agency Information Collection Activity Under OMB Review: TSA Customer Comment Card

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-21

...This notice announces that the Transportation Security Administration (TSA) has forwarded the Information Collection Request (ICR), Office of Management and Budget (OMB) control number 1652-0030, abstracted below to OMB for review and approval of an extension of the currently approved collection under the Paperwork Reduction Act (PRA). The ICR describes the nature of the information collection and its expected burden. TSA published a Federal Register notice, with a 60-day comment period soliciting comments, of the following collection of information on January 23, 2013 (78 FR 4856). This collection allows customers to provide feedback to TSA about their experiences with TSA's airport security process and procedures while traveling.

Trichostatin A-induced apoptosis is mediated by Kruppel-like factor 4 in ovarian and lung cancer.

PubMed

Zohre, Sadeghi; Kazem, Nejati-Koshki; Abolfazl, Akbarzadeh; Mohammad, Rahmati-Yamchi; Aliakbar, Movassaghpour; Effat, Alizadeh; Zahra, Davoudi; Hassan, Dariushnejad; Nosratollah, Zarghami

2014-01-01

The istone deacetylase (HDAC) inhibitor trichostatin A (TSA) is known to mediate the regulation of gene expression and anti proliferation activity in cancer cells. Kruppel-like factor 4 (klf4) is a zinc finger- containing transcription factor of the SP/KLF family, that is expressed in a variety of tissues and regulates cell proliferation, differentiation, tumorigenesis, and apoptosis. It may either either function as a tumor suppressor or an oncogene depending on genetic context of tumors. In this study, we tested the possibility that TSA may increase klf4 expression and cancer cell growth inhibition and apoptosis in SKOV-3 and A549 cells. The cytotoxicity of TSA was determined using the MTT assay test, while klf4 gene expression was assessed by real time PCR and to ability of TSA to induce apoptosis using a Vybrant Apoptosis Assay kit. Our results showed that TSA exerted dose and time dependent cytotoxicity effect on SKOV-3 and A549 cells. Moreover TSA up-regulated klf4 expression. Flow cytometric analysis demonstrated that apoptosis was increased after TSA treatment. Taken together, this study showed that TSA increased klf4 expression in SKOV3 and A549 cell lines, consequently, klf4 may played a tumor-suppressor role by increasing both cell growth inhibition and apoptosis. This study sheds light on the details of molecular mechanisms of HDACI-induced cell cycle arrest and apoptosis.

Oral and intraperitoneal administration of quercetin decreased lymphocyte DNA damage and plasma lipid peroxidation induced by TSA in vivo.

PubMed

Chan, Shu-Ting; Lin, Yi-Chin; Chuang, Cheng-Hung; Shiau, Rong-Jen; Liao, Jiunn-Wang; Yeh, Shu-Lan

2014-01-01

Our previous study showed that quercetin enhances the anticancer effect of trichostatin A (TSA) in xenograft mice given quercetin intraperitoneally (10 mg/kg, 3 times/week). Herein, we investigate whether quercetin administered orally exerts such an effect and prevents the cytotoxic side effects of TSA. We found that quercetin given orally (20 and 100 mg/kg, 3 times/week) failed to enhance the antitumor effect of TSA although it increased the total quercetin concentration more than quercetin administered intraperitoneally in the plasma. The compound quercetin-3-glucuronide (Q3G) increased the most. However, quercetin administered intraperitoneally increased the total quercetin level in tumor tissues more than oral quercetin. Oral and intraperitoneal administration of quercetin similarly decreased lymphocyte DNA damage and plasma lipid peroxidation level induced by TSA. Furthermore, we found that the enhancing effect of Q3G on the antitumor effect of TSA and the incorporation of Q3G was less than that of quercetin in A549 cells. However, we found that A549 cells possessed the ability to convert Q3G to quercetin. In conclusion, different from quercetin administered intraperitoneally, quercetin administered orally failed to enhance the antitumor effect of TSA because of its metabolic conversion. However, it prevented TSA-induced DNA damage and lipid peroxidation.

Oral and Intraperitoneal Administration of Quercetin Decreased Lymphocyte DNA Damage and Plasma Lipid Peroxidation Induced by TSA In Vivo

PubMed Central

Chan, Shu-Ting; Shiau, Rong-Jen; Liao, Jiunn-Wang; Yeh, Shu-Lan

2014-01-01

Our previous study showed that quercetin enhances the anticancer effect of trichostatin A (TSA) in xenograft mice given quercetin intraperitoneally (10 mg/kg, 3 times/week). Herein, we investigate whether quercetin administered orally exerts such an effect and prevents the cytotoxic side effects of TSA. We found that quercetin given orally (20 and 100 mg/kg, 3 times/week) failed to enhance the antitumor effect of TSA although it increased the total quercetin concentration more than quercetin administered intraperitoneally in the plasma. The compound quercetin-3-glucuronide (Q3G) increased the most. However, quercetin administered intraperitoneally increased the total quercetin level in tumor tissues more than oral quercetin. Oral and intraperitoneal administration of quercetin similarly decreased lymphocyte DNA damage and plasma lipid peroxidation level induced by TSA. Furthermore, we found that the enhancing effect of Q3G on the antitumor effect of TSA and the incorporation of Q3G was less than that of quercetin in A549 cells. However, we found that A549 cells possessed the ability to convert Q3G to quercetin. In conclusion, different from quercetin administered intraperitoneally, quercetin administered orally failed to enhance the antitumor effect of TSA because of its metabolic conversion. However, it prevented TSA-induced DNA damage and lipid peroxidation. PMID:24868531

Attenuated DNA damage repair by trichostatin A through BRCA1 suppression.

PubMed

Zhang, Yin; Carr, Theresa; Dimtchev, Alexandre; Zaer, Naghmeh; Dritschilo, Anatoly; Jung, Mira

2007-07-01

Recent studies have demonstrated that some histone deacetylase (HDAC) inhibitors enhance cellular radiation sensitivity. However, the underlying mechanism for such a radiosensitizing effect remains unexplored. Here we show evidence that treatment with the HDAC inhibitor trichostatin A (TSA) impairs radiation-induced repair of DNA damage. The effect of TSA on the kinetics of DNA damage repair was measured by performing the comet assay and gamma-H2AX focus analysis in radioresistant human squamous carcinoma cells (SQ-20B). TSA exposure increased the amount of radiation-induced DNA damage and slowed the repair kinetics. Gene expression profiling also revealed that a majority of the genes that control cell cycle, DNA replication and damage repair processes were down-regulated after TSA exposure, including BRCA1. The involvement of BRCA1 was further demonstrated by expressing ectopic wild-type BRCA1 in a BRCA1 null cell line (HCC-1937). TSA treatment enhanced radiation sensitivity of HCC-1937/wtBRCA1 clonal cells, which restored cellular radiosensitivity (D(0) = 1.63 Gy), to the control level (D(0) = 1.03 Gy). However, TSA had no effect on the level of radiosensitivity of BRCA1 null cells. Our data demonstrate for the first time that TSA treatment modulates the radiation-induced DNA damage repair process, in part by suppressing BRCA1 gene expression, suggesting that BRCA1 is one of molecular targets of TSA.

The endoscopic endonasal approach is not superior to the microscopic transcranial approach for anterior skull base meningiomas-a meta-analysis.

PubMed

Muskens, Ivo S; Briceno, Vanessa; Ouwehand, Tom L; Castlen, Joseph P; Gormley, William B; Aglio, Linda S; Zamanipoor Najafabadi, Amir H; van Furth, Wouter R; Smith, Timothy R; Mekary, Rania A; Broekman, Marike L D

2018-01-01

In the past decade, the endonasal transsphenoidal approach (eTSA) has become an alternative to the microsurgical transcranial approach (mTCA) for tuberculum sellae meningiomas (TSMs) and olfactory groove meningiomas (OGMs). The aim of this meta-analysis was to evaluate which approach offered the best surgical outcomes. A systematic review of the literature from 2004 and meta-analysis were conducted in accordance with the PRISMA guidelines. Pooled incidence was calculated for gross total resection (GTR), visual improvement, cerebrospinal fluid (CSF) leak, intraoperative arterial injury, and mortality, comparing eTSA and mTCA, with p-interaction values. Of 1684 studies, 64 case series were included in the meta-analysis. Using the fixed-effects model, the GTR rate was significantly higher among mTCA patients for OGM (eTSA: 70.9% vs. mTCA: 88.5%, p-interaction < 0.01), but not significantly higher for TSM (eTSA: 83.0% vs. mTCA: 85.8%, p-interaction = 0.34). Despite considerable heterogeneity, visual improvement was higher for eTSA than mTCA for TSM (p-interaction < 0.01), but not for OGM (p-interaction = 0.33). CSF leak was significantly higher among eTSA patients for both OGM (eTSA: 25.1% vs. mTCA: 10.5%, p-interaction < 0.01) and TSM (eTSA: 19.3%, vs. mTCA: 5.81%, p-interaction < 0.01). Intraoperative arterial injury was higher among eTSA (4.89%) than mTCA patients (1.86%) for TSM (p-interaction = 0.03), but not for OGM resection (p-interaction = 0.10). Mortality was not significantly different between eTSA and mTCA patients for both TSM (p-interaction = 0.14) and OGM resection (p-interaction = 0.88). Random-effect models yielded similar results. In this meta-analysis, eTSA was not shown to be superior to mTCA for resection of both OGMs and TSMs.

78 FR 44140 - Intent To Request Approval From OMB of One New Public Collection of Information: TSA PreTM

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-23

...-nationwide-expedited-screening-begins . TSA seeks to establish enrollment sites and implement a mobile... (or by money order at an enrollment center) to TSA's contracted vendor. Applicants then will submit...

Trans-scirpusin A showed antitumor effects via autophagy activation and apoptosis induction of colorectal cancer cells

PubMed Central

Song, Jae-Hyoung; Kwon, Bo-Eun; Lee, Jae-Young; Park, Yaejeong; Kim, Jinwoong; Chang, Sun-Young; Chin, Young-Won; Jeon, Sang-Min; Ko, Hyun-Jeong

2017-01-01

Trans-Scirpusin A (TSA) is a resveratrol oligomer found in Borassus flabellifer L. We found that TSA inhibited the growth of colorectal cancer Her2/CT26 cells in vivo in mice. Although some cytotoxic T lymphocytes (CTLs) were induced against the tumor-associated antigen Her2, TSA treatment did not significantly increase the level of Her2-specific CTL response compared to that with vehicle treatment. However, there was a significant increase in the level of TNF-α mRNA in tumor tissue and Her2-specific Ab (antibody) production. More importantly, we found that TSA overcomes the tumor-associated immunosuppressive microenvironment by reducing the number of CD25+FoxP3+ regulatory T cells and myeloid-derived suppressor cells (MDSCs). We detected the induction of autophagy in TSA-treated Her2/CT26 cells, based on the increased level of the mammalian autophagy protein LC3 puncta, and increased conversion of LC3-I to LC3-II. Further, TSA induced 5' AMP-activated protein kinase (p-AMPK) (T172) and inhibited mammalian target of rapamycin complex 1 (mTORC1) activity as estimated by phosphorylated ribosomal protein S6 kinase beta-1 (p-p70S6K) levels, thereby suggesting that TSA-mediated AMPK activation and inhibition of mTORC1 pathway might be associated with autophagy induction. TSA also induced apoptosis of Her2/CT26 cells, as inferred by the increased sub-G1 mitotic phases in these cells, Annexin V/PI-double positive results, and TUNEL-positive cells. Finally, we found that the combined treatment of mice with docetaxel and TSA successfully inhibited tumor growth to a greater extent than docetaxel alone. Therefore, we propose the use of TSA for supplementary anticancer therapy to support anti-neoplastic drugs, such as docetaxel, by inducing apoptosis in cancer cells and resulting in the induction of neighborhood anti-cancer immunity. PMID:28489607

Histone deacetylase inhibitor stimulates E2 and P4 secretion in sika deer ovarian granulosa cells at a moderate dose.

PubMed

Xing, Mingjie; Chen, Xiumin; Li, Xiaoxia; Yang, Yifeng; Wang, Xiaoxu; Cao, Xinyan; Xue, Hailong; Wang, Shiyong; Diao, Yunfei; Zhao, Weigang; Zhao, Meng; Cui, Xuezhe; Chang, Tong; Xu, Baozeng; Wei, Haijun

2018-03-01

The histone deacetylase inhibitor (HDACi) and tumor suppressor play an important role in genome reorganization and epigenetic regulation. In this study, granulosa cells (GCs) isolated from sika deer ovaries were cultured and treated with different concentrations of trichostatin A (TSA) for 48 h. It was found that TSA inhibited GCs proliferation and induced GCs apoptosis by upregulating expression of BAX, meanwhile, downregulating expression of GLUT3, GLUT8, BCL-XL. In addition, TSA caused cell cycle arrest at the G1 and G2/M phase accompanied by reducing expression of Cyclin D2 and CDK4. TSA pretreatment increased DNMT3a, DNMT1, HDAC1, and HAT1 expression, and attenuated them when TAS higher than 50 nM. The protein levels of H3K9ac and H4K8ac in GCs were increased at 48 h after TSA treatment. TSA stimulated the secretion of estradiol and progesterone at a moderate dose. Our data suggest that TSA is important as a regulator of steroid hormone synthesis in granulosa cells during follicular development in the sika deer ovary. © 2018 International Federation for Cell Biology.

Suppression of IL-1beta-induced COX-2 expression by trichostatin A (TSA) in human endometrial stromal cells.

PubMed

Wu, Yan; Guo, Sun-Wei

2007-11-01

Over-production of cyclooxygenase-2 (COX-2) plays an important role in the positive feedback loop that leads to proliferation and inflammation in endometriosis. Following our observation that histone deacetylase inhibitors (HDACIs) trichostatin A (TSA) and valproic acid (VPA) can suppress proliferation of endometrial stromal cells, we sought to determine whether TSA suppresses IL-1beta-induced COX-2 expression in endometrial stromal cells. In vitro study using a recently established immortalized endometrial stromal cell line. The stromal cells were pretreated with TSA before stimulation with IL-1beta, and COX-2 gene and protein expression was measured by real-time quantitative RT-PCR and Western blot analysis, respectively. IL-1beta stimulated COX-2 expression in a concentration-dependent manner in endometrial stromal cells. The induced COX-2 gene and protein expression were suppressed by TSA pretreatment. TSA suppresses IL-1beta-induced COX-2 gene and protein expression in endometrial stromal cells. This finding, coupled with the findings that TSA and another HDACI, valproic acid, suppress proliferation and induce cell cycle arrest, suggests that HDACIs are a promising class of compound that has therapeutic potential for endometriosis.

TSA protects H9c2 cells against thapsigargin-induced apoptosis related to endoplasmic reticulum stress-mediated mitochondrial injury.

PubMed

Li, Zhiping; Liu, Yan; Dai, Xinlun; Zhou, Qiangqiang; Liu, Xueli; Li, Zeyu; Chen, Xia

2017-05-01

Endoplasmic reticulum stress (ERS) activates an adaptive unfolded protein response (UPR) that facilitates cellular repair, however, under prolonged ER stress, the UPR can ultimately trigger apoptosis thereby terminating damaged cells. Recently, TSA has shown protective effects on ERS and its mechanisms related to ER pathway has been previously characterized. However, whether TSA exerts its protective role via metabolic events remain largely undefined. Objectives : To explore the possible involvement of the metabolic changes during ERS and to better understand how TSA influence mitochondrial function to facilitate cellular adaptation. Results : TSA is an inhibitor of histone deacetylase which could significantly inhibit H9c2 cell apoptosis induced by Thapsigargin (TG). It also intervene the decrease of mitochondrial membrane potential. By immunofluorescence staining, we have shown that GRP78 was concentrated in the perinuclear region and co-localized with ER. However, treatments with TG and TSA could let it overlap with the mitochondrial marker MitoTracker. Cellular fractionation also confirmed the location of GRP78 in mitochondrion. TSA decreases ERS-induced cell apoptosis and mitochondrial injury may related to enhance the location of GRP78 in mitochondrion.

Redox-dependent Regulation of Gluconeogenesis by a Novel Mechanism Mediated by a Peroxidatic Cysteine of Peroxiredoxin.

PubMed

Irokawa, Hayato; Tachibana, Tsuyoshi; Watanabe, Toshihiko; Matsuyama, Yuka; Motohashi, Hozumi; Ogasawara, Ayako; Iwai, Kenta; Naganuma, Akira; Kuge, Shusuke

2016-09-16

Peroxiredoxin is an abundant peroxidase, but its non-peroxidase function is also important. In this study, we discovered that Tsa1, a major peroxiredoxin of budding yeast cells, is required for the efficient flux of gluconeogenesis. We found that the suppression of pyruvate kinase (Pyk1) via the interaction with Tsa1 contributes in part to gluconeogenic enhancement. The physical interactions between Pyk1 and Tsa1 were augmented during the shift from glycolysis to gluconeogenesis. Intriguingly, a peroxidatic cysteine in the catalytic center of Tsa1 played an important role in the physical Tsa1-Pyk1 interactions. These interactions are enhanced by exogenous H2O2 and by endogenous reactive oxygen species, which is increased during gluconeogenesis. Only the peroxidatic cysteine, but no other catalytic cysteine of Tsa1, is required for efficient growth during the metabolic shift to obtain maximum yeast growth (biomass). This Tsa1 function is separable from the peroxidase function as an antioxidant. This is the first report to demonstrate that peroxiredoxin has a novel nonperoxidase function as a redox-dependent target modulator and that pyruvate kinase is modulated via an alternative mechanism.

75 FR 58331 - Revision of Enforcement Procedures

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

... recommended that TSA take these factors into account when TSA considers mitigating factors for purposes of... environment. Hence, TSA always considers multiple factors, including financial distress, when assessing civil... should be considered a mitigating factor for assessing penalties. Individuals who spend considerable time...

49 CFR 1522.101 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF HOMELAND SECURITY SECURITY RULES FOR ALL MODES OF TRANSPORTATION TSA-APPROVED VALIDATION FIRMS AND VALIDATORS TSA-Approved Validation Firms and Validators for the Certified Cargo Screening Program § 1522.101 Applicability. This subpart governs the use of TSA-approved validation firms and validators to...

49 CFR 1546.207 - Screening of individuals and property.

Code of Federal Regulations, 2013 CFR

2013-10-01

... SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY FOREIGN AIR CARRIER.... As required in its security program, each foreign air carrier must ensure that all individuals or... TSA is conducting screening using TSA employees or when using companies under contract with TSA. (c...

49 CFR 1546.207 - Screening of individuals and property.

Code of Federal Regulations, 2011 CFR

2011-10-01

... SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY FOREIGN AIR CARRIER.... As required in its security program, each foreign air carrier must ensure that all individuals or... TSA is conducting screening using TSA employees or when using companies under contract with TSA. (c...

49 CFR 1546.207 - Screening of individuals and property.

Code of Federal Regulations, 2014 CFR

2014-10-01

... SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY FOREIGN AIR CARRIER.... As required in its security program, each foreign air carrier must ensure that all individuals or... TSA is conducting screening using TSA employees or when using companies under contract with TSA. (c...

49 CFR 1546.207 - Screening of individuals and property.

Code of Federal Regulations, 2012 CFR

2012-10-01

... SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY FOREIGN AIR CARRIER.... As required in its security program, each foreign air carrier must ensure that all individuals or... TSA is conducting screening using TSA employees or when using companies under contract with TSA. (c...

49 CFR 1522.113 - Withdrawal of approval.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF HOMELAND SECURITY SECURITY RULES FOR ALL MODES OF TRANSPORTATION TSA-APPROVED VALIDATION FIRMS AND VALIDATORS TSA-Approved Validation Firms and Validators for the Certified Cargo Screening Program... TSA-approved validation firm if the validation firm ceases to meet the standards for approval, fails...

49 CFR 1522.123 - Conduct of assessments.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF HOMELAND SECURITY SECURITY RULES FOR ALL MODES OF TRANSPORTATION TSA-APPROVED VALIDATION FIRMS AND VALIDATORS TSA-Approved Validation Firms and Validators for the Certified Cargo Screening Program... immediately to TSA. (d) No authorization to take remedial or disciplinary action. Neither the validation firm...

Online Collaboration Processes of Career Changers Seeking Alternative Teacher Certification

ERIC Educational Resources Information Center

Moraes Varjao, Jaqueline Urania

2012-01-01

In March 2011, the U.S. Department of Education released a list of Teacher Shortage Area (TSA) nationwide. In most states the need for certified teachers fall in four main areas: English as a Second Language (ESOL), Mathematics and Science (6-12), and Foreign Language. The current study explored the ways in which career changers enrolled in online…

Inactivation of EGFR/AKT signaling enhances TSA-induced ovarian cancer cell differentiation.

PubMed

Shao, Genbao; Lai, Wensheng; Wan, Xiaolei; Xue, Jing; Wei, Ye; Jin, Jie; Zhang, Liuping; Lin, Qiong; Shao, Qixiang; Zou, Shengqiang

2017-05-01

Ovarian tumor is one of the most lethal gynecologic cancers, but differentiation therapy for this cancer is poorly characterized. Here, we show that thrichostatin A (TSA), the well known inhibitor of histone deacetylases (HDACs), can induce cell differentiation in HO8910 ovarian cancer cells. TSA-induced cell differentiation is characterized by typical morphological change, increased expression of the differentiation marker FOXA2, decreased expression of the pluripotency markers SOX2 and OCT4, suppressing cell proliferation, and cell cycle arrest in the G1 phase. TSA also induces an elevated expression of cell cycle inhibitory protein p21Cip1 along with a decrease in cell cycle regulatory protein cyclin D1. Significantly, blockage of epidermal growth factor receptor (EGFR) signaling pathway with specific inhibitors of this signaling cascade promotes the TSA-induced differentiation of HO8910 cells. These results imply that the EGFR cascade inhibitors in combination with TSA may represent a promising differentiation therapy strategy for ovarian cancer.

Effect of histone deacetylase inhibitor trichostatin A (TSA) on the microtubular system of Tetrahymena.

PubMed

Kovács, P; Pállinger, Eva; Csaba, G

2007-12-01

Histone deacetylases can also influence acetylation of tubulin. In the present experiments, after 60 min of 10 microM trichostatin (TSA) treatment the structure and amount of tubulin and acetylated-tubulin were studied immunocytochemically, by using confocal microscopy and flow cytometry. In TSA-treated Tetrahymena cells deep fibres were never labeled with antibody to acetylated tubulin. Flow cytometry with anti acetylated-tubulin antibody demonstrated that in the contol cell populations there were weaker and stronger labelled parts. After TSA treatment in the weaker labeled part the cell number decreased, and in the stronger labeled part increased significantly: this means that after the histone deacetylase inhibitor TSA treatment the amount of acetylated-tubulin in numerous Tetrahymena cells is significantly elevated. Labeling with anti-tubulin antibody was not changed significantly. On the basis of these results we postulate that histone deacetylase also in Tetrahymena influences the acetylation of tubulin, and this enzyme is sensitive to TSA treatments.

Improvement of porcine cloning efficiency by trichostain A through early-stage induction of embryo apoptosis.

PubMed

Ji, Qianqian; Zhu, Kongju; Liu, Zhiguo; Song, Zhenwei; Huang, Yuankai; Zhao, Haijing; Chen, Yaosheng; He, Zuyong; Mo, Delin; Cong, Peiqing

2013-03-15

Trichostain A (TSA), an inhibitor of histone deacetylases, improved developmental competence of SCNT embryos in many species, apparently by improved epigenetic reprogramming. The objective of the present study was to determine the effects of TSA-induced apoptosis in cloned porcine embryos. At various developmental stages, a comet assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining were used to detect apoptosis, and real-time polymerase chain reaction was used to assess expression of genes related to apoptosis and pluripotency. In this study, TSA significantly induced apoptosis (in a dose-dependent manner) at the one-, two-, and four-cell stages. However, in blastocyst stage embryos, TSA decreased the apoptotic index (P < 0.05). Expression levels of Caspase 3 were higher in TSA-treated versus control embryos at the two-cell stage (not statistically significant). The expression ratio of antiapoptotic Bcl-xl gene to proapoptotic Bax gene, an indicator of antiapoptotic potential, was higher in TSA-treated groups at the one-, two-, and four-cell and blastocyst stages. Furthermore, expression levels of pluripotency-related genes, namely, Oct4 and Nanog, were elevated at the morula stage (P < 0.05) in TSA treatment groups. We concluded that inducing apoptosis might be a mechanism by which TSA promotes development of reconstructed embryos. At the initial stage of apoptosis induction, abnormal cells were removed, thereby enhancing proliferation of healthy cells and improving embryo quality. Copyright © 2013 Elsevier Inc. All rights reserved.

Trichostatin A enhances estrogen receptor-alpha repression in MCF-7 breast cancer cells under hypoxia

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

Noh, Hyunggyun; Park, Joonwoo; Shim, Myeongguk

Estrogen receptor (ER) is a crucial determinant of resistance to endocrine therapy, which may change during the progression of breast cancer. We previously showed that hypoxia induces ESR1 gene repression and ERα protein degradation via proteasome-mediated pathway in breast cancer cells. HDAC plays important roles in the regulation of histone and non-histone protein post-translational modification. HDAC inhibitors can induce epigenetic changes and have therapeutic potential for targeting various cancers. Trichostatin A exerts potent antitumor activities against breast cancer cells in vitro and in vivo. In this report, we show that TSA augments ESR1 gene repression at the transcriptional level and downregulates ERαmore » protein expression under hypoxic conditions through a proteasome-mediated pathway. TSA-induced estrogen response element-driven reporter activity in the absence of estrogen was synergistically enhanced under hypoxia; however, TSA inhibited cell proliferation under both normoxia and hypoxia. Our data show that the hypoxia-induced repression of ESR1 and degradation of ERα are enhanced by concomitant treatment with TSA. These findings expand our understanding of hormone responsiveness in the tumor microenvironment; however, additional in-depth studies are required to elucidate the detailed mechanisms of TSA-induced ERα regulation under hypoxia. - Highlights: • TSA augments ESR1 gene repression at the transcriptional level under hypoxia. • TSA downregulates ERα protein expression under hypoxia. • TSA-induced ERα regulation under hypoxia is essential for understanding the behavior and progression of breast cancer.« less

TSA-induced DNMT1 down-regulation represses hTERT expression via recruiting CTCF into demethylated core promoter region of hTERT in HCT116.

PubMed

Choi, Jee-Hye; Min, Na Young; Park, Jina; Kim, Jin Hong; Park, Soo Hyun; Ko, Young Jong; Kang, Yoonsung; Moon, Young Joon; Rhee, Sangmyung; Ham, Seung Wook; Park, Ae Ja; Lee, Kwang-Ho

2010-01-01

Trichostatin A (TSA), an inhibitor of histone deacetylase, is a well-known antitumor agent that effectively and selectively induces tumor growth arrest and apoptosis. Recently, it was reported that hTERT is one of the primary targets for TSA-induced apoptosis in cancer cells but the mechanism of which has not yet been elucidated. In the present study, to better understand the epigenetic regulation mechanism responsible for the repression of hTERT by TSA, we examined expression of hTERT in the HCT116 colon cancer cell line after treatment with TSA and performed site-specific CpG methylation analysis of the hTERT promoter. We found that TSA-induced the demethylation of site-specific CpGs on the promoter of hTERT, which was caused by down-regulation of DNA methyltransferase 1 (DNMT1). Among the demethylated region, the 31st-33rd CpGs contained a binding site for CTCF, an inhibitor of hTERT transcription. ChIP analysis revealed that TSA-induced demethylation of the 31st-33rd CpGs promoted CTCF binding on hTERT promoter, leading to repression of hTERT. Taken together, down-regulation of DNMT1 by TSA caused demethylation of a CTCF binding site on the hTERT promoter, the result of which was repression of hTERT via recruitment of CTCF to the promoter. Copyright 2009 Elsevier Inc. All rights reserved.

The synergistic effect of 5Azadc and TSA on maintenance of pluripotency of chicken ESCs by overexpression of NANOG gene.

PubMed

Wang, Xiaoyan; Wang, Yingjie; Zuo, Qisheng; Li, Dong; Zhang, Wenhui; Lian, Chao; Tang, Beibei; Xiao, Tianrong; Wang, Man; Wang, Kehua; Li, Bichun; Zhang, Yani

2016-04-01

NANOG is a transcription factor that functions in embryonic stem cells (ESCs) and a key factor in maintaining pluripotency. Here, we cloned the NANOG gene promoter from the Rugao yellow chicken and constructed a dual luciferase reporter vector to detect its transcriptional activity and analyze the effects of 5-aza-2'-deoxycytidine (5-Azadc) and trichostatin A (TSA) on NANOG promoter activity and ESC pluripotency maintenance in vitro. NANOG transcriptional activity was enhanced when 5-Azadc and TSA were used alone or together, suggesting the possibility of elevated methylation of the CpG island in the NANOG regulatory region. When ESCs were cultured in basic medium with 5-Azadc and TSA in vitro, significantly more cell colonies were maintained in the 5-Azadc + TSA group than in the control group, which had many differentiated cells and few cell colonies after 6 d of induction. On the tenth day of induction, the cells in the control group fully differentiated and no cell colonies remained, but many cell colonies were present in the 5-Azadc + TSA group. The expression of NANOG in the cell colonies was confirmed by indirect immunofluorescence. Furthermore, ESCs could be passaged to the 12th generation under 5-Azadc and TSA treatment and maintained their pluripotency. Thus, we showed that 5-Azadc and TSA can effectively maintain chicken ESC pluripotency in vitro by increasing NANOG gene expression.

Traditional serrated adenoma (TSA): morphological questions, queries and quandaries.

PubMed

Chetty, Runjan

2016-01-01

Traditional serrated adenoma (TSA) is an uncommon type of serrated adenoma that can be a precursor to biologically aggressive colorectal cancer that invokes the serrated (accelerated) pathway. The purpose of this review is to address some of the more contentious issues around nomenclature, diagnostic criteria, histological variants, coexistence with other polyp types, the occurrence of dysplasia and the differential diagnosis. While the vast majority of TSAs are exophytic villiform polyps composed of deeply eosinophilic cells, flat top luminal serrations and numerous ectopic crypt foci, histological variants include flat TSA, filiform TSA and one composed of large numbers of mucin-containing cells. It is unlikely that there is any biological difference between the histological variants. There is a contention that TSAs are not dysplastic ab initio and that the majority do not show cytological atypia. Two types of dysplasia are associated with TSA. Serrated dysplasia is less well recognised and less commonly encountered than adenomatous dysplasia. TSA with dysplasia must be separated from TSA with coexisting conventional adenoma. TSA is a characteristic polyp that may be extremely exophytic, flat or composed of mucin-rich cells and is typified by numerous ectopic crypt foci. They may coexist with other serrated polyps and conventional adenomas. Approximately 20-25% will be accompanied by adenomatous dysplasia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

TSA Prepares Students for Career Success

ERIC Educational Resources Information Center

Gupta, Pratyusha

2012-01-01

So often, people assume that TSA is only the Transportation Security Administration, but another very important TSA is the Technology Student Association, an extracurricular organization that uses competitive events and leadership to help develop science, technology, engineering, and math (STEM) skills and knowledge in its membership. In this…

A Layman's Guide to Understanding TSA Compliance.

ERIC Educational Resources Information Center

Alioto, Nicholas C. A.; Simandl, Robert J.

1998-01-01

Since school district business offices are ill-equipped to administer tax shelter annuity (TSA) plans, the result has been inadequate legal compliance and significant financial exposure. This article explains the rules governing TSA planning (testing limitations), examines common pitfalls for districts conducting audits, and outlines steps for…

Technology Education Curriculum Guide for Connecticut-AIASA/TSA.

ERIC Educational Resources Information Center

Monty, Phil

This curriculum guide is designed to provide advisors with ways to manage technology student activities within their American Industrial Arts Student Association/Technology Student Association (AIASA/TSA) program. Section 1 focuses on how to organize a local AIASA/TSA chapter. It covers organizing procedures organizational meetings, chapter…

Approche de prise en charge du trouble du spectre de l’autisme

PubMed Central

Lee, Patrick F.; Thomas, Roger E.; Lee, Patricia A.

2015-01-01

Résumé Objectif Se pencher sur les critères diagnostiques du trouble du spectre de l’autisme (TSA) comme les définit le Manuel diagnostique et statistique des troubles mentaux, cinquième édition (DSM-V), et concevoir une approche de prise en charge du TSA à l’aide du cadre CanMEDS–Médecine familiale (CanMEDS-MF). Sources d’information Le DSM-V, publié par l’American Psychiatric Association en mai 2013, énonce de nouveaux critères diagnostiques du TSA. Le cadre CanMEDS-MF du Collège des médecins de famille du Canada fournit un plan d’orientation pour la prise en charge complexe du TSA. Nous avons utilisé des données recueillies par le Centers for Disease Control and Prevention afin de déterminer la prévalence du TSA, ainsi que la revue systématique et méta-analyse détaillée effectuée par le National Institute for Health and Care Excellence du R.-U. pour ses lignes directrices sur le TSA dans le but d’évaluer les données probantes issues de plus de 100 interventions. Message principal Selon les données du Centers for Disease Control and Prevention, la prévalence du TSA se chiffrait à 1 sur 88 en 2008 aux États-Unis. La classification du TSA dans la quatrième édition du DSM incluait l’autisme, le syndrome d’Asperger, le trouble envahissant du développement et le trouble désintégratif de l’enfance. La dernière révision du DSM-V réunit tous ces troubles sous la mention TSA, avec différents niveaux de sévérité. La prise en charge du TSA est complexe; elle exige les efforts d’une équipe multidisciplinaire ainsi que des soins continus. Les rôles CanMEDS-MF fournissent un cadre de prise en charge. Conclusion Les médecins de famille sont au cœur de l’équipe de soins multidisciplinaire pour le TSA, et le cadre CanMEDS-MF tient lieu de plan détaillé pour guider la prise en charge d’un enfant atteint de TSA et aider la famille de cet enfant.

49 CFR 1549.3 - TSA inspection authority.

Code of Federal Regulations, 2010 CFR

2010-10-01

... transportation facilities; (vi) Review security plans; and (vii) Carry out such other duties, and exercise such... access media or identification media issued or approved by a certified cargo screening facility or other person, except that the TSA and DHS officials will have identification media issued by TSA or DHS. ...

76 FR 31971 - New Agency Information Collection Activity Under OMB Review: Security Program for Hazardous...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-02

... INFORMATION CONTACT: Joanna Johnson, TSA PRA Officer, Office of Information Technology (OIT), TSA-11... other forms of information technology. Information Collection Requirement Title: Security Program for... surveyor tool that is managed at TSA. Participants who attend the classroom training sessions will also be...

78 FR 4856 - Intent To Request Renewal From OMB of One Current Public Collection of Information: TSA Customer...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-23

... DEPARTMENT OF HOMELAND SECURITY Transportation Security Administration Intent To Request Renewal...: Transportation Security Administration, DHS. ACTION: 60-Day notice. SUMMARY: The Transportation Security... provide feedback to TSA about their experiences with TSA's airport security process and procedures while...

49 CFR 1503.601 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Rules of Practice in TSA Civil Penalty Actions § 1503.601 Applicability. (a) This subpart applies to a... satisfied. (1) There is an alleged violation of a TSA requirement. (2) The amount in controversy does not... the adjudication of the validity of any TSA rule or other requirement under the U.S. Constitution, the...

GUIDELINES FOR TRAINING SITUATION ANALYSIS (TSA). FINAL REPORT.

ERIC Educational Resources Information Center

CHENZOFF, ANDREW P.; FOLLEY, JOHN D., JR.

THESE GUIDELINES REPRESENT A TEXTBOOK FOR INSTRUCTION IN THREE PHASES OF TRAINING SITUATION ANALYSIS (TSA), A STANDARDIZED PROCEDURE DEVELOPED BY THE NAVAL TRAINING DEVICE CENTER FOR SYSTEMATICALLY GATHERING AND INTERPRETING THE INFORMATION RELEVANT TO THE PLANNING OF TRAINING AND TRAINING DEVICES. THREE PHASES OF TSA ARE DESCRIBED IN…

76 FR 23326 - Intent To Request Renewal From OMB of One Current Public Collection of Information...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-26

... DEPARTMENT OF HOMELAND SECURITY Transportation Security Administration [Docket No. TSA-2006-24191... Notice. SUMMARY: The Transportation Security Administration (TSA) invites public comment on one currently... approved the collection of information for six months and TSA now seeks the maximum three-year approval...

49 CFR 1503.655 - Initial decision.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Rules of Practice in TSA Civil Penalty Actions § 1503.655 Initial decision. (a) Contents. The ALJ may... copies of that initial decision available to all parties and the TSA decision maker. (b) Written decision... ALJ is persuasive authority in any other civil penalty action, unless appealed and reversed by the TSA...

49 CFR 1546.207 - Screening of individuals and property.

Code of Federal Regulations, 2010 CFR

2010-10-01

... TSA is conducting screening using TSA employees or when using companies under contract with TSA. (c... 49 Transportation 9 2010-10-01 2010-10-01 false Screening of individuals and property. 1546.207... SECURITY Operations § 1546.207 Screening of individuals and property. (a) Applicability of this section...

49 CFR 1503.401 - Maximum penalty amounts.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Maximum penalty amounts. 1503.401 Section 1503.401... Assessment of Civil Penalties by TSA § 1503.401 Maximum penalty amounts. (a) General. TSA may assess civil.... TSA may adjust the maximum civil penalty amounts in conformity with the Federal Civil Penalties...

49 CFR 1522.109 - TSA review and approval.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF HOMELAND SECURITY SECURITY RULES FOR ALL MODES OF TRANSPORTATION TSA-APPROVED VALIDATION FIRMS AND VALIDATORS TSA-Approved Validation Firms and Validators for the Certified Cargo Screening Program... that the applicant is qualified to be a validation firm. (b) Notice.—(1) Approval. If an application is...

76 FR 58532 - Intent To Request Renewal From OMB of One Current Public Collection of Information; TSA Customer...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-21

...The Transportation Security Administration (TSA) invites public comment on one currently approved Information Collection Request (ICR), Office of Management and Budget (OMB) control number 1652-0030 abstracted below that we will submit to OMB for renewal in compliance with the Paperwork Reduction Act (PRA). The ICR describes the nature of the information collection and its expected burden. This collection allows customers to provide feedback to TSA about their experiences with TSA's airport security process and procedures while traveling.

Using temperature-switching approach to evaluate the ELDRS of bipolar devices

NASA Astrophysics Data System (ADS)

Li, Xiaolong; Lu, Wu; Wang, Xin; Guo, Qi; Yu, Xin; He, Chengfa; Sun, Jing; Liu, Mohan; Yao, Shuai; Wei, Xinyu

2017-12-01

Enhanced low-dose rate sensitivity (ELDRS) exhibited at low-dose rates (LDRs) by most bipolar devices is considered as one of the main concerns for spacecraft reliability. In this work, a time-saving and conservative approach - temperature-switching approach (TSA) - to simulate the ELDRS of bipolar devices is presented. Good agreement is observed between the predictive curve obtained with the TSA and the LDR data, and TSA provides us with a new insight into the test technique for ELDRS. Additionally, the mechanisms of TSA are analyzed in this paper.

Epigenetic modifiers reduce inflammation and modulate macrophage phenotype during endotoxemia-induced acute lung injury

PubMed Central

Thangavel, Jayakumar; Samanta, Saheli; Rajasingh, Sheeja; Barani, Bahar; Xuan, Yu-Ting; Dawn, Buddhadeb; Rajasingh, Johnson

2015-01-01

ABSTRACT Acute lung injury (ALI) during sepsis is characterized by bilateral alveolar infiltrates, lung edema and respiratory failure. Here, we examined the efficacy the DNA methyl transferase (DNMT) inhibitor 5-Aza 2-deoxycytidine (Aza), the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA), as well as the combination therapy of Aza and TSA (Aza+TSA) provides in the protection of ALI. In LPS-induced mouse ALI, post-treatment with a single dose of Aza+TSA showed substantial attenuation of adverse lung histopathological changes and inflammation. Importantly, these protective effects were due to substantial macrophage phenotypic changes observed in LPS-stimulated macrophages treated with Aza+TSA as compared with untreated LPS-induced macrophages or LPS-stimulated macrophages treated with either drug alone. Further, we observed significantly lower levels of pro-inflammatory molecules and higher levels of anti-inflammatory molecules in LPS-induced macrophages treated with Aza+TSA than in LPS-induced macrophages treated with either drug alone. The protection was ascribed to dual effects by an inhibition of MAPK–HuR–TNF and activation of STAT3–Bcl2 pathways. Combinatorial treatment with Aza+TSA reduces inflammation and promotes an anti-inflammatory M2 macrophage phenotype in ALI, and has a therapeutic potential for patients with sepsis. PMID:26116574

75 FR 9915 - Extension of Agency Information Collection Activity Under OMB Review: Certified Cargo Screening...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-04

...This notice announces that the Transportation Security Administration (TSA) has forwarded the Information Collection Request (ICR), OMB control number 1652-0053, abstracted below to the Office of Management and Budget (OMB) for renewal in compliance with the Paperwork Reduction Act. The ICR describes the nature of the information collection and its expected burden. TSA published a Federal Register notice, with a 60-day comment period soliciting comments, of the following collection of information on November 16, 2009, 74 FR 58967. TSA has received no comments. The collections include: (1) Applications from entities that wish to become Certified Cargo Screening Facilities (CCSF) or operate as a TSA-approved validation firm; (2) personal information to allow TSA to conduct security threat assessments on key individuals employed by the CCSFs and validation firms; (3) implementation of a standard security program or submission of a proposed modified security program; (4) information on the amount of cargo screened; (5) recordkeeping requirements for CCSFs and validation firms; and (6) submission of validation reports to TSA. TSA is seeking the renewal of the ICR for the continuation of the program in order to secure passenger aircraft carrying cargo by the deadlines set out in the Implementing Recommendations of the 9/11 Commission Act of 2007.

The Induction Effect of Am80 and TSA on ESC Differentiation via Regulation of Stra8 in Chicken.

PubMed

Zhang, Yani; Zuo, Qisheng; Liu, Zhiyong; Li, Dong; Tang, Beibei; Xiao, Tian-Rong; Lian, Chao; Wang, Yingjie; Jin, Kai; Wang, Yilin; Zhang, Wenhui; Li, Bichun

2015-01-01

Stra8 encodes stimulated by retinoic acid gene 8, a protein that is important for initiation of meiosis in mammals and birds. This study was aimed at identifying the active control area of chicken STRA8 gene core promoter, to screen optimum inducers of the STRA8 gene, thus to enhance the differentiation of embryonic stem cells (ESCs) into spermatogonial stem cells. Fragments of chicken STRA8 gene promoter were cloned into fluorescent reporter plasmids and transfected into DF-1 cells. Then Dual-Luciferase® Reporter Assay System was used to identify the activity of the STRA8 gene under different inducers. Our studies showed that the promoter fragment -1055 bp to +54 bp of Suqin chicken Stra8 revealed the strongest activity. The dual-luciferase® reporter showed that Tamibarotene (Am80) and TrichostatinA (TSA) could significantly enhance STRA8 transcription. The in vitro inductive culture of chicken ESCs demonstrated that spermatogonial stem cells (SSC)-like cells appeared and Integrinβ1 protein was expressed on day 10, indicating that Am80 and TSA can promote ESCs differentiation into SSCs via regulation of Stra8.

The Induction Effect of Am80 and TSA on ESC Differentiation via Regulation of Stra8 in Chicken

PubMed Central

Zhang, Yani; Zuo, Qisheng; Liu, Zhiyong; Li, Dong; Tang, Beibei; Xiao, Tian-rong; Lian, Chao; Wang, Yingjie; Jin, Kai; Wang, Yilin; Zhang, Wenhui; Li, Bichun

2015-01-01

Stra8 encodes stimulated by retinoic acid gene 8, a protein that is important for initiation of meiosis in mammals and birds. This study was aimed at identifying the active control area of chicken STRA8 gene core promoter, to screen optimum inducers of the STRA8 gene, thus to enhance the differentiation of embryonic stem cells (ESCs) into spermatogonial stem cells. Fragments of chicken STRA8 gene promoter were cloned into fluorescent reporter plasmids and transfected into DF-1 cells. Then Dual-Luciferase® Reporter Assay System was used to identify the activity of the STRA8 gene under different inducers. Our studies showed that the promoter fragment −1055 bp to +54 bp of Suqin chicken Stra8 revealed the strongest activity. The dual-luciferase® reporter showed that Tamibarotene (Am80) and TrichostatinA (TSA) could significantly enhance STRA8 transcription. The in vitro inductive culture of chicken ESCs demonstrated that spermatogonial stem cells (SSC)-like cells appeared and Integrinβ1 protein was expressed on day 10, indicating that Am80 and TSA can promote ESCs differentiation into SSCs via regulation of Stra8. PMID:26606052

Impact of cultivation on characterisation of species composition of soil bacterial communities.

PubMed

McCaig, A E.; Grayston, S J.; Prosser, J I.; Glover, L A.

2001-03-01

The species composition of culturable bacteria in Scottish grassland soils was investigated using a combination of Biolog and 16S rDNA analysis for characterisation of isolates. The inclusion of a molecular approach allowed direct comparison of sequences from culturable bacteria with sequences obtained during analysis of DNA extracted directly from the same soil samples. Bacterial strains were isolated on Pseudomonas isolation agar (PIA), a selective medium, and on tryptone soya agar (TSA), a general laboratory medium. In total, 12 and 21 morphologically different bacterial cultures were isolated on PIA and TSA, respectively. Biolog and sequencing placed PIA isolates in the same taxonomic groups, the majority of cultures belonging to the Pseudomonas (sensu stricto) group. However, analysis of 16S rDNA sequences proved more efficient than Biolog for characterising TSA isolates due to limitations of the Microlog database for identifying environmental bacteria. In general, 16S rDNA sequences from TSA isolates showed high similarities to cultured species represented in sequence databases, although TSA-8 showed only 92.5% similarity to the nearest relative, Bacillus insolitus. In general, there was very little overlap between the culturable and uncultured bacterial communities, although two sequences, PIA-2 and TSA-13, showed >99% similarity to soil clones. A cloning step was included prior to sequence analysis of two isolates, TSA-5 and TSA-14, and analysis of several clones confirmed that these cultures comprised at least four and three sequence types, respectively. All isolate clones were most closely related to uncultured bacteria, with clone TSA-5.1 showing 99.8% similarity to a sequence amplified directly from the same soil sample. Interestingly, one clone, TSA-5.4, clustered within a novel group comprising only uncultured sequences. This group, which is associated with the novel, deep-branching Acidobacterium capsulatum lineage, also included clones isolated during direct analysis of the same soil and from a wide range of other sample types studied elsewhere. The study demonstrates the value of fine-scale molecular analysis for identification of laboratory isolates and indicates the culturability of approximately 1% of the total population but under a restricted range of media and cultivation conditions.

Performance of a proposed determinative method for p-TSA in rainbow trout fillet tissue and bridging the proposed method with a method for total chloramine-T residues in rainbow trout fillet tissue

USGS Publications Warehouse

Meinertz, J.R.; Stehly, G.R.; Gingerich, W.H.; Greseth, Shari L.

2001-01-01

Chloramine-T is an effective drug for controlling fish mortality caused by bacterial gill disease. As part of the data required for approval of chloramine-T use in aquaculture, depletion of the chloramine-T marker residue (para-toluenesulfonamide; p-TSA) from edible fillet tissue of fish must be characterized. Declaration of p-TSA as the marker residue for chloramine-T in rainbow trout was based on total residue depletion studies using a method that used time consuming and cumbersome techniques. A simple and robust method recently developed is being proposed as a determinative method for p-TSA in fish fillet tissue. The proposed determinative method was evaluated by comparing accuracy and precision data with U.S. Food and Drug Administration criteria and by bridging the method to the former method for chloramine-T residues. The method accuracy and precision fulfilled the criteria for determinative methods; accuracy was 92.6, 93.4, and 94.6% with samples fortified at 0.5X, 1X, and 2X the expected 1000 ng/g tolerance limit for p-TSA, respectively. Method precision with tissue containing incurred p-TSA at a nominal concentration of 1000 ng/g ranged from 0.80 to 8.4%. The proposed determinative method was successfully bridged with the former method. The concentrations of p-TSA developed with the proposed method were not statistically different at p < 0.05 from p-TSA concentrations developed with the former method.

Nuclear quiescence and histone hyper-acetylation jointly improve protamine-mediated nuclear remodeling in sheep fibroblasts

PubMed Central

Palazzese, Luca; Czernik, Marta; Iuso, Domenico; Toschi, Paola

2018-01-01

Recently we have demonstrated the possibility to replace histones with protamine, through the heterologous expression of human protamine 1 (hPrm1) gene in sheep fibroblasts. Here we have optimized protaminization of somatic nucleus by adjusting the best concentration and exposure time to trichostatin A (TSA) in serum-starved fibroblasts (nuclear quiescence), before expressing Prm1 gene. To stop cell proliferation, we starved cells in 0.5% FBS in MEM (“starved”—ST group), whereas in the Control group (CTR) the cells were cultured in 10% FBS in MEM. To find the most effective TSA concentration, we treated the cells with increasing concentrations of TSA in MEM + 10% FBS. Our results show that combination of cell culture conditions in 50 nM TSA, is more effective in terminating cell proliferation than ST and CTR groups (respectively 8%, 17.8% and 90.2% p<0.0001). Moreover, nuclear quiescence marker genes expression (Dicer1, Smarca 2, Ezh1 and Ddx39) confirmed that our culture conditions kept the cells in a nuclear quiescent state. Finally, ST and 50 nM TSA jointly increased the number of spermatid-like cell (39.4%) at higher rate compared to 25 nM TSA (20.4%, p<0.05) and 100 nM TSA (13.7%, p<0.05). To conclude, we have demonstrated that nuclear quiescence in ST cells and the open nuclear structure conferred by TSA resulted in an improved Prm1-mediated conversion of somatic nuclei into spermatid-like structures. This finding might improve nuclear reprogramming of somatic cells following nuclear transfer. PMID:29543876

49 CFR 1503.631 - Interlocutory appeals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Rules of Practice in TSA Civil Penalty Actions § 1503.631 Interlocutory appeals. (a) General. Unless otherwise provided in this subpart, a party may not appeal a ruling or decision of the ALJ to the TSA decision maker until the initial decision has been entered on the record. A decision or order of the TSA...

49 CFR 1503.603 - Separation of functions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Rules of Practice in TSA Civil Penalty Actions § 1503.603 Separation of functions. (a) Civil penalty... the ALJ or by the TSA decision maker on appeal, except as counsel or a witness in the public... advise the TSA decision maker regarding an initial decision or any appeal of a civil penalty action to...

49 CFR 1503.429 - Filing of documents with the Enforcement Docket Clerk.

Code of Federal Regulations, 2010 CFR

2010-10-01

... INVESTIGATIVE AND ENFORCEMENT PROCEDURES Assessment of Civil Penalties by TSA § 1503.429 Filing of documents.... If this e-mail address changes, TSA will provide notice of the change by notice in the Federal Register. (3) By facsimile transmission, to 410-962-1746. If this number changes, TSA will provide notice...

49 CFR 1503.421 - Streamlined civil penalty procedures for certain security violations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PROCEDURAL RULES INVESTIGATIVE AND ENFORCEMENT PROCEDURES Assessment of Civil Penalties by TSA § 1503.421 Streamlined civil penalty procedures for certain security violations. (a) Notice of violation. TSA, at the... violations described in the section and as otherwise provided by the Administrator. TSA may serve a Notice of...

49 CFR 1503.425 - Compromise orders.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Assessment of Civil Penalties by TSA § 1503.425 Compromise orders. (a) Issuance. At any time before the... Violation, may agree to dispose of the case by the issuance of a compromise order by TSA. (b) Contents. A... that the person agrees to pay the civil penalty specified. (4) A statement that TSA makes no finding of...

49 CFR 1520.15 - SSI disclosed by TSA or the Coast Guard.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY SECURITY RULES FOR ALL MODES OF TRANSPORTATION PROTECTION OF SENSITIVE SECURITY INFORMATION § 1520.15 SSI disclosed by TSA or the Coast Guard. (a) In... allegations contained in a legal enforcement action document issued by TSA or the Coast Guard. (2) Security...

Perceptions and Practices of Technology Student Association Advisors on Implementation Strategies and Teaching Methods

ERIC Educational Resources Information Center

Haynie, W. J.; DeLuca, V. W.; Matthews, B.

2005-01-01

A study conducted in 1989 surveyed Technology Student Association (TSA) advisors to find their perceptions concerning characteristics of technology education programs with a TSA component and the relationship between participation in co-curricular organizations and the teaching methods used by TSA technology teachers (DeLuca & Haynie, 1991).…

Doping optimization of polypyrrole with toluenesulfonic acid using Box-Behnken design

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

Syed Draman, Sarifah Fauziah; Daik, Rusli; El-Sheikh, Said M.

A three-level Box-Behnken design was employed in doping optimization of polypyrrole with toluenesulfonic acid (TSA-doped PPy). The material was synthesized via chemical oxidative polymerization using pyrrole, toluenesulfonic acid (TSA) and ammonium persulfate (APS) as monomer, dopant and oxidant, respectively. The critical factors selected for this study were concentration of dopant, molar ratio between dopant to monomer (pyrrole) and concentration of oxidant. Obtaining adequate doping level of TSA-doped PPy is crucial because it affects the charge carriers for doped PPy and usually be responsible for electronic mobility along polymeric chain. Furthermore, the doping level also affects other properties such as electricalmore » and thermal conductivity. Doping level was calculated using elemental analysis. SEM images shows that the prepared TSA-doped PPy particles are spherical in shape with the diameters of about. The range of nanoparticles size is around 80-100 nm. The statistical analysis based on a Box–Behnken design showed that 0.01 mol of TSA, 1:1 mole ratio TSA to pyrrole and 0.25 M APS were the optimum conditions for sufficient doping level.« less

P53-dependent antiproliferative and pro-apoptotic effects of trichostatin A (TSA) in glioblastoma cells.

PubMed

Bajbouj, K; Mawrin, C; Hartig, R; Schulze-Luehrmann, J; Wilisch-Neumann, A; Roessner, A; Schneider-Stock, R

2012-05-01

Glioblastomas are known to be highly chemoresistant, but HDAC inhibitors (HDACi) have been shown to be of therapeutic relevance for this aggressive tumor type. We treated U87 glioblastoma cells with trichostatin A (TSA) to define potential epigenetic targets for HDACi-mediated antitumor effects. Using a cDNA array analysis covering 96 cell cycle genes, cyclin-dependent kinase inhibitor p21(WAF1) was identified as the major player in TSA-induced cell cycle arrest. TSA slightly inhibited proliferation and viability of U87 cells, cumulating in a G1/S cell cycle arrest. This effect was accompanied by a significant up-regulation of p53 and its transcriptional target p21(WAF1) and by down-regulation of key G1/S regulators, such as cdk4, cdk6, and cyclin D1. Nevertheless, TSA did not induce apoptosis in U87 cells. As expected, TSA promoted the accumulation of total acetylated histones H3 and H4 and a decrease in endogenous HDAC activity. Characterizing the chromatin modulation around the p21(WAF1) promoter after TSA treatment using chromatin immunoprecipitation, we found (1) a release of HDAC1, (2) an increase of acetylated H4 binding, and (3) enhanced recruitment of p53. p53-depleted U87 cells showed an abrogation of the G1/S arrest and re-entered the cell cycle. Immunofluorescence staining revealed that TSA induced the nuclear translocation of p21(WAF1) verifying a cell cycle arrest. On the other hand, a significant portion of p21(WAF1) was present in the cytoplasmic compartment causing apoptosis resistance. Furthermore, TSA-treated p53-mutant cell line U138 failed to show an induction in p21(WAF1), showed a deficient G2/M checkpoint, and underwent mitotic catastrophe. We suggest that HDAC inhibition in combination with other clinically used drugs may be considered an effective strategy to overcome chemoresistance in glioblastoma cells.

The histone deacetylase inhibitor trichostatin A suppresses murine innate allergic inflammation by blocking group 2 innate lymphoid cell (ILC2) activation

PubMed Central

Toki, Shinji; Goleniewska, Kasia; Reiss, Sara; Zhou, Weisong; Newcomb, Dawn C; Bloodworth, Melissa H; Stier, Matthew T; Boyd, Kelli L; Polosukhin, Vasiliy V; Subramaniam, Sriram; Peebles, R Stokes

2016-01-01

Background Group 2 innate lymphoid cells (ILC2) are an important source of the type 2 cytokines interleukin (IL)-5 and IL-13 that are critical to the allergic airway phenotype. Previous studies reported that histone deacetylase (HDAC) inhibition by trichostatin A (TSA) downregulated adaptive allergic immune responses; however, the effect of HDAC inhibition on the early innate allergic immune response is unknown. Therefore, we investigated the effect of TSA on innate airway inflammation mediated by ILC2 activation. Methods BALB/c mice were challenged intranasally with Alternaria extract, exogenous recombinant mouse IL-33 (rmIL-33) or the respective vehicles for four consecutive days following TSA or vehicle treatment. Bronchoalveolar lavage (BAL) fluids and lungs were harvested 24 h after the last challenge. Results We found that TSA treatment significantly decreased the number of ILC2 expressing IL-5 and IL-13 in the lungs challenged with Alternaria extract or rmIL-33 compared with vehicle treatment (p<0.05). TSA treatment significantly decreased protein expression of IL-5, IL-13, CCL11 and CCL24 in the lung homogenates from Alternaria extract-challenged mice or rmIL-33-challenged mice compared with vehicle treatment (p<0.05). Further, TSA treatment significantly decreased the number of perivascular eosinophils and mucus production in the large airways that are critical components of the asthma phenotype (p<0.05). TSA did not change early IL-33 release in the BAL fluids; however, TSA decreased lung IL-33 expression from epithelial cells 24 h after last Alternaria extract challenge compared with vehicle treatment (p<0.05). Conclusions These results reveal that TSA reduces allergen-induced ILC2 activation and the early innate immune responses to an inhaled protease-containing aeroallergen. PMID:27071418

A Simulation-based Approach to Measuring Team Situational Awareness in Emergency Medicine: A Multicenter, Observational Study.

PubMed

Rosenman, Elizabeth D; Dixon, Aurora J; Webb, Jessica M; Brolliar, Sarah; Golden, Simon J; Jones, Kerin A; Shah, Sachita; Grand, James A; Kozlowski, Steve W J; Chao, Georgia T; Fernandez, Rosemarie

2018-02-01

Team situational awareness (TSA) is critical for effective teamwork and supports dynamic decision making in unpredictable, time-pressured situations. Simulation provides a platform for developing and assessing TSA, but these efforts are limited by suboptimal measurement approaches. The objective of this study was to develop and evaluate a novel approach to TSA measurement in interprofessional emergency medicine (EM) teams. We performed a multicenter, prospective, simulation-based observational study to evaluate an approach to TSA measurement. Interprofessional emergency medical teams, consisting of EM resident physicians, nurses, and medical students, were recruited from the University of Washington (Seattle, WA) and Wayne State University (Detroit, MI). Each team completed a simulated emergency resuscitation scenario. Immediately following the simulation, team members completed a TSA measure, a team perception of shared understanding measure, and a team leader effectiveness measure. Subject matter expert reviews and pilot testing of the TSA measure provided evidence of content and response process validity. Simulations were recorded and independently coded for team performance using a previously validated measure. The relationships between the TSA measure and other variables (team clinical performance, team perception of shared understanding, team leader effectiveness, and team experience) were explored. The TSA agreement metric was indexed by averaging the pairwise agreement for each dyad on a team and then averaging across dyads to yield agreement at the team level. For the team perception of shared understanding and team leadership effectiveness measures, individual team member scores were aggregated within a team to create a single team score. We computed descriptive statistics for all outcomes. We calculated Pearson's product-moment correlations to determine bivariate correlations between outcome variables with two-tailed significance testing (p < 0.05). A total of 123 participants were recruited and formed three-person teams (n = 41 teams). All teams completed the assessment scenario and postsimulation measures. TSA agreement ranged from 0.19 to 0.9 and had a mean (±SD) of 0.61 (±0.17). TSA correlated with team clinical performance (p < 0.05) but did not correlate with team perception of shared understanding, team leader effectiveness, or team experience. Team situational awareness supports adaptive teams and is critical for high reliability organizations such as healthcare systems. Simulation can provide a platform for research aimed at understanding and measuring TSA. This study provides a feasible method for simulation-based assessment of TSA in interdisciplinary teams that addresses prior measure limitations and is appropriate for use in highly dynamic, uncertain situations commonly encountered in emergency department systems. Future research is needed to understand the development of and interactions between individual-, team-, and system (distributed)-level cognitive processes. © 2017 by the Society for Academic Emergency Medicine.

49 CFR 1503.645 - Expert or opinion witnesses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PROCEDURES Rules of Practice in TSA Civil Penalty Actions § 1503.645 Expert or opinion witnesses. An employee of the agency may not be called as an expert or opinion witness, for any party other than TSA, in any... an expert or opinion witness for TSA in any proceeding governed by this subpart to which the...

Kinematic analysis of dynamic shoulder motion in patients with reverse total shoulder arthroplasty.

PubMed

Kwon, Young W; Pinto, Vivek J; Yoon, Jangwhon; Frankle, Mark A; Dunning, Page E; Sheikhzadeh, Ali

2012-09-01

Reverse total shoulder arthroplasty (rTSA) has been used to treat patients with irreparable rotator cuff dysfunction. Despite the proven clinical efficacy, there is minimal information regarding the underlying changes to the shoulder kinematics associated with this construct. Therefore, we sought to examine the kinematics of dynamic shoulder motion in patients with well-functioning rTSA. We tested 12 healthy subjects and 17 patients with rTSA. All rTSA patients were able to elevate their arms to at least 90° and received the implant as the primary arthroplasty at least 6 months before testing. On average, the rTSA patients elevated their arms to 112° ± 12° (mean ± SD) and reported an American Shoulder and Elbow Surgeons outcome score of 90.6 ± 6.3. A 3-dimensional electromagnetic motion capture device was used to detect the dynamic motion of the trunk, scapula, and humerus during bilateral active shoulder elevation along the sagittal, scapular, and coronal planes. In both healthy and rTSA shoulders, the majority of the humeral-thoracic motion was provided by the glenohumeral motion. Therefore, the ratio of glenohumeral to scapulothoracic (ST) motion was always greater than 1.62 during elevation along the scapular plane. In comparison to healthy subjects, however, the contribution of ST motion to overall shoulder motion was significantly increased in the rTSA shoulders. This increased contribution was noted in all planes of shoulder elevation and was maintained when weights were attached to the arm. Kinematics of the rTSA shoulders are significantly altered, and more ST motion is used to achieve shoulder elevation. Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Outcomes of an anatomic total shoulder arthroplasty with a contralateral reverse total shoulder arthroplasty.

PubMed

Cox, Ryan M; Padegimas, Eric M; Abboud, Joseph A; Getz, Charles L; Lazarus, Mark D; Ramsey, Matthew L; Williams, Gerald R; Horneff, John G

2018-06-01

It is common for patients to require staged bilateral shoulder arthroplasties. There is a unique cohort of patients who require an anatomic total shoulder arthroplasty (TSA) and a contralateral reverse shoulder arthroplasty (RSA). This study compared the outcomes of patients with a TSA in 1 shoulder and an RSA in the contralateral shoulder. Our institutional database was queried to identify all patients with a TSA and a contralateral RSA. Data collection included patient demographics, preoperative and latest follow-up shoulder range of motion, radiographic analysis, and postoperative complications. Identified patients were assessed at follow-up visits or contacted by phone for functional outcome scores. Nineteen patients met our inclusion/exclusion criteria. There was statistically significant greater internal rotation in the TSA shoulder (P= .044) but no significant difference in forward elevation (P = .573) or external rotation (P= .368). There was no radiographic evidence of humeral or glenoid component loosening of any arthroplasty implants. There were no significant differences between TSA and RSA shoulders for the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment (P= .381), Simple Shoulder Test (P = .352), Single Assessment Numerical Evaluation (P = .709), and visual analog scale satisfaction (P= .448) or pain scores (P= .305). Thirteen patients (68.4%) preferred the RSA side, 1 patient (5.3%; z = 4.04, P < .001) patient preferred the TSA side, and 5 patients expressed no preference. Despite known limitations and differences between TSA and RSA designs, patients who have received both implants are highly satisfied with both. The only parameter in which the TSA had superior outcomes was internal rotation. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Trends in Joint Replacement Surgery in Patients with Rheumatoid Arthritis.

PubMed

Young, Bradley L; Watson, Shawna L; Perez, Jorge L; McGwin, Gerald; Singh, Jasvinder A; Ponce, Brent A

2018-02-01

This study analyzed trends in large total joint arthroplasties (TJA) and in the proportion of these procedures performed on patients with rheumatoid arthritis (RA). The US Nationwide Inpatient Sample (2002-2012) was used to identify the incidences of total shoulder (TSA), elbow (TEA), knee (TKA), hip (THA), and ankle (TAA) arthroplasty and the proportion of these performed with coexisting RA. The prevalence of RA among patients with TJA increased 3.0%. The prevalence of RA among cases of TEA and TSA decreased by 50% (p < 0.0001) and 18% (p = 0.0016), respectively; a 38.0% decrease occurred in the prevalence of RA among TAA (p = 0.06); and nonsignificant increases were seen among THA and TKA. The average age difference between RA and non-RA patients undergoing TJA narrowed by 2 years (p < 0.0001). There was a greater reduction in the proportion of TSA, TEA, and TAA groups among women with RA than men with RA. In the TSA and TEA groups, there was a reduction in the proportion of whites with RA, but not blacks. The proportion of privately insured TSA and TAA patients with RA decreased, while patients with RA undergoing TSA, TEA, or TAA who were receiving Medicaid (government medical insurance) remained relatively stable over time. The prevalence of RA has decreased among TSA and TEA patients. A nonsignificant decline occurred among TAA patients. The average age of TJA patients with RA is beginning to mirror those without RA. Sex ratios for TSA, TEA, and TAA patients are following a similar pattern. These results may be evidence of the success of modern RA treatment strategies.

LncRNA-uc002mbe.2 Interacting with hnRNPA2B1 Mediates AKT Deactivation and p21 Up-Regulation Induced by Trichostatin in Liver Cancer Cells.

PubMed

Chen, Ting; Gu, Chengxin; Xue, Cailin; Yang, Tao; Zhong, Yun; Liu, Shiming; Nie, Yuqiang; Yang, Hui

2017-01-01

Long non-coding RNAs (lncRNAs) have been implicated in liver carcinogenesis. We previously showed that the induction of lncRNA-uc002mbe.2 is positively associated with the apoptotic effect of trichostatin A (TSA) in hepatocellular carcinoma (HCC) cells. The current study further analyzed the role of uc002mbe.2 in TSA-induced liver cancer cell death. The level of uc002mbe.2 was markedly increased by TSA in the cytoplasm of HCC cells. Knockdown of uc002mbe.2 prohibited TSA-induced G2/M cell cycle arrest, p21 induction, and apoptosis of Huh7 cells and reversed the TSA-mediated decrease in p-AKT. RNA pull-down and RNA-binding protein immunoprecipitation (RIP) assays revealed that TSA induced an interaction between uc002mbe.2 and heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in Huh7 cells. This interaction mediated AKT deactivation and p21 induction in liver cancer cells. In an athymic xenograft mouse model, knockdown of uc002mbe.2 significantly prohibited the TSA-mediated reduction in tumor size and weight. In addition, the ability of TSA to reduce hnRNPA2B1 and p-AKT levels and induce p21 in the xenograft tumors was prevented by uc002mbe.2 knockdown. Therefore, the interaction of uc002mbe.2 and hnRNPA2B1 in mediating AKT deactivation and p21 induction is involved in the cytostatic effect of trichostatin in liver cancer cells.

The effects of anticancer drugs TSA and GSK on spermatogenesis in male mice.

PubMed

Song, Wen-Yan; Yang, Qing-Ling; Zhao, Wan-Li; Jin, Hai-Xia; Yao, Gui-Dong; Peng, Zhao-Feng; Shi, Sen-Lin; Yang, Hong-Yi; Zhang, Xiang-Yang; Sun, Ying-Pu

2016-01-01

The effect of anticancer drugs Trichostation A (TSA) and GSK2126458 (GSK) on genetic recombination of sperm meiosis in mice was investigated, and their clinical feasibility of fertility preservation in cancer patients was also assessed. Eighteen Kunming mice were randomly given TSA or GSK at the concentrations of 0, 0.1 and 0.2 umol/L for three months. Immunofluorescence was used to evaluate the genetic recombination of homologous chromosomes and fidelity of chromosome synapsis. Sperm density, motility and viability were also examined to investigate the spermatogenic function. The average number of MLH1 foci in each spermatocyte was greatly higher in TSA (0.1) group than that in control (P<0.05), but no difference with the TSA (0.2) group (P>0.05). The frequency of SC with no MLH1 foci was lower while the frequency of SC with one MLH1 foci was higher in spermatocyte of mice with different doses of TSA compared with controls (P<0.05). The weight of left testis in TSA (0.1) group was significant decreased compared with that in control (P<0.05). However, no significant differences were observed in average number of MLH1, frequency of SC with 0-3 MLH1 foci, spermatocyte percentage of XY chromosomes containing MLH1 foci and percentages of cells containing gaps and splits among groups with or without the treatment of GSK. Furthermore, there were no statistical differences in body weight, testicular weight, sperm density, sperm motility and sperm viability among the three groups. TSA increased genetic recombination frequency of spermatocyte meiosis. GSK had no significant effect on genetic recombination frequency of spermatocyte meiosis and spermatogenic function.

Comparison of the sensitivity and specificity of real-time PCR and in situ hybridization in HPV16 and 18 detection in archival cervical cancer specimens.

PubMed

Biesaga, Beata; Szostek, Sława; Klimek, Małgorzata; Jakubowicz, Jerzy; Wysocka, Joanna

2012-07-04

The aim of this study was to analyze the correlation between real-time PCR (RT-PCR) treated as a reference method and in situ hybridization with tyramide amplification system (ISH-TSA) in the detection of HPV16 and 18 infection and the assessment of viral genome status. The study was performed on cervical cancer biopsies fixed in 10% neutral buffered formalin and embedded in paraffin obtained from 85 women. TaqMan-based 5'exonuclease RT-PCR with type-specific primers was used to assess HPV16 and 18 infections and genome status. Viral infection and genome status was also assessed by ISH-TSA. RT-PCR revealed 76 (89.4%), and ISH-TSA 81 (95.3%) cancers with HPV16 and 18 infections. The ISH-TSA sensitivity and specificity were: 96.1% and 11.1% compared to RT-PCR. The difference between these techniques in HPV detection was significant (p = 0.000). Among 76 HPV16/18 positive cancers in RT-PCR, there were 30 (39.5%) with integrated and 46 (60.5%) with mixed viral genome form. According to ISH-TSA, there were 39 (51.3%) samples with integrated and 37 with mixed form (48.7%). The sensitivity and specificity of ISH-TSA in genome status assessment were 70.0% and 60.9%, respectively. The difference between RT-PCR and ISH-TSA in genome state detection was not statistically significant (p = 0.391). These results suggest that ISH-TSA shows insufficient specificity in HPV detection for use in clinical practice. However, this assay could be applied for viral genome status assessment.

Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation.

PubMed

He, Gang; Wang, Yan; Pang, Xueli; Zhang, Bo

2014-02-01

Radiotherapy is one of the main treatments for clinical cancer therapy. However, its application was limited due to lack of radiosensitivity in some cancers. Trichostatin A (TSA) is a classic histone deacetylases inhibitor (HDACi) that specifically inhibits the biochemical functions of HDAC and is demonstrated to be an active anticancer drug. However, whether it could sensitize colon cancer to radiation is not clear. Our results showed that TSA enhanced the radiosensitivity of colon cancer cells as determined by CCK-8 and clonogenic survival assay. Moreover, apoptotic cell death induced by radiation was enhanced by TSA treatment. Additionally, TSA also induced autophagic response in colon cancer cells, while autophagy inhibition led to cell apoptosis and enhanced the radiosensitivity of colon cancer cells. Our data suggested that inhibition of cytoprotective autophagy sensitizes cancer cell to radiation, which might be further investigated for clinical cancer radiotherapy.

Spatial diffusion of raccoon rabies in Pennsylvania, USA.

PubMed

Moore, D A

1999-05-14

Identification of the geographic pattern of diffusion of a wildlife disease could lead to information regarding its control. The objective of this study was to model raccoon-rabies diffusion in Pennsylvania to identify geographic constraints on the diffusion pattern for potential use in bait-vaccination strategies. A trend-surface analysis (TSA) was used as a spatial filter for month to first report by county location. A cubic polynomial model was fitted (R2 = 0.80). Velocity vectors were calculated from the partial derivatives of the model and mapped to demonstrate the instantaneous speed of diffusion at each location. A main corridor of diffusion through the ridge and valley section of the state was evident early in the outbreak. Once the disease reached the northern counties, the disease moved west toward Ohio. I believe that TSA was useful in identifying the pattern of raccoon-rabies diffusion across the stage from the inherent noise of disease-reporting data.

Targeting, Air Force Doctrine Document 2-1.9

DTIC Science & Technology

2006-06-08

Target system analysis ( TSA ), as its name implies, approaches targets and target sets as systems to determine vulnerabilities and exploitable...weaknesses. Targeteers review how a functional target system works as a whole and analyze the interactions between components. TSA takes a system-of...effectiveness of target development. TSA begins in peacetime, before the commencement of conflict, and is accomplished with federated support and

78 FR 59363 - New Agency Information Collection Activity Under OMB Review: TSA Pre✓TM

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-26

...This notice announces that the Transportation Security Administration (TSA) has forwarded the new Information Collection Request (ICR) abstracted below to the Office of Management and Budget (OMB) for review and approval under the Paperwork Reduction Act (PRA). The ICR describes the nature of the information collection and its expected burden. TSA published a Federal Register notice, with a 60-day comment period soliciting comments, of the following collection of information on July 23, 2013 (78 FR 44140). The collection involves the submission of biographic and biometric information by individuals seeking to enroll in the TSA Pre[check]TM Application Program.

Short, Medium and Long Term Complications After Total Anatomical Shoulder Arthroplasty

PubMed Central

Gregory, T.M.; Boukebous, B.; Gregory, J.; Pierrart, J.; Masemjean, E.

2017-01-01

Total shoulder arthroplasty (TSA) is an effective approach for the treatment of a variety of clinical conditions affecting the shoulder, including osteoarthritis, inflammatory arthritis and osteonecrosis, and the number of TSA implanted has grown exponentially over the past decade. This review gives an update of the major complications, mainly infections, instability and loosening, encountered after TSA, based on a corpus of recent publications and a dynamic approach: The review focuses on the causes of glenoid loosening, which account for 80% of the complication, and underlines the importance of glenoid positioning in the recovery of early shouder function and in the long term survival rate of TSA. PMID:29152008

A Study of Demand Response Effect of Thermal Storage Air-Conditioning Systems in Consideration of Electricity Market Prices

NASA Astrophysics Data System (ADS)

Omagari, Yuko; Sugihara, Hideharu; Tsuji, Kiichiro

This paper evaluates the economic impact of the introduction of customer-owned Thermal Storage Air-conditioning (TSA) systems, in an electricity market, from the viewpoint of the load service entity. We perform simulations on the condition that several thousand customers install TSA systems and shift peak demand in an electricity market by one percent. Our numerical results indicate that the purchase cost of the LSE was reduced through load management of customers with TSA systems. The introduction of TSA systems also reduced the volatility of market clearing price and reduced the whole-trade cost in an electricity market.

Synthesis, characterization and applications of a new cation exchanger tamarind sulphonic acid (TSA) resin.

PubMed

Singh, A V; Sharma, Naresh Kumar; Rathore, Abhay S

2012-01-01

A new composite cation exchanger, tamarind sulphonic acid (TSA) resin has been synthesized. The chemically modified TSA ion exchange resin has been used for the removal and preconcentration of Zn2+, Cd2+, Fe2+, Co2+ and Cu2+ ions in aqueous solution and effluent from the Laxmi steel plant in Jodhpur, India. This type of composite represents a new class of hybrid ion exchangers with good ion exchange capacity, stability, reproducibility and selectivity for toxic metal ions found in effluent from the steel industry. The characterization of the resin was carried out by determining the ion-exchange capacity, elemental analysis, pH titration, Fourier transform infrared spectra and thermal analysis. The distribution coefficients (K(d)) of toxic metal ions were determined in a reference aqueous solution and the steel plant effluent at different pH values; the absorbency of different metal ions on the TSA resin was studied for up to 10 cycles. The adsorption of different metal ions on TSA resin follows the order: Co2+ > Cu2+ > Zn2+ > Fe2+ > Cd2+. The ion exchange capacity of TSA resin is 2.87%.

Different effects of histone deacetylase inhibitors nicotinamide and trichostatin A (TSA) in C17.2 neural stem cells.

PubMed

Wang, Haifeng; Cheng, Hua; Wang, Kai; Wen, Tieqiao

2012-11-01

Histone deacetylase inhibitors are involved in proliferation, apoptosis, cell cycle, mRNA transcription, and protein expression in various cells. However, the molecular mechanism underlying such functions is still not fully clear. In this study, we used C17.2 neural stem cell (NSC) line as a model to evaluate the effects of nicotinamide and trichostatin A (TSA) on cell characteristics. Results show that nicotinamide and TSA greatly inhibit cell growth, lead to cell morphology changes, and effectively induce cell apoptosis in a dose-dependent manner. Western blot analyses confirmed that nicotinamide significantly decreases the expression of bcl-2 and p38. Further insight into the molecular mechanisms shows the suppression of phosphorylation in eukaryotic initiation factor 4E-binding protein 1 (4EBP1) by nicotinamide, whereas, an increased expression of bcl-2 and p38 and phosphorylation of 4EBP1 by TSA. However, both nicotinamide and TSA significantly increase the expression of cytochrome c (cyt c). These results strongly suggest that bcl-2, p38, cyt c, and p-4EBP1 could suppress proliferation and induce apoptosis of C17.2 NSCs mediated by histone deacetylase inhibitors, nicotinamide and TSA, involving different molecular mechanisms.

Amelioration of cognitive impairments in APPswe/PS1dE9 mice is associated with metabolites alteration induced by total salvianolic acid

PubMed Central

Shen, Li; Han, Bing; Geng, Yuan; Wang, Jinhua; Wang, Zhengmin

2017-01-01

Purpose Total salvianolic acid (TSA) is extracted from salvia miltiorrhiza; however, to date, there has been limited characterization of its effects on metabolites in Alzheimer’s disease model-APPswe/PS1dE9 mice. The main objective of this study was to investigate the metabolic changes in 7-month-old APPswe/PS1dE9 mice treated with TSA, which protects against learning and memory impairment. Methods APPswe/PS1dE9 mice were treated with TSA (30 mg/kg·d and 60 mg/kg·d, i.p.) and saline (i.p.) daily from 3.5 months old for 14 weeks; saline-treated (i.p.) WT mice were included as the controls. The effects of TSA on learning and memory were assessed by a series of behavioral tests, including the NOR, MWM and step-through tasks. The FBG and plasma lipid levels were subsequently assessed using the GOPOD and enzymatic color methods, respectively. Finally, the concentrations of Aβ42, Aβ40 and metabolites in the hippocampus of the mice were detected via ELISA and GC-TOF-MS, respectively. Results At 7 months of age, the APPswe/PS1dE9 mice treated with TSA exhibited an improvement in the preference index (PI) one hour after the acquisition phase in the NOR and the preservation of spatial learning and memory in the MWM. Treatment with TSA substantially decreased the LDL-C level, and 60 mg/kg TSA decreased the CHOL level compared with the plasma level of the APPswe/PS1dE9 group. The Aβ42 and Aβ40 levels in the hippocampus were decreased in the TSA-treated group compared with the saline-treated APPswe/PS1dE9 group. The regulation of metabolic pathways relevant to TSA predominantly included carbohydrate metabolism, such as sorbitol, glucose-6-phosphate, sucrose-6-phosphate and galactose, vitamin metabolism involved in cholecalciferol and ascorbate in the hippocampus. Conclusions TSA induced a remarkable amelioration of learning and memory impairments in APPswe/PS1dE9 mice through the regulation of Aβ42, Aβ40, carbohydrate and vitamin metabolites in the hippocampus and LDL-C and CHOL in the plasma. PMID:28358909

Detection of Orientia tsutsugamushi (Rickettsiales: rickettsiaceae) in unengorged chiggers (Acari: Trombiculidae) from Oita Prefecture, Japan, by nested polymerase chain reaction.

PubMed

Pham, X D; Otsuka, Y; Suzuki, H; Takaoka, H

2001-03-01

The current study surveyed the 56-kDa type-specific antigen (TSA) gene DNAs of Orientia tsutsugamushi (Hayashi) in approximately 4.000 unengorged chiggers obtained from the soil or ground surface in an endemic and a nonendemic area of the Tsutsugamushi disease in Oita Prefecture, southwestern Japan, by nested polymerase chain reaction (PCR). Serotypes of O. tsutsugamushi were identified by restriction fragment-length polymorphism (RFLP) analysis. In the endemic area, 242 pools from five species [234 pools of Leptotrombidium scutellare (Nagayo, Miyagawa, Mitamura, Tamiya and Tenjin), two L. pallidum (Nagayo, Miyagawa, Mitamura and Tamiya), four L. kitasatoi (Fukuzumi & Obata), one L. fuji (Kuwata, Berge and Philip), and one Neotrombicula japonica (Tanaka, Kaiwa, Teramura and Kagaya)] were tested, and eight (seven pools of L. scutellare and one N. japonica) were positive for O. tsutsugamushi. Among the seven positive pools of L. scutellare, the distribution of serotypes was as follows: Kuroki (4), Gilliam (1), Karp (1), and Kawasaki (1). The first two serotypes (Kuroki and Gilliam) were identified for the first time in this species. In the nonendemic area, 128 pools from eight species were tested, and 13 were positive for O. tsutsugamushi. The positive rate was as follows: L. pallidum (4/41). L. kitasatoi (1/18), Gahrliepia saduski Womersley (2/10), L. fuji (4/50), L. himizu (Sasa, Kumada, Hayashi, Enomoto, Fukuzumi and Obata) (1/2), and Miyatrombicula kochiensis (Sasa, Kawashima and Egashira) (1/3). The latter three species were shown for the first time to harbor O. tsutsugamushi. All ofthe positive pools were Kuroki, except for two pools (one L. pallidum and one L. fuji), which were Gilliam (this serotype was also detected for the first time in L. pallidum). Further analysis revealed no differences in the nucleotide sequences (125 bp of variable domain 1 of TSA gene) of the same serotypes (i.e., Kuroki and Gilliam) among the positive samples. These data indicate that O. tsutsugamushi was widely distributed in various trombiculid species, even in the nonendemic area. The data are also suggestive of a possible horizontal transmission of O. tsutsugamushi among trombiculid species.

The "July effect" in total shoulder arthroplasty.

PubMed

Rao, Allison J; Bohl, Daniel D; Frank, Rachel M; Cvetanovich, Gregory L; Nicholson, Gregory P; Romeo, Anthony A

2017-03-01

New medical doctors enter their residency fields in July, a time in the hospital in which patient morbidity and mortality rates are perceived to be higher. It remains controversial whether a "July effect" exists in different areas of medicine and surgery, including in orthopedic surgery. The purpose of this study is to test for the July effect in patients undergoing primary total shoulder arthroplasty (TSA). Patients who underwent primary TSA from 2005-2012 were identified using the American College of Surgeons National Surgical Quality Improvement Program database. Cases were categorized as involving residents or fellows and as occurring during the first academic quarter. Rates of composite and any adverse event outcomes were compared between patient groups using multivariate logistic regression. A total of 1591 patients met the inclusion criteria. Of these cases, 711 (44.7%) had resident or fellow involvement and 390 (24.5%) were performed in the first academic quarter. There were few demographic and comorbidity differences between cases with and without residents or fellows or between cases performed during the first quarter and during the rest of the year. Overall, the rate of serious adverse events was 1.6% and the rate of any adverse events was 6.5%. Using one of the largest cohorts of primary TSA patients, this study could not provide evidence for a July effect. In the context of the recent growth in the volume of TSA procedures, these findings provide important reassurance to patients that it is safe to schedule their elective procedures at training institutions during the first part of the academic year. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

The histone deacetylase inhibitor, trichostatin A, inhibits the development of 2,4-dinitrofluorobenzene-induced dermatitis in NC/Nga mice.

PubMed

Kim, Tae-Ho; Jung, Jung-A; Kim, Gun-Dong; Jang, An-Hee; Cho, Jeong-Je; Park, Yong Seek; Park, Cheung-Seog

2010-10-01

Repetitive skin contact with a chemical hapten like 2,4-dinitrofluorobenzene (DNFB) evokes an atopic dermatitis (AD)-like dermatitis reaction in NC/Nga mice maintained under specific pathogen-free (SPF) conditions. The histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), modulates the expression of several genes by inhibiting the activity of HDACs. Furthermore, TSA has been reported to suppress inflammatory cytokine expression and to induce T cell-suppression by increasing regulatory T cell (T reg cell) numbers. In addition, histone deacetylase inhibitors (HDACi) are currently undergoing clinical trials for the treatment of inflammatory disorders. In the present study, we examined whether treatment with TSA suppresses AD-like skin lesions in NC/Nga mice treated with DNFB under SPF conditions. Intraperitoneal (i.p.) administration of TSA to DNFB-treated NC/Nga mice was found to inhibit ear thickness increases and the skin lesions induced by DNFB. Furthermore, IL-4 production by CD4+ T cells from the lymph nodes of DNFB-treated NC/Nga mice was significantly inhibited by TSA, although levels of IFN-γ were not. Flow cytometric analysis of lymphocytes showed an increase in CD4+ CD25+ T cell proportions in mice given TSA-i.p. These findings suggest that TSA suppresses the development of AD-like dermatitis in DNFB-treated NC/Nga mice by reducing IL-4 production and increasing the T reg cell population. Copyright © 2010 Elsevier B.V. All rights reserved.

A multi-band semi-analytical algorithm for estimating chlorophyll-a concentration in the Yellow River Estuary, China.

PubMed

Chen, Jun; Quan, Wenting; Cui, Tingwei

2015-01-01

In this study, two sample semi-analytical algorithms and one new unified multi-band semi-analytical algorithm (UMSA) for estimating chlorophyll-a (Chla) concentration were constructed by specifying optimal wavelengths. The three sample semi-analytical algorithms, including the three-band semi-analytical algorithm (TSA), four-band semi-analytical algorithm (FSA), and UMSA algorithm, were calibrated and validated by the dataset collected in the Yellow River Estuary between September 1 and 10, 2009. By comparing of the accuracy of assessment of TSA, FSA, and UMSA algorithms, it was found that the UMSA algorithm had a superior performance in comparison with the two other algorithms, TSA and FSA. Using the UMSA algorithm in retrieving Chla concentration in the Yellow River Estuary decreased by 25.54% NRMSE (normalized root mean square error) when compared with the FSA algorithm, and 29.66% NRMSE in comparison with the TSA algorithm. These are very significant improvements upon previous methods. Additionally, the study revealed that the TSA and FSA algorithms are merely more specific forms of the UMSA algorithm. Owing to the special form of the UMSA algorithm, if the same bands were used for both the TSA and UMSA algorithms or FSA and UMSA algorithms, the UMSA algorithm would theoretically produce superior results in comparison with the TSA and FSA algorithms. Thus, good results may also be produced if the UMSA algorithm were to be applied for predicting Chla concentration for datasets of Gitelson et al. (2008) and Le et al. (2009).

DNA vaccination with a plasmid encoding LACK-TSA fusion against Leishmania major infection in BALB/c mice.

PubMed

Maspi, N; Ghaffarifar, F; Sharifi, Z; Dalimi, A; Khademi, S Z

2017-12-01

Vaccination would be the most important strategy for the prevention and elimination of leishmaniasis. The aim of the present study was to compare the immune responses induced following DNA vaccination with LACK (Leishmania analogue of the receptor kinase C), TSA (Thiol-specific-antioxidant) genes alone or LACK-TSA fusion against cutaneous leishmaniasis (CL). Cellular and humoral immune responses were evaluated before and after challenge with Leishmania major (L. major). In addition, the mean lesion size was also measured from 3th week post-infection. All immunized mice showed a partial immunity characterized by higher interferon (IFN)-γ and Immunoglobulin G (IgG2a) levels compared to control groups (p<0.05). IFN-γ/ Interleukin (IL)-4 and IgG2a/IgG1 ratios demonstrated the highest IFN-γ and IgG2a levels in the group receiving LACK-TSA fusion. Mean lesion sizes reduced significantly in all immunized mice compared with control groups at 7th week post-infection (p<0.05). In addition, there was a significant reduction in mean lesion size of LACK-TSA and TSA groups than LACK group after challenge (p<0.05). In the present study, DNA immunization promoted Th1 immune response and confirmed the previous observations on immunogenicity of LACK and TSA antigens against CL. Furthermore, this study demonstrated that a bivalent vaccine can induce stronger immune responses and protection against infectious challenge with L. major.

Strategic Improvements to TSA Spot Program

DTIC Science & Technology

2015-03-01

Willard Shepard , “TSA Agents Rescue Kidnapped Woman,” NBC 6 South Florida. July 31, 2012, http://www.nbcmiami.com/news/local/Kidnapped-Woman-Was...For example, a high percentage of Muslims being selected by the BDOs for additional screening at a Chicago airport does not necessarily indicate...Muslim.109 Further, the traveling population from Chicago airports could have an even higher Muslim population. Local TSA

Comparison of techniques for culture of dialysis water and fluid.

PubMed

Maltais, Jo-Ann B; Meyer, Klemens B; Foster, Meredith C

2017-04-01

Microbiological culture of dialysis water and fluid is a routine safety measure. In the United States (U.S.), laboratories perform these cultures on trypticase soy agar at 35-37°C for 48 h (TSA-48h), not on the tryptone glucose extract agar or Reasoner's 2A agar at 17-23°C for 7 days (TGEA-7d and R2A-7d, respectively) recommended by international standards. We compared culture methods to identify samples exceeding the accepted action level of 50 CFU/mL. Dialysis water and fluid samples collected from 41 U.S. dialysis programs between 2011 and 2014 were cultured at two U.S. laboratories. Each sample was cultured using (1) either TGEA-7d or R2A-7d and (2) TSA-48h. We compared proportions exceeding the action level by different methods and test characteristics of TSA-48h to those of TGEA-7d and R2A-7d. The proportion of water samples yielding colony counts ≥50 CFU/mL by TGEA-7d was significantly different from the proportion by TSA-48h (P = 0.001; difference in proportion 4.3% [95%CI 1.3-7.3%]). The proportions of dialysis fluid samples ≥50 CFU/mL by TGEA-7d and TSA-48h were not significantly different; there were no significant differences for comparisons of R2A-7d to TSA-48h. In dialysis fluid, TSA-48h was comparable to TGEA-7d and R2A-7d in identifying samples as having bacterial counts ≥50 CFU/mL. In dialysis water, TSA-48h was comparable to R2A-7d in identifying samples ≥50 CFU/mL, but TGEA-7d did yield significantly more results above 50 CFU/mL. Nonetheless, the negative predictive value of a TSA-48h result of <50 CFU/mL in dialysis water exceeded 95%. © 2016 The Authors Hemodialysis International published by Wiley Periodicals, Inc. on behalf of International Society for Hemodialysis.

Antitumor effect of interleukin (IL)-12 in the absence of endogenous IFN-gamma: a role for intrinsic tumor immunogenicity and IL-15.

PubMed

Gri, Giorgia; Chiodoni, Claudia; Gallo, Elena; Stoppacciaro, Antonella; Liew, Foo Y; Colombo, Mario P

2002-08-01

IFN-gamma knockout mice (GKO) rejected C26 colon carcinoma cells transduced to secrete interleukin(IL)-12 but do not reject similarly transduced TSA mammary adenocarcinoma (C26/12 and TSA/12 cells, respectively). To determine whether such difference could be because of a different tumor response to IFN-gamma, we injected BALB/c mice with TSA, C26, and their IL-12-transduced counterparts rendered unresponsive to IFN-gamma by stable transduction of a dominant negative (DN), truncated IFN-gamma receptor alpha chain. TSA/DN and C26/DN showed the same in vivo growth kinetics as parental cells, whereas coexpression of IL-12 induced rejection independent of tumor-cell responsiveness to IFN-gamma. This suggests that the role of IFN-gamma is primarily in activating the host immune response, which appears to depend on the intrinsic immunogenicity of the target tumor. C26 and TSA share a common tumor-associated antigen, yet C26 cells are more immunogenic than TSA. C26/12 expressed 10-fold higher levels of class I MHC molecules and induced higher CTL activity compared with TSA/12 cells in GKO mice. Moreover, whereas in GKO mice the TSA/12 tumor was associated with a greater number of infiltrating T cells, only those infiltrating C26/12 tumor expressed the activation marker OX40. The search for cytokine(s) that might contribute in determining the different T-cell response to these IL-12-transduced tumors in GKO mice revealed a role of IL-15. In situ hybridization showed IL-15 expression in C26/12 but not in TSA/12 tumors. In addition, injection of GKO mice with soluble IL-15 receptor-alpha to block IL-15 expression prevented rejection of C26/12 cells. Together, the results suggest that in the absence of IFN-gamma, IL-12 can exert antitumor activity through alternative mechanisms, depending on the tumor cell type and the availability of cytokines that can replace IFN-gamma in sustaining T-cell functions.

Synthesis and evaluation of [125I]I-TSA as a brain nicotinic acetylcholine receptor alpha7 subtype imaging agent.

PubMed

Ogawa, Mikako; Tatsumi, Ryo; Fujio, Masakazu; Katayama, Jiro; Magata, Yasuhiro

2006-04-01

Some in vitro investigations have suggested that the nicotinic acetylcholine receptor (nAChR) alpha7 subtype is implicated in Alzheimer's disease, schizophrenia and others. Recently, we developed (R)-3'-(5-bromothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-[1',3']oxazolidin]-2'-one (Br-TSA), which has a high affinity and selectivity for alpha7 nAChRs. Therefore we synthesized (R)-3'-(5-[125I]iodothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-[1',3']oxazolidin]-2'-one ([125I]I-TSA) and evaluated its potential for the in vivo detection of alpha7 nAChR in brain. In vitro binding affinity of I-TSA was measured in rat brain homogenates. Radioiodination was accomplished by a Br-I exchange reaction. Biodistribution studies were undertaken in mice by tail vein injection of [(125)I]I-TSA. In vivo receptor blocking studies were carried out by treating mice with methyllycaconitine (MLA; 5 nmol/5 mul, i.c.v.) or nonradioactive I-TSA (50 micromol/kg, i.v.). I-TSA exhibited a high affinity and selectivity for the alpha7 nAChR (K(i) for alpha7 nAChR = 0.54 nM). Initial uptake in the brain was high (4.42 %dose/g at 5 min), and the clearance of radioactivity was relatively slow in the hippocampus (alpha7 nAChR-rich region) and was rather rapid in the cerebellum (alpha7 nAChR poor region). The hippocampus to cerebellum uptake ratio was 0.9 at 5 min postinjection, but it was increased to 1.8 at 60 min postinjection. Although the effect was not statistically significant, administration of I-TSA and MLA decreased the accumulation of radioactivity in hippocampus. Despite its high affinity and selectivity, [125I]I-TSA does not appear to be a suitable tracer for in vivo alpha7 nAChR receptor imaging studies due to its high nonspecific binding. Further structural optimization is needed.

Tanshinone IIA promotes the proliferation of WB-F344 hepatic oval cells via Wnt/β-catenin signaling

PubMed Central

ZE, XINGYU; JIA, JIDONG; LI, XINMIN; YOU, HONG; ZHAO, XINYAN; ZHANG, DONG; WANG, BAOEN

2016-01-01

Tanshinone IIA (TSA) is a widely used traditional Chinese medicine, which has been demonstrated to protect damaged liver cells and is currently administered in the treatment of liver fibrosis. Liver precursor cells, also termed oval cells, are key in the repair of liver tissues following injury. However, whether TSA improves the function of liver cells and protects the liver from injury by enhancing the growth and proliferation of hepatic oval cells remains to be elucidated. In the present study, low to moderate concentrations of TSA were observed to stimulate proliferation, did not induce apoptosis in WB-F344 rat hepatic oval cells and the increased expression levels of β-catenin. WB-F344 cells were treated with various concentrations of TSA (0–80 µg/ml) for 24, 48, 72 and 96 h. Cell proliferation was measured using a Cell Counting kit-8 (CCK-8) assay, a 5-ethynyl-2′-deoxyuridine assay and a carboxyfluorescein diacetate succinimidyl ester (CFSE) assay. The CCK-8 assay demonstrated that treatment of WB-F344 cells with 20–40 µg/ml TSA for up to 72 h significantly increased proliferation. Similar results were observed in the subsequent EdU and CFSE assays. Furthermore, a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay demonstrated that 20–40 µg/ml TSA treatment for up to 96 h did not induce apoptosis of the WB-F344 cells. Notably, the results of western blot, immunofluorescence and reverse transcription-quantitative polymerase chain reaction analyses demonstrated that treatment of the WB-F344 cells with 20–40 µg/ml TSA for up to 72 h significantly increased the expression levels of β-catenin. These data indicated that TSA at concentrations between 20 and 40 µg/ml may induce WB-F344 cell proliferation by activating the canonical Wnt signaling pathway. The results of the present study suggest that TSA may be a useful natural agent to enhance repair and regeneration of the injured liver, and improve liver regeneration following orthotopic liver transplantation. PMID:26709094

Temperature Swing Adsorption Compressor Development

NASA Technical Reports Server (NTRS)

Finn, John E.; Mulloth, Lila M.; Affleck, Dave L.

2001-01-01

Closing the oxygen loop in an air revitalization system based on four-bed molecular sieve and Sabatier reactor technology requires a vacuum pump-compressor that can take the low-pressure CO, from the 4BMS and compress and store for use by a Sabatier reactor. NASA Ames Research Center proposed a solid-state temperature-swing adsorption (TSA) compressor that appears to meet performance requirements, be quiet and reliable, and consume less power than a comparable mechanical compressor/accumulator combination. Under this task, TSA compressor technology is being advanced through development of a complete prototype system. A liquid-cooled TSA compressor has been partially tested, and the rest of the system is being fabricated. An air-cooled TSA compressor is also being designed.

Comparison of media for detection of fungi on spacecraft

NASA Technical Reports Server (NTRS)

Herring, C. M.; Brandsberg, J. W.; Oxborrow, G. S.; Puleo, J. R.

1974-01-01

Five media, including Trypticase soy agar (TSA; BBL) pour plates, spread plates of TSA, Mycophil agar with chloromycetin, Mycophil agar with chloromycetin and Actidione, and cornmeal agar with chloromycetin were quantitatively and qualitatively compared for the detection of fungi on spacecraft. Cornmeal agar with chloromycetin yielded the highest number of fungal colonies, although not always significantly higher than Mycophil agar with chloromycetin or TSA spread plates. Cornmeal agar with chloromycetin also gave the best qualitative representation of fungi on the spacecraft, recovering 68% of the genera found from all media. This medium yielded 10 times the number of fungal colonies and 3 times the number of genera found on TSA pour plates as currently used for spacecraft assay.

Comparison of media for detection of fungi on spacecraft.

PubMed

Herring, C M; Brandsberg, J W; Oxborrow, G S; Puleo, J R

1974-03-01

Five media, including Trypticase soy agar (TSA; BBL) pour plates, spread plates of TSA, Mycophil agar with chloromycetin, Mycophil agar with chloromycetin and Actidione, and cornmeal agar with chloromycetin were quantitatively and qualitatively compared for the detection of fungi on spacecraft. Cornmeal agar with chloromycetin yielded the highest number of fungal colonies, although not always significantly higher than Mycophil agar with chloromycetin or TSA spread plates. Cornmeal agar with chloromycetin also gave the best qualitative representation of fungi on the spacecraft, recovering 68% of the genera found from all media. This medium yielded 10 times the number of fungal colonies and 3 times the number of genera found on TSA pour plates as currently used for spacecraft assay.

Modulation of mitomycin C-induced genotoxicity by acetyl- and thio- analogues of salicylic acid.

PubMed

Pawar, Amol Ashok; Vikram, Ajit; Tripathi, Durga Nand; Padmanabhan, Shweta; Ramarao, Poduri; Jena, Gopabandhu

2009-01-01

Recent reports regarding acetylsalicylic acid (ASA) and its metabolites suggest suppressive effects against mitomycin C (MMC)-induced genotoxicity in a mice chromosomal aberration assay. Keeping this in mind, the potential anti-genotoxic effect of the thio-analogue of salicylic acid namely thio-salicylic acid (TSA) was speculated upon. The present study investigated and compared the anti-genotoxic potential of ASA and TSA. The study was performed in male swiss mice (20+/-2 g) using single-cell gel electrophoresis and a peripheral blood micronucleus assay. ASA and TSA (5, 10 or 20 mg/kg) were administered 15 minutes after MMC (1 mg/kg) once daily for 3 or 7 days. Both ASA and TSA significantly decreased the DNA damage induced by MMC as indicated by a decrease in the comet parameters in bone marrow cells and decreased frequencies of micronucleated reticulocytes in peripheral blood. The results clearly demonstrate the anti-genotoxic potential of ASA and TSA.

Repeated transsphenoidal surgery or gamma knife radiosurgery in recurrent cushing disease after transsphenoidal surgery.

PubMed

Bodaghabadi, Mohammad; Riazi, Hooman; Aran, Shima; Bitaraf, Mohammad Ali; Alikhani, Mazdak; Alahverdi, Mahmud; Mohamadi, Masoumeh; Shalileh, Keivan; Azar, Maziar

2014-03-01

This study compared Gamma knife radiosurgery (GKRS) and repeated transsphenoidal adenomectomy (TSA) to find the best approach for recurrence of Cushing disease (CD) after unsuccessful first TSA. Fifty-two patients with relapse of CD after TSA were enrolled and randomly underwent a second surgery or GKRS as the next therapeutic approach. They were followed for a mean period of 3.05 ± 0.8 years by physical examination and hormone measurement as well as magnetic resonance imaging. No significant difference was observed in sex ratio, mean age, adenoma type, follow-up duration, and initial hormone level between the two groups. No significant relationship was found between preoperative 24-hour free urine cortisol and disease-free months or tumor volume among both groups. Our statistical analysis showed higher recurrence-free interval in the GKRS group compared with TSA group. With longer recurrence-free interval, GKRS could be considered a good treatment alternative to repeated TSA in recurrent CD. Georg Thieme Verlag KG Stuttgart · New York.

Communication and team situation awareness in the OR: Implications for augmentative information display.

PubMed

Parush, Avi; Kramer, Chelsea; Foster-Hunt, Tara; Momtahan, Kathryn; Hunter, Aren; Sohmer, Benjamin

2011-06-01

Team Situation Awareness (TSA) is one of the critical factors in effective Operating Room (OR) teamwork and can impact patient safety and quality of care. While previous research showed a relationship between situation awareness, as measured by communication events, and team performance, the implications for developing technology to augment and facilitate TSA were not examined. This research aims to further study situation-related communications in the cardiac OR in order to uncover potential degradation in TSA which may lead to adverse events. The communication loop construct-the full cycle of information flow between the participants in the sequence-was used to assess susceptibility to breakdown. Previous research and the findings here suggest that communication loops that are open, non-directed, or with delayed closure, can be susceptible to information loss. These were quantitatively related to communication indicators of TSA such as questions, replies, and announcements. Taken together, both qualitative and quantitative analyses suggest that a high proportion of TSA-related communication (63%) can be characterized as susceptible to information loss. The findings were then used to derive requirements and design a TSA augmentative display. The design principles and potential benefits of such a display are outlined and discussed. Copyright © 2010 Elsevier Inc. All rights reserved.

Liquid chromatography-tandem mass spectrometry assay for the quantification of free and total sialic acid in human cerebrospinal fluid.

PubMed

van der Ham, Maria; de Koning, Tom J; Lefeber, Dirk; Fleer, André; Prinsen, Berthil H C M T; de Sain-van der Velden, Monique G M

2010-05-01

Analysis of sialic acid (SA) metabolites in cerebrospinal fluid (CSF) is important for clinical diagnosis. In the present study, a high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS) method for free sialic acid (FSA) and total sialic acid (TSA) in human CSF was validated. The method utilized a simple sample-preparation procedure of protein precipitation for FSA and acid hydrolysis for TSA. Negative electrospray ionisation was used to monitor the transitions m/z 308.2-->87.0 (SA) and m/z 311.2--> 90.0 ((13)C(3)-SA). Conjugated sialic acid (CSA) was calculated by subtracting FSA from TSA. We established reference intervals for FSA, TSA and CSA in CSF in 217 control subjects. The method has been applied to patients' samples with known differences in SA metabolites like meningitis (n=6), brain tumour (n=2), leukaemia (n=5), and Salla disease (n=1). Limit of detection (LOD) was 0.54 microM for FSA and 0.45 mM for TSA. Intra- and inter-assay variation for FSA (21.8 microM) were 4.8% (n=10) and 10.4% (n=40) respectively. Intra- and inter-assay variation for TSA (35.6 microM) were 9.7% (n=10) and 12.8% (n=40) respectively. Tested patients showed values of TSA above established reference value. The validated method allows sensitive and specific measurement of SA metabolites in CSF and can be applied for clinical diagnoses. 2010 Elsevier B.V. All rights reserved.

76 FR 51847 - Air Cargo Screening

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-18

...This rule amends two provisions of the Air Cargo Screening Interim Final Rule (IFR) issued on September 16, 2009, and responds to public comments on the IFR. The IFR codified a statutory requirement of the Implementing Recommendations of the 9/11 Commission Act of 2007 that the Transportation Security Administration (TSA) establish a system to screen 100 percent of cargo transported on passenger aircraft not later than August 3, 2010. It established the Certified Cargo Screening Program, in which TSA certifies shippers, indirect air carriers, and other entities as Certified Cargo Screening Facilities (CCSFs) to screen cargo prior to transport on passenger aircraft. Under the IFR, each CCSF applicant had to successfully undergo an assessment of their facility by a TSA-approved validation firm or by TSA. In response to public comment, this Final Rule removes all validation firm and validator provisions, so that TSA will continue to conduct assessments of the applicant's facility to determine if certification is appropriate. The IFR also required that if an aircraft operator or foreign air carrier screens cargo off an airport, it must do so as a CCSF. The Final Rule deletes this requirement, as aircraft operators are already screening cargo on airport under a TSA-approved security program, and do not need a separate certification to screen cargo off airport. This rule also proposes a fee range for the processing of Security Threat Assessments, and seeks comment on the proposed fee range and the methodology used to develop the fee. TSA will announce the final fee in a future Federal Register notice.

Total Shoulder Arthroplasty: Is Less Time in the Hospital Better?

PubMed

Duchman, Kyle R; Anthony, Chris A; Westermann, Robert W; Pugely, Andrew J; Gao, Yubo; Hettrich, Carolyn M

2017-01-01

The incidence of total shoulder arthroplasty (TSA) has increased significantly over the last decade. Short-stay protocols for other highvolume procedures have been shown to be safe and effective but have yet to be fully explored for TSA. Our purpose in comparing short-stay and inpatient TSA was to determine: (1) patient demographics and comorbidities, (2) 30-day morbidity, mortality, and readmissions using a matched analysis, and (3) independent predictors of 30-day complications. The American College of Surgeons National Surgical Quality Improvement (ACS NSQIP) database was queried and all patients undergoing elective, primary TSA between 2006 and 2013 were identified. Patients were categorized as short-stay or inpatient based on day of discharge. Propensity score matching was used to adjust for selection bias. Univariate and multivariate statistical analysis was used to compare 30-day morbidity and mortality between the two cohorts. Overall, 4,619 cases were available, with inpatient admission occurring in 65.7% of patients. Prior to propensity score matching, short-stay patients were significantly younger, more frequently male, with fewer comorbid conditions. After matching, inpatient admission was associated with increased rates of urinary tract infection (1.1% vs. 0.1%; p = 0.001), blood transfusion (5.3% vs. 0.8%; p < 0.001), and total complications (4.7% vs. 1.8%; p < 0.001). Multivariate analysis identified inpatient admission as an independent risk factor for 30-day complication following TSA. Short-stay TSA is a safe option for the appropriately selected patient. Inpatient admission was an independent risk factor for complication following TSA. Level of Evidence: III.

Sp1 is a transcription repressor to stanniocalcin-1 expression in TSA-treated human colon cancer cells, HT29.

PubMed

Law, Alice Y S; Yeung, B H Y; Ching, L Y; Wong, Chris K C

2011-08-01

Our previous study demonstrated that, stanniocalcin-1 (STC1) was a target of histone deacetylase (HDAC) inhibitors and was involved in trichostatin A (TSA) induced apoptosis in the human colon cancer cells, HT29. In this study, we reported that the transcriptional factor, specificity protein 1 (Sp1) in association with retinoblastoma (Rb) repressed STC1 gene transcription in TSA-treated HT29 cells. Our data demonstrated that, a co-treatment of the cells with TSA and Sp1 inhibitor, mithramycin A (MTM) led to a marked synergistic induction of STC1 transcript levels, STC1 promoter (1 kb)-driven luciferase activity and an increase of apoptotic cell population. The knockdown of Sp1 gene expression in TSA treated cells, revealed the repressor role of Sp1 in STC1 transcription. Using a protein phosphatase inhibitor okadaic acid (OKA), an increase of Sp1 hyperphosphorylation and so a reduction of its transcriptional activity, led to a significant induction of STC1 gene expression. Chromatin immunoprecipitation (ChIP) assay revealed that Sp1 binding on STC1 proximal promoter in TSA treated cells. The binding of Sp1 to STC1 promoter was abolished by the co-treatment of MTM or OKA in TSA-treated cells. Re-ChIP assay illustrated that Sp1-mediated inhibition of STC1 transcription was associated with the recruitment of another repressor molecule, Rb. Collectively our findings identify STC1 is a downstream target of Sp1. Copyright © 2011 Wiley-Liss, Inc.

Patient perception of physician reimbursement in elective shoulder surgery.

PubMed

Nagda, Sameer; Wiesel, Brent; Abboud, Joseph; Salamone, Andrew; Sheth, Neil; Foran, Jared; Garstka, Johnny

2015-01-01

A previous study revealed that patients perceived physician reimbursement to be much higher than current Medicare schedules for hip and knee replacement. The purpose of this study was to evaluate patient perception of surgeon reimbursement for total shoulder replacement (TSA) and rotator cuff repair (RCR). The study surveyed 250 patients. Patients were asked what they believe a surgeon should be reimbursed for performing TSA and RCR. Patients were then asked to estimate what Medicare reimbursed for each of these procedures. We then revealed the Medicare reimbursement rate for TSA and RCR, and patients were asked to comment. Finally, patients were asked whether surgeons with advanced shoulder training should receive additional payments. Patients thought that surgeons should receive $13,178 for TSA and $8459 for RCR. Patients estimated actual Medicare reimbursement was $7177 for TSA and $4692 for RCR. Eighty percent of patients stated that Medicare reimbursement was too low for TSA, 75% thought that payment for RCR was lower than what it should be. Less than 1% of patients felt that it was higher than it should be. A total of 87% of patients thought that surgeons with advanced shoulder training should be reimbursed at a higher rate. Patients perceived the values of TSA and RCR were much higher than current Medicare schedules. This is in agreement with prior surveys. Continued decreases in Medicare reimbursements may force surgeons to not participate in Medicare and create a potential access issue. Further investigation should focus on identifying how many surgeons may opt out. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Tanshinone IIA attenuates the cerebral ischemic injury-induced increase in levels of GFAP and of caspases-3 and -8.

PubMed

Zhou, L; Bondy, S C; Jian, L; Wen, P; Yang, F; Luo, H; Li, W; Zhou, Jun

2015-03-12

Tanshinone IIA (TSA) is a lipid soluble agent derived from the root of Salvia miltiorrhiza (Danshen). This plant is a traditional Chinese herb, which has been used widely in China especially for enhancing circulation. However mechanisms underlying its efficacy remain poorly understood. The present study was designed to illuminate events that may underlie the apparently neuroprotective effects of TSA following ischemic insult. Adult Sprague-Dawley rats were subjected to transient focal cerebral ischemia by use of a middle cerebral artery occlusion model. They were then randomly divided into a sham-operated control group, and cerebral ischemia/reperfusion groups receiving a two-hour occlusion. Further subsets of groups received the same durations of occlusion or were sham-operated but then received daily i.p. injections of high or low doses of TSA, for seven or 15days. Hematoxylin and eosin staining revealed lesions in the entorhinal cortex of both rats subject to ischemia and to a lesser extent to those receiving TSA after surgery. Levels of glial fibrillary acidic protein (GFAP), caspase-3 and caspase-8, were quantified by both immunohistochemistry and Western blotting. TSA treatment after middle cerebral artery occlusion, markedly reduced infarct size, and reduced the expression of caspase-3 and caspase-8. These changes were considered protective and were generally proportional to the dose of TSA used. These results suggest that TSA may effect neuroprotection by way of reduction of the extent of cell inflammation and death within affected regions. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Autotaxin is induced by TSA through HDAC3 and HDAC7 inhibition and antagonizes the TSA-induced cell apoptosis

PubMed Central

2011-01-01

Background Autotaxin (ATX) is a secreted glycoprotein with the lysophospholipase D (lysoPLD) activity to convert lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a bioactive lysophospholipid involved in diverse biological actions. ATX is highly expressed in some cancer cells and contributes to their tumorigenesis, invasion, and metastases, while in other cancer cells ATX is silenced or expressed at low level. The mechanism of ATX expression regulation in cancer cells remains largely unknown. Results In the present study, we demonstrated that trichostatin A (TSA), a well-known HDAC inhibitor (HDACi), significantly induced ATX expression in SW480 and several other cancer cells with low or undetectable endogenous ATX expression. ATX induction could be observed when HDAC3 and HDAC7 were down-regulated by their siRNAs. It was found that HDAC7 expression levels were low in the cancer cells with high endogenous ATX expression. Exogenous over-expression of HDAC7 inhibited ATX expression in these cells in a HDAC3-dependent manner. These data indicate that HDAC3 and HDAC7 collaboratively suppress ATX expression in cancer cells, and suggest that TSA induce ATX expression by inhibiting HDAC3 and HDAC7. The biological significance of this regulation mechanism was revealed by demonstrating that TSA-induced ATX protected cancer cells against TSA-induced apoptosis by producing LPA through its lysoPLD activity, which could be reversed by BrP-LPA and S32826, the inhibitors of the ATX-LPA axis. Conclusions We have demonstrated that ATX expression is repressed by HDAC3 and HDAC7 in cancer cells. During TSA treatment, ATX is induced due to the HDAC3 and HDAC7 inhibition and functionally antagonizes the TSA-induced apoptosis. These results reveal an internal HDACi-resistant mechanism in cancer cells, and suggest that the inhibition of ATX-LPA axis would be helpful to improve the efficacy of HDACi-based therapeutics against cancer. PMID:21314984

Histone deacetylase inhibitors VPA and TSA induce apoptosis and autophagy in pancreatic cancer cells.

PubMed

Gilardini Montani, Maria Saveria; Granato, Marisa; Santoni, Claudio; Del Porto, Paola; Merendino, Nicolò; D'Orazi, Gabriella; Faggioni, Alberto; Cirone, Mara

2017-04-01

Histone deacetylase inhibitors (HDACi) are anti-neoplastic agents that are known to affect the growth of different cancer types, but their underlying mechanisms are still incompletely understood. Here, we compared the effects of two HDACi, i.e., Trichostatin A (TSA) and Valproic Acid (VPA), on the induction of cell death and autophagy in pancreatic cancer-derived cells that exhibit a high metastatic capacity and carry KRAS/p53 double mutations. Cell viability and proliferation tests were carried out using Trypan blue dye exclusion, MTT and BrdU assays. FACS analyses were carried out to assess cell cycle progression, apoptosis, reactive oxygen species (ROS) production and mitochondrial depolarization, while Western blot and immunoprecipitation analyses were employed to detect proteins involved in apoptosis and autophagy. We found that both VPA and TSA can induce apoptosis in Panc1 and PaCa44 pancreatic cancer-derived cells by triggering mitochondrial membrane depolarization, Cytochrome c release and Caspase 3 activation, although VPA was more effective than TSA, especially in Panc1 cells. As underlying molecular events, we found that ERK1/2 was de-phosphorylated and that the c-Myc and mutant p53 protein levels were reduced after VPA and, to a lesser extent, after TSA treatment. Up-regulation of p21 and Puma was also observed, concomitantly with mutant p53 degradation. In addition, we found that in both cell lines VPA increased the pro-apoptotic Bim level, reduced the anti-apoptotic Mcl-1 level and increased ROS production and autophagy, while TSA was able to induce these effects only in PaCA44 cells. From our results we conclude that both VPA and TSA can induce pancreatic cancer cell apoptosis and autophagy. VPA appears have a stronger and broader cytotoxic effect than TSA and, thus, may represent a better choice for anti-pancreatic cancer therapy.

TSA increases C/EBP‑α expression by increasing its lysine acetylation in hepatic stellate cells.

PubMed

Tao, Li-Li; Ding, Di; Yin, Wei-Hua; Peng, Ji-Ying; Hou, Chen-Jian; Liu, Xiu-Ping; Chen, Yao-Li

2017-11-01

CCAAT enhancer binding protein‑α (C/EBP‑α) is a transcription factor expressed only in certain tissues, including the liver. It has been previously demonstrated that C/EBP‑α may induce apoptosis in hepatic stellate cells (HSCs), raising the question of whether acetylation of C/EBP‑α is associated with HSCs, and the potential associated mechanism. A total of three histone deacetylase inhibitors (HDACIs), including trichostatin A (TSA), suberoylanilide hydroxamic acid and nicotinamide, were selected to determine whether acetylation affects C/EBP‑α expression. A Cell Counting Kit‑8 assay was used to determine the rate of proliferation inhibition following treatment with varying doses of the three HDACIs in HSC‑T6 and BRL‑3A cells. Western blot analysis was used to examine Caspase‑3, ‑8, ‑9, and ‑12 levels in HSC‑T6 cells treated with adenoviral‑C/EBP‑α and/or TSA. Following treatment with TSA, a combination of reverse transcription‑quantitative polymerase chain reaction and western blot analyses was used to determine the inherent C/EBP‑α mRNA and protein levels in HSC‑T6 cells at 0, 1, 2, 4, 8, 12, 24, 36 and 48 h. Nuclear and cytoplasmic proteins were extracted to examine C/EBP‑α distribution. Co‑immunoprecipitation analysis was used to examine the lysine acetylation of C/EBP‑α. It was observed that TSA inhibited the proliferation of HSC‑T6 cells to a greater extent compared with BRL‑3A cells, following treatment with the three HDACIs. TSA induced apoptosis in HSC‑T6 cells and enhanced the expression of C/EBP‑α. Following treatment of HSC‑T6 cells with TSA, inherent C/EBP‑α expression increased in a time‑dependent manner, and its lysine acetylation simultaneously increased. Therefore, the results of the present study suggested that TSA may increase C/EBP‑α expression by increasing its lysine acetylation in HSCs.

Autotaxin is induced by TSA through HDAC3 and HDAC7 inhibition and antagonizes the TSA-induced cell apoptosis.

PubMed

Li, Song; Wang, Baolu; Xu, Yan; Zhang, Junjie

2011-02-12

Autotaxin (ATX) is a secreted glycoprotein with the lysophospholipase D (lysoPLD) activity to convert lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a bioactive lysophospholipid involved in diverse biological actions. ATX is highly expressed in some cancer cells and contributes to their tumorigenesis, invasion, and metastases, while in other cancer cells ATX is silenced or expressed at low level. The mechanism of ATX expression regulation in cancer cells remains largely unknown. In the present study, we demonstrated that trichostatin A (TSA), a well-known HDAC inhibitor (HDACi), significantly induced ATX expression in SW480 and several other cancer cells with low or undetectable endogenous ATX expression. ATX induction could be observed when HDAC3 and HDAC7 were down-regulated by their siRNAs. It was found that HDAC7 expression levels were low in the cancer cells with high endogenous ATX expression. Exogenous over-expression of HDAC7 inhibited ATX expression in these cells in a HDAC3-dependent manner. These data indicate that HDAC3 and HDAC7 collaboratively suppress ATX expression in cancer cells, and suggest that TSA induce ATX expression by inhibiting HDAC3 and HDAC7. The biological significance of this regulation mechanism was revealed by demonstrating that TSA-induced ATX protected cancer cells against TSA-induced apoptosis by producing LPA through its lysoPLD activity, which could be reversed by BrP-LPA and S32826, the inhibitors of the ATX-LPA axis. We have demonstrated that ATX expression is repressed by HDAC3 and HDAC7 in cancer cells. During TSA treatment, ATX is induced due to the HDAC3 and HDAC7 inhibition and functionally antagonizes the TSA-induced apoptosis. These results reveal an internal HDACi-resistant mechanism in cancer cells, and suggest that the inhibition of ATX-LPA axis would be helpful to improve the efficacy of HDACi-based therapeutics against cancer.

[Nutritional status of urban and rural Chilean school children of the metropolitan area].

PubMed

Ivanović, R; Olivares, M; Ivanović, D

1990-01-01

The objective of this study was to assess the nutritional status of chilean students by geographic area. In this respect, a representative sample of 4,509 students from elementary and high school was chosen from the Metropolitan Region of Chile (representative of 38.0% of chilean school population). Nutritional status was assessed through anthropometric measurements. Percent weight for age (% W/A), height for age (% H/A) and weight for height (% W/H) were compared with WHO standard; head circumference for age (% HC/A) with Tanner standard; arm circumference for age (% AC/A), triceps skinfold for age (% TS/A), arm muscle area for age (% AMA/A) and arm fat area/age (% AFA/A) with Frisancho norms. Socioeconomic status (SES) was measured through Graffar modified scale. Percent W/H is a better indicator of nutritional status due to growth failure which was thus detected in 27.6% of the whole sample (24.2% and 46.8%, respectively, in urban and rural area, p less than 0.001). According to % W/H, the frequencies of obesity were 13.4% and 10.5%, and those for undernutrition 5.7% and 8.2%, in urban and rural area, respectively, (p less than 0.05). Students from rural area showed significantly lower values for % HC/A, % AC/A, % TS/A and % AFA/A (p less than 0.001). There were no differences for % AMA/A. The fact that 90.5% of rural students belong to low SES must be taken into account to explain differences in the nutritional status of students of different geographic areas.

Training Systems Product Group (TSPG) Training Systems Acquisition (TSA)

DTIC Science & Technology

2006-05-23

ES) 10. SPONSOR/MONITOR’S ACRONYM(S) 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12 . DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release...Planned Actions • TSA III – Acquisition Strategy – Small Business • TSA II Points of Contact 3 Dominant Air Power: Design For Tomorrow…Deliver Today...Provides ready access to Large and Small Businesses Specializing in Air Force Training Systems Primarily Supporting Wright Patterson AFB OH and Hill AFB

Synergistic efficacy in human ovarian cancer cells by histone deacetylase inhibitor TSA and proteasome inhibitor PS-341.

PubMed

Fang, Yong; Hu, Yi; Wu, Peng; Wang, Beibei; Tian, Yuan; Xia, Xi; Zhang, Qinghua; Chen, Tong; Jiang, Xuefeng; Ma, Quanfu; Xu, Gang; Wang, Shixuan; Zhou, Jianfeng; Ma, Ding; Meng, Li

2011-05-01

Histone deacetylase inhibitors and proteasome inhibitor are all emerging as new classes of anticancer agents. We chose TSA and PS-341 to identify whether they have a synergistic efficacy on human ovarian cancer cells. After incubated with 500 nM TSA or/and 40 nM PS-341, we found that combined groups resulted in a striking increase of apoptosis and G2/M blocking rates, no matter in A2780, cisplatin-sensitive ovarian cancer cell line OV2008 or its resistant variant C13*. This demonstrated that TSA interacted synergistically with PS-341, which raised the possibility that combined the two drugs may represent a novel strategy in ovarian cancer.

Comparison of Media for Detection of Fungi on Spacecraft

PubMed Central

Herring, C. M.; Brandsberg, J. W.; Oxborrow, G. S.; Puleo, J. R.

1974-01-01

Five media, including Trypticase soy agar (TSA; BBL) pour plates, spread plates of TSA, Mycophil agar with chloromycetin, Mycophil agar with chloromycetin and Actidione, and cornmeal agar with chloromycetin were quantitatively and qualitatively compared for the detection of fungi on spacecraft. Cornmeal agar with chloromycetin yielded the highest number of fungal colonies, although not always significantly higher than Mycophil agar with chloromycetin or TSA spread plates. Cornmeal agar with chloromycetin also gave the best qualitative representation of fungi on the spacecraft, recovering 68% of the genera found from all media. This medium yielded 10 times the number of fungal colonies and 3 times the number of genera found on TSA pour plates as currently used for spacecraft assay. PMID:4151044

Trichostatin A Enhances the Apoptotic Potential of Palladium Nanoparticles in Human Cervical Cancer Cells.

PubMed

Zhang, Xi-Feng; Yan, Qi; Shen, Wei; Gurunathan, Sangiliyandi

2016-08-19

Cervical cancer ranks seventh overall among all types of cancer in women. Although several treatments, including radiation, surgery and chemotherapy, are available to eradicate or reduce the size of cancer, many cancers eventually relapse. Thus, it is essential to identify possible alternative therapeutic approaches for cancer. We sought to identify alternative and effective therapeutic approaches, by first synthesizing palladium nanoparticles (PdNPs), using a novel biomolecule called saponin. The synthesized PdNPs were characterized by several analytical techniques. They were significantly spherical in shape, with an average size of 5 nm. Recently, PdNPs gained much interest in various therapies of cancer cells. Similarly, histone deacetylase inhibitors are known to play a vital role in anti-proliferative activity, gene expression, cell cycle arrest, differentiation and apoptosis in various cancer cells. Therefore, we selected trichostatin A (TSA) and PdNPs and studied their combined effect on apoptosis in cervical cancer cells. Cells treated with either TSA or PdNPs showed a dose-dependent effect on cell viability. The combinatorial effect, tested with 50 nM TSA and 50 nMPdNPs, had a more dramatic inhibitory effect on cell viability, than either TSA or PdNPs alone. The combination of TSA and PdNPs had a more pronounced effect on cytotoxicity, oxidative stress, mitochondrial membrane potential (MMP), caspase-3/9 activity and expression of pro- and anti-apoptotic genes. Our data show a strong synergistic interaction between TSA and PdNPs in cervical cancer cells. The combinatorial treatment increased the therapeutic potential and demonstrated relevant targeted therapy for cervical cancer. Furthermore, we provide the first evidence for the combinatory effect and cytotoxicity mechanism of TSA and PdNPs in cervical cancer cells.

Effect of lateral offset center of rotation in reverse total shoulder arthroplasty: a biomechanical study.

PubMed

Henninger, Heath B; Barg, Alexej; Anderson, Andrew E; Bachus, Kent N; Burks, Robert T; Tashjian, Robert Z

2012-09-01

Lateral offset center of rotation (COR) reduces the incidence of scapular notching and potentially increases external rotation range of motion (ROM) after reverse total shoulder arthroplasty (rTSA). The purpose of this study was to determine the biomechanical effects of changing COR on abduction and external rotation ROM, deltoid abduction force, and joint stability. A biomechanical shoulder simulator tested cadaveric shoulders before and after rTSA. Spacers shifted the COR laterally from baseline rTSA by 5, 10, and 15 mm. Outcome measures of resting abduction and external rotation ROM, and abduction and dislocation (lateral and anterior) forces were recorded. Resting abduction increased 20° vs native shoulders and was unaffected by COR lateralization. External rotation decreased after rTSA and was unaffected by COR lateralization. The deltoid force required for abduction significantly decreased 25% from native to baseline rTSA. COR lateralization progressively eliminated this mechanical advantage. Lateral dislocation required significantly less force than anterior dislocation after rTSA, and both dislocation forces increased with lateralization of the COR. COR lateralization had no influence on ROM (adduction or external rotation) but significantly increased abduction and dislocation forces. This suggests the lower incidence of scapular notching may not be related to the amount of adduction deficit after lateral offset rTSA but may arise from limited impingement of the humeral component on the lateral scapula due to a change in joint geometry. Lateralization provides the benefit of increased joint stability, but at the cost of increasing deltoid abduction forces. Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Cloning and characterization of indole synthase (INS) and a putative tryptophan synthase α-subunit (TSA) genes from Polygonum tinctorium.

PubMed

Jin, Zhehao; Kim, Jin-Hee; Park, Sang Un; Kim, Soo-Un

2016-12-01

Two cDNAs for indole-3-glycerol phosphate lyase homolog were cloned from Polygonum tinctorium. One encoded cytosolic indole synthase possibly in indigoid synthesis, whereas the other encoded a putative tryptophan synthase α-subunit. Indigo is an old natural blue dye produced by plants such as Polygonum tinctorium. Key step in plant indigoid biosynthesis is production of indole by indole-3-glycerol phosphate lyase (IGL). Two tryptophan synthase α-subunit (TSA) homologs, PtIGL-short and -long, were isolated by RACE PCR from P. tinctorium. The genome of the plant contained two genes coding for IGL. The short and the long forms, respectively, encoded 273 and 316 amino acid residue-long proteins. The short form complemented E. coli ΔtnaA ΔtrpA mutant on tryptophan-depleted agar plate signifying production of free indole, and thus was named indole synthase gene (PtINS). The long form, either intact or without the transit peptide sequence, did not complement the mutant and was tentatively named PtTSA. PtTSA was delivered into chloroplast as predicted by 42-residue-long targeting sequence, whereas PtINS was localized in cytosol. Genomic structure analysis suggested that a TSA duplicate acquired splicing sites during the course of evolution toward PtINS so that the targeting sequence-containing pre-mRNA segment was deleted as an intron. PtINS had about two to fivefolds higher transcript level than that of PtTSA, and treatment of 2,1,3-benzothiadiazole caused the relative transcript level of PtINS over PtTSA was significantly enhanced in the plant. The results indicate participation of PtINS in indigoid production.

Experimental study on inhibitory effects of histone deacetylase inhibitor MS-275 and TSA on bladder cancer cells.

PubMed

Qu, Wei; Kang, Yin-Dong; Zhou, Mei-Sheng; Fu, Li-Li; Hua, Zhen-Hao; Wang, Li-Ming

2010-01-01

To investigate the inhibitory effect of histone deacetylase (HDAC) inhibitors (MS-275 and TSA) on T24 human bladder cancer cells in vitro, and explore the possible mechanism. The MTT assay was employed to evaluate the inhibitory effect of MS-275 and TSA on T24 cell growth. FCM was used to analyze the variation of T24 cell cycle distribution and the apoptotic ratio after T24 cells were treated with MS-275 and TSA. Histone acetylation level was detected by Western blot. mRNA expression of p21 WAF1/CIP1, cyclin A, and cyclin E was measured by FQ-PCR. Dynamic changes of Bcl-2 and bax expression were detected by FCM. MS-275 and TSA inhibited T24 cell growth in a concentration and time-dependent manner. Treatment with 4 μmol/l MS-275 or 0.4 μmol/l TSA blocked cell cycling in the G0/G1 phase and induced a significant increase in cell apoptosis. MS-275 and TSA significantly increased the level of histone acetylation, induced p21CIP1WAF1 mRNA expression, and inhibited cyclin A mRNA expression, though no significant effect was observed on cyclin E. Bcl-2 expression was down-regulated, while bax expression was up-regulated. HDAC inhibitors can block bladder cancer cell cycle in vitro and induce apoptosis. The molecular mechanism may be associated with increased level of histone acetylation, down-regulation of p21WAF1/CIP1 expression, up-regulation of cyclin A expression, and dynamic change of bcl-2 and bax expression. Copyright © 2010 Elsevier Inc. All rights reserved.

A Trichostatin A (TSA)/Sp1-mediated mechanism for the regulation of SALL2 tumor suppressor in Jurkat T cells.

PubMed

Hepp, Matías I; Escobar, David; Farkas, Carlos; Hermosilla, Viviana; Álvarez, Claudia; Amigo, Roberto; Gutiérrez, José L; Castro, Ariel F; Pincheira, Roxana

2018-05-17

SALL2 is a transcription factor involved in development and disease. Deregulation of SALL2 has been associated with cancer, suggesting that it plays a role in the disease. However, how SALL2 is regulated and why is deregulated in cancer remain poorly understood. We previously showed that the p53 tumor suppressor represses SALL2 under acute genotoxic stress. Here, we investigated the effect of Histone Deacetylase Inhibitor (HDACi) Trichostatin A (TSA), and involvement of Sp1 on expression and function of SALL2 in Jurkat T cells. We show that SALL2 mRNA and protein levels were enhanced under TSA treatment. Both, TSA and ectopic expression of Sp1 transactivated the SALL2 P2 promoter. This transactivation effect was blocked by the Sp1-binding inhibitor mithramycin A. Sp1 bound in vitro and in vivo to the proximal region of the P2 promoter. TSA induced Sp1 binding to the P2 promoter, which correlated with dynamic changes on H4 acetylation and concomitant recruitment of p300 or HDAC1 in a mutually exclusive manner. Our results suggest that TSA-induced Sp1-Lys703 acetylation contributes to the transcriptional activation of the P2 promoter. Finally, using a CRISPR/Cas9 SALL2-KO Jurkat-T cell model and gain of function experiments, we demonstrated that SALL2 upregulation is required for TSA-mediated cell death. Thus, our study identified Sp1 as a novel transcriptional regulator of SALL2, and proposes a novel epigenetic mechanism for SALL2 regulation in Jurkat-T cells. Altogether, our data support SALL2 function as a tumor suppressor, and SALL2 involvement in cell death response to HDACi. Copyright © 2018. Published by Elsevier B.V.

Trichostatin A Enhances the Apoptotic Potential of Palladium Nanoparticles in Human Cervical Cancer Cells

PubMed Central

Zhang, Xi-Feng; Yan, Qi; Shen, Wei; Gurunathan, Sangiliyandi

2016-01-01

Cervical cancer ranks seventh overall among all types of cancer in women. Although several treatments, including radiation, surgery and chemotherapy, are available to eradicate or reduce the size of cancer, many cancers eventually relapse. Thus, it is essential to identify possible alternative therapeutic approaches for cancer. We sought to identify alternative and effective therapeutic approaches, by first synthesizing palladium nanoparticles (PdNPs), using a novel biomolecule called saponin. The synthesized PdNPs were characterized by several analytical techniques. They were significantly spherical in shape, with an average size of 5 nm. Recently, PdNPs gained much interest in various therapies of cancer cells. Similarly, histone deacetylase inhibitors are known to play a vital role in anti-proliferative activity, gene expression, cell cycle arrest, differentiation and apoptosis in various cancer cells. Therefore, we selected trichostatin A (TSA) and PdNPs and studied their combined effect on apoptosis in cervical cancer cells. Cells treated with either TSA or PdNPs showed a dose-dependent effect on cell viability. The combinatorial effect, tested with 50 nM TSA and 50 nMPdNPs, had a more dramatic inhibitory effect on cell viability, than either TSA or PdNPs alone. The combination of TSA and PdNPs had a more pronounced effect on cytotoxicity, oxidative stress, mitochondrial membrane potential (MMP), caspase-3/9 activity and expression of pro- and anti-apoptotic genes. Our data show a strong synergistic interaction between TSA and PdNPs in cervical cancer cells. The combinatorial treatment increased the therapeutic potential and demonstrated relevant targeted therapy for cervical cancer. Furthermore, we provide the first evidence for the combinatory effect and cytotoxicity mechanism of TSA and PdNPs in cervical cancer cells. PMID:27548148

Ab initio study of the binding of Trichostatin A (TSA) in the active site of histone deacetylase like protein (HDLP).

PubMed

Vanommeslaeghe, Kenno; Van Alsenoy, Christian; De Proft, Frank; Martins, José C; Tourwé, Dirk; Geerlings, Paul

2003-08-21

Histone deacetylase (HDAC) inhibitors have recently attracted considerable interest because of their therapeutic potential for the treatment of cell proliferative diseases. An X-ray structure of a very potent inhibitor, Trichostatin A (TSA), bound to HDLP (an HDAC analogue isolated from Aquifex aeolicus), is available. From this structure, an active site model (322 atoms), relevant for the binding of TSA and structural analogues, has been derived, and TSA has been minimized in this active site at HF 3-21G* level. The resulting conformation is in excellent accordance with the X-ray structure, and indicates a deprotonation of the hydroxamic acid in TSA by His 131. Also, a water molecule was minimized in the active site. In addition to a similar deprotonation, in accordance with a possible catalytic mechanism of HDAC as proposed by Finnin et al. (M. S. Finnin, J. R. Donigian, A. Cohen, V. M. Richon, R. A. Rifkind and P. A. Marks, Nature, 1999, 401, 188-193), a displacement of the resulting OH- ion in the active site was observed. Based on these results, the difference in energy of binding between TSA and water was calculated. The resulting value is realistic in respect to experimental binding affinities. Furthermore, the mechanism of action of the His 131-Asp 166 charge relay system was investigated. Although the Asp residue in this motif is known to substantially increase the basicity of the His residue, no proton transfer from His 131 to Asp 166 was observed on binding of TSA or water. However, in the empty protonated active site, this proton transfer does occur.

RUNX3 is involved in caspase-3-dependent apoptosis induced by a combination of 5-aza-CdR and TSA in leukaemia cell lines.

PubMed

Zhai, Feng-Xian; Liu, Xiang-Fu; Fan, Rui-Fang; Long, Zi-Jie; Fang, Zhi-Gang; Lu, Ying; Zheng, Yong-Jiang; Lin, Dong-Jun

2012-03-01

Epigenetic therapy has had a significant impact on the management of haematologic malignancies. The aim of this study was to assess whether 5-aza-CdR and TSA inhibit the growth of leukaemia cells and induce caspase-3-dependent apoptosis by upregulating RUNX3 expression. K562 and Reh cells were treated with 5-aza-CdR, TSA or both compounds. RT-PCR and Western blot analyses were used to examine the expression of RUNX3 at the mRNA and protein levels, respectively. Immunofluorescence microscopy was used to detect the cellular location of RUNX3. Additionally, after K562 cells were transfected with RUNX3, apoptosis and proliferation were studied using Annexin V staining and MTT assays. The expression of RUNX3 in leukaemia cell lines was markedly less than that in the controls. Demethylating drug 5-aza-CdR could induce RUNX3 expression, but the combination of TSA and 5-aza-CdR had a greater effect than did treatment with a single compound. The combination of 5-aza-CdR and TSA induced the translocation of RUNX3 from the cytoplasm into the nucleus. TSA enhanced apoptosis induced by 5-aza-CdR, and Annexin V and Hoechst 33258 staining showed that the combination induced apoptosis but not necrosis. Furthermore, apoptosis was dependent on the caspase-3 pathway. RUNX3 overexpression in K562 cells led to growth inhibition and apoptosis and potentiated the effects of 5-aza-CdR induction. RUNX3 plays an important role in leukaemia cellular functions, and the induction of RUNX3-mediated effects may contribute to the therapeutic value of combination TSA and 5-aza-CdR treatment.

Tract specific analysis in patients with sickle cell disease

NASA Astrophysics Data System (ADS)

Chai, Yaqiong; Coloigner, Julie; Qu, Xiaoping; Choi, Soyoung; Bush, Adam; Borzage, Matt; Vu, Chau; Lepore, Natasha; Wood, John

2015-12-01

Sickle cell disease (SCD) is a hereditary blood disorder in which the oxygen-carrying hemoglobin molecule in red blood cells is abnormal. It affects numerous people in the world and leads to a shorter life span, pain, anemia, serious infections and neurocognitive decline. Tract-Specific Analysis (TSA) is a statistical method to evaluate white matter alterations due to neurocognitive diseases, using diffusion tensor magnetic resonance images. Here, for the first time, TSA is used to compare 11 major brain white matter (WM) tracts between SCD patients and age-matched healthy subjects. Alterations are found in the corpus callosum (CC), the cortico-spinal tract (CST), inferior fronto-occipital fasciculus (IFO), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and uncinated fasciculus (UNC). Based on previous studies on the neurocognitive functions of these tracts, the significant areas found in this paper might be related to several cognitive impairments and depression, both of which are observed in SCD patients.

76 FR 792 - Intent To Request Approval From OMB of One New Public Collection of Information: Exercise...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-06

... Exercise Information System (EXIS) is an Internet-accessible knowledge-management system developed by TSA... we will submit to the Office of Management and Budget (OMB) for approval in compliance with the... modes, or their regulated areas of operation. EXIS is a data management system that provides end-to-end...

Achieving a hybrid brain-computer interface with tactile selective attention and motor imagery.

PubMed

Ahn, Sangtae; Ahn, Minkyu; Cho, Hohyun; Chan Jun, Sung

2014-12-01

We propose a new hybrid brain-computer interface (BCI) system that integrates two different EEG tasks: tactile selective attention (TSA) using a vibro-tactile stimulator on the left/right finger and motor imagery (MI) of left/right hand movement. Event-related desynchronization (ERD) from the MI task and steady-state somatosensory evoked potential (SSSEP) from the TSA task are retrieved and combined into two hybrid senses. One hybrid approach is to measure two tasks simultaneously; the features of each task are combined for testing. Another hybrid approach is to measure two tasks consecutively (TSA first and MI next) using only MI features. For comparison with the hybrid approaches, the TSA and MI tasks are measured independently. Using a total of 16 subject datasets, we analyzed the BCI classification performance for MI, TSA and two hybrid approaches in a comparative manner; we found that the consecutive hybrid approach outperformed the others, yielding about a 10% improvement in classification accuracy relative to MI alone. It is understood that TSA may play a crucial role as a prestimulus in that it helps to generate earlier ERD prior to MI and thus sustains ERD longer and to a stronger degree; this ERD may give more discriminative information than ERD in MI alone. Overall, our proposed consecutive hybrid approach is very promising for the development of advanced BCI systems.

Achieving a hybrid brain-computer interface with tactile selective attention and motor imagery

NASA Astrophysics Data System (ADS)

Ahn, Sangtae; Ahn, Minkyu; Cho, Hohyun; Jun, Sung Chan

2014-12-01

Objective. We propose a new hybrid brain-computer interface (BCI) system that integrates two different EEG tasks: tactile selective attention (TSA) using a vibro-tactile stimulator on the left/right finger and motor imagery (MI) of left/right hand movement. Event-related desynchronization (ERD) from the MI task and steady-state somatosensory evoked potential (SSSEP) from the TSA task are retrieved and combined into two hybrid senses. Approach. One hybrid approach is to measure two tasks simultaneously; the features of each task are combined for testing. Another hybrid approach is to measure two tasks consecutively (TSA first and MI next) using only MI features. For comparison with the hybrid approaches, the TSA and MI tasks are measured independently. Main results. Using a total of 16 subject datasets, we analyzed the BCI classification performance for MI, TSA and two hybrid approaches in a comparative manner; we found that the consecutive hybrid approach outperformed the others, yielding about a 10% improvement in classification accuracy relative to MI alone. It is understood that TSA may play a crucial role as a prestimulus in that it helps to generate earlier ERD prior to MI and thus sustains ERD longer and to a stronger degree; this ERD may give more discriminative information than ERD in MI alone. Significance. Overall, our proposed consecutive hybrid approach is very promising for the development of advanced BCI systems.

Supporting structures for team situation awareness and decision making: insights from four delivery suites.

PubMed

Mackintosh, Nicola; Berridge, Emma-Jane; Freeth, Della

2009-02-01

'Human factors' (non-technical skills such as communication and teamwork) have been strongly implicated in adverse events during labour and delivery. The importance of shared 'situation awareness' between team members is highlighted as a key factor in patient safety. Arising from an ethnographic study of safety culture in the delivery suites of four UK hospitals, the aim of this study is to describe the main mechanisms supporting team situation awareness (TSA) and examine contrasting configurations of supports. Stage I: 177 hours of lightly structured non-participant observation (sensitizing concepts: safety culture, non-technical skills, teamwork and decision making) analysed to identify a core organizing concept, main supporting categories and preliminary conceptual models. Stage II: (approximately 11 months after first observations) 104 hours of observation to test and elaborate stage I analyses. Handover, whiteboard use and a coordinator role emerged as the key processes facilitating work and team coordination. The interplay between these supporting processes and the contextual features of each site promoted or inhibited TSA. Three configurations of supports for TSA were evident. These are described. Context configurations of supporting mechanisms and artefacts influence TSA, with implications for the maintenance of patient safety on delivery suites. A balanced model of supports for TSA is commended. Examining contrasting configurations helps reveal how local mechanisms or organizational, environmental and temporal factors might be manipulated to improve TSA.

TSA and BIX-01294 Induced Normal DNA and Histone Methylation and Increased Protein Expression in Porcine Somatic Cell Nuclear Transfer Embryos

PubMed Central

Ding, Biao; Zuo, Xiaoyuan; Li, Hui; Ding, Jianping; Li, Yunsheng; Huang, Weiping; Zhang, Yunhai

2017-01-01

The poor efficiency of animal cloning is mainly attributed to the defects in epigenetic reprogramming of donor cells’ chromatins during early embryonic development. Previous studies indicated that inhibition of histone deacetylases or methyltransferase, such as G9A, using Trichostatin A (TSA) or BIX-01294 significantly enhanced the developmental efficiency of porcine somatic cell nuclear transfer (SCNT) embryos. However, potential mechanisms underlying the improved early developmental competence of SCNT embryos exposed to TSA and BIX-01294 are largely unclear. Here we found that 50 nM TSA or 1.0 μM BIX-01294 treatment alone for 24 h significantly elevated the blastocyst rate (P < 0.05), while further improvement was not observed under combined treatment condition. Furthermore, co-treatment or TSA treatment alone significantly reduced H3K9me2 level at the 4-cell stage, which is comparable with that in in vivo and in vitro fertilized counterparts. However, only co-treatment significantly decreased the levels of 5mC and H3K9me2 in trophectoderm lineage and subsequently increased the expression of OCT4 and CDX2 associated with ICM and TE lineage differentiation. Altogether, these results demonstrate that co-treatment of TSA and BIX-01294 enhances the early developmental competence of porcine SCNT embryos via improvements in epigenetic status and protein expression. PMID:28114389

HDAC inhibitor TSA ameliorates mechanical hypersensitivity and potentiates analgesic effect of morphine in a rat model of bone cancer pain by restoring μ-opioid receptor in spinal cord.

PubMed

Hou, Xinran; Weng, Yingqi; Ouyang, Bihan; Ding, Zhuofeng; Song, Zongbin; Zou, Wangyuan; Huang, Changsheng; Guo, Qulian

2017-08-15

Bone cancer pain (BCP) is a common complication with inadequate management in patients suffering from advanced cancer. Histone deacetylase inhibitors showed significant analgesic effect in multiple inflammatory and neuropathic pain models, but their effect in bone cancer pain has never been explored. In this study, we utilized a BCP rat model with intra-tibial inoculation of Walker 256 mammary gland carcinoma cells, which developed progressive mechanical hypersensitivity but not thermal hypersensitivity. Intrathecal application of trichostatin A (TSA), a classic pan-HDAC inhibitor, ameliorated tactile hypersensitivity and enhanced the analgesic effect of morphine in BCP rats. The analgesic effect of TSA was blocked by co-administration of CTAP, a specific MOR antagonist, confirming the involvement of mu-opioid receptor (MOR). A reduction of MOR expression was observed in the lumbar spinal cord of BCP rats and TSA treatment was able to partially reverse it. In vitro study in PC12 cells also demonstrated the dose-dependent enhancement of MOR expression by TSA treatment. Taking all into consideration, we could draw the conclusion that HDAC inhibitor TSA ameliorates mechanical hypersensitivity and potentiates analgesic effect of morphine in BCP rats, probably by restoring MOR expression in spinal cord. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhancement of inflammatory protein expression and nuclear factor Κb (NF-Κb) activity by trichostatin A (TSA) in OP9 preadipocytes.

PubMed

Sato, Taiki; Kotake, Daisuke; Hiratsuka, Masahiro; Hirasawa, Noriyasu

2013-01-01

The production of inflammatory proteins such as interleukin-6 (IL-6) by preadipocytes and mature adipocytes is closely associated with the impairment of systemic glucose homeostasis. However, precisely how the production is regulated and the roles of histone deacetylases (HDACs) remain largely unknown. The aim of this study was to establish whether HDAC inhibitors affect the expression of inflammatory proteins in pre/mature adipocytes, and, if so, to determine the mechanism involved. Trichostatin A (TSA), an HDAC inhibitor, enhanced lipopolysaccharide (LPS)-induced production of IL-6 in OP9 preadipocytes but not the mature adipocytes. Moreover, TSA also enhanced palmitic acid-induced IL-6 production and the expression of inflammatory genes induced by LPS in preadipocytes. Although TSA did not affect TLR4 mRNA expression or the activation of MAPKs, a reporter gene assay revealed that the LPS-induced increase in nuclear factor κB (NF-κB) activity was enhanced by TSA. Moreover, TSA increased the level of NF-κB p65 acetylation at lysine 310 and duration of its translocation into the nucleus, which leads to enhancement of NF-κB activity and subsequently expression of inflammatory genes. These findings shed new light on the regulatory roles of HDACs in preadipocytes in the production of inflammatory proteins.

Histone Deacetylase Inhibitor Induces the Expression of Select Epithelial Genes in Mouse Utricle Sensory Epithelia-Derived Progenitor Cells

PubMed Central

Wang, Jue

2014-01-01

Abstract Mouse utricle sensory epithelial cell–derived progenitor cells (MUCs), which have hair cell progenitor and mesenchymal features via epithelial-to-mesenchymal transition (EMT) as previously described, provide a potential approach for hair cell regeneration via cell transplantation. In this study, we treated MUCs with trichostatin A (TSA) to determine whether histone deacetylase inhibitor is able to stimulate the expression of epithelial genes in MUCs, an essential step for guiding mesenchymal-like MUCs to become sensory epithelial cells. After 72 h of TSA treatment, MUCs acquired epithelial-like features, which were indicated by increased expression of epithelial markers such as Cdh1, Krt18, and Dsp. Additionally, TSA decreased the expression of mesenchymal markers, including Zeb1, Zeb2, Snai1, and Snai2, and prosensory genes Lfng, Six1, and Dlx5. Moreover, the expression of the hair cell genes Atoh1 and Myo6 was increased in TSA-treated MUCs. We also observed significantly decreased expression of Hdac2 and Hdac3 in TSA-treated MUCs. However, no remarkable change was detected in protein expression using immunofluorescence, indicating that TSA-induced HDAC inhibition may contribute to the initial stage of the mesenchymal-to-epithelial phenotypic change. In the future, more work is needed to induce hair cell regeneration using inner ear tissue–derived progenitors to achieve an entire mesenchymal-to-epithelial transition. PMID:24945595

TSA and BIX-01294 Induced Normal DNA and Histone Methylation and Increased Protein Expression in Porcine Somatic Cell Nuclear Transfer Embryos.

PubMed

Cao, Zubing; Hong, Renyun; Ding, Biao; Zuo, Xiaoyuan; Li, Hui; Ding, Jianping; Li, Yunsheng; Huang, Weiping; Zhang, Yunhai

2017-01-01

The poor efficiency of animal cloning is mainly attributed to the defects in epigenetic reprogramming of donor cells' chromatins during early embryonic development. Previous studies indicated that inhibition of histone deacetylases or methyltransferase, such as G9A, using Trichostatin A (TSA) or BIX-01294 significantly enhanced the developmental efficiency of porcine somatic cell nuclear transfer (SCNT) embryos. However, potential mechanisms underlying the improved early developmental competence of SCNT embryos exposed to TSA and BIX-01294 are largely unclear. Here we found that 50 nM TSA or 1.0 μM BIX-01294 treatment alone for 24 h significantly elevated the blastocyst rate (P < 0.05), while further improvement was not observed under combined treatment condition. Furthermore, co-treatment or TSA treatment alone significantly reduced H3K9me2 level at the 4-cell stage, which is comparable with that in in vivo and in vitro fertilized counterparts. However, only co-treatment significantly decreased the levels of 5mC and H3K9me2 in trophectoderm lineage and subsequently increased the expression of OCT4 and CDX2 associated with ICM and TE lineage differentiation. Altogether, these results demonstrate that co-treatment of TSA and BIX-01294 enhances the early developmental competence of porcine SCNT embryos via improvements in epigenetic status and protein expression.

Retinoic acids and trichostatin A (TSA), a histone deacetylase inhibitor, induce human pyruvate dehydrogenase kinase 4 (PDK4) gene expression.

PubMed

Kwon, Hye-Sook; Huang, Boli; Ho Jeoung, Nam; Wu, Pengfei; Steussy, Calvin N; Harris, Robert A

2006-01-01

Induction of pyruvate dehydrogenase kinase 4 (PDK4) conserves glucose and substrates for gluconeogenesis and thereby helps regulate blood glucose levels during starvation. We report here that retinoic acids (RA) as well as Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), regulate PDK4 gene expression. Two retinoic acid response elements (RAREs) to which retinoid X receptor alpha (RXRalpha) and retinoic acid receptor alpha (RARalpha) bind and activate transcription are present in the human PDK4 (hPDK4) proximal promoter. Sp1 and CCAAT box binding factor (CBF) bind to the region between two RAREs. Mutation of either the Sp1 or the CBF site significantly decreases basal expression, transactivation by RXRalpha/RARalpha/RA, and the ability of TSA to stimulate hPDK4 gene transcription. By the chromatin immunoprecipitation assay, RA and TSA increase acetylation of histones bound to the proximal promoter as well as occupancy of CBP and Sp1. Interaction of p300/CBP with E1A completely prevented hPDK4 gene activation by RXRalpha/RARalpha/RA and TSA. The p300/CBP may enhance acetylation of histones bound to the hPDK4 promoter and cooperate with Sp1 and CBF to stimulate transcription of the hPDK4 gene in response to RA and TSA.

Trichostatin A down-regulates ZAP-70, LAT and SLP-76 content in Jurkat T cells.

PubMed

Januchowski, Radosław; Jagodzinski, Paweł P

2007-02-01

We exploited Jurkat leukemia T cell clone E6-1 as a model of Trichostatin A (TSA) effect on cellular levels of ZAP-70, LAT and SLP-76 molecules involved in the signal transduction pathway from T cell receptor to nucleus. Using reverse transcription real-time quantitative PCR and Western blotting analysis we observed that TSA resulted in ZAP-70, LAT and SLP-76 transcript and protein down-regulation in Jurkat leukemia T cells. We also found that TSA reduced half-life of ZAP-70, LAT and SLP-76 mRNAs from 4.8, 3.5, and 4.8 to approximately 2.3, 1.9 and 1.7 h, respectively. Employing the protein biosynthesis inhibitor cycloheximide, we demonstrated the involvement of RNase and/or mRNA stabilization protein in ZAP-70, LAT and SLP-76 mRNAs stabilization. The effect of TSA on ZAP-70, LAT and SLP-76 content in T cells confirms an immunosuppressive effect by TSA, and the usefulness of this histone deacetylase inhibitor in the treatment of autoimmune diseases.

Design of Ultra-Wideband Tapered Slot Antenna by Using Binomial Transformer with Corrugation

NASA Astrophysics Data System (ADS)

Chareonsiri, Yosita; Thaiwirot, Wanwisa; Akkaraekthalin, Prayoot

2017-05-01

In this paper, the tapered slot antenna (TSA) with corrugation is proposed for UWB applications. The multi-section binomial transformer is used to design taper profile of the proposed TSA that does not involve using time consuming optimization. A step-by-step procedure for synthesis of the step impedance values related with step slot widths of taper profile is presented. The smooth taper can be achieved by fitting the smoothing curve to the entire step slot. The design of TSA based on this method yields results with a quite flat gain and wide impedance bandwidth covering UWB spectrum from 3.1 GHz to 10.6 GHz. To further improve the radiation characteristics, the corrugation is added on the both edges of the proposed TSA. The effects of different corrugation shapes on the improvement of antenna gain and front-to-back ratio (F-to-B ratio) are investigated. To demonstrate the validity of the design, the prototypes of TSA without and with corrugation are fabricated and measured. The results show good agreement between simulation and measurement.

A Value Measure for Public-Sector Enterprise Risk Management: A TSA Case Study.

PubMed

Fletcher, Kenneth C; Abbas, Ali E

2018-05-01

This article presents a public value measure that can be used to aid executives in the public sector to better assess policy decisions and maximize value to the American people. Using Transportation Security Administration (TSA) programs as an example, we first identify the basic components of public value. We then propose a public value account to quantify the outcomes of various risk scenarios, and we determine the certain equivalent of several important TSA programs. We illustrate how this proposed measure can quantify the effects of two main challenges that government organizations face when conducting enterprise risk management: (1) short-term versus long-term incentives and (2) avoiding potential negative consequences even if they occur with low probability. Finally, we illustrate how this measure enables the use of various tools from decision analysis to be applied in government settings, such as stochastic dominance arguments and certain equivalent calculations. Regarding the TSA case study, our analysis demonstrates the value of continued expansion of the TSA trusted traveler initiative and increasing the background vetting for passengers who are afforded expedited security screening. © 2017 Society for Risk Analysis.

Trichostatin A (TSA) improves the development of rabbit-rabbit intraspecies cloned embryos, but not rabbit-human interspecies cloned embryos.

PubMed

Shi, Li-Hong; Miao, Yi-Liang; Ouyang, Ying-Chun; Huang, Jun-Cheng; Lei, Zi-Li; Yang, Ji-Wen; Han, Zhi-Ming; Song, Xiang-Fen; Sun, Qing-Yuan; Chen, Da-Yuan

2008-03-01

The interspecies somatic cell nuclear transfer (iSCNT) technique for therapeutic cloning gives great promise for treatment of many human diseases. However, the incomplete nuclear reprogramming and the low blastocyst rate of iSCNT are still big problems. Herein, we observed the effect of TSA on the development of rabbit-rabbit intraspecies and rabbit-human interspecies cloned embryos. After treatment with TSA for 6 hr during activation, we found that the blastocyst rate of rabbit-rabbit cloned embryos was more than two times higher than that of untreated embryos; however, the blastocyst rate of TSA-treated rabbit-human interspecies cloned embryos decreased. We also found evident time-dependent histone deacetylation-reacetylation changes in rabbit-rabbit cloned embryos, but not in rabbit-human cloned embryos from fusion to 6 hr after activation. Our results suggest that TSA-treatment does not improve blastocyst development of rabbit-human iSCNT embryos and that abnormal histone deacetylation-reacetylation changes in iSCNT embryos may account for their poor blastocyst development. (c) 2008 Wiley-Liss, Inc.

Autocorrelation-based time synchronous averaging for condition monitoring of planetary gearboxes in wind turbines

NASA Astrophysics Data System (ADS)

Ha, Jong M.; Youn, Byeng D.; Oh, Hyunseok; Han, Bongtae; Jung, Yoongho; Park, Jungho

2016-03-01

We propose autocorrelation-based time synchronous averaging (ATSA) to cope with the challenges associated with the current practice of time synchronous averaging (TSA) for planet gears in planetary gearboxes of wind turbine (WT). An autocorrelation function that represents physical interactions between the ring, sun, and planet gears in the gearbox is utilized to define the optimal shape and range of the window function for TSA using actual kinetic responses. The proposed ATSA offers two distinctive features: (1) data-efficient TSA processing and (2) prevention of signal distortion during the TSA process. It is thus expected that an order analysis with the ATSA signals significantly improves the efficiency and accuracy in fault diagnostics of planet gears in planetary gearboxes. Two case studies are presented to demonstrate the effectiveness of the proposed method: an analytical signal from a simulation and a signal measured from a 2 kW WT testbed. It can be concluded from the results that the proposed method outperforms conventional TSA methods in condition monitoring of the planetary gearbox when the amount of available stationary data is limited.

75 FR 63191 - Intent To Request Renewal From OMB of One Current Public Collection of Information: Certified...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-14

...The Transportation Security Administration (TSA) invites public comment on one currently approved Information Collection Request (ICR), OMB control number 1652-0053, abstracted below that we will submit to the Office of Management and Budget (OMB) for renewal in compliance with the Paperwork Reduction Act. The ICR describes the nature of the information collection and its expected burden. The collections include: (1) Applications from entities that wish to become Certified Cargo Screening Facilities (CCSF) or operate as a TSA- approved validation firm; (2) personal information to allow TSA to conduct security threat assessments on key individuals employed by the CCSFs and validation firms; (3) implementation of a standard security program or submission of a proposed modified security program; (4) information on the amount of cargo screened; (5) recordkeeping requirements for CCSFs and validation firms; and (6) submission of validation reports to TSA. TSA is seeking the renewal of the ICR for the continuation of the program in order to secure passenger aircraft carrying cargo by the deadlines set out in the Implementing Recommendations of the 9/11 Commission Act of 2007.

Homeland Security Airport Security Model

DTIC Science & Technology

2006-03-22

carrying a stapler in our briefcase. After the case went through the x-ray machine, and signaled an alert, the TSA agent asked to 38 open the case. She...saw that the "offending object" was the stapler . She then removed the stapler from the case, put it in a basket, and sent the case and basket through... stapler . Thus, the process should have stopped after the case was opened. Instead of paying TSA personnel to spend time on trivial searches, the TSA

Experimental and Theoretical Investigation of Innovative Broadband Microwave Devices

DTIC Science & Technology

1991-05-01

over conventional devices such as the helix TWT . The TSA is also a broad band device; however, the bandwidth of the configuration chosen ultimately...by the TSA over the helix TWT in regard to bandwidth as well. Although the high gain in the TSA confers the advantage of being relatively less...prebuncher for the output helix stage. Thus. the device is essentially a helix TWT im (k) =45C with enhanced bunching due to the two-stream interac-Re() 2+C

Regulation of RANKL promoter activity is associated with histone remodeling in murine bone stromal cells.

PubMed

Fan, Xian; Roy, Eileen M; Murphy, Tamara C; Nanes, Mark S; Kim, Sungtae; Pike, J Wesley; Rubin, Janet

2004-11-01

Receptor activator of NFkappa-B ligand (RANKL) is essential for osteoclast formation, function, and survival. Although RANKL mRNA and protein levels are modulated by 1,25(OH)2D3 and other osteoactive factors, regulatory mechanisms remain unclear. In this study, we show that 2 kb or 2 kb plus exon 1 of a RANKL promoter sequence conferred neither 1,25(OH)2D3 response nor tissue specificity. The histone deacetylase inhibitors trichostatin A (TSA) and sodium butyrate (SB), however, strongly increased RANKL promoter activity. A series of 5'-deleted RANKL promoter constructs from 2,020 to 110 bp showed fourfold increased activity after TSA treatment. TSA also dose dependently enhanced endogenous RANKL mRNA expression with 50 microM of TSA treatment causing equivalent RANKL expression to that seen with 1 nM 1,25(OH)2D3. Using a chromatin immunoprecipitation (ChIP) assay we showed that TSA significantly enhanced association of both acetylated histone H3 and H4 on the RANKL promoter, with H4 > H3. A similar increase in acetylated histone H4 on the RANKL gene locus was seen after 1,25(OH)2D3 treatment, but ChIP assay did not reveal localization of VDR/RXR heterodimers on the putative VDRE of the RANKL promoter. To explore the role of H4 acetylation of 1,25(OH)2D3 stimulated RANKL, we added both TSA and 1,25(OH)2D3 together. While the combination further increased acetylation of H4 on the RANKL locus, surprisingly, TSA inhibited 1,25(OH)2D3-induced RANKL mRNA expression by 70% at all doses of 1 ,25(OH)2D3 studied. These results suggest that TSA increases of endogenous expression of RANKL involve enhanced acetylation of histones on the proximal RANKL promoter. Preventing deacetylation, however, blocks 1,25(OH)2D3 action on this gene. Chromatin remodeling is therefore involved in RANKL expression.

49 CFR 1552.5 - Fees.

Code of Federal Regulations, 2014 CFR

2014-10-01

... HOMELAND SECURITY CIVIL AVIATION SECURITY FLIGHT SCHOOLS Flight Training for Aliens and Other Designated... information required under § 1552.3 to TSA. (2) TSA will not issue any fee refunds, unless a fee was paid in...

49 CFR 1552.5 - Fees.

Code of Federal Regulations, 2011 CFR

2011-10-01

... HOMELAND SECURITY CIVIL AVIATION SECURITY FLIGHT SCHOOLS Flight Training for Aliens and Other Designated... information required under § 1552.3 to TSA. (2) TSA will not issue any fee refunds, unless a fee was paid in...

49 CFR 1522.111 - Reconsideration of disapproval of an application.

Code of Federal Regulations, 2010 CFR

2010-10-01

... TRANSPORTATION TSA-APPROVED VALIDATION FIRMS AND VALIDATORS TSA-Approved Validation Firms and Validators for the... additional information from the applicant prior to rendering a decision. This disposition is a final agency...

TSA Should Stand for 'Thank Servicemembers Appropriately' | DoDLive

Science.gov Websites

civilians, Military Children, Transportation Security Administration, TSA. Bookmark the permalink. Comments children coalition forces Defense Department of Defense deployed deployment DoD DoD News families family

49 CFR 1503.419 - Order Assessing Civil Penalty.

Code of Federal Regulations, 2010 CFR

2010-10-01

... AND ENFORCEMENT PROCEDURES Assessment of Civil Penalties by TSA § 1503.419 Order Assessing Civil Penalty. (a) Issuance pursuant to a settlement. TSA will issue an Order Assessing Civil Penalty if the...

76 FR 70469 - Extension of Agency Information Collection Activity Under OMB Review: TSA Airspace Waiver Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-14

...This notice announces that the Transportation Security Administration (TSA) has forwarded the Information Collection Request (ICR), Office of Management and Budget (OMB) control number 1652-0033, abstracted below to OMB for review and approval of an extension of the currently approved collection under the Paperwork Reduction Act (PRA). The ICR describes the nature of the information collection and its expected burden. TSA published a Federal Register notice, with a 60-day comment period soliciting comments, of the following collection of information on July 27, 2011, 76 FR 44944. This collection of information allows TSA to conduct security threat assessments on individuals on board aircraft operating in restricted airspace pursuant to an airspace waiver. This collection will enhance aviation security and protect assets on the ground that are within the restricted airspace.

Transcardiac endograft delivery for endovascular treatment of the ascending aorta: a feasibility study in pigs.

PubMed

Wipper, Sabine; Lohrenz, Christina; Ahlbrecht, Oliver; Carpenter, Sebastian W; Tsilimparis, Nikolaos; Kersten, Jan Felix; Detter, Christian; Debus, Eike S; Kölbel, Tilo

2015-06-01

To compare the technical feasibility and hemodynamic alterations during antegrade transcardiac access routes vs conventional transfemoral access (TFA) for endovascular treatment of the ascending aorta in a porcine model. Antegrade transseptal access (TSA), transapical access (TAA), and TFA were used for implantation of custom-made endografts into the ascending aorta under fluoroscopy (6 pigs each). Hemodynamic parameters, myocardial and cerebral blood flow, and carotid artery blood flow were evaluated during baseline (T1), sheath advancement (T2), after sheath retraction (T3), and after endograft deployment (T4). Endograft deployment was feasible in all animals; all coronary arteries remained patent. Hemodynamic parameters were comparable in all 3 study groups during all measurements. During T2, transient hemodynamic alteration occurred in all groups, with transient severe valve insufficiency in TSA and TAA reflected by the higher pulmonary to mean arterial pressure ratio (p<0.05) as compared with TFA. Values stabilized again at T3 and remained stable until T4. The innominate artery was partially occluded in 4 (TSA), 3 (TAA), and 5 (TFA) animals. There was no deterioration of myocardial or cerebral perfusion during the procedures. Endograft deployment and fluoroscopy times during TAA were shorter than in TSA and TFA. TSA, TFA, and TAA to the ascending aorta are feasible for endograft delivery to the ascending aorta in a porcine model. Transient hemodynamic instability in TSA and TAA recovered to near preoperative values. TAA appeared technically easier. © The Author(s) 2015.

49 CFR 1546.213 - Access to cargo: Security threat assessments for cargo personnel in the United States.

Code of Federal Regulations, 2012 CFR

2012-10-01

... the cargo enters an airport Security Identification Display Area or is transferred to another TSA... under §§ 1546.101(a) or (b) accepts the cargo, until the cargo— (A) Enters an airport Security... 49 Transportation 9 2012-10-01 2012-10-01 false Access to cargo: Security threat assessments for...

49 CFR 1546.213 - Access to cargo: Security threat assessments for cargo personnel in the United States.

Code of Federal Regulations, 2014 CFR

2014-10-01

... the cargo enters an airport Security Identification Display Area or is transferred to another TSA... under §§ 1546.101(a) or (b) accepts the cargo, until the cargo— (A) Enters an airport Security... 49 Transportation 9 2014-10-01 2014-10-01 false Access to cargo: Security threat assessments for...

49 CFR 1546.213 - Access to cargo: Security threat assessments for cargo personnel in the United States.

Code of Federal Regulations, 2013 CFR

2013-10-01

... the cargo enters an airport Security Identification Display Area or is transferred to another TSA... under §§ 1546.101(a) or (b) accepts the cargo, until the cargo— (A) Enters an airport Security... 49 Transportation 9 2013-10-01 2013-10-01 false Access to cargo: Security threat assessments for...

49 CFR 1546.213 - Access to cargo: Security threat assessments for cargo personnel in the United States.

Code of Federal Regulations, 2011 CFR

2011-10-01

... the cargo enters an airport Security Identification Display Area or is transferred to another TSA... under §§ 1546.101(a) or (b) accepts the cargo, until the cargo— (A) Enters an airport Security... 49 Transportation 9 2011-10-01 2011-10-01 false Access to cargo: Security threat assessments for...

Transcription factor Sox4 is required for PUMA-mediated apoptosis induced by histone deacetylase inhibitor, TSA.

PubMed

Jang, Sang-Min; Kang, Eun-Jin; Kim, Jung-Woong; Kim, Chul-Hong; An, Joo-Hee; Choi, Kyung-Hee

2013-08-23

PUMA is a crucial regulator of apoptotic cell death mediated by p53-dependent and p53-independent mechanisms. In many cancer cells, PUMA expression is induced in response to DNA-damaging reagent in a p53-dependent manner. However, few studies have investigated transcription factors that lead to the induction of PUMA expression via p53-independent apoptotic signaling. In this study, we found that the transcription factor Sox4 increased PUMA expression in response to trichostatin A (TSA), a histone deacetylase inhibitor in the p53-null human lung cancer cell line H1299. Ectopic expression of Sox4 led to the induction of PUMA expression at the mRNA and protein levels, and TSA-mediated up-regulation of PUMA transcription was repressed by the knockdown of Sox4. Using luciferase assays and chromatin immunoprecipitation, we also determined that Sox4 recruits p300 on the PUMA promoter region and increases PUMA gene expression in response to TSA treatment. Taken together, these results suggest that Sox4 is required for p53-independent apoptotic cell death mediated by PUMA induction via TSA treatment. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Attenuation of Choroidal Neovascularization by Histone Deacetylase Inhibitor

PubMed Central

Chan, Nymph; He, Shikun; Spee, Christine K.; Ishikawa, Keijiro; Hinton, David R.

2015-01-01

Choroidal neovascularization (CNV) is a blinding complication of age-related macular degeneration that manifests as the growth of immature choroidal blood vessels through Bruch’s membrane, where they can leak fluid or hemorrhage under the retina. Here, we demonstrate that the histone deacetylase inhibitor (HDACi) trichostatin A (TSA) can down-regulate the pro-angiogenic hypoxia-inducible factor-1α and vascular endothelial growth factor (VEGF), and up-regulate the anti-angiogenic and neuro-protective pigment epithelium derived factor in human retinal pigment epithelial (RPE) cells. Most strikingly, TSA markedly down-regulates the expression of VEGF receptor-2 in human vascular endothelial cells and, thus, can knock down pro-angiogenic cell signaling. Additionally, TSA suppresses CNV-associated wound healing response and RPE epithelial-mesenchymal transdifferentiation. In the laser-induced model of CNV using C57Bl/6 mice, systemic administration of TSA significantly reduces fluorescein leakage and the size of CNV lesions at post—laser days 7 and 14 as well as the immunohistochemical expression of VEGF, VEGFR2, and smooth muscle actin in CNV lesions at post-laser day 7. This report suggests that TSA, and possibly HDACi’s in general, should be further evaluated for their therapeutic potential for the treatment of CNV. PMID:25807249

33 CFR 101.510 - Assessment tools.

Code of Federal Regulations, 2010 CFR

2010-07-01

... may include: (a) DHS/TSA's vulnerability self-assessment tool located at http://www.tsa.gov/risk; and (b) USCG assessment tools, available from the cognizant COTP or at http://www.uscg.mil/hq/g-m/nvic...

The TSA Dragon--How to Slay It.

ERIC Educational Resources Information Center

Jeffers, Robert D.; Lamkin, Robert

1983-01-01

Three types of structures used in university systems to permit faculty and staff to take advantage of voluntary Tax Sheltered Annuity (TSA) programs are discussed. An innovative system at the University of Nevada is described. (MLW)

49 CFR 1503.405 - Injunctions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Assessment of Civil Penalties by TSA § 1503.405 Injunctions. Whenever it is determined that a person has engaged, or is about to engage, in any act or practice constituting a violation of a TSA requirement, the...

49 CFR 1503.415 - Request for portions of the enforcement investigative report (EIR).

Code of Federal Regulations, 2010 CFR

2010-10-01

... AND PROCEDURAL RULES INVESTIGATIVE AND ENFORCEMENT PROCEDURES Assessment of Civil Penalties by TSA... Notice of Proposed Civil Penalty, a person charged with a violation of a TSA requirement, or a...

49 CFR 1572.405 - Procedures for collection by TSA.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Collection Fee is required for a TSA agent to collect and transmit fingerprints and applicant information, in... renew an HME: $34. (3) The following FBI Fee is required for the FBI to process fingerprint...

49 CFR 1572.405 - Procedures for collection by TSA.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Collection Fee is required for a TSA agent to collect and transmit fingerprints and applicant information, in... renew an HME: $34. (3) The following FBI Fee is required for the FBI to process fingerprint...

49 CFR 1572.405 - Procedures for collection by TSA.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Collection Fee is required for a TSA agent to collect and transmit fingerprints and applicant information, in... renew an HME: $34. (3) The following FBI Fee is required for the FBI to process fingerprint...

Economic Decision Model Suggests Total Shoulder Arthroplasty is Superior to Hemiarthroplasty in Young Patients with End-stage Shoulder Arthritis.

PubMed

Bhat, Suneel B; Lazarus, Mark; Getz, Charles; Williams, Gerald R; Namdari, Surena

2016-11-01

Young patients with severe glenohumeral arthritis pose a challenging management problem for shoulder surgeons. Two controversial treatment options are total shoulder arthroplasty (TSA) and hemiarthroplasty. This study aims to characterize costs, as expressed by reimbursements for episodes of acute care, and outcomes associated with each treatment. We asked: for patients 30 to 50 years old with severe end-stage glenohumeral arthritis refractory to conservative management, (1) are more years of patient-derived satisfactory outcome by the Neer criteria and quality-adjusted life-years (QALYs) achieved using a TSA or a hemiarthroplasty; (2) does a TSA or a hemiarthroplasty result in a greater number of revision procedures; and (3) does a TSA or a hemiarthroplasty result in greater associated costs to society? The incidence of glenohumeral arthritis among 30- to 50-year-old patients, outcomes, reoperation probabilities, and associated costs from TSA and hemiarthroplasty were derived from the literature. A Markov chain decision tree model was developed from these estimates with number of revisions, cost of management for patients to 70 years old as defined by reimbursement for acute-care episodes, years with "satisfactory" or "excellent" outcome by the modified Neer criteria, and QALYs gained as principle outcome measures. A Monte Carlo simulation was conducted with a cohort representing the at-risk population for shoulder arthritis between 30 and 50 years old in the United States. During the lifetime of a cohort of 5279 patients, hemiarthroplasty as the initial treatment resulted in 59,574 patient years of satisfactory or excellent results (11.29 per patient) and average QALYs gained of 6.55, whereas TSA as the initial treatment resulted in 85,969 patient years of satisfactory or excellent results (16.29 per patient) and average QALYs gained of 7.96. During the lifetime of a cohort of 5279 patients, a hemiarthroplasty as the initial treatment led to 2090 lifetime revisions (0.4 per patient), whereas a TSA as the initial treatment led to 1605 lifetime revisions (0.3 per patient). During the lifetime of a cohort of 5279 patients, a hemiarthroplasty as initial treatment resulted in USD 132,500,000 associated direct reimbursements (USD 25,000 per patient), whereas a TSA as initial treatment resulted in USD 125,500,000 associated direct reimbursements (USD 23,700 per patient). Treatment of end-stage glenohumeral arthritis refractory to conservative treatment in patients 30 to 50 years old in the United States with TSA, instead of hemiarthroplasty, would result in greater cost savings, avoid a substantial number of revision procedures, and result in greater years of satisfactory or excellent patient outcomes and greater QALYs gained. On a population level, TSA is the cost-effective treatment for glenohumeral arthritis in patients 30 to 50 years old. Level II, economic and decision analysis study.

Obesity is Not Associated with Increased Short-term Complications After Primary Total Shoulder Arthroplasty.

PubMed

Jiang, Jimmy J; Somogyi, Jason R; Patel, Pranay B; Koh, Jason L; Dirschl, Douglas R; Shi, Lewis L

2016-03-01

Few studies have analyzed the association between elevated BMI and complications after total shoulder arthroplasty (TSA). Previous studies have not consistently arrived at the same conclusion regarding whether obesity is associated with a greater number of postoperative complications. We used a national surgical database to compare the 30-day complication profile and hospitalization outcomes after primary TSA among patients in different BMI categories. We asked: (1) Is obesity associated with an increased risk of complications within 30 days of primary TSA? (2) Is obesity associated with increased operative time? The American College of Surgeons National Surgical Quality Improvement Program(®) database for 2006 to 2012 was queried to identify all patients who underwent a primary TSA for osteoarthritis of the shoulder. The ACS-NSQIP(®) database was selected for this study as it is a nationally representative database that provides prospectively collected perioperative data and a comprehensive patient medical profile. Exclusion criteria included revision TSA, infection, tumor, or fracture. We analyzed 4796 patients who underwent a primary TSA for osteoarthritis of the shoulder. Patients who underwent a TSA were divided in four BMI categories: normal (18.5-25 kg/m(2)), overweight (25-30 kg/m(2)), obesity Class 1 (30-35 kg/m(2)), and obesity Class 2 or greater (> 35 kg/m(2)). Perioperative hospitalization data and 30-day postoperative complications were compared among different BMI classes. Differences in patient demographics, preoperative laboratory values, and preexisting patient comorbidities also were analyzed among different BMI groups, and multivariate analysis was used to adjust for any potential confounding variables. There was no association between BMI and 30-day complications after surgery (normal as reference, overweight group relative risk: 0.57 [95% CI, 0.30-1.06], p = 0.076; obesity Class 1 relative risk: 0.52 [95% CI, 0.26-1.03], p = 0.061; obesity Class 2 or greater relative risk: 0.54 [95% CI, 0.25-1.17], p = 0.117). However, greater BMI was associated with longer surgical times (for normal BMI control group: 110 minutes, SD, 42 minutes; overweight group: 115 minutes, SD, 46 minutes, mean difference to control: 5 minutes [95% CI, -1 to 10 minutes], p = 0.096; obesity Class 1: 120 minutes, SD, 43 minutes, mean difference: 10 minutes [95% CI, 5-15 minutes], p < 0.001; obesity Class 2 or greater: 122 minutes, SD, 45 minutes, mean difference: 12 minutes [95% CI, 6-18 minutes], p < 0.001). Although the surgical time increased for patients with greater BMI, the 30-day complications and perioperative hospitalization data after TSA were not different in patients with increased BMI levels. Obesity alone should not be a contraindication for TSA, and obese patients can expect similar incidences of postoperative complications. The preoperative medical optimization plan should be consistent with that of patients who are not obese who undergo TSA. Level III, therapeutic study.

Complexity of type-specific 56 kDa antigen CD4 T-cell epitopes of Orientia tsutsugamushi strains causing scrub typhus in India

PubMed Central

Dasch, Gregory A.

2018-01-01

Orientia tsutsugamushi (Ots) is an obligate, intracellular, mite-transmitted human pathogen which causes scrub typhus. Understanding the diversity of Ots antigens is essential for designing specific diagnostic assays and efficient vaccines. The protective immunodominant type-specific 56 kDa antigen (TSA) of Ots varies locally and across its geographic distribution. TSA contains four hypervariable domains. We bioinformatically analyzed 345 partial sequences of TSA available from India, most of which contain only the three variable domains (VDI-III) and three spacer conserved domains (SVDI, SVDII/III, SVDIII). The total number (152) of antigenic types (amino acid variants) varied from 14–36 in the six domains of TSA that we studied. Notably, 55% (787/1435) of the predicted CD4 T-cell epitopes (TCEs) from all the six domains had high binding affinities (HBA) to at least one of the prevalent Indian human leukocyte antigen (HLA) alleles. A surprisingly high proportion (61%) of such TCEs were from spacer domains; indeed 100% of the CD4 TCEs in the SVDI were HBA. TSA sequences from India had more antigenic types (AT) than TSA from Korea. Overall, >90% of predicted CD4 TCEs from spacer domains were predicted to have HBA against one or more prevalent HLA types from Indian, Korean, Asia-Pacific region or global population data sets, while only <50% of CD4 TCEs in variable domains exhibited such HBA. The phylogenetically and immunologically important amino acids in the conserved spacer domains were identified. Our results suggest that the conserved spacer domains are predicted to be functionally more important than previously appreciated in immune responses to Ots infections. Changes occurring at the TCE level of TSA may contribute to the wide range of pathogenicity of Ots in humans and mouse models. CD4 T-cell functional experiments are needed to assess the immunological significance of these HBA spacer domains and their role in clearance of Ots from Indian patients. PMID:29698425

TSA suppresses miR-106b-93-25 cluster expression through downregulation of MYC and inhibits proliferation and induces apoptosis in human EMC.

PubMed

Zhao, Zhi-Ning; Bai, Jiu-Xu; Zhou, Qiang; Yan, Bo; Qin, Wei-Wei; Jia, Lin-Tao; Meng, Yan-Ling; Jin, Bo-Quan; Yao, Li-Bo; Wang, Tao; Yang, An-Gang

2012-01-01

Histone deacetylase (HDAC) inhibitors are emerging as a novel class of anti-tumor agents and have manifested the ability to decrease proliferation and increase apoptosis in different cancer cells. A significant number of genes have been identified as potential effectors responsible for the anti-tumor function of HDAC inhibitor. However, the molecular mechanisms of these HDAC inhibitors in this process remain largely undefined. In the current study, we searched for microRNAs (miRs) that were affected by HDAC inhibitor trichostatin (TSA) and investigated their effects in endometrial cancer (EMC) cells. Our data showed that TSA significantly inhibited the growth of EMC cells and induced their apoptosis. Among the miRNAs that altered in the presence of TSA, the miR-106b-93-25 cluster, together with its host gene MCM7, were obviously down-regulated in EMC cells. p21 and BIM, which were identified as target genes of miR-106b-93-25 cluster, increased in TSA treated tumor cells and were responsible for cell cycle arrest and apoptosis. We further identified MYC as a regulator of miR-106b-93-25 cluster and demonstrated its down-regulation in the presence of TSA resulted in the reduction of miR-106b-93-25 cluster and up-regulation of p21 and BIM. More important, we found miR-106b-93-25 cluster was up-regulated in clinical EMC samples in association with the overexpression of MCM7 and MYC and the down-regulation of p21 and BIM. Thus our studies strongly indicated TSA inhibited EMC cell growth and induced cell apoptosis and cell cycle arrest at least partially through the down-regulation of the miR-106b-93-25 cluster and up-regulation of it's target genes p21 and BIM via MYC.

Mapping of single-copy genes by TSA-FISH in the codling moth, Cydia pomonella.

PubMed

Carabajal Paladino, Leonela Z; Nguyen, Petr; Síchová, Jindra; Marec, František

2014-01-01

We work on the development of transgenic sexing strains in the codling moth, Cydia pomonella (Tortricidae), which would enable to produce male-only progeny for the population control of this pest using sterile insect technique (SIT). To facilitate this research, we have developed a number of cytogenetic and molecular tools, including a physical map of the codling moth Z chromosome using BAC-FISH (fluorescence in situ hybridization with bacterial artificial chromosome probes). However, chromosomal localization of unique, single-copy sequences such as a transgene cassette by conventional FISH remains challenging. In this study, we adapted a FISH protocol with tyramide signal amplification (TSA-FISH) for detection of single-copy genes in Lepidoptera. We tested the protocol with probes prepared from partial sequences of Z-linked genes in the codling moth. Using a modified TSA-FISH protocol we successfully mapped a partial sequence of the Acetylcholinesterase 1 (Ace-1) gene to the Z chromosome and confirmed thus its Z-linkage. A subsequent combination of BAC-FISH with BAC probes containing anticipated neighbouring Z-linked genes and TSA-FISH with the Ace-1 probe allowed the integration of Ace-1 in the physical map of the codling moth Z chromosome. We also developed a two-colour TSA-FISH protocol which enabled us simultaneous localization of two Z-linked genes, Ace-1 and Notch, to the expected regions of the Z chromosome. We showed that TSA-FISH represents a reliable technique for physical mapping of genes on chromosomes of moths and butterflies. Our results suggest that this technique can be combined with BAC-FISH and in the future used for physical localization of transgene cassettes on chromosomes of transgenic lines in the codling moth or other lepidopteran species. Furthermore, the developed protocol for two-colour TSA-FISH might become a powerful tool for synteny mapping in non-model organisms.

Mapping of single-copy genes by TSA-FISH in the codling moth, Cydia pomonella

PubMed Central

2014-01-01

Background We work on the development of transgenic sexing strains in the codling moth, Cydia pomonella (Tortricidae), which would enable to produce male-only progeny for the population control of this pest using sterile insect technique (SIT). To facilitate this research, we have developed a number of cytogenetic and molecular tools, including a physical map of the codling moth Z chromosome using BAC-FISH (fluorescence in situ hybridization with bacterial artificial chromosome probes). However, chromosomal localization of unique, single-copy sequences such as a transgene cassette by conventional FISH remains challenging. In this study, we adapted a FISH protocol with tyramide signal amplification (TSA-FISH) for detection of single-copy genes in Lepidoptera. We tested the protocol with probes prepared from partial sequences of Z-linked genes in the codling moth. Results Using a modified TSA-FISH protocol we successfully mapped a partial sequence of the Acetylcholinesterase 1 (Ace-1) gene to the Z chromosome and confirmed thus its Z-linkage. A subsequent combination of BAC-FISH with BAC probes containing anticipated neighbouring Z-linked genes and TSA-FISH with the Ace-1 probe allowed the integration of Ace-1 in the physical map of the codling moth Z chromosome. We also developed a two-colour TSA-FISH protocol which enabled us simultaneous localization of two Z-linked genes, Ace-1 and Notch, to the expected regions of the Z chromosome. Conclusions We showed that TSA-FISH represents a reliable technique for physical mapping of genes on chromosomes of moths and butterflies. Our results suggest that this technique can be combined with BAC-FISH and in the future used for physical localization of transgene cassettes on chromosomes of transgenic lines in the codling moth or other lepidopteran species. Furthermore, the developed protocol for two-colour TSA-FISH might become a powerful tool for synteny mapping in non-model organisms. PMID:25471491

Q-vector measurements: physical examination versus magnetic resonance imaging measurements and their relationship with tibial tubercle-trochlear groove distance.

PubMed

Graf, Kristin H; Tompkins, Marc A; Agel, Julie; Arendt, Elizabeth A

2018-03-01

An increased lateral quadriceps vector has been associated with lateral patellar dislocation. Surgical correction of this increased vector through tibial tubercle medialization is often recommended when the quadriceps vector is "excessive". This can be evaluated by physical examination measurements of Q-angle and/or tubercle sulcus angle (TSA), as well as the magnetic resonance imaging (MRI) measurement of tibial tubercle-trochlear groove (TT-TG) distance. This study examined the relationship between three objective measurements of lateral quadriceps vector (TT-TG, Q-angle, TSA). A secondary goal was to relate lateral patellar tilt to these measurements. Consecutive patients undergoing patellofemoral stabilization surgery from 9/2010 to 6/2011 were included. The Q-angle and TSA were measured on intra-operative physical examination. The TT-TG and patellar tilt were measured on MRI. TSA, Q-angle, and patellar tilt were compared to TT-TG using Pearson correlation coefficient. The study cohort included 49 patients, ages 12-37 (mean 23.2); 62% female. The Pearson correlation coefficients showed (+) significance (p < 0.01) between the TT-TG and both TSA and Q-angle. Tilt and TT-TG were (+) non-significantly correlated. Despite positive correlations of each measurement with TT-TG, there is not uniform intra-patient correlation. In other words, if TT-TG is elevated for a patient, it does not guarantee that all other measurements, including tilt, are elevated in that individual patient. The TT-TG distance has significant positive correlation with the measurements of TSA and Q-angle in patients undergoing surgery for patellofemoral instability. The clinical relevance is that the variability within individual patients demonstrates the need for considering both TSA and TT-TG before and during surgical intervention to avoid overcorrection with a medial tibial tubercle osteotomy. Diagnostic study, Level III.

49 CFR 1552.5 - Fees.

Code of Federal Regulations, 2010 CFR

2010-10-01

... threat assessment for a candidate for flight training subject to the requirements of § 1552.3: $130. (b... information required under § 1552.3 to TSA. (2) TSA will not issue any fee refunds, unless a fee was paid in...

49 CFR 1522.5 - TSA inspection authority.

Code of Federal Regulations, 2010 CFR

2010-10-01

... threats to transportation; (ii) Enforce security-related regulations, directives, and requirements: (iii... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY SECURITY RULES FOR ALL MODES OF TRANSPORTATION TSA-APPROVED VALIDATION FIRMS...

49 CFR 1503.423 - Consent orders.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Assessment of Civil Penalties by TSA § 1503.423 Consent orders. (a) Issuance. At any time before the issuance..., may agree to dispose of the case by the issuance of a consent order by TSA. (b) Contents. A consent...

49 CFR 1503.661 - Judicial review of a final order.

Code of Federal Regulations, 2010 CFR

2010-10-01

... AND ENFORCEMENT PROCEDURES Rules of Practice in TSA Civil Penalty Actions § 1503.661 Judicial review of a final order. For violations of a TSA requirement, a party may petition for review of a final...

A new physical method to assess handle properties of fabrics made from wood-based fibers

NASA Astrophysics Data System (ADS)

Abu-Rous, M.; Liftinger, E.; Innerlohinger, J.; Malengier, B.; Vasile, S.

2017-10-01

In this work, the handfeel of fabrics made of wood-based fibers such as viscose, modal and Lyocell was investigated in relation to cotton fabrics applying the Tissue Softness Analyzer (TSA) method in comparison to other classical methods. Two different construction groups of textile were investigated. The validity of TSA in assessing textile softness of these constructions was tested. TSA results were compared to human hand evaluation as well as to classical physical measurements like drape coefficient, ring pull-through and Handle-o-meter, as well as a newer device, the Fabric Touch Tester (FTT). Physical methods as well as human hand assessments mostly agreed on the softest and smoothest range, but showed different rankings in the harder/rougher side fabrics. TSA ranking of softness and smoothness corresponded to the rankings by other physical methods as well as with human hand feel for the basic textile constructions.

Localization of human coagulation factor VIII (hFVIII) in transgenic rabbit by FISH-TSA: identification of transgene copy number and transmission to the next generation.

PubMed

Krylov, V; Tlapáková, T; Mácha, J; Curlej, J; Ryban, L; Chrenek, P

2008-01-01

For chromosomal localization of the hFVIII human transgene in F2 and F3 generation of transgenic rabbits, FISH-TSA was applied. A short cDNA probe (1250 bp) targeted chromosomes 3, 7, 8, 9 and 18 of an F2 male (animal 1-3-8). Two transgenic offspring (F3) revealed signal positions in chromosome 3 and chromosomes 3 and 7, respectively. Sequencing and structure analysis of the rabbit orthologous gene revealed high similarity to its human counterpart. Part of the sequenced cDNA (1310 bp) served as a probe for FISH-TSA analysis. The rabbit gene was localized in the q arm terminus of the X chromosome. This result is in agreement with reciprocal chromosome painting between the rabbit and the human. The presented FISH-TSA method provides strong signals without any interspecies reactivity.

Digoxin for atrial fibrillation and atrial flutter: A systematic review with meta-analysis and trial sequential analysis of randomised clinical trials

PubMed Central

Gluud, Christian; Jakobsen, Janus C.

2018-01-01

Background During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the results of these reviews suggested that digoxin seems to increase the risk of all-cause mortality regardless of concomitant heart failure. Our objective was to assess the benefits and harms of digoxin for atrial fibrillation and atrial flutter based on randomized clinical trials. Methods We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, BIOSIS for eligible trials comparing digoxin versus placebo, no intervention, or other medical interventions in patients with atrial fibrillation or atrial flutter in October 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were heart failure, stroke, heart rate control, and conversion to sinus rhythm. We performed both random-effects and fixed-effect meta-analyses and chose the more conservative result as our primary result. We used Trial Sequential Analysis (TSA) to control for random errors. We used GRADE to assess the quality of the body of evidence. Results 28 trials (n = 2223 participants) were included. All were at high risk of bias and reported only short-term follow-up. When digoxin was compared with all control interventions in one analysis, we found no evidence of a difference on all-cause mortality (risk ratio (RR), 0.82; TSA-adjusted confidence interval (CI), 0.02 to 31.2; I2 = 0%); serious adverse events (RR, 1.65; TSA-adjusted CI, 0.24 to 11.5; I2 = 0%); quality of life; heart failure (RR, 1.05; TSA-adjusted CI, 0.00 to 1141.8; I2 = 51%); and stroke (RR, 2.27; TSA-adjusted CI, 0.00 to 7887.3; I2 = 17%). Our analyses on acute heart rate control (within 6 hours of treatment onset) showed firm evidence of digoxin being superior compared with placebo (mean difference (MD), -12.0 beats per minute (bpm); TSA-adjusted CI, -17.2 to -6.76; I2 = 0%) and inferior compared with beta blockers (MD, 20.7 bpm; TSA-adjusted CI, 14.2 to 27.2; I2 = 0%). Meta-analyses on acute heart rate control showed that digoxin was inferior compared with both calcium antagonists (MD, 21.0 bpm; TSA-adjusted CI, -30.3 to 72.3) and with amiodarone (MD, 14.7 bpm; TSA-adjusted CI, -0.58 to 30.0; I2 = 42%), but in both comparisons TSAs showed that we lacked information. Meta-analysis on acute conversion to sinus rhythm showed that digoxin compared with amiodarone reduced the probability of converting atrial fibrillation to sinus rhythm, but TSA showed that we lacked information (RR, 0.54; TSA-adjusted CI, 0.13 to 2.21; I2 = 0%). Conclusions The clinical effects of digoxin on all-cause mortality, serious adverse events, quality of life, heart failure, and stroke are unclear based on current evidence. Digoxin seems to be superior compared with placebo in reducing the heart rate, but inferior compared with beta blockers. The long-term effect of digoxin is unclear, as no trials reported long-term follow-up. More trials at low risk of bias and low risk of random errors assessing the clinical effects of digoxin are needed. Systematic review registration PROSPERO CRD42016052935 PMID:29518134

Effects of trichostatin A on In vitro development and DNA methylation level of the satellite I region of swamp buffalo (Bubalus bubalis) cloned embryos.

PubMed

Srirattana, Kanokwan; Ketudat-Cairns, Mariena; Nagai, Takashi; Kaneda, Masahiro; Parnpai, Rangsun

2014-01-01

Trichostatin A (TSA), a histone deacetylase inhibitor, has been widely used to improve the cloning efficiency in several species. This brings our attention to investigation of the effects of TSA on developmental potential of swamp buffalo cloned embryos. Swamp buffalo cloned embryos were produced by electrical pulse fusion of male swamp buffalo fibroblasts with swamp buffalo enucleated oocytes. After fusion, reconstructed oocytes were treated with 0, 25 or 50 nM TSA for 10 h. The results showed that there was no significant difference in the rates of fusion (82-85%), cleavage (79-84%) and development to the 8-cell stage (59-65%) among treatment groups. The highest developmental rates to the morula and blastocyst stages of embryos were found in the 25 nM TSA-treated group (42.7 and 30.1%, respectively). We also analyzed the DNA methylation level in the satellite I region of donor cells and in in vitro fertilized (IVF) and cloned embryos using the bisulfite DNA sequencing method. The results indicated that the DNA methylation levels in cloned embryos were significantly higher than those of IVF embryos but approximately similar to those of donor cells. Moreover, there was no significant difference in the methylation level among TSA-treated and untreated cloned embryos. Thus, TSA treatments at 25 nM for 10 h could enhance the in vitro developmental potential of swamp buffalo cloned embryos, but no beneficial effect on the DNA methylation level was observed.

Effects of Trichostatin A on In Vitro Development and DNA Methylation Level of the Satellite I Region of Swamp Buffalo (Bubalus bubalis) Cloned Embryos

PubMed Central

SRIRATTANA, Kanokwan; KETUDAT-CAIRNS, Mariena; NAGAI, Takashi; KANEDA, Masahiro; PARNPAI, Rangsun

2014-01-01

Trichostatin A (TSA), a histone deacetylase inhibitor, has been widely used to improve the cloning efficiency in several species. This brings our attention to investigation of the effects of TSA on developmental potential of swamp buffalo cloned embryos. Swamp buffalo cloned embryos were produced by electrical pulse fusion of male swamp buffalo fibroblasts with swamp buffalo enucleated oocytes. After fusion, reconstructed oocytes were treated with 0, 25 or 50 nM TSA for 10 h. The results showed that there was no significant difference in the rates of fusion (82–85%), cleavage (79–84%) and development to the 8-cell stage (59–65%) among treatment groups. The highest developmental rates to the morula and blastocyst stages of embryos were found in the 25 nM TSA-treated group (42.7 and 30.1%, respectively). We also analyzed the DNA methylation level in the satellite I region of donor cells and in in vitro fertilized (IVF) and cloned embryos using the bisulfite DNA sequencing method. The results indicated that the DNA methylation levels in cloned embryos were significantly higher than those of IVF embryos but approximately similar to those of donor cells. Moreover, there was no significant difference in the methylation level among TSA-treated and untreated cloned embryos. Thus, TSA treatments at 25 nM for 10 h could enhance the in vitro developmental potential of swamp buffalo cloned embryos, but no beneficial effect on the DNA methylation level was observed. PMID:24909601

Synergistic effect of p53 on TSA-induced stanniocalcin 1 expression in human nasopharyngeal carcinoma cells, CNE2.

PubMed

Ching, L Y; Yeung, Bonnie H Y; Wong, Chris K C

2012-06-01

Human stanniocalcin 1 (STC1) has recently been identified as a putative protein factor involved in cellular apoptosis. The use of histone deacetylase inhibitor (i.e. trichostatin A (TSA)) and doxorubicin (Dox) is one of the common treatment methods to induce apoptosis in human cancer cells. A study on TSA and Dox-mediated apoptosis may shed light on the regulation and function of STC1 in cancer treatment. In this study, TSA and Dox cotreatment in human nasopharyngeal carcinoma cells (CNE2) elicited synergistic effects on STC1 gene expression and cellular apoptosis. An activation of p53 (TP53) transcriptional activity in Dox- or Dox+TSA-treated cells was revealed by the increased expression levels of p53 mRNA/protein as well as p53-driven luciferase activities. To elucidate the possible involvement of p53 in STC1 gene transcription, a vector expressing wild-type or dominant negative (DN) p53 was transiently transfected into the cells. Both STC1 promoter luciferase constructs and chromatin immunoprecipitation assays did not support the direct role of p53 in STC1 gene transactivation. However, the synergistic effects of p53 on the induction of NF-κB phosphorylation and the recruitment of acetylated histone H3 in STC1 promoter were observed in TSA-cotreated cells. The overexpression of exogenous STC1 sensitized apoptosis in Dox-treated cells. Taken together, this study provides data to show the cross talk of NF-κB, p53, and histone protein in the regulation of STC1 expression and function.

Immunogenicity and efficacy of a bivalent DNA vaccine containing LeIF and TSA genes against murine cutaneous leishmaniasis.

PubMed

Maspi, Nahid; Ghaffarifar, Fatemeh; Sharifi, Zohreh; Dalimi, Abdolhossein; Dayer, Mohammad Saaid

2017-03-01

There is no effective vaccine for the prevention and elimination of leishmaniasis. For this reason, we assessed the protective effects of DNA vaccines containing LeIF, TSA genes alone, or LeIF-TSA fusion against cutaneous leishmaniasis pEGFP-N1 plasmid (empty vector) and phosphate buffer saline (PBS) were used as control groups. Therefore, cellular and humoral immune responses were evaluated before and after the challenge with Leishmania major. Lesion diameter was also measured 3-12 weeks after challenge. All immunized mice with plasmid DNA encoding Leishmania antigens induced the partial immunity characterized by increased IFN-γ and IgG2a levels compared with control groups (p < 0.001). Furthermore, the immunized mice showed significant reduction in mean lesion sizes compared with mice in empty vector and PBS groups (p < 0.05). The reduction in lesion diameter was 29.3%, 34.1%, and 46.2% less in groups vaccinated with LeIF, TSA, and LeIF-TSA, respectively, than in PBS group at 12th week post infection. IFN/IL-4 and IgG2a/IgG1 ratios indicated that group receiving LeIF-TSA fusion had the highest IFN-γ and IgG2a levels. In this study, DNA immunization promoted Th1 immune response characterized by higher IFN-γ and IgG2a levels and also reduction in lesion size. These results showed that a bivalent vaccine containing two distinct antigens may induce more potent immune responses against leishmaniasis. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Histone Deacetylase Inhibitor Improves the Development and Acetylation Levels of Cat–Cow Interspecies Cloned Embryos

PubMed Central

Wittayarat, Manita; Sato, Yoko; Do, Lanh Thi Kim; Morita, Yasuhiro; Chatdarong, Kaywalee; Techakumphu, Mongkol; Taniguchi, Masayasu

2013-01-01

Abstract Abnormal epigenetic reprogramming, such as histone acetylation, might cause low efficiency of interspecies somatic cell nuclear transfer (iSCNT). This study was conducted to evaluate the effects of trichostatin A (TSA) on the developmental competence and histone acetylation of iSCNT embryos reconstructed from cat somatic cells and bovine cytoplasm. The iSCNT cat and parthenogenetic bovine embryos were treated with various concentrations of TSA (0, 25, 50, or 100 nM) for 24 h, respectively, following fusion and activation. Treatment with 50 nM TSA produced significantly higher rates of cleavage and blastocyst formation (84.3% and 4.6%, respectively) of iSCNT embryos than the rates of non-TSA–treated iSCNT embryos (63.8% and 0%, respectively). Similarly, the treatment of 50 nM TSA increased the blastocyst formation rate of parthenogenetic bovine embryos. The acetylation levels of histone H3 lysine 9 (H3K9) in the iSCNT embryos with the treatment of 50 nM TSA were similar to those of in vitro–fertilized embryos and significantly higher (p<0.05) than those of non-TSA–treated iSCNT embryos (control), irrespective of the embryonic development stage (two-cell, four-cell, and eight-cell stages). These results indicated that the treatment of 50 nM TSA postfusion was beneficial for development to the blastocyst stage of iSCNT cat embryos and correlated with the increasing levels of acetylation at H3K9. PMID:23790014

49 CFR 1503.417 - Final Notice of Proposed Civil Penalty and Order.

Code of Federal Regulations, 2010 CFR

2010-10-01

... INVESTIGATIVE AND ENFORCEMENT PROCEDURES Assessment of Civil Penalties by TSA § 1503.417 Final Notice of Proposed Civil Penalty and Order. (a) Issuance. TSA may issue a Final Notice of Proposed Civil Penalty and...

Transportation Satellite Accounts : A New Way of Measuring Transportation Services in America : [2011

DOT National Transportation Integrated Search

2011-01-01

Transportation Satellite Accounts (TSA), produced by the Bureau of Economic Analysis and the Bureau of Transportation Statistics, provides measures of national transportation output. TSA includes both in-house and for-hire transportation services. Fo...

49 CFR 1546.3 - TSA inspection authority.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY FOREIGN AIR CARRIER SECURITY General § 1546.3 TSA... inspections or tests, including copying records, to determine compliance of an airport operator, aircraft...

49 CFR 1546.3 - TSA inspection authority.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY FOREIGN AIR CARRIER SECURITY General § 1546.3 TSA... inspections or tests, including copying records, to determine compliance of an airport operator, aircraft...

49 CFR 1546.3 - TSA inspection authority.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY FOREIGN AIR CARRIER SECURITY General § 1546.3 TSA... inspections or tests, including copying records, to determine compliance of an airport operator, aircraft...

49 CFR 1546.3 - TSA inspection authority.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY FOREIGN AIR CARRIER SECURITY General § 1546.3 TSA... inspections or tests, including copying records, to determine compliance of an airport operator, aircraft...

49 CFR 1546.3 - TSA inspection authority.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY FOREIGN AIR CARRIER SECURITY General § 1546.3 TSA... inspections or tests, including copying records, to determine compliance of an airport operator, aircraft...

[Effect of trichostatin A on the osteogenic differentiation potential of periodontal ligament stem cells in inflammatory microenvironment induced by tumor necrosis factor-α stimulation].

PubMed

Wang, H; Chen, Q; Liu, W J; Yang, Z H; Li, D; Jin, F

2016-04-09

To compare the expression of histone deacetylase(HDAC)1-11 of human periodontal ligament stem cells(PDLSC)in normal and inflammatory microenvironments, and to investigate the effect of histone deacetylase inhibitor trichostatin A(TSA)on the osteogenic differentiation potential of PDLSC in inflammatory microenvironment induced by tumor necrosis factor-α(TNF-α)stimulation. PDLSC were isolated from periodontal ligament tissues obtained from the surgically extracted human teeth and cultured by single-colony selection. The expression of HDAC1-11 in cells with or without TNF-α(10 μg/L)stimulation was evaluated by quantitative real time-PCR(RT-PCR). The effect of TSA on cell proliferation was investigated by methyl thiazolyl tetrazolium(MTT)assay. The influence of TSA on osteogenic differentiation of PDLSC in inflammatory microenvironment with TNF-α stimulation was assessed by alizarin red staining, quantitative RT-PCR and Western blotting, respectively. The expression of HDAC in PDLSC with TNF-α stimulation was significantly higher than that in normal PDLSC(P<0.05)(except HDAC7, P=0.243). TSA had no significant effect on PDLSC proliferation at the concentration of 50 nmol/L(P=0.232). The alizarin red staining showed that PDLSC in TNF-α group generated less mineralized nodule than the control group, while the cell matrix mineralization in TSA group was improved obviously. TNF-α had an inhibitory effect on the expression of osteogenesis related genes, runt-related transcription factor-2(RUNX2)and alkaline phosphatase(ALP), with relative gene expression ratio(experimental/control)decreased to 0.17 ± 0.02 and 0.32 ± 0.03, while TSA could significantly increase the genes' expression to 0.67±0.03 and 0.89±0.02(P<0.01). Western blotting test showed that in TNF-α group the expression of osteogenesis related proteins was obviously reduced, and compared with the TNF-α group, TSA could significantly promote the expression of proteinsin inflammatory microenvironment. PDLSC in inflammatory microenvironment by TNF-α stimulation had a higher expression of HDAC than that in normal conditions. TSA, as a histone deacetylase inhibitor, could significantly promote the osteogenic differentiation potential of PDLSC in inflammatory microenvironment by suppressing HDAC.

Economic importance of transportation services : highlights of the Transportation Satellite Accounts

DOT National Transportation Integrated Search

1998-04-01

A new accounting tool, called the Transportation Satellite Accounts (TSA), now provides a way to measure both in-house and for-hire transportation services. The TSA, developed jointly by the Bureau of Transportation Statistics (BTS) of the Department...

49 CFR 1522.127 - Assessment report.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF HOMELAND SECURITY SECURITY RULES FOR ALL MODES OF TRANSPORTATION TSA-APPROVED VALIDATION FIRMS AND VALIDATORS TSA-Approved Validation Firms and Validators for the Certified Cargo Screening Program...) The assessment report must include the following information, in addition to any other information...

49 CFR 1548.3 - TSA inspection authority.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., foreign air carrier, indirect air carrier, or airport tenant with— (1) This subchapter, and any security... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY INDIRECT AIR CARRIER SECURITY § 1548.3 TSA inspection...

49 CFR 1548.3 - TSA inspection authority.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., foreign air carrier, indirect air carrier, or airport tenant with— (1) This subchapter, and any security... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY INDIRECT AIR CARRIER SECURITY § 1548.3 TSA inspection...

49 CFR 1548.3 - TSA inspection authority.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., foreign air carrier, indirect air carrier, or airport tenant with— (1) This subchapter, and any security... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY INDIRECT AIR CARRIER SECURITY § 1548.3 TSA inspection...

49 CFR 1548.3 - TSA inspection authority.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., foreign air carrier, indirect air carrier, or airport tenant with— (1) This subchapter, and any security... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY INDIRECT AIR CARRIER SECURITY § 1548.3 TSA inspection...

49 CFR 1548.3 - TSA inspection authority.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., foreign air carrier, indirect air carrier, or airport tenant with— (1) This subchapter, and any security... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY INDIRECT AIR CARRIER SECURITY § 1548.3 TSA inspection...

Influence of skin cold sensation threshold in the occurrence of dental sensitivity during dental bleaching: a placebo controlled clinical trial.

PubMed

Rahal, Vanessa; Gallinari, Marjorie de Oliveira; Barbosa, Juliana Stuginski; Martins-Junior, Reynaldo Leite; Santos, Paulo Henrique Dos; Cintra, Luciano Tavares Angelo; Briso, André Luiz Fraga

2018-01-18

This study verified the occurrence of dental sensitivity in patients submitted to a 35% hydrogen peroxide based product (Whiteness HP Maxx 35% - FGM), skin cold sensation threshold (SCST) and its influence on dental sensitivity. Sixty volunteers were divided into 4 groups (n = 15), according to SCST (low: GI and GIII, and high: GII and IV) and bleaching treatment (hydrogen peroxide: GI and GII, and placebo: GIII and GIV). SCST was determined in the inner forearm for 6 different times using a neurosensory analyzer, the TSA II (Medoc Advanced Medical Systems, Ramat Yishai, Northern District, Israel). Dental sensitivity measurements were performed 10 different times using a thermal stimulus and an intraoral device attached to TSA II, positioned in the buccal surface of the upper right central incisor. Spontaneous dental sensitivity was also determined using the Visual Analogue Scale (VAS). Data were submitted to Student's t-test and Pearson's Correlation Test (α=0.05). SCST remained the same during bleaching treatment. Distinct responses of dental sensitivity were found in patients with low and high SCST during the first and third bleaching session (p≤0.05). The teeth submitted to the bleaching treatment became more sensitive to cold than those treated with placebo. Moreover, data obtained with TSA and VAS presented moderate correlation. Bleaching treatment increased dental sensitivity and skin cold sensation threshold might represent a determining factor in this occurrence, since low and high SCST patients had different responses to the thermal stimulus in the teeth.

Femtomole-Scale High-Throughput Screening of Protein Ligands with Droplet-Based Thermal Shift Assay.

PubMed

Liu, Wen-Wen; Zhu, Ying; Fang, Qun

2017-06-20

There is a great demand to measure protein-ligand interactions in rapid and low cost way. Here, we developed a microfluidic droplet-based thermal shift assay (dTSA) system for high-throughput screening of small-molecule protein ligands. The system is composed of a nanoliter droplet array chip, a microfluidic droplet robot, and a real-time fluorescence detection system. Total 324 assays could be performed in parallel in a single chip with an 18 × 18 droplet array. The consumption of dTSA for each protein or ligand sample was only 5 nL (femtomole scale), which is significantly reduced by over 3 orders of magnitude compared with those in 96- or 384-well plate-based systems. We also observed the implementation of TSA in nanoliter droplet format could substantially improve assay precision with relative standard deviation (RSD) of 0.2% (n = 50), which can be ascribed to the enhanced thermal conduction in small volume reactors. The dTSA system was optimized by studying the effect of droplet volumes, as well as protein and fluorescent dye (SYPRO Orange) concentrations. To demonstrate its potential in drug discovery, we applied the dTSA system in screening inhibitors of human thrombin with a commercial library containing 100 different small molecule compounds, and two inhibitors were successfully identified and confirmed.

Technologies to counter aviation security threats

NASA Astrophysics Data System (ADS)

Karoly, Steve

2017-11-01

The Aviation and Transportation Security Act (ATSA) makes TSA responsible for security in all modes of transportation, and requires that TSA assess threats to transportation, enforce security-related regulations and requirements, and ensure the adequacy of security measures at airports and other transportation facilities. Today, TSA faces a significant challenge and must address a wide range of commercial, military grade, and homemade explosives and these can be presented in an infinite number of configurations and from multiple vectors. TSA screens 2 million passengers and crew, and screens almost 5 million carry-on items and 1.2 million checked bags daily. As TSA explores new technologies for improving efficiency and security, those on the forefront of research and development can help identify unique and advanced methods to combat terrorism. Research and Development (R&D) drives the development of future technology investments that can address an evolving adversary and aviation threat. The goal is to rethink the aviation security regime in its entirety, and rather than focusing security at particular points in the enterprise, distribute security from the time a reservation is made to the time a passenger boards the aircraft. The ultimate objective is to reengineer aviation security from top to bottom with a continued focus on increasing security throughout the system.

Salivary Lipid Peroxidation and Total Sialic Acid Levels in Smokers and Smokeless Tobacco Users as Maraş Powder

PubMed Central

Kurtul, Naciye; Gökpınar, Engin

2012-01-01

Maraş powder (MP), a different type of smokeless tobacco (ST) and prepared from a tobacco of species Nicotiana rustica Linn, is widely used in Turkey. We aimed to investigate the effects of MP on salivary total sialic acid (TSA) and malondialdehyde (MDA) levels and to compare these parameters in smokers and MP users (MPUs). The salivary TSA and MDA concentrations were significantly higher in the smokers and MPU than those of control subjects and also in MPU than that of smokers. We have also observed that as the number of cigarettes consumed and MP amount increases, TSA and MDA levels increase too. In smokers, MDA values were significantly correlated with the number of cigarettes smoked and the duration of smoking. In MPU, both MDA and TSA levels were significantly correlated with the duration of MP use and the amount of daily consumed MP. We have concluded increased salivary TSA and MDA levels associated in MPU and smokers. Results can help to evaluate harmful effects of these habits. It is important to point out that bigger change in the measured parameters has been observed for MP use. This observation may be an important indication of harmful effects of ST use as MP. PMID:22577253

HDAC inhibitors TSA and sodium butyrate enhanced the human IL-5 expression by altering histone acetylation status at its promoter region.

PubMed

Han, Songyan; Lu, Jun; Zhang, Yu; Cheng, Cao; Li, Lin; Han, Liping; Huang, Baiqu

2007-02-15

The expression of IL-5 correlated tightly with the maturation and differentiation of eosinophils, and is considered as a cytokine responsible for allergic inflammation. We report here that inhibition of HDAC activity by Trichostatin A (TSA) and sodium butyrate (NaBu), the two specific HDAC inhibitors, resulted in the elevation of both endogenous and exogenous activity of IL-5 promoter. We demonstrated that both the mRNA expression and protein production of IL-5 were stimulated by TSA and NaBu treatments. ChIP assays showed that treatments of TSA and NaBu caused hyperacetylation of histones H3 and H4 on IL-5 promoter in Jurkat cells, which consequently promoted the exogenous luciferase activity driven by this promoter. Moreover, site-directed mutagenesis studies showed that the binding sites for transcription factors NFAT, GATA3 and YY1 on IL-5 promoter were critical for the effects of TSA and NaBu, suggesting that the transcriptional activation of IL-5 gene by these inhibitors was achieved by affecting HDAC function on IL-5 promoter via transcription factors. These data will contribute to elucidating the unique mechanism of IL-5 transcriptional control and to the therapy of allergic disorders related to IL-5.

Trichostatin A (TSA) facilitates formation of partner preference in male prairie voles (Microtus ochrogaster).

PubMed

Duclot, F; Wang, H; Youssef, C; Liu, Y; Wang, Z; Kabbaj, M

2016-05-01

In the socially monogamous prairie voles (Microtus ochrogaster), the development of a social bonding is indicated by the formation of partner preference, which involves a variety of environmental and neurochemical factors and brain structures. In a most recent study in female prairie voles, we found that treatment with the histone deacetylase inhibitor trichostatin A (TSA) facilitates the formation of partner preference through up-regulation of oxytocin receptor (OTR) and vasopressin V1a receptor (V1aR) genes expression in the nucleus accumbens (NAcc). In the present study, we tested the hypothesis that TSA treatment also facilitates partner preference formation and alters OTR and V1aR genes expression in the NAcc in male prairie voles. We thus observed that central injection of TSA dose-dependently promoted the formation of partner preference in the absence of mating in male prairie voles. Interestingly, TSA treatment up-regulated OTR, but not V1aR, gene expression in the NAcc similarly as they were affected by mating - an essential process for naturally occurring partner preference. These data, together with others, not only indicate the involvement of epigenetic events but also the potential role of NAcc oxytocin in the regulation of partner preference in both male and female prairie voles. Copyright © 2016 Elsevier Inc. All rights reserved.

Trichostatin A specifically improves the aberrant expression of transcription factor genes in embryos produced by somatic cell nuclear transfer

PubMed Central

Inoue, Kimiko; Oikawa, Mami; Kamimura, Satoshi; Ogonuki, Narumi; Nakamura, Toshinobu; Nakano, Toru; Abe, Kuniya; Ogura, Atsuo

2015-01-01

Although mammalian cloning by somatic cell nuclear transfer (SCNT) has been established in various species, the low developmental efficiency has hampered its practical applications. Treatment of SCNT-derived embryos with histone deacetylase (HDAC) inhibitors can improve their development, but the underlying mechanism is still unclear. To address this question, we analysed gene expression profiles of SCNT-derived 2-cell mouse embryos treated with trichostatin A (TSA), a potent HDAC inhibitor that is best used for mouse cloning. Unexpectedly, TSA had no effect on the numbers of aberrantly expressed genes or the overall gene expression pattern in the embryos. However, in-depth investigation by gene ontology and functional analyses revealed that TSA treatment specifically improved the expression of a small subset of genes encoding transcription factors and their regulatory factors, suggesting their positive involvement in de novo RNA synthesis. Indeed, introduction of one of such transcription factors, Spi-C, into the embryos at least partially mimicked the TSA-induced improvement in embryonic development by activating gene networks associated with transcriptional regulation. Thus, the effects of TSA treatment on embryonic gene expression did not seem to be stochastic, but more specific than expected, targeting genes that direct development and trigger zygotic genome activation at the 2-cell stage. PMID:25974394

Detection and analysis of tupaia hepatocytes via mAbs against tupaia serum albumin.

PubMed

Liu, Xuan; Yuan, Lunzhi; Yuan, Quan; Zhang, Yali; Wu, Kun; Zhang, Tianying; Wu, Yong; Hou, Wangheng; Wang, Tengyun; Liu, Pingguo; Shih, James Wai Kuo; Cheng, Tong; Xia, Ningshao

2016-05-20

On the basis of its close phylogenetic relationship with primates, the development of Tupaia belangeri as an infection animal model and drug metabolism model could provide a new option for preclinical studies, especially in hepatitis virus research. As a replacement for primary human hepatocytes (PHHs), primary tupaia hepatocytes (PTHs) have been widely used. Similar to human serum albumin, tupaia serum albumin (TSA) is the most common liver synthesis protein and is an important biomarker for PTHs and liver function. However, no detection or quantitative method for TSA has been reported. In this study, mouse monoclonal antibodies (mAbs) 4G5 and 9H3 against TSA were developed to recognize PTHs, and they did not show cross-reactivity with serum albumin from common experimental animals, such as the mouse, rat, cow, rabbit, goat, monkey, and chicken. The two mAbs also exhibited good performance in fluorescence activated cell sorting (FACS) analysis and immunofluorescence (IF) detection of PTHs. A chemiluminescent enzyme immune assay method using the two mAbs, with a linear range from 96.89 pg/ml to 49,609.38 pg/ml, was developed for the quantitative detection of TSA. The mAbs and the CLEIA method provide useful tools for research on TSA and PTHs.

77 FR 25187 - Extension of Agency Information Collection Activity Under OMB Review: Certified Cargo Screening...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-27

...This notice announces that the Transportation Security Administration (TSA) has forwarded the Information Collection Request (ICR), Office of Management and Budget (OMB) control number 1652-0053, abstracted below to OMB for renewal in compliance with the Paperwork Reduction Act. The ICR describes the nature of the information collection and its expected burden. TSA published a Federal Register notice, with a 60-day comment period soliciting comments, of the following collection of information on February 24, 2012, 77 FR 11146, and TSA received no comments. The collections include: (1) Applications from entities that wish to become Certified Cargo Screening Facilities (CCSFs); (2) personal information to allow TSA to conduct security threat assessments on key individuals employed by the CCSFs; (3) implementation of a standard security program or submission of a proposed modified security program; (4) information on the amount of cargo screened; (5) recordkeeping requirements for CCSFs, and any other requests for information relating to cargo screening required to meet the Implementing Recommendations of the 9/11 Commission Act of 2007 (9/ 11 Act) and the Aviation and Transportation Security Act (ATSA) mandates. TSA is seeking the renewal of the ICR for the continuation of the program in order to secure passenger aircraft transporting cargo as required in the 9/11 Act.

Self-adaptive thermal management - the fundamentals and applications in Li-polymer batteries

NASA Astrophysics Data System (ADS)

Geng, Xiaobao

The thermal management systems for electronic devices and their power sources are facing increasing challenge to accommodate the ever-changing environmental and operational conditions. The conventional thermal management systems, with a predominant focus on cooling, are often not sufficient in those cases. In addition, to support miniaturization, complex systems and broader applications (e.g., space and military), the thermal management system often needs to be compatible with smaller device and their fabrication processes, dissipate heat efficiently for localized heat spot, and meet the requirement of light weight and low power consumption. In order to address such issues, a self-adaptive thermal switch array (TSA) is proposed based on microelectromechanical systems (MEMS) technology which has the capability automatically change its thermal conductance according to the environmental and operational conditions. This TSA was actuated by low melting alloy (LMA) with neither control unit nor parasitic energy consumption. The idea has been first demonstrated by a prototype device with the stabilization temperatures under various power inputs investigated both experimentally and theoretically. When the power input was changed from 3.8W to 5.8W, the stabilization temperature of the device was increased only by 2.5°C due to the stabilization effect of TSA. The experimental data were found in good agreement with their theoretical value. Based on the theoretical model, two types of TSA, namely high-on and low-off, were further developed to increase on-state thermal conductance and decrease off-state thermal conductance, respectively. Compared with the low-off TSA, the high-on TSA can more efficiently cool the devices and stabilize their temperature at a value closer to the melting point of LMA even under higher power inputs. On the other hand, the startup time and energy consumption were significantly reduced with the low-off TSA design due to the enhanced off-state thermal insulation, making them more suitable for cold start applications. A few key design factors have been identified to increase the on-state thermal conductance, reduce the off-state thermal conductance and enhance their ratio (switching ratio). The TSAs were then applied to a Li-polymer battery stack to demonstrate the self-adaptive thermal management capability. When cold-started from -10°C, the TSA-regulated battery stack reached 20°C in ~10min. The operational temperature was sustained with a moderate discharge current until depletion, while maintaining a fairly uniform temperate distribution within the battery stack. Compared with the open-cooling case, the performance of the Li-polymer battery was significantly improved by TSA-regulated thermal management. The capacity and output energy were increased by 16% and 23%, respectively. With the low-off TSA, the cold-start time has been shortened to ~ 7min, while the capacity and output energy of battery stack were increased by 18% and 27%, respectively, as compared to open-cooling case. The promising results have also paved the way for improving the performance of self-adaptive thermal management through the key design parameters.

78 FR 45256 - Intent To Request Approval From OMB of One New Public Collection of Information: TSA Pre✓TM

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-26

...-begins . TSA seeks to establish enrollment sites and implement a mobile enrollment capability. Those... by submitting biographic information and paying the fee using a secure web portal (or by money order...

Aviation security : TSA has completed key activities associated with implementing secure flight, but additional actions are needed to mitigate risks.

DOT National Transportation Integrated Search

2009-05-01

To enhance aviation security, the Department of Homeland Securitys (DHS) Transportation Security Administration (TSA) developed a programknown as Secure Flightto assume from air carriers the function of matching passenger information against...

49 CFR 1542.303 - Security Directives and Information Circulars.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY... Information Circular to notify airport operators of security concerns. When TSA determines that additional... aviation, TSA issues a Security Directive setting forth mandatory measures. (b) Each airport operator must...

49 CFR 1542.303 - Security Directives and Information Circulars.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY... Information Circular to notify airport operators of security concerns. When TSA determines that additional... aviation, TSA issues a Security Directive setting forth mandatory measures. (b) Each airport operator must...

49 CFR 1542.303 - Security Directives and Information Circulars.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY... Information Circular to notify airport operators of security concerns. When TSA determines that additional... aviation, TSA issues a Security Directive setting forth mandatory measures. (b) Each airport operator must...

49 CFR 1542.303 - Security Directives and Information Circulars.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY... Information Circular to notify airport operators of security concerns. When TSA determines that additional... aviation, TSA issues a Security Directive setting forth mandatory measures. (b) Each airport operator must...

49 CFR 1522.119 - Training.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF HOMELAND SECURITY SECURITY RULES FOR ALL MODES OF TRANSPORTATION TSA-APPROVED VALIDATION FIRMS AND VALIDATORS TSA-Approved Validation Firms and Validators for the Certified Cargo Screening Program § 1522.119 Training. (a) Initial training. The validation firm must ensure that its validators and...

78 FR 11216 - Enforcement Actions Summary

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-15

...] Enforcement Actions Summary AGENCY: Transportation Security Administration, DHS. ACTION: Notice of... an annual summary of all enforcement actions taken by TSA under the authority granted in the... public with an annual summary of all enforcement actions taken by TSA under this subsection; and include...

77 FR 12865 - Enforcement Actions Summary

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-02

...] Enforcement Actions Summary AGENCY: Transportation Security Administration, DHS. ACTION: Notice of... an annual summary of all enforcement actions taken by TSA under the authority granted in the... public with an annual summary of all enforcement actions taken by TSA under this subsection; and include...

76 FR 9357 - Enforcement Actions Summary

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-17

...] Enforcement Actions Summary AGENCY: Transportation Security Administration, DHS. ACTION: Notice of... an annual summary of all enforcement actions taken by TSA under the authority granted in the... to provide the public with an annual summary of all enforcement actions taken by TSA under this...

Patient-specific targeting guides compared with traditional instrumentation for glenoid component placement in shoulder arthroplasty: a multi-surgeon study in 70 arthritic cadaver specimens.

PubMed

Throckmorton, Thomas W; Gulotta, Lawrence V; Bonnarens, Frank O; Wright, Stephen A; Hartzell, Jeffrey L; Rozzi, William B; Hurst, Jason M; Frostick, Simon P; Sperling, John W

2015-06-01

The purpose of this study was to compare the accuracy of patient-specific guides for total shoulder arthroplasty (TSA) with traditional instrumentation in arthritic cadaver shoulders. We hypothesized that the patient-specific guides would place components more accurately than standard instrumentation. Seventy cadaver shoulders with radiographically confirmed arthritis were randomized in equal groups to 5 surgeons of varying experience levels who were not involved in development of the patient-specific guidance system. Specimens were then randomized to patient-specific guides based off of computed tomography scanning, standard instrumentation, and anatomic TSA or reverse TSA. Variances in version or inclination of more than 10° and more than 4 mm in starting point were considered indications of significant component malposition. TSA glenoid components placed with patient-specific guides averaged 5° of deviation from the intended position in version and 3° in inclination; those with standard instrumentation averaged 8° of deviation in version and 7° in inclination. These differences were significant for version (P = .04) and inclination (P = .01). Multivariate analysis of variance to compare the overall accuracy for the entire cohort (TSA and reverse TSA) revealed patient-specific guides to be significantly more accurate (P = .01) for the combined vectors of version and inclination. Patient-specific guides also had fewer instances of significant component malposition than standard instrumentation did. Patient-specific targeting guides were more accurate than traditional instrumentation and had fewer instances of component malposition for glenoid component placement in this multi-surgeon cadaver study of arthritic shoulders. Long-term clinical studies are needed to determine if these improvements produce improved functional outcomes. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Neer Award 2016: Outpatient total shoulder arthroplasty in an ambulatory surgery center is a safe alternative to inpatient total shoulder arthroplasty in a hospital: a matched cohort study.

PubMed

Brolin, Tyler J; Mulligan, Ryan P; Azar, Frederick M; Throckmorton, Thomas W

2017-02-01

Recent emphasis on safe and efficient delivery of high-quality health care has increased interest in outpatient total joint arthroplasty. The purpose of this study was to evaluate the safety of outpatient total shoulder arthroplasty (TSA) by comparing episode-of-care complications in matched cohorts of patients with anatomic TSA as an outpatient or inpatient procedure. Thirty patients with outpatient TSA at a freestanding ambulatory surgery center (ASC) were compared with an age- and comorbidities-matched cohort of 30 patients with traditional inpatient TSA to evaluate 90-day episode-of-care complications, including hospital admissions or readmissions and reoperations. Two-tailed t-tests were used to evaluate differences, and differences of P < .05 were considered statistically significant. No significant differences were found between the ASC and hospital cohorts regarding average age, preoperative American Society of Anesthesiologists score, operative indications, or body mass index. No patient required reoperation. There were no hospital admissions from the ASC cohort and no readmissions from the hospital cohort. Minor complications in the ASC cohort were arthrofibrosis in 2 patients and mild asymptomatic anterior subluxation in 1 patient; the only major complication was in an outpatient who fell 11 weeks after surgery and disrupted his subscapularis repair. Three minor complications in the hospital cohort were mild asymptomatic anterior subluxation, blood transfusion, and superficial venous thrombosis. The complication rates (13% vs. 10%) were not significantly different. Outpatient TSA is a safe alternative to hospital admission in appropriately selected patients. Further investigation is warranted to evaluate the longer term outcomes and cost-effectiveness of outpatient TSA. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

[Telomere lengthening by trichostatin A treatment in cloned pigs].

PubMed

Xie, Bing-Teng; Ji, Guang-Zhen; Kong, Qing-Ran; Mao, Jian; Shi, Yong-Qian; Liu, Shi-Chao; Wu, Mei-Ling; Wang, Juan; Liu, Lin; Liu, Zhong-Hua

2012-12-01

Telomeres are repeated GC rich sequences at the end of chromosomes, and shorten with each cell division due to DNA end replication problem. Previously, reprogrammed somatic cells of cloned animals display variable telomere elongation. However, it was reported that the cloned animals including Dolly do not reset telomeres and show premature aging. In this study, we investigated telomere function in cloned or transgenic cloned pigs, including the cloned Northeast Min pigs, eGFP, Mx, and PGC1α transgenic cloned pigs, and found that the telomere lengths of cloned pigs were significantly shorter than the nuclear donor adult fibroblasts and age-matched noncloned pigs (P<0.05), indicating that nuclear reprogramming did not restore cellular age of donor cells after somatic cell nuclear transfer (SCNT). Trichostatin A (TSA), an inhibitor of histone deacetylase, has proven to enhance the efficiency of nuclear reprogramming in several species. In order to test whether TSA also can effectively enhance reprogramming of telomeres, TSA (40 nmol/L) was used to treat porcine cloned embryos at 1-cell stage for 24 h. Consistent with previous reports, the developmental rate of SCNT embryos to the blastocyst stage was significantly increased compared with those of the control group (16.35% vs. 27.09%, 21.60% vs. 34.90%, P<0.05). Notably, the telomere length of cloned porcine blastocysts was also significantly elongated (P<0.05). Although TSA did not improve the cloning efficiency (1.3% vs. 1.7%, TSA vs. control), the telomere lengths of cloned pig-lets were significantly longer compared with those of the control group and the donor fibroblasts (P<0.05). In conclusion, telomeres have not been effectively restored by SCNT in pigs but TSA can effectively lengthen the telomere lengths of cloned pigs.

Effects of alcohol on histone deacetylase 2 (HDAC2) and the neuroprotective role of trichostatin A (TSA).

PubMed

Agudelo, Marisela; Gandhi, Nimisha; Saiyed, Zainulabedin; Pichili, Vijaya; Thangavel, Samikkannu; Khatavkar, Pradnya; Yndart-Arias, Adriana; Nair, Madhavan

2011-08-01

Previous studies have implicated histone deacetylases (HDACs) and HDAC inhibitors (HDIs) such as trichostatin A (TSA) in the regulation of gene expression during drug addiction. Furthermore, an increase in HDAC activity has been linked to neurodegeneration. Alcohol has also been shown to promote abundant generation of reactive oxygen species (ROS) resulting in oxidative stress. TSA inhibits HDACs and has been shown to be neuroprotective in other neurodegenerative disease models. Although HDACs and HDIs have been associated with drug addiction, there is no evidence of the neurodegenerative role of HDAC2 and neuroprotective role of TSA in alcohol addiction. Therefore, we hypothesize that alcohol modulates HDAC2 through mechanisms involving oxidative stress. To test our hypothesis, the human neuronal cell line, SK-N-MC, was treated with different concentrations of ethanol (EtOH); HDAC2 gene and protein expression were assessed at different time points. Pharmacological inhibition of HDAC2 with TSA was evaluated at the gene level using qRT-PCR and at the protein level using Western blot and flow cytometry. ROS production was measured with a fluorescence microplate reader and fluorescence microscopy. Our results showed a dose-dependent increase in HDAC2 expression with EtOH treatment. Additionally, alcohol significantly induced ROS, and pharmacological inhibition of HDAC2 with TSA was shown to be neuroprotective by significantly inhibiting HDAC2 and ROS. These results suggest that EtOH can upregulate HDAC2 through mechanisms involving oxidative stress and HDACs may play an important role in alcohol use disorders (AUDs). Moreover, the use of HDIs may be of therapeutic significance for the treatment of neurodegenerative disorders including AUDs. Copyright © 2011 by the Research Society on Alcoholism.

A metabolic screening study of trichostatin A (TSA) and TSA-like histone deacetylase inhibitors in rat and human primary hepatocyte cultures.

PubMed

Elaut, G; Laus, G; Alexandre, E; Richert, L; Bachellier, P; Tourwé, D; Rogiers, V; Vanhaecke, T

2007-04-01

Hydroxamic acid (HA)-based histone deacetylase (HDAC) inhibitors, with trichostatin A (TSA) as the reference compound, are potential antitumoral drugs and show promise in the creation of long-term primary cell cultures. However, their metabolic properties have barely been investigated. TSA is rapidly inactivated in rodents both in vitro and in vivo. We previously found that 5-(4-dimethylaminobenzoyl)aminovaleric acid hydroxyamide or 4-Me2N-BAVAH (compound 1) is metabolically more stable upon incubation with rat hepatocyte suspensions. In this study, we show that human hepatocytes also metabolize TSA more rapidly than compound 1 and that similar pathways are involved. Furthermore, structural analogs of compound 1 (compounds 2-9) are reported to have the same favorable metabolic properties. Removal of the dimethylamino substituent of compound 1 creates a very stable but 50% less potent inhibitor. Chain lengthening (4 to 5 carbon spacer) slightly improves both potency and metabolic stability, favoring HA reduction to hydrolysis. On the other hand, Calpha-unsaturation and spacer methylation not only reduce HDAC inhibition but also increase the rate of metabolic inactivation approximately 2-fold, mainly through HA reduction. However, in rat hepatocyte monolayer cultures, compound 1 is shown to be extensively metabolized by phase II conjugation. In conclusion, this study suggests that simple structural modifications of amide-linked TSA analogs can improve their phase I metabolic stability in both rat and human hepatocyte suspensions. Phase II glucuronidation, however, can compensate for their lower phase I metabolism in rat hepatocyte monolayers and could play a yet unidentified role in the determination of their in vivo clearance.

In vivo optimisation study for multi-baseline MR-based thermometry in the context of hyperthermia using MR-guided high intensity focused ultrasound for head and neck applications.

PubMed

Pichardo, Samuel; Köhler, Max; Lee, Justin; Hynnyen, Kullervo

2014-12-01

In this in vivo study, the feasibility to perform hyperthermia treatments in the head and neck using magnetic resonance image-guided high intensity focused ultrasound (MRgHIFU) was established using a porcine acute model. Porcine specimens with a weight between 17 and 18 kg were treated in the omohyoid muscle in the neck. Hyperthermia was applied with a target temperature of 41 °C for 30 min using a Sonalleve MRgHIFU system. MR-based thermometry was calculated using water-proton resonance frequency shift and multi-baseline look-up tables indexed by peak-to-peak displacement (Dpp) measurements using a pencil-beam navigator. Three hyperthermia experiments were conducted at different Dpp values of 0.2, 1.0 and 3.0 mm. An optimisation study was carried out to establish the optimal parameters controlling the multi-baseline method that ensured a minimisation of spatial-average peak-to-peak temperature (TSA-pp) and temperature direct current bias (TSA-DC). The multi-baseline technique reduced considerably the noise on both TSA-pp and TSA-DC. The reduction of noise was more important when Dpp was higher. For Dpp = 3 mm the average (±standard deviation (SD)) of TSA-pp and TSA-DC was reduced from 4.5 (± 2.5) and 2.5 (±0.6) °C, respectively, to 0.8 (± 0.7) and 0.09 (± 0.2) °C. This in vivo study showed the level of noise in PRFS-based thermometry introduced by respiratory motion in the context of MRgHIFU hyperthermia treatment for head and neck and the feasibility of reducing this noise using a multi-baseline technique.

78 FR 72922 - TSA Pre✓TM

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-04

... enrollment sites at airports and at off-airport locations. TSA will also explore temporary mobile enrollment at corporate offices, conferences, and other venues that choose to provide this service to their... rollout strategy. First, CBP records show that of the approximately one million annual Global Entry...

49 CFR 1554.103 - Security Directives.

Code of Federal Regulations, 2014 CFR

2014-10-01

... necessary to respond to a threat assessment or to a specific threat against civil aviation, TSA issues a..., DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRCRAFT REPAIR STATION SECURITY Security Measures... each Security Directive TSA issues to the repair station within the time prescribed. Each repair...

49 CFR 1544.207 - Screening of individuals and property.

Code of Federal Regulations, 2013 CFR

2013-10-01

...: AIR CARRIERS AND COMMERCIAL OPERATORS Operations § 1544.207 Screening of individuals and property. (a... screening using TSA employees or when using companies under contract with TSA. (c) Aircraft operator... conducting screening using government employees or when using companies under contract with the government. ...

49 CFR 1544.207 - Screening of individuals and property.

Code of Federal Regulations, 2014 CFR

2014-10-01

...: AIR CARRIERS AND COMMERCIAL OPERATORS Operations § 1544.207 Screening of individuals and property. (a... screening using TSA employees or when using companies under contract with TSA. (c) Aircraft operator... conducting screening using government employees or when using companies under contract with the government. ...

49 CFR 1544.207 - Screening of individuals and property.

Code of Federal Regulations, 2011 CFR

2011-10-01

...: AIR CARRIERS AND COMMERCIAL OPERATORS Operations § 1544.207 Screening of individuals and property. (a... screening using TSA employees or when using companies under contract with TSA. (c) Aircraft operator... conducting screening using government employees or when using companies under contract with the government. ...

A Reevaluation of Needs Analysis in ESP.

ERIC Educational Resources Information Center

Chambers, F.

1980-01-01

Proposes use of target situation analysis (TSA) as means of removing superfluous terminology and establishing different levels of need in order to realize value of needs analysis in ESP. TSA goes into situations, collects and analyzes data to establish the communication that occurs. (Author/BK)

Classroom Dialogue and Science Achievement.

ERIC Educational Resources Information Center

Clarke, John A.

This study reports the application to classroom dialogue of the Thematic and Structural Analysis (TSA) Technique which has been used previously in the analysis of text materials. The TSA Technique identifies themes (word clusters) and their structural relationship throughout sequentially organized material. Dialogues from four Year 8 science…

Telemetry Simulation Assembly Implementation in the DSN

NASA Technical Reports Server (NTRS)

Alberda, M. E.

1984-01-01

The telemetry simulation was implemented as part of the MARK IV network implementation project. The telemetry simulation assembly (TSA) is replacing the Simulation Conversion Assembly (SCA) throughout the DSN. The development of the TSA is discussed, and the design is described to the block diagram level.

49 CFR 1542.109 - Alternate means of compliance.

Code of Federal Regulations, 2011 CFR

2011-10-01

... SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY Airport Security Program § 1542.109 Alternate means of compliance. If in TSA's judgment, the overall safety and security of the airport, and aircraft operator or foreign air carrier operations are not diminished, TSA...

49 CFR 1542.109 - Alternate means of compliance.

Code of Federal Regulations, 2013 CFR

2013-10-01

... SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY Airport Security Program § 1542.109 Alternate means of compliance. If in TSA's judgment, the overall safety and security of the airport, and aircraft operator or foreign air carrier operations are not diminished, TSA...

49 CFR 1542.109 - Alternate means of compliance.

Code of Federal Regulations, 2014 CFR

2014-10-01

... SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY Airport Security Program § 1542.109 Alternate means of compliance. If in TSA's judgment, the overall safety and security of the airport, and aircraft operator or foreign air carrier operations are not diminished, TSA...

49 CFR 1542.109 - Alternate means of compliance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY Airport Security Program § 1542.109 Alternate means of compliance. If in TSA's judgment, the overall safety and security of the airport, and aircraft operator or foreign air carrier operations are not diminished, TSA...

49 CFR 1542.109 - Alternate means of compliance.

Code of Federal Regulations, 2012 CFR

2012-10-01

... SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY Airport Security Program § 1542.109 Alternate means of compliance. If in TSA's judgment, the overall safety and security of the airport, and aircraft operator or foreign air carrier operations are not diminished, TSA...

Increased alternative lengthening of telomere phenotypes of telomerase-negative immortal cells upon trichostatin--a treatment.

PubMed

Jung, A Ra; Yoo, Jeong Eun; Shim, Yhong-Hee; Choi, Ye-Na; Jeung, Hei-Cheul; Chung, Hyun Cheol; Rha, Sun Young; Oh, Bong-Kyeong

2013-03-01

Human immortal cells maintain their telomeres either by telomerase or by alternative lengthening of telomeres (ALT) that is based on homologous telomeric recombination. Previous studies showed that the ALT mechanism is activated in non-ALT cells when heterochromatic features are reduced. In this study, we examined the ALT phenotypes of ALT cells after treatment with trichostatin-A (TSA), which is an inhibitor of histone deacetylases and causes global chromatin decondensation. The ALT cells remained telomerase-negative after TSA treatment. ALT-associated promyelocytic leukemia (PML) nuclear bodies and telomere sister chromatid exchanges, typical ALT phenotypes, markedly increased in the TSA-treated cells, while the telomere length remained unchanged. In addition, telomerase expression in the ALT cells suppressed TSA-mediated ALT phenotype enhancement. Our results show that certain ALT phenotypes become more pronounced when chromatin is decondensed, and also suggest that the ALT mechanism may compete with telomerase for telomere maintenance in cells that lack heterochromatin.

77 FR 24506 - Extension of Agency Information Collection Activity Under OMB Review: Air Cargo Security...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-24

...This notice announces that the Transportation Security Administration (TSA) has forwarded the Information Collection Request (ICR), Office of Management and Budget (OMB) control number 1652-0040, abstracted below to OMB for review and approval of an extension of the currently approved collection under the Paperwork Reduction Act (PRA). The ICR describes the nature of the information collection and its expected burden. TSA published a Federal Register notice, with a 60-day comment period soliciting comments, of the following collection of information on February 24, 2012, 77 FR 11145. TSA has not received any comments. The collection of information that make up this ICR involve five broad categories affecting airports, passenger aircraft operators, foreign air carriers, indirect air carriers and all-cargo carriers operating under a TSA-approved security program. These five categories are: Security programs, security threat assessments (STAs), known shipper data via the Known Shipper Management System (KSMS), cargo screening reporting, and evidence of compliance recordkeeping.

Dual-surface dielectric depth detector for holographic millimeter-wave security scanners

NASA Astrophysics Data System (ADS)

McMakin, Douglas L.; Keller, Paul E.; Sheen, David M.; Hall, Thomas E.

2009-05-01

The Transportation Security Administration (TSA) is presently deploying millimeter-wave whole body scanners at over 20 airports in the United States. Threats that may be concealed on a person are displayed to the security operator of this scanner. "Passenger privacy is ensured through the anonymity of the image. The officer attending the passenger cannot view the image, and the officer viewing the image is remotely located and cannot see the passenger. Additionally, the image cannot be stored, transmitted or printed and is deleted immediately after being viewed. Finally, the facial area of the image has been blurred to further ensure privacy." Pacific Northwest National Laboratory (PNNL) originated research into this novel security technology which has been independently commercialized by L-3 Communications, SafeView, Inc. PNNL continues to perform fundamental research into improved software techniques which are applicable to the field of holographic security screening technology. This includes performing significant research to remove human features from the imagery. Both physical and software imaging techniques have been employed. The physical imaging techniques include polarization diversity illumination and reception, dual frequency implementation, and high frequency imaging at 100 GHz. This paper will focus on a software privacy technique using a dual surface dielectric depth detector method.

Bone Grafting the Glenoid Versus Use of Augmented Glenoid Baseplates with Reverse Shoulder Arthroplasty.

PubMed

Jones, Richard B; Wright, Thomas W; Roche, Christopher P

2015-12-01

Large glenoid defects are a difficult reconstructive problem for surgeons performing reverse shoulder arthroplasty (rTSA). Options to address glenoid defects include eccentric reaming, bone grafting, and augmented glenoid baseplates. Augmented glenoid baseplates may provide a simpler, cost-effective, bone-preserving option compared to other techniques. No studies report the use of augmented baseplates to correct glenoid deformity in rTSA relative to the use of glenoid bone graft. We retrospectively reviewed 80 patients that received a primary rTSA and received either a structural bone graft or an augmented glenoid baseplate to address a significant glenoid defect. There were 39 patients in the augmented baseplate cohort and 41 patients in the bone graft cohort. The augmented baseplate cohort contained 24 8° posterior augment implants and 15 10° superior augment baseplates. The bone graft cohort consisted of 36 autograft humeral heads and 5 allograft femoral heads. The average follow-up for rTSA patients with an augmented baseplate was 28.3 ± 5.7 months, and the average follow-up for rTSA patients with glenoid bone graft was 34.1 ± 15.0 months. Each patient was scored preoperatively and at latest follow-up using the SST, UCLA, ASES, Constant, and SPADI metrics. Range of motion data was obtained as well. All patients demonstrated significant improvements in pain, ROM, and functional scores following treatment with rTSA using either augmented baseplates or glenoid bone graft to correct glenoid defects. The database contained no complications for the augmented glenoid baseplate cohort, and six complications (14.6%) for the glenoid bone graft cohort (including two glenoid loosenings and graft failures). Additionally, the augmented baseplate cohort showed a lower scapular notching rate of 10% as compared to the bone graft cohort which had a notching rate of 18.5%. The results of this study suggest that either augmented glenoid baseplates or glenoid bone graft can be used to address large glenoid defects during rTSA with significant improvement in outcomes. Augmented glenoid baseplates may achieve a lower complication and scapular notching rate, but additional and longer-term clinical follow-up is required to confirm these results.

Trichostatin A effects on gene expression in the protozoan parasite Entamoeba histolytica

PubMed Central

Ehrenkaufer, Gretchen M; Eichinger, Daniel J; Singh, Upinder

2007-01-01

Background Histone modification regulates chromatin structure and influences gene expression associated with diverse biological functions including cellular differentiation, cancer, maintenance of genome architecture, and pathogen virulence. In Entamoeba, a deep-branching eukaryote, short chain fatty acids (SCFA) affect histone acetylation and parasite development. Additionally, a number of active histone modifying enzymes have been identified in the parasite genome. However, the overall extent of gene regulation tied to histone acetylation is not known. Results In order to identify the genome-wide effects of histone acetylation in regulating E. histolytica gene expression, we used whole-genome expression profiling of parasites treated with SCFA and Trichostatin A (TSA). Despite significant changes in histone acetylation patterns, exposure of parasites to SCFA resulted in minimal transcriptional changes (11 out of 9,435 genes transcriptionally regulated). In contrast, exposure to TSA, a more specific inhibitor of histone deacetylases, significantly affected transcription of 163 genes (122 genes upregulated and 41 genes downregulated). Genes modulated by TSA were not regulated by treatment with 5-Azacytidine, an inhibitor of DNA-methyltransferase, indicating that in E. histolytica the crosstalk between DNA methylation and histone modification is not substantial. However, the set of genes regulated by TSA overlapped substantially with genes regulated during parasite development: 73/122 genes upregulated by TSA exposure were upregulated in E. histolytica cysts (p-value = 6 × 10-53) and 15/41 genes downregulated by TSA exposure were downregulated in E. histolytica cysts (p-value = 3 × 10-7). Conclusion This work represents the first genome-wide analysis of histone acetylation and its effects on gene expression in E. histolytica. The data indicate that SCFAs, despite their ability to influence histone acetylation, have minimal effects on gene transcription in cultured parasites. In contrast, the effect of TSA on E. histolytica gene expression is more substantial and includes genes involved in the encystation pathway. These observations will allow further dissection of the effects of histone acetylation and the genetic pathways regulating stage conversion in this pathogenic parasite. PMID:17612405

Loss of vacuolar H+-ATPase (V-ATPase) activity in yeast generates an iron deprivation signal that is moderated by induction of the peroxiredoxin TSA2.

PubMed

Diab, Heba I; Kane, Patricia M

2013-04-19

Vacuolar H(+)-ATPases (V-ATPases) acidify intracellular organelles and help to regulate overall cellular pH. Yeast vma mutants lack V-ATPase activity and allow exploration of connections between cellular pH, iron, and redox homeostasis common to all eukaryotes. A previous microarray study in a vma mutant demonstrated up-regulation of multiple iron uptake genes under control of Aft1p (the iron regulon) and only one antioxidant gene, the peroxiredoxin TSA2 (Milgrom, E., Diab, H., Middleton, F., and Kane, P. M. (2007) Loss of vacuolar proton-translocating ATPase activity in yeast results in chronic oxidative stress. J. Biol. Chem. 282, 7125-7136). Fluorescent biosensors placing GFP under transcriptional control of either an Aft1-dependent promoter (P(FIT2)-GFP) or the TSA2 promoter (P(TSA2)-GFP) were constructed to monitor transcriptional signaling. Both biosensors were up-regulated in the vma2Δ mutant, and acute V-ATPase inhibition with concanamycin A induced coordinate up-regulation from both promoters. PTSA2-GFP induction was Yap1p-dependent, indicating an oxidative stress signal. Total cell iron measurements indicate that the vma2Δ mutant is iron-replete, despite up-regulation of the iron regulon. Acetic acid up-regulated P(FIT2)-GFP expression in wild-type cells, suggesting that loss of pH control contributes to an iron deficiency signal in the mutant. Iron supplementation significantly decreased P(FIT2)-GFP expression and, surprisingly, restored P(TSA2)-GFP to wild-type levels. A tsa2Δ mutation induced both nuclear localization of Aft1p and P(FIT2)-GFP expression. The data suggest a novel function for Tsa2p as a negative regulator of Aft1p-driven transcription, which is induced in V-ATPase mutants to limit transcription of the iron regulon. This represents a new mechanism bridging the antioxidant and iron-regulatory pathways that is intimately linked to pH homeostasis.

Disinfection of preexisting contamination of bacillus cereus on stainless steel when using glycoconjugate solution

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

Pavan, Casey; Tarasenko, Olga

Stainless steel is ubiquitous in our modern world, however it can become contaminated. This can endanger our health. The aim of our study is to disinfect stainless steel using Bacillus cereus as a model organism. Bacillus cereus is a microbe that is ubiquitous in nature, specifically soil. B. cereus is known to cause illness in humans. To prevent this, we propose to use a glycoconjugate solution (GS) for disinfection of stainless steel after it is contamination by B. cereus spores. In this study, two GS (9, 10) were tested for disinfection effectiveness on B. cereus spores on the surface ofmore » stainless steel foil (AISI-Series 200/300/400, THERMA-FOIL, Dayville, CT 0241). The disinfection rate of each GS was assessed by exposing the steel surface to B. cereus spores first and allowing them to settle for 24 hours. GS was used to treat the contaminated surface. The steel is washed and the resulting solution is plated on tryptic soy agar (TSA) plates. The GS with the fewest colony forming unit (CFU) formed on TSA is determined to be the most efficient during disinfection. Results show that both GS demonstrate a strong ability to disinfect B. cereus spores. Between the two, GS 9 shows the highest disinfection efficacy by killing approximately 99.5% of spores. This is a drastic improvement over the 0-20% disinfection of the control. Based on this we find that studied GS do have the capacity to act as a disinfectant on stainless steel.« less

Environmental Assessment for Construct/Demolish Dog Kennel Facility MacDill AFB, Florida

DTIC Science & Technology

2003-04-01

on-base wastewater treatment plant is applied by spray irrigation. 26 APRIL 2003 Affected Environment Environmental Assessment for Construct...undecimalis sse Plants No State or Federally listed plant species are known to exist on MacDill AFB - - T =Threatened, T(SA) Threatcncd/Stmllanty of...Base-related economic impacts. The area includes all or part of Hillsborough, Pinellas , Polk, Pasco, Hardee, Manatee, Sarasota, and DeSoto Counties

76 FR 44944 - Intent To Request Renewal From OMB of One Current Public Collection of Information: TSA Airspace...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-27

...The Transportation Security Administration (TSA) invites public comment on one currently approved Information Collection Request (ICR), Office of Management and Budget (OMB) control number 1652-0033, abstracted below that we will submit to OMB for renewal in compliance with the Paperwork Reduction Act (PRA). The ICR describes the nature of the information collection and its expected burden. This collection of information allows TSA to conduct security threat assessments on individuals on board aircraft operating in restricted airspace pursuant to an airspace waiver. This collection will enhance aviation security and protect assets on the ground that are within the restricted airspace.

77 FR 31866 - Intent To Request Approval From OMB of One New Public Collection of Information: Baseline...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-30

... (BASE) Program for Public Transportation Systems AGENCY: Transportation Security Administration, DHS. ACTION: 60-day Notice. SUMMARY: The Transportation Security Administration (TSA) invites public comment... under contract with a public transportation agency. \\1\\ TSA, ``Transportation Sector-Specific Plan Mass...

49 CFR 1549.109 - Security Directives and Information Circulars.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Security Directives and Information Circulars... SCREENING PROGRAM Operations § 1549.109 Security Directives and Information Circulars. (a) TSA may issue an Information Circular to notify certified cargo screening facilities of security concerns. (b) When TSA...

49 CFR 1544.205 - Acceptance and screening of cargo.

Code of Federal Regulations, 2013 CFR

2013-10-01

... provided in its security program. Such methods may include TSA-approved x-ray systems, explosives detection systems, explosives trace detection, explosives detection canine teams certified by TSA, or a physical...) Preventing or deterring the carriage of any explosive or incendiary. Each aircraft operator operating under a...

49 CFR 1544.205 - Acceptance and screening of cargo.

Code of Federal Regulations, 2011 CFR

2011-10-01

... provided in its security program. Such methods may include TSA-approved x-ray systems, explosives detection systems, explosives trace detection, explosives detection canine teams certified by TSA, or a physical...) Preventing or deterring the carriage of any explosive or incendiary. Each aircraft operator operating under a...

49 CFR 1544.205 - Acceptance and screening of cargo.

Code of Federal Regulations, 2012 CFR

2012-10-01

... provided in its security program. Such methods may include TSA-approved x-ray systems, explosives detection systems, explosives trace detection, explosives detection canine teams certified by TSA, or a physical...) Preventing or deterring the carriage of any explosive or incendiary. Each aircraft operator operating under a...

49 CFR 1544.205 - Acceptance and screening of cargo.

Code of Federal Regulations, 2014 CFR

2014-10-01

... provided in its security program. Such methods may include TSA-approved x-ray systems, explosives detection systems, explosives trace detection, explosives detection canine teams certified by TSA, or a physical...) Preventing or deterring the carriage of any explosive or incendiary. Each aircraft operator operating under a...

49 CFR 1522.103 - Requirements for validation firms.

Code of Federal Regulations, 2010 CFR

2010-10-01

... firm's security program. (e) Change in information. (1) The validation firm must inform TSA, in a form... 49 Transportation 9 2010-10-01 2010-10-01 false Requirements for validation firms. 1522.103...-APPROVED VALIDATION FIRMS AND VALIDATORS TSA-Approved Validation Firms and Validators for the Certified...

Benefits of State-by-State Comparisons.

ERIC Educational Resources Information Center

Phillips, Gary W.

1991-01-01

Suggests that the National Assessment of Educational Progress's (NAEP) Trial State Assessment (TSA) will provide reliable and valid state-by-state comparisons of what students have learned and will assess their progress over time. The TSA will also provide information on home learning environments, instructional practices, educational resources,…

Learn, Grow, Become. TSA Edition.

ERIC Educational Resources Information Center

Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

This revised curriculum guide contains five units that are designed to help students develop an understanding of the mission of the Technology Student Association (TSA). Each unit follows a standard format that includes some or all of these basic components: performance objectives, suggested activities, handouts, information sheets, supplements,…

49 CFR 1544.207 - Screening of individuals and property.

Code of Federal Regulations, 2010 CFR

2010-10-01

... screening using TSA employees or when using companies under contract with TSA. (c) Aircraft operator... conducting screening using government employees or when using companies under contract with the government. ... 49 Transportation 9 2010-10-01 2010-10-01 false Screening of individuals and property. 1544.207...

78 FR 55274 - Privacy Act of 1974; Department of Homeland Security/Transportation Security Administration-DHS...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-10

... enforcement, immigration, and intelligence databases, including a fingerprint-based criminal history records... boarding pass printing instruction. If the passenger's identifying information matches the entry on the TSA... enforcement, immigration, intelligence, or other homeland security functions. In addition, TSA may share...

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

Kishigami, Satoshi; Mizutani, Eiji; Ohta, Hiroshi

The low success rate of animal cloning by somatic cell nuclear transfer (SCNT) is believed to be associated with epigenetic errors including abnormal DNA hypermethylation. Recently, we elucidated by using round spermatids that, after nuclear transfer, treatment of zygotes with trichostatin A (TSA), an inhibitor of histone deacetylase, can remarkably reduce abnormal DNA hypermethylation depending on the origins of transferred nuclei and their genomic regions [S. Kishigami, N. Van Thuan, T. Hikichi, H. Ohta, S. Wakayama. E. Mizutani, T. Wakayama, Epigenetic abnormalities of the mouse paternal zygotic genome associated with microinsemination of round spermatids, Dev. Biol. (2005) in press]. Here,more » we found that 5-50 nM TSA-treatment for 10 h following oocyte activation resulted in more efficient in vitro development of somatic cloned embryos to the blastocyst stage from 2- to 5-fold depending on the donor cells including tail tip cells, spleen cells, neural stem cells, and cumulus cells. This TSA-treatment also led to more than 5-fold increase in success rate of mouse cloning from cumulus cells without obvious abnormality but failed to improve ES cloning success. Further, we succeeded in establishment of nuclear transfer-embryonic stem (NT-ES) cells from TSA-treated cloned blastocyst at a rate three times higher than those from untreated cloned blastocysts. Thus, our data indicate that TSA-treatment after SCNT in mice can dramatically improve the practical application of current cloning techniques.« less

Development and validation of a gas chromatography/mass spectrometry procedure for confirmation of para-toluenesulfonamide in edible fish fillet tissue

USGS Publications Warehouse

Idowu, O.R.; Kijak, P.J.; Meinertz, J.R.; Schmidt, L.J.

2004-01-01

Chloramine-T is a disinfectant being developed as a treatment for bacterial gill disease in cultured fish. As part of the drug approval process, a method is required for the confirmation of chloramine-T residues in edible fish tissue. The marker residue that will be used to determine the depletion of chloramine-T residues from the edible tissue of treated fish is para-toluenesulfonamide (p-TSA), a metabolite of chloramine-T. The development and validation of a procedure for the confirmation of p-TSA is described. Homogenized fish tissue is dried by mixing with anhydrous sodium sulfate, and the mixture is extracted with methylene chloride. The extract is passed through a silica gel solid-phase extraction column, from which p-TSA is subsequently eluted with acetonitrile. The acetonitrile extract is evaporated, and the oily residue is dissolved in hexane. The hexane solution is shaken with fresh acetonitrile. The acetonitrile solution is evaporated and the residue is redissolved in dilute potassium hydroxide solution. The aqueous solution is extracted with methylene chloride to further remove more of the fat co-extractive. The aqueous solution is reacted with pentafluorobenzyl bromide in presence of tetrabutylammonium hydrogensulfate. The resulting di-(pentafluorobenzyl) derivative of p-TSA is analyzed by gas chromatography/mass spectrometry. This method permits the confirmation of p-TSA in edible fish tissue at 20 ppb.

Development and validation of a gas chromatography/mass spectrometry procedure for confirmation of para-toluenesulfonamide in edible fish fillet tissue.

PubMed

Idowu, Olutosin R; Kijak, Philip J; Meinertz, Jeffery R; Schmidt, Larry J

2004-01-01

Chloramine-T is a disinfectant being developed as a treatment for bacterial gill disease in cultured fish. As part of the drug approval process, a method is required for the confirmation of chloramine-T residues in edible fish tissue. The marker residue that will be used to determine the depletion of chloramine-T residues from the edible tissue of treated fish is para-toluenesulfonamide (p-TSA), a metabolite of chloramine-T. The development and validation of a procedure for the confirmation of p-TSA is described. Homogenized fish tissue is dried by mixing with anhydrous sodium sulfate, and the mixture is extracted with methylene chloride. The extract is passed through a silica gel solid-phase extraction column, from which p-TSA is subsequently eluted with acetonitrile. The acetonitrile extract is evaporated, and the oily residue is dissolved in hexane. The hexane solution is shaken with fresh acetonitrile. The acetonitrile solution is evaporated and the residue is redissolved in dilute potassium hydroxide solution. The aqueous solution is extracted with methylene chloride to further remove more of the fat co-extractive. The aqueous solution is reacted with pentafluorobenzyl bromide in presence of tetrabutylammonium hydrogensulfate. The resulting di-(pentafluorobenzyl) derivative of p-TSA is analyzed by gas chromatography/mass spectrometry. This method permits the confirmation of p-TSA in edible fish tissue at 20 ppb.

Return to sports after shoulder arthroplasty

PubMed Central

Johnson, Christine C; Johnson, Daniel J; Liu, Joseph N; Dines, Joshua S; Dines, David M; Gulotta, Lawrence V; Garcia, Grant H

2016-01-01

Many patients prioritize the ability to return to sports following shoulder replacement surgeries, including total shoulder arthroplasty (TSA), reverse total shoulder arthroplasty (RTSA), and hemiarthroplasty (HA). While activity levels after hip and knee replacements have been well-established in the literature, studies on this topic in the field of shoulder arthroplasty are relatively limited. A review of the literature regarding athletic activity after shoulder arthroplasty was performed using the PubMed database. All studies relevant to shoulder arthroplasty and return to sport were included. The majority of patients returned to their prior level of activity within six months following TSA, RTSA, and shoulder HA. Noncontact, low demand activities are permitted by most surgeons postoperatively and generally have higher return rates than contact sports or high-demand activities. In some series, patients reported an improvement in their ability to participate in sports following the arthroplasty procedure. The rates of return to sports following TSA (75%-100%) are slightly higher than those reported for HA (67%-76%) and RTSA (75%-85%). Patients undergoing TSA, RTSA, and shoulder HA should be counseled that there is a high probability that they will be able to return to their preoperative activity level within six months postoperatively. TSA has been associated with higher rates of return to sports than RTSA and HA, although this may reflect differences in patient population or surgical indication. PMID:27672564

49 CFR 1562.23 - Aircraft operator and passenger requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... United States. (vi) Alien registration number, if applicable. (3) Must successfully complete a TSA... naturalization if the individual is a naturalized citizen of the United States. (F) Alien registration number, if... crewmember on an aircraft operating into or out of DCA provides TSA with a valid government-issued picture...

49 CFR 1562.23 - Aircraft operator and passenger requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... United States. (vi) Alien registration number, if applicable. (3) Must successfully complete a TSA... naturalization if the individual is a naturalized citizen of the United States. (F) Alien registration number, if... crewmember on an aircraft operating into or out of DCA provides TSA with a valid government-issued picture...

Biological control of tropical soda apple (Solanaceae) in Florida: Post-release evaluation

USDA-ARS?s Scientific Manuscript database

The leaf feeding beetle Gratiana boliviana Spaeth (Coleoptera: Chrysomelidae) was released as a biological control agent against tropical soda apple (TSA) (Solanum viarum Dunal (Solanaceae)) in Sumter County, FL in 2006. Evaluation of beetle feeding damage to TSA plants and changes in the beetle po...

49 CFR 1542.219 - Supplementing law enforcement personnel.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Supplementing law enforcement personnel. 1542.219... Operations § 1542.219 Supplementing law enforcement personnel. (a) When TSA decides, after being notified by... private law enforcement personnel are available to carry out the requirements of § 1542.215, TSA may...

49 CFR 1546.205 - Acceptance and screening of cargo.

Code of Federal Regulations, 2014 CFR

2014-10-01

... in its security program. Such methods may include TSA-approved x-ray systems, explosives detection systems, explosives trace detection, explosives detection canine teams certified by TSA, a physical search... of any explosive or incendiary. Each foreign air carrier operating a program under § 1546.101(a), (b...

49 CFR 1546.205 - Acceptance and screening of cargo.

Code of Federal Regulations, 2012 CFR

2012-10-01

... in its security program. Such methods may include TSA-approved x-ray systems, explosives detection systems, explosives trace detection, explosives detection canine teams certified by TSA, a physical search... of any explosive or incendiary. Each foreign air carrier operating a program under § 1546.101(a), (b...

49 CFR 1546.205 - Acceptance and screening of cargo.

Code of Federal Regulations, 2013 CFR

2013-10-01

... in its security program. Such methods may include TSA-approved x-ray systems, explosives detection systems, explosives trace detection, explosives detection canine teams certified by TSA, a physical search... of any explosive or incendiary. Each foreign air carrier operating a program under § 1546.101(a), (b...

49 CFR 1546.205 - Acceptance and screening of cargo.

Code of Federal Regulations, 2011 CFR

2011-10-01

... in its security program. Such methods may include TSA-approved x-ray systems, explosives detection systems, explosives trace detection, explosives detection canine teams certified by TSA, a physical search... of any explosive or incendiary. Each foreign air carrier operating a program under § 1546.101(a), (b...

78 FR 13075 - Intent To Request Renewal From OMB of One Current Public Collection of Information: Pipeline...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-26

... From OMB of One Current Public Collection of Information: Pipeline Corporate Security Review Program... current security practices in the pipeline industry by way of TSA's Pipeline Corporate Security Review... Collection Requirement The TSA Pipeline Security Branch is responsible for conducting Pipeline Corporate...

49 CFR 1549.7 - Approval, amendment, renewal of the security program and certification of a certified cargo...

Code of Federal Regulations, 2010 CFR

2010-10-01

... information requested by TSA concerning Security Threat Assessments. (viii) A statement acknowledging and ensuring that each individual will successfully complete a Security Threat Assessment under § 1549.111... Security Coordinator for an applicant successfully completes a security threat assessment, TSA will provide...

Learn, Grow, Become. TSA Edition. Second Edition.

ERIC Educational Resources Information Center

Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

This curriculum guide contains seven Technology Student Association (TSA) units of study for secondary students. The units focus on helping students to develop and apply social, civic, and technology-related skills and achieve course competencies in applied technology courses. Each of the instructional units includes some or all of the basic…

Breaking Boundaries and Sparking Enthusiasm with TSA

ERIC Educational Resources Information Center

Hess, Timothy R.

2010-01-01

The Technology Student Association (TSA) provides opportunities for all students who excel in technology education classes. It is really an excellent way to enrich one's classroom--utilizing the resources of an organization that promotes the importance of technological literacy. In this article, the author presents the benefits for initiating a…

49 CFR 1503.419 - Order Assessing Civil Penalty.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 9 2013-10-01 2013-10-01 false Order Assessing Civil Penalty. 1503.419 Section... AND ENFORCEMENT PROCEDURES Assessment of Civil Penalties by TSA § 1503.419 Order Assessing Civil Penalty. (a) Issuance pursuant to a settlement. TSA will issue an Order Assessing Civil Penalty if the...

75 FR 44974 - Intent To Request Renewal From OMB of One Current Public Collection of Information: Sensitive...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-30

... TSA PRA Officer, Office of Information Technology (OIT), TSA-11, Transportation Security... technological collection techniques or other forms of information technology. Information Collection Requirement... history records check (CHRC), (2) a name-based check to determine whether the individual poses or is...

78 FR 54266 - Intent To Request Renewal From OMB of One Current Public Collection of Information: Department of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-03

... delivered to the TSA PRA Officer, Office of Information Technology (OIT), TSA-11, Transportation Security... technological collection techniques or other forms of information technology. Information Collection Requirement... Protection, U.S. Citizenship and Immigration Services, Office of Biometric Information Management, Office of...

Separation and Conditioning of Mars Atmospheric Gases via TSA

NASA Technical Reports Server (NTRS)

Finn, John E.; Luna, Bernadette (Technical Monitor)

2000-01-01

Space and planetary exploration almost always presents interesting and unusual engineering challenges. Separations engineering for chemical processes that are critical to humans working in space is no exception. The challenges are becoming clearer as we make the transition from concepts and planning to hardware development, and as we understand better the constraints and environments in which the processes must perform. The coming decade will see a robotic Mars exploration program that has recovered from recent setbacks and is building a knowledge and technology base for human exploration. One of the missions will carry a small chemical pilot plant for demonstrating the manufacture of rocket propellants and life support consumables from the low-pressure (0.01 atm) Martian atmosphere. By manufacturing and storing the fuel and consumables needed for human-return missions in situ, launch mass and landed mass are reduced by tons and missions become far less expensive. The front-end to the pilot plant is a solid-state atmosphere acquisition and separation unit based on temperature-swing adsorption (TSA). The unit produces purified and pressurized (to 1.0 atm) carbon dioxide to downstream reactors that will make methane and oxygen. The unit also produces a nitrogen-argon mixture as a valuable by-product for life support, inflatable structures, and propellant pressurization. With nighttime temperatures falling to -100 degrees C, power availability restricted to a few watts, and flawless operation critical to success, the dusty Martian surface is a difficult place to operate a remote plant. This talk will focus on how this TSA separation process is designed and implemented for this application, and how it might be used in the more distant future for human exploration.

Sonochemical surface functionalization of exfoliated LDH: Effect on textural properties, CO2 adsorption, cyclic regeneration capacities and subsequent gas uptake for simultaneous methanol synthesis.

PubMed

Ezeh, Collins I; Huang, Xiani; Yang, Xiaogang; Sun, Cheng-Gong; Wang, Jiawei

2017-11-01

To improve CO 2 adsorption, amine modified Layered double hydroxide (LDH) were prepared via a two stage process, SDS/APTS intercalation was supported by ultrasonic irradiation and then followed by MEA extraction. The prepared samples were characterised using Scanning electron microscope-Energy dispersive X-ray spectroscopy (SEM-EDX), X-ray Photoelectron Spectroscopy (XPS), X-ray diffraction (XRD), Temperature Programmed Desorption (TPD), Brunauer-Emmett-Teller (BET), and Thermogravimetric analysis (TGA), respectively. The characterisation results were compared with those obtained using the conventional preparation method with consideration to the effect of sonochemical functionalization on textural properties, adsorption capacity, regeneration and lifetime of the LDH adsorbent. It is found that LDHs prepared by sonochemical modification had improved pore structure and CO 2 adsorption capacity, depending on sonic intensity. This is attributed to the enhanced deprotonation of activated amino functional groups via the sonochemical process. Subsequently, this improved the amine loading and effective amine efficiency by 60% of the conventional. In addition, the sonochemical process improved the thermal stability of the adsorbent and also, reduced the irreversible CO 2 uptake, CUirrev, from 0.18mmol/g to 0.03mmol/g. Subsequently, improving the lifetime and ease of regenerating the adsorbent respectively. This is authenticated by subjecting the prepared adsorbents to series of thermal swing adsorption (TSA) cycles until its adsorption capacity goes below 60% of the original CO 2 uptake. While the conventional adsorbent underwent a 10 TSA cycles before breaking down, the sonochemically functionalized LDH went further than 30 TSA cycles. Copyright © 2017 Elsevier B.V. All rights reserved.

Reverse Shoulder Arthroplasty Prosthesis Design Classification System.

PubMed

Routman, Howard D; Flurin, Pierre-Henri; Wright, Thomas W; Zuckerman, Joseph D; Hamilton, Matthew A; Roche, Christopher P

2015-12-01

Multiple different reverse total shoulder arthroplasty (rTSA) prosthesis designs are available in the global marketplace for surgeons to perform this growing procedure. Subtle differences in rTSA prosthesis design parameters have been shown to have significant biomechanical impact and clinical consequences. We propose an rTSA prosthesis design classification system to objectively identify and categorize different designs based upon their specific glenoid and humeral prosthetic characteristics for the purpose of standardizing nomenclature that will help the orthopaedic surgeon determine which combination of design configurations best suit a given clinical scenario. The impact of each prosthesis classification type on shoulder muscle length and deltoid wrapping are also described to illustrate how each prosthesis classification type impacts these biomechanical parameters.

76 FR 27656 - Intent To Request Renewal From OMB of One Current Public Collection of Information: Flight Crew...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-12

... From OMB of One Current Public Collection of Information: Flight Crew Self-Defense Training... eligibility to participate in voluntary advanced self-defense training provided by TSA. Eligible training...), TSA is required to develop and provide a voluntary advanced self-defense training program for flight...

77 FR 70792 - Privacy Act of 1974; Retirement of Department of Homeland Security Transportation Security...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-27

... from its inventory of record systems. TSA will rely upon DHS/ALL-017 General Legal Records (November 23, 2011, 76 FR 72428) to cover its legal activities. Eliminating the system of records notice DHS/TSA-009... Department of Homeland Security Transportation Security Administration System of Records AGENCY: Privacy...

49 CFR 1522.115 - Renewal of TSA approval.

Code of Federal Regulations, 2010 CFR

2010-10-01

... operate as a validation firm. If the validation firm submits the information in the month before or after it is due, the validation firm is considered to have submitted the information in the month it is due... application. (b) Content. In addition to any other information required by TSA, the validation firm must...

The Effect of Topical Structure Analysis Instruction on University Students' Writing Quality

ERIC Educational Resources Information Center

Liangprayoon, Somlak; Chaya, Walaiporn; Thep-ackraphong, Tipa

2013-01-01

Coherence is considered one of the characteristics of effective writing. Topical structure analysis (TSA) has been taught to students as a revision strategy to raise their awareness of importance of textual coherence and helps them clearly understand its concept. This study aimed to investigate the effectiveness of TSA instruction in improving…

49 CFR 1546.103 - Form, content, and availability of security program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... security program is acceptable only if TSA finds that the security program provides a level of protection similar to the level of protection provided by U.S. aircraft operators serving the same airports. Foreign... the same airport, if TSA determines that such procedures are necessary to provide a similar level of...

The Application of Morpho-Syntactic Language Processing to Effective Phrase Matching.

ERIC Educational Resources Information Center

Sheridan, Paraic; Smeaton, Alan F.

1992-01-01

Describes a process of morpho-syntactic language analysis for information retrieval. Tree Structured Analytics (TSA) used for text representation is summarized; the matching process developed for such structures is outlined with an example appended; and experiments carried out to evaluate the effectiveness of TSA matching are discussed. (26…

Student Perceptions of Selected Technology Student Association Activities

ERIC Educational Resources Information Center

Taylor, Jerianne S.

2006-01-01

The Technology Student Association (TSA) is the only student organization dedicated exclusively to students enrolled in technology education classes in grades K-12. The effect that TSA has on a student member is often difficult to document. It is only through direct interaction with the student that these effects can be recorded; this in turn…

The Measurement of Motor Skill Assemblages and Successful Selection

ERIC Educational Resources Information Center

Worrall, N. R.

1974-01-01

This paper defines the required abilities for a given job as a Task Skill Assemblage (TSA), and the stored skill and knowledge is possessed by a candidate for that job as the Personal Skill Assemblage (PSA). A method is suggested for measuring the degree of match between the TSA and PSA. (Author)

49 CFR 1546.209 - Use of X-ray systems.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 9 2012-10-01 2012-10-01 false Use of X-ray systems. 1546.209 Section 1546.209... Use of X-ray systems. (a) TSA authorization required. No foreign air carrier may use any X-ray system... security program. TSA authorizes foreign air carriers to use X-ray systems for inspecting accessible...

75 FR 57049 - Extension of Agency Information Collection Activity Under OMB Review: Office of Law Enforcement...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-17

... their mental health history. DATES: Send your comments by October 18, 2010. A comment to OMB is most... INFORMATION CONTACT: Joanna Johnson, TSA PRA Officer, Office of Information Technology (OIT), TSA-11... other forms of information technology. Information Collection Requirement Title: Office of Law...

Is nothing sacred?

USGS Publications Warehouse

Hoffman, G.L.

1980-01-01

N-sodium-N-chloro-rho-toluenesulfonamide (chloramine-T) effectively controls bacterial gill disease (BGD) in cultured fishes, BGD, a common disease of hatchery-reared salmonids, causes more fish losses than any other disease among these species, This study describes a liquid chromatographic (LC) method that is capable of direct, simultaneous analysis of chloramine-T and its primary degradation product, rho-toluenesulfonamide (rho-TSA), in water. The procedure involves reversed-phase (C-18) LC analysis with ion suppression, using 0.01 M phosphate buffer at pH 3. The mobile phase is phosphate buffer-acetonitrile (60 + 40) at 1 mL/min. Both chemicals can be detected with a UV spectrophotometer at 229 nm; the method is linear up to 40 mg, chloramine-T or rho-TSA/L. Mean recoveries were 96.4 +/- 6.1% for water samples fortified with 0.03 mg chloramine-T/L and 95.3 +/- 4.6% for water samples fortified with 0.005 mg rho-TSA/L. Limits of detection without sample enrichment for chloramine-T and rho-TSA are 0.01 mg/L and 0.001 mg/L, respectively.

Liquid chromatographic determination of chloramine-T and its primary degradation product, p-toluenesulfonamide, in water

USGS Publications Warehouse

Dawson, Verdel K.; Davis, Ruth A.

1997-01-01

N-sodium-N-chloro-rho-toluenesulfonamide (chloramine-T) effectively controls bacterial gill disease (BGD) in cultured fishes, BGD, a common disease of hatchery-reared salmonids, causes more fish losses than any other disease among these species. This study describes a liquid chromatographic (LC) method that is capable of direct, simultaneous analysis of chloramine-T and its primary degradation product, rho-toluenesulfonamide (rho-TSA), in water. The procedure involves reversed-phase (C-18) LC analysis with ion suppression, using 0.01 M phosphate buffer at pH 3. The mobile phase is phosphate buffer-acetonitrile (60 + 40) at 1 mL/min. Both chemicals can be detected with a UV spectrophotometer at 229 nm; the method is linear up to 40 mg, chloramine-T or rho-TSA/L. Mean recoveries were 96.4 +/- 6.1% for water samples fortified with 0.03 mg chloramine-T/L and 95.3 +/- 4.6% for water samples fortified with 0.005 mg rho-TSA/L. Limits of detection without sample enrichment for chloramine-T and rho-TSA are 0.01 mg/L and 0.001 mg/L, respectively.

Liquid chromatographic determination of chloramine-T and its primary degradation product, p-toluenesulfonamide, in water

USGS Publications Warehouse

Dawson, V.K.; Davis, R.A.

1997-01-01

N-sodium-N-chloro-rho-toluenesulfonamide (chloramine-T) effectively controls bacterial gill disease (BGD) in cultured fishes, BGD, a common disease of hatchery-reared salmonids, causes more fish losses than any other disease among these species, This study describes a liquid chromatographic (LC) method that is capable of direct, simultaneous analysis of chloramine-T and its primary degradation product, rho-toluenesulfonamide (rho-TSA), in water. The procedure involves reversed-phase (C-18) LC analysis with ion suppression, using 0.01 M phosphate buffer at pH 3. The mobile phase is phosphate buffer-acetonitrile (60 + 40) at 1 mL/min. Both chemicals can be detected with a UV spectrophotometer at 229 nm; the method is linear up to 40 mg, chloramine-T or rho-TSA/L. Mean recoveries were 96.4 +/- 6.1% for water samples fortified with 0.03 mg chloramine-T/L and 95.3 +/- 4.6% for water samples fortified with 0.005 mg rho-TSA/L. Limits of detection without sample enrichment for chloramine-T and rho-TSA are 0.01 mg/L and 0.001 mg/L, respectively.

TSA-induced JMJD2B downregulation is associated with cyclin B1-dependent survivin degradation and apoptosis in LNCap cells.

PubMed

Zhu, Shan; Li, Yueyang; Zhao, Li; Hou, Pingfu; Shangguan, Chenyan; Yao, Ruosi; Zhang, Weina; Zhang, Yu; Tan, Jiang; Huang, Baiqu; Lu, Jun

2012-07-01

Histone deacetylase (HDAC) inhibitors are emerging as a novel class of anti-tumor agents and have manifested the ability to induce apoptosis of cancer cells, and a significant number of genes have been identified as potential effectors responsible for HDAC inhibitor-induced apoptosis. However, the mechanistic actions of these HDAC inhibitors in this process remain largely undefined. We here report that the treatment of LNCap prostate cancer cells with HDAC inhibitor trichostatin A (TSA) resulted in downregulation of the Jumonji domain-containing protein 2B (JMJD2B). We also found that the TSA-mediated decrease in survivin expression in LNCap cells was partly attributable to downregulation of JMJD2B expression. This effect was attributable to the promoted degradation of survivin protein through inhibition of Cyclin B1/Cdc2 complex-mediated survivin Thr34 phosphorylation. Consequently, knockdown of JMJD2B enhanced TSA-induced apoptosis by regulating the Cyclin B1-dependent survivin degradation to potentiate the apoptosis pathways. Copyright © 2012 Wiley Periodicals, Inc.

[Effect of TSA and VPA treatment on long-tailed macaque (Macaca fascicularis)-pig interspecies somatic cell nuclear transfer].

PubMed

Qin, Zu-Xing; Huang, Gao-Bo; Luo, Jun; Ning, Shu-Fang; Lu, Sheng-Sheng; Lu, Ke-Huan

2012-03-01

Long-tailed macaque-pig interspecies somatic cell nuclear transfer (iSCNT) is beneficial to yield embryonic stem cells from iSCNT embryos with similar genetic background as human, which can be used as materials for medical and basic research. The primary objective of this study was to investigate the effects of concentrations and treatment duration of two histone deacetylase inhibitors-Trichostatin A (TSA) and Valproic acid (VPA) and two different embryo culture media (PZM-3 and HECM-10) on the in vitro development of iSCNT embryos. The results suggested that when PZM-3 was used as the embryo culture medium, the blastocyst rate of 10 nmol/L TSA treatment for 48 h was significantly higher than the control group (22.78% vs 9.86%, P< 0.05). However, neither in PZM-3 nor in HECM-10, 2-10 mmol/L VPA treatment did not increase the in vitro developmental potential of iSCNT embryos. It was concluded that TSA treatment could enhance the in vitro developmental potential of long-tailed macaque-pig iSCNT embryos.

Web Page Content and Quality Assessed for Shoulder Replacement.

PubMed

Matthews, John R; Harrison, Caitlyn M; Hughes, Travis M; Dezfuli, Bobby; Sheppard, Joseph

2016-01-01

The Internet has become a major source for obtaining health-related information. This study assesses and compares the quality of information available online for shoulder replacement using medical (total shoulder arthroplasty [TSA]) and nontechnical (shoulder replacement [SR]) terminology. Three evaluators reviewed 90 websites for each search term across 3 search engines (Google, Yahoo, and Bing). Websites were grouped into categories, identified as commercial or noncommercial, and evaluated with the DISCERN questionnaire. Total shoulder arthroplasty provided 53 unique sites compared to 38 websites for SR. Of the 53 TSA websites, 30% were health professional-oriented websites versus 18% of SR websites. Shoulder replacement websites provided more patient-oriented information at 48%, versus 45% of TSA websites. In total, SR websites provided 47% (42/90) noncommercial websites, with the highest number seen in Yahoo, compared with TSA at 37% (33/90), with Google providing 13 of the 33 websites (39%). Using the nonmedical terminology with Yahoo's search engine returned the most noncommercial and patient-oriented websites. However, the quality of information found online was highly variable, with most websites being unreliable and incomplete, regardless of search term.

Histone Deacetylase Inhibitor Trichostatin A Ameliorated Endotoxin-Induced Neuroinflammation and Cognitive Dysfunction

PubMed Central

Chen, Yeong-Chang; Wei, Tsui-Shan; Sun, Ding-Ping; Wang, Jhi-Joung; Yeh, Ching-Hua

2015-01-01

Excessive production of cytokines by microglia may cause cognitive dysfunction and long-lasting behavioral changes. Activating the peripheral innate immune system stimulates cytokine secretion in the central nervous system, which modulates cognitive function. Histone deacetylases (HDACs) modulate cytokine synthesis and release. Trichostatin A (TSA), an HDAC inhibitor, is documented to be anti-inflammatory and neuroprotective. We investigated whether TSA reduces lipopolysaccharide- (LPS-) induced neuroinflammation and cognitive dysfunction. ICR mice were first intraperitoneally (i.p.) injected with vehicle or TSA (0.3 mg/kg). One hour later, they were injected (i.p.) with saline or Escherichia coli LPS (1 mg/kg). We analyzed the food and water intake, body weight loss, and sucrose preference of the injected mice and then determined the microglia activation and inflammatory cytokine expression in the brains of LPS-treated mice and LPS-treated BV-2 microglial cells. In the TSA-pretreated mice, microglial activation was lower, anhedonia did not occur, and LPS-induced cognitive dysfunction (anorexia, weight loss, and social withdrawal) was attenuated. Moreover, mRNA expression of HDAC2, HDAC5, indoleamine 2,3-dioxygenase (IDO), TNF-α, MCP-1, and IL-1β in the brain of LPS-challenged mice and in the LPS-treated BV-2 microglial cells was lower. TSA diminished LPS-induced inflammatory responses in the mouse brain and modulated the cytokine-associated changes in cognitive function, which might be specifically related to reducing HDAC2 and HDAC5 expression. PMID:26273133

Significant improvement of mouse cloning technique by treatment with trichostatin A after somatic nuclear transfer.

PubMed

Kishigami, Satoshi; Mizutani, Eiji; Ohta, Hiroshi; Hikichi, Takafusa; Thuan, Nguyen Van; Wakayama, Sayaka; Bui, Hong-Thuy; Wakayama, Teruhiko

2006-02-03

The low success rate of animal cloning by somatic cell nuclear transfer (SCNT) is believed to be associated with epigenetic errors including abnormal DNA hypermethylation. Recently, we elucidated by using round spermatids that, after nuclear transfer, treatment of zygotes with trichostatin A (TSA), an inhibitor of histone deacetylase, can remarkably reduce abnormal DNA hypermethylation depending on the origins of transferred nuclei and their genomic regions [S. Kishigami, N. Van Thuan, T. Hikichi, H. Ohta, S. Wakayama. E. Mizutani, T. Wakayama, Epigenetic abnormalities of the mouse paternal zygotic genome associated with microinsemination of round spermatids, Dev. Biol. (2005) in press]. Here, we found that 5-50 nM TSA-treatment for 10 h following oocyte activation resulted in more efficient in vitro development of somatic cloned embryos to the blastocyst stage from 2- to 5-fold depending on the donor cells including tail tip cells, spleen cells, neural stem cells, and cumulus cells. This TSA-treatment also led to more than 5-fold increase in success rate of mouse cloning from cumulus cells without obvious abnormality but failed to improve ES cloning success. Further, we succeeded in establishment of nuclear transfer-embryonic stem (NT-ES) cells from TSA-treated cloned blastocyst at a rate three times higher than those from untreated cloned blastocysts. Thus, our data indicate that TSA-treatment after SCNT in mice can dramatically improve the practical application of current cloning techniques.

Combinatorial Therapy with Acetylation and Methylation Modifiers Attenuates Lung Vascular Hyperpermeability in Endotoxemia-Induced Mouse Inflammatory Lung Injury

PubMed Central

Thangavel, Jayakumar; Malik, Asrar B.; Elias, Harold K.; Rajasingh, Sheeja; Simpson, Andrew D.; Sundivakkam, Premanand K.; Vogel, Stephen M.; Xuan, Yu-Ting; Dawn, Buddhadeb; Rajasingh, Johnson

2015-01-01

Impairment of tissue fluid homeostasis and migration of inflammatory cells across the vascular endothelial barrier are crucial factors in the pathogenesis of acute lung injury (ALI). The goal for treatment of ALI is to target pathways that lead to profound dysregulation of the lung endothelial barrier. Although studies have shown that chemical epigenetic modifiers can limit lung inflammation in experimental ALI models, studies to date have not examined efficacy of a combination of DNA methyl transferase inhibitor 5-Aza 2-deoxycytidine and histone deacetylase inhibitor trichostatin A (herein referred to as Aza+TSA) after endotoxemia-induced mouse lung injury. We tested the hypothesis that treatment with Aza+TSA after lipopolysaccharide induction of ALI through epigenetic modification of lung endothelial cells prevents inflammatory lung injury. Combinatorial treatment with Aza+TSA mitigated the increased endothelial permeability response after lipopolysaccharide challenge. In addition, we observed reduced lung inflammation and lung injury. Aza+TSA also significantly reduced mortality in the ALI model. The protection was ascribed to inhibition of the eNOS-Cav1-MLC2 signaling pathway and enhanced acetylation of histone markers on the vascular endothelial-cadherin promoter. In summary, these data show for the first time the efficacy of combinatorial Aza+TSA therapy in preventing ALI in lipopolysaccharide-induced endotoxemia and raise the possibility of an essential role of DNA methyl transferase and histone deacetylase in the mechanism of ALI. PMID:24929240

Role of glycogen synthase kinase 3 beta (GSK3beta) in mediating the cytotoxic effects of the histone deacetylase inhibitor trichostatin A (TSA) in MCF-7 breast cancer cells.

PubMed

Alao, John P; Stavropoulou, Alexandra V; Lam, Eric W-F; Coombes, R Charles

2006-10-03

Histone deacetylase inhibitors (HDACIs) have been shown to induce apoptotic and autophagic cell death in vitro and in vivo. The molecular mechanisms that underlie these cytotoxic effects are not yet clearly understood. Recently, HDACIs were shown to induce Akt dephosphorylation by disrupting HDAC-protein phosphatase 1 (PP1) complexes. This disruption results in the increased association of PP1 with Akt, resulting in the dephosphorylation and consequent inactivation of the kinase. Akt enhances cellular survival through the phosphorylation-dependent inhibition of several pro-apoptotic proteins. Akt is an important negative regulator of GSK3beta, a kinase that has been shown to regulate apoptosis in response to various stimuli. In the present study, we investigated the role of GSK3beta in mediating the cytotoxic effects in MCF-7 breast cancer cells treated with trichostatin A (TSA), a prototype HDACI. We show that TSA induces Akt dephosphorylation in a PP1-dependent manner, resulting in activation of GSK3beta in MCF-7 cells. Similarly, knockdown of HDAC1 and-2 by small interfering RNA (siRNA) resulted in the dephosphorylation of Akt and GSK3beta. Selective inhibition of GSK3beta attenuated TSA induced cytotoxicity and resulted in enhanced proliferation following drug removal. Our findings identify GSK3beta as an important mediator of TSA-induced cytotoxicity in MCF-7 breast cancer cells.

BJ-TSA-9, a novel human tumor-specific gene, has potential as a biomarker of lung cancer.

PubMed

Li, Yunyan; Dong, Xueyuan; Yin, Yanhui; Su, Yanrong; Xu, Qingwen; Zhang, Yuxia; Pang, Xuewen; Zhang, Yu; Chen, Weifeng

2005-12-01

Using bioinformatics, we have identified a novel tumor-specific gene BJ-TSA-9, which has been validated by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). BJ-TSA-9 mRNA was expressed in 52.5% (21 of 40) of human lung cancer tissues and was especially higher in lung adenocarcinoma (68.8%). To explore the potential application of BJ-TSA-9 for the detection of circulating cancer cells in lung cancer patients, nested RT-PCR was performed. The overall positive detection rate was 34.3% (24 of 70) in peripheral blood mononuclear cells (PBMCs) of patients with various types of lung cancers and was 53.6% (15 of 28) in PBMCs of lung adenocarcinoma patients. In combination with the detection of two known marker genes SCC and LUNX, the detection rate was increased to 81.4%. A follow-up study was performed in 37 patients after surgical removal of tumor mass. Among nine patients with persistent detection of two to three tumor marker transcripts in PBMCs, six patients had recurrence/metastasis. In contrast, 28 patients with transient detection of one tumor marker or without detection of any tumor marker were all in remission. Thus, BJ-TSA-9 may serve as a marker for lung cancer diagnosis and as a marker, in combination with two other tumor markers, for the prediction of the recurrence and prognosis of lung cancer patients.

A conserved intronic U1 snRNP-binding sequence promotes trans-splicing in Drosophila

PubMed Central

Gao, Jun-Li; Fan, Yu-Jie; Wang, Xiu-Ye; Zhang, Yu; Pu, Jia; Li, Liang; Shao, Wei; Zhan, Shuai; Hao, Jianjiang

2015-01-01

Unlike typical cis-splicing, trans-splicing joins exons from two separate transcripts to produce chimeric mRNA and has been detected in most eukaryotes. Trans-splicing in trypanosomes and nematodes has been characterized as a spliced leader RNA-facilitated reaction; in contrast, its mechanism in higher eukaryotes remains unclear. Here we investigate mod(mdg4), a classic trans-spliced gene in Drosophila, and report that two critical RNA sequences in the middle of the last 5′ intron, TSA and TSB, promote trans-splicing of mod(mdg4). In TSA, a 13-nucleotide (nt) core motif is conserved across Drosophila species and is essential and sufficient for trans-splicing, which binds U1 small nuclear RNP (snRNP) through strong base-pairing with U1 snRNA. In TSB, a conserved secondary structure acts as an enhancer. Deletions of TSA and TSB using the CRISPR/Cas9 system result in developmental defects in flies. Although it is not clear how the 5′ intron finds the 3′ introns, compensatory changes in U1 snRNA rescue trans-splicing of TSA mutants, demonstrating that U1 recruitment is critical to promote trans-splicing in vivo. Furthermore, TSA core-like motifs are found in many other trans-spliced Drosophila genes, including lola. These findings represent a novel mechanism of trans-splicing, in which RNA motifs in the 5′ intron are sufficient to bring separate transcripts into close proximity to promote trans-splicing. PMID:25838544

Kinetic and Thermodynamic Rationale for SAHA Being a Preferential Human HDAC8 Inhibitor as Compared to the Structurally Similar Ligand, TSA

PubMed Central

Singh, Raushan K.; Lall, Naveena; Leedahl, Travis S.; McGillivray, Abigail; Mandal, Tanmay; Haldar, Manas; Mallik, Sanku; Cook, Gregory; Srivastava, D.K.

2013-01-01

Of the different hydroxamate-based histone deacetylase (HDAC) inhibitors, Suberoylanilide hydroxamic acid (SAHA) has been approved by the FDA for treatment of T-cell lymphoma. Interestingly, a structurally similar inhibitor, Trichostatin A (TSA), which has a higher in vitro inhibitory-potency against HDAC8, reportedly shows a poor efficacy in clinical settings. In order to gain the molecular insight into the above discriminatory feature, we performed transient kinetic and isothermal titration calorimetric studies for the interaction of SAHA and TSA to the recombinant form of human HDAC8. The transient kinetic data revealed that the binding of both the inhibitors to the enzyme showed the biphasic profiles, which represented an initial encounter of enzyme with the inhibitor followed by the isomerization of the transient enzyme-inhibitor complexes. The temperature-dependent transient kinetic studies with the above inhibitors revealed that the bimolecular process is primarily dominated by favorable enthalpic changes, as opposed to the isomerization step; which is solely contributed by entropic changes. The standard binding-enthalpy (ΔH0) of SAHA, deduced from the transient kinetic as well as the isothermal titration calorimetric experiments, was 2–3 kcal/mol higher as compared to TSA. The experimental data presented herein suggests that SAHA serves as a preferential (target-specific/selective) HDAC8 inhibitor as compared to TSA. Arguments are presented that the detailed kinetic and thermodynamic studies may guide in the rational design of HDAC inhibitors as therapeutic agents. PMID:24079912

Clinicopathological observations of colorectal serrated lesions associated with invasive carcinoma and high-grade intraepithelial neoplasm

PubMed Central

XU, SHENG; WANG, LUPING; YANG, GUANGZHI; LI, LIN; WANG, JIN; XU, CHUNWEI; GE, CHANG

2013-01-01

The aim of this study was to investigate the clinicopathological characteristics of colorectal serrated lesions associated with invasive carcinoma and high-grade intraepithelial neoplasm (HIN), as well as to determine the immunohistochemical expression of MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), K-ras and O6-methylguanine-DNA methyltransferase (MGMT). A total of 5,347 cases diagnosed with colorectal polyp or adenoma were included in this study from October 2002 to September 2009. A total of 16 cases of colorectal serrated lesions associated with invasive carcinoma/HIN were screened. These comprised seven cases of traditional serrated adenoma (TSA) associated with invasive carcinoma and HIN, six cases of sessile serrated adenoma (SSA) associated with invasive carcinoma/HIN and three cases of hyperplastic polyp (HP) associated with invasive carcinoma/HIN. TSA associated with invasive carcinoma/HIN predominantly occurred in the rectum with a clearly serrated structure and ectopic crypts. High-grade dysplasia was observed in filiform TSA, which was more prone to carcinogenesis. SSA associated with invasive carcinoma/HIN mainly occurred in the ileocecal junction, with the SSA serrated glands closely located adjacent to the muscularis mucosa and the basal crypt expanded with inverted T- or L-shaped branches. HPs were observed in three cases in the cancer-adjacent tissues with invasive carcinoma, while a HP-SSA/TSA-carcinoma sequence was found in two cases. Immunohistochemistry showed that MGMT expression was significantly different in the serrated lesion tissues compared with that in cancer tissues (P=0.022), control cancer tissues (P=0.002) and normal colorectal epithelial tissues (P=0.003). TSA and SSA may progress to cancer or directly develop into invasive adenocarcinoma. Filiform TSA easily develops into HIN, followed by infiltration. HP may arise from the cancer-adjacent tissues of the invasive carcinoma, which are closely adjacent to the cancer tissues. Further research is needed to investigate the potential direct involvement of HP in carcinogenesis. PMID:24223631

The incidence and effect of fatty atrophy, positive tangent sign, and rotator cuff tears on outcomes after total shoulder arthroplasty.

PubMed

Choate, W Stephen; Shanley, Ellen; Washburn, Richard; Tolan, Stefan J; Salim, Tariq I; Tadlock, Josh; Shealy, Elizabeth C; Long, Catherine D; Crawford, Ashley E; Kissenberth, Michael J; Lonergan, Keith T; Hawkins, Richard J; Tokish, John M

2017-12-01

Treatment choices for total shoulder arthroplasty (TSA) in the absence of full-thickness rotator cuff tears (RCTs) are not clearly defined in current literature. This study investigated the prevalence and effect of preoperative partial-thickness RCTs and muscular degenerative changes on postoperative outcomes after TSA. Medical records and magnetic resonance imaging studies were reviewed for patients who underwent TSA for primary glenohumeral osteoarthritis with minimum 2-year follow-up to determine preoperative tear classification, Goutallier grade, and supraspinatus tangent sign. Postoperative pain on the visual analog scale, range of motion, and patient outcomes scores were obtained to correlate preoperative RCT status, Goutallier grading, tangent sign, and postoperative outcomes. Patients with full-thickness RCT on preoperative magnetic resonance imaging were excluded. Forty-five patients met all inclusion criteria (average age, 65 ± 10 years; average follow-up, 43 months). Of the patients undergoing TSA, 40% had a significant (>50% thickness) partial RCT. Grade 3 to 4 Goutallier changes were noted in 22% of all patients, and 13% demonstrated grade 3 to 4 changes in the context of no tear. Positive tangent sign was present in 7% of all patients. The preoperative Goutallier grade of the infraspinatus was significantly negatively correlated with postoperative forward elevation (P = .02) and external rotation (P = .05), but rotator cuff pathology, including tear status, Goutallier grade, and the presence of a tangent sign, did not correlate with postoperative functional outcome scores. Even in the absence of a full-thickness RCT, rotator cuff atrophy, fatty infiltration, and partial thickness tearing are common findings. Although postoperative range of motion is correlated to Goutallier changes of the infraspinatus, rotator cuff pathology is not correlated to outcomes after TSA; therefore, one may proceed with TSA without concern of their effect on postoperative outcomes. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Superoxide dismutase 1-mediated production of ethanol- and DNA-derived radicals in yeasts challenged with hydrogen peroxide: molecular insights into the genome instability of peroxiredoxin-null strains.

PubMed

Ogusucu, Renata; Rettori, Daniel; Netto, Luis E S; Augusto, Ohara

2009-02-27

Peroxiredoxins are receiving increasing attention as defenders against oxidative damage and sensors of hydrogen peroxide-mediated signaling events. In the yeast Saccharomyces cerevisiae, deletion of one or more isoforms of the peroxiredoxins is not lethal but compromises genome stability by mechanisms that remain under scrutiny. Here, we show that cytosolic peroxiredoxin-null cells (tsa1Deltatsa2Delta) are more resistant to hydrogen peroxide than wild-type (WT) cells and consume it faster under fermentative conditions. Also, tsa1Deltatsa2Delta cells produced higher yields of the 1-hydroxyethyl radical from oxidation of the glucose metabolite ethanol, as proved by spin-trapping experiments. A major role for Fenton chemistry in radical formation was excluded by comparing WT and tsa1Deltatsa2Delta cells with respect to their levels of total and chelatable metal ions and of radical produced in the presence of chelators. The main route for 1-hydroxyethyl radical formation was ascribed to the peroxidase activity of Cu,Zn-superoxide dismutase (Sod1), whose expression and activity increased approximately 5- and 2-fold, respectively, in tsa1Deltatsa2Delta compared with WT cells. Accordingly, overexpression of human Sod1 in WT yeasts led to increased 1-hydroxyethyl radical production. Relevantly, tsa1Deltatsa2Delta cells challenged with hydrogen peroxide contained higher levels of DNA-derived radicals and adducts as monitored by immuno-spin trapping and incorporation of (14)C from glucose into DNA, respectively. The results indicate that part of hydrogen peroxide consumption by tsa1Deltatsa2Delta cells is mediated by induced Sod1, which oxidizes ethanol to the 1-hydroxyethyl radical, which, in turn, leads to increased DNA damage. Overall, our studies provide a pathway to account for the hypermutability of peroxiredoxin-null strains.

Epigenetic modification with trichostatin A does not correct specific errors of somatic cell nuclear transfer at the transcriptomic level; highlighting the non-random nature of oocyte-mediated reprogramming errors.

PubMed

Hosseini, Sayyed Morteza; Dufort, Isabelle; Nieminen, Julie; Moulavi, Fariba; Ghanaei, Hamid Reza; Hajian, Mahdi; Jafarpour, Farnoosh; Forouzanfar, Mohsen; Gourbai, Hamid; Shahverdi, Abdol Hossein; Nasr-Esfahani, Mohammad Hossein; Sirard, Marc-André

2016-01-04

The limited duration and compromised efficiency of oocyte-mediated reprogramming, which occurs during the early hours following somatic cell nuclear transfer (SCNT), may significantly interfere with epigenetic reprogramming, contributing to the high incidence of ill/fatal transcriptional phenotypes and physiological anomalies occurring later during pre- and post-implantation events. A potent histone deacetylase inhibitor, trichostatin A (TSA), was used to understand the effects of assisted epigenetic modifications on transcriptional profiles of SCNT blastocysts and to identify specific or categories of genes affected. TSA improved the yield and quality of in vitro embryo development compared to control (CTR-NT). Significance analysis of microarray results revealed that of 37,238 targeted gene transcripts represented on the microarray slide, a relatively small number of genes were differentially expressed in CTR-NT (1592 = 4.3 %) and TSA-NT (1907 = 5.1 %) compared to IVF embryos. For both SCNT groups, the majority of downregulated and more than half of upregulated genes were common and as much as 15 % of all deregulated transcripts were located on chromosome X. Correspondence analysis clustered CTR-NT and IVF transcriptomes close together regardless of the embryo production method, whereas TSA changed SCNT transcriptome to a very clearly separated cluster. Ontological classification of deregulated genes using IPA uncovered a variety of functional categories similarly affected in both SCNT groups with a preponderance of genes required for biological processes. Examination of genes involved in different canonical pathways revealed that the WNT and FGF pathways were similarly affected in both SCNT groups. Although TSA markedly changed epigenetic reprogramming of donor cells (DNA-methylation, H3K9 acetylation), reconstituted oocytes (5mC, 5hmC), and blastocysts (DNA-methylation, H3K9 acetylation), these changes did not recapitulate parallel marked changes in chromatin remodeling, and nascent mRNA and OCT4-EGFP expression of TSA-NT vs. CRT-NT embryos. The results obtained suggest that despite the extensive reprogramming of donor cells that occurred by the blastocyst stage, SCNT-specific errors are of a non-random nature in bovine and are not responsive to epigenetic modifications by TSA.

Transcriptional Profiling Defines Histone Acetylation as a Regulator of Gene Expression during Human-to-Mosquito Transmission of the Malaria Parasite Plasmodium falciparum

PubMed Central

Ngwa, Che J.; Kiesow, Meike J.; Papst, Olga; Orchard, Lindsey M.; Filarsky, Michael; Rosinski, Alina N.; Voss, Till S.; Llinás, Manuel; Pradel, Gabriele

2017-01-01

Transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is mediated by the intraerythrocytic gametocytes, which, once taken up during a blood meal, become activated to initiate sexual reproduction. Because gametocytes are the only parasite stages able to establish an infection in the mosquito, they are crucial for spreading the tropical disease. During gametocyte maturation, different repertoires of genes are switched on and off in a well-coordinated sequence, pointing to regulatory mechanisms of gene expression. While epigenetic gene control has been studied during erythrocytic schizogony of P. falciparum, little is known about this process during human-to-mosquito transmission of the parasite. To unveil the potential role of histone acetylation during gene expression in gametocytes, we carried out a microarray-based transcriptome analysis on gametocytes treated with the histone deacetylase inhibitor trichostatin A (TSA). TSA-treatment impaired gametocyte maturation and lead to histone hyper-acetylation in these stages. Comparative transcriptomics identified 294 transcripts, which were more than 2-fold up-regulated during gametocytogenesis following TSA-treatment. In activated gametocytes, which were less sensitive to TSA, the transcript levels of 48 genes were increased. TSA-treatment further led to repression of ~145 genes in immature and mature gametocytes and 7 genes in activated gametocytes. Up-regulated genes are mainly associated with functions in invasion, cytoadherence, and protein export, while down-regulated genes could particularly be assigned to transcription and translation. Chromatin immunoprecipitation demonstrated a link between gene activation and histone acetylation for selected genes. Among the genes up-regulated in TSA-treated mature gametocytes was a gene encoding the ring finger (RING)-domain protein PfRNF1, a putative E3 ligase of the ubiquitin-mediated signaling pathway. Immunochemistry demonstrated PfRNF1 expression mainly in the sexual stages of P. falciparum with peak expression in stage II gametocytes, where the protein localized to the nucleus and cytoplasm. Pfrnf1 promoter and coding regions associated with acetylated histones, and TSA-treatment resulted in increased PfRNF1 levels. Our combined data point to an essential role of histone acetylation for gene regulation in gametocytes, which can be exploited for malaria transmission-blocking interventions. PMID:28791254

Pan-histone deacetylase inhibitors regulate signaling pathways involved in proliferative and pro-inflammatory mechanisms in H9c2 cells

PubMed Central

2012-01-01

Background We have shown previously that pan-HDAC inhibitors (HDACIs) m-carboxycinnamic acid bis-hydroxamide (CBHA) and trichostatin A (TSA) attenuated cardiac hypertrophy in BALB/c mice by inducing hyper-acetylation of cardiac chromatin that was accompanied by suppression of pro-inflammatory gene networks. However, it was not feasible to determine the precise contribution of the myocytes- and non-myocytes to HDACI-induced gene expression in the intact heart. Therefore, the current study was undertaken with a primary goal of elucidating temporal changes in the transcriptomes of cardiac myocytes exposed to CBHA and TSA. Results We incubated H9c2 cardiac myocytes in growth medium containing either of the two HDACIs for 6h and 24h and analyzed changes in gene expression using Illumina microarrays. H9c2 cells exposed to TSA for 6h and 24h led to differential expression of 468 and 231 genes, respectively. In contrast, cardiac myocytes incubated with CBHA for 6h and 24h elicited differential expression of 768 and 999 genes, respectively. We analyzed CBHA- and TSA-induced differentially expressed genes by Ingenuity Pathway (IPA), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Core_TF programs and discovered that CBHA and TSA impinged on several common gene networks. Thus, both HDACIs induced a repertoire of signaling kinases (PTEN-PI3K-AKT and MAPK) and transcription factors (Myc, p53, NFkB and HNF4A) representing canonical TGFβ, TNF-α, IFNγ and IL-6 specific networks. An overrepresentation of E2F, AP2, EGR1 and SP1 specific motifs was also found in the promoters of the differentially expressed genes. Apparently, TSA elicited predominantly TGFβ- and TNF-α-intensive gene networks regardless of the duration of treatment. In contrast, CBHA elicited TNF-α and IFNγ specific networks at 6 h, followed by elicitation of IL-6 and IFNγ-centered gene networks at 24h. Conclusions Our data show that both CBHA and TSA induced similar, but not identical, time-dependent, gene networks in H9c2 cardiac myocytes. Initially, both HDACIs impinged on numerous genes associated with adipokine signaling, intracellular metabolism and energetics, and cell cycle. A continued exposure to either CBHA or TSA led to the emergence of a number of apoptosis- and inflammation-specific gene networks that were apparently suppressed by both HDACIs. Based on these data we posit that the anti-inflammatory and anti-proliferative actions of HDACIs are myocyte-intrinsic. These findings advance our understanding of the mechanisms of actions of HDACIs on cardiac myocytes and reveal potential signaling pathways that may be targeted therapeutically. PMID:23249388

CHRPR Operations Manual

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

Windsor, Bradford T.; Woodring, Mitchell L.; Myjak, Mitchell J.

2012-08-21

1.0 Overview The TSA systems VM-250AGN portal monitor is a set of two pillars made to detect nuclear material in a vehicle. Each pillar contains two polyvinyl toluene (PVT) plastic gamma ray detectors and four 3He neutron detectors, as well as a power supply and electronics to process the output from these detectors. Pacific Northwest National Laboratory has designed and built a continuous high-resolution PVT readout (CHRPR) for the TSA portal to allow spectral readout from the gamma and neutron detectors. The CHRPR helps differentiate between different types of radioactive material through increased spectroscopic capability and associated developments. The TSAmore » VM-250AGN continually monitors the natural neutron and gamma ray background which occurs around the pillars. When the system is installed, the two pillars are placed on either side of a roadway, and a vehicle presence sensor records the passage of cars between them. When radiation measurements exceed a preset alarm threshold, the system alarms to let the user know that a radioactive material is present. Time-stamped measurements are continually sent to a computer, where they can be recorded via a Windows terminal or the TSA RAVEN software. For each pillar in the original TSA model, output from each detector is amplified and shaped by a single channel analyzer, the SCA-775. Information from both SCA-775’s are passed to the SC-770 in the master pillar. This is the detector interface module and main data processor. It counts electrical pulses and uses program software to output total readings to the computer, as well as trigger any appropriate alarms. The CHRPR allows a parallel approach to recording radiation readings from the TSA system. After installing the CHRPR system, all TSA power and signal connections are unchanged. The CHRPR captures electrical pulses containing detector and occupancy sensor information from the SCA-775 on either side. These pulses are converted to a signal with a time width proportional to the amplitude, via voltage to pulse width converters (VPW). These time widths are then digitized by a field programmable gate array (FPGA) and transmitted over Ethernet to a data acquisition computer. The CHRPR records the magnitude of each pulse to a continuous event mode file on or each detector and occupancy sensor This manual begins with CHRPR installation instructions, then a section on CHRPR software. Afterward is a brief overview of how the TSA system works, then an explanation of the CHRPR. This manual is meant as a supplement to the TSA VM-250AGN manual, which can be found at http://tsasystems.com/library/manuals/pm700agn-vm250agn_manual.pdf . That manual is the manufacturer’s guide for the installation, programming, and maintenance of the portal system.« less

NAEP 1994 Reading State Report for Department of Defense Education Activity Overseas Schools. Trial State Assessment.

ERIC Educational Resources Information Center

National Assessment of Educational Progress, Princeton, NJ.

In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in NAEP's history, voluntary state-by-state assessments were made. In 1994, TSA was expanded to include non-public school students. The 1994 reading assessment considered students' proficiency in situations that involved…

Effects of light intensity on Tropical Soda Apple and the consequences for performance of its biological control agent, Gratiana boliviana (Chrysomelidae).

USDA-ARS?s Scientific Manuscript database

The current research was directed at determining the impact of light intensity on the architecture, amino acid content and trichome density and characteristics of Tropical Soda Apple (TSA), Solanum viarum (Solanaceae). TSA plants were grown in a greenhouse either covered with a shade cloth (75% bloc...

49 CFR 1572.405 - Procedures for collection by TSA.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Collection Fee, Threat Assessment Fee, and FBI Fee. (a) Imposition of fees. (1) An individual who applies to... Collection Fee, Threat Assessment Fee, and FBI Fee, in a form and manner approved by TSA, when the individual... accordance with the provisions of 31 U.S.C. 9701 and other applicable Federal law. (3) The FBI Fee required...

49 CFR 1572.405 - Procedures for collection by TSA.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Collection Fee, Threat Assessment Fee, and FBI Fee. (a) Imposition of fees. (1) An individual who applies to... Collection Fee, Threat Assessment Fee, and FBI Fee, in a form and manner approved by TSA, when the individual... accordance with the provisions of 31 U.S.C. 9701 and other applicable Federal law. (3) The FBI Fee required...

Training Situation Analysis: Conducting a Needs Analysis for Teams and New Systems.

ERIC Educational Resources Information Center

Dell, Jay; Fox, John; Malcolm, Ralph

1998-01-01

The United States Coast Guard uses training situation analysis (TSA) to develop quantified training requirements, collect training and non-training performance data, and overcome turf issues to focus on performance outcomes. Presents the 1947 MLB (Motor Lifeboat Project) as a case study. Outlines 11 steps in the TSA needs analysis for teams and…

Fourier mode analysis of slab-geometry transport iterations in spatially periodic media

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

Larsen, E; Zika, M

1999-04-01

We describe a Fourier analysis of the diffusion-synthetic acceleration (DSA) and transport-synthetic acceleration (TSA) iteration schemes for a spatially periodic, but otherwise arbitrarily heterogeneous, medium. Both DSA and TSA converge more slowly in a heterogeneous medium than in a homogeneous medium composed of the volume-averaged scattering ratio. In the limit of a homogeneous medium, our heterogeneous analysis contains eigenvalues of multiplicity two at ''resonant'' wave numbers. In the presence of material heterogeneities, error modes corresponding to these resonant wave numbers are ''excited'' more than other error modes. For DSA and TSA, the iteration spectral radius may occur at these resonantmore » wave numbers, in which case the material heterogeneities most strongly affect iterative performance.« less

Biological effects of induced MYCN hyper-expression in MYCN-amplified neuroblastomas.

PubMed

Torres, Jaime; Regan, Paul L; Edo, Robby; Leonhardt, Payton; Jeng, Eric I; Rappaport, Eric F; Ikegaki, Naohiko; Tang, Xao X

2010-10-01

Neuroblastoma is a childhood malignancy of the sympathetic nervous system. The tumor exhibits two different phenotypes: favorable and unfavorable. MYCN amplification is associated with rapid tumor progression and the worst neuroblastoma disease outcome. We have previously reported that inhibitors of histone deacetylase (HDAC) and proteasome enhance favorable neuroblastoma gene expression in neuroblastoma cell lines and inhibit growth of these cells. In this study, we investigated the effect of trichostatin A or TSA (an HDAC inhibitor), and epoxomycin (a proteasome inhibitor) on MYCN and p53 expression in MYCN-amplified neuroblastoma cells. It was found that TSA down-regulated MYCN expression, but Epoxomycin and the TSA/Epoxomycin combination led to MYCN hyper-expression in MYCN-amplified neuroblastoma cell lines. Despite their contrasting effects on MYCN expression, TSA and Epoxomycin caused growth suppression and cell death of the MYCN-amplified cell lines examined. Consistent with these data, forced hyper-expression of MYCN in MYCN-amplified IMR5 cells via transfection resulted in growth suppression and the increased expression of several genes known to suppress growth or induce cell death. Furthermore, Epoxomycin as a single agent and its combination with TSA enhance p53 expression in the MYCN-amplified neuroblastoma cell lines. Unexpectedly, co-transfection of TP53 and MYCN in IMR5 cells resulted in high p53 expression but a reduction of MYCN expression. Together our data suggest that either down regulation or hyper-expression of MYCN results in growth inhibition and/or apoptosis of MYCN-amplified neuroblastoma cells. In addition, elevated p53 expression has a suppressive effect on MYCN expression in these cells.

Liquid chromatographic determination of para-toluenesulfonamide in edible fillet tissues from three species of fish

USGS Publications Warehouse

Meinertz, J.R.; Schmidt, L.J.; Stehly, G.R.; Gingerich, W.H.

1999-01-01

Chloramine-T (N-sodium-N-chloro-p-toluene-sulfonamide) is a candidate therapeutic drug for treating bacterial gill disease, a predominant disease of a variety of fish species. Research has been initiated to obtain the U.S. Food and Drug Administration's (FDA) approval for the use of chloramine-T on a variety of fish species. An attribute of a therapeutic aquaculture drug that must be characterized before the FDA approves its use is depletion of the drug's marker residue (the drug's parent compound or metabolite of highest concentration in an edible tissue). Para-Toluenesulfonamide (p-TSA) is the primary degradation product and marker residue for chloramine-T in rainbow trout. To conduct residue depletion studies for chloramine-T in fish, a robust analytical method sensitive and specific for p-TSA residues in edible fillet tissue from a variety of fish was required. Homogenized fillet tissues from rainbow trout (Oncorhynchus mykiss), walleye (Stizostedion vitreum), and channel catfish (Ictalurus punctatus) were fortified at nominal p-TSA concentrations of 17, 67, 200, 333, and 1000 ng/g. Samples were analyzed by isocratic reversed-phase liquid chromatography (LC) with absorbance detection at 226 nm. Mean recoveries of p-TSA ranged from 77 to 93.17%; relative standard deviations ranged from 1.5 to 14%; method quantitation limits ranged from 13 to 18 ng/g; and method detection limits ranged from 3.8 to 5.2 ng/g. The LC parameters produced p-TSA peaks without coelution of endogenous compounds and excluded chromatographic interference from at least 20 chemicals and drugs of potential use in aquaculture.

EDTA aggregates induce SYPRO orange-based fluorescence in thermal shift assay

PubMed Central

Kroeger, Tobias; Frieg, Benedikt; Zhang, Tao; Hansen, Finn K.; Marmann, Andreas; Proksch, Peter; Nagel-Steger, Luitgard; Groth, Georg; Smits, Sander H. J.

2017-01-01

Ethylenediaminetetraacetic acid (EDTA) is widely used in the life sciences as chelating ligand of metal ions. However, formation of supramolecular EDTA aggregates at pH > 8 has been reported, which may lead to artifactual assay results. When applied as a buffer component at pH ≈ 10 in differential scanning fluorimetry (TSA) using SYPRO Orange as fluorescent dye, we observed a sharp change in fluorescence intensity about 20°C lower than expected for the investigated protein. We hypothesized that this change results from SYPRO Orange/EDTA interactions. TSA experiments in the presence of SYPRO Orange using solutions that contain EDTA-Na+ but no protein were performed. The TSA experiments provide evidence that suggests that at pH > 9, EDTA4- interacts with SYPRO Orange in a temperature-dependent manner, leading to a fluorescence signal yielding a “denaturation temperature” of ~68°C. Titrating Ca2+ to SYPRO Orange and EDTA solutions quenched fluorescence. Ethylene glycol tetraacetic acid (EGTA) behaved similarly to EDTA. Analytical ultracentrifugation corroborated the formation of EDTA aggregates. Molecular dynamics simulations of free diffusion of EDTA-Na+ and SYPRO Orange of in total 27 μs suggested the first structural model of EDTA aggregates in which U-shaped EDTA4- arrange in an inverse bilayer-like manner, exposing ethylene moieties to the solvent, with which SYPRO Orange interacts. We conclude that EDTA aggregates induce a SYPRO Orange-based fluorescence in TSA. These results make it relevant to ascertain that future TSA results are not influenced by interference between EDTA, or EDTA-related molecules, and the fluorescent dye. PMID:28472107

A stress-free model for residual stress assessment using thermoelastic stress analysis

NASA Astrophysics Data System (ADS)

Howell, Geoffrey; Dulieu-Barton, Janice M.; Achintha, Mithila; Robinson, Andrew F.

2015-03-01

Thermoelastic Stress Analysis (TSA) has been proposed as a method of obtaining residual stresses. The results of a preliminary study demonstrated that when Al-2024 plate containing holes that were plastically deformed by cold expansion process to 2% and 4% strain the thermoelastic response in the material around the hole was different to that obtained from a plate that had not experienced any plastic cold expansion (i.e. a reference specimen). This observation provides an opportunity for obtaining residual stresses based on TSA data. In many applications a reference specimen (i.e. residual stress free specimen) may not be available for comparison, so a synthetic, digital bitmap has been proposed as an alternative. An elastic finite element model is created using commercially available software Abaqus/Standard and the resultant stress field is extracted. The simulated stress field from the model is mapped onto a grid that matches the TSA pixel data from a physical reference specimen. This stress field is then converted to a ΔT/T field that can be compared to the full-field TSA data. When the reference experimental data is subtracted from the, bitmap dataset the resultant ΔT/T field is approximately zero. Further work proposes replacing the experimental reference data with that from specimens that have undergone cold expansion with the aim of revealing the regions affected by residual stress through a departure from zero in the resultant stress field. The paper demonstrates the first steps necessary for deriving the residual stresses from a general specimen using TSA.

Antiproliferative effects of TSA, PXD‑101 and MS‑275 in A2780 and MCF7 cells: Acetylated histone H4 and acetylated tubulin as markers for HDACi potency and selectivity.

PubMed

Androutsopoulos, Vasilis P; Spandidos, Demetrios A

2017-12-01

Inhibition of histone deacetylase enzymes (HDACs) has been well documented as an attractive target for the development of chemotherapeutic drugs. The present study investigated the effects of two prototype hydroxamic acid HDAC inhibitors, namely Trichostatin A (TSA) and Belinostat (PXD‑101) and the benzamide Entinostat (MS‑275) in A2780 ovarian carcinoma and MCF7 breast adenocarcinoma cells. The three HDACi inhibited the proliferation of A2780 and MCF7 cells at comparable levels, below the µM range. Enzyme inhibition assays in a cell‑free system showed that TSA was the most potent inhibitor of total HDAC enzyme activity followed by PXD‑101 and MS‑275. Incubation of A2780 and MCF7 cells with the hydroxamates TSA and PXD‑101 for 24 h resulted in a dramatic increase of acetylated tubulin induction (up to 30‑fold for TSA). In contrast to acetylated tubulin, western blot analysis and flow cytometry indicated that the induction of acetylated histone H4 was considerably smaller. The benzamide MS‑275 exhibited nearly a 2‑fold induction of acetylated histone H4 and an even smaller induction of acetylated tubulin in A2780 and MCF7 cells. Taken together, these data suggest that although the three HDACi were equipotent in inhibiting proliferation of MCF7 and A2780 cells, only the benzamide MS‑275 did not induce acetylated tubulin expression, a marker of class IIb HDACs.

Exploiting multi-function Metal-Organic Framework nanocomposite Ag@Zn-TSA as highly efficient immobilization matrixes for sensitive electrochemical biosensing.

PubMed

Dong, Sheying; Zhang, Dandan; Suo, Gaochao; Wei, Wenbo; Huang, Tinglin

2016-08-31

A novel multi-function Metal-Organic Framework composite Ag@Zn-TSA (zinc thiosalicylate, Zn(C7H4O2S), Zn-TSA) was synthesized as highly efficient immobilization matrixes of myoglobin (Mb)/glucose oxidase (GOx) for electrochemical biosensing. The electrochemical biosensors based on Ag@Zn-TSA composite and ionic liquid (IL) modified carbon paste electrode (CPE) were fabricated successfully. Furthermore, the properties of the sensors were discussed by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and amperometric current-time curve, respectively. The results showed the proposed biosensors had wide linear response to hydrogen peroxide (H2O2) in the range of 0.3-20,000 μM, to nitrite (NO2(-)) for 1.3 μM-1660 μM and 2262 μM-1,33,000 μM, to glucose for 2.0-1022 μM, with a low detection limit of 0.08 μM for H2O2, 0.5 μM for NO2(-), 0.8 μM for glucose. The values of the apparent heterogeneous electron transfer rate constant (ks) for Mb and GOx were estimated as 2.05 s(-1) and 2.45 s(-1), respectively. Thus, Ag@Zn-TSA was a kind of ideal material as highly efficient immobilization matrixes for sensitive electrochemical biosensing. In addition, this work indicated that MOF nanocomposite had a great potential for constructing wide range of sensing interface. Copyright © 2016 Elsevier B.V. All rights reserved.

The t6A modification acts as a positive determinant for the anticodon nuclease PrrC, and is distinctively nonessential in Streptococcus mutans.

PubMed

Bacusmo, Jo Marie; Orsini, Silvia S; Hu, Jennifer; DeMott, Michael; Thiaville, Patrick C; Elfarash, Ameer; Paulines, Mellie June; Rojas-Benítez, Diego; Meineke, Birthe; Deutsch, Chris; Iwata-Reuyl, Dirk; Limbach, Patrick A; Dedon, Peter C; Rice, Kelly C; Shuman, Stewart; Crécy-Lagard, Valérie de

2017-07-20

Endoribonuclease toxins (ribotoxins) are produced by bacteria and fungi to respond to stress, eliminate non-self competitor species, or interdict virus infection. PrrC is a bacterial ribotoxin that targets and cleaves tRNA Lys UUU in the anticodon loop. In vitro studies suggested that the post-transcriptional modification threonylcarbamoyl adenosine (t 6 A) is required for PrrC activity but this prediction had never been validated in vivo. Here, by using t 6 A-deficient yeast derivatives, it is shown that t 6 A is a positive determinant for PrrC proteins from various bacterial species. Streptococcus mutans is one of the few bacteria where the t 6 A synthesis gene tsaE (brpB) is dispensable and its genome encodes a PrrC toxin. We had previously shown using an HPLC-based assay that the S. mutans tsaE mutant was devoid of t 6 A. However, we describe here a novel and a more sensitive hybridization-based t 6 A detection method (compared to HPLC) that showed t 6 A was still present in the S. mutans ΔtsaE, albeit at greatly reduced levels (93% reduced compared with WT). Moreover, mutants in 2 other S. mutans t 6 A synthesis genes (tsaB and tsaC) were shown to be totally devoid of the modification thus confirming its dispensability in this organism. Furthermore, analysis of t 6 A modification ratios and of t 6 A synthesis genes mRNA levels in S. mutans suggest they may be regulated by growth phase.

78 FR 46358 - Extension of Agency Information Collection Activity Under OMB Review: Security Programs for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

.... Specifically, TSA requires foreign air carriers to submit the following information: (1) A master crew list of all flight and cabin crew members flying to and from the United States; (2) the flight crew list on a..., 49 CFR part 1546. TSA uses the information collected to determine compliance with 49 CFR part 1546...

On-Wafer Characterization of Millimeter-Wave Antennas for Wireless Applications

NASA Technical Reports Server (NTRS)

Simons, Rainee N.; Lee, Richard Q.

1998-01-01

The paper demonstrates a de-embedding technique and a direct on-substrate measurement technique for fast and inexpensive characterization of miniature antennas for wireless applications at millimeter-wave frequencies. The technique is demonstrated by measurements on a tapered slot antenna (TSA). The measured results at Ka-Band frequencies include input impedance, mutual coupling between two TSAs and absolute gain of TSA.

Factors Affecting Student Learning Outcomes: A School-Level Analysis of the 1990 NAEP Mathematics Trial State Assessment.

ERIC Educational Resources Information Center

Kim, Lori Yoonkyung

Data from the 1990 National Assessment of Educational Progress (NAEP) Trial State Assessment (TSA) in mathematics were analyzed to determine what educational factors influence student learning, how these factors influence learning, and how important these factors are to student achievement. NAEP TSA data were collected from more than 100,000…

The National Assessment of Educational Progress: Changes in Reporting and Dissemination for 1992 and Beyond.

ERIC Educational Resources Information Center

Fromboluti, Carol Sue

Changes that have been made in reporting and disseminating information from the National Assessment of Educational Progress are discussed, focusing on those changes brought about by the first Trial State Assessment (TSA). The TSA collected data on the mathematics performance of students in grades 4, 8, and 12 in public and private schools in 40…

FY2007 Supplemental Appropriations for Defense, Foreign Affairs, and Other Purposes

DTIC Science & Technology

2007-05-02

73 Liquidation of TSA Contract and Grant Obligations . . . . . . . . . . . . . . . . . . . . . . 76 Ongoing Katrina Recovery...Administration ( TSA ) contract and grant obligations incurred during FY2002 and FY2003. Congress is also considering additions of unrequested funds for...funding shown in brackets) : ! $520 million for Bradley base sustainment ($1.4 billion in bridge); ! $1.6 billion for the Family of Medium Tactical

Successful mouse cloning of an outbred strain by trichostatin A treatment after somatic nuclear transfer.

PubMed

Kishigami, Satoshi; Bui, Hong-Thuy; Wakayama, Sayaka; Tokunaga, Kenzo; Van Thuan, Nguyen; Hikichi, Takafusa; Mizutani, Eiji; Ohta, Hiroshi; Suetsugu, Rinako; Sata, Tetsutaro; Wakayama, Teruhiko

2007-02-01

Although the somatic cloning technique has been used for numerous applications and basic research of reprogramming in various species, extremely low success rates have plagued this technique for a decade. Further in mice, the "clonable" strains have been limited to mainly hybrid F1 strains such as B6D2F1. Recently, we established a new efficient cloning technique using trichostatin A (TSA) which leads to a 2-5 fold increase in success rates for mouse cloning of B6D2F1 cumulus cells. To further test the validity of this TSA cloning technique, we tried to clone the adult ICR mouse, an outbred strain, which has never been directly cloned before. Only when TSA was used did we obtain both male and female cloned mice from cumulus and fibroblast cells of adult ICR mice with 4-5% success rates, which is comparable to 5-7% of B6D2F1. Thus, the TSA treatment is the first cloning technique to allow us to successfully clone outbred mice, demonstrating that this technique not only improves the success rates of cloning from hybrid strains, but also enables mouse cloning from normally "unclonable" strains.

Modelling the removal of p-TSA (para-toluenesulfonamide) during rapid sand filtration used for drinking water treatment.

PubMed

Meffe, Raffaella; Kohfahl, Claus; Holzbecher, Ekkehard; Massmann, Gudrun; Richter, Doreen; Dünnbier, Uwe; Pekdeger, Asaf

2010-01-01

A finite element model was set-up to determine degradation rate constants for p-TSA during rapid sand filtration (RSF). Data used for the model originated from a column experiment carried out in the filter hall of a drinking water treatment plant in Berlin (Germany). Aerated abstracted groundwater was passed through a 1.6m long column-shaped experimental sand filter applying infiltration rates from 2 to 6mh(-1). Model results were fitted to measured profiles and breakthrough curves of p-TSA for different infiltration rates using both first-order reaction kinetics and Michaelis-Menten kinetics. Both approaches showed that degradation rates varied both in space and time. Higher degradation rates were observed in the upper part of the column, probably related to higher microbial activity in this zone. Measured and simulated breakthrough curves revealed an adaption phase with lower degradation rates after infiltration rates were changed, followed by an adapted phase with more elevated degradation rates. Irrespective of the mathematical approach and the infiltration rate, degradation rates were very high, probably owing to the fact that filter sands have been in operation for decades, receiving high p-TSA concentrations with the raw water.

Extrachromosomal HPV-16 LCR transcriptional activation by HDACi opposed by cellular differentiation and DNA integration.

PubMed

Bojilova, Ekaterina Dimitrova; Weyn, Christine; Antoine, Marie-Hélène; Fontaine, Véronique

2016-11-15

Histone deacetylase inhibitors (HDACi) have been shown to render HPV-carrying cells susceptible to intrinsic and extrinsic apoptotic signals. As such, these epigenetic drugs have entered clinical trials in the effort to treat cervical cancer. Here, we studied the effect of common HDACi, with an emphasis on Trichostatin A (TSA), on the transcriptional activity of the HPV-16 Long Control Region (LCR) in order to better understand the impact of these agents in the context of the HPV life cycle and infection. HDACi strongly induced transcription of the firefly luciferase reporter gene under the control of the HPV-16 LCR in a variety of cell lines. In the HaCaT keratinocyte cell line undergoing differentiation induced by TSA, we observed a reduction in LCR-controlled transcription. Three major AP-1 binding sites in the HPV-16 LCR are involved in the regulation by TSA. However, whatever the status of differentiation of the HaCaT cells, TSA induced integration of extra-chromosomal transfected DNA into the cellular genome. Although these data suggest caution using HDACi in the treatment of HR HPV infection, further in vivo studies are necessary to better assess the risk.

Extrachromosomal HPV-16 LCR transcriptional activation by HDACi opposed by cellular differentiation and DNA integration

PubMed Central

Bojilova, Ekaterina Dimitrova; Weyn, Christine; Antoine, Marie-Hélène; Fontaine, Véronique

2016-01-01

Histone deacetylase inhibitors (HDACi) have been shown to render HPV-carrying cells susceptible to intrinsic and extrinsic apoptotic signals. As such, these epigenetic drugs have entered clinical trials in the effort to treat cervical cancer. Here, we studied the effect of common HDACi, with an emphasis on Trichostatin A (TSA), on the transcriptional activity of the HPV-16 Long Control Region (LCR) in order to better understand the impact of these agents in the context of the HPV life cycle and infection. HDACi strongly induced transcription of the firefly luciferase reporter gene under the control of the HPV-16 LCR in a variety of cell lines. In the HaCaT keratinocyte cell line undergoing differentiation induced by TSA, we observed a reduction in LCR-controlled transcription. Three major AP-1 binding sites in the HPV-16 LCR are involved in the regulation by TSA. However, whatever the status of differentiation of the HaCaT cells, TSA induced integration of extra-chromosomal transfected DNA into the cellular genome. Although these data suggest caution using HDACi in the treatment of HR HPV infection, further in vivo studies are necessary to better assess the risk. PMID:27705914

Biomonitoring of atmospheric pollution: a novel approach for the evaluation of natural and anthropogenic contribution to atmospheric aerosol particles.

PubMed

Caggiano, Rosa; Calamita, Giuseppe; Sabia, Serena; Trippetta, Serena

2017-03-01

The investigation of the potential natural and anthropogenic contribution to atmospheric aerosol particles by using lichen-bag technique was performed in the Agri Valley (Basilicata region, southern Italy). This is an area of international concern since it houses one of the largest European on-shore reservoirs and the biggest oil/gas pre-treatment plant (i.e., Centro Olio Val d'Agri (COVA)) within an anthropized context. In particular, the concentrations of 17 trace elements (Al, Ca, Cd, Cr, Cu, Fe, K, Li, Mg, Mn, Na, Ni, P, Pb, S, Ti, and Zn) were measured in lichen bags exposed in 59 selected monitoring points over periods of 6 months (from October 2011 to April 2012) and 12 months (from October 2011 to October 2012). The general origin of the main air masses affecting the sampling site during the study period was assessed by the back trajectories clustering calculated using the HYbrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model. The results allowed the identification and characterization of the crustal material, smoke, sea salt, sulfate, and anthropogenic trace element contributions to the atmospheric aerosol particles in the study area. Finally, the application of the trend surface analysis (TSA) allowed the study of the spatial distribution of the considered contributions highlighting the existence of a continuous broad variation of these contributions in the area of interest.

Genetic Algorithm for Initial Orbit Determination with Too Short Arc (Continued)

NASA Astrophysics Data System (ADS)

Li, Xin-ran; Wang, Xin

2017-04-01

When the genetic algorithm is used to solve the problem of too short-arc (TSA) orbit determination, due to the difference of computing process between the genetic algorithm and the classical method, the original method for outlier deletion is no longer applicable. In the genetic algorithm, the robust estimation is realized by introducing different loss functions for the fitness function, then the outlier problem of the TSA orbit determination is solved. Compared with the classical method, the genetic algorithm is greatly simplified by introducing in different loss functions. Through the comparison on the calculations of multiple loss functions, it is found that the least median square (LMS) estimation and least trimmed square (LTS) estimation can greatly improve the robustness of the TSA orbit determination, and have a high breakdown point.

[HDAC1 expression and effect of TSA on proliferation and apoptosis of A549 cells].

PubMed

Huang, Hong; Zhang, Zhen-Xiang; Xu, Yong-Jian; Shao, Jing-Fang

2003-09-01

Histone deacetylase (HDAC) shows a high expression in many cancer cells and the inhibitor of HDAC1, trichostatin A (TSA), can inhibit the growth of cancer cells. Hypoxia is a common feature of malignant tumors. This paper was designed to investigate the expression of HDAC1 of A549 cell strains in hypoxia condition and the effect of TSA on their proliferation and apoptosis. The authors designed 1 normoxia group (control group) and 5 hypoxia groups (test groups): hypoxia 6h group (A), TSA + hypoxia 6h (B), hypoxia 12h group (C), hypoxia 24h group (D), TSA + hypoxia 24h (E), hypoxia 48h group (F). The expression of HDAC1 in A549 cells was examined using Western blot analysis. Proliferation, the apoptotic rates of A549 cells and the effect of TSA on them were determined using MTT method, immunohistochemistry, TUNEL method, and flow cytometry. The expression of mRNA of HDAC1 and the effect of TSA on it were determined using reverse transcription-polymerase chain reaction (RT-PCR). The A values expressed by HDAC1 in A549 cell strains were 138+/-11 in the control group, 78+/-4, 86+/-5, 124+/-3, and 120+/-9 in test groups A, C, D, and F, respectively. The A values of HDAC1mRNA versus the A values of beta-Atin mRNA were 0.68+/-0.03 in the control group, 0.46+/-0.03, 0.45+/-0.02, 0.70+/-0.03, and 0.33+/-0.02 in test groups A, C, D, and F, respectively. The A values of the expression of PCNA in A549 cell strains were 0.13+/-0.03 in the control group, 0.10+/-0.02, 0.11+/-0.02, 0.16+/-0.02, and 0.11+/-0.03 in test groups A, B, D, and E, respectively. The A values of MTT in A549 cell strains were 0.50+/-0.06 in the control group, 0.41+/-0.04, 0.45+/-0.03, 0.59+/-0.02, and 0.45+/-0.03 in test groups A, B, D, and E, respectively. The A values of positive cells of apoptosis in A549 cell strains were 0.16+/-0.04 in the control group, 0.18+/-0.02, 0.18+/-0.05, 0.20+/-0.05, and 0.23+/-0.05 in test groups A, B, D, and E, respectively. The apoptotic rates in A549 cells were 1.11% in the control group, 18.91%,14.30%, 36.99%, and 51.92% in test groups A, B, D, and E, respectively. The expression of HDAC1 plays an important role in the proliferation and apoptosis of A549 cells, which is regulated by hypoxia. TSA may serve as a new target for therapy of lung cancer.

Activity and distribution of intracellular carbonic anhydrase II and their effects on the transport activity of anion exchanger AE1/SLC4A1.

PubMed

Al-Samir, Samer; Papadopoulos, Symeon; Scheibe, Renate J; Meißner, Joachim D; Cartron, Jean-Pierre; Sly, William S; Alper, Seth L; Gros, Gerolf; Endeward, Volker

2013-10-15

We have investigated the previously published 'metabolon hypothesis' postulating that a close association of the anion exchanger 1 (AE1) and cytosolic carbonic anhydrase II (CAII) exists that greatly increases the transport activity of AE1. We study whether there is a physical association of and direct functional interaction between CAII and AE1 in the native human red cell and in tsA201 cells coexpressing heterologous fluorescent fusion proteins CAII-CyPet and YPet-AE1. In these doubly transfected tsA201 cells, YPet-AE1 is clearly associated with the cell membrane, whereas CAII-CyPet is homogeneously distributed throughout the cell in a cytoplasmic pattern. Förster resonance energy transfer measurements fail to detect close proximity of YPet-AE1 and CAII-CyPet. The absence of an association of AE1 and CAII is supported by immunoprecipitation experiments using Flag-antibody against Flag-tagged AE1 expressed in tsA201 cells, which does not co-precipitate native CAII but co-precipitates coexpressed ankyrin. Both the CAII and the AE1 fusion proteins are fully functional in tsA201 cells as judged by CA activity and by cellular HCO3(-) permeability (P(HCO3(-))) sensitive to inhibition by 4,4-Diisothiocyano-2,2-stilbenedisulfonic acid. Expression of the non-catalytic CAII mutant V143Y leads to a drastic reduction of endogenous CAII and to a corresponding reduction of total intracellular CA activity. Overexpression of an N-terminally truncated CAII lacking the proposed site of interaction with the C-terminal cytoplasmic tail of AE1 substantially increases intracellular CA activity, as does overexpression of wild-type CAII. These variously co-transfected tsA201 cells exhibit a positive correlation between cellular P(HCO3(-)) and intracellular CA activity. The relationship reflects that expected from changes in cytoplasmic CA activity improving substrate supply to or removal from AE1, without requirement for a CAII-AE1 metabolon involving physical interaction. A functional contribution of the hypothesized CAII-AE1 metabolon to erythroid AE1-mediated HCO3(-) transport was further tested in normal red cells and red cells from CAII-deficient patients that retain substantial CA activity associated with the erythroid CAI protein lacking the proposed AE1-binding sequence. Erythroid P(HCO3(-)) was indistinguishable in these two cell types, providing no support for the proposed functional importance of the physical interaction of CAII and AE1. A theoretical model predicts that homogeneous cytoplasmic distribution of CAII is more favourable for cellular transport of HCO3(-) and CO2 than is association of CAII with the cytoplasmic surface of the plasma membrane. This is due to the fact that the relatively slow intracellular transport of H(+) makes it most efficient to place the CA in the vicinity of the haemoglobin molecules, which are homogeneously distributed over the cytoplasm.

Cinnamaldehyde, Cinnamic Acid, and Cinnamyl Alcohol, the Bioactives of Cinnamomum cassia Exhibit HDAC8 Inhibitory Activity: An In vitro and In silico Study

PubMed Central

Patil, Mangesh; Choudhari, Amit S.; Pandita, Savita; Islam, Md Ataul; Raina, Prerna; Kaul-Ghanekar, Ruchika

2017-01-01

Background: The altered expression of histone deacetylase family member 8 (HDAC8) has been found to be linked with various cancers, thereby making its selective inhibition a potential strategy in cancer therapy. Recently, plant secondary metabolites, particularly phenolic compounds, have been shown to possess HDAC inhibitory activity. Objective: In the present work, we have evaluated the potential of cinnamaldehyde (CAL), cinnamic acid (CA), and cinnamyl alcohol (CALC) (bioactives of Cinnamomum) as well as aqueous cinnamon extract (ACE), to inhibit HDAC8 activity in vitro and in silico. Materials and Methods: HDAC8 inhibitory activity of ACE and cinnamon bioactives was determined in vitro using HDAC8 inhibitor screening kit. Trichostatin A (TSA), a well-known anti-cancer agent and HDAC inhibitor, was used as a positive control. In silico studies included molecular descriptor Analysis molecular docking absorption, distribution, metabolism, excretion, and toxicity prediction, density function theory calculation and synthetic accessibility program. Results: Pharmacoinformatics studies implicated that ACE and its Bioactives (CAL, CA, and CALC) exhibited comparable activity with that of TSA. The highest occupied molecular orbitals and lowest unoccupied molecular orbitals along with binding energy of cinnamon bioactives were comparable with that of TSA. Molecular docking results suggested that all the ligands maintained two hydrogen bond interactions within the active site of HDAC8. Finally, the synthetic accessibility values showed that cinnamon bioactives were easy to synthesize compared to TSA. Conclusion: It was evident from both the experimental and computational data that cinnamon bioactives exhibited significant HDAC8 inhibitory activity, thereby suggesting their potential therapeutic implications against cancer. SUMMARY Pharmacoinformatics studies revealed that cinnamon bioactives bound to the active site of HDAC8 enzyme in a way similar to that of TSAThe molecular descriptors of cinnamon compounds successfully correlated with TSA values. The binding interactions and energies were also found to be close to TSASynthetic accessibility values showed that cinnamon bioactives were easy to synthesize compared to TSA. Abbreviations used: ACE: Aqueous Cinnamon Extract; DFT: Density Function Theory; CAL: Cinnamaldehyde; CA: Cinnamic Acid; CALC: Cinnamyl Alcohol; MW: Molecular Weight; ROTBs: Rotatable Bonds; ROF: Lipinski's Rule of Five; TSA: Trichostatin A; PDB: Protein Data Bank; RMSD: Root Mean Square Deviation; HBA: Hydrogen Bond Acceptor; HBD: Hydrogen Bond Donor; ADMET: Absorption, Distribution, Metabolism, Excretion and Toxicity; FO: Frontier Orbital; HOMOs: Highest Occupied Molecular Orbitals; LUMOs: Lowest Unoccupied Molecular Orbitals; BE: Binding Energy. PMID:29142427

9/11 Commission Recommendations: Implementation Status

DTIC Science & Technology

2006-12-04

that occurred from 2004-2005. U.S., Afghan, and international officials have cited the cultivation and trafficking as a serious strategic threat to U.S...Administration ( TSA ). alien smuggling in certain circumstances and required the Secretary of Homeland Security to develop an outreach program in the...the Transportation Security Administration ( TSA ) take over the function of prescreening passenger names using the larger set of watchlists maintained

Cytotoxic, phytotoxic, and mutagenic appraisal to ascertain toxicological potential of particulate matter emitted from automobiles.

PubMed

Anwar, Khaleeq; Ejaz, Sohail; Ashraf, Muhammad; Altaf, Imran; Anjum, Aftab Ahmad

2013-07-01

Vehicular air pollution is a mounting health issue of the modern age, particularly in urban populations of the developing nations. Auto-rickshaws are not considered eco-friendly as to their inefficient engines producing large amount of particulate matter (PM), thus posing significant environmental threat. The present study was conducted to ascertain the cytotoxic, phytotoxic, and mutagenic potential of PM from gasoline-powered two-stroke auto-rickshaws (TSA) and compressed natural gas-powered four-stroke auto-rickshaws (FSA). Based on the increased amount of aluminum quantified during proton-induced X-ray emission analysis of PM from TSA and FSA, different concentrations of aluminum sulfate were also tested to determine its eco-toxicological potential. The MTT assay demonstrated significant (p < 0.001) dose-dependent cytotoxic effects of different concentrations of TSA, FSA, and aluminum sulfate on BHK-21 cell line. LC50 of TSA, FSA, and aluminum sulfate was quantified at 16, 11, and 23.8 μg/ml, respectively, establishing PM from FSA, a highly cytotoxic material. In case of phytotoxicity screening using Zea mays, the results demonstrated that all three tested materials were equally phytotoxic at higher concentrations producing significant reduction (p < 0.001) in seed germination. Aluminum sulfate proved to be a highly phytotoxic agent even at its lowest concentration. Mutagenicity was assessed by fluctuation Salmonella reverse mutation assay adopting TA100 and TA98 mutant strains with (+S9) and without (-S9) metabolic activation. Despite the fact that different concentrations of PM from both sources, i.e., TSA and FSA were highly mutagenic (p < 0.001) even at lower concentrations, the mutagenic index was higher in TSA. Data advocate that all tested materials are equally ecotoxic, and if the existing trend of atmospheric pollution by auto-rickshaws is continued, airborne heavy metals will seriously affect the normal growth of local inhabitants and increased contamination of agricultural products, which will amplify the dietary intake of the toxic elements and could result in genetic mutation or long-term health implications.

General anesthesia versus segmental thoracic or conventional lumbar spinal anesthesia for patients undergoing laparoscopic cholecystectomy.

PubMed

Yousef, Gamal T; Lasheen, Ahmed E

2012-01-01

Laparoscopic cholecystectomy became the standard surgery for gallstone disease because of causing less postoperative pain, respiratory compromise and early ambulation. This study was designed to compare spinal anesthesia, (segmental thoracic or conventional lumbar) vs the gold standard general anesthesia as three anesthetic techniques for healthy patients scheduled for elective laparoscopic cholecystectomy, evaluating intraoperative parameters, postoperative recovery and analgesia, complications as well as patient and surgeon satisfaction. A total of 90 patients undergoing elective laparoscopic cholecystectomy, between January 2010 and May 2011, were randomized into three equal groups to undergo laparoscopic cholecystectomy with low-pressure CO2 pneumoperitoneum under segmental thoracic (TSA group) or conventional lumbar (LSA group) spinal anesthesia or general anesthesia (GA group). To achieve a T3 sensory level we used (hyperbaric bupivacaine 15 mg, and fentanyl 25 mg at L2/L3) for LSAgroup, and (hyperbaric bupivacaine 7.5 mg, and fentanyl 25 mg at T10/T11) for TSAgroup. Propofol, fentanyl, atracurium, sevoflurane, and tracheal intubation were used for GA group. Intraoperative parameters, postoperative recovery and analgesia, complications as well as patient and surgeon satisfaction were compared between the three groups. All procedures were completed laparoscopically by the allocated method of anesthesia with no anesthetic conversions. The time for the blockade to reach T3 level, intraoperative hypotensive and bradycardic events and vasopressor use were significantly lower in (TSA group) than in (LSA group). Postoperative pain scores as assessed throughout any time, postoperative right shoulder pain and hospital stay was lower for both (TSA group) and (LSA group) compared with (GA group). The higher degree of patients satisfaction scores were recorded in patients under segmental TSA. The present study not only confirmed that both segmental TSA and conventional lumber spinal anesthesia (LSA) are safe and good alternatives to general anesthesia (GA) in healthy patients undergoing laparoscopic cholecystectomy but also showed better postoperative pain control of both spinal techniques when compared with general anesthesia. Segmental TSA provides better hemodynamic stability, lesser vasopressor use and early ambulation and discharge with higher degree of patient satisfaction making it excellent for day case surgery compared with conventional lumbar spinal anesthesia.

Age-related differences in the use of total shoulder arthroplasty over time: use and outcomes.

PubMed

Singh, J A; Ramachandran, R

2015-10-01

We assessed the age-related differences in the use of total shoulder arthroplasty (TSA) and outcomes, and associated time-trends using the United States Nationwide Inpatient Sample (NIS) between 1998 and 2010. Age was categorised as < 50, 50 to 64, 65 to 79 and ≥ 80 years. Time-trends in the use of TSA were compared using logistic regression or the Cochran Armitage test. The overall use of TSA increased from 2.96/100 000 in 1998 to 12.68/100,000 in 2010. Significantly lower rates were noted between 2009 and 2010, compared with between 1998 and 2000, for: mortality, 0.1% versus 0.2% (p = 0.004); discharge to an inpatient facility, 13.3% versus 14.5% (p = 0.039), and hospital stay > median, 29.4% versus 51.2% (p < 0.001). The rates of use of TSA/100,000 by age groups, < 50, 50 to 64, 65 to 79 and ≥ 80 years were: 0.32, 4.62, 17.82 and 12.56, respectively in 1998 (p < 0.001); and 0.65, 17.49, 75.27 and 49.05, respectively in 2010 (p < 0.001) with an increasing age-related difference over time (p < 0.001). Across the age categories, there were significant differences in the proportion: discharged to an inpatient facility, 3.2% versus 4.2% versus 14.7% versus 36.5%, respectively in 1998 (p < 0.001) and 1.8% versus 4.3% versus 12.5% versus 35.5%, respectively in 2010 (p < 0.001) and the proportion with hospital stay > median, 39.7% versus 40.2% versus 53% versus 69%, respectively in 1998 (p < 0.001) and 17.2% versus 20.6% versus 28.7% versus 50.7%, respectively in 2010 (p < 0.001). In a nationally representative sample, we noted a time-related increase in the use of TSA and increasing age-related differences in outcomes indicating a changing epidemiology of the use of TSA. Age-related differences in outcomes suggest that attention should focus on groups with the worst outcomes. ©2015 The British Editorial Society of Bone & Joint Surgery.

Trypanosoma cruzi vaccine candidate antigens Tc24 and TSA-1 recall memory immune response associated with HLA-A and -B supertypes in Chagasic chronic patients from Mexico.

PubMed

Villanueva-Lizama, Liliana E; Cruz-Chan, Julio V; Aguilar-Cetina, Amarú Del C; Herrera-Sanchez, Luis F; Rodriguez-Perez, Jose M; Rosado-Vallado, Miguel E; Ramirez-Sierra, Maria J; Ortega-Lopez, Jaime; Jones, Kathryn; Hotez, Peter; Bottazzi, Maria Elena; Dumonteil, Eric

2018-01-01

Trypanosoma cruzi antigens TSA-1 and Tc24 have shown promise as vaccine candidates in animal studies. We evaluated here the recall immune response these antigens induce in Chagasic patients, as a first step to test their immunogenicity in humans. We evaluated the in vitro cellular immune response after stimulation with recombinant TSA-1 (rTSA-1) or recombinant Tc24 (rTc24) in mononuclear cells of asymptomatic Chagasic chronic patients (n = 20) compared to healthy volunteers (n = 19) from Yucatan, Mexico. Proliferation assays, intracellular cytokine staining, cytometric bead arrays, and memory T cell immunophenotyping were performed by flow cytometry. Peripheral blood mononuclear cells (PBMC) from Chagasic patients showed significant proliferation after stimulation with rTc24 and presented a phenotype of T effector memory cells (CD45RA-CCR7-). These cells also produced IFN-γ and, to a lesser extent IL10, after stimulation with rTSA-1 and rTc24 proteins. Overall, both antigens recalled a broad immune response in some Chagasic patients, confirming that their immune system had been primed against these antigens during natural infection. Analysis of HLA-A and HLA-B allele diversity by PCR-sequencing indicated that HLA-A03 and HLA-B07 were the most frequent supertypes in this Mexican population. Also, there was a significant difference in the frequency of HLA-A01 and HLA-A02 supertypes between Chagasic patients and controls, while the other alleles were evenly distributed. Some aspects of the immune response, such as antigen-induced IFN-γ production by CD4+ and CD8+ T cells and CD8+ proliferation, showed significant association with specific HLA-A supertypes, depending on the antigen considered. In conclusion, our results confirm the ability of both TSA-1 and Tc24 recombinant proteins to recall an immune response induced by the native antigens during natural infection in at least some patients. Our data support the further development of these antigens as therapeutic vaccine against Chagas disease.

Trichostatin A, a histone deacetylase inhibitor, suppresses JAK2/STAT3 signaling via inducing the promoter-associated histone acetylation of SOCS1 and SOCS3 in human colorectal cancer cells.

PubMed

Xiong, Hua; Du, Wan; Zhang, Yan-Jie; Hong, Jie; Su, Wen-Yu; Tang, Jie-Ting; Wang, Ying-Chao; Lu, Rong; Fang, Jing-Yuan

2012-02-01

Aberrant janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling is involved in the oncogenesis of several cancers. Suppressors of cytokine signaling (SOCS) genes and SH2-containing protein tyrosine phosphatase 1 (SHP1) proteins, which are negative regulators of JAK/STAT signaling, have been reported to have tumor suppressor functions. However, in colorectal cancer (CRC) cells, the mechanisms that regulate SOCS and SHP1 genes, and the cause of abnormalities in the JAK/STAT signaling pathway, remain largely unknown. The present study shows that trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, leads to the hyperacetylation of histones associated with the SOCS1 and SOCS3 promoters, but not the SHP1 promoter in CRC cells. This indicates that histone modifications are involved in the regulation of SOCS1 and SOCS3. Moreover, upregulation of SOCS1 and SOCS3 expression was achieved using TSA, which also significantly downregulated JAK2/STAT3 signaling in CRC cells. We also demonstrate that TSA suppresses the growth of CRC cells, and induces G1 cell cycle arrest and apoptosis through the regulation of downstream targets of JAK2/STAT3 signaling, including Bcl-2, survivin and p16(ink4a) . Therefore, our data demonstrate that TSA may induce SOCS1 and SOCS3 expression by inducing histone modifications and consequently inhibits JAK2/STAT3 signaling in CRC cells. These results also establish a mechanistic link between the inhibition of JAK2/STAT3 signaling and the anticancer action of TSA in CRC cells. Copyright © 2011 Wiley Periodicals, Inc.

Depletion of the chloramine-T marker residue, para-toluenesulfonamide, from skin-on fillet tissue of hybrid striped bass, rainbow trout, and yellow perch

USGS Publications Warehouse

Meinertz, J.R.; Stehly, G.R.; Greseth, Shari L.; Gaikowski, M.P.; Gingerich, W.H.

2004-01-01

Waterborne exposure to n-sodium-n-chloro-p-toluenesulfonamide (chloramine-T) is an effective treatment for controlling fish mortalities caused by bacterial gill disease (BGD). Currently, data are being generated to gain United States Food and Drug Administration (FDA) approval for the use of chloramine-T in aquaculture. As part of the data required for an approval, depletion of the chloramine-T marker residue (para-toluenesulfonamide [p-TSA]) from the edible fillet tissue of exposed fish must be determined. Hybrid striped bass (Morone saxatilis??Morone chrysops; mean weight 357 g), rainbow trout (Oncorhynchus mykiss; mean weight 457 g), and yellow perch (Perca flavescens; mean weight 144 g) were exposed to 20 mg/l of chloramine-T for 60 min on 4 consecutive days (the most aggressive treatment expected for approved use in the United States). Groups of fish (n=15 or 19) were sampled immediately after the last treatment and periodically through 48 or 168 h after the treatment phase. Duplicate subsamples of skin-on fillet tissue from each fish were analyzed for p-TSA. Mean p-TSA concentrations in fillet tissue from fish sampled immediately after the last treatment were 142 ng/g (hybrid striped bass), 97 ng/g (rainbow trout), and 150 ng/g (yellow perch). Mean p-TSA concentrations at terminal sample times were 94 (168 h; hybrid striped bass), 74 (48 h; rainbow trout), and 35 ng/g (168 h; yellow perch). The half-lives of p-TSA in fillet tissue from fish near or at market size were 11.4 (hybrid striped bass), 4.3 (rainbow trout), and 3.2 days (yellow perch).

Nephrotoxicity of Epigenetic Inhibitors Used for the Treatment of Cancer

PubMed Central

Scholpa, N.E.; Kolli, R.T.; Moore, M.; Arnold, R.D.; Glenn, T.C.; Cummings, B.S.

2016-01-01

This study determined the anti-neoplastic activity and nephrotoxicity of epigenetic inhibitors in vitro. The therapeutic efficacy of epigenetic inhibitors was determined in human prostate cancer cells (PC-3 and LNCaP) using the DNA methyltransferase inhibitor 5-azacytidine (5-Aza) and the histone deacetylase inhibitor trichostatin A (TSA). Cells were also treated with carbamazepine (CBZ), an anti-convulsant with histone deacetylase inhibitor-like properties. 5-Aza, TSA or CBZ alone did not decrease MTT staining in PC-3 or LNCaP cells after 48 hr. In contrast, docetaxel, a frontline chemotherapeutic induced concentration-dependent decreases in MTT staining. Pretreatment with 5-Aza or TSA increased docetaxel-induced cytotoxicity in LNCaP cells, but not PC-3 cells. TSA pretreatment also increased cisplatin-induced toxicity in LNCaP cells. Carfilzomib (CFZ), a protease inhibitor approved for the treatment of multiple myeloma had minimal effect on LNCaP cell viability, but reduced MTT staining 50% in PC-3 cells compared to control, and pretreatment with 5-Aza further enhanced toxicity. Treatment of normal rat kidney (NRK) and human embryonic kidney 293 (HEK293) cells with the same concentrations of epigenetic inhibitors used in prostate cancer cells significantly decreased MTT staining in all cell lines after 48 hr. Interestingly, we found that the toxicity of epigenetic inhibitors to kidney cells was dependent on both the compound and the stage of cell growth. The effect of 5-Aza and TSA on DNA methyltransferase and histone deacetylase activity, respectively, was confirmed by assessing the methylation and acetylation of the CDK inhibitor p21. Collectively, these data show that combinatorial treatment with epigenetic inhibitors alters the efficacy of chemotherapeutics in cancer cells in a compound- and cell-specific manner; however, this treatment also has the potential to induce nephrotoxic cell injury. PMID:27543423

Comparing the Levels of Acute-Phase Reactants Between Smoker and Nonsmoker Diabetic Patients: More Predicted Risk for Cardiovascular Diseases in Smoker Compared to Nonsmoker Diabetics.

PubMed

Rezaei-Adl, Sepideh; Ghahroudi Tali, Arash; Saffar, Hiva; Rajabiani, Afsaneh; Abdollahi, Alireza

2017-09-01

 Due to a close link between cardiovascular disorders and increased acute phase responses, it is now proposed the relation of total sialic acid (TSA) and C Reactive Protein (CRP) as main components of acute phase proteins and cardiovascular risk profiles such as diabetes mellitus and smoking. We hypothesized that the elevation in the level of TSA along with other prototype acute phase reactants such as CRP is expected more in the coexistence of diabetes and smoking than in diabetes mellitus alone. Ninety diabetic patients were randomly selected and entered into this case-control study. Using block randomization method, the patients were randomly assigned into smokers (n=45) and nonsmokers (n=45). A group of ten healthy individuals was also included as the control. The serum levels of TSA, CRP, iron, and hemoglobin were measured by the specific techniques. Comparing laboratory parameters across the three groups indicated significantly higher levels of TSA and CRP in smoker diabetics as compared to non-smoker diabetics and the healthy controls, while there was no difference in other parameters including serum iron and hemoglobin. A significant positive correlation was also revealed between TCA and CRP (r=0.324, P=0.030), but no significant association was found between other parameters. In the background of smoking, increasing the level of both TSA and CRP is predicted more than the existence of diabetes mellitus alone. In fact, the increase in these biomarkers is more predictable in smoker than in nonsmoker diabetics. This finding emphasizes the increased risk for cardiovascular disorders in smoker compared to non-smoker diabetics.

Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin

PubMed Central

Furumai, Ryohei; Komatsu, Yasuhiko; Nishino, Norikazu; Khochbin, Saadi; Yoshida, Minoru; Horinouchi, Sueharu

2001-01-01

Trichostatin A (TSA) and trapoxin (TPX) are potent inhibitors of histone deacetylases (HDACs). TSA is proposed to block the catalytic reaction by chelating a zinc ion in the active-site pocket through its hydroxamic acid group. On the other hand, the epoxyketone is suggested to be the functional group of TPX capable of alkylating the enzyme. We synthesized a novel TPX analogue containing a hydroxamic acid instead of the epoxyketone. The hybrid compound cyclic hydroxamic acid-containing peptide (CHAP) 1 inhibited HDAC1 at low nanomolar concentrations. The HDAC1 inhibition by CHAP1 was reversible as it was by TSA, in contrast to the irreversible inhibition by TPX. CHAP with an aliphatic chain length of five, which corresponded to that of acetylated lysine, was stronger than those with other lengths. These results suggest that TPX is a substrate mimic and that the replacement of the epoxyketone with the hydroxamic acid converted TPX to an inhibitor chelating the zinc like TSA. Interestingly, HDAC6, but not HDAC1 or HDAC4, was resistant to TPX and CHAP1, whereas TSA inhibited these HDACs to a similar extent. HDAC6 inhibition by TPX at a high concentration was reversible, probably because HDAC6 is not alkylated by TPX. We further synthesized the counterparts of all known naturally occurring cyclic tetrapeptides containing the epoxyketone. HDAC1 was highly sensitive to all these CHAPs much more than HDAC6, indicating that the structure of the cyclic tetrapeptide framework affects the target enzyme specificity. These results suggest that CHAP is a unique lead to develop isoform-specific HDAC inhibitors. PMID:11134513

Sp1 and Sp3 Are the Transcription Activators of Human ek1 Promoter in TSA-Treated Human Colon Carcinoma Cells.

PubMed

Kuan, Chee Sian; See Too, Wei Cun; Few, Ling Ling

2016-01-01

Ethanolamine kinase (EK) catalyzes the phosphorylation of ethanolamine, the first step in the CDP-ethanolamine pathway for the biosynthesis of phosphatidylethanolamine (PE). Human EK exists as EK1, EK2α and EK2β isoforms, encoded by two separate genes, named ek1 and ek2. EK activity is stimulated by carcinogens and oncogenes, suggesting the involvement of EK in carcinogenesis. Currently, little is known about EK transcriptional regulation by endogenous or exogenous signals, and the ek gene promoter has never been studied. In this report, we mapped the important regulatory regions in the human ek1 promoter. 5' deletion analysis and site-directed mutagenesis identified a Sp site at position (-40/-31) that was essential for the basal transcription of this gene. Treatment of HCT116 cells with trichostatin A (TSA), a histone deacetylase inhibitor, significantly upregulated the ek1 promoter activity through the Sp(-40/-31) site and increased the endogenous expression of ek1. Chromatin immunoprecipitation assay revealed that TSA increased the binding of Sp1, Sp3 and RNA polymerase II to the ek1 promoter in HCT116 cells. The effect of TSA on ek1 promoter activity was cell-line specific as TSA treatment did not affect ek1 promoter activity in HepG2 cells. In conclusion, we showed that Sp1 and Sp3 are not only essential for the basal transcription of the ek1 gene, their accessibility to the target site on the ek1 promoter is regulated by histone protein modification in a cell line dependent manner.

Functional link between DNA damage responses and transcriptional regulation by ATM in response to a histone deacetylase inhibitor TSA.

PubMed

Lee, Jong-Soo

2007-09-01

Mutations in the ATM (ataxia-telangiectasia mutated) gene, which encodes a 370 kd protein with a kinase catalytic domain, predisposes people to cancers, and these mutations are also linked to ataxia-telangiectasia (A-T). The histone acetylaion/deacetylation- dependent chromatin remodeling can activate the ATM kinase-mediated DNA damage signal pathway (in an accompanying work, Lee, 2007). This has led us to study whether this modification can impinge on the ATM-mediated DNA damage response via transcriptional modulation in order to understand the function of ATM in the regulation of gene transcription. To identify the genes whose expression is regulated by ATM in response to histone deaceylase (HDAC) inhibition, we performed an analysis of oligonucleotide microarrays with using the appropriate cell lines, isogenic A-T (ATM(-)) and control (ATM(+)) cells, following treatment with a HDAC inhibitor TSA. Treatment with TSA reprograms the differential gene expression profile in response to HDAC inhibition in ATM(-) cells and ATM(+) cells. We analyzed the genes that are regulated by TSA in the ATM-dependent manner, and we classified these genes into different functional categories, including those involved in cell cycle/DNA replication, DNA repair, apoptosis, growth/differentiation, cell- cell adhesion, signal transduction, metabolism and transcription. We found that while some genes are regulated by TSA without regard to ATM, the patterns of gene regulation are differentially regulated in an ATM-dependent manner. Taken together, these finding indicate that ATM can regulate the transcription of genes that play critical roles in the molecular response to DNA damage, and this response is modulated through an altered HDAC inhibition-mediated gene expression.

Assessing the growth and recovery of Salmonella Enteritidis SE86 after sodium dichloroisocyanurate exposure

PubMed Central

Ferreira, Fernanda Stoduto; Horvath, Mariana Bandeira; Tondo, Eduardo Cesar

2013-01-01

The objective of the present study was to assess the growth and the recovery of Salmonella (S.) Enteritidis SE86 in different diluents, culture media and using different plating methods after the exposure to 200 mg/kg sodium dichloroisocyanurate (NaDCC). Before and after NaDCC exposure, SE86 was cultured at 30 °C and 7 °C in the following diluents: Peptone water (P), Saline solution (SaS), Peptone water+Saline solution (P+SaS), Peptone water+Tween 80+Lecithin+Sodium thiosulfate (P+N) and Saline solution+Tween 80+Lecithin+Sodium thiosulfate (SaS+N). The SaS diluent was chosen because it was able to maintain cells viable without growth and was further used for plating SE86 on non selective medium (Tryptic Soy Agar-TSA) and on selective media (Mannitol Lysine Crystal Violet Brilliant Green Agar-MLCB; Brilliant Green Agar-BGA; Salmonella Shigella Agar-SS and Xylose Lysine Dextrose–XLD). The Thin Agar Layer method (TAL) i.e., selective media overlayed with non selective TSA was also evaluated. Results indicated that SE86 not exposed to NaDCC was able to grow in P, P+N, SaS+N and P+SaS, but not in SaS, that was able to maintain cells viable. SE86 exposed to NaDCC demonstrated similar counts after dilution in SaS and the plating on non selective TSA, selective media MLCB, BGA, SS and XLD and on TAL media. SE86, S. Typhimurium and S. Bredeney, exposed or not exposed to NaDCC, showed no significant differences in counts on TSA, XLD and XLD overlayed with TSA, suggesting that all those media may be used to quantify NaDCC-exposed Salmonella by plating method. PMID:24516446

Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis.

PubMed

Krag, Mette; Perner, Anders; Wetterslev, Jørn; Wise, Matt P; Hylander Møller, Morten

2014-01-01

To assess the effects of stress ulcer prophylaxis (SUP) versus placebo or no prophylaxis on all-cause mortality, gastrointestinal (GI) bleeding and hospital-acquired pneumonia in adult critically ill patients in the intensive care unit (ICU). We performed a systematic review using meta-analysis and trial sequential analysis (TSA). Eligible trials were randomised clinical trials comparing proton pump inhibitors or histamine 2 receptor antagonists with either placebo or no prophylaxis. Two reviewers independently assessed studies for inclusion and extracted data. The Cochrane Collaboration methodology was used. Risk ratios/relative risks (RR) with 95% confidence intervals (CI) were estimated. The predefined outcome measures were all-cause mortality, GI bleeding, and hospital-acquired pneumonia. Twenty trials (n = 1,971) were included; all were judged as having a high risk of bias. There was no statistically significant difference in mortality (fixed effect: RR 1.00, 95% CI 0.84-1.20; P = 0.87; I(2) = 0%) or hospital-acquired pneumonia (random effects: RR 1.23, 95% CI 0.86-1.78; P = 0.28; I(2) = 19%) between SUP patients and the no prophylaxis/placebo patients. These findings were confirmed in the TSA. With respect to GI bleeding, a statistically significant difference was found in the conventional meta-analysis (random effects: RR 0.44, 95% CI 0.28-0.68; P = 0.01; I(2) = 48%); however, TSA (TSA adjusted 95% CI 0.18-1.11) and subgroup analyses could not confirm this finding. This systematic review using meta-analysis and TSA demonstrated that both the quality and the quantity of evidence supporting the use of SUP in adult ICU patients is low. Consequently, large randomised clinical trials are warranted.

Analysis of load distribution in tooth-implant supported fixed partial dentures by the use of resilient abutment.

PubMed

Glisić, Mirko; Stamenković, Dragoslav; Grbović, Aleksandar; Todorović, Aleksandar; Marković, Aleksa; Trifković, Branka

2016-01-01

Differences between the tooth and implant response to load can lead to many biological and technical implications in the conditions of occlusal forces. The objective of this study was to analyze load distribution in tooth/implant-supported fixed partial dentures with the use of resilient TSA (Titan Shock Absorber, BoneCare GmbH, Augsburg, Germany) abutment and conventional non-resilient abutment using finite element method. This study presents two basic 3D models. For one model a standard non-resilient abutment is used, and on the implant of the second model a resilient TSA abutment is applied. The virtual model contains drawn contours of tooth, mucous membranes, implant, cortical bones and spongiosa, abutment and suprastructure. The experiment used 500 N of vertical force, applied in three different cases of axial load. Calculations of von Mises equivalent stresses of the tooth root and periodontium, implants and peri-implant tissue were made. For the model to which a non-resilient abutment is applied, maximum stress values in all three cases are observed in the cortical part of the bone (maximum stress value of 49.7 MPa). Measurements of stress and deformation in the bone tissue in the model with application of the resilientTSA abutment demonstrated similar distribution; however, these values are many times lower than in the model with non-resilient TSA abutment (maximum stress value of 28.9 MPa). Application of the resilient TSA abutment results in more equal distribution of stress and deformations in the bone tissue under vertical forces. These values are many times lower than in the model with the non-resilient abutment.

gp-91 mediates histone deacetylase inhibition-induced cardioprotection

PubMed Central

Zhao, Ting C; Zhang, Ling X; Cheng, Guangmao; Liu, Jun T

2010-01-01

We have recently shown that the inhibition of histone deacetylases (HDAC) protects the heart against ischemia and reperfusion (I/R) injury. The mechanism by which HDAC inhibition induces cardioprotection remains unknown. We sought to investigate whether the genetic disruption of gp-91, a subunit of NADPH-oxidase, would mitigate cardioprotection of HDAC inhibition. Wild-type and gp-91−/− mice were treated with a potent inhibitor of HDACs, trichostatin A (TSA, 0.1mg/kg, i.p.). Twenty-four hours later, the perfused hearts were subjected to 30 min of ischemia and 30 min of reperfusion. HDAC inhibition in wild-type mice produced marked improvements in ventricular functional recovery and the reduction of infarct size. TSA-induced cardioprotection was eliminated with genetic deletion of gp91. Notably, Western blot and immunostaining displayed a significant increase in gp-91 in myocardium following HDAC inhibition, which resulted in a mildly subsequent increase in the production of reactive oxygen species (ROS). The pretreatment of H9c2 cardiomyoblasts with TSA (50 nmol/L) decreased cell necrosis and increased viability in response to simulated ischemia (SI), which was abrogated by the transfection of cells with gp-91 siRNA, but not by scrambled siRNA. Furthermore, treatment of PLB-985 gp91+/+cells with TSA increased the resistance to SI, which also diminished with genetic disruption of gp91 in gp91phox-deficient PLB-985 cells. TSA treatment inhibited the increased active caspase-3 in H9c2 cardiomyoblasts and PLB-985 gp91+/+cells exposed to SI, which were prevented by knockdown of gp-91 by siRNA. These results suggest that a cascade consisting of gp-91 and HDAC inhibition plays an essential role in orchestrating the cardioprotective effect. PMID:20433879

Antibodies and a cysteine-modifying reagent show correspondence of M current in neurons to KCNQ2 and KCNQ3 K+ channels

PubMed Central

Roche, John P; Westenbroek, Ruth; Sorom, Abraham J; Hille, Bertil; Mackie, Ken; Shapiro, Mark S

2002-01-01

KCNQ K+ channels are thought to underlie the M current of neurons. To probe if the KCNQ2 and KCNQ3 subtypes underlie the M current of rat superior cervical ganglia (SCG) neurons and of hippocampus, we raised specific antibodies against them and also used the cysteine-alkylating agent N-ethylmaleimide (NEM) as an additional probe of subunit composition. Tested on tsA-201 (tsA) cells transfected with cloned KCNQ1-5 subunits, our antibodies showed high affinity and selectivity for the appropriate subtype. The antibodies immunostained SCG neurons and hippocampal sections at levels similar to those for channels expressed in tsA cells, indicating that KCNQ2 and KCNQ3 are present in SCG and hippocampal neurons. Some hippocampal regions contained only KCNQ2 or KCNQ3 subunits, suggesting the presence of M currents produced by channels other than KCNQ2/3 heteromultimers. We found that NEM augmented M currents in SCG neurons and KCNQ2/3 currents in tsA cells via strong voltage-independent and modest voltage-dependent actions. Expression of individual KCNQ subunits in tsA cells revealed voltage-independent augmentation of KCNQ2, but not KCNQ1 nor KCNQ3, currents by NEM indicating that this action on SCG M currents likely localizes to KCNQ2. Much of the voltage-independent action is lost after the C242T mutation in KCNQ2. The correspondence of NEM effects on expressed KCNQ2/3 and SCG M currents, along with the antibody labelling, provide further evidence that KCNQ2 and KCNQ3 subunits strongly contribute to the M current of neurons. The site of NEM action may be important for treatment of diseases caused by under-expression of these channels. PMID:12466226

Curcumin enhances the anticancer effects of trichostatin a in breast cancer cells.

PubMed

Yan, Guang; Graham, Kimmer; Lanza-Jacoby, Susan

2013-05-01

Breast cancer patients with HER-2 positive or estrogen receptor negative tumors have a poor prognosis because these tumors are aggressive and respond poorly to standard therapies. Histone deacetylase (HDAC) inhibitors have been shown to decreased cell survival, which suggests that HDAC inhibitors may be developed for preventing and treating breast cancer. Curcumin has anti-inflammatory and proapoptotic effects in cancer cells. We determined whether the HDAC inhibitor, Tricostatin A (TSA) in combination with curcumin would produce greater antiproliferative and apoptotic effects than either agent alone. Increasing the concentration of curcumin from 10 to 20 µM enhanced the growth inhibitory effects of the combination in SkBr3 and 435eB breast cancer cells, which was accompanied by decreased viability along with decreased phosphorylation of ERK and Akt. The decreased cell viability observed in SkBr3 cells when curcumin was combined with TSA led to a G0/G1 cell cycle arrest and increased p21 and p27, and decreased Cyclin D1 protein expression. The combination induced cleavage of caspase 3 and poly(ADP-ribose) polymerase-1, suggesting that cell death occurred by apoptosis. There were no changes in protein expression of Bcl2, Bax, or Bcl-xL and decreased expression of p53. The combination increased protein expression of phosphorylated JNK and phosphorylated p38. Pharmacological inhibition of JNK, but not p38, attenuated the decreased viability induced by the curcumin and TSA combination. We conclude that p53 independent apoptosis induced by combining curcumin and TSA involves JNK activation. These findings provide a rationale for exploring the potential benefits of the combination of curcumin with TSA for treatment of breast cancer. Copyright © 2012 Wiley Periodicals, Inc.

A Cell Culture Model of Latent and Lytic Herpes Simplex Virus Type 1 Infection in Spiral Ganglion.

PubMed

Liu, Yuehong; Li, Shufeng

2015-01-01

Reactivation of latent herpes simplex virus type 1 (HSV-1) in spiral ganglion neurons (SGNs) is supposed to be one of the causes of idiopathic sudden sensorineural hearing loss. This study aims to establish a cell culture model of latent and lytic HSV-1 infection in spiral ganglia. In the presence of acyclovir, primary cultures of SGNs were latently infected with HSV-1 expressing green fluorescent protein. Four days later, these cells were treated with trichostatin A (TSA), a known chemical reactivator of HSV-1. TCID50 was used to measure the titers of virus in cultures on Vero cells. RNA from cultures was detected for the presence of transcripts of ICP27 and latency-associated transcript (LAT) using reverse transcription polymerase chain reaction. There is no detectable infectious HSV-1 in latently infected cultures, whereas they could be observed in both lytically infected and latently infected/TSA-treated cultures. LAT was the only detectable transcript during latent infection, whereas lytic ICP27 transcript was detected in lytically infected and latently infected/TSA-treated cultures. Cultured SGNs can be both latently and lytically infected with HSV-1. Furthermore, latently infected SGNs can be reactivated using TSA, yielding infectious virus.

Photocatalytic activity and antimicrobial properties of paper sheets modified with TiO2/Sodium alginate nanocomposites.

PubMed

Abdel Rehim, Mona H; El-Samahy, Magda A; Badawy, Abdelrahman A; Mohram, Maysa E

2016-09-05

Photocatalytic paper sheets were prepared by addition of different ratios of TiO2/Sodium alginate (TSA) nanocomposite. The modified paper sheets were characterized by XRD, TGA. Their morphology was studied by scanning electron microscope (SEM) and energy dispersive X-ray (EDX). Photocatalytic activity of modified paper has been studied by analysis of chemical oxygen demand (COD) of waste-water. The results confirmed the mineralization of the waste-water and enhanced removal of chemical oxygen demand (COD) by increasing the amount of photocatalyst in the paper. Moreover, the results also confirmed that presence of sodium alginate as biopolymer increased adhesion of nanoparticles to paper fibers and reduced the harmful effect of the photocatalyst on them. The paper sheets containing 7% as well as 15% TSA showed high photocatalytic activity and anti-bacterial effect against Salmonella typhimurium higher than standard antibiotic beside other microorganisms such as Candida albicans. The maximum antimicrobial effect was found in case of specimen loaded with 15% TSA. Moreover, it was found that by adding 20% TSA to the paper matrix, the properties of the paper composite collapse. The obtained results confirm the possible utilization of the modified paper in both hygienic and food packaging applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

A simulated training model for laparoscopic pyloromyotomy: Is 3D printing the way of the future?

PubMed

Williams, Andrew; McWilliam, Morgan; Ahlin, James; Davidson, Jacob; Quantz, Mackenzie A; Bütter, Andreana

2018-05-01

Hypertrophic pyloric stenosis (HPS) is a common neonatal condition treated with open or laparoscopic pyloromyotomy. 3D-printed organs offer realistic simulations to practice surgical techniques. The purpose of this study was to validate a 3D HPS stomach model and assess model reliability and surgical realism. Medical students, general surgery residents, and adult and pediatric general surgeons were recruited from a single center. Participants were videotaped three times performing a laparoscopic pyloromyotomy using box trainers and 3D-printed stomachs. Attempts were graded independently by three reviewers using GOALS and Task Specific Assessments (TSA). Participants were surveyed using the Index of Agreement of Assertions on Model Accuracy (IAAMA). Participants reported their experience levels as novice (22%), inexperienced (26%), intermediate (19%), and experienced (33%). Interrater reliability was similar for overall average GOALS and TSA scores. There was a significant improvement in GOALS (p<0.0001) and TSA scores (p=0.03) between attempts and overall. Participants felt the model accurately simulated a laparoscopic pyloromyotomy (82%) and would be a useful tool for beginners (100%). A 3D-printed stomach model for simulated laparoscopic pyloromyotomy is a useful training tool for learners to improve laparoscopic skills. The GOALS and TSA provide reliable technical skills assessments. II. Copyright © 2018 Elsevier Inc. All rights reserved.

Perspectives on the Impact of the 1994 Trial State Assessments: State Assessment Directors, State Mathematics Specialists, and State Reading Specialists.

ERIC Educational Resources Information Center

Hartka, Liz; Stancavage, Fran

This paper is the fourth in a series prepared for the National Academy of Education on the evaluation of the National Assessment of Educational Progress Trial State Assessment (TSA) and the impact of reporting TSA results. This paper provides a perspective on the last of the TSAs, an assessment of fourth-grade reading that was carried out in 44…

p-TSA/Base-Promoted Propargylation/Cyclization of β-Ketothioamides for the Regioselective Synthesis of Highly Substituted (Hydro)thiophenes.

PubMed

Nandi, Ganesh Chandra; Singh, Maya Shankar

2016-07-15

Metal-free, p-toluenesulfonic acid (p-TSA)-mediated, straightforward propargylation of β-ketothioamides with aryl propargyl alcohol has been achieved at room temperature. In addition, the reaction also provided thiazole rings as byproducts. Furthermore, the propargylated thioamides undergo intramolecular 1,5-cyclization to afford fully substituted (hydro)thiophenes in the presence of base. Notably, the approach is pot, atom, and step economical (PASE).

Assessing Student Achievement in the States. The First Report of the National Academy of Education Panel on the Evaluation of the NAEP Trial State Assessment: 1990 Trial State Assessment.

ERIC Educational Resources Information Center

National Academy of Education, Stanford, CA.

This report presents findings of the National Academy of Education Panel on the Evaluation of the Trial State Assessment (TSA) concerning the 1990 National Assessment of Educational Progress (NAEP) mathematics TSA program. The Panel's recommendations regarding the continuation of TSAs for review by the Congress, states, and Executive Branch of the…

Homeland Defense: Continued Actions Needed to Improve Management of Air Sovereignty Alert Operations

DTIC Science & Technology

2012-01-01

Better Outcomes, GAO-10-374T (Washington, D.C.: May 20, 2009); Aviation Security : DHS and TSA Have Researched, Developed and Begun Deploying Passenger... Security : TSA Has Made Progress, but Additional Efforts Are Needed to Improve Security. GAO-11-938T. Washington, D.C.: September 16, 2011. Aviation ...Washington, D.C.: October 23, 2009. Related GAO Products Homeland Defense DOD Tactical Aircraft Aviation Security Risk Management Related GAO