Arthroscopic transtendinous repair of articular-sided pasta (partial articular supraspinatus tendon avulsion) injury.

PubMed

Wang, Yi; Lu, Liangyu; Lu, Zhe; Xiao, Lei; Kang, Yifan; Wang, Zimin

2015-01-01

To evaluate clinical efficacy of arthroscopic transtendinous repair of partial articular-sided PASTA (partial articular supraspinatus tendon avulsion) injury. From February 2011 to July 2014, 12 cases of PASTA, aged 29 to 72 years with an average of 52.9 ± 13.3 years, were treated arthoscopically. To repair PASTA, articular-sided rotator cuff tear was explored, injury site was punctured and labeled with PDS absorbable monofilament suture (Ethicon, Somerville, NJ, USA) suture, subacromial bursa was cleaned up with acromioplasty, and integrity of bursa-side rotator cuff was assessed. Then with arthroscope in glenohumeral joint, footprint of the bursa-side supraspinatus tendon was preserved, rivets were introduced into the joint through supraspinatus tendon, joint-side partial tear was sutured, and anatomical reconstruction of the rotator cuff footprint was established. The patients were followed up post-operatively for 12-36 months, average 22 ± 7.3 months. The clinical outcomes were emulated with ASES (American Shoulder and Elbow Surgeons) Shoulder Score system and UCLA (University of California at Los Angeles) Shoulder rating scale. The post-operative ASES score was 89.7 ± 5.6, higher than the pre-operative one 49.8 ± 9.8 (t = 12.25, P <0.0001). While UCLA scale increased from the pre-operative 17.3, ± 3.3 to the post-operative 30.4 ± 3.2 points (t = 9.87, P <0.0001), with a satisfaction rate of 11/12 (91.7%). Trans-tendon repair is ideal for PASTA with advantage of maximal preservation of the normal rotator cuff tissue, anatomical reconstruction of the rotator cuff footprint and stable fixation of tendon-bone interface.

A study on role of triiodothyronine (T3) hormone on the improvement of articular cartilage surface architecture.

PubMed

Jia, Pei-Tong; Zhang, Xing-Lin; Zuo, Hai-Ning; Lu, Xing; Gai, Peng-Zhou

2017-10-02

The present study was aimed to investigate the effect of triiodothyronine (T3) on the improvement of articular cartilage surface architecture at in vitro level. The T3 hormone was applied to neo-tissues in the range of 50, 100, 150 and 200ng/ml for 5 weeks. At the end of the treatment, biochemical and histological evaluation was carried out in the neo-tissues. T3 hormone application significantly increased the collagen production in neo-cartilage tissues. The properties of tensile and compressive were significantly increased compared to the controls. However, T3 hormone application also induced hypertrophy. At the higher dose concentration of T3 hormone application, tensile and compressive properties were tremendously increased 4.3 and 4.6 fold respectively. Taking all these data together, it suggested that the T3 hormone application could be a potential agent to increase the functional properties such tensile and compressive in neo-tissues. Copyright © 2017 Elsevier GmbH. All rights reserved.

Longitudinal evaluation of T1ρ and T2 spatial distribution in osteoarthritic and healthy medial knee cartilage.

PubMed

Schooler, J; Kumar, D; Nardo, L; McCulloch, C; Li, X; Link, T M; Majumdar, S

2014-01-01

To investigate longitudinal changes in laminar and spatial distribution of knee articular cartilage magnetic resonance imaging (MRI) T1ρ and T2 relaxation times, in individuals with and without medial compartment cartilage defects. All subjects (at baseline n = 88, >18 years old) underwent 3-Tesla knee MRI at baseline and annually thereafter for 3 years. The MR studies were evaluated for presence of cartilage defects (modified Whole-Organ Magnetic Resonance Imaging Scoring - mWORMS), and quantitative T1ρ and T2 relaxation time maps. Subjects were segregated into those with (mWORMS ≥2) and without (mWORMS ≤1) cartilage lesions at the medial tibia (MT) or medial femur (MF) at each time point. Laminar (bone and articular layer) and spatial (gray level co-occurrence matrix - GLCM) distribution of the T1ρ and T2 relaxation time maps were calculated. Linear regression models (cross-sectional) and Generalized Estimating Equations (GEEs) (longitudinal) were used. Global T1ρ, global T2 and articular layer T2 relaxation times at the MF, and global and articular layer T2 relaxation times at the MT, were higher in subjects with cartilage lesions compared to those without lesions. At the MT global T1ρ relaxation times were higher at each time point in subjects with lesions. MT T1ρ and T2 became progressively more heterogeneous than control compartments over the course of the study. Spatial distribution of T1ρ and T2 relaxation time maps in medial knee OA using GLCM technique may be a sensitive indicator of cartilage deterioration, in addition to whole-compartment relaxation time data. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

[3T magnetic resonance T2 mapping for evaluation of cartilage repair after matrix-associated autologous chondrocyte transplantation].

PubMed

Zhang, Jun; Xu, Xian; Li, Xue; Chen, Min; Dong, Tian-Ming; Zuo, Pan-Li; An, Ning-Yu

2015-01-01

To assess the value of magnetic resonance imaging (MRI) T2 mapping in quantitative evaluation of cartilage repair following matrix-associated autologous chondrocyte transplantation (MACT). Six patients (with 9 plug cartilages) following MACT underwent MRI on a 3.0 Tesla MR scan system at 3, 6 and 12 months after the surgery. The full-thickness and zonal areas (deep and superficial layers) T2 values were calculated for the repaired cartilage and control cartilage. The mean T2 values of the repaired cartilage after MACT were significantly higher than that of the control cartilages at 3 and 6 months (P<0.05), but not at 12 months (P=0.063). At 6 and 12 months, the T2 values of the superficial layers were significantly higher than those of the deep layers in the repaired cartilages (P<0.05). The zonal (deep and superficial layers) T2 values of the repaired cartilages decreased significantly over time at 6 and 12 months as compared to those at 3 months after the surgery (P<0.05). MRI T2 mapping can serve as an important modality for assessing the repair of the articular cartilage following MACT.

Progress towards mapping the constitutional t(11:22) breakpoint

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

Barnoski, B.L.; Emanuel, B.S.; Bell, C.J.

1994-09-01

The reciprocal t(11;22)(q23;q11) is the most frequent, recurrent, non-Robertsonian, constitutional translocation in humans. Balanced carriers of this rearrangement are phenotypically normal, but are at risk for producing abnormal offspring with the Supernumerary der(22)t(11;22) Syndrome. Further, a recent report of association between t(11;22) balanced translocation carriers and breast cancer, suggests the involvement of genes on 11q and/or 22q in breast cancer tumorigenesis. Studies are in progress to examine the similarity between 11q23 and 22q11 breakpoints in multiple families with the constitutional t(11;22). A 750 kb YAC, which contains markers known to flank the 11q23 breakpoint, was identified in CEPH/Genethon database. FISHmore » with this YAC to two independent t(11;22) cell lines demonstrates signal on both derivative chromosomes. Numerous YACs containing BCRL2, the closest marker proximal to the breakpoint, were identified. Analysis of these YACs to determine which contain the actual breakpoint sequences is complicated by the presence of a duplicated segment of 22q11 which contains a GGTL and a BCRL locus. Sequences homologous to these loci are present at several other locations in 22q11. The BCRL positive YACs were analyzed by Southern hybridization under conditions which distinguish the four members of the BCR/BCRL family. FISH of total yeast DNA plus YAC DNA labeled by nick translation, or biotin-labeled inter-Alu PCR products confirmed the localization of these YACs to 22q11. Additional FISH with these YACS to metaphase spreads prepared from balanced t(11;22) carriers confirm that these clones span the breakpoint, and will allow rapid isolation and definition of the genetic region adjacent to the t(11;22) breakpoint.« less

T1ρ Dispersion in Articular Cartilage

PubMed Central

Besier, Thor F.; Pauly, John M.; Smith, R. Lane; Delp, Scott L.; Beaupre, Gary S.; Gold, Garry E.

2015-01-01

Objective This study assessed T1ρ relaxation dispersion, measured by magnetic resonance imaging (MRI), as a tool to noninvasively evaluate cartilage material and biochemical properties. The specific objective was to answer two questions: (1) does cartilage initial elastic modulus (E0) correlate with T1ρ dispersion effects and (2) does collagen or proteoglycan content correlate with T1ρ dispersion effects? Design Cadaveric patellae with and without visible cartilage damage on conventional MR were included. T2 and T1ρ relaxation times at 500 and 1000 Hz spin-lock field amplitudes were measured. We estimated T1ρ dispersion effects by measuring T1ρ relaxation time at 500 and 1000 Hz and T2 relaxation time and using a new tool, the ratio T1ρ/T2. Cartilage initial elastic modulus, E0, was measured from initial response of mechanical indentation creep tests. Collagen and proteoglycan contents were measured at the indentation test sites; proteoglycan content was measured by their covalently linked sulfated glycosaminoglycans (sGAG). Pearson correlation coefficients were determined, taking into account the clustering of multiple samples within a single patella specimen. Results Cartilage initial elastic modulus, E0, increased with decreasing values of T1ρ/T2 measurements at both 500 Hz (P = 0.034) and 1000 Hz (P = 0.022). 1/T1ρ relaxation time (500 Hz) increased with increasing sGAG content (P = 0.041). Conclusions T1ρ/T2 ratio, a new tool, and cartilage initial elastic modulus are both measures of water–protein interactions, are dependent on the cartilage structure, and were correlated in this study. PMID:26069714

The Bimotor Turboprop Multi-Purpose Aircraft, the Yun-11T (Y-11),

DTIC Science & Technology

1982-08-13

TRANSLATION FTD-ID(RS)T-0521-82 13 August 1982 MICROFICHE N : FrD-82-C-001105 THE BIMOTOR TURBOPROP MULTI-PURPOSE AIRCRAFT, THE YUll 11T ( Y -11) By...AD-A142 848 THE BIMOTOR TURBOPROP MULTI-PURPOSE AIRCRAFT THE i/i YUN-jiT ( Y -ii)(U) FOREIGN TECHNOLOGY DIV WRIGHT-PATTERSON RFB OH X WENJIE 03 AUG 82...BUREAU OF STANDARDS- 1963-A -. -q 4 ,,> 1 .77. ADA1 42848 -. -,. FOREIGN TECHNOLOGY DIVISION THE BIMOTOR TURBOPROP MULTI-PURPOSE SAIRCRAFr, THE YTN-1T ( Y

Effect of intra-articular injection of intermediate-weight hyaluronic acid on hip and knee cartilage: in-vivo evaluation using T2 mapping.

PubMed

Ferrero, Giulio; Sconfienza, Luca Maria; Fiz, Francesco; Fabbro, Emanuele; Corazza, Angelo; Dettore, Daniele; Orlandi, Davide; Castellazzo, Carlo; Tornago, Stefano; Serafini, Giovanni

2018-06-01

We used T2 mapping to quantify the effect of intra-articular hyaluronic acid administration (IAHAA) on cartilage with correlation to clinical symptoms. One hundred two patients with clinical and MRI diagnosis of hip or knee grade I-III chondropathy were prospectively included. All patients received a standard MRI examination of the affected hip/knee (one joint/patient) and T2-mapping multiecho sequence for cartilage evaluation. T2 values of all slices were averaged and used for analysis. One month after MR evaluation 72 patients (38 males; mean age 51±10 years) underwent IAHAA. As a control group, 30 subjects (15 males; 51 ± 9 years) were not treated. MR and WOMAC evaluation was performed at baseline and after 3, 9, and 15 months in all patients. T2 mapping in hyaluronic acid (HA) patients showed a significant increase in T2 relaxation times from baseline to the first time point after therapy in knees (40.7 ± 9.8 ms vs. 45.8 ± 8.6 ms) and hips (40.9 ± 9.7 ms; 45.9 ± 9.5 ms) (p < 0.001). At the 9- and 15-month evaluations, T2 relaxation dropped to values similar to the baseline ones (p < 0.001 vs. 3 month). The correlation between T2 increase and pain reduction after IAHAA was statistically significant (r = 0.54, p < 0.01) in patients with grade III chondropathy. T2 mapping can be used to evaluate the effect over time of IAHAA in patients with hip and knee chondropathy. • T2 relaxation times change over time after hyaluronic acid intra-articular administration • T2 relaxation times of the medial femoral condyle correlate with WOMAC variation • T2 relaxation times are different between Outerbridge I and II-III.

Comparison of 1.5- and 3-T MR imaging for evaluating the articular cartilage of the knee.

PubMed

Van Dyck, Pieter; Kenis, Christoph; Vanhoenacker, Filip M; Lambrecht, Valérie; Wouters, Kristien; Gielen, Jan L; Dossche, Lieven; Parizel, Paul M

2014-06-01

The aim of this prospective study was to compare routine MRI scans of the knee at 1.5 and 3 T obtained in the same individuals in terms of their performance in the diagnosis of cartilage lesions. One hundred patients underwent MRI of the knee at 1.5 and 3 T and subsequent knee arthroscopy. All MR examinations consisted of multiplanar 2D turbo spin-echo sequences. Three radiologists independently graded all articular surfaces of the knee joint seen at MRI. With arthroscopy as the reference standard, the sensitivity, specificity, and accuracy of 1.5- and 3-T MRI for detecting cartilage lesions and the proportion of correctly graded cartilage lesions within the knee joint were determined and compared using resampling statistics. For all readers and surfaces combined, the respective sensitivity, specificity, and accuracy for detecting all grades of cartilage lesions in the knee joint using MRI were 60, 96, and 87% at 1.5 T and 69, 96, and 90% at 3 T. There was a statistically significant improvement in sensitivity (p < 0.05), but not specificity or accuracy (n.s.) for the detection of cartilage lesions at 3 T. There was also a statistically significant (p < 0.05) improvement in the proportion of correctly graded cartilage lesions at 3 T as compared to 1.5 T. A 3-T MR protocol significantly improves diagnostic performance for the purpose of detecting cartilage lesions within the knee joint, when compared with a similar protocol performed at 1.5 T. III.

Review of renal carcinoma with t(6;11)(p21;q12) with focus on clinical and pathobiological aspects.

PubMed

Kuroda, Naoto; Tanaka, Azusa; Sasaki, Naomi; Ishihara, Akira; Matsuura, Keiko; Moriyama, Masatsugu; Nagashima, Yoji; Inoue, Keiji; Petersson, Fredrik; Martignoni, Guido; Michal, Michal; Hes, Ondrej

2013-06-01

Recently, a new category of MiTF/TFE family translocation carcinomas of the kidney has been proposed. This category includes Xp11.2 renal cell carcinoma (RCC) and the t(6;11) RCC. These tumors share clinical, morphological, immunohistochemical and molecular genetic features. In this article, we review t(6;11) RCC. This tumor predominantly affects children and young adults. Macroscopically, the tumor generally forms a well circumscribed mass. Satellite nodules may be observed. Histologically, the tumor comprises large cells and small cells surrounded by basement membrane material. Immunohistochemically, tumor cells show nuclear immunolabeling for TFEB and usually express Cathepsin-K in the cytoplasm. Karyotyping detects the rearrangement between chromosome 6p21 and chromosome 11q12. Alpha-TFEB fusion can be detected by reverse transcriptase polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH). Most cases affecting children and young adults seem to be indolent, but some adult cases have presented with metastasis or caused death. As previously reported cases remain limited to date, further examination in a large scale study will be needed in order to elucidate clinical behavior and molecular characteristics.

Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951.

PubMed

Cavé, Hélène; Suciu, Stefan; Preudhomme, Claude; Poppe, Bruce; Robert, Alain; Uyttebroeck, Anne; Malet, Michèle; Boutard, Patrick; Benoit, Yves; Mauvieux, Laurent; Lutz, Patrick; Méchinaud, Françoise; Grardel, Nathalie; Mazingue, Francoise; Dupont, Madeleine; Margueritte, Geneviève; Pages, Marie-Pierre; Bertrand, Yves; Plouvier, Emmanuel; Brunie, Ghislaine; Bastard, Christian; Plantaz, Dominique; Vande Velde, Isabel; Hagemeijer, Anne; Speleman, Frank; Lessard, Michel; Otten, Jacques; Vilmer, Etienne; Dastugue, Nicole

2004-01-15

In a series of 153 children with T-cell malignancies enrolled in 2 consecutive European Organization for Research and Treatment of Cancer (EORTC) trials, we assessed the HOX11L2 expression and/or the presence of a t(5;14)(q35;q32). Additionally, in 138 of these patients, HOX11 expression and SIL-TAL rearrangement were also assessed. These alterations were mutually exclusive, and their frequency was 23% (n = 35), 7% (n = 10), and 12% (n = 17), respectively. HOX11L2/t(5;14) positivity was more frequent in acute lymphoblastic leukemia (ALL) with cortical T immunophenotype and in children aged between 6 and 9 years. In contrast with previously reported data, patients positive and negative for HOX11L2/t(5;14) were comparable with regard to clinical outcome as well as to the response to a 7-day prephase treatment or to residual disease at completion of induction therapy. The 3-year event-free survival (EFS) rate (+/- SE percentage) for patients positive and negative for HOX11L2/t(5;14) was 75.5% (+/- 8.1%) and 68.3% (+/- 5.0%), respectively; the hazard ratio was 0.84 (95% confidence interval, 0.40-1.80). Patients with HOX11-high expression and those with SIL-TAL fusion had low levels of residual disease at the end of induction and a favorable prognosis: the 3-year EFS rate was 83.3% (+/- 8.5%) and 75.3% (+/- 12.6%), respectively. The results obtained in HOX11L2/t(5;14) patients in this study do not confirm the unfavorable prognosis reported in previous studies.

Evaluation of grades 3 and 4 chondromalacia of the knee using T2*-weighted 3D gradient-echo articular cartilage imaging.

PubMed

Murphy, B J

2001-06-01

To determine the accuracy of T2*-weighted three-dimensional (3D) gradient-echo articular cartilage imaging in the identification of grades 3 and 4 chondromalacia of the knee. A retrospective evaluation of 80 patients who underwent both arthroscopic and MRI evaluation was performed. The 3D images were interpreted by one observer without knowledge of the surgical results. The medial and lateral femoral condyles, the medial and lateral tibial plateau, the patellar cartilage and trochlear groove were evaluated. MR cartilage images were considered positive if focal reduction of cartilage thickness was present (grade 3 chondromalacia) or if complete loss of cartilage was present (grade 4 chondromalacia). Comparison of the 3D MR results with the arthroscopic findings was performed. Eighty patients were included in the study group. A total of 480 articular cartilage sites were evaluated with MRI and arthroscopy. Results of MR identification of grades 3 and 4 chondromalacia, all sites combined, were: sensitivity 83%, specificity 97%, false negative rate 17%, false positive rate 3%, positive predictive value 87%, negative predictive value 95%, overall accuracy 93%. The results demonstrate that T2*-weighted 3D gradient-echo articular cartilage imaging can identify grades 3 and 4 chondromalacia of the knee.

Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells

PubMed Central

Takachi, Takayuki; Takahashi, Masahiko; Takahashi-Yoshita, Manami; Higuchi, Masaya; Obata, Miki; Mishima, Yukio; Okuda, Shujiro; Tanaka, Yuetsu; Matsuoka, Masao; Saitoh, Akihiko; Green, Patrick L; Fujii, Masahiro

2015-01-01

Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T cell leukemia (ATL), which is an aggressive form of T-cell malignancy. HTLV-1 oncoproteins, Tax and HBZ, play crucial roles in the immortalization of T-cells and/or leukemogenesis by dysregulating the cellular functions in the host. Recent studies show that HTLV-1-infected T-cells have reduced expression of the BCL11B tumor suppressor protein. In the present study, we explored whether Tax and/or HBZ play a role in downregulating BCL11B in HTLV-1-infected T-cells. Lentiviral transduction of Tax in a human T-cell line repressed the expression of BCL11B at both the protein and mRNA levels, whereas the transduction of HBZ had little effect on the expression. Tax mutants with a decreased activity for the NF-κB, CREB or PDZ protein pathways still showed a reduced expression of the BCL11B protein, thereby implicating a different function of Tax in BCL11B downregulation. In addition, the HTLV-2 Tax2 protein reduced the BCL11B protein expression in T-cells. Seven HTLV-1-infected T-cell lines, including three ATL-derived cell lines, showed reduced BCL11B mRNA and protein expression relative to an uninfected T-cell line, and the greatest reductions were in the cells expressing Tax. Collectively, these results indicate that Tax is responsible for suppressing BCL11B protein expression in HTLV-1-infected T-cells; Tax-mediated repression of BCL11B is another mechanism that Tax uses to promote oncogenesis of HTLV-1-infected T-cells. PMID:25613934

Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells.

PubMed

Takachi, Takayuki; Takahashi, Masahiko; Takahashi-Yoshita, Manami; Higuchi, Masaya; Obata, Miki; Mishima, Yukio; Okuda, Shujiro; Tanaka, Yuetsu; Matsuoka, Masao; Saitoh, Akihiko; Green, Patrick L; Fujii, Masahiro

2015-04-01

Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T cell leukemia (ATL), which is an aggressive form of T-cell malignancy. HTLV-1 oncoproteins, Tax and HBZ, play crucial roles in the immortalization of T-cells and/or leukemogenesis by dysregulating the cellular functions in the host. Recent studies show that HTLV-1-infected T-cells have reduced expression of the BCL11B tumor suppressor protein. In the present study, we explored whether Tax and/or HBZ play a role in downregulating BCL11B in HTLV-1-infected T-cells. Lentiviral transduction of Tax in a human T-cell line repressed the expression of BCL11B at both the protein and mRNA levels, whereas the transduction of HBZ had little effect on the expression. Tax mutants with a decreased activity for the NF-κB, CREB or PDZ protein pathways still showed a reduced expression of the BCL11B protein, thereby implicating a different function of Tax in BCL11B downregulation. In addition, the HTLV-2 Tax2 protein reduced the BCL11B protein expression in T-cells. Seven HTLV-1-infected T-cell lines, including three ATL-derived cell lines, showed reduced BCL11B mRNA and protein expression relative to an uninfected T-cell line, and the greatest reductions were in the cells expressing Tax. Collectively, these results indicate that Tax is responsible for suppressing BCL11B protein expression in HTLV-1-infected T-cells; Tax-mediated repression of BCL11B is another mechanism that Tax uses to promote oncogenesis of HTLV-1-infected T-cells. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

33 CFR 165.T11-0551 - Safety Zone; America's Cup Sailing Events.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Sailing Events. 165.T11-0551 Section 165.T11-0551 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... § 165.T11-0551 Safety Zone; America's Cup Sailing Events. (a) Definitions—(1) America's Cup Racing... 34th America's Cup sailing events. (2) Patrol Commander. As used in this section, “Patrol Commander” or...

T2* mapping and delayed gadolinium-enhanced magnetic resonance imaging in cartilage (dGEMRIC) of humeral articular cartilage--a histologically controlled study.

PubMed

Bittersohl, Bernd; Kircher, Jörn; Miese, Falk R; Dekkers, Christin; Habermeyer, Peter; Fröbel, Julia; Antoch, Gerald; Krauspe, Rüdiger; Zilkens, Christoph

2015-10-01

Cartilage biochemical imaging modalities that include the magnetic resonance imaging (MRI) techniques of T2* mapping (sensitive to water content and collagen fiber network) and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC, sensitive to the glycosaminoglycan content) can be effective instruments for early diagnosis and reliable follow-up of cartilage damage. The purpose of this study was to provide T2* mapping and dGEMRIC values in various histologic grades of cartilage degeneration in humeral articular cartilage. A histologically controlled in vitro study was conducted that included human humeral head cartilage specimens with various histologic grades of cartilage degeneration. High-resolution, 3-dimensional (3D) T2* mapping and dGEMRIC were performed that enabled the correlation of MRI and histology data. Cartilage degeneration was graded according to the Mankin score, which evaluates surface morphology, cellularity, toluidine blue staining, and tidemark integrity. SPSS software was used for statistical analyses. Both MRI mapping values decreased significantly (P < .001) with increasing cartilage degeneration. Spearman rank analysis revealed a significant correlation (correlation coefficients ranging from -0.315 to 0.784; P < .001) between the various histologic parameters and the T2* and T1Gd mapping values. This study demonstrates the feasibility of 3D T2* and dGEMRIC to identify various histologic grades of cartilage damage of humeral articular cartilage. With regard to the advantages of these mapping techniques with high image resolution and the ability to accomplish a 3D biochemically sensitive imaging, we consider that these imaging techniques can make a positive contribution to the currently evolving science and practice of cartilage biochemical imaging. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

IEEE 802.11ah: A Technology to Face the IoT Challenge.

PubMed

Baños-Gonzalez, Victor; Afaqui, M Shahwaiz; Lopez-Aguilera, Elena; Garcia-Villegas, Eduard

2016-11-22

Since the conception of the Internet of things (IoT), a large number of promising applications and technologies have been developed, which will change different aspects in our daily life. This paper explores the key characteristics of the forthcoming IEEE 802.11ah specification. This future IEEE 802.11 standard aims to amend the IEEE 802.11 legacy specification to support IoT requirements. We present a thorough evaluation of the foregoing amendment in comparison to the most notable IEEE 802.11 standards. In addition, we expose the capabilities of future IEEE 802.11ah in supporting different IoT applications. Also, we provide a brief overview of the technology contenders that are competing to cover the IoT communications framework. Numerical results are presented showing how the future IEEE 802.11ah specification offers the features required by IoT communications, thus putting forward IEEE 802.11ah as a technology to cater the needs of the Internet of Things paradigm.

IEEE 802.11ah: A Technology to Face the IoT Challenge

PubMed Central

Baños-Gonzalez, Victor; Afaqui, M. Shahwaiz; Lopez-Aguilera, Elena; Garcia-Villegas, Eduard

2016-01-01

Since the conception of the Internet of things (IoT), a large number of promising applications and technologies have been developed, which will change different aspects in our daily life. This paper explores the key characteristics of the forthcoming IEEE 802.11ah specification. This future IEEE 802.11 standard aims to amend the IEEE 802.11 legacy specification to support IoT requirements. We present a thorough evaluation of the foregoing amendment in comparison to the most notable IEEE 802.11 standards. In addition, we expose the capabilities of future IEEE 802.11ah in supporting different IoT applications. Also, we provide a brief overview of the technology contenders that are competing to cover the IoT communications framework. Numerical results are presented showing how the future IEEE 802.11ah specification offers the features required by IoT communications, thus putting forward IEEE 802.11ah as a technology to cater the needs of the Internet of Things paradigm. PMID:27879688

Evaluation of the articular cartilage of the knee joint: value of adding a T2 mapping sequence to a routine MR imaging protocol.

PubMed

Kijowski, Richard; Blankenbaker, Donna G; Munoz Del Rio, Alejandro; Baer, Geoffrey S; Graf, Ben K

2013-05-01

To determine whether the addition of a T2 mapping sequence to a routine magnetic resonance (MR) imaging protocol could improve diagnostic performance in the detection of surgically confirmed cartilage lesions within the knee joint at 3.0 T. This prospective study was approved by the institutional review board, and the requirement to obtain informed consent was waived. The study group consisted of 150 patients (76 male and 74 female patients with an average age of 41.2 and 41.5 years, respectively) who underwent MR imaging and arthroscopy of the knee joint. MR imaging was performed at 3.0 T by using a routine protocol with the addition of a sagittal T2 mapping sequence. Images from all MR examinations were reviewed in consensus by two radiologists before surgery to determine the presence or absence of cartilage lesions on each articular surface, first by using the routine MR protocol alone and then by using the routine MR protocol with T2 maps. Each articular surface was then evaluated at arthroscopy. Generalized estimating equation models were used to compare the sensitivity and specificity of the routine MR imaging protocol with and without T2 maps in the detection of surgically confirmed cartilage lesions. The sensitivity and specificity in the detection of 351 cartilage lesions were 74.6% and 97.8%, respectively, for the routine MR protocol alone and 88.9% and 93.1% for the routine MR protocol with T2 maps. Differences in sensitivity and specificity were statistically significant (P < .001). The addition of T2 maps to the routine MR imaging protocol significantly improved the sensitivity in the detection of 24 areas of cartilage softening (from 4.2% to 62%, P < .001), 41 areas of cartilage fibrillation (from 20% to 66%, P < .001), and 96 superficial partial-thickness cartilage defects (from 71% to 88%, P = .004). The addition of a T2 mapping sequence to a routine MR protocol at 3.0 T improved sensitivity in the detection of cartilage lesions within the knee

Treatment of juvenile idiopathic arthritis with intra-articular triamcinolone hexacetonide: evaluation of clinical effectiveness correlated with circulating ANA and T gamma/delta + and B CD5+ lymphocyte populations of synovial fluid.

PubMed

Lepore, L; Del Santo, M; Malorgio, C; Presani, G; Perticarari, S; Prodan, M; Di Leo, G; Leone, V; Tommasini, A

2002-01-01

The aims of the study were to assess the effect of intra-articular treatment with triamcinolone hexacetonide (TH) in juvenile idiopathic arthritis (JIA) and to investigate whether treatment response correlates with the presence of antinuclear antibodies (ANA) in the serum and/or B CD5+ and T gamma/delta + lymphocytes in the synovial fluid. A total of 37 patients (81% females, 56% ANA+) with oligoarticular JIA involving knees were treated with intra-articular injections of TH after failing to respond to NSAIDs for two months. Eighteen patients were treated within 6 months of onset, 19 were treated more than 6 months after onset. Mean duration of remission was 13.9 months. Twelve patients (7 ANA+) had stable remission after a single injection; 13 patients (3 ANA+) experienced more than 6 months' remission but subsequently had a relapse; 12 patients (11 ANA+) had a relapse within six months of injection. Of 20 patients treated within 6 months of onset, 17 had stable remission whereas only 8 out of 17 who were treated during relapse attained stable remission (p = 0.03). The mean percentage of T gamma/delta + and of B CD5+ lymphocytes in synovial fluid was the same as in peripheral blood of normal subjects. Our data indicate that local treatment with slow-release steroids is very effective in oligoarticular JIA. Prolonged remission was less likely in the presence of ANA positivity, probably because the disease is immunologically more active. Finally, our data suggest that the earlier the treatment, the easier it is to obtain a protracted, and possibly permanent, response.

Early Articular Cartilage MRI T2 Changes After Anterior Cruciate Ligament Reconstruction Correlate With Later Changes in T2 and Cartilage Thickness

PubMed Central

Williams, Ashley; Winalski, Carl S.; Chu, Constance R.

2018-01-01

Anterior cruciate ligament (ACL) injury is a known risk factor for future development of osteoarthritis (OA). This human clinical study seeks to determine if early changes to cartilage MRI T2 maps between baseline and 6 months following ACL reconstruction (ACLR) are associated with changes to cartilage T2 and cartilage thickness between baseline and 2 years after ACLR. Changes to T2 texture metrics and T2 mean values in medial knee cartilage of 17 human subjects 6 months after ACLR were compared to 2-year changes in T2 and in cartilage thickness of the same areas. T2 texture and mean assessments were also compared to that of 11 uninjured controls. In ACLR subjects, six-month changes in mean T2 correlated to 2-year changes in mean T2 (R = 0.80, p = 0.0001), and 6-month changes to T2 texture metrics, but not T2 mean, correlated with 2-year changes in medial femoral cartilage thickness in 9 of the 20 texture features assessed (R = 0.48–0.72, p ≤ 0.05). Both mean T2 and texture differed (p < 0.05) between ALCR subjects and uninjured controls. Clinical Significance These results show that short-term longitudinal evaluation of T2 map and textural changes may provide early warning of cartilage at risk for progressive degeneration after ACL injury and reconstruction. PMID:27381512

CCR6 and NK1.1 distinguish between IL-17A and IFN-gamma-producing gammadelta effector T cells.

PubMed

Haas, Jan D; González, Frano H Malinarich; Schmitz, Susanne; Chennupati, Vijaykumar; Föhse, Lisa; Kremmer, Elisabeth; Förster, Reinhold; Prinz, Immo

2009-12-01

Gammadelta T cells are a potent source of innate IL-17A and IFN-gamma, and they acquire the capacity to produce these cytokines within the thymus. However, the precise stages and required signals that guide this differentiation are unclear. Here we show that the CD24(low) CD44(high) effector gammadelta T cells of the adult thymus are segregated into two lineages by the mutually exclusive expression of CCR6 and NK1.1. Only CCR6+ gammadelta T cells produced IL-17A, while NK1.1+ gammadelta T cells were efficient producers of IFN-gamma but not of IL-17A. Their effector phenotype correlated with loss of CCR9 expression, particularly among the NK1.1+ gammadelta T cells. Accordingly, both gammadelta T-cell subsets were rare in gut-associated lymphoid tissues, but abundant in peripheral lymphoid tissues. There, they provided IL-17A and IFN-gamma in response to TCR-specific and TCR-independent stimuli. IL-12 and IL-18 induced IFN-gamma and IL-23 induced IL-17A production by NK1.1+ or CCR6+ gammadelta T cells, respectively. Importantly, we show that CCR6+ gammadelta T cells are more responsive to TCR stimulation than their NK1.1+ counterparts. In conclusion, our findings support the hypothesis that CCR6+ IL-17A-producing gammadelta T cells derive from less TCR-dependent selection events than IFN-gamma-producing NK1.1+ gammadelta T cells.

33 CFR 165.T11-534 - Safety zone; Bay Bridge construction, San Francisco Bay, San Francisco, CA.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Francisco, CA. (a) Location. This temporary safety zone is established in the navigable waters of the San... construction, San Francisco Bay, San Francisco, CA. 165.T11-534 Section 165.T11-534 Navigation and Navigable... within a box connected by the following points: 37°49′06″ N, 122°21′17″ W; 37°49′01″ N, 122°21′12″ W; 37...

Renal cell carcinoma with t(6:11) (p21;q12). A case report highlighting distinctive immunohistologic features of this rare tumor.

PubMed

Arneja, Sarabjeet Kaur; Gujar, Neeraj

2015-01-01

Renal cell carcinoma (RCC) with t(6:11) (p21;q12) are extremely rare, fewer than 30 cases have been reported in literature. These tumors are characterized by specific chromosomal translocation involving TFEB, as against the more commonly known TFE3 (Xp11.2) translocation associated RCCs. The distinctive immnohistologic features are helpful in enabling a diagnosis of this rare tumor, otherwise diagnosed by fluorescence in situ hybridization assay, specific for detecting TFEB gene rearrangement. Herein, we report a case of this rare tumor in a 11 years old boy, with the objective of highlighting distinctive light microscopic and immuno-phenotypic features of this rare sub-type of translocation associated renal cell carcinoma, otherwise diagnosed by fluorescence in situ hybridization technique. Morphologically tumor showed distinctive biphasic population of cells, large epitheloid cells with voluminous eosinophillic cytoplasm and smaller cells with much lesser amount of cytoplasm and small rounded nuclei. The smaller cells at places clustered around hyaline pink material forming "pseudorosettes". population. Immunohistochemically both types of tumor cells showed negativity for pan CK (cytokeratin), EMA (epitheleal membrane antigen) and TFE3 (transcription factor E3). HMB 45 (human melanoma black 45) and Melan- A /MART 1 (melanoma antigen recognized by T cells) were moderate to strongly expressed. On review of literature, most RCCs with t(6;11) translocation have been reported to be negative for pan cytokeratins and EMA. Published literature also shows that the most distinctive immunohistochemical feature of t(6;11) translocation RCC is nuclear staining for TFEB protein. Immunostains for TFE3 have always been negative in the reported cases. It is noteworthy that immunoreactivity for melanocytic markers HMB45 and Melan A and immunonegativity for epithelial markers pan CK and EMA may lead to misdiagnosis of angiomyolipoma to the unwary. Knowledge of distinctive

Precision half-life measurement of 11C: The most precise mirror transition F t value

NASA Astrophysics Data System (ADS)

Valverde, A. A.; Brodeur, M.; Ahn, T.; Allen, J.; Bardayan, D. W.; Becchetti, F. D.; Blankstein, D.; Brown, G.; Burdette, D. P.; Frentz, B.; Gilardy, G.; Hall, M. R.; King, S.; Kolata, J. J.; Long, J.; Macon, K. T.; Nelson, A.; O'Malley, P. D.; Skulski, M.; Strauss, S. Y.; Vande Kolk, B.

2018-03-01

Background: The precise determination of the F t value in T =1 /2 mixed mirror decays is an important avenue for testing the standard model of the electroweak interaction through the determination of Vu d in nuclear β decays. 11C is an interesting case, as its low mass and small QE C value make it particularly sensitive to violations of the conserved vector current hypothesis. The present dominant source of uncertainty in the 11CF t value is the half-life. Purpose: A high-precision measurement of the 11C half-life was performed, and a new world average half-life was calculated. Method: 11C was created by transfer reactions and separated using the TwinSol facility at the Nuclear Science Laboratory at the University of Notre Dame. It was then implanted into a tantalum foil, and β counting was used to determine the half-life. Results: The new half-life, t1 /2=1220.27 (26 ) s, is consistent with the previous values but significantly more precise. A new world average was calculated, t1/2 world=1220.41 (32 ) s, and a new estimate for the Gamow-Teller to Fermi mixing ratio ρ is presented along with standard model correlation parameters. Conclusions: The new 11C world average half-life allows the calculation of a F tmirror value that is now the most precise value for all superallowed mixed mirror transitions. This gives a strong impetus for an experimental determination of ρ , to allow for the determination of Vu d from this decay.

Intra-articular injection with triamcinolone hexacetonide in patients with rheumatoid arthritis: prospective assessment of goniometry and joint inflammation parameters.

PubMed

Furtado, Rita Nely Vilar; Machado, Flávia Soares; Luz, Karine Rodrigues da; Santos, Marla Francisca Dos; Konai, Monique Sayuri; Lopes, Roberta Vilela; Natour, Jamil

To evaluate local joint variables after intra-articular injection with triamcinolone hexacetonide in rheumatoid arthritis patients. We blindly and prospectively (baseline, 1, 4, 12 and 24 weeks) evaluated metacarpophalangeal, wrist, elbow, shoulder, knee and ankle joints after triamcinolone hexacetonide intra-articular injection by the following outcome measures: visual analogue scale 0-10cm (VAS) for rest pain (VASR); VAS for movement pain (VASM); VAS for joint swelling (VASSw); flexion (FlexG) and extension (ExtG). 289 patients (635 joints) were studied. VASSw (p<0.001) and VASR (0.001T0 to T4, T12 and T24 for all joints. VASM improved from T0 to T4 (p<0.021) for all joints; T0 to T12 (p<0.023) for MCF and knee; T0 to T24 (p<0.019) only for MCF and knee. FlexG improved from T0 to T4 (p<0.001) for all joints; T0 to T12 (p<0.001) and T0 to T24 (p<0.02) only for MCF and knee. ExtG improved from T0 to T4 (p<0.001) for all joints except for elbow; T0 to T12 (p=0.003) for wrist, metacarpophalangeal and knee; and T0 to T24 (p=0.014) for MCF and knee. VASSw responded better at short and medium term after IAI with triamcinolone hexacetonide in our sample of RA patients. Copyright © 2016. Published by Elsevier Editora Ltda.

Intra-tumoral delivery of CXCL11 via a vaccinia virus, but not by modified T cells, enhances the efficacy of adoptive T cell therapy and vaccines.

PubMed

Moon, Edmund K; Wang, Liang-Chuan S; Bekdache, Kheng; Lynn, Rachel C; Lo, Albert; Thorne, Stephen H; Albelda, Steven M

2018-01-01

T cell trafficking into tumors depends on a "match" between chemokine receptors on effector cells (e.g., CXCR3 and CCR5) and tumor-secreted chemokines. There is often a chemokine/chemokine receptor "mismatch", with tumors producing minute amounts of chemokines, resulting in inefficient targeting of effectors to tumors. We aimed to alter tumors to produce higher levels of CXCL11, a CXCR3 ligand, to attract more effector cells following immunotherapy. Mice bearing established subcutaneous tumors were studied. In our first approach, we used modified chimeric antigen receptor (CAR)-transduced human T cells to deliver CXCL11 (CAR/CXCL11) into tumors. In our second approach, we intravenously (iv) administered a modified oncolytic vaccinia virus (VV) engineered to produce CXCL11 (VV.CXCL11). The effect of these treatments on T cell trafficking into the tumors and anti-tumor efficacy after subsequent CAR T cell injections or anti-tumor vaccines was determined. CAR/CXCL11 and VV.CXCL11 significantly increased CXCL11 protein levels within tumors. For CAR/CXCL11, injection of a subsequent dose of CAR T cells did not result in increased intra-tumoral trafficking, and appeared to decrease the function of the injected CAR T cells. In contrast, VV.CXCL11 increased the number of total and antigen-specific T cells within tumors after CAR T cell injection or vaccination and significantly enhanced anti-tumor efficacy. Both approaches were successful in increasing CXCL11 levels within the tumors; however, only the vaccinia approach was successful in recruiting T cells and augmenting anti-tumor efficacy. VV.CXCL11 should be considered as a potential approach to augment adoptive T cell transfer or vaccine immunotherapy.

der(11)t(11;17): a distinct cytogenetic pathway of advanced stage neuroblastoma (NBL) - detected by spectral karyotyping (SKY).

PubMed

Stark, Batia; Jeison, Marta; Glaser-Gabay, Leticia; Bar-Am, Irit; Mardoukh, Jacques; Ash, Shifra; Atias, Dina; Stein, Jerry; Zaizov, Rina; Yaniv, Isaac

2003-07-18

Conventional cytogenetic, molecular cytogenic and genetic methods disclosed a broad spectrum of genetic abnormalities leading to gain and loss of chromosomal segments in advanced stage neuroblastoma (NBL). Specific correlation between the genetic findings could delineate distinct genetic pathways, of which the biology and prognostic significance is as yet undetermined. Using spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) on metaphases from 16 patients with advanced stage NBL, it was possible to explore the whole spectrum of rearrangement within complex karyotypes and to detect hidden recurrent translocations. All translocations were unbalanced. The most prevalent recurrent unbalanced translocations resulted in 17q gain in 12 patients (75%), 11q loss in nine patients (56%), and 1p deletion/imbalance in eight patients (50%). The most frequent recurrent translocation was der(11)t(11;17) in six patients. Three cytogenetic pathways could be delineated. The first, with six patients, was characterized by the unbalanced translocation der(11)t(11;17), detected only by SKY, resulting in the concomitant 17q gain and 11q loss. No MYCN amplification or 1p deletion (except one patient with 1p imbalance) were found, while 3p deletion, and complex karyotypes were common. The second subgroup, with four patients, had 17q gain and 1p deletion, and in two patients 11q loss, that was apparent only by FISH. 1p deletion occurred through der(1)t(1;17) or del(1p). The third subgroup of four patients was characterized by MYCN amplification with 17q gain and 1p deletion, very rarely with 11q loss (one patient) through a translocation with a non-17q partner. The SKY subclassifications were in accordance with the findings reported by molecular genetic techniques, and may indicate that distinct oncogenes and suppressor genes are involved in the der(11)t(11;17) pathway of advanced stage NBL.

T1ρ MR Imaging of Human Musculoskeletal System

PubMed Central

Wang, Ligong; Regatte, Ravinder R.

2014-01-01

Magnetic resonance imaging (MRI) offers the direct visualization of human musculoskeletal (MSK) system, especially all diarthrodial tissues including cartilage, bone, menisci, ligaments, tendon, hip, synovium etc. Conventional MR imaging techniques based on T1- and T2-weighted, proton density (PD) contrast are inconclusive in quantifying early biochemically degenerative changes in MSK system in general and articular cartilage in particular. In recent years, quantitative MR parameter mapping techniques have been used to quantify the biochemical changes in articular cartilage with a special emphasis on evaluating joint injury, cartilage degeneration, and soft tissue repair. In this article, we will focus on cartilage biochemical composition, basic principles of T1ρ MR imaging, implementation of T1ρ pulse sequences, biochemical validation, and summarize the potential applications of T1ρ MR imaging technique in MSK diseases including osteoarthritis (OA), anterior cruciate ligament (ACL) injury, and knee joint repair. Finally, we will also review the potential advantages, challenges, and future prospects of T1ρ MR imaging for widespread clinical translation. PMID:24935818

Total vertebrectomy and spine shortening for the treatment of T12-L1 spine dislocation: Management with suboptimal resources.

PubMed

Lorente, Alejandro; Palacios, Pablo; Burgos, Jesús; Barrios, Carlos; Lorente, Rafael

2018-04-21

Total vertebrectomy with spine shortening has been reported for the treatment of difficult cases of traumatic spine dislocation, both in acute and chronic phase. We report an exceptional case of a five-week-old T12-L1 spine dislocation in a 25-year-old female with complete paraplegia as a result of trauma in Ciudad de León (Nicaragua). In view of the time since the dislocation, we performed a complete L1 vertebrectomy in order to reduce the dorsolumbar hinge. For osteosynthesis material we had only eight screws and two Steffee plates. We therefore introduced pedicle screws at levels T11, T12, L2 and L3 on the right side and T11, T12, L3 and L4 on the left, and performed manual reduction of the spine. Steffee plates were placed and we added sublaminar wires to reinforce the osteosynthesis. Fifteen months after surgery, there has been no neurological improvement. Copyright © 2018 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Surgical anesthesia with a combination of T12 paravertebral block and lumbar plexus, sacral plexus block for hip replacement in ankylosing spondylitis: CARE-compliant 4 case reports.

PubMed

Ke, Xijian; Li, Ji; Liu, Yong; Wu, Xi; Mei, Wei

2017-06-26

Anesthesia management for patients with severe ankylosing spondylitis scheduled for total hip arthroplasty is challenging due to a potential difficult airway and difficult neuraxial block. We report 4 cases with ankylosing spondylitis successfully managed with a combination of lumbar plexus, sacral plexus and T12 paravertebral block. Four patients were scheduled for total hip arthroplasty. All of them were diagnosed as severe ankylosing spondylitis with rigidity and immobilization of cervical and lumbar spine and hip joints. A combination of T12 paravertebral block, lumbar plexus and sacral plexus block was successfully used for the surgery without any additional intravenous anesthetic or local anesthetics infiltration to the incision, and none of the patients complained of discomfort during the operations. The combination of T12 paravertebral block, lumbar plexus and sacral plexus block, which may block all nerves innervating the articular capsule, surrounding muscles and the skin involved in total hip arthroplasty, might be a promising alternative for total hip arthroplasty in ankylosing spondylitis.

Quantitative evaluation of knee cartilage and meniscus destruction in patients with rheumatoid arthritis using T1ρ and T2 mapping.

PubMed

Meng, Xiang Hong; Wang, Zhi; Guo, Li; Liu, Xiu Chan; Zhang, Yu Wei; Zhang, Ze Wei; Ma, Xin Long

2017-11-01

To calculate T1ρ and T2 values of articular cartilage and menisci in knee joints of patients with RA, and compare the values between RA patients and healthy volunteers, to gain insight into the pathogenesis of cartilage and meniscus degradation in patients with RA. Nine patients with RA and knee joints symptoms were enrolled in the study, twenty healthy volunteers without knee joint diseases were included as controls. Sagittal fat-saturated T1ρ and T2 mapping images were obtained on a 3T MR scanner (GE750, GE Healthcare, Waukesha, WI), using a dedicated 8-channel knee coil. In the T1rho mapping sequence, the amplitude of the spin-lock pulse was 500Hz, spin lock durations=10/20/30/50ms. In the T2 mapping sequence,TR/TE were 1794/6.5, 13.4, 27, 40.7ms. Both sequences were performed with the following parameters: flip angle (FA)=90°, matrix: 320×256, FOV: 16×16cm 2 , slice thickness: 3mm, bandwidth: 62.5kHZ, and a total scan time of 5:11min. T1ρ- and T2-mapping images were used for the segmentation of the articular cartilage of the patella, femoral trochlea, medial and lateral femoral condyle, medial and lateral tibial plateau. These images were also used for the segmentation of the anterior and posterior horns of the medial and lateral menisci with livewire semi-automatic segmentation algorithm of MATLAB. A Mann-Whitney U test was performed to compare the T1ρ and T2 values of the above mentioned regions between the two groups. T1ρ (Z=-3.913 to -2.121, P=0.000-0.034) and T2 (Z=-3.866 to -2.216, P=0.000-0.026) values of knee cartilage in patients with RA were higher than that in healthy volunteers, except the cartilage of the patella (T1ρ: Z=-1.273, P=0.203,T2: Z=-0.236, P=0.814) and lateral tibial plateau (T1ρ:Z=-1.037, P=0.317). The T1ρ (Z=-1.462 to 0.572, P=0.095-0.908) and T2 (Z=-1.461 to 0.278, P=0.153-0.764) values of medial and lateral menisci showed no difference between the two groups. Patients with RA exhibit diffuse knee cartilage destruction in

Inconspicuous Insertion 22;12 in Myxoid/Round Cell Liposarcoma Accompanied by the Secondary Structural Abnormality der(16)t(1;16)

PubMed Central

Birch, Nathan C.; Antonescu, Cristina R.; Nelson, Marilu; Sarran, Lisa; Neff, James R.; Seemayer, Thomas; Bridge, Julia A.

2003-01-01

In myxoid/round cell liposarcoma, the t(12;16)(q13;p11) and its associated fusion transcript, FUS-CHOP, characterize greater than 95% of cases. The variant translocation t(12;22)(q13;q12) and associated EWS-CHOP fusion transcript are rare. A second non-random aberration observed in roughly 20% of Ewing’s sarcomas, and to a lesser extent other select sarcomas, is the unbalanced 1;16 translocation. Recognition of this secondary aberration in the absence of an obvious primary karyotypic abnormality strongly suggests that the use of other genetic approaches will be informative in uncovering a clinically suspected primary anomaly. The following case illustrates the utility of molecular cytogenetic and reverse transcriptase-polymerase chain reaction techniques in diagnosing an ins(22;12)(q12;q13q14) and associated EWS-CHOP fusion transcript in a myxoid/round cell liposarcoma exhibiting a der(16)t(1;16)(q11;q11). PMID:12876210

Inconspicuous insertion 22;12 in myxoid/round cell liposarcoma accompanied by the secondary structural abnormality der(16)t(1;16).

PubMed

Birch, Nathan C; Antonescu, Cristina R; Nelson, Marilu; Sarran, Lisa; Neff, James R; Seemayer, Thomas; Bridge, Julia A

2003-08-01

In myxoid/round cell liposarcoma, the t(12;16)(q13;p11) and its associated fusion transcript, FUS-CHOP, characterize greater than 95% of cases. The variant translocation t(12;22)(q13;q12) and associated EWS-CHOP fusion transcript are rare. A second non-random aberration observed in roughly 20% of Ewing's sarcomas, and to a lesser extent other select sarcomas, is the unbalanced 1;16 translocation. Recognition of this secondary aberration in the absence of an obvious primary karyotypic abnormality strongly suggests that the use of other genetic approaches will be informative in uncovering a clinically suspected primary anomaly. The following case illustrates the utility of molecular cytogenetic and reverse transcriptase-polymerase chain reaction techniques in diagnosing an ins(22;12)(q12;q13q14) and associated EWS-CHOP fusion transcript in a myxoid/round cell liposarcoma exhibiting a der(16)t(1;16)(q11;q11).

33 CFR 165.T11-577 - Security Zone; Naval Exercise; Pacific Ocean, Coronado, CA.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Security Zone; Naval Exercise; Pacific Ocean, Coronado, CA. 165.T11-577 Section 165.T11-577 Navigation and Navigable Waters COAST GUARD... § 165.T11-577 Security Zone; Naval Exercise; Pacific Ocean, Coronado, CA. (a) Location. The limits of...

Herpes simplex virus requires VP11/12 to induce phosphorylation of the activation loop tyrosine (Y394) of the Src family kinase Lck in T lymphocytes.

PubMed

Wagner, Melany J; Smiley, James R

2009-12-01

Herpes simplex virus (HSV) tegument proteins are released into the cytoplasm during viral entry and hence are among the first viral proteins encountered by an infected cell. Despite the implied importance of these proteins in the evasion of host defenses, the function of some, like virion protein 11/12 (VP11/12), have not been clearly defined. Previously, we reported that VP11/12 is strongly tyrosine phosphorylated during the infection of lymphocytes but not in fibroblasts or an epithelial cell line (G. Zahariadis, M. J. Wagner, R. C. Doepker, J. M. Maciejko, C. M. Crider, K. R. Jerome, and J. R. Smiley, J. Virol. 82:6098-6108, 2008). We also showed that tyrosine phosphorylation depends in part on the activity of the lymphocyte-specific Src family kinase (SFK) Lck in Jurkat T cells. These data suggested that VP11/12 is a substrate of Lck and that Lck is activated during HSV infection. Here, we show that HSV infection markedly increases the fraction of Lck phosphorylated on its activation loop tyrosine (Y394), a feature characteristic of activated Lck. A previous report implicated the immediate-early protein ICP0 and the viral serine/threonine kinases US3 and UL13 in the induction of a similar activated phenotype of SFKs other than Lck in fibroblasts and suggested that ICP0 interacts directly with SFKs through their SH3 domain. However, we were unable to detect an interaction between ICP0 and Lck in T lymphocytes, and we show that ICP0, US3, and UL13 are not strictly required for Lck activation. In contrast, VP11/12 interacted with Lck or Lck signaling complexes and was strictly required for Lck activation during HSV infection. Thus, VP11/12 likely modulates host cell signaling pathways for the benefit of the virus.

17 CFR 240.11a1-4(T) - Bond transactions on national securities exchanges.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Bond transactions on national securities exchanges. 240.11a1-4(T) Section 240.11a1-4(T) Commodity and Securities Exchanges SECURITIES AND....11a1-4(T) Bond transactions on national securities exchanges. A transaction in a bond, note, debenture...

17 CFR 240.11a1-4(T) - Bond transactions on national securities exchanges.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Bond transactions on national securities exchanges. 240.11a1-4(T) Section 240.11a1-4(T) Commodity and Securities Exchanges SECURITIES AND....11a1-4(T) Bond transactions on national securities exchanges. A transaction in a bond, note, debenture...

Acanthamoeba belonging to T3, T4, and T11: genotypes isolated from air-conditioning units in Santiago, Chile.

PubMed

Astorga, Berbeli; Lorenzo-Morales, Jacob; Martín-Navarro, Carmen M; Alarcón, Verónica; Moreno, Johanna; González, Ana C; Navarrete, Elizabeth; Piñero, José E; Valladares, Basilio

2011-01-01

Free-living amoebae (FLA) of the genus Acanthamoeba are widely distributed in the environment, in the air, soil, and water, and have also been isolated from air-conditioning units. The objective of this work was to investigate the presence of this genus of FLA in the air-conditioning equipment at the Institute of Public Health of Chile in Santiago, Chile. Water and air samples were collected from air-conditioning systems and were checked for the presence of Acanthamoeba spp. Positive samples were further classified at the genotype level after sequencing the highly variable diagnostic fragment 3 (DF3) region of the 18S rRNA gene. This is the first report of the T3, T4, and T11 genotypes of Acanthamoeba in air-conditioning units from Chile. Overall, the widespread distribution of potentially pathogenic Acanthamoeba strains in the studied source demands more awareness within the public and health professionals in Chile as this pathogen is emerging as a risk for human health worldwide. © 2011 The Author(s) Journal of Eukaryotic Microbiology © 2011 International Society of Protistologists.

c9t11-Conjugated linoleic acid-rich oil fails to attenuate wasting in colon-26 tumor-induced late-stage cancer cachexia in male CD2F1 mice.

PubMed

Tian, Min; Kliewer, Kara L; Asp, Michelle L; Stout, Michael B; Belury, Martha A

2011-02-01

Cancer cachexia is characterized by muscle and adipose tissue wasting caused partly by chronic, systemic inflammation. Conjugated linoleic acids (CLAs) are a group of fatty acids with various properties including anti-inflammatory cis9, trans11 (c9t11)-CLA and lipid-mobilizing trans10, cis12 (t10c12)-CLA. The purpose of this study was to test whether dietary supplementation of a c9t11-CLA-rich oil (6:1 c9t11:t10c12) could attenuate wasting of muscle and adipose tissue in colon-26 adenocarcinoma-induced cachexia in mice. Loss of body weight, muscle and adipose tissue mass caused by tumors were not rescued by supplementation with the c9t11-CLA-rich oil. In quadriceps muscle, c9t11-CLA-rich oil exacerbated tumor-induced gene expression of inflammatory markers tumor necrosis factor-α, IL-6 receptor and the E3 ligase MuRF-1 involved in muscle proteolysis. In epididymal adipose tissue, tumor-driven delipidation and atrophy was aggravated by the c9,t11-CLA-rich oil, demonstrated by further reduced adipocyte size and lower adiponectin expression. However, expression of inflammatory cytokines and macrophage markers were not altered by tumors, or CLA supplementation. These data suggest that addition of c9t11-CLA-rich oil (0.6% c9t11, 0.1% t10c12) in diet did not ameliorate wasting in mice with cancer cachexia. Instead, it increased expression of inflammatory markers in the muscle and increased adipose delipidation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

17 CFR 240.11a1-3(T) - Bona fide hedge transactions in certain securities.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Bona fide hedge transactions in certain securities. 240.11a1-3(T) Section 240.11a1-3(T) Commodity and Securities Exchanges... (rule 11a-1) § 240.11a1-3(T) Bona fide hedge transactions in certain securities. A bona fide hedge...

17 CFR 240.11a1-3(T) - Bona fide hedge transactions in certain securities.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Bona fide hedge transactions in certain securities. 240.11a1-3(T) Section 240.11a1-3(T) Commodity and Securities Exchanges... (rule 11a-1) § 240.11a1-3(T) Bona fide hedge transactions in certain securities. A bona fide hedge...

The breast cancer antigen 5T4 interacts with Rab11, and is a target and regulator of Rab11 mediated trafficking.

PubMed

Harris, Janelle L; Dave, Keyur; Gorman, Jeffrey; Khanna, Kum Kum

2018-06-01

5T4 is a transmembrane glycoprotein with limited expression in normal adult tissues and expression in some solid tumours. It is unclear whether 5T4 is preferentially expressed by stem or differentiated cell types. Modes of 5T4 regulation are unknown despite its ongoing development as a cancer immunotherapy target. Our aims were to clarify the differentiation status of 5T4 expressing cells in breast cancer and to understand the mechanism underlying 5T4 membrane presentation. We analysed 5T4 expression in breast cancer cell populations by flow cytometery and found that 5T4 is highly expressed on differentiated cells, where it localizes to focal adhesions. Using immunoprecipitation and mass spectrometry, we identified interactions between 5T4 and the membrane trafficking proteins Rab11, Rab18 and ARF6. Mechanistically we found that Rab11 and Rab18 have oppositional roles in controlling expression and surface presentation of 5T4. 5T4 depletion stabilizes Rab11 protein expression with a consequent stimulation transferrin surface labelling, indicating that 5T4 represses endocytic activity. Successful immunotherapeutic targeting of 5T4 requires surface presentation and different immunotherapy strategies require surface presentation versus endocytosis. While breast cancer cells with high 5T4 surface expression and rapid cell surface turnover would be susceptible to antibody-drug conjugates that rely on intracellular release, 5T4 positive cells with lower expression or lower turnover may still be responsive to T-cell mediated approaches. We find that endocytosis of 5T4 is strongly Rab11 dependent and as such Rab11 activity could affect the success or failure of 5T4-targetted immunotherapy, particularly for antibody-drug conjugate approaches. In fact, 5T4 itself represses Rab11 expression. This newly uncovered relationship between Rab11 and 5T4 suggests that breast tumours with high 5T4 expression may not have efficient endocytic uptake of 5T4-targetted immunotherapeutics

Herpes Simplex Virus Requires VP11/12 To Induce Phosphorylation of the Activation Loop Tyrosine (Y394) of the Src Family Kinase Lck in T Lymphocytes ▿

PubMed Central

Wagner, Melany J.; Smiley, James R.

2009-01-01

Herpes simplex virus (HSV) tegument proteins are released into the cytoplasm during viral entry and hence are among the first viral proteins encountered by an infected cell. Despite the implied importance of these proteins in the evasion of host defenses, the function of some, like virion protein 11/12 (VP11/12), have not been clearly defined. Previously, we reported that VP11/12 is strongly tyrosine phosphorylated during the infection of lymphocytes but not in fibroblasts or an epithelial cell line (G. Zahariadis, M. J. Wagner, R. C. Doepker, J. M. Maciejko, C. M. Crider, K. R. Jerome, and J. R. Smiley, J. Virol. 82:6098-6108, 2008). We also showed that tyrosine phosphorylation depends in part on the activity of the lymphocyte-specific Src family kinase (SFK) Lck in Jurkat T cells. These data suggested that VP11/12 is a substrate of Lck and that Lck is activated during HSV infection. Here, we show that HSV infection markedly increases the fraction of Lck phosphorylated on its activation loop tyrosine (Y394), a feature characteristic of activated Lck. A previous report implicated the immediate-early protein ICP0 and the viral serine/threonine kinases US3 and UL13 in the induction of a similar activated phenotype of SFKs other than Lck in fibroblasts and suggested that ICP0 interacts directly with SFKs through their SH3 domain. However, we were unable to detect an interaction between ICP0 and Lck in T lymphocytes, and we show that ICP0, US3, and UL13 are not strictly required for Lck activation. In contrast, VP11/12 interacted with Lck or Lck signaling complexes and was strictly required for Lck activation during HSV infection. Thus, VP11/12 likely modulates host cell signaling pathways for the benefit of the virus. PMID:19776125

t(6;11) Renal Cell Carcinoma (RCC) Expanded Immunohistochemical Profile Emphasizing Novel RCC Markers and Report of 10 New Genetically Confirmed Cases

PubMed Central

Smith, Nathaniel E.; Illei, Peter B.; Allaf, Mohamed; Gonzalez, Nilda; Morris, Kerry; Hicks, Jessica; DeMarzo, Angelo; Reuter, Victor E.; Amin, Mahul B.; Epstein, Jonathan I.; Netto, George J.; Argani, Pedram

2015-01-01

Renal cell carcinomas (RCCs) harboring the t(6;11)(p21;q12) translocation were first described in 2001 and recently recognized by the 2013 International Society of Uro-logical Pathology Vancouver Classification of Renal Neoplasia. Although these RCCs are known to label for melanocytic markers HMB45 and Melan A and the cysteine protease cath-epsin K by immunohistochemistry (IHC), a comprehensive IHC profile has not been reported. We report 10 new t(6;11) RCCs, all confirmed by break-apart TFEB fluorescence in situ hybridization. A tissue microarray containing 6 of these cases and 7 other previously reported t(6;11) RCCs was constructed and immunolabeled for 21 different antigens. Additional whole sections of t(6;11) RCC were labeled with selected IHC markers. t(6;11) RCC labeled diffusely and consistently for cathepsin K and Melan A (13 of 13 cases) and almost always at least focally for HMB45 (12 of 13 cases). They labeled frequently for PAX8 (14 of 23 cases), CD117 (10 of 14 cases), and vimentin (9 of 13 cases). A majority of cases labeled at least focally for cytokeratin Cam5.2 (8 of 13 cases) and CD10 and RCC marker antigen (10 of 14 cases each). In contrast to a prior study's findings, only a minority of cases labeled for Ksp-cadherin (3 of 19 cases). The median H score (product of intensity score and percentage labeling) for phosphorylated S6, a marker of mTOR pathway activation, was 101, which is high relative to most other RCC subtypes. In summary, IHC labeling for PAX8, Cam5.2, CD10, and RCC marker antigen supports classification of the t(6;11) RCC as carcinomas despite frequent negativity for broad-spectrum cytokeratins and EMA. Labeling for PAX8 distinguishes the t(6;11) RCC from epithelioid angiomyolipoma, which otherwise shares a similar immunoprofile. CD117 labeling is more frequent in the t(6;11) RCC compared with the related Xp11 translocation RCC. Increased pS6 expression suggests a possible molecular target for the uncommon t(6;11) RCCs that

t(6;11) renal cell carcinoma (RCC): expanded immunohistochemical profile emphasizing novel RCC markers and report of 10 new genetically confirmed cases.

PubMed

Smith, Nathaniel E; Illei, Peter B; Allaf, Mohamed; Gonzalez, Nilda; Morris, Kerry; Hicks, Jessica; Demarzo, Angelo; Reuter, Victor E; Amin, Mahul B; Epstein, Jonathan I; Netto, George J; Argani, Pedram

2014-05-01

Renal cell carcinomas (RCCs) harboring the t(6;11)(p21;q12) translocation were first described in 2001 and recently recognized by the 2013 International Society of Urological Pathology Vancouver Classification of Renal Neoplasia. Although these RCCs are known to label for melanocytic markers HMB45 and Melan A and the cysteine protease cathepsin K by immunohistochemistry (IHC), a comprehensive IHC profile has not been reported. We report 10 new t(6;11) RCCs, all confirmed by break-apart TFEB fluorescence in situ hybridization. A tissue microarray containing 6 of these cases and 7 other previously reported t(6;11) RCCs was constructed and immunolabeled for 21 different antigens. Additional whole sections of t(6;11) RCC were labeled with selected IHC markers. t(6;11) RCC labeled diffusely and consistently for cathepsin K and Melan A (13 of 13 cases) and almost always at least focally for HMB45 (12 of 13 cases). They labeled frequently for PAX8 (14 of 23 cases), CD117 (10 of 14 cases), and vimentin (9 of 13 cases). A majority of cases labeled at least focally for cytokeratin Cam5.2 (8 of 13 cases) and CD10 and RCC marker antigen (10 of 14 cases each). In contrast to a prior study's findings, only a minority of cases labeled for Ksp-cadherin (3 of 19 cases). The median H score (product of intensity score and percentage labeling) for phosphorylated S6, a marker of mTOR pathway activation, was 101, which is high relative to most other RCC subtypes. In summary, IHC labeling for PAX8, Cam5.2, CD10, and RCC marker antigen supports classification of the t(6;11) RCC as carcinomas despite frequent negativity for broad-spectrum cytokeratins and EMA. Labeling for PAX8 distinguishes the t(6;11) RCC from epithelioid angiomyolipoma, which otherwise shares a similar immunoprofile. CD117 labeling is more frequent in the t(6;11) RCC compared with the related Xp11 translocation RCC. Increased pS6 expression suggests a possible molecular target for the uncommon t(6;11) RCCs that

Kinematics of the thoracic T10-T11 motion segment: locus of instantaneous axes of rotation in flexion and extension.

PubMed

Qiu, Tian-Xia; Teo, Ee-Chon; Lee, Kim-Kheng; Ng, Hong-Wan; Yang, Kai

2004-04-01

The purpose of this study was to determine the locations and loci of instantaneous axes of rotation (IARs) of the T10-T11 motion segment in flexion and extension. An anatomically accurate three-dimensional model of thoracic T10-T11 functional spinal unit (FSU) was developed and validated against published experimental data under flexion, extension, lateral bending, and axial rotation loading configurations. The validated model was exercised under six load configurations that produced motions only in the sagittal plane to characterize the loci of IARs for flexion and extension. The IARs for both flexion and extension under these six load types were directly below the geometric center of the moving vertebra, and all the loci of IARs were tracked superoanteriorly for flexion and inferoposteriorly for extension with rotation. These findings may offer an insight to better understanding of the kinematics of the human thoracic spine and provide clinically relevant information for the evaluation of spinal stability and implant device functionality.

Synthesis and characterization of two layered aluminophosphates, ( T) 2HAl 2P 3O 12 ( T=2-BuNH 3+) and ( T)H 2Al 2P 3O 12 ( T=pyH +)

NASA Astrophysics Data System (ADS)

Chippindale, Ann M.; Powell, Anthony V.; Bull, Lucy M.; Jones, Richard H.; Cheetham, Anthony K.; Thomas, John M.; Xu, Ruren

1992-01-01

Two new aluminophosphates, ( T) 2HAl 2P 3O 12 ( T=2-BuNH 3+) ( I) and ( T)H 2Al 2P 3O 12 ( T=pyH +) ( II) with the same framework stoichiometry but different layer structures have been prepared under nonaqueous conditions and the structures determined by single-crystal X-ray diffraction. Compound ( I) crystallizes in the monoclinic space group P2 1/ c ( Z=4), with lattice parameters a=9.261(1) b=8.365(6), c=27.119(4) Å, β=91.50(1)δ, and V=2100.1 Å 3 ( R=0.072 and R w=0.090). The structure consists of Al-and P-centered tetrahedra linked to form layers. Protonated 2-butylamine molecules are located in the interlayer spaces and hydrogen bonded to the layers through NH 3+ groups. Weak hydrophobic van der Waals' interactions between alkyl groups of the 2-BuNH 3+ cations hold the layers together. Compound ( II) crystallizes in the triclinic space group P-1 ( Z=2), with a=8.574(2), b=8.631(3), c=10.371(2) Å, α=81.84(3), β=87.53(2), γ=69.07(2)δ, and V=709.49Å 3 ( R=0.039 and R w=0.052). The structure contains tetrahedrally coordinated P atoms and both tetrahedral and trigonal pyramidal Al atoms linked to form layers which are held together through hydrogen bonding, creating cavities in which pyH + cations reside.

2. T12, exterior overall view, view from just outside the ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. T-12, exterior overall view, view from just outside the security fence looking southeast. Lyon - Whiteman Air Force Base, Minuteman Missile Launch Facility Trainer T-12, Northeast of Oscar-01 Missile Alert Facility, Knob Noster, Johnson County, MO

Trans-10,cis-12 conjugated linoleic acid (t10-c12 CLA) treatment and caloric restriction differentially affect adipocyte cell turnover in obese and lean mice.

PubMed

Yeganeh, Azadeh; Zahradka, Peter; Taylor, Carla G

2017-11-01

Caloric restriction (CR) is one of the most promising strategies for weight loss but is associated with loss of lean mass, whereas compounds such as trans-10,cis-12 conjugated linoleic acid (t10-c12 CLA) have been promoted as antiobesity agents. To compare the mechanisms of weight reduction by CR and t10-c12 CLA, body composition, glucose control, and characteristics of adipose tissue with respect to cell turnover (stem cells and preadipocytes, apoptosis and autophagy) and Tbx-1 localization were examined in obese db/db mice and lean C57BL/6J mice undergoing CR or fed CLA isomers (0.4% w/w c9-t11 or t10-c12) for 4 weeks. Our findings show that the t10-c12 CLA reduced whole-body fat mass by decreasing all fat depots (visceral, inguinal, brown/interscapular), while CR lowered both whole-body fat and lean mass in obese mice. t10-c12 CLA elevated blood glucose in both obese and lean mice, while glycemia was not altered by CR. The adipocyte stem cell population remained unchanged; however, t10-c12 CLA reduced and CR elevated the proportion of immature adipocytes in obese mice, suggesting differential effects on adipocyte maturation. t10-c12 CLA reduced apoptosis (activated caspase-3) in both obese and lean mice but did not alter autophagy (LC3II/LC3I). Nuclear Tbx-1, a marker of metabolically active beige adipocytes, was greater in the adipose of t10-c12 CLA-fed animals. Thus, weight loss achieved via t10-c12 CLA primarily involves fat loss and more cells with Tbx-1 localized to the nucleus, while CR operates through a mechanism that reduces both lean and fat mass and blocks adipocyte differentiation. Copyright © 2017 Elsevier Inc. All rights reserved.

33 CFR 165.T11-589 - Safety zone; SFOBB Demolition Safety Zone, San Francisco, CA.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Guard District § 165.T11-589 Safety zone; SFOBB Demolition Safety Zone, San Francisco, CA. (a) Location... Safety Zone, San Francisco, CA. 165.T11-589 Section 165.T11-589 Navigation and Navigable Waters COAST... paragraph (a) of this section will be in effect from 6 a.m. to 7 p.m. daily from September 1, 2013 until...

MRI of articular cartilage at microscopic resolution

PubMed Central

Xia, Y.

2013-01-01

This review briefly summarises some of the definitive studies of articular cartilage by microscopic MRI (µMRI) that were conducted with the highest spatial resolutions. The article has four major sections. The first section introduces the cartilage tissue, MRI and µMRI, and the concept of image contrast in MRI. The second section describes the characteristic profiles of three relaxation times (T1, T2 and T1ρ) and self-diffusion in healthy articular cartilage. The third section discusses several factors that can influence the visualisation of articular cartilage and the detection of cartilage lesion by MRI and µMRI. These factors include image resolution, image analysis strategies, visualisation of the total tissue, topographical variations of the tissue properties, surface fibril ambiguity, deformation of the articular cartilage, and cartilage lesion. The final section justifies the values of multidisciplinary imaging that correlates MRI with other technical modalities, such as optical imaging. Rather than an exhaustive review to capture all activities in the literature, the studies cited in this review are merely illustrative. PMID:23610697

Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma.

PubMed

Kumar, Shaji; Kaufman, Jonathan L; Gasparetto, Cristina; Mikhael, Joseph; Vij, Ravi; Pegourie, Brigitte; Benboubker, Lofti; Facon, Thierry; Amiot, Martine; Moreau, Philippe; Punnoose, Elizabeth A; Alzate, Stefanie; Dunbar, Martin; Xu, Tu; Agarwal, Suresh K; Enschede, Sari Heitner; Leverson, Joel D; Ross, Jeremy A; Maciag, Paulo C; Verdugo, Maria; Touzeau, Cyrille

2017-11-30

Venetoclax is a selective, orally bioavailable BCL-2 inhibitor that induces cell death in multiple myeloma (MM) cells, particularly in those harboring t(11;14), which express high levels of BCL-2 relative to BCL-X L and MCL-1. In this phase 1 study, patients with relapsed/refractory MM received venetoclax monotherapy. After a 2-week lead-in with weekly dose escalation, daily venetoclax was given at 300, 600, 900, or 1200 mg in dose-escalation cohorts and 1200 mg in the safety expansion. Dexamethasone could be added on progression during treatment. Sixty-six patients were enrolled (30, dose-escalation cohorts; 36, safety expansion). Patients received a median of 5 prior therapies (range, 1-15); 61% were bortezomib and lenalidomide double refractory, and 46% had t(11;14). Venetoclax was generally well tolerated. Most common adverse events included mild gastrointestinal symptoms (nausea [47%], diarrhea [36%], vomiting [21%]). Cytopenias were the most common grade 3/4 events, with thrombocytopenia (32%), neutropenia (27%), anemia (23%), and leukopenia (23%) reported. The overall response rate (ORR) was 21% (14/66), and 15% achieved very good partial response or better (≥VGPR). Most responses (12/14 [86%]) were reported in patients with t(11;14). In this group, ORR was 40%, with 27% of patients achieving ≥VGPR. Biomarker analysis confirmed that response to venetoclax correlated with higher BCL2:BCL2L1 and BCL2:MCL1 mRNA expression ratios. Venetoclax monotherapy at a daily dose up to 1200 mg has an acceptable safety profile and evidence of single-agent antimyeloma activity in patients with relapsed/refractory MM, predominantly in patients with t(11;14) abnormality and those with a favorable BCL2 family profile. Registered at www.clinicaltrials.gov: #NCT01794520. © 2017 by The American Society of Hematology.

Inferior outcomes of stage III T lymphoblastic lymphoma relative to stage IV lymphoma and T-acute lymphoblastic leukemia: long-term comparison of outcomes in the JACLS NHL T-98 and ALL T-97 protocols.

PubMed

Kobayashi, Ryoji; Takimoto, Tetsuya; Nakazawa, Atsuko; Fujita, Naoto; Akazai, Ayumi; Yamato, Kazumi; Yazaki, Makoto; Deguchi, Takao; Hashii, Yoshiko; Kato, Koji; Hatakeyama, Naoki; Horibe, Keizo; Hori, Hiroki; Oda, Megumi

2014-06-01

T cell lymphoblastic lymphoma (T-LBL) accounts for 30 % of all childhood non-Hodgkin's lymphomas (NHL) in Japan. Twenty-nine patients with T-LBL in stages III and IV were eligible for and enrolled in the JACLS NHL-T98 trial (1998-2002), and 72 patients with T-ALL were enrolled in the JACLS ALL-T97 trial (1997-2001). The 10-year overall survival (OS) (61.1 ± 11.5 %) and the 10-year event-free survival (EFS) (44.4 ± 11.7 %) of stage III LBL were lower than those of other diseases, and the OS and EFS were nearly the same when comparing stage IV LBL and ALL (OS: stage IV LBL, 80.0 ± 12.7 % vs. ALL, 80.2 ± 4.9 %; EFS: stage IV, LBL 70.0 ± 14.5 % vs. ALL, 70.7 ± 5.5 %). Outcomes were worse for stage III LBL than for stage IV LBL or T-ALL. Given that the treatment results of T-ALL and LBL stage IV did not differ when compared with previous reports, LBL stage III in Japanese children may differ from LBL stage III in children in other countries.

Comparison of intra-articular methotrexate with intra-articular triamcinolone hexacetonide by thermography.

PubMed

Bird, H A; Ring, E F; Daniel, R; Bacon, P A

1977-01-01

A comparison of intra-articular methotrexate and intra-articular triamcinolone hexacetonide was made in 42 arthritic patients with persistent bilateral knee effusions. One knee was injected with either 5 mg methotrexate (two injections of 2.5 mg a week apart) or a single injection of 20 mg triamcinolone. An objective assessment of both knees was made by quantitative thermography at 0,3,7,14 and 21 days. Joints injected with triamcinolone showed a greater fall in thermographic index (T.I) than the joints injected with methotrexate, which showed similar change to the non-injected knee joints in both groups. Four patients received larger doses of methotrexate, up to 20 mg, though the fall in T.I. was still less than the mean fall for triamcinolone injected joints. Peak venous blood levels of methotrexate were reached 1 hour after intra-articular injection, and a sphygmomanometer cuff inflated around the leg above the injected knee for periods of up to 1 hour did not appreciably delay this. Methotrexate had no immediate anti-inflammatory effect, even in psoriatic arthropathy, and did not give the relief of intra-articular steroid.

17 CFR 240.11a2-2(T) - Transactions effected by exchange members through other members.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Transactions effected by exchange members through other members. 240.11a2-2(T) Section 240.11a2-2(T) Commodity and Securities... Regulation (rule 11a-1) § 240.11a2-2(T) Transactions effected by exchange members through other members. (a...

17 CFR 240.11a2-2(T) - Transactions effected by exchange members through other members.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Transactions effected by exchange members through other members. 240.11a2-2(T) Section 240.11a2-2(T) Commodity and Securities... Regulation (rule 11a-1) § 240.11a2-2(T) Transactions effected by exchange members through other members. (a...

Treatment of a Focal Articular Cartilage Defect of the Talus with Polymer-Based Autologous Chondrocyte Implantation: A 12-Year Follow-Up Period.

PubMed

Kreuz, Peter Cornelius; Kalkreuth, Richard Horst; Niemeyer, Philipp; Uhl, Markus; Erggelet, Christoph

Autologous chondrocyte implantation (ACI) is a first-line treatment option for large articular cartilage defects. Although well-established for cartilage defects in the knee, studies of the long-term outcomes of matrix-assisted ACI to treat cartilage defects in the ankle are rare. In the present report, we describe for the first time the long-term clinical and radiologic results 12 years after polymer-based matrix-assisted ACI treat a full-thickness talar cartilage defect in a 25-year-old male patient. The clinical outcome was assessed using the visual analog scale and Freiburg ankle score, magnetic resonance imaging evaluation using the Henderson-Kreuz scoring system and T2 mapping. Clinical assessment revealed improved visual analog scale and Freiburg ankle scores. The radiologic analysis and T2 relaxation time values indicated the formation of hyaline-like repair tissue. Polymer-based autologous chondrocytes has been shown to be a safe and clinically effective long-term treatment of articular cartilage defects in the talus. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Local delivery of interleukin-12 using T cells targeting VEGF receptor-2 eradicates multiple vascularized tumors in mice.

PubMed

Chinnasamy, Dhanalakshmi; Yu, Zhiya; Kerkar, Sid P; Zhang, Ling; Morgan, Richard A; Restifo, Nicholas P; Rosenberg, Steven A

2012-03-15

We investigated the feasibility of delivering the proinflammatory cytokine interleukin (IL)-12 into tumor using T cells genetically engineered to express a chimeric antigen receptor (CAR) against the VEGF receptor-2 (VEGFR-2). Two different strains of mice bearing five different established subcutaneous tumors were treated with syngeneic T cells cotransduced with an anti-VEGFR-2 CAR and a constitutively expressed single-chain murine IL-12 or an inducible IL-12 gene after host lymphodepletion. Tumor regression, survival of mice, and persistence of the transferred cells were evaluated. Adoptive transfer of syngeneic T cells cotransduced with an anti-VEGFR-2 CAR and a constitutively expressing single-chain IL-12 resulted in the regression of five different established tumors of different histologies without the need for IL-2 administration. T cells transduced with either anti-VEGFR-2 CAR or single-chain IL-12 alone did not alter the tumor growth indicating that both of them had to be expressed in the same cell to mediate tumor regression. Anti-VEGFR-2 CAR and IL-12-cotransduced T cells infiltrated the tumors, expanded, and persisted for prolonged periods. The antitumor effect did not require the presence of host T and B cells but was dependent on host IL-12R-expressing cells. The anti-VEGFR-2 CAR changed the immunosuppressive tumor environment by altering/reducing both the systemic and the intratumoral CD11b(+)Gr1(+) myeloid suppressor cell subsets that expressed VEGFR-2. These results suggest that targeted delivery of IL-12 into the tumor environment with T cells redirected against VEGFR-2 is a promising approach for treating patients with a variety of solid tumor types.

Quantitative evaluation of hyaline articular cartilage T2 maps of knee and determine the relationship of cartilage T2 values with age, gender, articular changes.

PubMed

Cağlar, E; Şahin, G; Oğur, T; Aktaş, E

2014-11-01

To identify changes in knee joint cartilage transverse relaxation values depending on the patient's age and gender and to investigate the relationship between knee joint pathologies and the transverse relaxation time. Knee MRI images of 107 symptomatic patients with various pathologic knee conditions were analyzed retrospectively. T2 values were measured at patellar cartilage, posteromedial and posterolateral femoral cartilage adjacent to the central horn of posterior meniscus. 963 measurements were done for 107 knees MRI. Relationship of T2 values with seven features including subarticular bone marrow edema, subarticular cysts, marginal osteophytes, anterior-posterior cruciate and collateral ligament tears, posterior medial and posterior lateral meniscal tears, synovial thickening and effusion were analyzed. T2 values in all three compartments were evaluated according to age and gender. A T2 value increase correlated with age was present in all three compartments measured in the subgroup with no knee joint pathology and in all patient groups. According to the ROC curve, an increase showing a statistically significant difference was present in the patient group aged over 40 compared to the patient group aged 40 and below in all patient groups. There is a statistically difference at T2 values with and without subarticular cysts, marginal osteophytes, synovial thickening and effusion. T2 relaxation time showed a statistically significant increase in the patients with a medial meniscus tear compared to those without a tear and no statistically significant difference was found in T2 relaxation times of patients with and without a posterior lateral meniscus tear. T2 cartilage mapping on MRI provides opportunity to exhibit biochemical and structural changes related with cartilage extracellular matrix without using invasive diagnostic methods.

[A rare case of myeloproliferative disease with t(8;13)(p11;q12) associated with eosinophilia and lymphadenopathy].

PubMed

Tsyba, N N; Turkina, A G; Chelysheva, E Yu; Nemchenko, I S; Kovrigina, A M; Obukhova, T N; Urnova, E S; Kuzmina, L A; Savchenko, V G

Myeloproliferative disease associated with FGFR1 rearrangement (8p11), which is included in the 2008 WHO Classification of Myeloid Neoplasms, is a rare and extremely aggressive abnormality. The paper describes a clinical case of a 39-year-old female patient who was detected to have leukocytosis (as high as 47.2·109/l), absolute eosinophilia (as high as 3.1·109/l), and enlarged peripheral lymph nodes during her visit to a doctor. The bone marrow (BM) showed the changes typically encountered in myeloproliferative disease with eosinophilia. The patient was found to have t(8;13)(p11;q12) translocation associated with the rearrangement of the FGFR1 gene located at the 8p11 locus. Molecular and cytogenetic examinations failed to reveal BCR-ABL chimeric transcript, Jak2 V617F mutation, and deletions and translocations involving PDGFRA (4q12) and PDGFRB (5q32-33). The similar changes in the karyotype were also found in the lymph node cells. The undertaken treatment with hydroxyurea and the tyrosine kinase inhibitor dasatinib turned out to be ineffective. The patient underwent allogeneic BM transplantation from a HLA-identical sibling. Graft rejection occurred 6 months later. Allogeneic BM transplantation from the same donor (100% donor chimerism; FGFR1/8р11 translocation was not detected), which was complicated by the development of chronic graft-versus-host reaction, was performed again in March 2015. The patient is being followed up and continues to receive immunosuppressive therapy.

Large NLO corrections in t\\overline{t}{W}^{± } and t\\overline{t}t\\overline{t} hadroproduction from supposedly subleading EW contributions

NASA Astrophysics Data System (ADS)

Frederix, Rikkert; Pagani, Davide; Zaro, Marco

2018-02-01

We calculate the complete-NLO predictions for t\\overline{t}{W}^{± } and t\\overline{t}t\\overline{t} production in proton-proton collisions at 13 and 100 TeV. All the non-vanishing contributions of O({α}_s^i{α}^j) with i + j = 3 , 4 for t\\overline{t}{W}^{± } and i + j = 4 , 5 for t\\overline{t}t\\overline{t} are evaluated without any approximation. For t\\overline{t}{W}^{± } we find that, due to the presence of tW → tW scattering, at 13(100) TeV the O({α}_s{α}^3) contribution is about 12(70)% of the LO, i.e., it is larger than the so-called NLO EW corrections (the O({α}_s^2{α}^2) terms) and has opposite sign. In the case of t\\overline{t}t\\overline{t} production, large contributions from electroweak tt → tt scattering are already present at LO in the O({α}_s^3α ) and O({α}_s^2{α}^2) terms. For the same reason we find that both NLO terms of O({α}_s^4α ) , i.e., the NLO EW corrections, and O({α}_s^3{α}^2) are large (±15% of the LO) and their relative contributions strongly depend on the values of the renormalisation and factorisation scales. However, large accidental cancellations are present (away from the threshold region) between these two contributions. Moreover, the NLO corrections strongly depend on the kinematics and are particularly large at the threshold, where even the relative contribution from O({α}_s^2{α}^3) terms amounts to tens of percents.

33 CFR 165.T11-405 - Safety zone; Sea World Fireworks; Mission Bay, San Diego, CA.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Safety zone; Sea World Fireworks; Mission Bay, San Diego, CA. 165.T11-405 Section 165.T11-405 Navigation and Navigable Waters COAST GUARD... § 165.T11-405 Safety zone; Sea World Fireworks; Mission Bay, San Diego, CA. (a) Location. The safety...

Mapping of the Pim-1 oncogene in mouse t-haplotypes and its use to define the relative map positions of the tcl loci t0(t6) and tw12 and the marker tf (tufted).

PubMed

Ark, B; Gummere, G; Bennett, D; Artzt, K

1991-06-01

Pim-1 is an oncogene activated in mouse T-cell lymphomas induced by Moloney and AKR mink cell focus (MCF) viruses. Pim-1 was previously mapped to chromosome 17 by somatic cell hybrids, and subsequently to the region between the hemoglobin alpha-chain pseudogene 4 (Hba-4ps) and the alpha-crystalline gene (Crya-1) by Southern blot analysis of DNA obtained from panels of recombinant inbred strains. We have now mapped Pim-1 more accurately in t-haplotypes by analysis of recombinant t-chromosomes. The recombinants were derived from Tts6tf/t12 parents backcrossed to + tf/ + tf, and scored for recombination between the loci of T and tf. For simplicity all t-complex lethal genes properly named tcl-tx are shortened to tx. The Pim-1 gene was localized 0.6 cM proximal to the tw12 lethal gene, thus placing the Pim-1 gene 5.2 cM distal to the H-2 region in t-haplotypes. Once mapped, the Pim-1 gene was used as a marker for further genetic analysis of t-haplotypes. tw12 is so close to tf that even with a large number of recombinants it was not possible to determine whether it is proximal or distal to tf. Southern blot analysis of DNA from T-tf recombinants with a separation of tw12 and tf indicated that tw12 is proximal to tf. The mapping of two allelic t-lethals, t0 and t6 with respect to tw12 and tf has also been a problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative MRI T2 relaxation time evaluation of knee cartilage: comparison of meniscus-intact and -injured knees after anterior cruciate ligament reconstruction.

PubMed

Li, Hong; Chen, Shuang; Tao, Hongyue; Chen, Shiyi

2015-04-01

Associated meniscal injury is well recognized at anterior cruciate ligament (ACL) reconstruction, and it is a known risk factor for osteoarthritis. To evaluate and characterize the postoperative appearance of articular cartilage after different meniscal treatment in ACL-reconstructed knees using T2 relaxation time evaluation on MRI. Cohort study; Level of evidence, 3. A total of 62 consecutive patients who under ACL reconstruction were recruited in this study, including 23 patients undergoing partial meniscectomy (MS group), 21 patients undergoing meniscal repair (MR group), and 18 patients with intact menisci (MI group) at time of surgery. Clinical evaluation, including subjective functional scores and physical examination, was performed on the same day as the MRI examination and at follow-up times ranging from 2 to 4.2 years. The MRI multiecho sagittal images were segmented to determine the T2 relaxation time value of each meniscus and articular cartilage plate. Differences in each measurement were compared among groups. No patient had joint-line tenderness or reported pain or clicking on McMurray test or instability. There were also no statistically significant differences in functional scores or medial or lateral meniscus T2 values among the 3 groups (P > .05 for both). There was a significantly higher articular cartilage T2 value in the medial femorotibial articular cartilage for the MS group (P < .01) and the MR group (P < .05) compared with that of the MI group, while there was no significant difference in articular cartilage T2 value between the MS and MR groups (P > .05) in each articular cartilage plate. The medial tibial articular cartilage T2 value had a significant positive correlation with medial meniscus T2 value (r = 0.287; P = .024) CONCLUSION: This study demonstrates that knees with meniscectomy or meniscal repair had articular cartilage degeneration at 2 to 4 years postoperatively, with higher articular cartilage T2 relaxation time values

Translocation Renal Cell Carcinoma t(6;11)(p21;q12) and Sickle Cell Anemia: First Report and Review of the Literature.

PubMed

Chaste, Damien; Vian, Emmanuel; Verhoest, Gregory; Blanchet, Pascal

2014-02-01

Translocation renal cell carcinoma (RCC) is a family of rare tumors recently identified in the pediatric and young adult population. We report the first case of a young woman from French West Indies with sickle cell anemia who developed a translocation RCC t(6;11)(p21;q12). Usually people with the sickle cell condition are known to develop renal medullary carcinoma (RMC). To our knowledge, this is the first case described in the literature of a translocation RCC associated with sickle cell disease. Here we discuss the relation between translocation RCC, RMC, and sickle cell disease.

Methionine Regulates mTORC1 via the T1R1/T1R3-PLCβ-Ca2+-ERK1/2 Signal Transduction Process in C2C12 Cells.

PubMed

Zhou, Yuanfei; Ren, Jiao; Song, Tongxing; Peng, Jian; Wei, Hongkui

2016-10-11

The mammalian target of rapamycin complex 1 (mTORC1) integrates amino acid (AA) availability to support protein synthesis and cell growth. Taste receptor type 1 member (T1R) is a G protein-coupled receptor that functions as a direct sensor of extracellular AA availability to regulate mTORC1 through Ca 2+ stimulation and extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation. However, the roles of specific AAs in T1R1/T1R3-regulated mTORC1 are poorly defined. In this study, T1R1 and T1R3 subunits were expressed in C2C12 myotubes, and l-AA sensing was accomplished by T1R1/T1R3 to activate mTORC1. In response to l-AAs, such as serine (Ser), arginine (Arg), threonine (Thr), alanine (Ala), methionine (Met), glutamine (Gln), and glycine (Gly), Met induced mTORC1 activation and promoted protein synthesis. Met also regulated mTORC1 via T1R1/T1R3-PLCβ-Ca 2+ -ERK1/2 signal transduction. Results revealed a new role for Met-regulated mTORC1 via an AA receptor. Further studies should be performed to determine the role of T1R1/T1R3 in mediating extracellular AA to regulate mTOR signaling and to reveal its mechanism.

High percentage of regulatory T cells before and after vitamin B12 treatment in patients with pernicious anemia.

PubMed

Watanabe, Satoru; Ide, Norifumi; Ogawara, Hatsue; Yokohama, Akihiko; Mitsui, Takeki; Handa, Hiroshi; Koiso, Hiromi; Tsukamoto, Norifumi; Saitoh, Takayuki; Murakami, Hirokazu

2015-01-01

In some previous studies, vitamin B12 treatment showed immunomodulatory effects and restored the immunological abnormalities in patients with pernicious anemia (PA). In the present study, peripheral blood T cell subsets, including regulatory T cells (T(reg)s), were examined before and after vitamin B12 treatment in PA patients. The percentages of CD4, CD8, Th1, Th2 and T(reg)s were examined in 23 PA patients before vitamin B12 treatment, in 23 other PA patients after vitamin B12 treatment and in 28 healthy controls. The mean percentage of CD8+ T cells was significantly higher in the control group (23.0%; 95% CI, 20.4-25.6%) than in the pre- (16.0%; 95% CI, 12.1-20.0%) and posttreatment groups (15.2%; 95% CI, 11.8-18.6%; p < 0.05). The CD4/CD8 ratio was significantly lower in the control group (2.01; 95% CI, 1.66-2.34) than in the pre- (3.45; 95% CI, 2.55-7.80) and posttreatment groups (2.97; 95% CI, 2.22-3.72; p < 0.05). There was no significant difference in the mean Th1/Th2 ratio among these groups. There were significant increases in the mean percentage of T(reg)s in the pre- (6.29%; 95% CI, 5.04-7.54%) and posttreatment groups (7.77%; 95% CI, 6.34-9.20%) compared with the control group (4.18%; 95% CI, 3.92-4.47%; p < 0.05). The percentage of T(reg)s was significantly higher in PA patients than in normal subjects, and this high T(reg) percentage was not different before and after vitamin B12 treatment. Other immunological alterations also did not recover after vitamin B12 treatment, so that these immunological changes appear to be the cause of PA and are not induced by vitamin B12 deficiency. © 2014 S. Karger AG, Basel.

Expression of Master Regulators of T-cell, Helper T-cell and Follicular Helper T-cell Differentiation in Angioimmunoblastic T-cell Lymphoma.

PubMed

Matsumoto, Yosuke; Nagoshi, Hisao; Yoshida, Mihoko; Kato, Seiichi; Kuroda, Junya; Shimura, Kazuho; Kaneko, Hiroto; Horiike, Shigeo; Nakamura, Shigeo; Taniwaki, Masafumi

2017-11-01

Objective It has been postulated that the normal counterpart of angioimmunoblastic T-cell lymphoma (AITL) is the follicular helper T-cell (TFH). Recent immunological studies have identified several transcription factors responsible for T-cell differentiation. The master regulators associated with T-cell, helper T-cell (Th), and TFH differentiation are reportedly BCL11B, Th-POK, and BCL6, respectively. We explored the postulated normal counterpart of AITL with respect to the expression of the master regulators of T-cell differentiation. Methods We performed an immunohistochemical analysis in 15 AITL patients to determine the expression of the master regulators and several surface markers associated with T-cell differentiation. Results BCL11B was detected in 10 patients (67%), and the surface marker of T-cells (CD3) was detected in all patients. Only 2 patients (13%) expressed the marker of naïve T-cells (CD45RA), but all patients expressed the marker of effector T-cells (CD45RO). Nine patients expressed Th-POK (60%), and 7 (47%) expressed a set of surface antigens of Th (CD4-positive and CD8-negative). In addition, BCL6 and the surface markers of TFH (CXCL13, PD-1, and SAP) were detected in 11 (73%), 8 (53%), 14 (93%), and all patients, respectively. Th-POK-positive/BCL6-negative patients showed a significantly shorter overall survival (OS) than the other patients (median OS: 33.0 months vs. 74.0 months, p=0.020; log-rank test). Conclusion Many of the AITL patients analyzed in this study expressed the master regulators of T-cell differentiation. The clarification of the diagnostic significance and pathophysiology based on the expression of these master regulators in AITL is expected in the future.

MiT translocation renal cell carcinomas: two subgroups of tumours with translocations involving 6p21 [t (6; 11)] and Xp11.2 [t (X;1 or X or 17)].

PubMed

Hora, Milan; Urge, Tomáš; Trávníček, Ivan; Ferda, Jiří; Chudáček, Zdeněk; Vaněček, Tomáš; Michal, Michal; Petersson, Fredrik; Kuroda, Naoto; Hes, Ondřej

2014-01-01

MiT translocation renal cell carcinomas (TRCC) predominantly occur in younger patients with only 25% of patients being over 40 years. TRCC contains two main subgroups with translocations involving 6p21 or Xp11.2. Herein we present 10 cases. Eight cases were treated at main author's institution (identified among 1653 (0.48%) cases of kidney tumours in adults). Two cases were retrieved from the Pilsen (CZ) Tumour Registry. Six cases were type Xp11.2 and four 6p21; 7 female, 3 male patients; Xp11.2 4:2, 6p21 3:1. The mean age 49 years (range: 21-80), 5 patients (50%) over 40 years. The mean age of the group with Xp11.2 TRCCs was 55 (median 51) and 6p21 41 (32) years. One female with a 6p21 tumour (24 years) underwent nephrectomy at 4 months of pregnancy. Stage (UICC, 7th ed. 2009) was 5xI, 3xIII, 2xIV. The mean size of tumour was 80 (40-165) mm. The mean follow-up was 33.2 (1-92) months. In patients with 6p21 tumours, one (25%) died after 3 months due to widely metastatic disease. In patients with Xp11.2 tumours, 3 (50%) succumbed due to metastatic disease (range 1-8 months). Three patients with Xp11.2 are alive at 7, 52 and 92 months of follow-up, were diagnosed at early stage (T1a). TRCCs were more common in females. Patient with 6p21 tumours were younger than those with Xp11.2. Both types have definitive malignant potential Type Xp11.2 seems to be a more aggressive neoplasm than 6p21. The case with metastatic 6p21 tumour is the 4th case described in the English literature.

The episodic ataxia type 1 mutation I262T alters voltage-dependent gating and disrupts protein biosynthesis of human Kv1.1 potassium channels.

PubMed

Chen, Szu-Han; Fu, Ssu-Ju; Huang, Jing-Jia; Tang, Chih-Yung

2016-01-18

Voltage-gated potassium (Kv) channels are essential for setting neuronal membrane excitability. Mutations in human Kv1.1 channels are linked to episodic ataxia type 1 (EA1). The EA1-associated mutation I262T was identified from a patient with atypical phenotypes. Although a previous report has characterized its suppression effect, several key questions regarding the impact of the I262T mutation on Kv1.1 as well as other members of the Kv1 subfamily remain unanswered. Herein we show that the dominant-negative effect of I262T on Kv1.1 current expression is not reversed by co-expression with Kvβ1.1 or Kvβ2 subunits. Biochemical examinations indicate that I262T displays enhanced protein degradation and impedes membrane trafficking of Kv1.1 wild-type subunits. I262T appears to be the first EA1 mutation directly associated with impaired protein stability. Further functional analyses demonstrate that I262T changes the voltage-dependent activation and Kvβ1.1-mediated inactivation, uncouples inactivation from activation gating, and decelerates the kinetics of cumulative inactivation of Kv1.1 channels. I262T also exerts similar dominant effects on the gating of Kv1.2 and Kv1.4 channels. Together our data suggest that I262T confers altered channel gating and reduced functional expression of Kv1 channels, which may account for some of the phenotypes of the EA1 patient.

Histopathology of chondronecrosis development in knee articular cartilage in a rat model of Kashin-Beck disease using T-2 toxin and selenium deficiency conditions.

PubMed

Guan, Fang; Li, Siyuan; Wang, Zhi-Lun; Yang, Haojie; Xue, Senghai; Wang, Wei; Song, Daiqing; Zhou, Xiaorong; Zhou, Wang; Chen, Jing-Hong; Caterson, Bruce; Hughes, Clare

2013-01-01

The objective of this study is to observe pathogenic lesions of joint cartilages in rats fed with T-2 toxin under a selenium deficiency nutrition status in order to determine possible etiological factors causing Kashin-Beck disease (KBD). Sprague-Dawley rats were fed selenium-deficient or control diets for 4 weeks prior to their being exposed to T-2 toxin. Six dietary groups were formed and studied 4 weeks later, i.e., controls, selenium-deficient, low T-2 toxin, high T-2 toxin, selenium-deficient diet plus low T-2 toxin, and selenium-deficient diet plus high T-2 toxin. Selenium deficiencies were confirmed by the determination of glutathione peroxidase activity and selenium levels in serum. The morphology and pathology (chondronecrosis) of knee joint cartilage of experimental rats were observed using light microscopy and the expression of proteoglycans was determined by histochemical staining. Chondronecrosis in deep zone of articular cartilage of knee joints was seen in both the low and high T-2 toxin plus selenium-deficient diet groups, these chondronecrotic lesions being very similar to chondronecrosis observed in human KBD. However, the chondronecrosis observed in the rat epiphyseal growth plates of animals treated with T-2 toxin alone or T-2 toxin plus selenium-deficient diets were not similar to that found in human KBD. Our results indicate that the rat can be used as a suitable animal model for studying etiological factors contributing to the pathogenesis (chondronecrosis) observed in human KBD. However, those changes seen in epiphyseal growth plate differ from those seen in human KBD probably because of the absence of growth plate closure in the rat.

HLA-A02:01-restricted epitopes identified from the herpes simplex virus tegument protein VP11/12 preferentially recall polyfunctional effector memory CD8+ T cells from seropositive asymptomatic individuals and protect humanized HLA-A*02:01 transgenic mice against ocular herpes.

PubMed

Srivastava, Ruchi; Khan, Arif A; Spencer, Doran; Vahed, Hawa; Lopes, Patricia P; Thai, Nhi Thi Uyen; Wang, Christine; Pham, Thanh T; Huang, Jiawei; Scarfone, Vanessa M; Nesburn, Anthony B; Wechsler, Steven L; BenMohamed, Lbachir

2015-03-01

The HSV type 1 tegument virion phosphoprotein (VP) 11/12 (VP11/12) is a major Ag targeted by CD8(+) T cells from HSV-seropositive individuals. However, whether and which VP11/12 epitope-specific CD8(+) T cells play a role in the "natural" protection seen in seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) remain to be determined. In this study, we used multiple prediction computer-assisted algorithms to identify 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the 718-aa sequence of VP11/12. Three of 10 epitopes exhibited high-to-moderate binding affinity to HLA-A*02:01 molecules. In 10 sequentially studied HLA-A*02:01-positive and HSV-1-seropositive ASYMP individuals, the most frequent, robust, and polyfunctional effector CD8(+) T cell responses, as assessed by a combination of tetramer frequency, granzyme B, granzyme K, perforin, CD107(a/b) cytotoxic degranulation, IFN-γ, and multiplex cytokines assays, were predominantly directed against three epitopes: VP11/1266-74, VP11/12220-228, and VP11/12702-710. Interestingly, ASYMP individuals had a significantly higher proportion of CD45RA(low)CCR7(low)CD44(high)CD62L(low)CD27(low)CD28(low)CD8(+) effector memory CD8(+) T cells (TEMs) specific to the three epitopes, compared with symptomatic individuals (with a history of numerous episodes of recurrent ocular herpetic disease). Moreover, immunization of HLA-A*02:01 transgenic mice with the three ASYMP CD8(+) TEM cell epitopes induced robust and polyfunctional epitope-specific CD8(+) TEM cells that were associated with a strong protective immunity against ocular herpes infection and disease. Our findings outline phenotypic and functional features of protective HSV-specific CD8(+) T cells that should guide the development of an effective T cell-based herpes vaccine. Copyright © 2015 by The American Association of Immunologists, Inc.

HLA-A02:01-Restricted Epitopes Identified from the Herpes Simplex Virus Tegument Protein VP11/12 Preferentially Recall Polyfunctional Effector Memory CD8+ T Cells from Seropositive Asymptomatic Individuals and Protect “Humanized” HLA-A*02:01 Transgenic Mice Against Ocular Herpes

PubMed Central

Srivastava, Ruchi; Khan, Arif A.; Spencer, Doran; Vahed, Hawa; Lopes, Patricia P.; Thai, Nhi Thi Uyen; Wang, Christine; Pham, Thanh T.; Huang, Jiawei; Scarfone, Vanessa M.; Nesburn, Anthony B.; Wechsler, Steven L.; BenMohamed, Lbachir

2014-01-01

The Herpes Simplex Virus type 1 virion tegument phosphoprotein 11/12 (HSV-1 VP11/12) is a major antigen targeted by CD8+ T cells from HSV-seropositive individuals. However, whether and which VP11/12-epitope-specific CD8+ T cells play a role in the “natural” protection seen in seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) remain to be determined. In this study, we used multiple prediction computer-assisted algorithms to identify 10 potential HLA-A*02:01-restricted CD8+ T cell epitopes from the 716 amino acids sequence of VP11/12. Three out of ten epitopes exhibited high to moderate binding affinity to HLA-A*02:01 molecules. In ten sequentially studied HLA-A*02:01 positive and HSV-1-seropositive ASYMP individuals, the most frequent, robust and polyfunctional effector CD8+ T-cell responses, as assessed by a combination of tetramer frequency, granzyme B, granzyme K, perforin, CD107a/b cytotoxic degranulation, IFN-γ and multiplex cytokines assays, were predominantly directed against three epitopes: VP11/1266–74, VP11/12220–228 and VP11/12702–710. Interestingly, ASYMP individuals had significantly higher proportion of CD45RAlowCCR7lowCD44highCD62LlowCD27lowCD28lowCD8+ effector memory T cells (TEM) specific to the three epitopes, compared to symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent ocular herpetic disease). Moreover, immunization of HLA-A*02:01 transgenic mice with the three ASYMP CD8+ TEM cell epitopes induced robust and polyfunctional epitope-specific CD8+ TEM cells that were associated with a strong protective immunity against ocular herpes infection and disease. Our findings outline phenotypic and functional features of protective HSV-specific CD8+ T cells that should guide the development of an effective T-cell-based herpes vaccine. PMID:25617474

33 CFR 165.T11-281 - Safety Zone; Lake Mead Intake Construction; Lake Mead, Boulder City, NV.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety Zone; Lake Mead Intake Construction; Lake Mead, Boulder City, NV. 165.T11-281 Section 165.T11-281 Navigation and Navigable Waters... Coast Guard District § 165.T11-281 Safety Zone; Lake Mead Intake Construction; Lake Mead, Boulder City...

A comparison of multi-echo spin-echo and triple-echo steady-state T2 mapping for in vivo evaluation of articular cartilage.

PubMed

Juras, Vladimir; Bohndorf, Klaus; Heule, Rahel; Kronnerwetter, Claudia; Szomolanyi, Pavol; Hager, Benedikt; Bieri, Oliver; Zbyn, Stefan; Trattnig, Siegfried

2016-06-01

To assess the clinical relevance of T2 relaxation times, measured by 3D triple-echo steady-state (3D-TESS), in knee articular cartilage compared to conventional multi-echo spin-echo T2-mapping. Thirteen volunteers and ten patients with focal cartilage lesions were included in this prospective study. All subjects underwent 3-Tesla MRI consisting of a multi-echo multi-slice spin-echo sequence (CPMG) as a reference method for T2 mapping, and 3D TESS with the same geometry settings, but variable acquisition times: standard (TESSs 4:35min) and quick (TESSq 2:05min). T2 values were compared in six different regions in the femoral and tibial cartilage using a Wilcoxon signed ranks test and the Pearson correlation coefficient (r). The local ethics committee approved this study, and all participants gave written informed consent. The mean quantitative T2 values measured by CPMG (mean: 46±9ms) in volunteers were significantly higher compared to those measured with TESS (mean: 31±5ms) in all regions. Both methods performed similarly in patients, but CPMG provided a slightly higher difference between lesions and native cartilage (CPMG: 90ms→61ms [31%],p=0.0125;TESS 32ms→24ms [24%],p=0.0839). 3D-TESS provides results similar to those of a conventional multi-echo spin-echo sequence with many benefits, such as shortening of total acquisition time and insensitivity to B1 and B0 changes. • 3D-TESS T 2 mapping provides clinically comparable results to CPMG in shorter scan-time. • Clinical and investigational studies may benefit from high temporal resolution of 3D-TESS. • 3D-TESS T 2 values are able to differentiate between healthy and damaged cartilage.

Characterization of 1:1 Random Copolymers Obtained from 6-, 7-, 11-, and 12-Carbon Amino Acids.

DTIC Science & Technology

1993-10-22

Random Copolymers Obtained From 6-, 7-, 11-, and 12-Carbon Amino Acids by C. G. Johnson and L. J. Mathias 0 T .... Prepared for Publication r. t in the...NOOOG4-f-j- From 6-, 7-, 11-, and 12-Carbon Amino Acids 1225 ~~~ :: V Co~de 413m(iUK C. G Johnson, and Lo J. Mathias ś RFORMING ORGANIZA7,iCN ;fAMjjS...distribution is unlimited. Copolymers were prepared from the title amino acids by rr ilt condensation under dry nitrogen. The resulting copolymers were

Identification of T-cell Receptors Targeting KRAS-mutated Human Tumors

PubMed Central

Wang, Qiong J.; Yu, Zhiya; Griffith, Kayla; Hanada, Ken-ichi; Restifo, Nicholas P.; Yang, James C.

2015-01-01

KRAS is one of the most frequently mutated proto-oncogenes in human cancers. The dominant oncogenic mutations of KRAS are single amino acid substitutions at codon 12, in particular G12D and G12V present in 60–70% of pancreatic cancers and 20–30% of colorectal cancers. The consistency, frequency, and tumor specificity of these “neo-antigens” make them attractive therapeutic targets. Recent data associates T cells that target mutated antigens with clinical immunotherapy responses in patients with metastatic melanoma, lung cancer, or cholangiocarcinoma. Using HLA-peptide prediction algorithms, we noted that HLA-A*11:01 could potentially present mutated KRAS variants. By immunizing HLA-A*11:01 transgenic mice, we generated murine T cells and subsequently isolated T-cell receptors (TCRs) highly reactive to the mutated KRAS variants G12V and G12D. Peripheral blood lymphocytes (PBLs) transduced with these TCRs could recognize multiple HLA-A*11:01+ tumor lines bearing the appropriate KRAS mutations. In a xenograft model of large established tumor, adoptive transfer of these transduced PBLs reactive with an HLA-A*11:01, G12D-mutated pancreatic cell line could significantly reduce its growth in NSG mice (P = 0.002). The success of adoptive transfer of TCR-engineered T cells against melanoma and other cancers support clinical trials with these T cells that recognize mutated KRAS in patients with a variety of common cancer types. PMID:26701267

[Risk of type 2 diabetes mellitus in the Kyrgyz population in the presence of ADIPOQ (G276T), KCNJ11 (Glu23Lys), TCF7L2 (IVS3C>T) gene polymorphisms].

PubMed

Isakova, Zh T; Talaibekova, E T; Asambaeva, D A; Kerimkulova, A S; Lunegova, O S; Aldasheva, N M; Aldashev, A A

To analyze the association of genotype combinations of the polymorphic markers G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene with the development of type 2 diabetes mellitus (T2DM) in the Kyrgyz population. The investigation enrolled 23 Kyrgyz people, of whom there were 114 patients with T2DM and 109 without T2DM (a control group). T2DM was diagnosed in accordance with the WHO criteria (1999). The genotypes of ADIPOQ (G276T), KCNJ11 (Glu23Lys), and TCF7L2 (IVS3C>T) gene polymorphisms were identified using the restriction fragment length polymorphism analysis. When typing at the polymorphic loci G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene, the development of T2DM in the Kyrgyz population was associated with the T allele (odds ratio (OR), 1.68; p=0.025), the heterozygous G276T genotype (OR 1,8; p=0.036) in the ADIPOQ gene; the 23Lys allele (OR, 1.62; p=0.019) in the KCNJ11 gene; a two-locus genotype combination in the genes ADIPOQ/KCNJ11: G276T/Glu23Lys (OR, 4.88; p=0.0013), G276G/Lys23Lys (OR, 4.65; p=0.019), G276T/Glu23Glu (OR, 3.10; p=0.022), a two-locus genotype combination in the genes ADIPOQ/TCF7L2: G276T/СС (OR, 1.97; p=0.04); two-locus genotype combinations in the genes KCNJ11/TCF7L2: Lys23Lys/CC (ОR, 2.65; p=0.042), Glu23Lys/CT (OR, 3.88; p=0.027); and a three-locus genotype combination in the genes ADIPOQ/KCNJ11/TCF7L2: G276T/Glu23Lys/CT (OR, 14.48; p=0.02). The development of T2DM in the Kyrgyz population is genetically determined by ADIPOQ (G276T) gene, KCNJ11 (Glu23Lys), and TCF7L (IVS3C>T) gene polymorphisms with the predisposing value of the T allele of the heterozygous G276T genotype in the ADIPOQ gene; the 23Lys allele in the KCNJ1 gene; as well as by genotype combinations in the genes ADIPOQ/KCNJ11 (G276T/Glu23Lys, G276G/Lys23Lys, G276T/Glu23Glu); ADIPOQ/TCF7L2 (G276T/SS); KCNJ11/TCF7L2 (Lys23Lys/CC, Glu23Lys/CT); ADIPOQ/KCNJ11/TCF7L2 (G276T/Glu23Lys /CT). The IVS3C>T

T9 versus T10 as the upper instrumented vertebra for correction of adult deformity-rationale and recommendations.

PubMed

Hey, Hwee Weng Dennis; Tan, Kimberly-Anne; Neo, Christabel Shao-En; Lau, Eugene Tze-Chun; Choong, Denise Ai-Wen; Lau, Leok-Lim; Liu, Gabriel Ka-Po; Wong, Hee-Kit

2017-05-01

Adult spinal deformity correction sometimes involves long posterior pedicle screw constructs extending from the lumbosacral spine to the thoracic vertebra. As fusion obliterates motion and places supraphysiological stress on adjacent spinal segments, it is crucial to ascertain the ideal upper instrumented vertebra (UIV) to minimize risk of proximal junctional failure (PJF). The T10 vertebra is often chosen to allow bridging of the thoracolumbar junction into the immobile thoracic vertebrae on the basis that it is the lowest immobile thoracic vertebra strut by the rib cage. This study aimed to characterize the range of motion (ROM) of each vertebral segment from T7 to S1 to determine if T10 is truly the lowest immobile thoracic vertebra. This is a prospective, comparative study. Seventy-nine adults (mean age of 45.4 years) presenting with low back pain or lower limb radiculopathy or both, without previous spinal intervention, metastases, fractures, infection, or congenital deformities of the spine, were included in the study. A ROM >5° across two vertebral segments as determined by the Cobb method from radiographs. Lumbar flexion-extension and neutral erect radiographs were obtained in randomized order using a slot scanner. Segmental ROM was measured from T7-T8 to L5-S1 and analyzed for significant differences using t tests. Age, gender, radiographical indices such as standard spinopelvic parameters, sagittal vertical axis (SVA), C7-T12 SVA, T1 slope, thoracic kyphosis (TK), and lumbar lordosis (LL) were studied via multivariate analysis to identify predictive factors for >5° change in ROM at the various segmental levels. There were no sources of funding and no conflicts of interest associated with this study. In the thoracolumbar spine, significant decreases in ROM when compared with the adjacent caudad segment occurs up to T9-T10, with mean total ROM of 1.98±1.47° (p<.001) seen in T9-T10, 2.19±1.67° (p<.001) in T10-T11, and 3.92±3.21°(p<.001) in T11-T12

Measurement of T1 of human arterial and venous blood at 7T.

PubMed

Rane, Swati D; Gore, John C

2013-04-01

Techniques for measuring cerebral perfusion require accurate longitudinal relaxation (T1) of blood, an MRI parameter that is field dependent. T1 of arterial and venous human blood was measured at 7T using three different sources - pathology laboratory, blood bank and in vivo. The T1 of venous blood was measured from sealed samples from a pathology lab and in vivo. Samples from a blood bank were oxygenated and mixed to obtain different physiological concentrations of hematocrit and oxygenation. T1 relaxation times were estimated using a three-point fit to a simple inversion recovery equation. At 37°C, the T1 of blood at arterial pO2 was 2.29±0.1s and 2.07±0.12 at venous pO2. The in vivo T1 of venous blood, in three subjects, was slightly longer at 2.45±0.11s. T1 of arterial and venous blood at 7T was measured and found to be significantly different. The T1 values were longer in vivo than in vitro. While the exact cause for the discrepancy is unknown, the additives in the blood samples, degradation during experiment, oxygenation differences, and the non-stagnant nature of blood in vivo could be potential contributors to the lower values of T1 in the venous samples. Copyright © 2013 Elsevier Inc. All rights reserved.

Local NMR relaxation rates T1-1 and T2-1 depending on the d -vector symmetry in the vortex state of chiral and helical p -wave superconductors

NASA Astrophysics Data System (ADS)

Tanaka, Kenta K.; Ichioka, Masanori; Onari, Seiichiro

2018-04-01

Local NMR relaxation rates in the vortex state of chiral and helical p -wave superconductors are investigated by the quasiclassical Eilenberger theory. We calculate the spatial and resonance frequency dependences of the local NMR spin-lattice relaxation rate T1-1 and spin-spin relaxation rate T2-1. Depending on the relation between the NMR relaxation direction and the d -vector symmetry, the local T1-1 and T2-1 in the vortex core region show different behaviors. When the NMR relaxation direction is parallel to the d -vector component, the local NMR relaxation rate is anomalously suppressed by the negative coherence effect due to the spin dependence of the odd-frequency s -wave spin-triplet Cooper pairs. The difference between the local T1-1 and T2-1 in the site-selective NMR measurement is expected to be a method to examine the d -vector symmetry of candidate materials for spin-triplet superconductors.

PLDLA/PCL-T Scaffold for Meniscus Tissue Engineering

PubMed Central

Moda, Marlon; Cattani, Silvia Mara de Melo; de Santana, Gracy Mara; Barbieri, Juliana Abreu; Munhoz, Monique Moron; Cardoso, Túlio Pereira; Barbo, Maria Lourdes Peris; Russo, Teresa; D'Amora, Ugo; Gloria, Antonio; Ambrosio, Luigi; Duek, Eliana Aparecida de Rezende

2013-01-01

Abstract The inability of the avascular region of the meniscus to regenerate has led to the use of tissue engineering to treat meniscal injuries. The aim of this study was to evaluate the ability of fibrochondrocytes preseeded on PLDLA/PCL-T [poly(L-co-D,L-lactic acid)/poly(caprolactone-triol)] scaffolds to stimulate regeneration of the whole meniscus. Porous PLDLA/PCL-T (90/10) scaffolds were obtained by solvent casting and particulate leaching. Compressive modulus of 9.5±1.0 MPa and maximum stress of 4.7±0.9 MPa were evaluated. Fibrochondrocytes from rabbit menisci were isolated, seeded directly on the scaffolds, and cultured for 21 days. New Zealand rabbits underwent total meniscectomy, after which implants consisting of cell-free scaffolds or cell-seeded scaffolds were introduced into the medial knee meniscus; the negative control group consisted of rabbits that received no implant. Macroscopic and histological evaluations of the neomeniscus were performed 12 and 24 weeks after implantation. The polymer scaffold implants adapted well to surrounding tissues, without apparent rejection, infection, or chronic inflammatory response. Fibrocartilaginous tissue with mature collagen fibers was observed predominantly in implants with seeded scaffolds compared to cell-free implants after 24 weeks. Similar results were not observed in the control group. Articular cartilage was preserved in the polymeric implants and showed higher chondrocyte cell number than the control group. These findings show that the PLDLA/PCL-T 90/10 scaffold has potential for orthopedic applications since this material allowed the formation of fibrocartilaginous tissue, a structure of crucial importance for repairing injuries to joints, including replacement of the meniscus and the protection of articular cartilage from degeneration. PMID:23593566

26 CFR 1.163-11T - Allocation of certain prepaid qualified mortgage insurance premiums (temporary).

Code of Federal Regulations, 2010 CFR

2010-04-01

... insurance premiums (temporary). 1.163-11T Section 1.163-11T Internal Revenue INTERNAL REVENUE SERVICE... insurance premiums (temporary). (a) Allocation—(1) In general. As provided in section 163(h)(3)(E), premiums... section applies whether the qualified mortgage insurance premiums are paid in cash or are financed...

26 CFR 1.163-11T - Allocation of certain prepaid qualified mortgage insurance premiums (temporary).

Code of Federal Regulations, 2011 CFR

2011-04-01

... insurance premiums (temporary). 1.163-11T Section 1.163-11T Internal Revenue INTERNAL REVENUE SERVICE... insurance premiums (temporary). (a) Allocation—(1) In general. As provided in section 163(h)(3)(E), premiums... section applies whether the qualified mortgage insurance premiums are paid in cash or are financed...

Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13)(p12;q12)

PubMed Central

Popovici, Cornel; Adélaïde, José; Ollendorff, Vincent; Chaffanet, Max; Guasch, Géraldine; Jacrot, Michèle; Leroux, Dominique; Birnbaum, Daniel; Pébusque, Marie-Josèphe

1998-01-01

Chromosome 8p11–12 is the site of a recurrent breakpoint in a myeloproliferative disorder that involves lymphoid (T- or B-cell), myeloid hyperplasia and eosinophilia, and evolves toward acute leukemia. This multilineage involvement suggests the malignant transformation of a primitive hematopoietic stem cell. In this disorder, the 8p11–12 region is associated with three different partners 6q27, 9q33, and 13q12. We describe here the molecular characterization of the t(8;13) translocation that involves the FGFR1 gene from 8p12, encoding a tyrosine kinase receptor for members of the fibroblast growth factor family, and a gene from 13q12, tentatively named FIM (Fused In Myeloproliferative disorders). FIM is related to DXS6673E, a candidate gene for X-linked mental retardation in Xq13.1; this defines a gene family involved in different human pathologies. The two reciprocal fusion transcripts, FIM/FGFR1 and FGFR1/FIM are expressed in the malignant cells. The FIM/FGFR1 fusion protein contains the FIM putative zinc finger motifs and the catalytic domain of FGFR1. We show that it has a constitutive tyrosine kinase activity. PMID:9576949

Knee Cartilage Thickness, T1ρ and T2 Relaxation Time Are Related to Articular Cartilage Loading in Healthy Adults

PubMed Central

Van Rossom, Sam; Smith, Colin Robert; Zevenbergen, Lianne; Thelen, Darryl Gerard; Vanwanseele, Benedicte; Van Assche, Dieter; Jonkers, Ilse

2017-01-01

Cartilage is responsive to the loading imposed during cyclic routine activities. However, the local relation between cartilage in terms of thickness distribution and biochemical composition and the local contact pressure during walking has not been established. The objective of this study was to evaluate the relation between cartilage thickness, proteoglycan and collagen concentration in the knee joint and knee loading in terms of contact forces and pressure during walking. 3D gait analysis and MRI (3D-FSE, T1ρ relaxation time and T2 relaxation time sequence) of fifteen healthy subjects were acquired. Experimental gait data was processed using musculoskeletal modeling to calculate the contact forces, impulses and pressure distribution in the tibiofemoral joint. Correlates to local cartilage thickness and mean T1ρ and T2 relaxation times of the weight-bearing area of the femoral condyles were examined. Local thickness was significantly correlated with local pressure: medial thickness was correlated with medial condyle contact pressure and contact force, and lateral condyle thickness was correlated with lateral condyle contact pressure and contact force during stance. Furthermore, average T1ρ and T2 relaxation time correlated significantly with the peak contact forces and impulses. Increased T1ρ relaxation time correlated with increased shear loading, decreased T1ρ and T2 relaxation time correlated with increased compressive forces and pressures. Thicker cartilage was correlated with higher condylar loading during walking, suggesting that cartilage thickness is increased in those areas experiencing higher loading during a cyclic activity such as gait. Furthermore, the proteoglycan and collagen concentration and orientation derived from T1ρ and T2 relaxation measures were related to loading. PMID:28076431

New approach for T-wave peak detection and T-wave end location in 12-lead paced ECG signals based on a mathematical model.

PubMed

Madeiro, João P V; Nicolson, William B; Cortez, Paulo C; Marques, João A L; Vázquez-Seisdedos, Carlos R; Elangovan, Narmadha; Ng, G Andre; Schlindwein, Fernando S

2013-08-01

This paper presents an innovative approach for T-wave peak detection and subsequent T-wave end location in 12-lead paced ECG signals based on a mathematical model of a skewed Gaussian function. Following the stage of QRS segmentation, we establish search windows using a number of the earliest intervals between each QRS offset and subsequent QRS onset. Then, we compute a template based on a Gaussian-function, modified by a mathematical procedure to insert asymmetry, which models the T-wave. Cross-correlation and an approach based on the computation of Trapezium's area are used to locate, respectively, the peak and end point of each T-wave throughout the whole raw ECG signal. For evaluating purposes, we used a database of high resolution 12-lead paced ECG signals, recorded from patients with ischaemic cardiomyopathy (ICM) in the University Hospitals of Leicester NHS Trust, UK, and the well-known QT database. The average T-wave detection rates, sensitivity and positive predictivity, were both equal to 99.12%, for the first database, and, respectively, equal to 99.32% and 99.47%, for QT database. The average time errors computed for T-wave peak and T-wave end locations were, respectively, -0.38±7.12 ms and -3.70±15.46 ms, for the first database, and 1.40±8.99 ms and 2.83±15.27 ms, for QT database. The results demonstrate the accuracy, consistency and robustness of the proposed method for a wide variety of T-wave morphologies studied. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved.

Interleukin-12 in patients with cancer is synthesized by peripheral helper T lymphocytes.

PubMed

Michelin, Marcia A; Montes, Leticia; Nomelini, Rosekeila S; Abdalla, Douglas R; Aleixo, Andre A R; Murta, Eddie F C

2015-09-01

The production of cytokines by helper T lymphocytes is a critical event in the immune response, as alterations in the regulation of this process may result in an appropriate immune response, persistent infection or the development of autoimmune disease. Previously, this group has used flow cytometry to demonstrate the expression of interleukin-12 (IL-12) in peripheral blood CD4+ T lymphocytes from patients and mice with advanced cancer. The aim of the present study was to investigate whether CD4+ T lymphocytes from the peripheral blood (PB) of patients with cancer produce IL-12, using molecular approaches, flow cytometry and cellular imaging techniques. CD3+ and CD4+ cells, and cells producing IL-12, were isolated from the PB obtained from patients with cancer, using a cell sorting flow cytometry technique. The positivity of cells for CD3, CD4 and IL-12, which were identified by cell sorting, was visualized using immunofluorescent cellular imaging. Total RNA was extracted from the CD3+CD4+IL-12+ cells, obtained by cell sorting, for confirmation of the presence of IL-12 mRNA, using reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR demonstrated the presence of IL-12 mRNA in all patients (n=14), in contrast to the control group, in whom IL-12 expression was not detected. Immunofluorescent analysis of CD4+ T lymphocytes showed positive intracytoplasmatic IL-12 staining. These results demonstrated that CD3+CD4+ T lymphocytes in the PB of patients with cancer have the capacity to synthesize and express IL-12.

Interleukin-12 in patients with cancer is synthesized by peripheral helper T lymphocytes

PubMed Central

MICHELIN, MARCIA A.; MONTES, LETICIA; NOMELINI, ROSEKEILA S.; ABDALLA, DOUGLAS R.; ALEIXO, ANDRE A. R.; MURTA, EDDIE F. C.

2015-01-01

The production of cytokines by helper T lymphocytes is a critical event in the immune response, as alterations in the regulation of this process may result in an appropriate immune response, persistent infection or the development of autoimmune disease. Previously, this group has used flow cytometry to demonstrate the expression of interleukin-12 (IL-12) in peripheral blood CD4+ T lymphocytes from patients and mice with advanced cancer. The aim of the present study was to investigate whether CD4+ T lymphocytes from the peripheral blood (PB) of patients with cancer produce IL-12, using molecular approaches, flow cytometry and cellular imaging techniques. CD3+ and CD4+ cells, and cells producing IL-12, were isolated from the PB obtained from patients with cancer, using a cell sorting flow cytometry technique. The positivity of cells for CD3, CD4 and IL-12, which were identified by cell sorting, was visualized using immunofluorescent cellular imaging. Total RNA was extracted from the CD3+CD4+IL-12+ cells, obtained by cell sorting, for confirmation of the presence of IL-12 mRNA, using reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR demonstrated the presence of IL-12 mRNA in all patients (n=14), in contrast to the control group, in whom IL-12 expression was not detected. Immunofluorescent analysis of CD4+ T lymphocytes showed positive intracytoplasmatic IL-12 staining. These results demonstrated that CD3+CD4+ T lymphocytes in the PB of patients with cancer have the capacity to synthesize and express IL-12. PMID:26622702

Antitumour activity mediated by CD4+ cytotoxic T lymphocytes against MHC class II-negative mouse hepatocellular carcinoma induced by dendritic cell vaccine and interleukin-12.

PubMed

Homma, Sadamu; Komita, Hideo; Sagawa, Yukiko; Ohno, Tsuneya; Toda, Gotaro

2005-08-01

When BALA/c mice with BNL hepatocellular carcinoma (HCC) were treated with dendritic cells fused with BNL cells (DC/BNL) and recombinant murine interleukin (IL)-12, tumour development was significantly suppressed, whereas treatment with either DC/BNL or IL-12 alone did not show a tumour-suppressive effect. Antitumour activity induced by DC/BNL + IL-12 was abrogated by depletion of CD4+ T cells, but not by depletion of CD8+ T cells or natural killer cells. Splenic CD4+ T cells and CD8+ T cells from DC/BNL-treated mice showed cytotoxic activity against BNL cells after 3 days of incubation with DC/BNL, although BNL cells do not express major histocompatibility complex (MHC) class II molecules even after treatment with interferon (INF)-gamma. Furthermore, CD4+ T cells killed syngeneic-irrelevant CT26 cells and even allogeneic Hepa1-6 cells. This cytotoxicity was blocked by concanamycin A, but not by an anti-Fas ligand (FasL) monoclonal antibody, indicating that cytotoxic activity was mediated by perforin. Immunofluorescence microscopy demonstrated that abundant CD4+ T cells and MHC class II-positive macrophages, but not CD8(+) T cells, had infiltrated tumour tissue in mice treated with DC/BNL + IL-12. Flow cytometric analysis of tumour-infiltrating cells in mice treated with DC/BNL + IL-12 showed increases in CD4+ T cells and MHC class II+ CD11b+ cells but not in CD8+ T cells or MHC class I+ CD11b+ cells. Our results suggest that, in BNL-bearing mice treated with DC/BNL + IL-12, tumour macrophages activated by INF-gamma produced by IL-12-stimulated T cells might present BNL tumour antigens and activate DC/BNL-primed CD4+ cytotoxic T lymphocytes (CTLs) in a MHC class II-dependent manner, leading to perforin-mediated bystander killing of neighbouring MHC class II-negative tumour cells.

Antitumour activity mediated by CD4+ cytotoxic T lymphocytes against MHC class II-negative mouse hepatocellular carcinoma induced by dendritic cell vaccine and interleukin-12

PubMed Central

Homma, Sadamu; Komita, Hideo; Sagawa, Yukiko; Ohno, Tsuneya; Toda, Gotaro

2005-01-01

When BALA/c mice with BNL hepatocellular carcinoma (HCC) were treated with dendritic cells fused with BNL cells (DC/BNL) and recombinant murine interleukin (IL)-12, tumour development was significantly suppressed, whereas treatment with either DC/BNL or IL-12 alone did not show a tumour-suppressive effect. Antitumour activity induced by DC/BNL + IL-12 was abrogated by depletion of CD4+ T cells, but not by depletion of CD8+ T cells or natural killer cells. Splenic CD4+ T cells and CD8+ T cells from DC/BNL-treated mice showed cytotoxic activity against BNL cells after 3 days of incubation with DC/BNL, although BNL cells do not express major histocompatibility complex (MHC) class II molecules even after treatment with interferon (INF)-γ. Furthermore, CD4+ T cells killed syngeneic-irrelevant CT26 cells and even allogeneic Hepa1-6 cells. This cytotoxicity was blocked by concanamycin A, but not by an anti-Fas ligand (FasL) monoclonal antibody, indicating that cytotoxic activity was mediated by perforin. Immunofluorescence microscopy demonstrated that abundant CD4+ T cells and MHC class II-positive macrophages, but not CD8+ T cells, had infiltrated tumour tissue in mice treated with DC/BNL + IL-12. Flow cytometric analysis of tumour-infiltrating cells in mice treated with DC/BNL + IL-12 showed increases in CD4+ T cells and MHC class II+ CD11b+ cells but not in CD8+ T cells or MHC class I+ CD11b+ cells. Our results suggest that, in BNL-bearing mice treated with DC/BNL + IL-12, tumour macrophages activated by INF-γ produced by IL-12-stimulated T cells might present BNL tumour antigens and activate DC/BNL-primed CD4+ cytotoxic T lymphocytes (CTLs) in a MHC class II-dependent manner, leading to perforin-mediated bystander killing of neighbouring MHC class II-negative tumour cells. PMID:16011514

Critical roles of conventional dendritic cells in promoting T cell‐dependent hepatitis through regulating natural killer T cells

PubMed Central

Wang, J.; Cao, X.; Zhao, J.; Zhao, H.; Wei, J.; Li, Q.; Qi, X.; Yang, Z.; Wang, L.; Zhang, H.; Bai, L.; Wu, Z.; Zhao, L.; Hong, Z.

2017-01-01

Summary Dendritic cells (DCs) play critical roles in initiating and regulating innate immunity as well as adaptive immune responses. However, the role of conventional dendritic cells (cDCs) in concanavalin A (ConA)‐induced fulminant hepatitis is unknown. In this study, we demonstrated that depletion of cDCs using either CD11c‐diphtheria toxin receptor transgenic mice (DTR Tg) mice or anti‐CD11c antibody reduced the severity of liver injury significantly, indicating a detrimental role of cDCs in ConA‐induced hepatitis. We elucidated further the pathological role of cDCs as being the critical source of interleukin (IL)‐12, which induced the secretion of interferon (IFN)‐γ by natural killer (NK) T cells. Reconstitution of cDCs‐depleted mice with IL‐12 restored ConA‐induced hepatitis significantly. Furthermore, we determined that NK T cells were the target of DC‐derived IL‐12, and NK T cells contributed to liver inflammation and injury through production of IFN‐γ. In summary, our study demonstrated a novel function of cDCs in mediating ConA‐induced hepatitis through regulating IFN‐γ secretion of NK T cells in an IL‐12‐dependent fashion. Targeting cDCs might provide potentially therapeutic applications in treating autoimmune related liver diseases. PMID:27891589

Dandy-Walker malformations in a case of partial trisomy 9p (p12.1→pter) due to maternal translocation t(9;12)(p12.1;p13.3)

PubMed Central

Vundinti, Babu Rao; Kerketta, Lily; Korgaonkar, Seema; Ghosh, Kanjaksha

2007-01-01

We describe a five-year-old proband presented with Dandy-Walker malformations, right microopthalmia, hamstring contractures, undescended testis with absence of testis in right scrotum in addition to typical trisomy 9p clinical features. Routine cytogenetic studies with GTG - banding showed 46,XY,der(12)t(9;12) (p12;q13.3),mat karyotype (trisomy 9p). Chromosomal analysis of the father was normal and phenotypically normal mother had 46,XX,t(9;12)(p12;q13) karyotype. Fluorescence in situ hybridization analysis with single copy probes bA5OIA2 (9p11.2), bA562M8 (12p12.1) and centromere probes (9) showed break point at 9p12.1 region. The gene dosage effect of Chromosome 9p along with environmental factors might be associated with Dandy- Walker malformations in the patient. PMID:21957340

BCL11B is frequently downregulated in HTLV-1-infected T-cells through Tax-mediated proteasomal degradation.

PubMed

Permatasari, Happy Kurnia; Nakahata, Shingo; Ichikawa, Tomonaga; Morishita, Kazuhiro

2017-08-26

Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia-lymphoma (ATLL). The HTLV-1-encoded protein Tax plays important roles in the proliferation of HTLV-1-infected T-cells by affecting cellular proteins. In this study, we showed that Tax transcriptionally and post-transcriptionally downregulates the expression of the tumor suppressor gene B-cell leukemia/lymphoma 11B (BCL11B), which encodes a lymphoid-related transcription factor. BCL11B expression was downregulated in HTLV-1-infected T-cell lines at the mRNA and protein levels, and forced expression of BCL11B suppressed the proliferation of these cells. The proteasomal inhibitor MG132 increased BCL11B expression in HTLV-1-infected cell lines, and colocalization of Tax with BCL11B was detected in the cytoplasm of HTLV-1-infected T-cells following MG132 treatment. shRNA knock-down of Tax expression also increased the expression of BCL11B in HTLV-1-infected cells. Moreover, we found that Tax physically binds to BCL11B protein and induces the polyubiquitination of BCL11B and proteasome-dependent degradation of BCL11B. Thus, inactivation of BCL11B by Tax protein may play an important role in the Tax-mediated leukemogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Investigation of Regional Influence of Magic-Angle Effect on T2 in Human Articular Cartilage with Osteoarthritis at 3 T

PubMed Central

Wang, Ligong; Regatte, Ravinder R.

2014-01-01

Rationale and Objectives The objectives of this research study were to determine the magic-angle effect on different subregions of in vivo human femoral cartilage through the quantitative assessment of the effect of static magnetic field orientation (B0) on transverse (T2) relaxation time at 3.0 T. Materials and Methods Healthy volunteers (n = 5l; mean age, 36.4 years) and clinical patients (n = 5; mean age, 64 years) with early osteoarthritis (OA) were scanned at 3.0-T magnetic resonance using an 8-channel phased-array knee coil (transmit-receive). Results The T2 maps revealed significantly greater values in ventral than in dorsal regions. When the cartilage regions were oriented at 55° to B0 (magic angle), the longest T2 values were detected in comparison with the neighboring regions oriented 90° and 180° (0°) to B0. The subregions oriented 180° (0°) to B0 showed the lowest T2 values. Conclusions The differences in T2 values of different subregions suggest that magic-angle effect needs to be considered when interpreting cartilage abnormalities in OA patients. PMID:25481517

Correlation study between facet joint cartilage and intervertebral discs in early lumbar vertebral degeneration using T2, T2* and T1ρ mapping

PubMed Central

Zhang, Yi; Hu, Jianzhong; Duan, Chunyue; Hu, Ping; Lu, Hongbin; Peng, Xianjing

2017-01-01

Recent advancements in magnetic resonance imaging have allowed for the early detection of biochemical changes in intervertebral discs and articular cartilage. Here, we assessed the feasibility of axial T2, T2* and T1ρ mapping of the lumbar facet joints (LFJs) to determine correlations between cartilage and intervertebral discs (IVDs) in early lumbar vertebral degeneration. We recruited 22 volunteers and examined 202 LFJs and 101 IVDs with morphological (sagittal and axial FSE T2-weighted imaging) and axial biochemical (T2, T2* and T1ρ mapping) sequences using a 3.0T MRI scanner. IVDs were graded using the Pfirrmann system. Mapping values of LFJs were recorded according to the degeneration grades of IVDs at the same level. The feasibility of T2, T2* and T1ρ in IVDs and LFJs were analyzed by comparing these mapping values across subjects with different rates of degeneration using Kruskal-Wallis tests. A Pearson’s correlation analysis was used to compare T2, T2* and T1ρ values of discs and LFJs. We found excellent reproducibility in the T2, T2* and T1ρ values for the nucleus pulposus (NP), anterior and posterior annulus fibrosus (PAF), and LFJ cartilage (intraclass correlation coefficients 0.806–0.955). T2, T2* and T1ρ mapping (all P<0.01) had good Pfirrmann grade performances in the NP with IVD degeneration. LFJ T2* values were significantly different between grades I and IV (PL = 0.032, PR = 0.026), as were T1ρ values between grades II and III (PL = 0.002, PR = 0.006) and grades III and IV (PL = 0.006, PR = 0.001). Correlations were moderately negative for T1ρ values between LFJ cartilage and NP (rL = −0.574, rR = −0.551), and between LFJ cartilage and PAF (rL = −0.551, rR = −0.499). T1ρ values of LFJ cartilage was weakly correlated with T2 (r = 0.007) and T2* (r = −0.158) values. Overall, we show that axial T1ρ effectively assesses early LFJ cartilage degeneration. Using T1ρ analysis, we propose a link between LFJ degeneration and IVD NP or

Comparative differences between T1a/b and T1e/m as substages in T1 urothelial carcinoma of the bladder.

PubMed

Turan, Turgay; Efiloğlu, Özgür; Günaydin, Bilal; Özkanli, Şeyma; Nikerel, Emrah; Atiş, Gökhan; Çaşkurlu, Turhan; Yildirim, Asif

2018-01-01

To evaluate the prognostic value of the depth of lamina propria invasion in patients with T1 bladder cancer and to display comparative differences between the T1a/b and T1e/m substaging systems. This study included 106 patients with primary stage T1 urothelial bladder tumours who underwent surgery between January 2009 and December 2014. Pathologic specimens were re-evaluated to confirm the diagnosis of T1 and substaging by the same pathologist using two systems: T1a and T1b, and T1m and T1e. Age, tumour size, multiplicity, associated carcinoma in situ, tumour grade, and T1 substaging system were investigated to detect the relation between disease progression and recurrence. The recurrence rate was 52% for T1a (n=42) vs. 76% for T1b (n=20) (p=0.028) and 55% for T1m (n=32) vs. 62% for T1e (n=30), respectively (p=0.446). There was no significant difference between the substaging groups for disease progression: T1a (n=12, 15%) vs. T1b (n=7, 27%), and T1m (n=8, 13.8%) vs. T1e (n=11, 23%) (p>0.05). In the multivariate analysis, tumour size >3 cm (p=0.008), multiplicity (p=0.049), and substaging T1b (p=0.043) were independent predictive factors for tumour recurrence. According to the Kaplan-Meier actuarial method, recurrence-free survival was significantly different in patients with pT1a tumours compared with those with pT1b tumours (p=0.033). Substaging T1 provides a prediction of disease recurrence. Regarding recurrence, T1a/b substaging can provide better knowledge of disease behaviour because it is predicted as more superior than T1 m/e, and it can help in determining the requirement for early cystectomy. Copyright® by the International Brazilian Journal of Urology.

The SPO11-C631T gene polymorphism and male infertility risk: a meta-analysis.

PubMed

Ren, Zheng-Ju; Ren, Peng-Wei; Yang, Bo; Liao, Jian; Liu, Sheng-Zhuo; Fang, Kun; Ren, Shang-Qing; Liu, Liang-Ren; Dong, Qiang

2017-11-01

To evaluate the association between the SPO11 gene C631T polymorphism and the risk of male infertility. We conducted a search on PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China biology medical literature database (CBM), VIP, and Chinese literature database (Wan Fang) on 31 March 2016. Odds ratio (OR) and 95% confidence interval (95%CI) were used to assess the strength of associations. A total of five studies including 542 cases and 510 controls were involved in this meta-analysis. The pooled results indicated that the SPO11 gene C631T polymorphism was significantly associated with increased risk of male infertility (TT + CT vs. CC: OR = 4.14, 95%CI = 2.48-6.89; CT vs. CC: OR = 4.34, 95%CI = 2.56-7.34; T vs. C: OR = 4.35, 95%CI = 2.58-7.34). Subgroup analysis of different countries proved the relationship between SPO11 gene C631T polymorphism and male infertility risk in Chinese, but not in Iranian peoples. In conclusion, this study suggested that SPO11 gene C631T polymorphism may contribute as a genetic factor susceptible to cause male infertility. Furthermore, more large sample and representative population-based cases and well-matched controls are needed to validate our results.

The diagnostic performance of non-contrast 3-Tesla magnetic resonance imaging (3-T MRI) versus 1.5-Tesla magnetic resonance arthrography (1.5-T MRA) in femoro-acetabular impingement.

PubMed

Crespo-Rodríguez, Ana M; De Lucas-Villarrubia, Jose C; Pastrana-Ledesma, Miguel; Hualde-Juvera, Ana; Méndez-Alonso, Santiago; Padron, Mario

2017-03-01

The aim of this study was to evaluate the diagnostic accuracy of 3-T non-contrast MRI versus 1.5-T MRA for assessing labrum and articular cartilage lesions in patients with clinical suspicion of femoro-acetabular impingement (FAI). Fifty patients (thirty men and twenty women, mean age 42.5 years) underwent 1.5-T MRA, 3-T MRI and arthroscopy on the same hip. An optimized high-resolution proton density spin echo pulse sequence was included in the 3-T non-contrast MRI protocol. The 3-T non-contrast MRI identified forty-two of the forty-three arthroscopically proven tears at the labral-chondral transitional zone (sensitivity, 97.7%; specificity, 100%; positive predictive value (PPV), 100%; negative predictive value (NPV), 87.5%; accuracy 98%). With 1.5-T MRA, forty-four tears were diagnosed. However, there was one false positive (sensitivity, 100%; specificity, 85.7%; PPV, 97.7%; NPV, 100%; accuracy 98%). Agreement between arthroscopy and MRI, whether 3-T non-contrast MRI or 1.5-T MRA, as to the degree of chondral lesion in the acetabulum was reached in half of the patients and in the femur in 76% of patients. Non-invasive assessment of the hip is possible with 3-T MR magnet. 3-T non-contrast MRI could replace MRA as the workhorse technique for assessing hip internal damage. MRA would then be reserved for young adults with a strong clinical suspicion of FAI but normal findings on 3-T non-contrast MRI. When compared with 1.5-T MRA, optimized sequences with 3-T non-contrast MRI help in detecting normal variants and in diagnosing articular cartilage lesions. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

11. Detail of Bed Plate Showing Name of Manufacturer (T.W. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

11. Detail of Bed Plate Showing Name of Manufacturer (T.W. Phillips Manufacturing Co.), Looking Southwest - Heckert Oil Pumping Jack, 0.6 mile North of Connoquenessing Creek, 0.15 mile East of Powder Mill Creek, Renfrew, Butler County, PA

Direct visualization of antigen-specific T cells: HTLV-1 Tax11-19- specific CD8(+) T cells are activated in peripheral blood and accumulate in cerebrospinal fluid from HAM/TSP patients.

PubMed

Greten, T F; Slansky, J E; Kubota, R; Soldan, S S; Jaffee, E M; Leist, T P; Pardoll, D M; Jacobson, S; Schneck, J P

1998-06-23

Human T lymphotropic virus type 1 (HTLV-1) -associated myelopathy/tropic spastic paraparesis is a demyelinating inflammatory neurologic disease associated with HTLV-1 infection. HTLV-1 Tax11-19-specific cytotoxic T cells have been isolated from HLA-A2-positive patients. We have used a peptide-loaded soluble HLA-A2-Ig complex to directly visualize HTLV-1 Tax11-19-specific T cells from peripheral blood and cerebrospinal fluid without in vitro stimulation. Five of six HTLV-1-associated myelopathy/tropic spastic paraparesis patients carried a significant number (up to 13.87%) of CD8(+) lymphocytes specific for the HTLV-1 Tax11-19 peptide in their peripheral blood, which were not found in healthy controls. Simultaneous comparison of peripheral blood and cerebrospinal fluid from one patient revealed 2.5-fold more Tax11-19-specific T cells in the cerebrospinal fluid (23.7% vs. 9.4% in peripheral blood lymphocyte). Tax11-19-specific T cells were seen consistently over a 9-yr time course in one patient as far as 19 yrs after the onset of clinical symptoms. Further analysis of HTLV-1 Tax11-19-specific CD8(+) T lymphocytes in HAM/TSP patients showed different expression patterns of activation markers, intracellular TNF-alpha and gamma-interferon depending on the severity of the disease. Thus, visualization of antigen-specific T cells demonstrates that HTLV-1 Tax11-19-specific CD8(+) T cells are activated, persist during the chronic phase of the disease, and accumulate in cerebrospinal fluid, showing their pivotal role in the pathogenesis of this neurologic disease.

CD11c-Expressing Cells Affect Regulatory T Cell Behavior in the Meninges during Central Nervous System Infection.

PubMed

O'Brien, Carleigh A; Overall, Christopher; Konradt, Christoph; O'Hara Hall, Aisling C; Hayes, Nikolas W; Wagage, Sagie; John, Beena; Christian, David A; Hunter, Christopher A; Harris, Tajie H

2017-05-15

Regulatory T cells (Tregs) play an important role in the CNS during multiple infections, as well as autoimmune inflammation, but the behavior of this cell type in the CNS has not been explored. In mice, infection with Toxoplasma gondii leads to a Th1-polarized parasite-specific effector T cell response in the brain. Similarly, Tregs in the CNS during T. gondii infection are Th1 polarized, as exemplified by their T-bet, CXCR3, and IFN-γ expression. Unlike effector CD4 + T cells, an MHC class II tetramer reagent specific for T. gondii did not recognize Tregs isolated from the CNS. Likewise, TCR sequencing revealed minimal overlap in TCR sequence between effector T cells and Tregs in the CNS. Whereas effector T cells are found in the brain parenchyma where parasites are present, Tregs were restricted to the meninges and perivascular spaces. The use of intravital imaging revealed that activated CD4 + T cells within the meninges were highly migratory, whereas Tregs moved more slowly and were found in close association with CD11c + cells. To test whether the behavior of Tregs in the meninges is influenced by interactions with CD11c + cells, mice were treated with anti-LFA-1 Abs to reduce the number of CD11c + cells in this space. The anti-LFA-1 treatment led to fewer contacts between Tregs and the remaining CD11c + cells and increased the speed of Treg migration. These data suggest that Tregs are anatomically restricted within the CNS, and their interaction with CD11c + populations regulates their local behavior during T. gondii infection. Copyright © 2017 by The American Association of Immunologists, Inc.

33 CFR 165.T11-568 - Safety Zone; San Diego Symphony Summer POPS Fireworks 2013 Season, San Diego, CA.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Safety Zone; San Diego Symphony Summer POPS Fireworks 2013 Season, San Diego, CA. 165.T11-568 Section 165.T11-568 Navigation and... Areas Eleventh Coast Guard District § 165.T11-568 Safety Zone; San Diego Symphony Summer POPS Fireworks...

Activation of mouse liver natural killer cells and NK1.1(+) T cells by bacterial superantigen-primed Kupffer cells.

PubMed

Dobashi, H; Seki, S; Habu, Y; Ohkawa, T; Takeshita, S; Hiraide, H; Sekine, I

1999-08-01

Although bacterial superantigens have been well characterized as potent stimulators of T cells, their role in natural killer (NK)-type cells remains largely unknown. In the present study, we examined the effect of bacterial superantigens on mouse liver NK cells and NK1.1 Ag(+) (NK1(+)) T cells. C57BL/6 mice were intravenously injected with staphylococcal enterotoxin B (SEB) or streptococcal pyrogenic exotoxin A (SPE-A), and mononuclear cells (MNC) of various organs were obtained from mice 4 hours after being injected with superantigen. MNC were cultured for 48 hours, and interferon gamma (IFN-gamma) levels of supernatants were measured. The antitumor cytotoxicities of the liver and spleen MNC were also evaluated 24 hours after the mice were injected with superantigen. Liver MNC produced more IFN-gamma than did splenocytes, and peripheral blood and lung MNC did not produce any detectable IFN-gamma. In addition, liver MNC acquired a potent antitumor cytotoxicity by the SEB injection, and both NK cells and NK1(+)T cells but not cluster of differentiation (CD)8(+) T cells were responsible for the cytotoxicity as demonstrated by either in vivo or in vitro cell depletion experiments, and the NK-type cells were partly responsible for the increased serum IFN-gamma. Activation of liver NK-type cells was also supported by the fact that liver NK cells proportionally increased and NK1(+) T cells augmented their CD11a expressions after SEB injection. The pretreatment of mice with anti-IFN-gamma Ab and/or with anti-interleukin-12 (IL-12) Ab diminished the SEB-induced cytotoxicity of liver MNC. Furthermore, the in vivo depletion of Kupffer cells decreased the SEB-induced cytotoxicity of liver MNC. Consistent with these results, liver MNC stimulated with superantigens in the presence of Kupffer cells in vitro produced a greater amount of IFN-gamma than did the liver MNC without Kupffer cells or splenocytes. Our results suggest that bacterial superantigen-primed Kupffer cells

T1ρ MRI Quantification of Arthroscopically-Confirmed Cartilage Degeneration

PubMed Central

Witschey, Walter RT; Borthakur, Arijitt; Fenty, Matt; Kneeland, J Bruce; Lonner, Jess H; McArdle, Erin L.; Sochor, Matt; Reddy, Ravinder

2010-01-01

9 asymptomatic subjects and 6 patients underwent T1ρ MRI to determine whether Outerbridge grade 1 or 2 cartilage degeneration observed during arthroscopy could be detected noninvasively. MRI was performed 2–3 months post-arthroscopy using sagittal T1-weighted and axial and coronal T1ρ MRI from which spatial T1ρ relaxation maps were calculated from segmented T1-weighted images. Median T1ρ relaxation times of patients with arthroscopically documented cartilage degeneration and asymptomatic subjects were significantly different (p < 0.001) and median T1ρ exceeded asymptomatic articular cartilage median T1ρ by 2.5 to 9.2 ms. In 8 observations of mild cartilage degeneration at arthroscopy (Outerbridge grades 1 and 2), mean compartment T1ρ was elevated in 5, but in all observations, large foci of increased T1ρ were observed. It was determined that T1ρ could detect some, but not all, Outerbridge grade 1 and 2 cartilage degeneration but that a larger patient population is needed to determine the sensitivity to these changes. PMID:20432308

Patellar cartilage lesions: comparison of magnetic resonance imaging and T2 relaxation-time mapping.

PubMed

Hannila, I; Nieminen, M T; Rauvala, E; Tervonen, O; Ojala, R

2007-05-01

To evaluate the detection and the size of focal patellar cartilage lesions in T2 mapping as compared to standard clinical magnetic resonance imaging (MRI) at 1.5T. Fifty-five consecutive clinical patients referred to knee MRI were imaged both with a standard knee MRI protocol (proton-density-weighted sagittal and axial series, T2-weighted sagittal and coronal series, and T1-weighted coronal series) and with an axial multislice multi-echo spin-echo measurement to determine the T2 relaxation time of the patellar cartilage. MR images and T2 maps of patellar cartilage were evaluated for focal lesions. The lesions were evaluated for lesion width (mm), lesion depth (1/3, 2/3, or 3/3 of cartilage thickness), and T2 value (20-40 ms, 40-60 ms, or 60-80 ms) based on visual evaluation. Altogether, 36 focal patellar cartilage lesions were detected from 20 human subjects (11 male, nine female, mean age 40+/-15 years). Twenty-eight lesions were detected both on MRI and T2 maps, while eight lesions were only visible on T2 maps. Cartilage lesions were significantly wider (P = 0.001) and thicker (P<0.001) on T2 maps as compared to standard knee MRI. Most lesions 27 had moderately (T2 40-60 ms) increased T2 values, while two lesions had slightly (T2 20-40 ms) and seven lesions remarkably (T2 60-80 ms) increased T2 relaxation times. T2 mapping of articular cartilage is feasible in the clinical setting and may reveal early cartilage lesions not visible with standard clinical MRI.

An Authentication and Key Management Mechanism for Resource Constrained Devices in IEEE 802.11-based IoT Access Networks.

PubMed

Kim, Ki-Wook; Han, Youn-Hee; Min, Sung-Gi

2017-09-21

Many Internet of Things (IoT) services utilize an IoT access network to connect small devices with remote servers. They can share an access network with standard communication technology, such as IEEE 802.11ah. However, an authentication and key management (AKM) mechanism for resource constrained IoT devices using IEEE 802.11ah has not been proposed as yet. We therefore propose a new AKM mechanism for an IoT access network, which is based on IEEE 802.11 key management with the IEEE 802.1X authentication mechanism. The proposed AKM mechanism does not require any pre-configured security information between the access network domain and the IoT service domain. It considers the resource constraints of IoT devices, allowing IoT devices to delegate the burden of AKM processes to a powerful agent. The agent has sufficient power to support various authentication methods for the access point, and it performs cryptographic functions for the IoT devices. Performance analysis shows that the proposed mechanism greatly reduces computation costs, network costs, and memory usage of the resource-constrained IoT device as compared to the existing IEEE 802.11 Key Management with the IEEE 802.1X authentication mechanism.

An Authentication and Key Management Mechanism for Resource Constrained Devices in IEEE 802.11-based IoT Access Networks

PubMed Central

Han, Youn-Hee; Min, Sung-Gi

2017-01-01

Many Internet of Things (IoT) services utilize an IoT access network to connect small devices with remote servers. They can share an access network with standard communication technology, such as IEEE 802.11ah. However, an authentication and key management (AKM) mechanism for resource constrained IoT devices using IEEE 802.11ah has not been proposed as yet. We therefore propose a new AKM mechanism for an IoT access network, which is based on IEEE 802.11 key management with the IEEE 802.1X authentication mechanism. The proposed AKM mechanism does not require any pre-configured security information between the access network domain and the IoT service domain. It considers the resource constraints of IoT devices, allowing IoT devices to delegate the burden of AKM processes to a powerful agent. The agent has sufficient power to support various authentication methods for the access point, and it performs cryptographic functions for the IoT devices. Performance analysis shows that the proposed mechanism greatly reduces computation costs, network costs, and memory usage of the resource-constrained IoT device as compared to the existing IEEE 802.11 Key Management with the IEEE 802.1X authentication mechanism. PMID:28934152

Development of mRuby2-Transfected C3H10T1/2 Fibroblasts for Musculoskeletal Tissue Engineering

PubMed Central

Yang, Yunzhi Peter

2015-01-01

Mouse C3H10T1/2 fibroblasts are multipotent, mesenchymal stem cell (MSC)-like progenitor cells that are widely used in musculoskeletal research. In this study, we have established a clonal population of C3H10T1/2 cells stably-transfected with mRuby2, an orange-red fluorescence reporter gene. Flow cytometry analysis and fluorescence imaging confirmed successful transfection of these cells. Cell counting studies showed that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells proliferated at similar rates. Adipogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for Oil Red O and showed increased expression of adipogenic genes including adiponectin and lipoprotein lipase. Chondrogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for Alcian Blue and showed increased expression of chondrogenic genes including aggrecan. Osteogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for alkaline phosphatase (ALP) as well as Alizarin Red and showed increased expression of osteogenic genes including alp, ocn and osf-1. When seeded on calcium phosphate-based ceramic scaffolds, mRuby2-transfected C3H10T1/2 cells maintained even fluorescence labeling and osteogenic differentiation. In summary, mRuby2-transfected C3H10T1/2 cells exhibit mRuby2 fluorescence and showed little-to-no difference in terms of cell proliferation and differentiation as untransfected C3H10T1/2 cells. These cells will be available from American Type Culture Collection (ATCC; CRL-3268™) and may be a valuable tool for preclinical studies. PMID:26407291

Development of mRuby2-Transfected C3H10T1/2 Fibroblasts for Musculoskeletal Tissue Engineering.

PubMed

Ker, Dai Fei Elmer; Sharma, Rashmi; Wang, Evelyna Tsi Hsin; Yang, Yunzhi Peter

2015-01-01

Mouse C3H10T1/2 fibroblasts are multipotent, mesenchymal stem cell (MSC)-like progenitor cells that are widely used in musculoskeletal research. In this study, we have established a clonal population of C3H10T1/2 cells stably-transfected with mRuby2, an orange-red fluorescence reporter gene. Flow cytometry analysis and fluorescence imaging confirmed successful transfection of these cells. Cell counting studies showed that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells proliferated at similar rates. Adipogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for Oil Red O and showed increased expression of adipogenic genes including adiponectin and lipoprotein lipase. Chondrogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for Alcian Blue and showed increased expression of chondrogenic genes including aggrecan. Osteogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for alkaline phosphatase (ALP) as well as Alizarin Red and showed increased expression of osteogenic genes including alp, ocn and osf-1. When seeded on calcium phosphate-based ceramic scaffolds, mRuby2-transfected C3H10T1/2 cells maintained even fluorescence labeling and osteogenic differentiation. In summary, mRuby2-transfected C3H10T1/2 cells exhibit mRuby2 fluorescence and showed little-to-no difference in terms of cell proliferation and differentiation as untransfected C3H10T1/2 cells. These cells will be available from American Type Culture Collection (ATCC; CRL-3268™) and may be a valuable tool for preclinical studies.

Correlation of Meniscal T2* with Multiphoton Microscopy, and Change of Articular Cartilage T2 in an Ovine Model of Meniscal Repair

PubMed Central

Koff, Matthew F.; Shah, Parina; Pownder, Sarah; Romero, Bethsabe; Williams, Rebecca; Gilbert, Susannah; Maher, Suzanne; Fortier, Lisa A.; Rodeo, Scott A.; Potter, Hollis G.

2013-01-01

Objective To correlate meniscal T2* relaxation times using ultra-short echo time (UTE) magnetic resonance imaging (MRI) with quantitative microscopic methods, and to determine the effect of meniscal repair on post-operative cartilage T2 values. Design A medial meniscal tear was created and repaired in the anterior horn of one limb of 28 crossbred mature ewes. MR scans for morphological evaluation, meniscal T2* values, and cartilage T2 values were acquired at 0, 4 and 8 months post-operatively for the Tear and Non-Op limb. Samples of menisci from both limbs were analyzed using multiphoton microscopy (MPM) analysis and biomechanical testing. Results Significantly prolonged meniscal T2* values were found in repaired limbs than in control limbs, p<0.0001. No regional differences of T2* were detected for either the repaired or control limbs in the anterior horn. Repaired limbs had prolonged cartilage T2 values, primarily anteriorly, and tended to have lower biomechanical force to failure at 8 months than Non-Op limbs. MPM autofluorescence and second harmonic generation data correlated with T2* values at 8 months (ρ=−0.48, p=0.06). Conclusions T2* mapping is sensitive to detecting temporal and zonal differences of meniscal structure and composition. Meniscal MPM and cartilage T2 values indicate changes in tissue integrity in the presence of meniscal repair. PMID:23680878

Quench Protection Studies of 11T Nb$$_3$$Sn Dipole Models for LHC Upgrades

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

Zlobin, Alexander; Chlachidze, Guram; Nobrega, Alfred

CERN and FNAL are developing 11 T Nb3Sn dipole magnets for the LHC collimation system upgrade. Due to the large stored energy, protection of these magnets during a quench is a challenging problem. This paper reports the results of experimental studies of key quench protection parameters including longitudinal and radial quench propagation in the coil, coil heating due to a quench, and energy extraction and quench-back effect. The studies were performed using a 1 m long 11 T Nb3Sn dipole coil tested in a magnetic mirror configuration.

12. Historic American Buildings Survey Josiah T. Tubby, Photographer Oct. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

12. Historic American Buildings Survey Josiah T. Tubby, Photographer Oct. 2, 1936 DETAIL OF MANTEL AND PANELLING (N. W. bed room) SERVANTS' ROOM - Hodge House, Hodge Street & Route 1, Wiscasset, Lincoln County, ME

Transverse water relaxation in whole blood and erythrocytes at 3T, 7T, 9.4T, 11.7T and 16.4T; determination of intracellular hemoglobin and extracellular albumin relaxivities.

PubMed

Grgac, Ksenija; Li, Wenbo; Huang, Alan; Qin, Qin; van Zijl, Peter C M

2017-05-01

Blood is a physiological substance with multiple water compartments, which contain water-binding proteins such as hemoglobin in erythrocytes and albumin in plasma. Knowing the water transverse (R 2 ) relaxation rates from these different blood compartments is a prerequisite for quantifying the blood oxygenation level-dependent (BOLD) effect. Here, we report the Carr-Purcell-Meiboom-Gill (CPMG) based transverse (R 2CPMG ) relaxation rates of water in bovine blood samples circulated in a perfusion system at physiological temperature in order to mimic blood perfusion in humans. R 2CPMG values of blood plasma, lysed packed erythrocytes, lysed plasma/erythrocyte mixtures, and whole blood at 3 T, 7 T, 9.4 T, 11.7 T and 16.4 T were measured as a function of hematocrit or hemoglobin concentration, oxygenation, and CPMG inter-echo spacing (τ cp ). R 2CPMG in lysed cells showed a small τ cp dependence, attributed to the water exchange rate between free and hemoglobin-bound water to be much faster than τ cp . This was contrary to the tangential dependence in whole blood, where a much slower exchange between cells and blood plasma applies. Whole blood data were fitted as a function of τ cp using a general tangential correlation time model applicable for exchange as well as diffusion contributions to R 2CPMG , and the intercept R 20blood at infinitely short τ cp was determined. The R 20blood values at different hematocrit and the R 2CPMG values of lysed erythrocyte/plasma mixtures at different hemoglobin concentration were used to determine the relaxivity of hemoglobin inside the erythrocyte (r 2Hb ) and albumin (r 2Alb ) in plasma. The r 2Hb values obtained from lysed erythrocytes and whole blood were comparable at full oxygenation. However, while r 2Hb determined from lysed cells showed a linear dependence on oxygenation, this dependence became quadratic in whole blood. This possibly suggests an additional relaxation effect inside intact cells, perhaps due to hemoglobin

IL-12 Influence mTOR to Modulate CD8+ T Cells Differentiation through T-bet and Eomesodermin in Response to Invasive Pulmonary Aspergillosis.

PubMed

Wang, Hao; Li, Jingdong; Han, Qiyang; Yang, Fei; Xiao, Yu; Xiao, Meng; Xu, Yingchun; Su, Longxiang; Cui, Na; Liu, Dawei

2017-01-01

Objective: To investigate whether mTOR signaling pathway regulate the proliferation and differentiation of CD8 + T cells by transcription factors T-bet and Eomes, and explore the role of IL-12 in this biological procedure. Methods: Aspergillus fumigatus spore suspension nasal inhalation was used to establish the invasive pulmonary aspergillosis (IPA) mouse model. After inoculation, rapamycin (2mg/kg) each day or IL-12 (5ug/kg) every other day was given for 7 days. The blood samples were obtained before the mice sacrificed and lung specimens were taken. Pathological sections were stained with hematoxylin and eosin (HE). The number of CD8 + effective memory T cells (Tem) and the expression of IFN-γ, mTOR, ribosomal protein S6 kinase (S6K), T-bet and EOMES were measured by flow cytometry. The levels of IL-6, IL-10 and Galactomannan (GM) were determined by ELISA. Results: After IL-12 treatment, the number of CD8 + Tem and the expression of IFN-γ increased significantly; while quite the opposite results were observed when the mTOR pathway was blocked by rapamycin. The expression of mTOR and S6K as well as the level of IFN-γ of the IL-12 treatment group were significantly higher than those in IPA and IPA + rapamycin groups. In addition, IL-12 promoted increasing T-bet and down regulating Eomes to make the Tem transformation. The final immune effector was high level of inflammatory cytokines (IL-6) and low level of anti-inflammatory factors (IL-10) and this strengthened immune response to the Aspergillus infection. Conclusions: The biological effects of Tem could significantly affect IPA infection host immune regulation, which depended on the activation of mTOR signaling pathway by IL-12.

Cluster analysis of quantitative MRI T2 and T1ρ relaxation times of cartilage identifies differences between healthy and ACL-injured individuals at 3T.

PubMed

Monu, U D; Jordan, C D; Samuelson, B L; Hargreaves, B A; Gold, G E; McWalter, E J

2017-04-01

To identify focal lesions of elevated MRI T 2 and T 1ρ relaxation times in articular cartilage of an ACL-injured group using a novel cluster analysis technique. Eighteen ACL-injured patients underwent 3T MRI T 2 and T 1ρ relaxometry at baseline, 6 months and 1 year and six healthy volunteers at baseline, 1 day and 1 year. Clusters of contiguous pixels above or below T 2 and T 1ρ intensity and area thresholds were identified on a projection map of the 3D femoral cartilage surface. The total area of femoral cartilage plate covered by clusters (%CA) was split into areas above (%CA+) and below (%CA-) the thresholds and the differences in %CA(+ or -) over time in the ACL-injured group were determined using the Wilcoxon signed rank test. %CA+ was greater in the ACL-injured patients than the healthy volunteers at 6 months and 1 year with average %CA+ of 5.2 ± 4.0% (p = 0.0054) and 6.6 ± 3.7% (p = 0.0041) for T 2 and 6.2 ± 7.1% (p = 0.063) and 8.2 ± 6.9% (p = 0.042) for T 1ρ , respectively. %CA- at 6 months and 1 year was 3.0 ± 1.8% (p > 0.1) and 5.9 ± 5.0% (p > 0.1) for T 2 and 4.4 ± 4.9% (p > 0.1) and 4.5 ± 4.6% (p > 0.1) for T 1ρ , respectively. With the proposed cluster analysis technique, we have quantified cartilage lesion coverage and demonstrated that the ACL-injured group had greater areas of elevated T 2 and T 1ρ relaxation times as compared to healthy volunteers. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

An expanded calibration study of the explicitly correlated CCSD(T)-F12b method using large basis set standard CCSD(T) atomization energies.

PubMed

Feller, David; Peterson, Kirk A

2013-08-28

The effectiveness of the recently developed, explicitly correlated coupled cluster method CCSD(T)-F12b is examined in terms of its ability to reproduce atomization energies derived from complete basis set extrapolations of standard CCSD(T). Most of the standard method findings were obtained with aug-cc-pV7Z or aug-cc-pV8Z basis sets. For a few homonuclear diatomic molecules it was possible to push the basis set to the aug-cc-pV9Z level. F12b calculations were performed with the cc-pVnZ-F12 (n = D, T, Q) basis set sequence and were also extrapolated to the basis set limit using a Schwenke-style, parameterized formula. A systematic bias was observed in the F12b method with the (VTZ-F12/VQZ-F12) basis set combination. This bias resulted in the underestimation of reference values associated with small molecules (valence correlation energies <0.5 E(h)) and an even larger overestimation of atomization energies for bigger systems. Consequently, caution should be exercised in the use of F12b for high accuracy studies. Root mean square and mean absolute deviation error metrics for this basis set combination were comparable to complete basis set values obtained with standard CCSD(T) and the aug-cc-pVDZ through aug-cc-pVQZ basis set sequence. However, the mean signed deviation was an order of magnitude larger. Problems partially due to basis set superposition error were identified with second row compounds which resulted in a weak performance for the smaller VDZ-F12/VTZ-F12 combination of basis sets.

33 CFR 165.T11-560 - Safety Zone; Sea World San Diego Fireworks 2013 Season, Mission Bay; San Diego, CA.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Safety Zone; Sea World San Diego Fireworks 2013 Season, Mission Bay; San Diego, CA. 165.T11-560 Section 165.T11-560 Navigation and Navigable... Eleventh Coast Guard District § 165.T11-560 Safety Zone; Sea World San Diego Fireworks 2013 Season, Mission...

Dectin-1 diversifies Aspergillus fumigatus–specific T cell responses by inhibiting T helper type 1 CD4 T cell differentiation

PubMed Central

Hohl, Tobias M.; Collins, Nichole; Leiner, Ingrid; Gallegos, Alena; Saijo, Shinobu; Coward, Jesse W.; Iwakura, Yoichiro

2011-01-01

Pulmonary infection of mice with Aspergillus fumigatus induces concurrent T helper type 1 (Th1) and Th17 responses that depend on Toll-like receptor/MyD88 and Dectin-1, respectively. However, the mechanisms balancing Th1 and Th17 CD4 T cell populations during infection remain incompletely defined. In this study, we show that Dectin-1 deficiency disproportionally increases Th1 responses and decreases Th17 differentiation after A. fumigatus infection. Dectin-1 signaling in A. fumigatus–infected wild-type mice reduces IFN-γ and IL-12p40 expression in the lung, thereby decreasing T-bet expression in responding CD4 T cells and enhancing Th17 responses. Absence of IFN-γ or IL-12p35 in infected mice or T-bet in responding CD4 T cells enhances Th17 differentiation, independent of Dectin-1 expression, in A. fumigatus–infected mice. Transient deletion of monocyte-derived dendritic cells also reduces Th1 and boosts Th17 differentiation of A. fumigatus–specific CD4 T cells. Our findings indicate that Dectin-1–mediated signals alter CD4 T cell responses to fungal infection by decreasing the production of IL-12 and IFN-γ in innate cells, thereby decreasing T-bet expression in A. fumigatus–specific CD4 T cells and enabling Th17 differentiation. PMID:21242294

IL-12 is required for differentiation of pathogenic CD8+ T cell effectors that cause myocarditis

PubMed Central

Grabie, Nir; Delfs, Michael W.; Westrich, Jason R.; Love, Victoria A.; Stavrakis, George; Ahmad, Ferhaan; Seidman, Christine E.; Seidman, Jonathan G.; Lichtman, Andrew H.

2003-01-01

Cardiac antigen–specific CD8+ T cells are involved in the autoimmune component of human myocarditis. Here, we studied the differentiation and migration of pathogenic CD8+ T cell effector cells in a new mouse model of autoimmune myocarditis. A transgenic mouse line was derived that expresses cardiac myocyte restricted membrane-bound ovalbumin (CMy-mOva). The endogenous adaptive immune system of CMy-mOva mice displays tolerance to ovalbumin. Adoptive transfer of naive CD8+ T cells from the ovalbumin-specific T cell receptor–transgenic (TCR-transgenic) OT-I strain induces myocarditis in CMy-mOva mice only after subsequent inoculation with ovalbumin-expressing vesicular stomatitis virus (VSV-Ova). OT-I effector T cells derived in vitro in the presence or absence of IL-12 were adoptively transferred into CMy-mOva mice, and the consequences were compared. Although IL-12 was not required for the generation of cytolytic and IFN-γ–producing effector T cells, only effectors primed in the presence of IL-12 infiltrated CMy-mOva hearts in significant numbers, causing lethal myocarditis. Furthermore, analysis of OT-I effectors collected from a mediastinal draining lymph node indicated that only effectors primed in vitro in the presence of IL-12 proliferated in vivo. These data demonstrate the importance of IL-12 in the differentiation of pathogenic CD8+ T cells that can cause myocarditis. PMID:12618521

Meiotic Recombination and Spatial Proximity in the Etiology of the Recurrent t(11;22)

PubMed Central

Ashley, Terry; Gaeth, Ann P.; Inagaki, Hidehito; Seftel, Allen; Cohen, Maimon M.; Anderson, Lorinda K.; Kurahashi, Hiroki; Emanuel, Beverly S.

2006-01-01

Although balanced translocations are among the most common human chromosomal aberrations, the constitutional t(11;22)(q23;q11) is the only known recurrent non-Robertsonian translocation. Evidence indicates that de novo formation of the t(11;22) occurs during meiosis. To test the hypothesis that spatial proximity of chromosomes 11 and 22 in meiotic prophase oocytes and spermatocytes plays a role in the rearrangement, the positions of the 11q23 and 22q11 translocation breakpoints were examined. Fluorescence in situ hybridization with use of DNA probes for these sites demonstrates that 11q23 is closer to 22q11 in meiosis than to a control at 6q26. Although chromosome 21p11, another control, often lies as close to 11q23 as does 22q11 during meiosis, chromosome 21 rarely rearranges with 11q23, and the DNA sequence of chromosome 21 appears to be less susceptible than 22q11 to double-strand breaks (DSBs). It has been suggested that the rearrangement recurs as a result of the palindromic AT-rich repeats at both 11q23 and 22q11, which extrude hairpin structures that are susceptible to DSBs. To determine whether the DSBs at these sites coincide with normal hotspots of meiotic recombination, immunocytochemical mapping of MLH1, a protein involved in crossing over, was employed. The results indicate that the translocation breakpoints do not coincide with recombination hotspots and therefore are unlikely to be the result of meiotic programmed DSBs, although MRE11 is likely to be involved. Previous analysis indicated that the DSBs appear to be repaired by a mechanism similar to nonhomologous end joining (NHEJ), although NHEJ is normally suppressed during meiosis. Taken together, these studies support the hypothesis that physical proximity between 11q23 and 22q11—but not typical meiotic recombinational activity in meiotic prophase—plays an important role in the generation of the constitutional t(11;22) rearrangement. PMID:16909390

Impact of t(11;14)(q13;q32) on the outcome of autologous hematopoietic cell transplantation in multiple myeloma.

PubMed

Sasaki, Koji; Lu, Gary; Saliba, Rima M; Bashir, Qaiser; Hosing, Chitra; Popat, Uday; Shah, Nina; Parmar, Simrit; Dinh, Yvonne; Ahmed, Sairah; Shpall, Elizabeth J; Kebriaei, Partow; Shah, Jatin J; Orlowski, Robert Z; Champlin, Richard; Qazilbash, Muzaffar H

2013-08-01

The t(11;14)(q13;q32) translocation is seen in 15%-20% patients with multiple myeloma (MM). It generally is not associated with worse outcomes. We studied the impact of t(11;14)(q13;q32) on outcome in patients with MM who received high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HCT). Eligible patients underwent high-dose chemotherapy followed by auto-HCT at the M.D. Anderson Cancer Center between February 2000 and August 2010, and had conventional cytogenetic (CC) or fluorescence in situ hybridization (FISH) results available before auto-HCT (n = 993). The cohort was divided into 3 groups of patients: (1) normal (diploid by CC and negative by FISH; n = 869); (2) t(11;14)(q13;q32) by CC or FISH (n = 27); and (3) high-risk (HR) abnormalities by CC or FISH (n = 97). Of the 27 patients with t(11;14)(q13;q32), 18 had isolated t(11;14)(q13;q32) and 9 had concurrent HR abnormalities. The primary objective was to compare outcomes in patients with t(11;14)(q13;q32) and patients with diploid or HR markers detected by CC or FISH studies. The median duration of follow-up in surviving patients was 37 months. The 3-year progression-free survival (PFS) was 47% for the normal group, 27% for the t(11;14)(q13;q32) group, and 13% for the HR group (P < .00001). The 3-year OS was 83% for the normal group, 63% for the t(11;14)(q13;q32) group, and 34% for the HR group (P < .00001). On multivariate analysis, t(11;14)(q13;q32) and HR abnormalities by CC or FISH and relapsed disease at auto-HCT were associated with shorter PFS, whereas t(11;14)(q13;q32) and HR abnormalities by CC or FISH, β2 microglobulin of >3.5, and relapsed disease at the time of auto-HCT were associated with shorter OS. In conclusion, patients with t(11;14)(q13;q32) had worse outcomes than patients with normal CC or FISH studies, but better outcomes than patients with HR markers detected by CC or FISH studies. Copyright © 2013 American Society for Blood and

Techniques and Applications of in vivo Diffusion Imaging of Articular Cartilage

PubMed Central

Raya, José G.

2014-01-01

Early in the process of osteoarthritis (OA) the composition (water, proteoglycan [PG], and collagen) and structure of articular cartilage is altered leading to changes in its mechanical properties. A technique that can assess the composition and structure of the cartilage in vivo can provide insight in the mechanical integrity of articular cartilage and become a powerful tool for the early diagnosis of OA. Diffusion tensor imaging (DTI) has been proposed as a biomarker for cartilage composition and structure. DTI is sensitive to the PG content through the mean diffusivity (MD) and to the collagen architecture through the fractional anisotropy (FA). However, the acquisition of DTI of articular cartilage in vivo is challenging due to the short T2 of articular cartilage (~40 ms at 3 T) and the high resolution needed (0.5–0.7 mm in plane) to depict the cartilage anatomy. We describe the pulse sequences used for in vivo DTI of articular cartilage and discus general strategies for protocol optimization. We provide a comprehensive review of measurements of DTI of articular cartilage from ex vivo validation experiments to its recent clinical applications. PMID:25865215

17 CFR 240.15b12-1T - Brokers or dealers engaged in a retail forex business.

Code of Federal Regulations, 2012 CFR

2012-04-01

... a retail forex business. 240.15b12-1T Section 240.15b12-1T Commodity and Securities Exchanges... § 240.15b12-1T Brokers or dealers engaged in a retail forex business. (a) Definitions. In addition to... et seq.). (2) Retail forex business means engaging in one or more retail forex transactions with the...

17 CFR 240.15b12-1T - Brokers or dealers engaged in a retail forex business.

Code of Federal Regulations, 2013 CFR

2013-04-01

... a retail forex business. 240.15b12-1T Section 240.15b12-1T Commodity and Securities Exchanges... § 240.15b12-1T Brokers or dealers engaged in a retail forex business. (a) Definitions. In addition to... et seq.). (2) Retail forex business means engaging in one or more retail forex transactions with the...

Toward a W4-F12 approach: Can explicitly correlated and orbital-based ab initio CCSD(T) limits be reconciled?

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

Sylvetsky, Nitai, E-mail: gershom@weizmann.ac.il; Martin, Jan M. L., E-mail: gershom@weizmann.ac.il; Peterson, Kirk A., E-mail: kipeters@wsu.edu

2016-06-07

In the context of high-accuracy computational thermochemistry, the valence coupled cluster with all singles and doubles (CCSD) correlation component of molecular atomization energies presents the most severe basis set convergence problem, followed by the (T) component. In the present paper, we make a detailed comparison, for an expanded version of the W4-11 thermochemistry benchmark, between, on the one hand, orbital-based CCSD/AV{5,6}Z + d and CCSD/ACV{5,6}Z extrapolation, and on the other hand CCSD-F12b calculations with cc-pVQZ-F12 and cc-pV5Z-F12 basis sets. This latter basis set, now available for H–He, B–Ne, and Al–Ar, is shown to be very close to the basis setmore » limit. Apparent differences (which can reach 0.35 kcal/mol for systems like CCl{sub 4}) between orbital-based and CCSD-F12b basis set limits disappear if basis sets with additional radial flexibility, such as ACV{5,6}Z, are used for the orbital calculation. Counterpoise calculations reveal that, while total atomization energies with V5Z-F12 basis sets are nearly free of BSSE, orbital calculations have significant BSSE even with AV(6 + d)Z basis sets, leading to non-negligible differences between raw and counterpoise-corrected extrapolated limits. This latter problem is greatly reduced by switching to ACV{5,6}Z core-valence basis sets, or simply adding an additional zeta to just the valence orbitals. Previous reports that all-electron approaches like HEAT (high-accuracy extrapolated ab-initio thermochemistry) lead to different CCSD(T) limits than “valence limit + CV correction” approaches like Feller-Peterson-Dixon and Weizmann-4 (W4) theory can be rationalized in terms of the greater radial flexibility of core-valence basis sets. For (T) corrections, conventional CCSD(T)/AV{Q,5}Z + d calculations are found to be superior to scaled or extrapolated CCSD(T)-F12b calculations of similar cost. For a W4-F12 protocol, we recommend obtaining the Hartree-Fock and valence CCSD components from

Metastatic adrenal cortical carcinoma to T12 vertebrae.

PubMed

Lee, Daniel; Yanamadala, Vijay; Shankar, Ganesh M; Shin, John H

2016-05-01

We report spinal metastasis of adrenal cortical carcinoma (ACC) to the T12 vertebrae with epidural extension. ACC is a rare malignancy with poor prognosis and high rates of metastasis. However, spinal lesions of ACC are rare, and few have been reported in the literature. We discuss our management of this lesion and review the current understanding and treatment of ACC and spinal metastasis. Copyright © 2015 Elsevier Ltd. All rights reserved.

The degeneration and destruction of femoral articular cartilage shows a greater degree of deterioration than that of the tibial and patellar articular cartilage in early stage knee osteoarthritis: a cross-sectional study.

PubMed

Hada, S; Kaneko, H; Sadatsuki, R; Liu, L; Futami, I; Kinoshita, M; Yusup, A; Saita, Y; Takazawa, Y; Ikeda, H; Kaneko, K; Ishijima, M

2014-10-01

The aim of the present study was to examine whether the degenerative and morphological changes of articular cartilage in early stage knee osteoarthritis (OA) occurred equally for both femoral- and tibial- or patellar- articular cartilage using magnetic resonance imaging (MRI)-based analyses. This cross-sectional study was approved by the ethics committee of our university. Fifty patients with early stage painful knee OA were enrolled. The patients underwent 3.0 T MRI on the affected knee joint. Healthy volunteers who did not show MRI-based OA changes were also recruited as controls (n = 19). The degenerative changes of the articular cartilage were quantified by a T2 mapping analysis, and any structural changes were conducted using Whole Organ Magnetic Resonance Imaging Score (WORMS) technique. All patients showed MRI-detected OA morphological changes. The T2 values of femoral condyle (FC) (P < 0.0001) and groove (P = 0.0001) in patients with early stage knee OA were significantly increased in comparison to those in the control, while no significant differences in the T2 values of patellar and tibial plateau (TP) were observed between the patients and the control. The WORMS cartilage and osteophyte scores of the femoral articular cartilage were significantly higher than those in the patellar- (P = 0.001 and P = 0.007, respectively) and tibial- (P = 0.0001 and P < 0.0001, respectively) articular cartilage in the patients with early stage knee OA. The degradation and destruction of the femoral articular cartilage demonstrated a greater degree of deterioration than those of the tibial- and patellar- articular cartilage in patients with early stage knee OA. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Quantifying NMR relaxation correlation and exchange in articular cartilage with time domain analysis

NASA Astrophysics Data System (ADS)

Mailhiot, Sarah E.; Zong, Fangrong; Maneval, James E.; June, Ronald K.; Galvosas, Petrik; Seymour, Joseph D.

2018-02-01

Measured nuclear magnetic resonance (NMR) transverse relaxation data in articular cartilage has been shown to be multi-exponential and correlated to the health of the tissue. The observed relaxation rates are dependent on experimental parameters such as solvent, data acquisition methods, data analysis methods, and alignment to the magnetic field. In this study, we show that diffusive exchange occurs in porcine articular cartilage and impacts the observed relaxation rates in T1-T2 correlation experiments. By using time domain analysis of T2-T2 exchange spectroscopy, the diffusive exchange time can be quantified by measurements that use a single mixing time. Measured characteristic times for exchange are commensurate with T1 in this material and so impacts the observed T1 behavior. The approach used here allows for reliable quantification of NMR relaxation behavior in cartilage in the presence of diffusive fluid exchange between two environments.

Interluekin-12 enhances the function and anti-tumor activity in murine and human CD8+ T cells

PubMed Central

Rubinstein, Mark P.; Su, Ee Wern; Suriano, Samantha; Cloud, Colleen A.; Andrijauskaite, Kristina; Kesarwani, Pravin; Schwartz, Kristina M.; Williams, Katelyn; Johnson, C. Bryce; Li, Mingli; Scurti, Gina M.; Salem, Mohamed L.; Paulos, Chrystal M.; Garrett-Mayer, Elizabeth; Mehrotra, Shikhar; Cole, David J.

2016-01-01

Mouse CD8+ T cells conditioned with Interleukin (IL)-12 ex vivo mediate the potent regression of established melanoma when transferred into lymphodepleted mice. However, the quantitative and qualitative changes induced by IL-12 in the responding mouse CD8+ T cells have not been well defined. Moreover, the mechanisms by which IL-12-conditioning impacts human CD8+ T cells, and how such cells might be expanded prior to infusion into patients is not known. We found that ex vivo IL-12-conditioning of mouse CD8+ T cells led to a 10- to 100-fold increase in persistence and anti-tumor efficacy upon adoptive transfer into lymphodepleted mice. The enhancing effect of IL-12 was associated with maintenance of functional avidity. Importantly, in the context of ongoing ACT clinical trials, human CD8+ T cells genetically modified with a tyrosinase-specific T-cell receptor exhibited significantly enhanced functional activity when conditioned with IL-12 as indicated by heightened granzyme B expression and elevated peptide-specific CD107a degranulation. This effect was sustainable despite the 20 days of in vitro cellular expansion required to expand cells over 1,000-fold allowing adequate cell numbers for administration to cancer patients. Overall, these findings support the efficacy and feasibility of ex vivo IL-12-conditioning of TCR-modified human CD8+ T cells for adoptive transfer and cancer therapy. PMID:25676709

Melanoma exosomes deliver a complex biological payload that upregulates PTPN11 to suppress T lymphocyte function

PubMed Central

Wu, Yueting; Deng, Wentao; McGinley, Emily Chambers; Klinke, David J.

2017-01-01

Summary As exosomes are emerging as a new mode of intercellular communication, we hypothesized that the payload contained within exosomes is shaped by somatic evolution. To test this, we assayed the impact on primary CD8+ T cell function, a key mechanism for anti-tumor immunity, of exosomes derived from three melanoma-related cell lines. While morphologically similar, exosomes from each cell line were functionally different, as B16F0 exosomes dose-dependently suppressed T cell proliferation. In contrast, Cloudman S91 exosomes promoted T cell proliferation and Melan-A exosomes had a negligible effect on primary CD8+ T cells. Mechanistically, transcript profiling suggested that exosomal mRNA is enriched for full-length mRNAs that target immune-related pathways. Interestingly, B16F0 exosomes were unique in that they contained both protein and mRNA for Ptpn11, which inhibited T cell proliferation. Collectively, the results suggest that upregulation of PTPN11 by B16F0 exosomes to tumor infiltrating lymphocytes would bypass the extracellular control of the immune checkpoints. PMID:27930879

Evaluation of the Subscapularis Tendon Tears on 3T Magnetic Resonance Arthrography: Comparison of Diagnostic Performance of T1-Weighted Spectral Presaturation with Inversion-Recovery and T2-Weighted Turbo Spin-Echo Sequences.

PubMed

Lee, Hoseok; Ahn, Joong Mo; Kang, Yusuhn; Oh, Joo Han; Lee, Eugene; Lee, Joon Woo; Kang, Heung Sik

2018-01-01

To compare the T1-weighted spectral presaturation with inversion-recovery sequences (T1 SPIR) with T2-weighted turbo spin-echo sequences (T2 TSE) on 3T magnetic resonance arthrography (MRA) in the evaluation of the subscapularis (SSC) tendon tear with arthroscopic findings as the reference standard. This retrospective study included 120 consecutive patients who had undergone MRA within 3 months between April and December 2015. Two musculoskeletal radiologists blinded to the arthroscopic results evaluated T1 SPIR and T2 TSE images in separate sessions for the integrity of the SSC tendon, examining normal/articular-surface partial-thickness tear (PTTa)/full-thickness tear (FTT). Diagnostic performance of T1 SPIR and T2 TSE was calculated with arthroscopic results as the reference standard, and sensitivity, specificity, and accuracy were compared using the McNemar test. Interobserver agreement was measured with kappa (κ) statistics. There were 74 SSC tendon tears (36 PTTa and 38 FTT) confirmed by arthroscopy. Significant differences were found in the sensitivity and accuracy between T1 SPIR and T2 TSE using the McNemar test, with respective rates of 95.9-94.6% vs. 71.6-75.7% and 90.8-91.7% vs. 79.2-83.3% for detecting tear; 55.3% vs. 31.6-34.2% and 85.8% vs. 78.3-79.2%, respectively, for FTT; and 91.7-97.2% vs. 58.3-61.1% and 89% vs. 78-79.3%, respectively, for PTTa. Interobserver agreement for T1 SPIR was almost perfect for T1 SPIR (κ = 0.839) and substantial for T2 TSE (κ = 0.769). T1-weighted spectral presaturation with inversion-recovery sequences is more sensitive and accurate compared to T2 TSE in detecting SSC tendon tear on 3T MRA.

Use of GPS ASHTECH Z12T receivers for accurate time and frequency comparisons.

PubMed

Petit, G; Thomas, C; Jiang, Z; Uhrich, P; Taris, F

1999-01-01

The GPS phase measurements described in this paper were obtained using two similar multichannel GPS ASHTECH Z12T receivers belonging to the Bureau International des Poids et Mesures, BIPM, and the Laboratoire Primaire du Temps et des Frequences, BNM-LPTF. These receivers are based on the conventional geodetic ASHTECH Z12 unit, which has been modified to meet the stability requirements of time and frequency comparisons. Comparison of the two receivers operated side by side in different antenna configurations shows typical short-term noise of 1.1 to 3.5 ps. Longer term variations indicate a temperature sensitivity in the equipment, which limits the performance of the GPS phase method. One of the receivers was successfully operated using a temperature-stabilized antenna TSA from 3S Navigation, and the ASHTECH antenna, which feeds the second receiver, was placed in a home-built oven maintained at a constant temperature. These precautions made it possible to reduce a number of systematic effects. A separate study of frequency comparison was carried out between two hydrogen-masers located at the BNM-LPTF (Paris, France) and the PTB (Braunschweig, Germany) using receivers similar to ASHTECH Z12T receivers. The relative frequency stability obtained was about 3.3x10(-15) for an average time of 15 000 s, an interesting result comparable with the outstanding performance of new ultrastable frequency standards.

Unusually long survival after autografting in second partial remission of translocation t(4;11) acute infant leukemia.

PubMed

Emminger, W; Emminger-Schmidmeier, W; Ambros, P; Haas, O A; Höcker, P; Köller, U; Gadner, H

1991-10-01

About 70% of children with acute lymphoblastic leukemia may be cured by conventional chemotherapy. The prognosis is considerably worse in infant leukemia with a translocation t(4;11). We report an infant with a diagnosis of cytochemically undifferentiated acute hybrid leukemia (pre pre B-ALL coexpressing one myelomonocytic marker) and t(4;11). Initial clinical presentation and the course of the disease were typical for t(4;11) acute leukemia. After an early hematologic relapse intensive chemotherapy resulted only in a second partial remission 7 months after initial diagnosis. Subsequent bone marrow transplantation with 16 mg/kg busulfan and 200 mg/kg cyclophosphamide followed by the infusion of autologous purged bone marrow resulted in a continuous second remission which has lasted 46 months so far.

Three-Dimensional Algebraic Models of the tRNA Code and 12 Graphs for Representing the Amino Acids.

PubMed

José, Marco V; Morgado, Eberto R; Guimarães, Romeu Cardoso; Zamudio, Gabriel S; de Farías, Sávio Torres; Bobadilla, Juan R; Sosa, Daniela

2014-08-11

Three-dimensional algebraic models, also called Genetic Hotels, are developed to represent the Standard Genetic Code, the Standard tRNA Code (S-tRNA-C), and the Human tRNA code (H-tRNA-C). New algebraic concepts are introduced to be able to describe these models, to wit, the generalization of the 2n-Klein Group and the concept of a subgroup coset with a tail. We found that the H-tRNA-C displayed broken symmetries in regard to the S-tRNA-C, which is highly symmetric. We also show that there are only 12 ways to represent each of the corresponding phenotypic graphs of amino acids. The averages of statistical centrality measures of the 12 graphs for each of the three codes are carried out and they are statistically compared. The phenotypic graphs of the S-tRNA-C display a common triangular prism of amino acids in 10 out of the 12 graphs, whilst the corresponding graphs for the H-tRNA-C display only two triangular prisms. The graphs exhibit disjoint clusters of amino acids when their polar requirement values are used. We contend that the S-tRNA-C is in a frozen-like state, whereas the H-tRNA-C may be in an evolving state.

Measurements of Dynamic Effects in FNAL 11 T Nb 3Sn Dipole Models

DOE PAGES

Velev, Gueorgui; Strauss, Thomas; Barzi, Emanuela; ...

2018-01-17

Fermilab, in collaboration with CERN, has developed a twin-aperture 11 T Nb 3Sn dipole suitable for the high-luminosity LHC upgrade. During 2012-2014, a 2-m long single-aperture dipole demonstrator and three 1-m long single-aperture dipole models were fabricated by FNAL and tested at its Vertical Magnet Test Facility. Collared coils from two of the 1-m long models were then used to assemble the first twin-aperture dipole demonstrator. This magnet had extensive testing in 2015-2016, including quench performance, quench protection, and field quality studies. Here, this paper reports the results of measurements of persistent current effects in the single-aperture and twin-aperture 11more » T Nb 3Sn dipoles and compares them with similar measurements in previous NbTi magnets« less

Measurements of Dynamic Effects in FNAL 11 T Nb 3Sn Dipole Models

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

Velev, Gueorgui; Strauss, Thomas; Barzi, Emanuela

Fermilab, in collaboration with CERN, has developed a twin-aperture 11 T Nb 3Sn dipole suitable for the high-luminosity LHC upgrade. During 2012-2014, a 2-m long single-aperture dipole demonstrator and three 1-m long single-aperture dipole models were fabricated by FNAL and tested at its Vertical Magnet Test Facility. Collared coils from two of the 1-m long models were then used to assemble the first twin-aperture dipole demonstrator. This magnet had extensive testing in 2015-2016, including quench performance, quench protection, and field quality studies. Here, this paper reports the results of measurements of persistent current effects in the single-aperture and twin-aperture 11more » T Nb 3Sn dipoles and compares them with similar measurements in previous NbTi magnets« less

Fast T1 and T2 mapping methods: the zoomed U-FLARE sequence compared with EPI and snapshot-FLASH for abdominal imaging at 11.7 Tesla.

PubMed

Pastor, Géraldine; Jiménez-González, María; Plaza-García, Sandra; Beraza, Marta; Reese, Torsten

2017-06-01

A newly adapted zoomed ultrafast low-angle RARE (U-FLARE) sequence is described for abdominal imaging applications at 11.7 Tesla and compared with the standard echo-plannar imaging (EPI) and snapshot fast low angle shot (FLASH) methods. Ultrafast EPI and snapshot-FLASH protocols were evaluated to determine relaxation times in phantoms and in the mouse kidney in vivo. Owing to their apparent shortcomings, imaging artefacts, signal-to-noise ratio (SNR), and variability in the determination of relaxation times, these methods are compared with the newly implemented zoomed U-FLARE sequence. Snapshot-FLASH has a lower SNR when compared with the zoomed U-FLARE sequence and EPI. The variability in the measurement of relaxation times is higher in the Look-Locker sequences than in inversion recovery experiments. Respectively, the average T1 and T2 values at 11.7 Tesla are as follows: kidney cortex, 1810 and 29 ms; kidney medulla, 2100 and 25 ms; subcutaneous tumour, 2365 and 28 ms. This study demonstrates that the zoomed U-FLARE sequence yields single-shot single-slice images with good anatomical resolution and high SNR at 11.7 Tesla. Thus, it offers a viable alternative to standard protocols for mapping very fast parameters, such as T1 and T2, or dynamic processes in vivo at high field.

Prospective In Vivo Comparison of Damaged and Healthy-Appearing Articular Cartilage Specimens in Patients With Femoroacetabular Impingement: Comparison of T2 Mapping, Histologic Endpoints, and Arthroscopic Grading.

PubMed

Ho, Charles P; Surowiec, Rachel K; Frisbie, David D; Ferro, Fernando P; Wilson, Katharine J; Saroki, Adriana J; Fitzcharles, Eric K; Dornan, Grant J; Philippon, Marc J

2016-08-01

To describe T2 mapping values in arthroscopically determined International Cartilage Repair Society (ICRS) grades in damaged and healthy-appearing articular cartilage waste specimens from arthroscopic femoroacetabular impingement (FAI) treatment. Furthermore, we sought to compare ICRS grades of the specimens with biochemical, immunohistochemistry and histologic endpoints and assess correlations with T2 mapping. Twenty-four patients were prospectively enrolled, consecutively, between December 2011 and August 2012. Patients were included if they were aged 18 years or older and met criteria that followed the clinical indications for arthroscopy to treat FAI. Patients with prior hip trauma including fracture or dislocation or who have undergone prior hip surgery were excluded. All patients received a preoperative sagittal T2 mapping scan of the hip joint. Cartilage was graded intraoperatively using the ICRS grading system, and graded specimens were collected as cartilage waste for histologic, biochemical, and immunohistochemistry analysis. Forty-four cartilage specimens (22 healthy-appearing, 22 damaged) were analyzed. Median T2 values were significantly higher among damaged specimens (55.7 ± 14.9 ms) than healthy-appearing specimens (49.3 ± 12.3 ms; P = .043), which was most exaggerated among mild (grade 1 or 2) defects where the damaged specimens (58.1 ± 16.4 ms) were significantly higher than their paired healthy-appearing specimens (48.7 ± 15.4 ms; P = .026). Severely damaged specimens (grade 3 or 4) had significantly lower cumulative H&E than their paired healthy-appearing counterparts (P = .02) but was not statistically significant among damaged specimens with mild (grade 1 or 2) defects (P = .198). Among healthy-appearing specimens, median T2 and the percentage of collagen fibers oriented parallel were significantly correlated (rho = 0.425, P = .048). This study outlines the potential for T2 mapping to identify early cartilage degeneration in

Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning

PubMed Central

Pegram, Hollie J.; Lee, James C.; Hayman, Erik G.; Imperato, Gavin H.; Tedder, Thomas F.; Sadelain, Michel

2012-01-01

Adoptive cell therapy with tumor-targeted T cells is a promising approach to cancer therapy. Enhanced clinical outcome using this approach requires conditioning regimens with total body irradiation, lymphodepleting chemotherapy, and/or additional cytokine support. However, the need for prior conditioning precludes optimal application of this approach to a significant number of cancer patients intolerant to these regimens. Herein, we present preclinical studies demonstrating that treatment with CD19-specific, chimeric antigen receptor (CAR)–modified T cells that are further modified to constitutively secrete IL-12 are able to safely eradicate established disease in the absence of prior conditioning. We demonstrate in a novel syngeneic tumor model that tumor elimination requires both CD4+ and CD8+ T-cell subsets, autocrine IL-12 stimulation, and subsequent IFNγ secretion by the CAR+ T cells. Importantly, IL-12–secreting, tumor-targeted T cells acquire intrinsic resistance to T regulatory cell–mediated inhibition. Based on these preclinical data, we anticipate that adoptive therapy using CAR-targeted T cells modified to secrete IL-12 will obviate or reduce the need for potentially hazardous conditioning regimens to achieve optimal antitumor responses in cancer patients. PMID:22354001

Focal articular prosthetic resurfacing for the treatment of full-thickness articular cartilage defects in the knee: 12-year follow-up of two cases and review of the literature.

PubMed

Becher, C; Cantiller, E B

2017-09-01

The rationale of focal articular prosthetic resurfacing used as a primary arthroplasty procedure in the treatment of articular cartilage defects is still under debate. Conflicting reports raise concern about high rates of re-operations and continued development of osteoarthritis, while others have reported good outcomes. The goal of this paper is to present the long-term results of two patients with a 12-year follow-up and to report the results of a literature review. Two patients (male, 70 years; female 63 years) with a follow-up of 12 years were reviewed. Patients were evaluated with standard radiographs to assess the progression of osteoarthritis (OA), a clinical examination including the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Tegner activity scale. The literature review was performed using the search terms HemiCAP, focal, femoral, condyle, inlay, and resurfacing to identify articles published in the English language up until September 25, 2016. The clinical and radiographic follow-ups of the patients were 11.9 and 11.8 years, respectively. Both patients were satisfied with their outcome and would have the operation again. Comparing the first postoperative to 12-year follow-up X-rays, the radiographic results demonstrated no signs of periprosthetic loosening, preservation of joint space, and no change in the osteoarthritic stage. KOOS Scores were 86 and 83 for pain, 89 and 93 for symptoms, 88 and 100 for activities of daily living (ADL), 75 and 65 for sports and recreation, and 75 and 81 for quality of life (QOL). The Tegner activity level was 5 and 4. The literature review comprised 6 studies with 169 focal articular prosthetic resurfacing procedures in 169 patients (84 male, 85 female) with a mean age at implantation ranging from 44.7 to 53.7 years and a follow-up range of 20 months to 7 years. Five studies were classified as level 4 and one as level 3. Clinical and radiographic results showed mainly good to excellent outcomes but were

Melanoma exosomes deliver a complex biological payload that upregulates PTPN11 to suppress T lymphocyte function.

PubMed

Wu, Yueting; Deng, Wentao; McGinley, Emily Chambers; Klinke, David J

2017-03-01

As exosomes are emerging as a new mode of intercellular communication, we hypothesized that the payload contained within exosomes is shaped by somatic evolution. To test this, we assayed the impact on primary CD8+ T-cell function, a key mechanism for antitumor immunity, of exosomes derived from three melanoma-related cell lines. While morphologically similar, exosomes from each cell line were functionally different, as B16F0 exosomes dose-dependently suppressed T-cell proliferation. In contrast, Cloudman S91 exosomes promoted T-cell proliferation and Melan-A exosomes had a negligible effect on primary CD8+ T cells. Mechanistically, transcript profiling suggested that exosomal mRNA is enriched for full-length mRNAs that target immune-related pathways. Interestingly, B16F0 exosomes were unique in that they contained both protein and mRNA for PTPN11, which inhibited T-cell proliferation. Collectively, the results suggest that upregulation of PTPN11 by B16F0 exosomes to tumor infiltrating lymphocytes would bypass the extracellular control of the immune checkpoints. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Topographical Variation of Human Femoral Articular Cartilage Thickness, T1rho and T2 Relaxation Times Is Related to Local Loading during Walking.

PubMed

Van Rossom, Sam; Wesseling, Mariska; Van Assche, Dieter; Jonkers, Ilse

2018-01-01

Objective Early detection of degenerative changes in the cartilage matrix composition is essential for evaluating early interventions that slow down osteoarthritis (OA) initiation. T1rho and T2 relaxation times were found to be effective for detecting early changes in proteoglycan and collagen content. To use these magnetic resonance imaging (MRI) methods, it is important to document the topographical variation in cartilage thickness, T1rho and T2 relaxation times in a healthy population. As OA is partially mechanically driven, the relation between these MRI-based parameters and localized mechanical loading during walking was investigated. Design MR images were acquired in 14 healthy adults and cartilage thickness and T1rho and T2 relaxation times were determined. Experimental gait data was collected and processed using musculoskeletal modeling to identify weight-bearing zones and estimate the contact force impulse during gait. Variation of the cartilage properties (i.e., thickness, T1rho, and T2) over the femoral cartilage was analyzed and compared between the weight-bearing and non-weight-bearing zone of the medial and lateral condyle as well as the trochlea. Results Medial condyle cartilage thickness was correlated to the contact force impulse ( r = 0.78). Lower T1rho, indicating increased proteoglycan content, was found in the medial weight-bearing zone. T2 was higher in all weight-bearing zones compared with the non-weight-bearing zones, indicating lower relative collagen content. Conclusions The current results suggest that medial condyle cartilage is adapted as a long-term protective response to localized loading during a frequently performed task and that the weight-bearing zone of the medial condyle has superior weight bearing capacities compared with the non-weight-bearing zones.

Inheritance of a Balanced t(12;20)(q24.33;p12.2) and Unbalanced der(13)t(7;13)(p21.3;q33.2) from a Maternally Derived Double Balanced Translocation Carrier.

PubMed

Peterson, Jess F; Geddes, Gabrielle C; Basel, Donald G; Schippman, Dana; Grignon, John W; vanTuinen, Peter; Kappes, Ulrike P

2018-03-01

We report a 4-month-old male proband with a history of prominent forehead, hypertelorism, ear abnormalities, micrognathia, hypospadias, and multiple cardiac abnormalities. Initial microarray analysis detected a concurrent 7p21.3-p22.3 duplication and 13q33.2-q34 deletion indicating an unbalanced rearrangement. However, subsequent conventional cytogenetic studies only revealed what appeared to be a balanced t(12;20)(q24.33;p12.2). Fluorescence in situ hybridization (FISH) using chromosome-specific subtelomere probes confirmed the presence of an unbalanced der(13)t(7;13)(p21.3;q33.2) and balanced t(12;20)(q24.33;p12.2), both of maternal origin. In addition to our unique clinical findings, this case highlights the benefits and limitations of both conventional cytogenetic studies and microarray analysis and how FISH complements each methodology.

Three-Dimensional Algebraic Models of the tRNA Code and 12 Graphs for Representing the Amino Acids

PubMed Central

José, Marco V.; Morgado, Eberto R.; Guimarães, Romeu Cardoso; Zamudio, Gabriel S.; de Farías, Sávio Torres; Bobadilla, Juan R.; Sosa, Daniela

2014-01-01

Three-dimensional algebraic models, also called Genetic Hotels, are developed to represent the Standard Genetic Code, the Standard tRNA Code (S-tRNA-C), and the Human tRNA code (H-tRNA-C). New algebraic concepts are introduced to be able to describe these models, to wit, the generalization of the 2n-Klein Group and the concept of a subgroup coset with a tail. We found that the H-tRNA-C displayed broken symmetries in regard to the S-tRNA-C, which is highly symmetric. We also show that there are only 12 ways to represent each of the corresponding phenotypic graphs of amino acids. The averages of statistical centrality measures of the 12 graphs for each of the three codes are carried out and they are statistically compared. The phenotypic graphs of the S-tRNA-C display a common triangular prism of amino acids in 10 out of the 12 graphs, whilst the corresponding graphs for the H-tRNA-C display only two triangular prisms. The graphs exhibit disjoint clusters of amino acids when their polar requirement values are used. We contend that the S-tRNA-C is in a frozen-like state, whereas the H-tRNA-C may be in an evolving state. PMID:25370377

BCL11B-Mediated Epigenetic Repression Is a Crucial Target for Histone Deacetylase Inhibitors in Cutaneous T-Cell Lymphoma.

PubMed

Fu, Wenjing; Yi, Shengguo; Qiu, Lei; Sun, Jingru; Tu, Ping; Wang, Yang

2017-07-01

The treatment options for advanced cutaneous T-cell lymphoma (CTCL) are limited because of its unclear pathogenesis. Histone deacetylase (HDAC) inhibitors (HDACis) are recently developed therapeutics approved for refractory CTCL. However, the response rate is relatively low and unpredictable. Previously, we discovered that BCL11B, a key T-cell development regulator, was aberrantly overexpressed in mycosis fungoides, the most common CTCL, as compared with benign inflammatory skin. In this study, we identified a positive correlation between BCL11B expression and sensitivity to HDACi in CTCL lines. BCL11B suppression in BCL11B-high cells induced cell apoptosis by de-repressing apoptotic pathways and showed synergistic effects with suberoylanilide hydroxamic acid (SAHA), a pan-HDACi. Next, we identified the physical interaction and shared downstream genes between BCL11B and HDAC1/2 in CTCL lines. This interaction was essential in the anti-apoptosis effect of BCL11B, and the synergism between BCL11B suppression and HDACi treatment. Further, in clinical samples from 46 mycosis fungoides patients, BCL11B showed increased but varied expression in advanced tumor stage. Analysis of four patients receiving SAHA treatment suggested a positive correlation between BCL11B expression and favorable response to SAHA treatment. In conclusion, BCL11B may serve as a therapeutic target and a useful marker for improving HDACi efficacy in advanced CTCL. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

33 CFR 165.T11-630 - Safety zone; Giants Enterprises Fireworks Display, San Francisco Bay, San Francisco, CA.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Francisco Bay, San Francisco, CA. (a) Location. This temporary safety zone is established in the navigable waters of the San Francisco Bay near Pier 48 in San Francisco, CA as depicted in National Oceanic and... Fireworks Display, San Francisco Bay, San Francisco, CA. 165.T11-630 Section 165.T11-630 Navigation and...

Novel in vivo model of inducible multidrug resistance in acute lymphoblastic leukemia with chromosomal translocation t(4;11)

USDA-ARS?s Scientific Manuscript database

Acute lymphoblastic leukemia (ALL) with translocation t(4;11) is found in 60-85% of infants with ALL and is classified as high-risk due to the generally poor prognosis for survival. Using the SEM cell line established from a patient with t(4;11) ALL, we evaluated the resistance of these cells to the...

Three-dimensional T1rho-weighted MRI at 1.5 Tesla.

PubMed

Borthakur, Arijitt; Wheaton, Andrew; Charagundla, Sridhar R; Shapiro, Erik M; Regatte, Ravinder R; Akella, Sarma V S; Kneeland, J Bruce; Reddy, Ravinder

2003-06-01

To design and implement a magnetic resonance imaging (MRI) pulse sequence capable of performing three-dimensional T(1rho)-weighted MRI on a 1.5-T clinical scanner, and determine the optimal sequence parameters, both theoretically and experimentally, so that the energy deposition by the radiofrequency pulses in the sequence, measured as the specific absorption rate (SAR), does not exceed safety guidelines for imaging human subjects. A three-pulse cluster was pre-encoded to a three-dimensional gradient-echo imaging sequence to create a three-dimensional, T(1rho)-weighted MRI pulse sequence. Imaging experiments were performed on a GE clinical scanner with a custom-built knee-coil. We validated the performance of this sequence by imaging articular cartilage of a bovine patella and comparing T(1rho) values measured by this sequence to those obtained with a previously tested two-dimensional imaging sequence. Using a previously developed model for SAR calculation, the imaging parameters were adjusted such that the energy deposition by the radiofrequency pulses in the sequence did not exceed safety guidelines for imaging human subjects. The actual temperature increase due to the sequence was measured in a phantom by a MRI-based temperature mapping technique. Following these experiments, the performance of this sequence was demonstrated in vivo by obtaining T(1rho)-weighted images of the knee joint of a healthy individual. Calculated T(1rho) of articular cartilage in the specimen was similar for both and three-dimensional and two-dimensional methods (84 +/- 2 msec and 80 +/- 3 msec, respectively). The temperature increase in the phantom resulting from the sequence was 0.015 degrees C, which is well below the established safety guidelines. Images of the human knee joint in vivo demonstrate a clear delineation of cartilage from surrounding tissues. We developed and implemented a three-dimensional T(1rho)-weighted pulse sequence on a 1.5-T clinical scanner. Copyright 2003

33 CFR 165.T11-304 - Safety zone; Sea World Summer Nights Fireworks; Mission Bay, San Diego, California.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety zone; Sea World Summer Nights Fireworks; Mission Bay, San Diego, California. 165.T11-304 Section 165.T11-304 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY REGULATED NAVIGATION AREAS AND LIMITED ACCESS AREA...

Comparison of 7T and 3T MRI in patients with moyamoya disease.

PubMed

Oh, Byeong Ho; Moon, Hyeong Cheol; Baek, Hyeon Man; Lee, Youn Joo; Kim, Sang Woo; Jeon, Young Jai; Lee, Gun Seok; Kim, Hong Rae; Choi, Jai Ho; Min, Kyung Soo; Lee, Mou Seop; Kim, Young Gyu; Kim, Dong Ho; Kim, Won Seop; Park, Young Seok

2017-04-01

Magnetic resonance imaging and magnetic resonance angiography (MRI/MRA) are widely used for evaluating the moyamoya disease (MMD). This study compared the diagnostic accuracy of 7Tesla (T) and 3T MRI/MRA in MMD. In this case control study, 12 patients [median age: 34years; range (10-66years)] with MMD and 12 healthy controls [median age: 25years; range (22-59years)] underwent both 7T and 3T MRI/MRA. To evaluate the accuracy of MRI/MRA in MMD, five criteria were compared between imaging systems of 7T and 3T: Suzuki grading system, internal carotid artery (ICA) diameter, ivy sign, flow void of the basal ganglia on T2-weighted images, and high signal intensity areas of the basal ganglia on time-of-flight (TOF) source images. No difference was observed between 7T and 3T MRI/MRA in Suzuki stage, ICA diameter, and ivy sign score; while, 7T MRI/MRA showed a higher detection rate in the flow void on T2-weighted images and TOF source images (p<0.001). Receiver operating characteristic curves of both T2 and TOF criteria showed that 7T MRI/MRA had higher sensitivity and specificity than 3T MRI/MRA. Our findings indicate that 7T MRI/MRA is superior to 3T MRI/MRA for the diagnosis of MMD in point of detecting the flow void in basal ganglia by T2-weighted and TOF images. Copyright © 2016. Published by Elsevier Inc.

Quench protection studies of the 11-T Nb 3Sn dipole for the LHC upgrade

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

Bermudez, Susana Izquierdo; Auchmann, Bernhard; Bajas, Hugues

The planned upgrade of the LHC collimation system foresees additional collimators to be installed in the dispersion suppressor areas. Fermilab and CERN are developing an 11 T Nb 3Sn dipole to replace some 8.33 T-15-m-long Nb-Ti LHC main dipoles providing longitudinal space for the collimators. In case of a quench, the large stored energy and the low copper stabilizer fraction make the protection of the 11 T Nb 3Sn dipoles challenging. This paper presents the results of quench protection analysis, including quench protection heater design and efficiency, quench propagation and coil heating. The numerical results are compared with the experimentalmore » data from the 2-m-long Nb 3Sn dipole models. Here, the validated model is used to predict the current decay and hot spot temperature under operating conditions in the LHC and the presently foreseen magnet protection scheme is discussed.« less

Quench protection studies of the 11-T Nb 3Sn dipole for the LHC upgrade

DOE PAGES

Bermudez, Susana Izquierdo; Auchmann, Bernhard; Bajas, Hugues; ...

2016-06-01

The planned upgrade of the LHC collimation system foresees additional collimators to be installed in the dispersion suppressor areas. Fermilab and CERN are developing an 11 T Nb 3Sn dipole to replace some 8.33 T-15-m-long Nb-Ti LHC main dipoles providing longitudinal space for the collimators. In case of a quench, the large stored energy and the low copper stabilizer fraction make the protection of the 11 T Nb 3Sn dipoles challenging. This paper presents the results of quench protection analysis, including quench protection heater design and efficiency, quench propagation and coil heating. The numerical results are compared with the experimentalmore » data from the 2-m-long Nb 3Sn dipole models. Here, the validated model is used to predict the current decay and hot spot temperature under operating conditions in the LHC and the presently foreseen magnet protection scheme is discussed.« less

Effects of Interleukin-12 and Interleukin-15 on Measles-Specific T-Cell Responses in Vaccinated Infants

PubMed Central

YASUKAWA, LINDA L.; ZHANG, CATHRYN Z.; WAKIM, RIMA HANNA; RINKI, MARY; DEHOVITZ, ROSS; ARVIN, ANN M.

2008-01-01

Abstract Understanding the infant host response to measles vaccination is important because of their increased mortality from measles and the need to provide effective protection during the first year of life. Measles-specific T- and B-cell responses are lower in infants after measles vaccination than in adults. To define potential mechanisms, we investigated age-related differences in measles-specific T-cell proliferation, CD40-L expression, and IFN-γ production after measles immunization, and the effects of rhIL-12 and rhIL-15 on these responses. Measles-specific T-cell proliferation and mean IFN-γ release from infant PBMCs were significantly lower when compared with responses of vaccinated children and adults. Infant responses increased to ranges observed in children and adults when both rhIL-12 and rhIL-15 were added to PBMC cultures. Furthermore, a significant rise in T-cell proliferation and IFN-γ release was observed when infant PBMCs were stimulated with measles antigen in the presence of rhIL-12 and rhIL-15 compared to measles antigen alone. CD40-L expression by infant and adult T cells stimulated with measles antigen was comparable, but fewer infant CD40-L+ T cells expressed IFN-γ. These observations suggest that lower measles-specific T-cell immune responses elicited by measles vaccine in infants may be due to diminished levels of key cytokines. PMID:18419254

The relationships between half-life (t1/2) and mean residence time (MRT) in the two-compartment open body model.

PubMed

Sobol, Eyal; Bialer, Meir

2004-05-01

In the one-compartment model following i.v. administration the mean residence time (MRT) of a drug is always greater than its half-life (t(1/2)). However, following i.v. administration, drug plasma concentration (C) versus time (t) is best described by a two-compartment model or a two exponential equation:C=Ae(-alpha t)+Be(-beta t), where A and B are concentration unit-coefficients and alpha and beta are exponential coefficients. The relationships between t(1/2) and MRT in the two-compartment model have not been explored and it is not clear whether in this model too MRT is always greater than t(1/2). In the current paper new equations have been developed that describe the relationships between the terminal t(1/2) (or t(1/2 beta)) and MRT in the two-compartment model following administration of i.v. bolus, i.v. infusion (zero order input) and oral administration (first order input). A critical value (CV) equals to the quotient of (1-ln2) and (1-beta/alpha) (CV=(1-ln2)/(1-beta/alpha)=0.307/(1-beta/alpha)) has been derived and was compared with the fraction (f(1)) of drug elimination or AUC (AUC-area under C vs t curve) associated with the first exponential term of the two-compartment equation (f(1)=A/alpha/AUC). Following i.v. bolus, CV ranges between a minimal value of 0.307 (1-ln2) and infinity. As long as f(1)t(1/2) and vice versa, and when f(1)=CV, then MRT=t(1/2). Following i.v. infusion and oral administration the denominator of the CV equation does not change but its numerator increases to (0.307+beta T/2) (T-infusion duration) and (0.307+beta/ka) (ka-absorption rate constant), respectively. Examples of various drugs are provided. For every drug that after i.v. bolus shows two-compartment disposition kinetics the following conclusions can be drawn (a) When f(1)<0.307, then f(1)t(1/2). (b) When beta/alpha>ln2, then CV>1>f(1) and thus(,) MRT>t(1/2). (c) When ln2>beta/alpha>(ln4-1), then 1>CV>0.5 and thus, in order for t(1/2)>MRT, f(1

Osseous associated cervical spondylomyelopathy at the C2-C3 articular facet joint in 11 dogs.

PubMed

Cooper, C; Gutierrez-Quintana, R; Penderis, J; Gonçalves, R

2015-11-21

In dogs, vertebral canal stenosis at C2-C3 due to articular facet joint degeneration is only sporadically identified. The authors' aims were to review the clinical presentation, MRI characteristics, treatment and outcome of dogs presenting with this condition. Eleven cases were eligible for inclusion. Neurological examination revealed tetraparesis and proprioceptive ataxia in all 4 limbs in 3/11, proprioceptive tetra-ataxia only in 4/11, pelvic limb proprioceptive ataxia in 2/11 and no gait abnormalities in 2/11 dogs. Cervical hyperaesthesia was present in 7/11 dogs. MRI revealed bilateral articular facet joint degeneration in 10/11 cases and unilateral degeneration in one. Surgery was performed in six cases and medical management elected in five. Long-term follow-up information was available for 11 animals. Four of the surgical cases are alive and have no neurological deficits, one was euthanased for an unrelated condition and one lost to follow-up. Of the cases managed medically, three are alive showing no neurological deficits, one is alive still displaying neurological deficits and one euthanased for an unrelated condition whilst still ataxic. This study shows that both medical and surgical management can result in good outcomes in dogs with vertebral canal stenosis resulting from articular facet joint degeneration at the level of C2-C3. British Veterinary Association.

The Relationship between MR Parameters and Biomechanical Quantities of Loaded Human Articular Cartilage in Osteoarthritis: An In-Vitro Study

NASA Astrophysics Data System (ADS)

Juráš, V.; Szomolányi, P.; Gäbler, S.; Frollo, I.; Trattnig, S.

2009-01-01

The aim of this study was to assess the changes in MRI parameters during applied load directly in MR scanner and correlate these changes with biomechanical parameters of human articular cartilage. Cartilage explants from patients who underwent total knee replacement were examined in the micro-imaging system in 3T scanner. Respective MRI parameters (T1 without- and T1 with contrast agent as a marker of proteoglycan content, T2 as a marker of collagen network anisotropy and ADC as a measure of diffusivity) were calculated in pre- and during compression state. Subsequently, these parameters were compared to the biomechanical properties of articular cartilage, instantaneous modulus (I), equilibrium modulus (Eq) and time of tissue relaxation (τ). Significant load-induced changes of T2 and ADC were recorded. High correlation between T1Gd and I (r = 0.6324), and between ADC and Eq (r = -0.4884) was found. Multi-parametric MRI may have great potential in analyzing static and dynamic biomechanical behavior of articular cartilage in early stages of osteoarthritis (OA).

Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection.

PubMed

Ng, Oi-Wing; Chia, Adeline; Tan, Anthony T; Jadi, Ramesh S; Leong, Hoe Nam; Bertoletti, Antonio; Tan, Yee-Joo

2016-04-12

Severe acute respiratory syndrome (SARS) is a highly contagious infectious disease which first emerged in late 2002, caused by a then novel human coronavirus, SARS coronavirus (SARS-CoV). The virus is believed to have originated from bats and transmitted to human through intermediate animals such as civet cats. The re-emergence of SARS-CoV remains a valid concern due to the continual persistence of zoonotic SARS-CoVs and SARS-like CoVs (SL-CoVs) in bat reservoirs. In this study, the screening for the presence of SARS-specific T cells in a cohort of three SARS-recovered individuals at 9 and 11 years post-infection was carried out, and all memory T cell responses detected target the SARS-CoV structural proteins. Two CD8(+) T cell responses targeting the SARS-CoV membrane (M) and nucleocapsid (N) proteins were characterized by determining their HLA restriction and minimal T cell epitope regions. Furthermore, these responses were found to persist up to 11 years post-infection. An absence of cross-reactivity of these CD8(+) T cell responses against the newly-emerged Middle East respiratory syndrome coronavirus (MERS-CoV) was also demonstrated. The knowledge of the persistence of SARS-specific celullar immunity targeting the viral structural proteins in SARS-recovered individuals is important in the design and development of SARS vaccines, which are currently unavailable. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sodium and T1ρ MRI for molecular and diagnostic imaging of articular cartilage†

PubMed Central

Borthakur, Arijitt; Mellon, Eric; Niyogi, Sampreet; Witschey, Walter; Kneeland, J. Bruce; Reddy, Ravinder

2010-01-01

In this article, both sodium magnetic resonance (MR) and T1ρ relaxation mapping aimed at measuring molecular changes in cartilage for the diagnostic imaging of osteoarthritis are reviewed. First, an introduction to structure of cartilage, its degeneration in osteoarthritis (OA) and an outline of diagnostic imaging methods in quantifying molecular changes and early diagnostic aspects of cartilage degeneration are described. The sodium MRI section begins with a brief overview of the theory of sodium NMR of biological tissues and is followed by a section on multiple quantum filters that can be used to quantify both bi-exponential relaxation and residual quadrupolar interaction. Specifically, (i) the rationale behind the use of sodium MRI in quantifying proteoglycan (PG) changes, (ii) validation studies using biochemical assays, (iii) studies on human OA specimens, (iv) results on animal models and (v) clinical imaging protocols are reviewed. Results demonstrating the feasibility of quantifying PG in OA patients and comparison with that in healthy subjects are also presented. The section concludes with the discussion of advantages and potential issues with sodium MRI and the impact of new technological advancements (e.g. ultra-high field scanners and parallel imaging methods). In the theory section on T1ρ, a brief description of (i) principles of measuring T1ρ relaxation, (ii) pulse sequences for computing T1ρ relaxation maps, (iii) issues regarding radio frequency power deposition, (iv) mechanisms that contribute to T1ρ in biological tissues and (v) effects of exchange and dipolar interaction on T1ρ dispersion are discussed. Correlation of T1ρ relaxation rate with macromolecular content and biomechanical properties in cartilage specimens subjected to trypsin and cytokine-induced glycosaminoglycan depletion and validation against biochemical assay and histopathology are presented. Experimental T1ρ data from osteoarthritic specimens, animal models, healthy human

Sodium and T1rho MRI for molecular and diagnostic imaging of articular cartilage.

PubMed

Borthakur, Arijitt; Mellon, Eric; Niyogi, Sampreet; Witschey, Walter; Kneeland, J Bruce; Reddy, Ravinder

2006-11-01

In this article, both sodium magnetic resonance (MR) and T1rho relaxation mapping aimed at measuring molecular changes in cartilage for the diagnostic imaging of osteoarthritis are reviewed. First, an introduction to structure of cartilage, its degeneration in osteoarthritis (OA) and an outline of diagnostic imaging methods in quantifying molecular changes and early diagnostic aspects of cartilage degeneration are described. The sodium MRI section begins with a brief overview of the theory of sodium NMR of biological tissues and is followed by a section on multiple quantum filters that can be used to quantify both bi-exponential relaxation and residual quadrupolar interaction. Specifically, (i) the rationale behind the use of sodium MRI in quantifying proteoglycan (PG) changes, (ii) validation studies using biochemical assays, (iii) studies on human OA specimens, (iv) results on animal models and (v) clinical imaging protocols are reviewed. Results demonstrating the feasibility of quantifying PG in OA patients and comparison with that in healthy subjects are also presented. The section concludes with the discussion of advantages and potential issues with sodium MRI and the impact of new technological advancements (e.g. ultra-high field scanners and parallel imaging methods). In the theory section on T1rho, a brief description of (i) principles of measuring T1rho relaxation, (ii) pulse sequences for computing T1rho relaxation maps, (iii) issues regarding radio frequency power deposition, (iv) mechanisms that contribute to T1rho in biological tissues and (v) effects of exchange and dipolar interaction on T1rho dispersion are discussed. Correlation of T1rho relaxation rate with macromolecular content and biomechanical properties in cartilage specimens subjected to trypsin and cytokine-induced glycosaminoglycan depletion and validation against biochemical assay and histopathology are presented. Experimental T1rho data from osteoarthritic specimens, animal models

12. TOOL ROOM SHOWING LANDIS MACHINE CO. BOL/T THREADER (L), ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

12. TOOL ROOM SHOWING LANDIS MACHINE CO. BOL/T THREADER (L), OSTER MANUFACTURING CO. PIPE MASTER (R), AND OLDMAN KINK, A SHOP-MADE WELDING STRENGTH TESTER (L, BACKGROUND). VIEW NORTHEAST - Oldman Boiler Works, Office/Machine Shop, 32 Illinois Street, Buffalo, Erie County, NY

A Measurement of the t anti-t Cross Section in p anti-p Collisions at s**(1/2) = 1.96-TeV using Dilepton Events with a Lepton plus Track Selection

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

Aaltonen, T.; /Helsinki Inst. of Phys.; Adelman, Jahred A.

This paper reports a measurement of the cross section for the pair production of top quarks in p{bar p} collisions at {radical}s = 1.96 TeV at the Fermilab Tevatron. The data was collected from the CDF II detector in a set of runs with a total integrated luminosity of 1.1 fb{sup -1}. The cross section is measured in the dilepton channel, the subset of t{bar t} events in which both top quarks decay through t {yields} Wb {yields} {ell}{nu}b, where {ell} = e, {mu}, or {tau}. The lepton pair is reconstructed as one identified electron or muon and one isolatedmore » track. The use of an isolated track to identify the second lepton increases the t{bar t} acceptance, particularly for the case in which one W decays as W {yields} {tau}{nu}. The purity of the sample may be further improved at the cost of a reduction in the number of signal events, by requiring an identified b-jet. They present the results of measurements performed with and without the request of an identified b-jet. the former is the first published CDF result for which a b-jet requirement is added to the dilepton selection. In the CDF data there are 129 pretag lepton + track candidate events, of which 69 are tagged. With the tagging information, the sample is divided into tagged and untagged sub-samples, and a combined cross section is calculated by maximizing a likelihood. The result is {sigma}{sub t{bar t}} = 9.6 {+-} 1.2(stat.){sub -0.5}{sup +0.6}(sys.) {+-} 0.6(lum.) pb, assuming a branching ratio of BR(W {yields} {ell}{nu}) = 10.8% and a top mass of m{sub t} = 175 GeV/c{sup 2}.« less

Signalling through NK1.1 triggers NK cells to die but induces NK T cells to produce interleukin-4.

PubMed

Asea, A; Stein-Streilein, J

1998-02-01

In vivo inoculation of specific antibody is an accepted protocol for elimination of specific cell populations. Except for anti-CD3 and anti-CD4, it is not known if the depleted cells are eliminated by signalling through the target molecule or through a more non-specific mechanism. C57BL/6 mice were inoculated with anti-natural killer (NK1.1) monoclonal antibody (mAb). Thereafter spleen cells were harvested, stained for both surface and intracellular markers, and analysed by flow cytometry. As early as 2 hr post inoculation, NK cells were signalled to become apoptotic while signalling through the NK1.1 molecule activated NK1.1+ T-cell receptor (TCR)+ (NK T) cells to increase in number, and produce interleukin-4 (IL-4). Anti NK1.1 mAb was less efficient at signalling apoptosis in NK cells when NK T-cell deficient [beta 2-microglobulin beta 2m-deficient] mice were used compared with wild type mice. Efficient apoptotic signalling was restored when beta 2m-deficient mice were reconstituted with NK T cells. NK-specific antibody best signals the apoptotic process in susceptible NK cells when resistant NK T cells are present, activated, and secrete IL-4.

mhpT encodes an active transporter involved in 3-(3-hydroxyphenyl)propionate catabolism by Escherichia coli K-12.

PubMed

Xu, Ying; Chen, Bing; Chao, Hongjun; Zhou, Ning-Yi

2013-10-01

Escherichia coli K-12 utilizes 3-(3-hydroxyphenyl)propionate (3HPP) as a sole carbon and energy source. Among the genes in its catabolic cluster in the genome, mhpT was proposed to encode a hypothetical transporter. Since no transporter for 3HPP uptake has been identified, we investigated whether MhpT is responsible for 3HPP uptake. MhpT fused with green fluorescent protein was found to be located at the periphery of cells by confocal microscopy, consistent with localization to the cytoplasmic membrane. Gene knockout and complementation studies clearly indicated that mhpT is essential for 3HPP catabolism in E. coli K-12 W3110 at pH 8.2. Uptake assays with (14)C-labeled substrates demonstrated that strain W3110 and strain W3110ΔmhpT containing recombinant MhpT specifically transported 3HPP but not benzoate, 3-hydroxybenzoate, or gentisate into cells. Energy dependence assays suggested that MhpT-mediated 3HPP transport was driven by the proton motive force. The change of Ala-272 of MhpT to a histidine, surprisingly, resulted in enhanced transport activity, and strain W3110ΔmhpT containing the MhpT A272H mutation had a slightly higher growth rate than the wild-type strain at pH 8.2. Hence, we demonstrated that MhpT is a specific 3HPP transporter and vital for E. coli K-12 W3110 growth on this substrate under basic conditions.

Toxicity of lanthanum oxide nanoparticles to the fungus Moniliella wahieum Y12T isolated from biodiesel.

PubMed

Zhang, Lin; Zhou, Lingyan; Li, Qing X; Liang, Hong; Qin, Huaming; Masutani, Stephen; Yoza, Brandon

2018-05-01

Moniliella wahieum Y12 T , isolated from biodiesel was used as a model organism to assess the use of lanthanum oxide (La 2 O 3 ) (60-80 nm) and silver oxide (AgO) (10-40 nm) nanoparticles as potential fungal inhibitors. This is the first study to investigate the use of nanoscale La 2 O 3 as a eukaryotic bio-inhibitor. The AgO nanoparticles were relatively effective at inhibiting the growth of M. wahieum Y12 T . The half maximal effective concentration (EC 50 ) for AgO was 0.012 mg/mL as compared with 4.63 mg/mL of La 2 O 3 . Fluorescein diacetate analysis showed that AgO nanoparticles significantly reduced metabolic activity in M. wahieum Y12 T . The results of this study indicated that AgO nanoparticles can be a nonspecific inhibitor for the treatment of M. wahieum Y12 T , a eukaryotic biodiesel contaminant. Copyright © 2018 Elsevier Ltd. All rights reserved.

Isoflavone Malonyltransferases GmIMaT1 and GmIMaT3 Differently Modify Isoflavone Glucosides in Soybean (Glycine max) under Various Stresses

PubMed Central

Ahmad, Muhammad Z.; Li, Penghui; Wang, Junjie; Rehman, Naveed Ur; Zhao, Jian

2017-01-01

Malonylated isoflavones are the major forms of isoflavonoids in soybean plants, the genes responsible for their biosyntheses are not well understood, nor their physiological functions. Here we report a new benzylalcohol O-acetyltransferase, anthocyanin O-hydroxycinnamoyltransferase, anthranilate N-hydroxycinnamoyl/benzoyltransferase, deacetylvindoline 4-O-acetyltransferase (BAHD) family isoflavone glucoside malonyltransferase GmIMaT1, and GmIMaT3, which is allelic to the previously characterized GmMT7 and GmIF7MaT. Biochemical studies showed that recombinant GmIMaT1 and GmIMaT3 enzymes used malonyl-CoA and several isoflavone 7-O-glucosides as substrates. The Km values of GmIMaT1 for glycitin, genistin, and daidzin were 13.11, 23.04, and 36.28 μM, respectively, while these of GmIMaT3 were 12.94, 26.67, and 30.12 μM, respectively. Transgenic hairy roots overexpressing both GmIMaTs had increased levels of malonyldaidzin and malonylgenistin, and contents of daidzin and glycitin increased only in GmIMaT1-overexpression lines. The increased daidzein and genistein contents were detected only in GmIMaT3-overexpression lines. Knockdown of GmIMaT1 and GmIMaT3 reduced malonyldaidzin and malonylgenistin contents, and affected other isoflavonoids differently. GmIMaT1 is primarily localized to the endoplasmic reticulum while GmIMaT3 is primarily in the cytosol. By examining their transcript changes corresponding to the altered isoflavone metabolic profiles under various environmental and hormonal stresses, we probed the possible functions of GmIMaTs. Two GmIMaTs displayed distinct tissue expression patterns and respond differently to various factors in modifying isoflavone 7-O-glucosides under various stresses. PMID:28559900

Yang-Baxter deformations of W2,4 × T1,1 and the associated T-dual models

NASA Astrophysics Data System (ADS)

Sakamoto, Jun-ichi; Yoshida, Kentaroh

2017-08-01

Recently, for principal chiral models and symmetric coset sigma models, Hoare and Tseytlin proposed an interesting conjecture that the Yang-Baxter deformations with the homogeneous classical Yang-Baxter equation are equivalent to non-abelian T-dualities with topological terms. It is significant to examine this conjecture for non-symmetric (i.e., non-integrable) cases. Such an example is the W2,4 ×T 1 , 1 background. In this note, we study Yang-Baxter deformations of type IIB string theory defined on W2,4 ×T 1 , 1 and the associated T-dual models, and show that this conjecture is valid even for this case. Our result indicates that the conjecture would be valid beyond integrability.

hisT is part of a multigene operon in Escherichia coli K-12.

PubMed Central

Marvel, C C; Arps, P J; Rubin, B C; Kammen, H O; Penhoet, E E; Winkler, M E

1985-01-01

The Escherichia coli K-12 hisT gene has been cloned, and its organization and expression have been analyzed on multicopy plasmids. The hisT gene, which encodes tRNA pseudouridine synthase I (PSUI), was isolated on a Clarke-Carbon plasmid known to contain the purF gene. The presence of the hisT gene on this plasmid was suggested by its ability to restore both production of PSUI enzymatic activity and suppression of amber mutations in a hisT mutant strain. A 2.3-kilobase HindIII-ClaI restriction fragment containing the hisT gene was subcloned into plasmid pBR322, and the resulting plasmid (designated psi 300) was mapped with restriction enzymes. Complementation analysis with different kinds of hisT mutations and tRNA structural analysis confirmed that plasmid psi 300 contained the hisT structural gene. Enzyme assays showed that plasmid psi 300 overproduced PSUI activity by ca. 20-fold compared with the wild-type level. Subclones containing restriction fragments from plasmid psi 300 inserted downstream from the lac promoter established that the hisT gene is oriented from the HindIII site toward the ClaI site. Other subclones and derivatives of plasmid psi 300 containing insertion or deletion mutations were constructed and assayed for production of PSUI activity and production of proteins in minicells. These experiments showed that: (i) the proximal 1.3-kilobase HindIII-BssHII restriction fragment contains a promoter for the hisT gene and encodes a 45,000-dalton polypeptide that is not PSUI; (ii) the distal 1.0-kilobase BssHII-ClaI restriction fragment encodes the 31,000-dalton PSUI polypeptide; (iii) the 45,000-dalton polypeptide is synthesized in an approximately eightfold excess compared with PSUI; and (iv) synthesis of the two polypeptides is coupled, suggesting that the two genes are part of an operon. Insertion of mini-Mu d1 (lac Km) phage into plasmid psi 300 confirmed that the hisT gene is the downstream gene in the operon. Images PMID:2981810

Tumor-targeted IL-2 amplifies T cell-mediated immune response induced by gene therapy with single-chain IL-12

PubMed Central

Lode, Holger N.; Xiang, Rong; Duncan, Steven R.; Theofilopoulos, Argyrios N.; Gillies, Stephen D.; Reisfeld, Ralph A.

1999-01-01

Induction, maintenance, and amplification of tumor-protective immunity after cytokine gene therapy is essential for the clinical success of immunotherapeutic approaches. We investigated whether this could be achieved by single-chain IL-12 (scIL-12) gene therapy followed by tumor-targeted IL-2 using a fusion protein containing a tumor-specific recombinant anti-ganglioside GD2 antibody and IL-2 (ch14.18-IL-2) in a poorly immunogenic murine neuroblastoma model. Herein, we demonstrate the absence of liver and bone marrow metastases after a lethal challenge with NXS2 wild-type cells only in mice (five of six animals) vaccinated with scIL-12-producing NXS2 cells and given a booster injection of low-dose ch14.18-IL-2 fusion protein. This tumor-protective immunity was effective 3 months after initial vaccination, in contrast to control animals treated with a nonspecific fusion protein or an equivalent mixture of antibody and IL-2. Only vaccinated mice receiving the tumor-specific ch14.18-IL-2 fusion protein revealed a reactivation of CD8+ T cells and subsequent MHC class I-restricted tumor target cell lysis in vitro. The sequential increase in the usage of TCR chains Vβ11 and -13 in mouse CD8+ T cells after vaccination and amplification with ch14.18-IL-2 suggests that the initial polyclonal CD8+ T cell response is effectively boosted by targeted IL-2. In conclusion, we demonstrate that a successful boost of a partially protective memory T cell immune response that is induced by scIL-12 gene therapy could be generated by tumor-specific targeting of IL-2 with a ch14.18-IL-2 fusion protein. This approach could increase success rates of clinical cancer vaccine trials. PMID:10411920

IL-12 and IL-23 Production in Toxoplasma gondii- or LPS-Treated Jurkat T Cells via PI3K and MAPK Signaling Pathways.

PubMed

Ismail, Hassan Ahmed Hassan Ahmed; Kang, Byung-Hun; Kim, Jae-Su; Lee, Jae-Hyung; Choi, In-Wook; Cha, Guang-Ho; Yuk, Jae-Min; Lee, Young-Ha

2017-12-01

IL-12 and IL-23 are closely related in structure, and have been shown to play crucial roles in regulation of immune responses. However, little is known about the regulation of these cytokines in T cells. Here, we investigated the roles of PI3K and MAPK pathways in IL-12 and IL-23 production in human Jurkat T cells in response to Toxoplasma gondii and LPS. IL-12 and IL-23 production was significantly increased in T cells after stimulation with T. gondii or LPS. T. gondii and LPS increased the phosphorylation of AKT, ERK1/2, p38 MAPK, and JNK1/2 in T cells from 10 min post-stimulation, and peaked at 30-60 min. Inhibition of the PI3K pathway reduced IL-12 and IL-23 production in T. gondii-infected cells, but increased in LPS-stimulated cells. IL-12 and IL-23 production was significantly reduced by ERK1/2 and p38 MAPK inhibitors in T. gondii- and LPS-stimulated cells, but not in cells treated with a JNK1/2 inhibitor. Collectively, IL-12 and IL-23 production was positively regulated by PI3K and JNK1/2 in T. gondii-infected Jurkat cells, but negatively regulated in LPS-stimulated cells. And ERK1/2 and p38 MAPK positively regulated IL-12 and IL-23 production in Jurkat T cells. These data indicate that T. gondii and LPS induced IL-12 and IL-23 production in Jurkat T cells through the regulation of the PI3K and MAPK pathways; however, the mechanism underlying the stimulation of IL-12 and IL-23 production by T. gondii in Jurkat T cells is different from that of LPS.

40 CFR Appendix B to Subpart T of... - General Provisions Applicability to Subpart T

Code of Federal Regulations, 2014 CFR

2014-07-01

... Subpart T B Appendix B to Subpart T of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... CATEGORIES National Emission Standards for Halogenated Solvent Cleaning Pt. 63, Subpt. T, App. B Appendix B... specified in an applicable requirement. 63.1(a) (12)-(14) Yes Yes 63.1(b)(1) No No Subpart T specifies...

High-temperature creep properties and life predictions for T91 and T92 steels

NASA Astrophysics Data System (ADS)

Pan, J. P.; Tu, S. H.; Sun, G. L.; Zhu, X. W.; Tan, L. J.; Hu, B.

2018-01-01

9-11%Cr heat-resistant steels are widely used in high-temperature and high-pressure boilers of advanced power plants. In the current paper, high-temperature creep behaviors of T91 and T92 steels have been investigated. Creep tests were performed for both steels at varied temperatures. The creep mechanisms of T91 and T92 steels were elucidated by analyzing the creep rupture data of the two steels. In addition, Manson-Haferd model was employed to predict the creep life of T91 and T92 steels, the results of which indicate that the Manson-Haferd model works well for the two steels.

T-614, a novel immunomodulator, attenuates joint inflammation and articular damage in collagen-induced arthritis

PubMed Central

Du, Fang; Lü, Liang-jing; Fu, Qiong; Dai, Min; Teng, Jia-lin; Fan, Wei; Chen, Shun-le; Ye, Ping; Shen, Nan; Huang, Xin-fang; Qian, Jie; Bao, Chun-de

2008-01-01

Introduction T-614 is a novel oral antirheumatic agent for the treatment of rheumatoid arthritis. Whether it has immunomodulatory or disease-modifying properties and its mechanism of action are largely undetermined. Methods Rats with collagen-induced arthritis (CIA) were treated with T-614 (5 and 20 mg/kg) daily. Animals receiving methotrexate (1 mg/kg every 3 days) and the nonsteroidal anti-inflammatory agent nimesulide (10 mg/kg per day) were used as controls. A combination therapy group was treated with both T-614(10 mg/kg per day) and methotrexate (1 mg/kg every 3 days). Hind paw swelling was evaluated and radiographic scores calculated. Serum cytokine levels were assessed by Bio-plex analysis. Quantitative PCR was used to evaluate expression of mRNA for interferon-γ, IL-4 and IL-17. Serum IL-17 and anti-type II collagen antibodies (total IgG, IgG1, IgG2a, IgG2b and IgM) were measured using ELISA. Results Oral T-614 inhibited paw swelling and offered significant protection against arthritis-induced cartilage and bone erosion, comparable to the effects of methotrexate. CIA rats treated with T-614 exhibited decreases in both mRNA expression of IL-17 in peripheral blood mononuclear cells and lymph node cells, and circulating IL-17 in a dose-dependent manner. T-614 also reduced serum levels of tumor necrosis factor-α, IL-1β and IL-6. A synergistic effect was observed for the combination of methotrexate and T-614. In addition, T-614 (20 mg/kg per day) depressed production of anti-type II collagen antibodies and differentially affected levels of IgG2a subclasses in vivo, whereas IgM level was decreased without any change in the IgG1 level. Together, the findings presented here indicate that the novel agent T-614 has disease-modifying effects against experimental arthritis, as opposed to nimesulide. Conclusions Our data suggested that T-614 is an effective disease-modifying agent that can prevent bone/cartilage destruction and inflammation in in CIA rats

Regeneration of hyaline articular cartilage with irradiated transforming growth factor beta1-producing fibroblasts.

PubMed

Song, Sun U; Hong, Young-Jin; Oh, In-Suk; Yi, Youngsuk; Choi, Kyoung Baek; Lee, Jung Woo; Park, Kwang-Won; Han, Jeoung-Uk; Suh, Jun-Kyu; Lee, Kwan Hee

2004-01-01

The regeneration of hyaline articular cartilage by cell-mediated gene therapy using transforming growth factor beta(1) (TGF-beta(1))-producing fibroblasts (NIH 3T3-TGF-beta(1)) has been reported previously. In this study, we investigated whether TGF-beta(1)-producing fibroblasts irradiated with a lethal dose of radiation are still capable of inducing the regeneration of hyaline articular cartilage. NIH 3T3TGF-beta(1) fibroblasts were exposed to doses of 20, 40, or 80 Gy, using a irradiator, and then injected into artificially made partial defects on the femoral condyle of rabbit knee joints. The rabbits were killed 3 or 6 weeks postinjection and hyaline articular cartilage regeneration was evaluated by histological and immunohistochemical staining (n = 5 per each group). Irradiated NIH 3T3-TGFbeta(1) fibroblasts started to die rapidly 3 days after irradiation; moreover, the kinetics of their viability were similar regardless of the radiation intensity. TGF-beta1 expression, measured by ELISA, showed that the TGF-beta(1) protein produced from the irradiated cells peaked 5 days after irradiation and thereafter declined rapidly. Complete filling of the defect with reparative tissue occurred in all the groups, although variations were observed in terms of the nature of the repair tissue. Histological and immunohistochemical staining of the repair tissue showed that the tissue newly formed by irradiated NIH 3T3-TGF-beta(1) fibroblasts after exposure to 20 Gy had hyaline cartilage-like characteristics, as was observed in the nonirradiated controls. On the other hand, the repair tissue formed by NIH 3T3-TGF-beta(1) fibroblasts irradiated with 40 or 80 Gy showed more fibrous cartilage-like tissue. These results suggest that TGF-beta(1)-producing fibroblasts irradiated up to a certain level of lethal dose (i.e., 20 Gy) are able to induce normal-appearing articular cartilage in vivo. Therefore, irradiated heterologous cell-mediated TGF-beta(1) gene therapy may be clinically

Spallation of Cu by. pi. /sup -/ across the T = 1/2 resonances and at high energy

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

Haustein, P.E.

1979-09-01

Relative yields of 11 selected products (/sup 24/Na, /sup 43,44,46,47,48/Sc, /sup 55,56,57,58,60/Co) have been measured for the interaction of 0.6- and 0.9-GeV negative pions with Cu. In addition, the yields of /sup 24/Na and /sup 58/Co from Cu have been measured for 12-GeV ..pi../sup -/. Results at the two lower energies which correspond to the first two isospin T = 1/2 pion-nucleon resonances are compared with earlier studies of Cu spallation by ..pi../sup -/ at energies across the first T = 3/2 resonance, i.e., 50 to 350 MeV. The 12-GeV ..pi../sup -/ results are compared with similar investigations in whichmore » both energetic protons and heavy ions were used. For E/sub ..pi../ > or = 0.5 GeV no evidence of strong resonance effects can be found in the pattern of the spallation yields. As the pion energy is raised a smooth trend of enhanced yields of deep spallation products to near-target yields closely parallels the same trend observed for both high-energy proton and heavy-ion spallation of Cu. These results indicate that at high energy, pi-mesic spallation exhibits the same features of limiting fragmentation and factorization of the isotopic yields that have been observed previously in hadron induced spallation.« less

Tumor cell-released TLR4 ligands stimulate Gr-1+CD11b+F4/80+ cells to induce apoptosis of activated T cells.

PubMed

Liu, Yan-Yan; Sun, Ling-Cong; Wei, Jing-Jing; Li, Dong; Yuan, Ye; Yan, Bin; Liang, Zhi-Hui; Zhu, Hui-Fen; Xu, Yong; Li, Bo; Song, Chuan-Wang; Liao, Sheng-Jun; Lei, Zhang; Zhang, Gui-Mei; Feng, Zuo-Hua

2010-09-01

Gr-1(+)CD11b(+)F4/80(+) cells play important roles in tumor development and have a negative effect on tumor immunotherapy. So far, the mechanisms underlying the regulation of their immunosuppressive phenotype by classical and alternative macrophage activation stimuli are not well elucidated. In this study, we found that molecules from necrotic tumor cells (NTC-Ms) stimulated Gr-1(+)CD11b(+)F4/80(+) cells to induce apoptosis of activated T cells but not nonstimulated T cells. The apoptosis-inducing capacity was determined by higher expression levels of arginase I and IL-10 relative to those of NO synthase 2 and IL-12 in Gr-1(+)CD11b(+)F4/80(+) cells, which were induced by NTC-Ms through TLR4 signaling. The apoptosis-inducing capacity of NTC-Ms-stimulated Gr-1(+)CD11b(+)F4/80(+) cells could be enhanced by IL-10. IFN-gamma may reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells only if their response to IFN-gamma was not attenuated. However, the potential of Gr-1(+)CD11b(+)F4/80(+) cells to express IL-12 in response to IFN-gamma could be attenuated by tumor, partially due to the existence of active STAT3 in Gr-1(+)CD11b(+)F4/80(+) cells and NTC-Ms from tumor. In this situation, IFN-gamma could not effectively reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells. Tumor immunotherapy with 4-1BBL/soluble programmed death-1 may significantly reduce, but not abolish the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells in local microenvironment. Blockade of TLR4 signaling could further reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and enhance the suppressive effect of 4-1BBL/soluble form of programmed death-1 on tumor growth. These findings indicate the relationship of distinct signaling pathways with apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and emphasize the importance of blocking TLR4 signaling to prevent the induction of T cell apoptosis by Gr-1(+)CD11b(+)F4/80(+) cells.

The T-100-12.8 family of cogeneration steam turbines: Yesterday, today, and tomorrow

NASA Astrophysics Data System (ADS)

Valamin, A. E.; Kultyshev, A. Yu.; Shibaev, T. L.; Sakhnin, Yu. A.; Stepanov, M. Yu.

2013-08-01

The T-100-12.8 turbine and its versions, a type of cogeneration steam turbines that is among best known, unique, and most widely used ones in Russia and abroad, are considered. A list of turbine design versions and quantities in which they were produced, their technical and economic indicators, design features, schematic solutions used in different design versions, and a list of solutions available in a comprehensive portfolio offered for modernizing type T-100-12.8 turbines are presented. Information about amounts in which turbines of the last version are supplied currently and supposed to be supplied soon is given.

Molecular t-matrices for Low-Energy Electron Diffraction (TMOL v1.1)

NASA Astrophysics Data System (ADS)

Blanco-Rey, Maria; de Andres, Pedro; Held, Georg; King, David A.

2004-08-01

We describe a FORTRAN-90 program that computes scattering t-matrices for a molecule. These can be used in a Low-Energy Electron Diffraction program to solve the molecular structural problem very efficiently. The intramolecular multiple scattering is computed within a Dyson-like approach, using free space Green propagators in a basis of spherical waves. The advantage of this approach is related to exploiting the chemical identity of the molecule, and to the simplicity to translate and rotate these t-matrices without performing a new multiple-scattering calculation for each configuration. FORTRAN-90 routines for rotating the resulting t-matrices using Wigner matrices are also provided. Program summaryTitle of program: TMOL Catalogue number: ADUF Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADUF Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland. Computers: Alpha ev6-21264 (700 MHz) and Pentium-IV. Operating systems: Digital UNIX V5.0 and Linux (Red Hat 8.0). Programming language: FORTRAN-90/95 (Compaq True64 compiler, and Intel Fortran Compiler 7.0 for Linux). High-speed storage required for the test run: minimum 64 Mbytes, it can grow to more depending on the system considered. Disk storage required: None. No. of bits in a word: 64 and 32. No. of lines in distributed program, including test data etc.: 5404 No. of bytes in distributed program, including test data etc.: 59 856 Distribution format: tar.gz Nature of problem: We describe the FORTRAN-90 program TMOL (v1.1) for the computation of non-diagonal scattering t-matrices for molecules or any other poly-atomic sub-unit of surface structures. These matrices can be used in an standard Low-Energy Electron Diffraction program, such as LEED90 or CLEED. Method of solution: A general non-diagonal t-matrix is assumed for the atoms or more general scatterers forming the molecule. The molecular t-matrix is solved adding the possible intramolecular multiple scattering events

Early postoperative cartilage evaluation by magnetic resonance imaging using T2 mapping after arthroscopic partial medial meniscectomy.

PubMed

Kato, Kammei; Arai, Yuji; Ikoma, Kazuya; Nakagawa, Shuji; Inoue, Hiroaki; Kan, Hiroyuki; Matsuki, Tomohiro; Fujiwara, Hiroyoshi; Kubo, Toshikazu

2015-12-01

This study was performed to quantitatively evaluate postoperative changes in cartilage by T2 mapping after arthroscopic partial medial meniscectomy. The study enrolled 17 patients with 20 knees that underwent arthroscopic partial medial meniscectomy. MRI was performed preoperatively and at six months postoperatively, with subjects evaluated by T2 mapping of the central part of the medial condyle of the femur in the sagittal plane. Regions of interest (ROIs) were set at 10 points between the point of intersection of the anatomical axis of the femur and the articular surface of the medial condyle and posterior area approximately 90 degrees to the anatomical axis. Pre- and postoperative T2 values at each ROI were evaluated. Postoperative T2 values were significantly longer than preoperative values at approximately 20, 30, 40, and 50 degrees to the anatomical axis of the femur. The maximum change between pre- and postoperative T2 values was +6.65% at 30 degrees to the anatomical axis. Mechanical stress at positions approximately 20, 30, 40, and 50 degrees relative to the anatomical axis of the femur increased soon after arthroscopic medial meniscectomy. These findings indicate the start of degeneration, via disorganization of collagen arrays, of the articular cartilage and increased water content. Copyright © 2015. Published by Elsevier Inc.

Oncologic Safety of Local Excision Compared With Total Mesorectal Excision for ypT0-T1 Rectal Cancer: A Propensity Score Analysis.

PubMed

Jung, Sung Min; Yu, Chang Sik; Park, In Ja; Kim, Tae Won; Kim, Jong Hoon; Yoon, Yong Sik; Lim, Seok-Byung; Kim, Jin Cheon

2016-05-01

Good oncologic outcomes, demonstrated by a complete pathologic response after preoperative chemoradiotherapy (PCRT), have led to local excision (LE) in selected patients with rectal cancer. We evaluated the oncologic safety of LE compared with total mesorectal excision (TME) in patients with ypT0-T1 rectal cancer.A retrospective review of 304 patients who underwent PCRT, followed by LE or TME, for ypT0-T1 rectal cancer was performed. Propensity scores were computed and used to match groups (LE:TME = 1:1), and analysis of disease-free survival (DFS) and overall survival (OS) was made by comparing patients who underwent LE or TME. Prognostic factors of relapse were analyzed for all patients.Tumor categories were ypT0 in 25 (61.9%) cases, ypTis in 6 (14.3%) cases, and ypT1 in 11 (26.2%) cases for the LE group, and ypT0 in 28 (66.7%) cases, ypTis in 4 (9.5%) cases, and ypT1 in 10 (23.8%) cases for the matched TME patients. There was no significant difference between the matched LE and TME groups in relapse (4.8% and 7.14%, respectively; P = 0.646), 5-year DFS (95.2% vs 91.6%; P = 0.33) and 5-year OS (96.6% vs 88.0%; P = 0.238). In the multivariate Cox regression analysis, tumor distance from the anal verge (hazard ratio [HR] = 0.78; 95% confidence interval (CI) = 0.616-0.992) and the tumor grade (HR = 4.29; 95% CI = 1.430-12.886) were significantly associated with the recurrence risk.LE results in oncologic outcomes that are comparable to those achieved by TME in selected patients with ypT0-T1 rectal cancer after PCRT.

Total resection of any segment of the lateral meniscus may cause early cartilage degeneration: Evaluation by magnetic resonance imaging using T2 mapping.

PubMed

Murakami, Koji; Arai, Yuji; Ikoma, Kazuya; Kato, Kammei; Inoue, Hiroaki; Nakagawa, Shuji; Fujii, Yuta; Ueshima, Keiichiro; Fujiwara, Hiroyoshi; Kubo, Toshikazu

2018-06-01

The aim of this study was to perform quantitative evaluation of degeneration of joint cartilage using T2 mapping in magnetic resonance imaging (MRI) after arthroscopic partial resection of the lateral meniscus.The subjects were 21 patients (23 knees) treated with arthroscopic partial resection of the lateral meniscus. MRI was performed for all knees before surgery and 6 months after surgery to evaluate the center of the lateral condyle of the femur in sagittal images for T2 mapping. Ten regions of interest (ROIs) on the articular cartilage were established at 10-degree intervals, from the point at which the femur shaft crossed the lateral femoral condyle joint to the articular cartilage 90° relative to the femur shaft. Preoperative and postoperative T2 values were evaluated at each ROI. Age, sex, body mass index, femorotibial angle, Tegner score, and amount of meniscal resection were evaluated when the T2 value increased more than 6% at 30°.T2 values at approximately 10 °, 20 °, 30 °, 40 °, 50 °, and 60 ° degrees relative to the anatomical axis of the femur were significantly greater postoperatively (3.1, 3.6, 5.5, 4.4, 5.0, 6.4%, respectively) than preoperatively. A >6% increase at 30° was associated with total resection of any segment of the meniscus.Degeneration of the articular cartilage, as shown by the disorganization of collagen arrays at positions approximately 10 °, 20 °, 30 °, 40 °, 50 °, and 60 ° relative to the anatomical axis of the femur, may start soon after arthroscopic lateral meniscectomy. Total resection of any segment of the lateral meniscus may cause T2 elevation of articular cartilage of lateral femoral condyle.

Modulation of collagen-induced arthritis by adenovirus-mediated intra-articular expression of modified collagen type II.

PubMed

Tang, Bo; Cullins, David L; Zhou, Jing; Zawaski, Janice A; Park, Hyelee; Brand, David D; Hasty, Karen A; Gaber, M Waleed; Stuart, John M; Kang, Andrew H; Myers, Linda K

2010-01-01

Rheumatoid arthritis (RA) is a systemic disease manifested by chronic inflammation in multiple articular joints, including the knees and small joints of the hands and feet. We have developed a unique modification to a clinically accepted method for delivering therapies directly to the synovium. Our therapy is based on our previous discovery of an analog peptide (A9) with amino acid substitutions made at positions 260 (I to A), 261 (A to B), and 263 (F to N) that could profoundly suppress immunity to type II collagen (CII) and arthritis in the collagen-induced arthritis model (CIA). We engineered an adenoviral vector to contain the CB11 portion of recombinant type II collagen and used PCR to introduce point mutations at three sites within (CII124-402, 260A, 261B, 263D), (rCB11-A9) so that the resulting molecule contained the A9 sequence at the exact site of the wild-type sequence. We used this construct to target intra-articular tissues of mice and utilized the collagen-induced arthritis model to show that this treatment strategy provided a sustained, local therapy for individual arthritic joints, effective whether given to prevent arthritis or as a treatment. We also developed a novel system for in vivo bioimaging, using the firefly luciferase reporter gene to allow serial bioluminescence imaging to show that luciferase can be detected as late as 18 days post injection into the joint. Our therapy is unique in that we target synovial cells to ultimately shut down T cell-mediated inflammation. Its effectiveness is based on its ability to transform potential inflammatory T cells and/or bystander T cells into therapeutic (regulatory-like) T cells which secrete interleukin (IL)-4. We believe this approach has potential to effectively suppress RA with minimal side effects.

Modulation of collagen-induced arthritis by adenovirus-mediated intra-articular expression of modified collagen type II

PubMed Central

2010-01-01

Introduction Rheumatoid arthritis (RA) is a systemic disease manifested by chronic inflammation in multiple articular joints, including the knees and small joints of the hands and feet. We have developed a unique modification to a clinically accepted method for delivering therapies directly to the synovium. Our therapy is based on our previous discovery of an analog peptide (A9) with amino acid substitutions made at positions 260 (I to A), 261 (A to B), and 263 (F to N) that could profoundly suppress immunity to type II collagen (CII) and arthritis in the collagen-induced arthritis model (CIA). Methods We engineered an adenoviral vector to contain the CB11 portion of recombinant type II collagen and used PCR to introduce point mutations at three sites within (CII124-402, 260A, 261B, 263D), (rCB11-A9) so that the resulting molecule contained the A9 sequence at the exact site of the wild-type sequence. Results We used this construct to target intra-articular tissues of mice and utilized the collagen-induced arthritis model to show that this treatment strategy provided a sustained, local therapy for individual arthritic joints, effective whether given to prevent arthritis or as a treatment. We also developed a novel system for in vivo bioimaging, using the firefly luciferase reporter gene to allow serial bioluminescence imaging to show that luciferase can be detected as late as 18 days post injection into the joint. Conclusions Our therapy is unique in that we target synovial cells to ultimately shut down T cell-mediated inflammation. Its effectiveness is based on its ability to transform potential inflammatory T cells and/or bystander T cells into therapeutic (regulatory-like) T cells which secrete interleukin (IL)-4. We believe this approach has potential to effectively suppress RA with minimal side effects. PMID:20615221

The constitutional t(11;22): implications for a novel mechanism responsible for gross chromosomal rearrangements

PubMed Central

Kurahashi, H; Inagaki, H; Ohye, T; Kogo, H; Tsutsumi, M; Kato, T; Tong, M; Emanuel, BS

2012-01-01

The constitutional t(11;22)(q23;q11) is the most common recurrent non-Robertsonian translocation in humans. The breakpoint sequences of both chromosomes are characterized by several hundred base pairs of palindromic AT-rich repeats (PATRRs). Similar PATRRs have also been identified at the breakpoints of other nonrecurrent translocations, suggesting that PATRR-mediated chromosomal translocation represents one of the universal pathways for gross chromosomal rearrangement in the human genome. We propose that PATRRs have the potential to form cruciform structures through intrastrand-base pairing in single-stranded DNA, creating a source of genomic instability and leading to translocations. Indeed, de novo examples of the t(11;22) are detected at a high frequency in sperm from normal healthy males. This review synthesizes recent data illustrating a novel paradigm for an apparent spermatogenesis-specific translocation mechanism. This observation has important implications pertaining to the predominantly paternal origin of de novo gross chromosomal rearrangements in humans. PMID:20507342

Evaluation of Water Retention in Lumbar Intervertebral Disks Before and After Exercise Stress With T2 Mapping.

PubMed

Chokan, Kou; Murakami, Hideki; Endo, Hirooki; Mimata, Yoshikuni; Yamabe, Daisuke; Tsukimura, Itsuko; Oikawa, Ryosuke; Doita, Minoru

2016-04-01

T2 mapping was used to quantify moisture content of the lumbar spinal disk nucleus pulposus (NP) and annulus fibrosus before and after exercise stress, and after rest, to evaluate the intervertebral disk function. To clarify water retention in intervertebral disks of the lumbar vertebrae by performing magnetic resonance imaging before and after exercise stress and quantitatively measuring changes in moisture content of intervertebral disks with T2 mapping. To date, a few case studies describe functional evaluation of articular cartilage with T2 mapping; however, T2 mapping to the functional evaluation of intervertebral disks has rarely been applied. Using T2 mapping might help detect changes in the moisture content of intervertebral disks, including articular cartilage, before and after exercise stress, thus enabling the evaluation of changes in water retention shock absorber function. Subjects, comprising 40 healthy individuals (males: 26, females: 14), underwent magnetic resonance imaging T2 mapping before and after exercise stress and after rest. Image J image analysis software was then used to set regions of interest in the obtained images of the anterior annulus fibrosus, posterior annulus fibrosus, and NP. T2 values were measured and compared according to upper vertebrae position and degeneration grade. T2 values significantly decreased in the NP after exercise stress and significantly increased after rest. According to upper vertebrae position, in all of the upper vertebrae positions, T2 values for the NP significantly decreased after exercise stress and significantly increased after rest. According to the degeneration grade, in the NP of grade 1 and 2 cases, T2 values significantly decreased after exercise stress and significantly increased after rest. T2 mapping could be used to not only diagnose the degree of degeneration but also evaluate intervertebral disk function. 3.

Cardio Respiratory Adaptations with Long Term Personalized Exercise Program in a T12 Spinal Cord Injured Person

ERIC Educational Resources Information Center

Vasiliadis, Angelo; Christoulas, Kosmas; Evaggelinou, Christina; Vrabas, Ioannis

2009-01-01

The purpose of this study was to investigate the physiological adaptations in cardio respiratory endurance with a personalized exercise program with arm-cranking exercise in a paraplegic person (incomplete T12 spinal cord injury). A 32 year-old man with spinal cord injury (T12) participated in the present study performing 30 minutes arm cranking…

IDEAL 3D spoiled gradient echo of the articular cartilage of the knee on 3.0 T MRI: a comparison with conventional 3.0 T fast spin-echo T2 fat saturation image.

PubMed

Han, Chul Hee; Park, Hee Jin; Lee, So Yeon; Chung, Eun Chul; Choi, Seon Hyeong; Yun, Ji Sup; Rho, Myung Ho

2015-12-01

Many two-dimensional (2D) morphologic cartilage imaging sequences have disadvantages such as long acquisition time, inadequate spatial resolution, suboptimal tissue contrast, and image degradation secondary to artifacts. IDEAL imaging can overcome these disadvantages. To compare sound-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and quality of two different methods of imaging that include IDEAL 3D SPGR and 3.0-T FSE T2 fat saturation (FS) imaging and to evaluate the utility of IDEAL 3D SPGR for knee joint imaging. SNR and CNR of the patellar and femoral cartilages were measured and calculated. Two radiologists performed subjective scoring of all images for three measures: general image quality, FS, and cartilage evaluation. SNR and CNR values were compared by paired Student's t-tests. Mean SNRs of patellar and femoral cartilages were 90% and 66% higher, respectively, for IDEAL 3D SPGR. CNRs of patellar cartilages and joint fluids were 2.4 times higher for FSE T2 FS, and CNR between the femoral cartilage and joint fluid was 2.2 times higher for FSE T2 FS. General image quality and FS were superior using FSE T2 FS compared to those of IDEAL 3D SPGR imaging according to both readers, while cartilage evaluation was superior using IDEAL 3D SPGR. Additionally, cartilage injuries were more prominent in IDEAL 3D SPGR than in FSE T2FS according to both readers. IDEAL 3D SPGR images show excellent visualization of patellar and femoral cartilages in 3.0 T and can compensate for the weaknesses of FSE T2 FS in the evaluation of cartilage injuries. © The Foundation Acta Radiologica 2014.

Generation of Potent T-cell Immunotherapy for Cancer using DAP12-based, Multichain, Chimeric Immunoreceptors

PubMed Central

Wang, Enxiu; Wang, Liang-Chuan; Tsai, Ching-Yi; Bhoj, Vijay; Gershenson, Zack; Moon, Edmund; Newick, Kheng; Sun, Jing; Lo, Albert; Baradet, Timothy; Feldman, Michael D.; Barrett, David; Puré, Ellen; Albelda, Steven; Milone, Michael C.

2015-01-01

Chimeric antigen receptors (CAR) bearing an antigen-binding domain linked in cis to the cytoplasmic domains of CD3ζ and costimulatory receptors have provided a potent method for engineering T-cell cytotoxicity towards B-cell leukemia and lymphoma. However, resistance to immunotherapy due to loss of T-cell effector function remains a significant barrier, especially in solid malignancies. We describe an alternative chimeric immunoreceptor design in which we have fused a single-chain variable fragment for antigen recognition to the transmembrane and cytoplasmic domains of KIR2DS2, a stimulatory killer immunoglobulin-like receptor (KIR). We show that this simple, KIR-based CAR (KIR-CAR) triggers robust antigen-specific proliferation and effector function in vitro when introduced into human T cells with DAP12, an immunotyrosine-based activation motifs (ITAM)-containing adaptor. T cells modified to express a KIR-CAR and DAP12 exhibit superior antitumor activity compared to standard first and second generation CD3ζ-based CARs in a xenograft model of mesothelioma highly resistant to immunotherapy. The enhanced antitumor activity is associated with improved retention of chimeric immunoreceptor expression and improved effector function of isolated tumor-infiltrating lymphocytes. These results support the exploration of KIR-CARs for adoptive T-cell immunotherapy, particularly in immunotherapy-resistant solid tumors. PMID:25941351

Analgesic Effect of Intra-Articular Injection of Temperature-Responsive Hydrogel Containing Bupivacaine on Osteoarthritic Pain in Rats

PubMed Central

Kim, Taemin; Seol, Dong Rim; Hahm, Suk-Chan; Ko, Cheolwoong; Kim, Eun-Hye; Chun, Keyoungjin; Kim, Junesun; Lim, Tae-Hong

2015-01-01

The present study examined the analgesic effects of slow-releasing bupivacaine from hydrogel on chronic arthritic pain in rats. Osteoarthritis (OA) was induced by monosodium iodoacetate (MIA) injection into the right knee joint. Hydrogel (HG: 20, 30, and 50 μL) and temperature-sensitive hydrogel containing bupivacaine (T-gel: 20, 30, and 50 μL) were injected intra-articularly 14 days after MIA injection. Behavioral tests were conducted. The rats showed a significant decrease in weight load and paw withdrawal threshold (PWT). Intra-articular 0.5% bupivacaine (10 and 20 μL) significantly reversed MIA-induced decreased PWT, with no effect on weight load. In normal rats, hydrogel did not produce significant changes in PWT but at 30 and 50 μL slightly decreased weight bearing; T-gel did not cause any changes in both the weight load and PWT. In OA rats, T-gel at 20 μL had a significant analgesic effect for 2 days, even though T-gel at 50 μL further reduced the weight load, demonstrating that intra-articular T-gel (20 μL) has long-lasting analgesic effects in OA rats. Thus, T-gel designed to deliver analgesics into the joint cavity could be an effective therapeutic tool in the clinical setting. PMID:26881207

Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: a collaborative study by the International-Berlin-Frankfurt-Münster AML-study group

PubMed Central

Coenen, Eva A.; Zwaan, C. Michel; Reinhardt, Dirk; Harrison, Christine J.; Haas, Oskar A.; de Haas, Valerie; Mihál, Vladimir; De Moerloose, Barbara; Jeison, Marta; Rubnitz, Jeffrey E.; Tomizawa, Daisuke; Johnston, Donna; Alonzo, Todd A.; Hasle, Henrik; Auvrignon, Anne; Dworzak, Michael; Pession, Andrea; van der Velden, Vincent H. J.; Swansbury, John; Wong, Kit-fai; Terui, Kiminori; Savasan, Sureyya; Winstanley, Mark; Vaitkeviciene, Goda; Zimmermann, Martin; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

2013-01-01

In pediatric acute myeloid leukemia (AML), cytogenetic abnormalities are strong indicators of prognosis. Some recurrent cytogenetic abnormalities, such as t(8;16)(p11;p13), are so rare that collaborative studies are required to define their prognostic impact. We collected the clinical characteristics, morphology, and immunophenotypes of 62 pediatric AML patients with t(8;16)(p11;p13) from 18 countries participating in the International Berlin-Frankfurt-Münster (I-BFM) AML study group. We used the AML-BFM cohort diagnosed from 1995-2005 (n = 543) as a reference cohort. Median age of the pediatric t(8;16)(p11;p13) AML patients was significantly lower (1.2 years). The majority (97%) had M4-M5 French-American-British type, significantly different from the reference cohort. Erythrophagocytosis (70%), leukemia cutis (58%), and disseminated intravascular coagulation (39%) occurred frequently. Strikingly, spontaneous remissions occurred in 7 neonates with t(8;16)(p11;p13), of whom 3 remain in continuous remission. The 5-year overall survival of patients diagnosed after 1993 was 59%, similar to the reference cohort (P = .14). Gene expression profiles of t(8;16)(p11;p13) pediatric AML cases clustered close to, but distinct from, MLL-rearranged AML. Highly expressed genes included HOXA11, HOXA10, RET, PERP, and GGA2. In conclusion, pediatric t(8;16)(p11;p13) AML is a rare entity defined by a unique gene expression signature and distinct clinical features in whom spontaneous remissions occur in a subset of neonatal cases. PMID:23974201

The tRNA(Gly) T10003C mutation in mitochondrial haplogroup M11b in a Chinese family with diabetes decreases the steady-state level of tRNA(Gly), increases aberrant reactive oxygen species production, and reduces mitochondrial membrane potential.

PubMed

Li, Wei; Wen, Chaowei; Li, Weixing; Wang, Hailing; Guan, Xiaomin; Zhang, Wanlin; Ye, Wei; Lu, Jianxin

2015-10-01

Mitochondrial diabetes originates mainly from mutations located in maternally transmitted, mitochondrial tRNA-coding genes. In a genetic screening program of type 2 diabetes conducted with a Chinese Han population, we found one family with suggestive maternally transmitted diabetes. The proband's mitochondrial genome was analyzed using DNA sequencing. Total 42 known nucleoside changes and 1 novel variant were identified, and the entire mitochondrial DNA sequence was assigned to haplogroup M11b. Phylogenetic analysis showed that a homoplasmic mutation, 10003T>C transition, occurred at the highly conserved site in the gene encoding tRNA(Gly). Using a transmitochondrial cybrid cell line harboring this mutation, we observed that the steady-state level of tRNA(Gly) significantly affected and the amount of tRNA(Gly) decreased by 97%, production of reactive oxygen species was enhanced, and mitochondrial membrane potential, mtDNA copy number and cellular oxygen consumption rate were remarkably decreased compared with wild-type cybrid cells. The homoplasmic 10003T>C mutation in the mitochondrial tRNA(Gly) gene suggested to be as a pathogenesis-related mutation which might contribute to the maternal inherited diabetes in the Han Chinese family.

[Prognostic differences of phenotypes in pT1-2N0 invasive breast cancer: a large cohort study with cluster analysis].

PubMed

Wang, Z; Wang, W H; Wang, S L; Jin, J; Song, Y W; Liu, Y P; Ren, H; Fang, H; Tang, Y; Chen, B; Qi, S N; Lu, N N; Li, N; Tang, Y; Liu, X F; Yu, Z H; Li, Y X

2016-06-23

To find phenotypic subgroups of patients with pT1-2N0 invasive breast cancer by means of cluster analysis and estimate the prognosis and clinicopathological features of these subgroups. From 1999 to 2013, 4979 patients with pT1-2N0 invasive breast cancer were recruited for hierarchical clustering analysis. Age (≤40, 41-70, 70+ years), size of primary tumor, pathological type, grade of differentiation, microvascular invasion, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) were chosen as distance metric between patients. Hierarchical cluster analysis was performed using Ward's method. Cophenetic correlation coefficient (CPCC) and Spearman correlation coefficient were used to validate clustering structures. The CPCC was 0.603. The Spearman correlation coefficient was 0.617 (P<0.001), which indicated a good fit of hierarchy to the data. A twelve-cluster model seemed to best illustrate our patient cohort. Patients in cluster 5, 9 and 12 had best prognosis and were characterized by age >40 years, smaller primary tumor, lower histologic grade, positive ER and PR status, and mainly negative HER-2. Patients in the cluster 1 and 11 had the worst prognosis, The cluster 1 was characterized by a larger tumor, higher grade and negative ER and PR status, while the cluster 11 was characterized by positive microvascular invasion. Patients in other 7 clusters had a moderate prognosis, and patients in each cluster had distinctive clinicopathological features and recurrent patterns. This study identified distinctive clinicopathologic phenotypes in a large cohort of patients with pT1-2N0 breast cancer through hierarchical clustering and revealed different prognosis. This integrative model may help physicians to make more personalized decisions regarding adjuvant therapy.

CD4+ T cells defined by their Vβ T cell receptor expression are associated with immunoregulatory profiles and lesion size in human leishmaniasis

PubMed Central

Keesen, T S L; Antonelli, L R V; Faria, D R; Guimarães, L H; Bacellar, O; Carvalho, E M; Dutra, W O; Gollob, K J

2011-01-01

Leishmaniasis is caused by infection with the protozoan parasite, Leishmania, that parasitizes human cells, and the cellular immune response is essential for controlling infection. In order to measure the host T cell response to Leishmania infection, we have measured the expansion, activation state and functional potential of specific T cells as identified by their T cell receptor Vβ region expression. In a group of cutaneous leishmaniasis (CL) patients, we evaluated these characteristics in nine different T cell subpopulations as identified by their Vβ region expression, before and after specific Leishmania antigen stimulation. Our results show: (1) an increase in CD4+ T cells expressing Vβ 5·2 and Vβ 24 in CL compared to controls; (2) a Leishmania antigen-induced increase in CD4+ T cells expressing Vβ 5·2, 11, 12 and 17; (3) a profile of previous activation of CD4+ Vβ 5·2-, 11- and 24-positive T cells, with higher expression of CD45RO, HLA-DR, interferon-γ, tumour necrosis factor-α and interleukin-10 compared to other Vβ-expressing subpopulations; (4) a positive correlation between higher frequencies of CD4+Vβ5·2+ T cells and larger lesions; and (5) biased homing of CD4+ T cells expressing Vβ 5·2 to the lesion site. Given that CL disease involves a level of pathology (ulcerated lesions) and is often followed by long-lived protection and cure, the identification of specific subpopulations active in this form of disease could allow for the discovery of immunodominant Leishmania antigens important for triggering efficient host responses against the parasite, or identify cell populations most involved in pathology. PMID:21726211

Progress on the Development of the Nb 3Sn 11T Dipole for the High Luminosity Upgrade of LHC

DOE PAGES

Savary, Frederic; Bajko, Marta; Bordini, Bernardo; ...

2017-02-08

The high-luminosity large hadron collider (LHC) project at CERN entered into the production phase in October 2015 after the completion of the design study phase. In the meantime, the development of the 11 T dipole needed for the upgrade of the collimation system of the machine made significant progress with very good performance of the first two-in-one magnet model of 2-m length made at CERN. The 11 T dipole, which is more powerful than the current main dipoles of LHC, can be made shorter with an equivalent integrated field. This will allow creating space for the installation of additional collimatorsmore » in specific locations of the dispersion suppressor regions. Following tests carried out during heavy ions runs of LHC in the end of 2015, and a more recent review of the project budget, the installation plan for the 11 T dipole was revised. Consequently, one 11 T dipole full assembly containing two 11 T dipoles of 5.5-m length will be installed on either side of interaction point 7. These two units shall be installed during the long shutdown 2 in years 2019-2020. After a brief reminder on the design features of the magnet, this paper describes the current status of the development activities, in particular the short model programme and the construction of the first full scale prototype at CERN. Finally, critical operations such as the reaction treatment and the coil impregnation are discussed, the quench performance tests results of the two-in-one model are reviewed and finally, the plan toward the production for the long shut down 2 is described.« less

In vitro determination of biomechanical properties of human articular cartilage in osteoarthritis using multi-parametric MRI

NASA Astrophysics Data System (ADS)

Juras, Vladimir; Bittsansky, Michal; Majdisova, Zuzana; Szomolanyi, Pavol; Sulzbacher, Irene; Gäbler, Stefan; Stampfl, Jürgen; Schüller, Georg; Trattnig, Siegfried

2009-03-01

The objective of this study was to evaluate the correlations between MR parameters and the biomechanical properties of naturally degenerated human articular cartilage. Human cartilage explants from the femoral condyles of patients who underwent total knee replacement were evaluated on a micro-imaging system at 3 T. To quantify glycosaminoglycan (GAG) content, delayed gadolinium-enhanced MRI of the cartilage (dGEMRIC) was used. T2 maps were created by using multi-echo, multi-slice spin echo sequences with six echoes: 15, 30, 45, 60, 75, and 90 ms. Data for apparent diffusion constant (ADC) maps were obtained from pulsed gradient spin echo (PGSE) sequences with five b-values: 10.472, 220.0, 627.0, 452.8, 724.5, and 957.7. MR parameters were correlated with mechanical parameters (instantaneous ( I) and equilibrium ( Eq) modulus and relaxation time ( τ)), and the OA stage of each cartilage specimen was determined by histological evaluation of hematoxylin-eosin stained slices. For some parameters, a high correlation was found: the correlation of T1Gd vs Eq ( r = 0.8095), T1Gd vs I/ Eq ( r = -0.8441) and T1Gd vs τ ( r = 0.8469). The correlation of T2 and ADC with selected biomechanical parameters was not statistically significant. In conclusion, GAG content measured by dGEMRIC is highly related to the selected biomechanical properties of naturally degenerated articular cartilage. In contrast, T2 and ADC were unable to estimate these properties. The results of the study imply that some MR parameters can non-invasively predict the biomechanical properties of degenerated articular cartilage.

Use of monoclonal antibodies in a study of the development of T lymphocytes in the human fetus.

PubMed Central

Asma, G E; Van den Bergh, R L; Vossen, J M

1983-01-01

A panel of monoclonal antibodies (OKT3, 4, 6, 8, 10, 11) was used for the identification of T lymphocyte subpopulations in cell suspensions of human fetal liver, thymus, bone marrow and spleen. In liver suspensions of 8-16 week old fetuses and in bone marrow suspensions (12-20 weeks) less than 5% of lymphocytes reacted with either OKT3, 11, 4, 8 or 6, whereas the OKT10 antibody bound to, respectively, 35 and 86% of lymphocytes in these tissues. In liver suspensions of 17-20 week old fetuses, about 20% of lymphocytes carried either the T3, 11, 4 or 8 antigen and more than 60% of lymphocytes were OKT10+. The maturation stages in fetal thymus (11-20 weeks) are comparable to those in the post-natal thymus, with the exception that a substantial proportion of fetal thymocytes expresses the T3 and T6 antigen simultaneously. In the fetal spleen (12-20 weeks), 40% of lymphocytes reacts with OKT3. These OKT3+ spleen cells may be divided into two subsets expressing either the T4 antigen or the T8 antigen. These OKT3+/OKT4+ and OKT3+/OKT8+ lymphoid cells of the fetal spleen can be further subdivided into a T10+ and T10- subpopulation. These data suggest that T lymphoid precursor cells, reacting with either none of the monoclonal antibodies or only with OKT10, are generated in fetal liver (up till 16 weeks gestational age) and bone marrow. Further maturation takes place in the fetal thymus, but also to a certain extent in peripheral lymphoid organs such as the fetal spleen, as evidenced by the coexistence of a T3+/T10+ and T3+/T10- subpopulation in this organ. PMID:6349881

Absence of PDGF-induced, PKC-independent c-fos expression in a chemically transformed C3H/10T1/2 cell clone.

PubMed

Vassbotn, F S; Skar, R; Holmsen, H; Lillehaug, J R

1992-09-01

The effect of platelet-derived growth factor (PDGF) on c-fos mRNA transcription was studied in the immortalized mouse embryo fibroblast C3H/10T1/2 Cl 8 (10T1/2) cells and the chemically transformed, tumorigenic subclone C3H/10T1/2 Cl 16 (Cl 16). In the 10T1/2 cells as well as the Cl 16 subclone, the dose-dependent PDGF stimulation of c-fos mRNA synthesis was similar in both logarithmically growing and confluent cultures. c-fos mRNA was induced severalfold by 12-O-tetradecanoylphorbol-13-acetate (TPA) in both 10T1/2 and Cl 16. Down-regulation of protein kinase C (PKC) activity by TPA pretreatment inhibited PDGF-stimulated c-fos mRNA expression in Cl 16 cells but did not affect this induction in the 10T1/2 cells. This inhibition was not a general phenomenon of 3-methylcholanthrene-mediated transformation of 10T1/2 cells since experiments with another transformed 10T1/2 cell clone, C3H/10T1/2 TPA 482, gave qualitatively the same results as the 10T1/2 cells. Receptor binding experiments showed that the nontransformed and transformed cells had a comparable number of PDGF receptors, 1.3 x 10(5) and 0.7 x 10(5) receptors per cell, respectively. Furthermore, cAMP-induced c-fos expression induced by forskolin is formerly shown to be independent of PKC down-regulation. In our experiments, forskolin induced c-fos expression in both clones. However, PKC down-regulation inhibited the forskolin-induced c-fos expression in Cl 16 cells. This apparently demonstrates cross talk between PKC and PKA in the c-fos induction pathway. The present results provide evidence for an impaired mechanism for activating c-fos expression through PKC-independent, PDGF-induced signal transduction in the chemically transformed Cl 16 fibroblasts compared to that in nontransformed 10T1/2 cells.

26 CFR 301.9100-11T - Election by a qualified bank holding corporation to pay in installments the tax attributable to...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Election by a qualified bank holding corporation to pay in installments the tax attributable to sales under the Bank Holding Company Act. 301.9100-11T Section 301.9100-11T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY...

Anti-osteoarthritic effects of ChondroT in a rat model of collagenase-induced osteoarthritis.

PubMed

Jeong, Jiwon; Bae, Kiljoon; Kim, Sun-Gil; Kwak, Dongwook; Moon, Young-Joo; Choi, Chan-Hun; Kim, Young-Ran; Na, Chang-Su; Kim, Seon-Jong

2018-04-19

Previously, we reported that ChondorT showed significant anti-arthritis and anti-inflammatory effects. ChondroT, a new herbal medication, consists of the water extracts of Osterici Radix, Lonicerae Folium, Angelicae Gigantis Radix, Clematidis Radix, and Phellodendri Cortex (6:4:4:4:3). The objective of this study was to investigate the effects of ChondroT in collagenase-induced osteoarthritis rat model. Osteoarthritis was induced by the injection of collagenase into the right knee joint cavity of rats. The samples were divided into seven groups [intact (n = 6), control (n = 6), indomethacin (n = 6), Joins tab (n = 6), ChondroT50 (n = 6), ChondroT100 (n = 6), and ChondroT200 (n = 6)]. The control group was administered normal saline, indomethacin group was administered indomethacin (2 mg/kg), and Joins tab group was administered Joins Tab (20 mg/kg). The ChondroT50, ChondroT100, and ChondroT200 groups were administered 50, 100, and 200 mg/kg of ChondroT, respectively. All oral administrations were initiated 7 days after the induction of arthritis and were continued for a total of 12 days. At the end of the experiment, serum aminotransferase, albumin, blood urea nitrogen, creatinine, leukocyte, and inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6] were analyzed. Hematoxylin and eosin (H&E) and safranin O-fast green staining of the articular structures of the knee joint were performed. TNF-α and IL-1β decreased in the ChondroT100 and ChondroT200 groups compared with those in the control group. IL-6 and aspartate aminotransferase decreased in the ChondroT50, ChondroT100, and ChondroT200 groups compared with that in the control group. Albumin, WBC and lymphocytes decreased in the ChondroT100 and ChondroT200 groups compared with those in the control group. In H&E stain, synoviocytes, cartilage lacunae, and chondrocytes were well preserved in the ChondroT100 and ChondroT200 groups, and safranin O

The Safe Correction Angle of Osteotomy at T12 and L1 for Ankylosing Spondylitis Kyphosis: Patients With 2-level Osteotomy.

PubMed

Liu, Chao; Yu, Wen; Zheng, Guoquan; Guo, Yue; Song, Kai; Tang, Xiangyu; Wang, Zheng; Wang, Yan; Zhang, Yonggang

2017-08-01

This is a retrospective clinical study. To investigate the correction angle and safety of the spinal osteotomy at the T12 or L1 vertebra. Monosegment subtraction osteotomy cannot effectively correct severe kyphosis in ankylosing spondylitis (AS), generally 2-level spinal osteotomy was taken for achieving expected correction. According to literature, the T12 or L1 were usually taken as the upper spinal osteotomy vertebra. Because of the canalis vertebralis at the T12 and L1 were spinal cord and medullary cone, so the spinal osteotomy at the T12 or L1 vertebra were more dangerous than at lower level. The correction angle and safety of the spinal osteotomy at the T12 or L1 vertebra have not yet been reported. From July 2009 to 2014, 33 patients in our department with severe AS kyphosis underwent 2-level pedicle subtraction osteotomy were studied. Preoperative and postoperative relevant parameters and complications were recorded. The upper spinal osteotomy was taken at the T12 vertebra for 10 patients. The upper spinal osteotomy was taken at the L1 vertebra for 23 patients. The mean amount of correction of T12 and L1 was 26.230 and 27.952 degrees, respectively. All patients could walk with orthophoria and lie horizontally postoperatively. No deadly vascular and neurological lesion occurred. Performing pedicle subtraction osteotomy at T12 and L1 can safely achieve a mean correction of 26.230 and 27.952 degrees, respectively. Two-level osteotomy was safely and advocated for correcting severe AS kyphosis. Level III.

Crystal structures of K2[XSi5O12] (X = Fe2+, Co, Zn) and Rb2[XSi5O12] (X = Mn) leucites: comparison of monoclinic P21/c and Ia{\\overline 3}d polymorph structures and inverse relationship between tetrahedral cation (T = Si and X)-O bond distances and intertetrahedral T-O-T angles.

PubMed

Bell, Anthony M T; Henderson, C Michael B

2018-06-01

The leucite tectosilicate mineral analogues K 2 X 2+ Si 5 O 12 (X = Fe 2+ , Co, Zn) and Rb 2 X 2+ Si 5 O 12 (X = Mn) have been synthesized at elevated temperatures both dry at atmospheric pressure and at controlled water vapour pressure; for X = Co and Zn both dry and hydrothermally synthesized samples are available. Rietveld refinement of X-ray data for hydrothermal K 2 X 2+ Si 5 O 12 (X = Fe 2+ , Co, Zn) samples shows that they crystallize in the monoclinic space group P2 1 /c and have tetrahedral cations (Si and X) ordered onto distinct framework sites [cf. hydrothermal K 2 MgSi 5 O 12 ; Bell et al. (1994a), Acta Cryst. B50, 560-566]. Dry-synthesized K 2 X 2+ Si 5 O 12 (X = Co, Zn) and Rb 2 X 2+ Si 5 O 12 (X = Mn) samples crystallize in the cubic space group Ia{\\overline 3}d and with Si and X cations disordered in the tetrahedral framework sites as typified by dry K 2 MgSi 5 O 12 . Both structure types have tetrahedrally coordinated SiO 4 and XO 4 sharing corners to form a partially substituted silicate framework. Extraframework K + and Rb + cations occupy large channels in the framework. Structural data for the ordered samples show that mean tetrahedral Si-O and X-O bond lengths cover the ranges 1.60 Å (Si-O) to 2.24 Å (Fe 2+ -O) and show an inverse relationship with the intertetrahedral angles (T-O-T) which range from 144.7° (Si-O-Si) to 124.6° (Si-O-Fe 2+ ). For the compositions with both disordered and ordered tetrahedral cation structures (K 2 MgSi 5 O 12 , K 2 CoSi 5 O 12 , K 2 ZnSi 5 O 12 , Rb 2 MnSi 5 O 12 and Cs 2 CuSi 5 O 12 leucites) the disordered polymorphs always have larger unit-cell volumes, larger intertetrahedral T-O-T angles and smaller mean T-O distances than their isochemical ordered polymorphs. The ordered samples clearly have more flexible frameworks than the disordered structures which allow the former to undergo a greater degree of tetrahedral collapse around the interframework cavity cations. Multivariant linear regression has

Chromosomal imbalances are associated with outcome of Helicobacter pylori eradication in t(11;18)(q21;q21) negative gastric mucosa-associated lymphoid tissue lymphomas.

PubMed

Fukuhara, Noriko; Nakamura, Tsuneya; Nakagawa, Masao; Tagawa, Hiroyuki; Takeuchi, Ichiro; Yatabe, Yasushi; Morishima, Yasuo; Nakamura, Shigeo; Seto, Masao

2007-08-01

Approximately 70% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas can be successfully treated with H. pylori eradication. The translocation t(11;18)(q21;q21) characteristic of MALT lymphoma is recognized as a marker for H. pylori independency, but this marker is found in only a half of the MALT lymphomas resistant to H. pylori eradication. Detailed analyses of the genomic features of eradication resistant as well as responsive groups are important for understanding their molecular basis. We performed array-based comparative genomic hybridization (array-CGH) for 29 gastric MALT lymphomas treated with H. pylori eradication. These comprised ten cases of t(11;18) positive MALT, nine cases of t(11;18) negative MALT with H. pylori dependency, and ten cases of t(11;18) negative MALT with H. pylori independency. Array-CGH analysis demonstrated that no significant genetic alterations were found in t(11;18) positive MALT lymphomas, but numerous genomic alterations were detected in t(11;18) negative MALT lymphomas. Many of these alterations were similar to those found in diffuse large B-cell lymphoma with trisomy 3 being the most recurrent alteration. Within the t(11;18) negative MALT lymphoma without large cell components group, genomic imbalances occurred more frequently in the H. pylori independent than in the H. pylori dependent group (P = 0.02). Genomic imbalances are associated with H. pylori independency in t(11;18) negative gastric MALT lymphomas. They may thus play an important role in the development of H. pylori independency.

26 CFR 1.1(i)-1T - Questions and answers relating to the tax on unearned income certain minor children (Temporary).

Code of Federal Regulations, 2010 CFR

2010-04-01

... legal title to the property in the child although an adult custodian is given certain rights to deal... unearned income certain minor children (Temporary). 1.1(i)-1T Section 1.1(i)-1T Internal Revenue INTERNAL... Questions and answers relating to the tax on unearned income certain minor children (Temporary). In General...

Combination therapy incorporating Bcl-2 inhibition with Venetoclax for the treatment of refractory primary plasma cell leukemia with t (11;14).

PubMed

Gonsalves, Wilson I; Buadi, Francis K; Kumar, Shaji K

2018-02-01

Primary plasma cell leukemia (pPCL) is the most aggressive form of the plasma cell (PC) malignancy, multiple myeloma (MM). It has been commonly associated with the presence of a chromosome translocation involving the immunoglobulin heavy chain (IgH) locus on 14q32, that is t (11;14). Results from early phase clinical trials utilizing the selective Bcl-2 inhibitor, venetoclax, as a single agent in patients with relapsed MM have had remarkable efficacy among patients with t (11;14) abnormality. The present case demonstrates the ability of a combination regimen incorporating Bcl-2 inhibition with daratumumab, bortezomib, venetoclax, and dexamethasone to induce a rapid and very deep hematologic response in a pPCL patient with t (11;14), even in a setting of very refractory disease. This case highlights the need to further study Bcl-2 inhibition-based therapy as an option for therapy in patients with pPCL with t (11;14). © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fatty acid composition of porcine cumulus oocyte complexes (COC) during maturation: effect of the lipid modulators trans-10, cis-12 conjugated linoleic acid (t10,c12 CLA) and forskolin.

PubMed

Prates, E G; Alves, S P; Marques, C C; Baptista, M C; Horta, A E M; Bessa, R J B; Pereira, R M

2013-05-01

The effect of maturation and of two lipid modulators supplementation along in vitro maturation (IVM) on fatty acid (FA) and dimethylacetal (DMA) composition of porcine cumulus oocyte complexes (COC) were studied. Abattoir-derived immature COC were analyzed for FA and DMA or submitted to IVM as follows: control group; t10,c12 CLA group, t10,c12 CLA supplementation for 44 h; Forskolin group, forskolin supplementation during the initial 2 h; t10,c12 CLA + forskolin group, t10,c12 CLA for 44 h and forskolin for just 2h. Each experimental group had five replicates. FA analysis of oocytes, cumulus cells (CC), follicular fluid, and culture media were performed by gas-liquid chromatography. Oocytes and their CC had different FA composition. Oocytes were richer in saturated FA (SFA) preferentially maintaining their FA profile during maturation. Mature CC had the highest polyunsaturated FA (PUFA) content. Five individual and total SFA, and monounsaturated FA (MUFA), notably oleic acid (c9-18:1), percentages were lower (P ≤ 0.023) in mature than in immature CC. t10,c12 CLA was accumulated by COC from t10,c12 CLA and t10,c12 CLA + forskolin groups, mostly in CC where MUFA and an eicosatrienoic isomer decreased (P ≤ 0.043). Nevertheless, PUFA or FA and DMA total content were not affected. Arachidonic acid was reduced in t10,c12 CLA + forskolin CC and hexadecanal-DMA-16:0 in t10,c12 CLA CC. Forskolin alone increased (P ≤ 0.043) c9-18:1 in oocytes. In conclusion, maturation process clearly changed porcine COC FA and DMA profiles, mostly of CC, also more susceptible to modifications induced by t10,c12 CLA. This possibility of manipulating COC lipid composition during IVM could be used to improve oocyte quality/cryopreservation efficiency.

Naive T-cell receptor transgenic T cells help memory B cells produce antibody

PubMed Central

Duffy, Darragh; Yang, Chun-Ping; Heath, Andrew; Garside, Paul; Bell, Eric B

2006-01-01

Injection of the same antigen following primary immunization induces a classic secondary response characterized by a large quantity of high-affinity antibody of an immunoglobulin G class produced more rapidly than in the initial response – the products of memory B cells are qualitatively distinct from that of the original naive B lymphocytes. Very little is known of the help provided by the CD4 T cells that stimulate memory B cells. Using antigen-specific T-cell receptor transgenic CD4 T cells (DO11.10) as a source of help, we found that naive transgenic T cells stimulated memory B cells almost as well (in terms of quantity and speed) as transgenic T cells that had been recently primed. There was a direct correlation between serum antibody levels and the number of naive transgenic T cells transferred. Using T cells from transgenic interleukin-2-deficient mice we showed that interleukin-2 was not required for a secondary response, although it was necessary for a primary response. The results suggested that the signals delivered by CD4 T cells and required by memory B cells for their activation were common to both antigen-primed and naive CD4 T cells. PMID:17067314

Zinc transporter ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory.

PubMed

Sindreu, Carlos; Palmiter, Richard D; Storm, Daniel R

2011-02-22

The physiological role of vesicular zinc at central glutamatergic synapses remains poorly understood. Here we show that mice lacking the synapse-specific vesicular zinc transporter ZnT3 (ZnT3KO mice) have reduced activation of the Erk1/2 MAPK in hippocampal mossy fiber terminals, disinhibition of zinc-sensitive MAPK tyrosine phosphatase activity, and impaired MAPK signaling during hippocampus-dependent learning. Activity-dependent exocytosis is required for the effect of zinc on presynaptic MAPK and phosphatase activity. ZnT3KO mice have complete deficits in contextual discrimination and spatial working memory. Local blockade of zinc or MAPK in the mossy fiber pathway of wild-type mice impairs contextual discrimination. We conclude that ZnT3 is important for zinc homeostasis modulating presynaptic MAPK signaling and is required for hippocampus-dependent memory.

Can T1 w/T2 w ratio be used as a myelin-specific measure in subcortical structures? Comparisons between FSE-based T1 w/T2 w ratios, GRASE-based T1 w/T2 w ratios and multi-echo GRASE-based myelin water fractions.

PubMed

Uddin, Md Nasir; Figley, Teresa D; Marrie, Ruth Ann; Figley, Chase R

2018-03-01

Given the growing popularity of T 1 -weighted/T 2 -weighted (T 1 w/T 2 w) ratio measurements, the objective of the current study was to evaluate the concordance between T 1 w/T 2 w ratios obtained using conventional fast spin echo (FSE) versus combined gradient and spin echo (GRASE) sequences for T 2 w image acquisition, and to compare the resulting T 1 w/T 2 w ratios with histologically validated myelin water fraction (MWF) measurements in several subcortical brain structures. In order to compare these measurements across a relatively wide range of myelin concentrations, whole-brain T 1 w magnetization prepared rapid acquisition gradient echo (MPRAGE), T 2 w FSE and three-dimensional multi-echo GRASE data were acquired from 10 participants with multiple sclerosis at 3 T. Then, after high-dimensional, non-linear warping, region of interest (ROI) analyses were performed to compare T 1 w/T 2 w ratios and MWF estimates (across participants and brain regions) in 11 bilateral white matter (WM) and four bilateral subcortical grey matter (SGM) structures extracted from the JHU_MNI_SS 'Eve' atlas. Although the GRASE sequence systematically underestimated T 1 w/T 2 w values compared to the FSE sequence (revealed by Bland-Altman and mountain plots), linear regressions across participants and ROIs revealed consistently high correlations between the two methods (r 2 = 0.62 for all ROIs, r 2 = 0.62 for WM structures and r 2 = 0.73 for SGM structures). However, correlations between either FSE-based or GRASE-based T 1 w/T 2 w ratios and MWFs were extremely low in WM structures (FSE-based, r 2 = 0.000020; GRASE-based, r 2 = 0.0014), low across all ROIs (FSE-based, r 2 = 0.053; GRASE-based, r 2 = 0.029) and moderate in SGM structures (FSE-based, r 2 = 0.20; GRASE-based, r 2 = 0.17). Overall, our findings indicated a high degree of correlation (but not equivalence) between FSE-based and GRASE-based T 1 w/T 2 w ratios, and low correlations between T 1 w/T 2 w ratios and MWFs. This

T cell costimulation by chemokine receptors.

PubMed

Molon, Barbara; Gri, Giorgia; Bettella, Monica; Gómez-Moutón, Concepción; Lanzavecchia, Antonio; Martínez-A, Carlos; Mañes, Santos; Viola, Antonella

2005-05-01

Signals mediated by chemokine receptors may compete with T cell receptor stop signals and determine the duration of T cell-antigen-presenting cell interactions. Here we show that during T cell stimulation by antigen-presenting cells, T cell chemokine receptors coupled to G(q) and/or G(11) protein were recruited to the immunological synapse by a G(i)-independent mechanism. When chemokine receptors were sequestered at the immunological synapse, T cells became insensitive to chemotactic gradients, formed more stable conjugates and finally responded with enhanced proliferation and cytokine production. We suggest that chemokine receptor trapping at the immunological synapse enhances T cell activation by improving T cell-antigen-presenting cell attraction and impeding the 'distraction' of successfully engaged T cells by other chemokine sources.

MRI features of cervical articular process degenerative joint disease in Great Dane dogs with cervical spondylomyelopathy.

PubMed

Gutierrez-Quintana, Rodrigo; Penderis, Jacques

2012-01-01

Cervical spondylomyelopathy or Wobbler syndrome commonly affects the cervical vertebral column of Great Dane dogs. Degenerative changes affecting the articular process joints are a frequent finding in these patients; however, the correlation between these changes and other features of cervical spondylomyelopathy are uncertain. We described and graded the degenerative changes evident in the cervical articular process joints from 13 Great Danes dogs with cervical spondylomyelopathy using MR imaging, and evaluated the relationship between individual features of cervical articular process joint degeneration and the presence of spinal cord compression, vertebral foraminal stenosis, intramedullary spinal cord changes, and intervertebral disc degenerative changes. Degenerative changes affecting the articular process joints were common, with only 13 of 94 (14%) having no degenerative changes. The most severe changes were evident between C4-C5 and C7-T1 intervertebral spaces. Reduction or loss of the hyperintense synovial fluid signal on T2-weighted MR images was the most frequent feature associated with articular process joint degenerative changes. Degenerative changes of the articular process joints affecting the synovial fluid or articular surface, or causing lateral hypertrophic tissue, were positively correlated with lateral spinal cord compression and vertebral foraminal stenosis. Dorsal hypertrophic tissue was positively correlated with dorsal spinal cord compression. Disc-associated spinal cord compression was recognized less frequently. © 2011 Veterinary Radiology & Ultrasound.

3.0T MR imaging of the ankle: Axial traction for morphological cartilage evaluation, quantitative T2 mapping and cartilage diffusion imaging-A preliminary study.

PubMed

Jungmann, Pia M; Baum, Thomas; Schaeffeler, Christoph; Sauerschnig, Martin; Brucker, Peter U; Mann, Alexander; Ganter, Carl; Bieri, Oliver; Rummeny, Ernst J; Woertler, Klaus; Bauer, Jan S

2015-08-01

To determine the impact of axial traction during high resolution 3.0T MR imaging of the ankle on morphological assessment of articular cartilage and quantitative cartilage imaging parameters. MR images of n=25 asymptomatic ankles were acquired with and without axial traction (6kg). Coronal and sagittal T1-weighted (w) turbo spin echo (TSE) sequences with a driven equilibrium pulse and sagittal fat-saturated intermediate-w (IMfs) TSE sequences were acquired for morphological evaluation on a four-point scale (1=best, 4=worst). For quantitative assessment of cartilage degradation segmentation was performed on 2D multislice-multiecho (MSME) SE T2, steady-state free-precession (SSFP; n=8) T2 and SSFP diffusion-weighted imaging (DWI; n=8) images. Wilcoxon-tests and paired t-tests were used for statistical analysis. With axial traction, joint space width increased significantly and delineation of cartilage surfaces was rated superior (P<0.05). Cartilage surfaces were best visualized on coronal T1-w images (P<0.05). Differences for cartilage matrix evaluation were smaller. Subchondral bone evaluation, motion artifacts and image quality were not significantly different between the acquisition methods (P>0.05). T2 values were lower at the tibia than at the talus (P<0.001). Reproducibility was better for images with axial traction. Axial traction increased the joint space width, allowed for better visualization of cartilage surfaces and improved compartment discrimination and reproducibility of quantitative cartilage parameters. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Reversal of human allergen-specific CRTH2+ T(H)2 cells by IL-12 or the PS-DSP30 oligodeoxynucleotide.

PubMed

Annunziato, F; Cosmi, L; Manetti, R; Brugnolo, F; Parronchi, P; Maggi, E; Nagata, K; Romagnani, S

2001-11-01

The chemoattractant receptor homologous molecule expressed on T(H)2 cells (CRTH2) is a receptor for prostaglandin D(2), which among human T cells is selectively expressed by T(H)2 and type 2 cytotoxic effectors. Our purpose was to assess whether the cytokine production profile of T(H)2 effectors could be reversed by exploiting their selective expression of CRTH2. CRTH2(+) T cells were purified from the blood of allergic subjects, stimulated with the specific allergen in the absence or presence of IL-12, and assessed by flow cytometry at the single-cell level for their ability to produce IL-4 and/or IFN-gamma after antigen or polyclonal stimulation. Both IL-12 and the PS-DSP30 oligodeoxynucleotide enabled CRTH2(+) allergen-stimulated T(H)2 cells to produce IFN-gamma. This change in the profile of cytokine production by T(H)2 cells from allergic subjects was related to the upregulation of IL-12 receptor beta2 chain and was associated with the loss of CRTH2. These data demonstrate that the cytokine production pattern of fully differentiated T(H)2 effectors can be changed to a less polarized profile, thus providing the physiologic basis for new immunotherapeutic strategies in allergic disorders.

Simultaneous acquisition for T2 -T2 Exchange and T1 -T2 correlation NMR experiments

NASA Astrophysics Data System (ADS)

Montrazi, Elton T.; Lucas-Oliveira, Everton; Araujo-Ferreira, Arthur G.; Barsi-Andreeta, Mariane; Bonagamba, Tito J.

2018-04-01

The NMR measurements of longitudinal and transverse relaxation times and its multidimensional correlations provide useful information about molecular dynamics. However, these experiments are very time-consuming, and many researchers proposed faster experiments to reduce this issue. This paper presents a new way to simultaneously perform T2 -T2 Exchange and T1 -T2 correlation experiments by taking the advantage of the storage time and the two steps phase cycling used for running the relaxation exchange experiment. The data corresponding to each step is either summed or subtracted to produce the T2 -T2 and T1 -T2 data, enhancing the information obtained while maintaining the experiment duration. Comparing the results from this technique with traditional NMR experiments it was possible to validate the method.

Increased numbers of preexisting memory CD8 T cells and decreased T-bet expression can restrain terminal differentiation of secondary effector and memory CD8 T cells.

PubMed

Joshi, Nikhil S; Cui, Weiguo; Dominguez, Claudia X; Chen, Jonathan H; Hand, Timothy W; Kaech, Susan M

2011-10-15

Memory CD8 T cells acquire effector memory cell properties after reinfection and may reach terminally differentiated, senescent states ("Hayflick limit") after multiple infections. The signals controlling this process are not well understood, but we found that the degree of secondary effector and memory CD8 T cell differentiation was intimately linked to the amount of T-bet expressed upon reactivation and preexisting memory CD8 T cell number (i.e., primary memory CD8 T cell precursor frequency) present during secondary infection. Compared with naive cells, memory CD8 T cells were predisposed toward terminal effector (TE) cell differentiation because they could immediately respond to IL-12 and induce T-bet, even in the absence of Ag. TE cell formation after secondary (2°) or tertiary infections was dependent on increased T-bet expression because T-bet(+/-) cells were resistant to these phenotypic changes. Larger numbers of preexisting memory CD8 T cells limited the duration of 2° infection and the amount of IL-12 produced, and consequently, this reduced T-bet expression and the proportion of 2° TE CD8 T cells that formed. Together, these data show that over repeated infections, memory CD8 T cell quality and proliferative fitness is not strictly determined by the number of serial encounters with Ag or cell divisions, but is a function of the CD8 T cell differentiation state, which is genetically controlled in a T-bet-dependent manner. This differentiation state can be modulated by preexisting memory CD8 T cell number and the intensity of inflammation during reinfection. These results have important implications for vaccinations involving prime-boost strategies.

Zinc transporter ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory

PubMed Central

Sindreu, Carlos; Palmiter, Richard D.; Storm, Daniel R.

2011-01-01

The physiological role of vesicular zinc at central glutamatergic synapses remains poorly understood. Here we show that mice lacking the synapse-specific vesicular zinc transporter ZnT3 (ZnT3KO mice) have reduced activation of the Erk1/2 MAPK in hippocampal mossy fiber terminals, disinhibition of zinc-sensitive MAPK tyrosine phosphatase activity, and impaired MAPK signaling during hippocampus-dependent learning. Activity-dependent exocytosis is required for the effect of zinc on presynaptic MAPK and phosphatase activity. ZnT3KO mice have complete deficits in contextual discrimination and spatial working memory. Local blockade of zinc or MAPK in the mossy fiber pathway of wild-type mice impairs contextual discrimination. We conclude that ZnT3 is important for zinc homeostasis modulating presynaptic MAPK signaling and is required for hippocampus-dependent memory. PMID:21245308

Solid-state NMR characterization of copolymers of nylon 11 and nylon 12.

PubMed

Johnson, C G; Mathias, L J

1997-05-01

Solid-state 13C and 15N NMR spectroscopy, in conjunction with differential scanning calorimetry, wide-angle X-ray diffraction and infrared spectroscopy, were used to characterize a series of nylon 11 and 12 copolymers with mole percentages of nylon 12 monomer of 0, 15, 35, 50, 65, 85, and 100%. Monotonic melting point (Tm) and heat of fusion depressions were observed for the copolymer series with the 65 mol% nylon 12 copolymer having the lowest apparent crystallinity and Tm at 148 degrees C. Solid-state 15N NMR spectra showed a smooth shift of the main peak position for the as-prepared copolymers from 84 ppm for the alpha-form of pure nylon 11 to 89 ppm for the gamma-form of pure nylon 12. Similar behavior was seen for FTIR amide V and VI modes which are also sensitive to the alpha- and gamma-crystal forms. 13C NMR T1 measurements showed that the overall most mobile sample was the 65:35 copolymer. The amide group of the 1:1 copolymer was labelled using 15N-labelled amino acids available through the Gabriel synthesis; an annealed, solution-cast film of this sample showed a T1N value of 349 s, similar to values seen for annealed nylon 11 and nylon 12 homopolymers. The WAXS pattern for the 65 mol% nylon 12 sample showed a sharp peak at 2 theta = 21.3, overlapping a broad peak centered at 2 theta = 21.0. These are consistent with the values seen for gamma-form nylon 12. The 1:1 copolymer (15N labelled) was shown to be polymorphic, like the homopolymers after specific treatments, with a gamma-like phase formed upon solvent casting, and an alpha-like phase dominating for as-polymerized material and precipitated flakes.

Biological knee reconstruction for combined malalignment, meniscal deficiency, and articular cartilage disease.

PubMed

Harris, Joshua D; Hussey, Kristen; Wilson, Hillary; Pilz, Kyle; Gupta, Anil K; Gomoll, Andreas; Cole, Brian J

2015-02-01

The aim of this study was to analyze patient-reported outcomes in those undergoing the triad of simultaneous osteotomy, meniscal transplantation, and articular cartilage repair. Patients undergoing simultaneous meniscal transplantation, distal femoral or proximal tibial osteotomy, and articular cartilage surgery by a single surgeon (B.J.C.) were analyzed. Meniscal transplantation was performed using bone-in-slot techniques. Distal femoral and high tibial osteotomies were performed for valgus and varus malalignment, respectively. Microfracture, autologous chondrocyte implantation, and osteochondral autograft or allograft were performed for articular cartilage disease. Validated patient-reported and surgeon-measured outcomes were collected. Preoperative and postoperative outcomes and medial versus lateral disease were compared using Student t tests. Eighteen participants (mean age, 34 ± 7.8 years; symptomatic patients, 7.4 ± 5.6 years; 2.4 ± 1.0 surgical procedures before study enrollment; mean follow-up, 6.5 ± 3.2 years) were analyzed. Two thirds of participants had medial compartment pathologic conditions and one third had lateral compartment pathologic processes. At final follow-up, there were statistically significant clinically meaningful improvements in International Knee Documentation Committee (IKDC) subjective classification, Lysholm score, and 4 Knee Injury and Osteoarthritis Outcome Score (KOOS) subscores. Postoperative 12-item short form (SF-12) physical and mental component scores were not significantly different from preoperative scores. The Kellgren-Lawrence classification grade was 1.5 ± 1.1 at 2.5 ± 3.0 years after surgery. There was a significantly higher preoperative SF-12 physical composite score (PCS) in participants with lateral compartment pathologic conditions (v medial compartment conditions) (P = .011). Although there were 13 reoperations in 10 patients (55.5% reoperation rate), only one patient was converted to knee arthroplasty (5

Resveratrol given intraperitoneally does not inhibit growth of high-risk t(4;11) acute lymphoblastic leukemia cells in NOD/SCID mouse model

USDA-ARS?s Scientific Manuscript database

The efficacy of the phytochemical resveratrol as a preventive agent against the growth of t(4;11) acute lymphoblastic leukemia (ALL) was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) ALL line SEM. SEM cells were injected into the tail vein and engraftment was monitored by ...

Cartilage T2 assessment: differentiation of normal hyaline cartilage and reparative tissue after arthroscopic cartilage repair in equine subjects.

PubMed

White, Lawrence M; Sussman, Marshall S; Hurtig, Mark; Probyn, Linda; Tomlinson, George; Kandel, Rita

2006-11-01

To prospectively assess T2 mapping characteristics of normal articular cartilage and of cartilage at sites of arthroscopic repair, including comparison with histologic results and collagen organization assessed at polarized light microscopy (PLM). Study protocol was compliant with the Canadian Council on Animal Care Guidelines and approved by the institutional animal care committee. Arthroscopic osteochondral autograft transplantation (OAT) and microfracture arthroplasty (MFx) were performed in knees of 10 equine subjects (seven female, three male; age range, 3-5 years). A site of arthroscopically normal cartilage was documented in each joint as a control site. Joints were harvested at 12 (n = 5) and 24 (n = 5) weeks postoperatively and were imaged at 1.5-T magnetic resonance (MR) with a 10-echo sagittal fast spin-echo acquisition. T2 maps of each site (21 OAT harvest, 10 MFx, 12 OAT plug, and 10 control sites) were calculated with linear least-squares curve fitting. Cartilage T2 maps were qualitatively graded as "organized" (normal transition of low-to-high T2 signal from deep to superficial cartilage zones) or "disorganized." Quantitative mean T2 values were calculated for deep, middle, and superficial cartilage at each location. Results were compared with histologic and PLM assessments by using kappa analysis. T2 maps were qualitatively graded as organized at 20 of 53 sites and as disorganized at 33 sites. Perfect agreement was seen between organized T2 and histologic findings of hyaline cartilage and between disorganized T2 and histologic findings of fibrous reparative tissue (kappa = 1.0). Strong agreement was seen between organized T2 and normal PLM findings and between disorganized T2 and abnormal PLM findings (kappa = .92). Quantitative assessment of the deep, middle, and superficial cartilage, respectively, showed mean T2 values of 53.3, 58.6, and 54.9 msec at reparative fibrous tissue sites and 40.7, 53.6, and 61.6 msec at hyaline cartilage sites. A

Negative differential resistance and switch behavior of T-BxNy (x, y = 5, 6, 11) molecular junctions

NASA Astrophysics Data System (ADS)

Wang, Shi-Liang; Yang, Chuan-Lu; Wang, Mei-Shan; Ma, Xiao-Guang; Xin, Jian-Guo

2017-05-01

The electronic transport properties of T-BxNy (x, y = 5, 6, 11) molecular junction are investigated based on first-principle density functional theory and non-equilibrium Green's function method. Strong negative differential resistance (NDR) behavior is observed for T-B5N6 molecule under negative and positive bias voltages, with an obvious switch effect for T-B6N5. However, only small NDR is shown for the complex of the two molecules. The projected device density of states, the spatial distribution of molecular orbitals, and the effect of transmission spectra under various bias voltages on the electronic transport properties are analyzed. The obvious effect of bias voltage on the changes in the electronic distribution of frontier molecular orbitals is responsible for the NDR or switch behavior. Therefore, different functional molecular devices can be obtained with different structures of T-BxNy.

Aberrant phenotypes in peripheral T cell lymphomas.

PubMed Central

Hastrup, N; Ralfkiaer, E; Pallesen, G

1989-01-01

Seventy six peripheral T cell lymphomas were examined immunohistologically to test their reactivity with a panel of monoclonal antibodies against 11 T cell associated antigens (CD1-8, CD27, UCHL1, and the T cell antigen receptor). Sixty two (82%) lymphomas showed aberrant phenotypes, and four main categories were distinguished as follows: (i) lack of one or several pan-T cell antigens (49, 64% of the cases); (ii) loss of both the CD4 and CD8 antigens (11, 15% of the cases); (iii) coexpression of the CD4 and CD8 antigens (13, 17% of the cases); and (iv) expression of the CD1 antigen (eight, 11% of the cases). No correlation was seen between the occurrence of aberrant phenotypes and the histological subtype. It is concluded that the demonstration of an aberrant phenotype is a valuable supplement to histological assessment in the diagnosis of peripheral T cell lymphomas. It is recommended that the panel of monoclonal antibodies against T cell differentiation antigens should be fairly large, as apparently any antigen may be lost in the process of malignant transformation. Images Figure PMID:2469701

Simultaneous quantification of T4, T3, rT3, 3,5-T2 and 3,3'-T2 in larval zebrafish (Danio rerio) as a model to study exposure to polychlorinated biphenyls.

PubMed

Chen, Xiaopeng; Walter, Kyla M; Miller, Galen W; Lein, Pamela J; Puschner, Birgit

2018-06-01

Environmental toxicants that interfere with thyroid hormone (TH) signaling can impact growth and development in animals and humans. Zebrafish represent a model to study chemically induced TH disruption, prompting the need for sensitive detection of THs. Simultaneous quantification of 3,3',5-triiodo-l-thyronine (T3), thyroxine (T4), 3,3',5'-triiodo-l-thyronine (rT3), 3,5-diiodo-l-thyronine (3,5-T2) and 3,3'-diiodo-l-thyronine (3,3'-T2) in zebrafish larvae was achieved by ultra-performance liquid chromatography-tandem mass spectrometry in positive ion mode. Solid-phase extraction with SampliQ cartridges and derivatization with 3 m hydrochloric acid in n-butanol reduced matrix effects. Derivatized compounds were separated on an Acquity UPLC BEH C 18 column with mobile phases consisting of 0.1% acetic acid in deionized water and 0.1% acetic acid in methanol. The limits of detection ranged from 0.5 to 0.6 pg injected on column. The method was validated by evaluating recovery (77.1-117.2%), accuracy (87.3-123.9%) and precision (0.5-12.4%) using diluted homogenized zebrafish embryos spiked with all target compounds. This method was then applied to zebrafish larvae collected after 114 h of exposure to polychlorinated biphenyls (PCBs), including PCB 28, PCB 66 and PCB 95, or the technical mixture Aroclor 1254. Exposure to PCB 28 and PCB 95 increased the T4:T3 ratio and decreased the T3:rT3 ratio, demonstrating that this method can effectively detect PCB-induced alterations in THs. Copyright © 2018 John Wiley & Sons, Ltd.

When Deriving the Spatial QRS-T Angle from the 12-lead ECG, which Transform is More Frank: Regression or Inverse Dower?

NASA Technical Reports Server (NTRS)

Schlegel, Todd T.; Cortez, Daniel

2010-01-01

Our primary objective was to ascertain which commonly used 12-to-Frank-lead transformation yields spatial QRS-T angle values closest to those obtained from simultaneously collected true Frank-lead recordings. Simultaneous 12-lead and Frank XYZ-lead recordings were analyzed for 100 post-myocardial infarction patients and 50 controls. Relative agreement, with true Frank-lead results, of 12-to-Frank-lead transformed results for the spatial QRS-T angle using Kors regression versus inverse Dower was assessed via ANOVA, Lin s concordance and Bland-Altman plots. Spatial QRS-T angles from the true Frank leads were not significantly different than those derived from the Kors regression-related transformation but were significantly smaller than those derived from the inverse Dower-related transformation (P less than 0.001). Independent of method, spatial mean QRS-T angles were also always significantly larger than spatial maximum (peaks) QRS-T angles. Spatial QRS-T angles are best approximated by regression-related transforms. Spatial mean and spatial peaks QRS-T angles should also not be used interchangeably.

Reproducibility of MR-Based Liver Fat Quantification Across Field Strength: Same-Day Comparison Between 1.5T and 3T in Obese Subjects

PubMed Central

Artz, Nathan S.; Haufe, William M.; Hooker, Catherine A.; Hamilton, Gavin; Wolfson, Tanya; Campos, Guilherme M.; Gamst, Anthony C.; Schwimmer, Jeffrey B.; Sirlin, Claude B.; Reeder, Scott B.

2016-01-01

Purpose To examine the reproducibility of quantitative magnetic resonance (MR) methods to estimate hepatic proton density fat-fraction (PDFF) at different magnetic field strengths. Materials and Methods This Health Insurance Portability and Accountability Act (HIPAA)-compliant study was approved by the Institutional Review Board. Following informed consent, 25 severely obese subjects (mean body mass index [BMI]: 45 ± 4, range: 38–53 kg/m2) were scanned at 1.5T and 3T on the same day. Two confounder-corrected multiecho chemical shift-encoded gradient-echo-based imaging methods were acquired to estimate PDFF over the entire liver: 3D complex-based (MRI-C) and 2D magnitude-based (MRI-M) MRI. Single-voxel MR spectroscopy (MRS) was performed in the right liver lobe. Using linear regression, pairwise comparisons of estimated PDFF were made between methods (MRI-C, MRI-M, MRS) at each field strength and for each method across field strengths. Results 1.5T vs. 3T regression analyses for MRI-C, MRI-M, and MRS PDFF measurements yielded R2 values of 0.99, 0.97, and 0.90, respectively. The best-fit line was near unity (slope(m) = 1, intercept(b) = 0), indicating excellent agreement for each case: MRI-C (m = 0.92 [0.87, 0.99], b = 1.4 [0.7, 1.8]); MRI-M (m = 1.0 [0.90, 1.08], b = −1.4 [−2.4, −0.5]); MRS (m = 0.98 [0.82, 1.15], b = 1.2 [−0.2, 3.0]). Comparing MRI-C and MRI-M yielded an R2 = 0.98 (m = 1.1 [1.02, 1.16], b = −1.8 [−2.8, −1.1]) at 1.5T, and R2 = 0.99 (m = 0.98 [0.93, 1.03], b = 1.2 [0.7, 1.7]) at 3T. Conclusion This study demonstrates that PDFF estimation is reproducible across field strengths and across two confounder-corrected MR-based methods. PMID:25620624

Reproducibility of MR-based liver fat quantification across field strength: Same-day comparison between 1.5T and 3T in obese subjects.

PubMed

Artz, Nathan S; Haufe, William M; Hooker, Catherine A; Hamilton, Gavin; Wolfson, Tanya; Campos, Guilherme M; Gamst, Anthony C; Schwimmer, Jeffrey B; Sirlin, Claude B; Reeder, Scott B

2015-09-01

To examine the reproducibility of quantitative magnetic resonance (MR) methods to estimate hepatic proton density fat-fraction (PDFF) at different magnetic field strengths. This Health Insurance Portability and Accountability Act (HIPAA)-compliant study was approved by the Institutional Review Board. Following informed consent, 25 severely obese subjects (mean body mass index [BMI]: 45 ± 4, range: 38-53 kg/m(2) ) were scanned at 1.5T and 3T on the same day. Two confounder-corrected multiecho chemical shift-encoded gradient-echo-based imaging methods were acquired to estimate PDFF over the entire liver: 3D complex-based (MRI-C) and 2D magnitude-based (MRI-M) MRI. Single-voxel MR spectroscopy (MRS) was performed in the right liver lobe. Using linear regression, pairwise comparisons of estimated PDFF were made between methods (MRI-C, MRI-M, MRS) at each field strength and for each method across field strengths. 1.5T vs. 3T regression analyses for MRI-C, MRI-M, and MRS PDFF measurements yielded R(2) values of 0.99, 0.97, and 0.90, respectively. The best-fit line was near unity (slope(m) = 1, intercept(b) = 0), indicating excellent agreement for each case: MRI-C (m = 0.92 [0.87, 0.99], b = 1.4 [0.7, 1.8]); MRI-M (m = 1.0 [0.90, 1.08], b = -1.4 [-2.4, -0.5]); MRS (m = 0.98 [0.82, 1.15], b = 1.2 [-0.2, 3.0]). Comparing MRI-C and MRI-M yielded an R(2)  = 0.98 (m = 1.1 [1.02, 1.16], b = -1.8 [-2.8, -1.1]) at 1.5T, and R(2)  = 0.99 (m = 0.98 [0.93, 1.03], b = 1.2 [0.7, 1.7]) at 3T. This study demonstrates that PDFF estimation is reproducible across field strengths and across two confounder-corrected MR-based methods. © 2015 Wiley Periodicals, Inc.

Low temperature structural transformation in T[Ni(CN){sub 4}].xpyz with x=1,2; T=Mn,Co,Ni,Zn,Cd; pyz=pyrazine

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

Rodriguez-Hernandez, J.; Instituto de Ciencia y Tecnologia de Materiales, Universidad de La Habana; Lemus-Santana, A.A.

2010-01-15

The materials under study are pillared solids T[Ni(CN){sub 4}].xpyz with one and two (x=1,2) pyrazine (pyz) molecules and where T=Mn, Co, Ni, Zn, Cd. Stimulated by their structural features and potential role as prototype of porous solids for hydrogen storage, the structural stability under cryogenic conditions for this series of pillared solids was studied. At low temperature, in the 100-200 K range, the occurrence of a reversible structural transformation was found. For T=Mn, Co, Zn, Cd, with x=2, the structural transformation was observed to occur around 185 K, and the low temperature phase crystallizes with a monoclinic unit cell (spacemore » group Pc). This structure change results from certain charge redistribution on cooling within the involved ligands. For T=Ni with x=1, both the low and high temperature phases crystallize with unit cells of tetragonal symmetry, within the same space group but with a different unit cell volume. In this case the structure change is observed around 120 K. Above that temperature the rotational states for the pyrazine molecule are thermally excited and all the pyrazine molecules in the structure become equivalent. Under this condition the material structure is described using a smaller structural unit. The structural study using X-ray powder diffraction data was complemented with calorimetric and Raman spectroscopy measurements. For the low temperature phases the crystal structures were solved from Patterson methods and then refined using the Rietveld method. - Graphical abstract: Low temperature ordered structure for pyrazine in T[Ni(CN){sub 4}].pyz.« less

T2 relaxation times of the glenohumeral joint at 3.0 T MRI in patients with and without primary and secondary osteoarthritis.

PubMed

Lee, So-Yeon; Park, Hee-Jin; Kwon, Heon-Ju; Kim, Mi Sung; Choi, Seon Hyeong; Choi, Yoon Jung; Kim, Eugene

2015-11-01

Quantitative magnetic resonance imaging (MRI) of cartilage has recently been applied to patients with osteoarthritis (OA). T2 mapping is a sensitive method of detecting changes in the chemical composition and structure of cartilage. To establish baseline T2 values of glenohumeral joint cartilage at 3.0 T and compare T2 values among subjects with and without OA. The study involved 30 patients (18 women, 12 men; median age, 67 years; age range, 51-78 years) with primary (n = 7) and secondary OA (n = 23) in the glenohumeral joint and 34 subjects without OA (19 women, 15 men; median age, 49 years; age range, 23-63 years). All subjects were evaluated by radiography and 3.0 T MRI including a multi-echo T2-weighted spin echo pulse sequence. The T2 value of the cartilage was measured by manually drawing the region of interest on the T2 map. Per-zone comparison of T2 values was performed using Mann-Whitney U test. Median T2 values differed significantly between subjects without OA (36.00 ms [interquartile range, 33.89-37.31 ms]) and those with primary (37.52 ms [36.84-39.11], P = 0.028), but not secondary (36.87 ms [34.70-41.10], P = 0.160) OA. Glenohumeral cartilage T2 values were higher in different zones between patients with primary and secondary OA than in subjects without OA. These T2 values can be used for comparison to assess cartilage degeneration in patients with shoulder OA. Significant differences in T2 were observed among subjects without OA and those with primary and secondary OA. © The Foundation Acta Radiologica 2014.

The mechanism of T-cell mediated cytotoxicity. VI. T-cell projections and their role in target cell killing.

PubMed Central

Sanderson, C J; Glauert, A M

1979-01-01

Electron micrographs of material fixed during the first 10 min of a T-cell cytotoxic system showed T-cell projections and T-cell burrowing into target cells. These observations were made possible by using a system with a very high rate of killing. The projections vary in shape and size, and can push deeply into the target cell, distorting organelles in their path, including the nucleus. The projections contain fine fibrillar material, to the exclusion of organelles. They push the target cell membrane in front of them to form pockets approximating to the shape of the projection. Areas of close contact occur between the projections and the target cell membrane, particularly at the leading edges. The likelihood that these projections develop as a result of contact with specific antigen, and are involved in the cytotoxic mechanism is discussed. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 PMID:311336

Modifications modulate anticodon loop dynamics and codon recognition of E. coli tRNA(Arg1,2).

PubMed

Cantara, William A; Bilbille, Yann; Kim, Jia; Kaiser, Rob; Leszczyńska, Grażyna; Malkiewicz, Andrzej; Agris, Paul F

2012-03-02

Three of six arginine codons are read by two tRNA(Arg) isoacceptors in Escherichia coli. The anticodon stem and loop of these isoacceptors (ASL(Arg1,2)) differs only in that the position 32 cytidine of tRNA(Arg1) is posttranscriptionally modified to 2-thiocytidine (s(2)C(32)). The tRNA(Arg1,2) are also modified at positions 34 (inosine, I(34)) and 37 (2-methyladenosine, m(2)A(37)). To investigate the roles of modifications in the structure and function, we analyzed six ASL(Arg1,2) constructs differing in their array of modifications by spectroscopy and codon binding assays. Thermal denaturation and circular dichroism spectroscopy indicated that modifications contribute thermodynamic and base stacking properties, resulting in more order but less stability. NMR-derived structures of the ASL(Arg1,2) showed that the solution structures of the ASLs were nearly identical. Surprisingly, none possessed the U-turn conformation required for effective codon binding on the ribosome. Yet, all ASL(Arg1,2) constructs efficiently bound the cognate CGU codon. Three ASLs with I(34) were able to decode CGC, whereas only the singly modified ASL(Arg1,2)(ICG) with I(34) was able to decode CGA. The dissociation constants for all codon bindings were physiologically relevant (0.4-1.4 μM). However, with the introduction of s(2)C(32) or m(2)A(37) to ASL(Arg1,2)(ICG), the maximum amount of ASL bound to CGU and CGC was significantly reduced. These results suggest that, by allowing loop flexibility, the modifications modulate the conformation of the ASL(Arg1,2), which takes one structure free in solution and two others when bound to the cognate arginyl-tRNA synthetase or to codons on the ribosome where modifications reduce or restrict binding to specific codons. Copyright © 2011 Elsevier Ltd. All rights reserved.

t10,c12-Conjugated linoleic acid stimulates mammary tumor progression in Her2/ErbB2 mice through activation of both proliferative and survival pathways

PubMed Central

Meng, Xiaojing; Shoemaker, Suzanne F.; McGee, Sibel O.; Ip, Margot M.

2008-01-01

The t10,c12 isomer of conjugated linoleic acid (CLA) inhibits rat mammary carcinogenesis, metastasis from a transplantable mouse mammary tumor and angiogenesis; however, it stimulates mammary tumorigenesis in transgenic mice overexpressing ErbB2 in the mammary epithelium (ErbB2 transgenic mice). In the current study, we report that a 4-week supplementation of the diet with 0.5% trans-10, cis-12 conjugated linoleic acid (t10,c12-CLA) stimulated the growth of established ErbB2-overexpressing mammary tumors by 30% and increased the number of new tumors from 11% to 82%. Additionally, when t10,c12-CLA supplementation of ErbB2 transgenic mice was initiated at 21 weeks of age, a time just prior to tumor appearance, overall survival was decreased from 46.4 weeks in the control to 39.0 weeks in the CLA group, and survival after detection of a palpable tumor from 7.5 to 4.6 weeks. Short-term supplementation from 10 to 14 weeks or 21 to 25 weeks of age temporarily accelerated tumor development, but over the long term, there was no significant effect on mammary tumorigenesis. Long term as well as a short 4-week supplementation increased mammary epithelial hyperplasia and lobular development, and altered the mammary stroma; this was reversible in mice returned to the control diet. t10,c12-CLA altered proliferation and apoptosis of the mammary epithelium, although this differed depending on the length of administration and/or the age of the mice. The increased tumor development with t10,c12-CLA was associated with increased phosphorylation of the IGF-I/insulin receptor, as well as increased signaling through the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways; however, neither phospho-ErbB2 nor ErbB2 was altered. PMID:18339686

Oncolytic adenovirus co-expressing IL-12 and IL-18 improves tumor-specific immunity via differentiation of T cells expressing IL-12Rβ2 or IL-18Rα

PubMed Central

Choi, I-K; Lee, J-S; Zhang, S-N; Park, J; Lee, K-M; Sonn, C H; Yun, C-O

2011-01-01

The oncolytic adenovirus (Ad) is currently being advanced as a promising antitumor remedy as it selectively replicates in tumor cells and can transfer and amplify therapeutic genes. Interleukin (IL)-12 induces a potent antitumor effect by promoting natural killer (NK) cell and cytotoxic T cell activities. IL-18 also augments cytotoxicity of NK cells and proliferation of T cells. This effect further enhances the function of IL-12 in a synergistic manner. Therefore, we investigated for the first time an effective cancer immunogene therapy of syngeneic tumors via intratumoral administration of oncolytic Ad co-expressing IL-12 and IL-18, RdB/IL-12/IL-18. Intratumoral administration of RdB/IL-12/IL-18 improved antitumor effects, as well as increased survival, in B16-F10 murine melanoma model. The ratio of T-helper type 1/2 cytokine as well as the levels of IL-12, IL-18, interferon-γ and granulocyte–macrophage colony-stimulating factor was markedly elevated in RdB/IL-12/IL-18-treated tumors. Mice injected with RdB/IL-12/IL-18 also showed enhanced cytotoxicity of tumor-specific immune cells. Consistent with these results, immense necrosis and infiltration of NK cells, as well as CD4+ and CD8+ T cells, were observed in RdB/IL-12/IL-18-treated tumor tissues. Importantly, tumors treated with RdB/IL-12/IL-18 showed an elevated number of T cells expressing IL-12Rβ2 or IL-18Rα. These results provide a new insight into therapeutic mechanisms of IL-12 plus IL-18 and provide a potential clinical cancer immunotherapeutic agent for improved antitumor immunity. PMID:21451575

Evidence for Biomass Burning from 14C and 13C/12C Measurements at T-0 and T-1 during MILAGRO.

NASA Astrophysics Data System (ADS)

Gaffney, J. S.; Marley, N. A.; Tackett, M. J.; Sturchio, N. C.; Heraty, L. J.; Martinez, N.; Hardy, K.; Guilderson, T.

2007-12-01

Both stable carbon isotopic and radiocarbon characterizations of aerosols can yield important information regarding the sources of carbonaceous aerosols in urban and regional environments. Biomass derived materials are labeled due to their recent photochemical activity in radiocarbon and vary depending upon the photochemical pathway (either C-4 or C-3) in stable carbon-13 content. C-4 being enriched over C-3. During the MILAGRO campaign, quartz filter samples were taken at 12 hour intervals from 5 am to 5 pm (day) and from 5 pm to 5 am (night) during the month of March 2006. These samples were taken at the two super-sites, T-0 (Instituto Mexicano de Petroleo in Mexico City) and T-1 (Universidad Technologica de Tecamac, State of Mexico). The total carbon content was analyzed for stable carbon isotopic composition as well as for radiocarbon. Stable isotope mass spectroscopy was used to determine the carbon-13 to carbon-12 isotopic ratios on carbon dioxide. The carbon dioxide was then converted to graphite for analysis by accelerator mass spectrometry at the Center for Accelerator Mass Spectrometry at Lawrence Livermore National Laboratory. Results are presented for the carbon-13 content relative to the PDB standard and radiocarbon is given relative to recent carbon. The results for total radiocarbon content show that the carbonaceous aerosol content in Mexico City has more than half of the carbon coming from biomass derived sources. These can include inflow of biomass burning aerosols into the T-0 site as well as the input from local burning of biofuels and trash containing biomass derived materials (paper, boxes, etc.). Data also indicate that at the T-1 site biomass burning of C-4 grasses appears to be significant in that the carbon-13 values observed are enriched. Also at T-1 the radiocarbon levels are also found to be slightly higher indicating regional biomass burning as a significant contributor to aerosol carbon in the 0.1 to 1.0 micron size fraction. Some day

Maturation of monocyte derived dendritic cells with OK432 boosts IL-12p70 secretion and conveys strong T-cell responses

PubMed Central

2011-01-01

Background Design of tumour specific immunotherapies using the patients' own dendritic cells (DC) is a fast advancing scientific field. The functional qualities of the DC generated in vitro are critical, and today's gold standard for maturation is a cytokine cocktail consisting of IL-1β, IL-6, TNF-α and PGE2 generating cells lacking IL-12p70 production. OK432 is an immunotherapeutic agent derived from killed Streptococcus pyogenes that has been used clinically to treat malignant and benign neoplasms for decades. Methods In this study, we analysed the effects of OK432 on DC maturation, DC migration, cytokine and chemokine secretion as well as T-cell stimulatory capacity, and compared it to the cytokine cocktail alone and combinations of OK432 with the cytokine cocktail. Results OK432 induced a marked up-regulation of CD40 on the cell surface as well as a strong inflammatory response from the DC with significantly more secretion of 19 different cytokines and chemokines compared to the cytokine cocktail. Interestingly, secretion of IL-15 and IL-12p70 was detected at high concentrations after maturation of DC with OK432. However, the OK432 treated DC did not migrate as well as DC treated with cytokine cocktail in a transwell migration assay. During allogeneic T-cell stimulation OK432 treated DC induced proliferation of over 50 percent of CD4 and 30 percent of CD8 T-cells for more than two cell divisions, whereas cytokine cocktail treated DC induced proliferation of 12 and 11 percent of CD4 and CD8 T-cells, respectively. Conclusions The clinically approved compound OK432 has interesting properties that warrants its use in DC immunotherapy and should be considered as a potential immunomodulating agent in cancer immunotherapy. PMID:21208424

Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS). A new prognostic model developed by the International T cell Project Network.

PubMed

Federico, Massimo; Bellei, Monica; Marcheselli, Luigi; Schwartz, Marc; Manni, Martina; Tarantino, Vittoria; Pileri, Stefano; Ko, Young-Hyeh; Cabrera, Maria E; Horwitz, Steven; Kim, Won S; Shustov, Andrei; Foss, Francine M; Nagler, Arnon; Carson, Kenneth; Pinter-Brown, Lauren C; Montoto, Silvia; Spina, Michele; Feldman, Tatyana A; Lechowicz, Mary J; Smith, Sonali M; Lansigan, Frederick; Gabus, Raul; Vose, Julie M; Advani, Ranjana H

2018-06-01

Different models to investigate the prognosis of peripheral T cell lymphoma not otherwise specified (PTCL-NOS) have been developed by means of retrospective analyses. Here we report on a new model designed on data from the prospective T Cell Project. Twelve covariates collected by the T Cell Project were analysed and a new model (T cell score), based on four covariates (serum albumin, performance status, stage and absolute neutrophil count) that maintained their prognostic value in multiple Cox proportional hazards regression analysis was proposed. Among patients registered in the T Cell Project, 311 PTCL-NOS were retained for study. At a median follow-up of 46 months, the median overall survival (OS) and progression-free survival (PFS) was 20 and 10 months, respectively. Three groups were identified at low risk (LR, 48 patients, 15%, score 0), intermediate risk (IR, 189 patients, 61%, score 1-2), and high risk (HiR, 74 patients, 24%, score 3-4), having a 3-year OS of 76% [95% confidence interval 61-88], 43% [35-51], and 11% [4-21], respectively (P < 0·001). Comparing the performance of the T cell score on OS to that of each of the previously developed models, it emerged that the new score had the best discriminant power. The new T cell score, based on clinical variables, identifies a group with very unfavourable outcomes. © 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

[Evaluation of Artificial Hip Joint with Radiofrequency Heating Issues during MRI Examination: A Comparison between 1.5 T and 3 T].

PubMed

Yamazaki, Masaru; Ideta, Takahiro; Kudo, Sadahiro; Nakazawa, Masami

2016-06-01

In magnetic resonance imaging (MRI), when radiofrequency (RF) is irradiated to a subject with metallic implant, it can generate heat by RF irradiation. Recently 3 T MRI scanner has spread widely and imaging for any regions of whole body has been conducted. However specific absorption rate (SAR) of 3 T MRI becomes approximately four times as much as the 1.5 T, which can significantly affect the heat generation of metallic implants. So, we evaluated RF heating of artificial hip joints in different shapes and materials in 1.5 T and 3 T MRI. Three types of artificial hip joints made of stainless alloy, titanium alloy and cobalt chrome alloy were embedded in the human body-equivalent phantom respectively and their temperature change were measured for twenty minutes by 1.5 T and 3 T MRI. The maximum temperature rise was observed at the bottom head in all of three types of artificial hip joints, the rise being 12°C for stainless alloy, 11.9°C for titanium alloy and 6.1°C for cobalt chrome alloy in 1.5 T. The temperature rise depended on SAR and the increase of SAR had a good linear relationship with the temperature rise. It was found from the result that the RF heating of metallic implants can take place in various kinds of material and the increase of SAR has a good linear relationship with the temperature rise. This experience shows that reduction of SAR can decrease temperature of metallic implants.

Field Quality Measurements in the FNAL Twin-Aperture 11 T Dipole for LHC Upgrades

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

Strauss, T.; Apollinari, G.; Apollinari, G.

2016-11-08

FNAL and CERN are developing an 11 T Nb3Sn dipole suitable for installation in the LHC to provide room for additional collimators. Two 1 m long collared coils previously tested at FNAL in single-aperture dipole configuration were assembled into the twin-aperture configuration and tested including magnet quench performance and field quality. The results of magnetic measurements are reported and discussed in this paper.

Effects of potassium iodide in concentrations of TSH, tT3 and tT4 in serum of subjects with sporotrichosis.

PubMed

Ramírez Soto, Max Carlos

2014-08-01

The saturated potassium iodide solution (SSKI) as treatment for sporotrichosis may cause hypothyroidism by suppressing the synthesis of thyroid hormones (tT3 and tT4 ) and the iodine excess could lead to thyrotoxicosis. Evaluating the changes in serum levels of TSH, tT3 and tT4 in euthyroid patients with sporotrichosis treated with SSKI. For the selection of euthyroid patients, TSH, tT3 and tT4 concentrations were measured for those adults and children diagnosed with sporotrichosis. Each paediatric patient was administered SSKI orally in increasing doses of 2-20 drops/3 times/day and 4-40 drops/3 times/day in adults. Serum concentrations of TSH, tT3 and tT4 were measured 20 days after started the treatment and 15 days posttreatment. Eight euthyroid patients aged between 2 to 65 years old were included. After 20 days of treatment, two suffered subclinical hypothyroidism, one developed subclinical hyperthyroidism, and one hyperthyroxinaemia euthyroid. At 15 days posttreatment only four patients were evaluated and all serum levels of TSH, tT3 and tT4 were normal. Some euthyroid patients with sporotrichosis can develop hyperthyroidism or subclinical iodine-induced hypothyroidism, during the administration of 3 or 6 g SSKI/day. © 2014 Blackwell Verlag GmbH.

The C-type lectin OCILRP2 costimulates EL4 T cell activation via the DAP12-Raf-MAP kinase pathway.

PubMed

Lou, Qiang; Zhang, Wei; Liu, Guangchao; Ma, Yuanfang

2014-01-01

OCILRP2 is a typical Type-II transmembrane protein that is selectively expressed in activated T lymphocytes, dendritic cells, and B cells and functions as a novel co-stimulator of T cell activation. However, the signaling pathways underlying OCILRP2 in T cell activation are still not completely understood. In this study, we found that the knockdown of OCILRP2 expression with shRNA or the blockage of its activity by an anti-OCILRP2 antagonist antibody reduced CD3/CD28-costimulated EL4 T cell viability and IL-2 production, inhibit Raf1, MAPK3, and MAPK8 activation, and impair NFAT and NF-κB transcriptional activities. Furthermore, immunoprecipitation results indicated that OCILRP2 could interact with the DAP12 protein, an adaptor containing an intracellular ITAM motif that can transduce signals to induce MAP kinase activation for T cell activation. Our data reveal that after binding with DAP12, OCILRP2 activates the Raf-MAP kinase pathways, resulting in T cell activation.

Contribution of herpesvirus specific CD8 T cells to anti-viral T cell response in humans.

PubMed

Sandalova, Elena; Laccabue, Diletta; Boni, Carolina; Tan, Anthony T; Fink, Katja; Ooi, Eng Eong; Chua, Robert; Shafaeddin Schreve, Bahar; Ferrari, Carlo; Bertoletti, Antonio

2010-08-19

Herpesviruses infect most humans. Their infections can be associated with pathological conditions and significant changes in T cell repertoire but evidences of symbiotic effects of herpesvirus latency have never been demonstrated. We tested the hypothesis that HCMV and EBV-specific CD8 T cells contribute to the heterologous anti-viral immune response. Volume of activated/proliferating virus-specific and total CD8 T cells was evaluated in 50 patients with acute viral infections: 20 with HBV, 12 with Dengue, 12 with Influenza, 3 with Adenovirus infection and 3 with fevers of unknown etiology. Virus-specific (EBV, HCMV, Influenza) pentamer+ and total CD8 T cells were analyzed for activation (CD38/HLA-DR), proliferation (Ki-67/Bcl-2(low)) and cytokine production. We observed that all acute viral infections trigger an expansion of activated/proliferating CD8 T cells, which differs in size depending on the infection but is invariably inflated by CD8 T cells specific for persistent herpesviruses (HCMV/EBV). CD8 T cells specific for other non-related non persistent viral infection (i.e. Influenza) were not activated. IL-15, which is produced during acute viral infections, is the likely contributing mechanism driving the selective activation of herpesvirus specific CD8 T cells. In addition we were able to show that herpesvirus specific CD8 T cells displayed an increased ability to produce the anti-viral cytokine interferon-gamma during the acute phase of heterologous viral infection. Taken together, these data demonstrated that activated herpesvirus specific CD8 T cells inflate the activated/proliferating CD8 T cells population present during acute viral infections in human and can contribute to the heterologous anti-viral T cell response.

Co-existence of t(6;13)(p21;q14.1) and trisomy 12 in chronic lymphocytic leukemia.

PubMed

de Oliveira, Fábio Morato; de Figueiredo Pontes, Lorena Lobo; Bassi, Sarah Cristina; Dalmazzo, Leandro Felipe Figueiredo; Falcão, Roberto Passetto

2012-06-01

We report a case of a 57-year-old man diagnosed with chronic lymphocytic leukemia (CLL) and presence of a rare t(6;13)(p21;q14.1) in association with an extra copy of chromosome 12. Classical cytogenetic analysis using the immunostimulatory combination of DSP30 and IL-2 showed the karyotype 47,XY,t(6;13)(p21;q14.1), +12 in 75% of the metaphase cells. Spectral karyotype analysis (SKY) confirmed the abnormality previously seen by G-banding. Additionally, interphase fluorescence in situ hybridization using an LSI CEP 12 probe performed on peripheral blood cells without any stimulant agent showed trisomy of chromosome 12 in 67% of analyzed cells (134/200). To the best of our knowledge, the association of t(6;13)(p21;q14.1) and +12 in CLL has never been described. The prognostic significance of these new findings in CLL remains to be elucidated. However, the patient has been followed up since 2009 without any therapeutic intervention and has so far remained stable.

Li experiments at the tokamak T-11 M in field of steady state PFC investigations

NASA Astrophysics Data System (ADS)

Mirnov, S. V.; Lazarev, V. B.

2011-08-01

The renewable plasma facing components (PFCs) of steady state tokamak-reactor can be created in framework of Lithium emitter-collector concept, which suggests Li-loop development close the Li-PFC and plasma periphery. It should ensure: Li-emission from PFC into the plasma, plasma periphery cooling by non-coronal Li radiation, Li ions collection before their loss on the wall and Li return into emitter. The subjects of the last T-11 M investigations were the Lithium collection by limiters and Lithium removal from the wall during tokamak conditioning. The Lithium behavior was studied with witness samples and mobile graphite probe. It was shown that Li-deposit on the sides of rail Li-limiter (collector) is proportional to the Li-emission from the Li-limiter (emitter). Lithium deposit on the ion-drift side of Li-limiter is up to 2-3 times more than on the electron-side. The efficiency of Li-collection by T-11 M limiters can be 60 ± 20% of total Lithium emission from Li-limiter during plasma discharges.

A novel homozygous mutation IVS6+5G>T in CYP11B1 gene in a Vietnamese patient with 11β-hydroxylase deficiency.

PubMed

Nguyen, Thi Phuong Mai; Nguyen, Thu Hien; Ngo, Diem Ngoc; Vu, Chi Dung; Nguyen, Thi Kim Lien; Nong, Van Hai; Nguyen, Huy Hoang

2015-07-10

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease which is characterized by a deficiency of one of the enzymes involved in the synthesis of cortisol from cholesterol by the adrenal cortex. CAH cases arising from impaired 11β-hydroxylase are the second most common form. Mutations in the CYP11B1 gene are the cause of 11β-hydroxylase deficiency. This study was performed on a patient with congenital adrenal hyperplasia and with premature development such as enlarged penis, muscle development, high blood pressure, and bone age equivalent of 5 years old at 2 years of chronological age. Biochemical tests for steroids confirmed the diagnosis of CAH. We used PCR and sequencing to screen for mutations in CYP11B1 gene. Results showed that the patient has a novel homozygous mutation of guanine (G) to thymine (T) in intron 6 (IVS6+5G>T). The analysis of this mutation by MaxEntScan boundary software indicated that this mutant could affect the gene splicing during transcription. Copyright © 2015 Elsevier B.V. All rights reserved.

Increased numbers of pre-existing memory CD8 T cells and decreased T-bet expression can restrain terminal differentiation of secondary effector and memory CD8 T cells1

PubMed Central

Joshi, Nikhil S.; Cui, Weiguo; Dominguez, Claudia; Chen, Jonathan H.; Hand, Timothy W.; Kaech, Susan M.

2011-01-01

Memory CD8 T cells acquire TEM properties following reinfection, and may reach terminally differentiated, senescent states (“Hayflick limit”) after multiple infections. The signals controlling this process are not well understood, but we found that the degree of 2o effector and memory CD8 T cell differentiation was intimately linked to the amount of T-bet expressed upon reactivation and pre-existing memory CD8 T cell number (i.e., 1o memory CD8 T cell precursor frequency) present during secondary infection. Compared to naïve cells, memory CD8 T cells were predisposed towards terminal effector (TE) cell differentiation because they could immediately respond to IL-12 and induce T-bet, even in the absence of antigen. TE cell formation following 2o or 3o infections was dependent on increased T-bet expression because T-bet+/− cells were resistant to these phenotypic changes. Larger numbers of pre-existing memory CD8 T cells limited the duration of 2o infection and the amount of IL-12 produced, and consequently, this reduced T-bet expression and the proportion of 2o TE CD8 T cells that formed. Together, these data show that, over repeated infections, memory CD8 T cell quality and proliferative fitness is not strictly determined by the number of serial encounters with antigen or cell divisions, but is a function of the CD8 T cell differentiation state, which is genetically controlled in a T-bet-dependent manner. This differentiation state can be modulated by pre-existing memory CD8 T cell number and the intensity of inflammation during reinfection. These results have important implications for vaccinations involving prime-boost strategies. PMID:21930973

Simultaneous occurrence of t(9;22)(q34;q11.2) and t(16;16)(p13;q22) in a patient with chronic myeloid leukemia in blastic phase.

PubMed

Zámecníkova, Adriana; Al Bahar, Soad; Ramesh, Pandita

2008-06-01

Coexistence of two specific chromosomal translocations in the same clone is an infrequent phenomenon and has only rarely been reported in hematological malignancies. We report a combination of t(16;16)(p13;q22), the Philadelphia translocation t(9;22)(q34;q11.2), and deletion of the long arm of chromosome 7 in a patient with chronic myeloid leukemia in blast phase. Monotherapy treatment with imatinib mesylate resulted in the disappearance of the Ph-positive clone, but with persistence of t(16;16) and del(7) in all of the metaphases examined. The case illustrates that, although imatinib mesylate can be an effective treatment in eradication of the BCR-ABL fusion gene cells, the occurrence of additional specific abnormalities in Philadelphia-positive leukemias may pose a significant therapeutic challenge. (c) 2008 Elsevier Inc.

Five New Records of Soil-Derived Trichoderma in Korea: T. albolutescens, T. asperelloides, T. orientale, T. spirale, and T. tomentosum

PubMed Central

Jang, Seokyoon; Jang, Yeongseon; Kim, Chul-Whan; Lee, Hanbyul; Hong, Joo-Hyun; Heo, Young Mok; Lee, Young Min; Lee, Dong Wan; Lee, Hyang Burm

2017-01-01

Despite the huge worldwide diversity of Trichoderma (Hypocreaceae, Ascomycota), only about 22 species have been reported in Korea. Thus, between 2013 and 2015, soil-derived Trichoderma spp. were isolated to reveal the diversity of Korean Trichoderma. Phylogenetic analysis of translation elongation factor 1 alpha gene was used for identification. Among the soil-derived Trichoderma, Trichoderma albolutescens, T. asperelloides, T. orientale, T. spirale, and T. tomentosum have not been previously reported in Korea. Thus, we report the five Trichoderma species as new in Korea with morphological descriptions and images. PMID:28435347

Mutations in STAT3 and IL12RB1 impair the development of human IL-17–producing T cells

PubMed Central

de Beaucoudrey, Ludovic; Puel, Anne; Filipe-Santos, Orchidée; Cobat, Aurélie; Ghandil, Pegah; Chrabieh, Maya; Feinberg, Jacqueline; von Bernuth, Horst; Samarina, Arina; Jannière, Lucile; Fieschi, Claire; Stéphan, Jean-Louis; Boileau, Catherine; Lyonnet, Stanislas; Jondeau, Guillaume; Cormier-Daire, Valérie; Le Merrer, Martine; Hoarau, Cyrille; Lebranchu, Yvon; Lortholary, Olivier; Chandesris, Marie-Olivia; Tron, François; Gambineri, Eleonora; Bianchi, Lucia; Rodriguez-Gallego, Carlos; Zitnik, Simona E.; Vasconcelos, Julia; Guedes, Margarida; Vitor, Artur Bonito; Marodi, Laszlo; Chapel, Helen; Reid, Brenda; Roifman, Chaim; Nadal, David; Reichenbach, Janine; Caragol, Isabel; Garty, Ben-Zion; Dogu, Figen; Camcioglu, Yildiz; Gülle, Sanyie; Sanal, Ozden; Fischer, Alain; Abel, Laurent; Stockinger, Birgitta; Picard, Capucine; Casanova, Jean-Laurent

2008-01-01

The cytokines controlling the development of human interleukin (IL) 17–producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17–producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) β, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17–producing T cells. These data suggest that IL-12Rβ1– and STAT-3–dependent signals play a key role in the differentiation and/or expansion of human IL-17–producing T cell populations in vivo. PMID:18591412

Efficient Recreation of t(11;22) EWSR1-FLI1+ in Human Stem Cells Using CRISPR/Cas9.

PubMed

Torres-Ruiz, Raul; Martinez-Lage, Marta; Martin, Maria C; Garcia, Aida; Bueno, Clara; Castaño, Julio; Ramirez, Juan C; Menendez, Pablo; Cigudosa, Juan C; Rodriguez-Perales, Sandra

2017-05-09

Efficient methodologies for recreating cancer-associated chromosome translocations are in high demand as tools for investigating how such events initiate cancer. The CRISPR/Cas9 system has been used to reconstruct the genetics of these complex rearrangements at native loci while maintaining the architecture and regulatory elements. However, the CRISPR system remains inefficient in human stem cells. Here, we compared three strategies aimed at enhancing the efficiency of the CRISPR-mediated t(11;22) translocation in human stem cells, including mesenchymal and induced pluripotent stem cells: (1) using end-joining DNA processing factors involved in repair mechanisms, or (2) ssODNs to guide the ligation of the double-strand break ends generated by CRISPR/Cas9; and (3) all-in-one plasmid or ribonucleoprotein complex-based approaches. We report that the generation of targeted t(11;22) is significantly increased by using a combination of ribonucleoprotein complexes and ssODNs. The CRISPR/Cas9-mediated generation of targeted t(11;22) in human stem cells opens up new avenues in modeling Ewing sarcoma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

High-quality-draft genome sequence of the fermenting bacterium Anaerobium acetethylicum type strain GluBS11T (DSM 29698)

DOE PAGES

Patil, Yogita; Müller, Nicolai; Schink, Bernhard; ...

2017-02-20

Anaerobium acetethylicum strain GluBS11 T belongs to the family Lachnospiraceae within the order Clostridiales. It is a Gram-positive, non-motile and strictly anaerobic bacterium isolated from biogas slurry that was originally enriched with gluconate as carbon source (Patil, et al., Int J Syst Evol Microbiol 65:3289-3296, 2015). Here we describe the draft genome sequence of strain GluBS11 T and provide a detailed insight into its physiological and metabolic features. The draft genome sequence generated 4,609,043 bp, distributed among 105 scaffolds assembled using the SPAdes genome assembler method. It comprises in total 4,132 genes, of which 4,008 were predicted to be proteinmore » coding genes, 124 RNA genes and 867 pseudogenes. The content was 43.51 mol %. The annotated genome of strain GluBS11 T contains putative genes coding for the pentose phosphate pathway, the Embden-Meyerhoff-Parnas pathway, the Entner-Doudoroff pathway and the tricarboxylic acid cycle. The genome revealed the presence of most of the necessary genes required for the fermentation of glucose and gluconate to acetate, ethanol, and hydrogen gas. However, a candidate gene for production of formate was not identified.« less

High-quality-draft genome sequence of the fermenting bacterium Anaerobium acetethylicum type strain GluBS11T (DSM 29698)

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

Patil, Yogita; Müller, Nicolai; Schink, Bernhard

Anaerobium acetethylicum strain GluBS11 T belongs to the family Lachnospiraceae within the order Clostridiales. It is a Gram-positive, non-motile and strictly anaerobic bacterium isolated from biogas slurry that was originally enriched with gluconate as carbon source (Patil, et al., Int J Syst Evol Microbiol 65:3289-3296, 2015). Here we describe the draft genome sequence of strain GluBS11 T and provide a detailed insight into its physiological and metabolic features. The draft genome sequence generated 4,609,043 bp, distributed among 105 scaffolds assembled using the SPAdes genome assembler method. It comprises in total 4,132 genes, of which 4,008 were predicted to be proteinmore » coding genes, 124 RNA genes and 867 pseudogenes. The content was 43.51 mol %. The annotated genome of strain GluBS11 T contains putative genes coding for the pentose phosphate pathway, the Embden-Meyerhoff-Parnas pathway, the Entner-Doudoroff pathway and the tricarboxylic acid cycle. The genome revealed the presence of most of the necessary genes required for the fermentation of glucose and gluconate to acetate, ethanol, and hydrogen gas. However, a candidate gene for production of formate was not identified.« less

Foxp3+ regulatory T cells impede the priming of protective CD8+ T cells

PubMed Central

Ertelt, James M.; Rowe, Jared H.; Mysz, Margaret A.; Singh, Charanjeet; Roychowdhury, Monika; Aguilera, Marijo N.; Way, Sing Sing

2011-01-01

T cell activation is controlled by incompletely defined opposing stimulation and suppression signals that together sustain the balance between optimal host defense against infection and peripheral tolerance. Herein, we explored the impacts of Foxp3+ regulatory T cell (Treg) suppression in priming antigen-specific T cell activation under non-infection and infection conditions. We find the transient ablation of Foxp3+ Tregs unleashes the robust expansion and activation of peptide stimulated CD8+ T cells that provide protection against Listeria monocytogenes (Lm) infection in an antigen-specific fashion. By contrast, Treg-ablation had non-significant impacts on the CD8+ T cell response primed by infection with recombinant Lm. Similarly, non-recombinant Lm administered with peptide stimulated the expansion and activation of CD8+ T cells that paralleled the response primed by Treg-ablation. Interestingly, these adjuvant properties of Lm did not require CD8+ T cell stimulation by IL-12 produced in response to infection, but instead were associated with sharp reductions in Foxp3+ Treg suppressive potency. Therefore, Foxp3+ Tregs impose critical barriers that when overcome naturally during infection or artificially with ablation allows the priming of protective antigen-specific CD8+ T cells. PMID:21810602

[The effect of Foxc2 overexpression on the osteogenic properties of C3H10T1/2 cells].

PubMed

Wang, Min-Jiao; Si, Jia-Wen; Li, Hong-Liang; Ouyang, Ning-Juan; Shen, Guo-Fang

2016-08-01

To investigate the effect of Foxc2 overexpression on osteogenic and adipogenic differentiation of C3H10T1/2 cells. C3H10T1/2 cells were transfected with plenti-Foxc2 and selected with puromycin for stable clones. The expression of Foxc2 was determined by real-time PCR and Western blot. Cell proliferation was detected by CCK-8 kit. Cell cycle and apoptosis were detected by flow cytometry. The level of osteogenic biomarkers Runx2, OPN, OCN and adipogenic biomarker PPARγ were quantified by real-time PCR and Western blot. Alkaline phosphatase (ALP) staining and oil red staining were conducted to evaluate the effect of Foxc2 overexpression on osteogenic and adipogenic differentiation. Statistical analysis was performed using SPSS 17.0 software package. C3H10T1/2-Foxc2 cell line was successfully constructed and verified by direct sequencing and Foxc2 overexpression in vitro. Cell proliferation was reduced and cell cycle was blocked in G1/G0 phase. Enhanced ALP staining and reduced oil red staining were observed in C3H10T1/2-Foxc2 cells as compared with the control. Foxc2 overexpression up-regulated Runx2, OPN, OCN during osteogenic differentiation and down-regulated PPARγduring adipogenic differentiation. C3H10T1/2 cell line stably expressing Foxc2 gene was successfully established, cell proliferation was reduced, osteogenesis biomarkers were up-regulated during the osteogenesis by overexpression Foxc2, PPARγwas down-regulated during adipogenesis.

MR fingerprinting for rapid quantification of myocardial T1 , T2 , and proton spin density.

PubMed

Hamilton, Jesse I; Jiang, Yun; Chen, Yong; Ma, Dan; Lo, Wei-Ching; Griswold, Mark; Seiberlich, Nicole

2017-04-01

To introduce a two-dimensional MR fingerprinting (MRF) technique for quantification of T 1 , T 2 , and M 0 in myocardium. An electrocardiograph-triggered MRF method is introduced for mapping myocardial T 1 , T 2 , and M 0 during a single breath-hold in as short as four heartbeats. The pulse sequence uses variable flip angles, repetition times, inversion recovery times, and T 2 preparation dephasing times. A dictionary of possible signal evolutions is simulated for each scan that incorporates the subject's unique variations in heart rate. Aspects of the sequence design were explored in simulations, and the accuracy and precision of cardiac MRF were assessed in a phantom study. In vivo imaging was performed at 3 Tesla in 11 volunteers to generate native parametric maps. T 1 and T 2 measurements from the proposed cardiac MRF sequence correlated well with standard spin echo measurements in the phantom study (R 2  > 0.99). A Bland-Altman analysis revealed good agreement for myocardial T 1 measurements between MRF and MOLLI (bias 1 ms, 95% limits of agreement -72 to 72 ms) and T 2 measurements between MRF and T 2 -prepared balanced steady-state free precession (bias, -2.6 ms; 95% limits of agreement, -8.5 to 3.3 ms). MRF can provide quantitative single slice T 1 , T 2 , and M 0 maps in the heart within a single breath-hold. Magn Reson Med 77:1446-1458, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumour efficacy.

PubMed

Yeku, Oladapo O; Brentjens, Renier J

2016-04-15

Chimaeric antigen receptor (CAR) T-cells are T-cells that have been genetically modified to express an artificial construct consisting of a synthetic T-cell receptor (TCR) targeted to a predetermined antigen expressed on a tumour. Coupling the T-cell receptor to a CD3ζ signalling domain paved the way for first generation CAR T-cells that were efficacious against cluster of differentiation (CD)19-expressing B-cell malignancies. Optimization with additional signalling domains such as CD28 or 4-1BB in addition to CD3ζ provided T-cell activation signal 2 and further improved the efficacy and persistence of these second generation CAR T-cells. Third generation CAR T-cells which utilize two tandem costimulatory domains have also been reported. In this review, we discuss a different approach to optimization of CAR T-cells. Through additional genetic modifications, these resultant armored CAR T-cells are typically modified second generation CAR T-cells that have been further optimized to inducibly or constitutively secrete active cytokines or express ligands that further armor CAR T-cells to improve efficacy and persistence. The choice of the 'armor' agent is based on knowledge of the tumour microenvironment and the roles of other elements of the innate and adaptive immune system. Although there are several variants of armored CAR T-cells under investigation, here we focus on three unique approaches using interleukin-12 (IL-12), CD40L and 4-1BBL. These agents have been shown to further enhance CAR T-cell efficacy and persistence in the face of a hostile tumour microenvironment via different mechanisms. © 2016 Authors; published by Portland Press Limited.

Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumour efficacy

PubMed Central

Yeku, Oladapo O.; Brentjens, Renier J.

2017-01-01

Chimaeric antigen receptor (CAR) T-cells are T-cells that have been genetically modified to express an artificial construct consisting of a synthetic T-cell receptor (TCR) targeted to a predetermined antigen expressed on a tumour. Coupling the T-cell receptor to a CD3ζ signalling domain paved the way for first generation CAR T-cells that were efficacious against cluster of differentiation (CD)19-expressing B-cell malignancies. Optimization with additional signalling domains such as CD28 or 4-1BB in addition to CD3ζ provided T-cell activation signal 2 and further improved the efficacy and persistence of these second generation CAR T-cells. Third generation CAR T-cells which utilize two tandem costimulatory domains have also been reported. In this review, we discuss a different approach to optimization of CAR T-cells. Through additional genetic modifications, these resultant armored CAR T-cells are typically modified second generation CAR T-cells that have been further optimized to inducibly or constitutively secrete active cytokines or express ligands that further armor CAR T-cells to improve efficacy and persistence. The choice of the ‘armor’ agent is based on knowledge of the tumour microenvironment and the roles of other elements of the innate and adaptive immune system. Although there are several variants of armored CAR T-cells under investigation, here we focus on three unique approaches using interleukin-12 (IL-12), CD40L and 4-1BBL. These agents have been shown to further enhance CAR T-cell efficacy and persistence in the face of a hostile tumour microenvironment via different mechanisms. PMID:27068948

Investigation of the B1 field distribution and RF power deposition in a birdcage coil as functions of the number of coil legs at 4.7 T, 7.0 T, and 11.7 T

NASA Astrophysics Data System (ADS)

Seo, Jeung-Hoon; Han, Sang-Doc; Kim, Kyoung-Nam

2015-06-01

The proper design of birdcage (BC) coils plays a very important role in the acquisition of highresolution magnetic resonance imaging (MRI) of small animals such as rodents. In this context, we investigate multiple-leg (8-, 16-, 32-, 64-, and 128-leg) BC coils operating at ultra-high fields (UHF) of 7.0 T and 11.7 T and a high-field (HF) of 4.7 T for rodent magnetic resonance imaging (MRI). Primarily, Our study comparatively examines the parameters of the radiofrequency (RF) transmission (|B1 +|)-field, the magnetic flux (|B1|)-field, and RF power deposition (RF-PD) as functions of the number of BC-coil legs via finite-difference time-domain (FDTD) calculations under realistic loading conditions with a biological phantom. In particular, the specific ratio |E/B1 +| is defined for predicting RF-PD values in different coil structures. Our results indicate that the optimal number of legs of the BC coil can be chosen for different resonance frequencies of 200 MHz, 300 MHz, and 500 MHz and that this choice can be lead to superior |B1 +|-field intensity and |B1|-field homogeneity and decreased RF-PD. We believe that our approach to determining the optimal number of legs for a BC coil can contribute to rodent MR imaging.

Frequency of Inverted Electrocardiographic T Waves (Cerebral T Waves) in Patients With Acute Strokes and Their Relation to Left Ventricular Wall Motion Abnormalities.

PubMed

Stone, Jeremy; Mor-Avi, Victor; Ardelt, Agnieszka; Lang, Roberto M

2018-01-01

Transient, symmetric, and deep inverted electrocardiogram (ECG) T waves in the setting of stroke, commonly referred to as cerebral T waves, are rare, and the underlying mechanism is unclear. Our study aimed to test the hypothesis that cerebral T waves are associated with transient cardiac dysfunction. This retrospective study included 800 patients admitted with the primary diagnosis of hemorrhagic or ischemic stroke. ECGs were examined for cerebral T waves, defined as T-wave inversion of ≥5 mm depth in ≥4 contiguous precordial leads. Echocardiograms of those meeting these criteria were examined for the presence of left ventricular (LV) wall motion abnormalities. Follow-up evaluation included both ECG and echocardiogram. Of the 800 patients, 17 had cerebral T waves on ECG (2.1%). All 17 patients had ischemic strokes, of which 11 were in the middle cerebral artery distribution (65%), and 2 were cerebellar (12%), whereas the remaining 4 involved other locations. Follow-up ECG showed resolution of the T-wave changes in all 17 patients. Of these patients, 14 (82%) had normal wall motion, and 3 had transient wall motion abnormalities (18%). Two of these patients had Takotsubo-like cardiomyopathy with apical ballooning, and the third had globally reduced LV function. Coronary angiography showed no significant disease to explain the LV dysfunction. In summary, in our cohort of patients with acute stroke, cerebral T waves were rare and occurred only in ischemic stroke. Eighteen percent of patients with cerebral T waves had significant transient wall motion abnormalities. Patients with stroke with cerebral T waves, especially in those with ischemic strokes, should be assessed for cardiac dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

Differential Regulation of ERK1/2 and mTORC1 Through T1R1/T1R3 in MIN6 Cells.

PubMed

Wauson, Eric M; Guerra, Marcy L; Dyachok, Julia; McGlynn, Kathleen; Giles, Jennifer; Ross, Elliott M; Cobb, Melanie H

2015-08-01

The MAPKs ERK1/2 respond to nutrients and other insulin secretagogues in pancreatic β-cells and mediate nutrient-dependent insulin gene transcription. Nutrients also stimulate the mechanistic target of rapamycin complex 1 (mTORC1) to regulate protein synthesis. We showed previously that activation of both ERK1/2 and mTORC1 in the MIN6 pancreatic β-cell-derived line by extracellular amino acids (AAs) is at least in part mediated by the heterodimeric T1R1/T1R3, a G protein-coupled receptor. We show here that AAs differentially activate these two signaling pathways in MIN6 cells. Pretreatment with pertussis toxin did not prevent the activation of either ERK1/2 or mTORC1 by AAs, indicating that G(I) is not central to either pathway. Although glucagon-like peptide 1, an agonist for a G(s-)coupled receptor, activated ERK1/2 well and mTORC1 to a small extent, AAs had no effect on cytosolic cAMP accumulation. Ca(2+) entry is required for ERK1/2 activation by AAs but is dispensable for AA activation of mTORC1. Pretreatment with UBO-QIC, a selective G(q) inhibitor, reduced the activation of ERK1/2 but had little effect on the activation of mTORC1 by AAs, suggesting a differential requirement for G(q). Inhibition of G(12/13) by the overexpression of the regulator of G protein signaling domain of p115 ρ-guanine nucleotide exchange factor had no effect on mTORC1 activation by AAs, suggesting that these G proteins are also not involved. We conclude that AAs regulate ERK1/2 and mTORC1 through distinct signaling pathways.

Differential Regulation of ERK1/2 and mTORC1 Through T1R1/T1R3 in MIN6 Cells

PubMed Central

Wauson, Eric M.; Guerra, Marcy L.; Dyachok, Julia; McGlynn, Kathleen; Giles, Jennifer; Ross, Elliott M.

2015-01-01

The MAPKs ERK1/2 respond to nutrients and other insulin secretagogues in pancreatic β-cells and mediate nutrient-dependent insulin gene transcription. Nutrients also stimulate the mechanistic target of rapamycin complex 1 (mTORC1) to regulate protein synthesis. We showed previously that activation of both ERK1/2 and mTORC1 in the MIN6 pancreatic β-cell-derived line by extracellular amino acids (AAs) is at least in part mediated by the heterodimeric T1R1/T1R3, a G protein-coupled receptor. We show here that AAs differentially activate these two signaling pathways in MIN6 cells. Pretreatment with pertussis toxin did not prevent the activation of either ERK1/2 or mTORC1 by AAs, indicating that Gi is not central to either pathway. Although glucagon-like peptide 1, an agonist for a Gs-coupled receptor, activated ERK1/2 well and mTORC1 to a small extent, AAs had no effect on cytosolic cAMP accumulation. Ca2+ entry is required for ERK1/2 activation by AAs but is dispensable for AA activation of mTORC1. Pretreatment with UBO-QIC, a selective Gq inhibitor, reduced the activation of ERK1/2 but had little effect on the activation of mTORC1 by AAs, suggesting a differential requirement for Gq. Inhibition of G12/13 by the overexpression of the regulator of G protein signaling domain of p115 ρ-guanine nucleotide exchange factor had no effect on mTORC1 activation by AAs, suggesting that these G proteins are also not involved. We conclude that AAs regulate ERK1/2 and mTORC1 through distinct signaling pathways. PMID:26168033

Antimicrobial Activity and Chemical Composition of "Kpètè-Kpètè": A Starter of Benin Traditional Beer Tchoukoutou.

PubMed

N'tcha, Christine; Sina, Haziz; Kayodé, Adéchola Pierre Polycarpe; Gbenou, Joachim D; Baba-Moussa, Lamine

2017-01-01

The aim of this study was to investigate the antibacterial effect of the crude starter " kpètè-kpètè " and lactic acid bacteria used during the production of "tchoukoutou." To achieve this, a total of 11 lactic acid bacteria and 40 starter samples were collected from four communes. The samples were tested on 29 gram + and - strains by disk diffusion method. The minimum inhibitory and bactericidal concentrations of starter and lactic acid bacteria were determined by conventional methods. Organic acids, sugar, and volatile compounds were determined using the HPLC method. The "kpètè-kpètè" displays a high antibacterial activity against the tested strains. The most sensitive strain was S. epidermidis (12.5 mm) whereas the resistance strain was Proteus mirabilis (8 mm). All the tested ferment has not any inhibitory effect on Enterococcus faecalis . The lactic acid bacteria isolates of Parakou showed the highest (17.48 mm) antibacterial activity whereas the smallest diameter was obtained with the ferment collected from Boukoumbé (9.80 mm). The starters' chemical screening revealed the presence of tannins, anthocyanin flavonoids, triterpenes, steroids, reducing compounds, and mucilage O-glycosides. These compounds are probably the source of recorded inhibition effect. The lactic acid bacteria of the "kpètè-kpètè" could be used to develop a food ingredient with probiotic property.

High-pT Physics in the Heavy Ion Era

NASA Astrophysics Data System (ADS)

Rak, Jan; Tannenbaum, Michael J.

2013-04-01

1. Introduction and overview; 2. Basic observables; 3. Some experimental techniques; 4. The search for structure; 5. Origins of high pT physics - the search for the W boson; 6. Discovery of hard scattering in p-p collisions; 7. Direct single lepton production and the discovery of charm; 8. J/ ψ, u and Drell-Yan pair production; 9. Two particle correlations; 10. Direct photon production; 11. The search for jets; 12. QCD in hard scattering; 13. Heavy ion physics in the high pT era; 14. RHIC and LHC; Appendix A. Probability and statistics; Appendix B. Methods of Monte Carlo calculations; Appendix C. TAB and the Glauber Monte Carlo calculation; Appendix D. Fits including systematic errors; Appendix E. The shape of the xE distribution triggered by a jet fragment, for example, π0; Appendix F. kT phenomenology and Gaussian smearing; References; Index.

The C-Type Lectin OCILRP2 Costimulates EL4 T Cell Activation via the DAP12-Raf-MAP Kinase Pathway

PubMed Central

Lou, Qiang; Zhang, Wei; Liu, Guangchao; Ma, Yuanfang

2014-01-01

OCILRP2 is a typical Type-II transmembrane protein that is selectively expressed in activated T lymphocytes, dendritic cells, and B cells and functions as a novel co-stimulator of T cell activation. However, the signaling pathways underlying OCILRP2 in T cell activation are still not completely understood. In this study, we found that the knockdown of OCILRP2 expression with shRNA or the blockage of its activity by an anti-OCILRP2 antagonist antibody reduced CD3/CD28-costimulated EL4 T cell viability and IL-2 production, inhibit Raf1, MAPK3, and MAPK8 activation, and impair NFAT and NF-κB transcriptional activities. Furthermore, immunoprecipitation results indicated that OCILRP2 could interact with the DAP12 protein, an adaptor containing an intracellular ITAM motif that can transduce signals to induce MAP kinase activation for T cell activation. Our data reveal that after binding with DAP12, OCILRP2 activates the Raf-MAP kinase pathways, resulting in T cell activation. PMID:25411776

f(T,T) gravity and cosmology

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

Harko, Tiberiu; Lobo, Francisco S.N.; Otalora, G.

2014-12-01

We present an extension of f(T) gravity, allowing for a general coupling of the torsion scalar T with the trace of the matter energy-momentum tensor T. The resulting f(T,T) theory is a new modified gravity, since it is different from all the existing torsion or curvature based constructions. Applied to a cosmological framework, it leads to interesting phenomenology. In particular, one can obtain a unified description of the initial inflationary phase, the subsequent non-accelerating, matter-dominated expansion, and then the transition to a late-time accelerating phase. Additionally, the effective dark energy sector can be quintessence or phantom-like, or exhibit the phantom-dividemore » crossing during the evolution. Moreover, in the far future the universe results either to a de Sitter exponential expansion, or to eternal power-law accelerated expansions. Finally, a detailed study of the scalar perturbations at the linear level reveals that f(T,T) cosmology can be free of ghosts and instabilities for a wide class of ansatzes and model parameters.« less

Strong and frequent T-cell responses to the minor allergen Phl p 12 in Spanish patients IgE-sensitized to Profilins.

PubMed

Lund, G; Brand, S; Ramos, T; Jimeno, L; Boissy, P; Vega, F; Arina, M; Christensen, L H; Hoof, I; Meno, K H; Barber, D; Blanco, C; Würtzen, P A; Andersen, P S

2018-05-01

Profilins are dominant pan-allergens known to cause cross-sensitization, leading to clinical symptoms such as pollen-food syndrome. This study aimed to determine the T-cell response to Phl p 12 in profilin-sensitized patients, by measuring the prevalence, strength and cross-reactivity to clinically relevant profilins. The release of Phl p allergens from pollen was determined by mass spectrometry and immunochemistry. T-cell responses, epitope mapping and cross-reactivity to profilins (Phl p 12, Ole e 2, Bet v 2 and Mal d 4) were measured in vitro using PBMCs from 26 Spanish grass-allergic donors IgE-sensitized to profilin. Cross-reactivity was addressed in vivo using 2 different mouse strains (BALB/c and C3H). Phl p 12 and Phl p 1 are released from pollen simultaneously and in similar amounts. Both T-cell response frequency (17/26 donors) and strength were comparable between Phl p 12 and Phl p 1. T-cell cross-reactivity to other profilins correlated with overall sequence homology, and 2 immunodominant epitope regions of Phl p 12 were identified. Data from mice immunized with Phl p 12 showed that cross-reactivity to Bet v 2 was mediated by conserved epitopes and further influenced by additional genetic factors, likely to be MHC II. The strength, prevalence and cross-reactivity of T-cell responses towards Phl p 12 are comparable to the major allergen Phl p 1, which supports the hypothesis that T cells to Phl p 12 can play an important role in development of allergic symptoms, such as those associated with pollen-food syndrome. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

MASH test 3-11 on the Texas T101 bridge rail

DOT National Transportation Integrated Search

2011-03-01

The Texas T101 bridge rail is widely used in the state of Texas. Previous testing demonstrated its ability to contain and redirect passenger cars and a 20,000-lb school bus. Based on this testing, the Federal Highway Administration accepted the T101 ...

P- V- T equation of state of CaAl4Si2O11 CAS phase

NASA Astrophysics Data System (ADS)

Gréaux, Steeve; Nishiyama, Norimasa; Kono, Yoshio; Irifune, Tetsuo; Gautron, Laurent

2011-09-01

The thermoelastic parameters of the CAS phase (CaAl4Si2O11) were examined by in situ high-pressure (up to 23.7 GPa) and high-temperature (up to 2,100 K) synchrotron X-ray diffraction, using a Kawai-type multi-anvil press. P- V data at room temperature fitted to a third-order Birch-Murnaghan equation of state (BM EOS) yielded: V 0,300 = 324.2 ± 0.2 Å3 and K 0,300 = 164 ± 6 GPa for K' 0,300 = 6.2 ± 0.8. With K' 0,300 fixed to 4.0, we obtained: V 0,300 = 324.0 ± 0.1 Å3 and K 0,300 = 180 ± 1 GPa. Fitting our P- V- T data with a modified high-temperature BM EOS, we obtained: V 0,300 = 324.2 ± 0.1 Å3, K 0,300 = 171 ± 5 GPa, K' 0,300 = 5.1 ± 0.6 (∂ K 0 ,T /∂ T) P = -0.023 ± 0.006 GPa K-1, and α0 ,T = 3.09 ± 0.25 × 10-5 K-1. Using the equation of state parameters of the CAS phase determined in the present study, we calculated a density profile of a hypothetical continental crust that would contain ~10 vol% of CaAl4Si2O11. Because of the higher density compared with the coexisting minerals, the CAS phase is expected to be a plunging agent for continental crust subducted in the transition zone. On the other hand, because of the lower density compared with lower mantle minerals, the CAS phase is expected to remain buoyant in the lowermost part of the transition zone.

26 CFR 1.1445-11T - Special rules requiring withholding under § 1.1445-5 (temporary).

Code of Federal Regulations, 2010 CFR

2010-04-01

... OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Withholding of Tax on Nonresident Aliens and Foreign Corporations and Tax-Free Covenant Bonds § 1.1445-11T Special rules requiring... that, if and when adopted as a final regulation will add certain new paragraphs within § 1.1445-5 (b...

Differences in Aspergillus-specific immune recovery between T-cell-replete and T-cell-depleted hematopoietic transplants.

PubMed

Perruccio, Katia; Topini, Fabiana; Tosti, Antonella; Gazzola, Maria Vittoria; Messina, Chiara; Martelli, Massimo F; Caniglia, Maurizio; Velardi, Andrea; Cesaro, Simone

2015-12-01

After hematopoietic stem cell transplantation, invasive aspergillosis remains one of the most lethal infections. Susceptibility may be due to prophylaxis and treatment of graft-vs.-host disease in T-cell-replete transplants, and delayed immune rebuilding due to T-cell depletion in haploidentical transplantation. We monitored CD4(+) T-cell recovery and anti-Aspergillus immune competence in pediatric recipients of T-cell-replete matched transplants and of prevalently adult recipients of T-cell-depleted matched or haploidentical transplants for hematological malignancies. Although CD4(+) T-cell counts were higher in T-cell-replete transplant recipients at all post-transplant time points, Aspergillus-specific T cells were first detected 15-18 months after T-cell-replete matched, 7-9 months after T-cell-depleted matched, and 9-12 months after haploidentical transplantation, respectively. Incidence of invasive aspergillosis was 22% with 10% mortality after T-cell-replete transplants, 0% after T-cell-depleted matched, and 7% with 4% mortality after haploidentical transplants. Although T-cell counts were significantly higher after T-cell-replete transplants, post-transplant immune suppression/GvHD appeared to impair their function. Specific Aspergillus immune competence recovered faster after T-cell-depleted transplants, whether matched or haploidentical. T-cell-replete transplants were associated with a higher incidence of invasive aspergillosis and Aspergillus-related deaths. These results showed that T-cell depletion without post-transplant immunosuppression is associated to a faster immune recovery than T-cell-replete transplantation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effectiveness of intra-articular injection in wrist joints according to triamcinolone hexacetonide dose in rheumatoid arthritis: a randomized controlled double-blind study.

PubMed

Pereira, Daniele Freitas; Natour, Jamil; Machado, Natália Pereira; Furtado, Rita Nely Vilar

2015-02-01

The aim of this study was to compare the effectiveness in the medium term between low and high doses of triamcinolone hexacetonide used in intra-articular injection in medium-sized joints of rheumatoid arthritis (RA) patients. A randomized double-blind study was carried out in rheumatoid arthritis patients with wrist painful refractory synovitis. Sixty wrists were included and randomized to receive low dose (20 mg) or high dose (40 mg). The outcomes assessed in T0, T1, T4, T8, and T12 weeks were visual analog scale for pain and for swelling, chronic disease activity index, goniometry, simplified Stanford Health Assessment Questionnaire, and side effects. Baseline mean (standard deviation) values were pain visual analog scale of 6.1 (1.6) and 6.3 (1.7), P = 0.562; swelling visual analog scale of 5.9 and 6.4, P = 0.466; chronic disease activity index of 17.8 and 16.8, P = 0.366; and Health Assessment Questionnaire of 0.8 and 0.7, P = 0.238, in the high- and low-dose groups, respectively. Both groups improved pain and swelling assessed by the visual analog scale, P < 0.001, in the intragroup analysis. Chronic disease activity index, goniometry, and Health Assessment Questionnaire also improved equally over time in both groups in the intragroup analysis (P < 0.001, 0.001, and 0.002, respectively). No serious side effects were detected. High and low triamcinolone hexacetonide doses had good effectiveness in wrist-blinded intra-articular injection of rheumatoid arthritis patients, without statistical difference between them.

An alternative explanation of the change in T-dependence of the effective Debye-Waller factor at T{sub c} or T{sub B}

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

Ngai, K. L.; CNR-IPCF, Largo Bruno Pontecorvo 3, I-56127 Pisa; Habasaki, J.

The cusp-like temperature dependence of the Debye-Waller factor or non-ergodicity parameter f{sub Q}(T) at some temperature T{sub c} above T{sub g} found by experiments in several fragile glassformers has been considered as critical evidence for validity of the ideal Mode Coupling Theory (MCT). A comprehensive review of experimental data of f{sub Q}(T) and beyond brings out various problems of the MCT predictions. For example, the molten salt, 0.4Ca(NO{sub 3}){sub 2}-0.6KNO{sub 3} (CKN), was the first glassformer measured by neutron scattering to verify the cusp-like behavior of f{sub Q}(T) at T{sub c} predicted by ideal MCT. While the fits of themore » other scaling laws of MCT to viscosity, light scattering, and dielectric relaxation data all give T{sub c} in the range from 368 to 375 K, there is no evidence of cusp-like behavior of f{sub Q}(T) at T{sub c} from more accurate neutron scattering data obtained later on by Mezei and Russina [J. Phys.: Condens. Matter 11, A341 (1999)] at temperatures below 400 K. In several molecular glass-formers, experiments have found at temperatures below T{sub c} that [1−f{sub Q}(T)] is manifested as nearly constant loss (NCL) in the frequency dependent susceptibility. The NCL persists down to below T{sub g} and is not predicted by the ideal MCT. No clear evidence of the change of T-dependence of f{sub Q}(T) at any T{sub c} was found in intermediate and strong glassformers, although ideal MCT does not distinguish fragile and strong glassformers in predicting the critical behavior of f{sub Q}(T) a priori. Experiments found f{sub Q}(T) changes T-dependence not only at T{sub c} but also at the glass transition temperature T{sub g}. The changes of T-dependence of f{sub Q}(T) at T{sub c} and T{sub g} are accompanied by corresponding changes of dynamic variables and thermodynamic quantities at T{sub B} ≈ T{sub c} and at T{sub g}. The dynamic variables include the relaxation time τ{sub α}(T), the non-exponentiality parameter n(T

LPS-treated bone marrow-derived dendritic cells induce immune tolerance through modulating differentiation of CD4+ regulatory T cell subpopulations mediated by 3G11 and CD127.

PubMed

Zhou, Fang; Zhang, Guang-Xian; Rostami, Abdolmohamad

2017-06-01

Intravenous transfer of LPS-treated bone marrow-derived dendritic cells blocks development of autoimmunity induced by CD4 + T cells in vivo. However, cellular mechanisms of dendritic cell-mediated immune tolerance have not yet been fully elucidated. Here, we report that there are two new subpopulations of CD4 + CD25 + FoxP3 + GITR + regulatory T cells (CD127 + 3G11 + and CD127 + 3G11 - cells). LPS-treated dendritic cells facilitate development of CD4 + CD127 + 3G11 - regulatory T cells but inhibit that of CD4 + CD127 + 3G11 + regulatory T cells. LPS-induced tolerogenic dendritic cells may cause immune tolerance through modulating balance of different subsets of CD4 + regulatory T cells mediated by CD127 and 3G11. Our results imply a new potential cellular mechanism of dendritic cell-mediated immune tolerance.

Caudal articular process dysplasia of thoracic vertebrae in neurologically normal French bulldogs, English bulldogs, and Pugs: Prevalence and characteristics.

PubMed

Bertram, Simon; Ter Haar, Gert; De Decker, Steven

2018-02-20

The aims of this study were to evaluate the prevalence and anatomical characteristics of thoracic caudal articular process dysplasia in French bulldogs, English bulldogs and Pugs presenting for problems unrelated to spinal disease. In this retrospective cross-sectional study, computed tomography scans of the thoracic vertebral column of these three breeds were reviewed for the presence and location of caudal articular process hypoplasia and aplasia, and compared between breeds. A total of 271 dogs met the inclusion criteria: 108 French bulldogs, 63 English bulldogs, and 100 Pugs. A total of 70.4% of French bulldogs, 84.1% of English bulldogs, and 97.0% of Pugs showed evidence of caudal articular process dysplasia. Compared to French and English bulldogs, Pugs showed a significantly higher prevalence of caudal articular process aplasia, but also a lower prevalence of caudal articular process hypoplasia, a higher number of affected vertebrae per dog and demonstrated a generalized and bilateral spatial pattern more frequently. Furthermore, Pugs showed a significantly different anatomical distribution of caudal articular process dysplasia along the vertebral column, with a high prevalence of caudal articular process aplasia between T10 and T13. This area was almost completely spared in French and English bulldogs. As previously suggested, caudal articular process dysplasia is a common finding in neurologically normal Pugs but this also seems to apply to French and English bulldogs. The predisposition of clinically relevant caudal articular process dysplasia in Pugs is possibly not only caused by the higher prevalence of caudal articular process dysplasia, but also by breed specific anatomical characteristics. © 2018 American College of Veterinary Radiology.

Whodunit? The Contribution of Interleukin (IL)-17/IL-22-Producing γδ T Cells, αβ T Cells, and Innate Lymphoid Cells to the Pathogenesis of Spondyloarthritis

PubMed Central

Reinhardt, Annika; Prinz, Immo

2018-01-01

γδ T cells, αβ T cells, and innate lymphoid cells (ILCs) are capable of producing interleukin (IL)-17A, IL-17F, and IL-22. Among these three families of lymphocytes, it is emerging that γδ T cells are, at least in rodents, the main source of these key pro-inflammatory cytokines. γδ T cells were implicated in multiple inflammatory and autoimmune diseases, including psoriasis, experimental autoimmune encephalomyelitis and uveitis, colitis, and rheumatoid arthritis. Recent findings pointed toward a central role of γδ T cells in the pathogenesis of spondyloarthritis (SpA), a group of inflammatory rheumatic diseases affecting the axial skeleton. SpA primarily manifests as inflammation and new bone formation at the entheses, which are connecting tendons or ligaments with bone. In SpA patients, joint inflammation is frequently accompanied by extra-articular manifestations, such as inflammatory bowel disease or psoriasis. In humans, genome-wide association studies could link the IL-23/IL-17 cytokine axis to SpA. Accordingly, antibodies targeting IL-23/IL-17 for SpA treatment already showed promising results in clinical studies. However, the contribution of IL-17-producing γδ T cells to SpA pathogenesis is certainly not an open-and-shut case. Indeed, the cell types that are chiefly involved in local inflammation in human SpA still remain largely unclear. Some studies focusing on blood or synovium from SpA patients reported augmented IL-17-producing and IL-23 receptor-expressing γδ T cells, but other cell types might contribute as well. Here, we summarize the current understanding of how γδ T cells, αβ T cells, and ILCs contribute to the pathogenesis of human and experimental SpA. PMID:29922283

Possible association of 3' UTR +357 A>G, IVS11-nt 93 T>C, c.1311 C>T polymorphism with G6PD deficiency.

PubMed

Sirdah, Mahmoud M; Shubair, Mohammad E; Al-Kahlout, Mustafa S; Al-Tayeb, Jamal M; Prchal, Josef T; Reading, N Scott

2017-07-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked inherited enzymopathic disorder affecting more than 500 million people worldwide. It has so far been linked to 217 distinct genetic variants in the exons and exon-intron boundaries of the G6PD gene, giving rise to a wide range of biochemical heterogeneity and clinical manifestations. Reports from different settings suggested the association of intronic and other mutations outside the reading frame of the G6PD gene with reduced enzyme activity and presenting clinical symptoms. The present study aimed to investigate any association of other variations apart of the exonic or exonic intronic boundaries in the development of G6PD deficiency. Sixty-seven unrelated Palestinian children admitted to the pediatric hospital with hemolytic crises due to G6PD deficiency were studied. In our Palestinian cohort of 67 [59 males (M) and 8 females (F)] G6PD-deficient children, previously hospitalized for acute hemolytic anemia due to favism, molecular sequencing of the G6PD gene revealed four cases (3M and 1F) that did not have any of the variants known to cause G6PD deficiency, but the 3' UTR c.*+357A>G (rs1050757) polymorphism in association with IVS 11 (c.1365-13T>C; rs2071429), and c.1311C>T (rs2230037). We now provide an additional evidence form Palestinian G6PD-deficient subjects for a possible role of 3' UTR c.*+357 A>G, c.1365-13T>C, and/or c.1311C>T polymorphism for G6PD deficiency, suggesting that not only a single variation in the exonic or exonic intronic boundaries, but also a haplotype of G6PD should considered as a cause for G6PD deficiency.

Use of T12 lighting systems in retrofit applications within New York Office of Mental Health Facilities - A case history

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

Henry, C.P.; Marsh, E.J.

1997-06-01

In 1990, the Governor of New York State issued Executive Order No. 132, directing all state agencies to reduce energy consumption by 20% from the base year of 1988/89 by the year 2000. To assist in meeting this goal, the New York State Office of Mental Health (OMH) established the Lighting Revitalization Program in 1992. State facilities are divided into five regions, each served by existing Environmental Revitalization Teams. OMH supplemented these teams with lighting technicians in this new program. The program`s goal was to rehabilitate outdated, inefficient lighting systems throughout 28 OMH facilities, totaling 28 million square feet inmore » area. OMH requested the former Facility Development Corporation (FDC), now the Dormitory Authority of the State of New York (DASNY), to contract with Novus Engineering to evaluate the relative efficiency of T8 and T12 ballasts. Novus contracted an independent laboratory, Eastern Testing Laboratories (ETL), for performance testing. ETL tested four ballast/lamp configurations for light Output and input power, and Novus analyzed the results for relative efficiency and also calculated 25-year life cycle costs. The test results indicated that the efficiencies of the T12/34W and T8/32W ballast/lamp technologies were nearly identical. The input power and light output of these systems were similar. The lumens per Watt ratings for the two systems were nearly equal, with the T8 technology being only about two percent more efficient, generating more light with similar input power. The life cycle costs for the two systems were nearly identical, with the T12 system providing a slightly lower life cycle cost. Given the above considerations, the agency has been installing T12 electronic ballasts and 34W lamps in buildings where fluorescent fixtures warranted upgrading. This type of retrofit goes against current trends, but the use of T8 system could not be justified in buildings undergoing minor retrofitting.« less

Field Quality Study of a 1-m-Long Single-Aperture 11-T Nb$$_3$$Sn Dipole Model for LHC Upgrades

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

Chlachidze, G.; DiMarco, J.; Andreev, N.

2014-01-01

FNAL and CERN are carrying out a joint R&D program with the goal of building a 5.5-m-long twin-aperture 11-T Nb_3Sn dipole prototype that is suitable for installation in the LHC. An important part of the program is the development and test of a series of short single-aperture and twin-aperture dipole models with a nominal field of 11 T at the LHC operation current of 11.85 kA and 20% margin. This paper presents the results of magnetic measurements of a 1-m-long single-aperture Nb_3Sn dipole model fabricated and tested recently at FNAL, including geometrical field harmonics and effects of coil magnetization andmore » iron yoke saturation.« less

Growth hormone facilitates 5'-azacytidine-induced myogenic but inhibits 5'-azacytidine-induced adipogenic commitment in C3H10T1/2 mesenchymal stem cells.

PubMed

Jia, Dan; Zheng, Weijiang; Jiang, Honglin

2018-06-01

The C3H10T1/2 cells are considered mesenchymal stem cells (MSCs) because they can be induced to become the progenitor cells for myocytes, adipocytes, osteoblasts, and chondrocytes by the DNA methyltransferase inhibitor 5'-azacytidine. In this study, we determined the effect of growth hormone (GH) on the myogenic and adipogenic lineage commitment in C3H10T1/2 cells. The C3H10T1/2 cells were treated with recombinant bovine GH in the presence or absence of 5'-azacytidine for 4 days. The myogenic commitment in C3H10T1/2 cells was assessed by immunostaining them for MyoD, the marker for myoblasts, and by determining their capacity to differentiate into the multinucleated myotubes. The adipogenic commitment in C3H10T1/2 cells was assessed by determining their ability to differentiate into adipocytes. Myotubes and adipocyteswere identified by immunocytochemistry and Oil Red O staining, respectively. C3H10T1/2 cells treated with 5'-azacytidine and GH for 4 days contained a greater percentage of MyoD-positive cells than those treated with 5'-axacytidine alone (P < 0.05). The former generated more myotubes than the latter upon induced myoblast differentiation (P < 0.05). However, C3H10T1/2 cells treated with GH alone did not form any myotubes. C3H10T1/2 cells treated with 5'-azacytidine formed adipocytes upon adipocyte differentiation induction, whereas C3H10T1/2 cells treated with GH alone did not form any adipocytes. C3H10T1/2 cells treated with both 5'-azacytidine and GH formed fewer adipocytes than those treated with 5'-azacytidine alone (P < 0.05). Both GHR and IGF-I mRNA expression in C3H10T1/2 cells were increased by 5'-azacytidine (P < 0.05), but neither was affected by GH. Overall, this study showed that GH enhanced 5'-azacytidine-induced commitment in C3H10T1/2 cells to myoblasts but inhibited 5'-azacytidine-induced commitment to preadipocytes. These results support the possibility that GH stimulates skeletal muscle growth and inhibits adipose

Is There an Additional Value of {sup 11}C-Choline PET-CT to T2-weighted MRI Images in the Localization of Intraprostatic Tumor Nodules?

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

Van den Bergh, Laura, E-mail: laura.vandenbergh@uzleuven.be; Koole, Michel; Isebaert, Sofie

2012-08-01

Purpose: To investigate the additional value of {sup 11}C-choline positron emission tomography (PET)-computed tomography (CT) to T2-weighted (T2w) magnetic resonance imaging (MRI) for localization of intraprostatic tumor nodules. Methods and Materials: Forty-nine prostate cancer patients underwent T2w MRI and {sup 11}C-choline PET-CT before radical prostatectomy and extended lymphadenectomy. Tumor regions were outlined on the whole-mount histopathology sections and on the T2w MR images. Tumor localization was recorded in the basal, middle, and apical part of the prostate by means of an octant grid. To analyze {sup 11}C-choline PET-CT images, the same grid was used to calculate the standardized uptake valuesmore » (SUV) per octant, after rigid registration with the T2w MR images for anatomic reference. Results: In total, 1,176 octants were analyzed. Sensitivity, specificity, and accuracy of T2w MRI were 33.5%, 94.6%, and 70.2%, respectively. For {sup 11}C-choline PET-CT, the mean SUV{sub max} of malignant octants was significantly higher than the mean SUV{sub max} of benign octants (3.69 {+-} 1.29 vs. 3.06 {+-} 0.97, p < 0.0001) which was also true for mean SUV{sub mean} values (2.39 {+-} 0.77 vs. 1.94 {+-} 0.61, p < 0.0001). A positive correlation was observed between SUV{sub mean} and absolute tumor volume (Spearman r = 0.3003, p = 0.0362). No correlation was found between SUVs and prostate-specific antigen, T-stage or Gleason score. The highest accuracy (61.1%) was obtained with a SUV{sub max} cutoff of 2.70, resulting in a sensitivity of 77.4% and a specificity of 44.9%. When both modalities were combined (PET-CT or MRI positive), sensitivity levels increased as a function of SUV{sub max} but at the cost of specificity. When only considering suspect octants on {sup 11}C-choline PET-CT (SUV{sub max} {>=} 2.70) and T2w MRI, 84.7% of these segments were in agreement with the gold standard, compared with 80.5% for T2w MRI alone. Conclusions: The additional value

26 CFR 1.1445-11T - Special rules requiring withholding under § 1.1445-5 (temporary).

Code of Federal Regulations, 2011 CFR

2011-04-01

... OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Withholding of Tax on Nonresident Aliens and Foreign Corporations and Tax-Free Covenant Bonds § 1.1445-11T Special rules requiring... that, if and when adopted as a final regulation will add certain new paragraphs within § 1.1445-5 (b...

26 CFR 1.1445-11T - Special rules requiring withholding under § 1.1445-5 (temporary).

Code of Federal Regulations, 2014 CFR

2014-04-01

... OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Withholding of Tax on Nonresident Aliens and Foreign Corporations and Tax-Free Covenant Bonds § 1.1445-11T Special rules requiring... that, if and when adopted as a final regulation will add certain new paragraphs within § 1.1445-5 (b...

26 CFR 1.1445-11T - Special rules requiring withholding under § 1.1445-5 (temporary).

Code of Federal Regulations, 2012 CFR

2012-04-01

... OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Withholding of Tax on Nonresident Aliens and Foreign Corporations and Tax-Free Covenant Bonds § 1.1445-11T Special rules requiring... that, if and when adopted as a final regulation will add certain new paragraphs within § 1.1445-5 (b...

26 CFR 1.1445-11T - Special rules requiring withholding under § 1.1445-5 (temporary).

Code of Federal Regulations, 2013 CFR

2013-04-01

... OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Withholding of Tax on Nonresident Aliens and Foreign Corporations and Tax-Free Covenant Bonds § 1.1445-11T Special rules requiring... that, if and when adopted as a final regulation will add certain new paragraphs within § 1.1445-5 (b...

MASH Test 3-11 on the T131RC Bridge Rail

DOT National Transportation Integrated Search

2012-10-01

Texas Department of Transportation (TxDOT) currently uses the TxDOT Type T101RC Bridge Rail, : a steel post and beam bridge rail anchored to the top of concrete curbs. The T101RC Bridge Rail is : 27 inches in height and can be anchored to the top of ...

Analysis of the T-cell receptor repertoire of human T-cell leukemia virus type 1 (HTLV-1) Tax-specific CD8+ cytotoxic T lymphocytes from patients with HTLV-1-associated disease: evidence for oligoclonal expansion.

PubMed

Utz, U; Banks, D; Jacobson, S; Biddison, W E

1996-02-01

Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive neurological disease characterized by marked degeneration of the spinal cord and the presence of antibodies against HTLV-1. Patients with HAM/TSP, but not asymptomatic carriers, show very high precursor frequencies of HTLV-1-specific CD8+ T cells in peripheral blood and cerebrospinal fluid, suggestive of a role of these T cells in the pathogenesis of the disease. In HLA-A2+ HAM/TSP patients, HTLV-1-specific T cells were demonstrated to be directed predominantly against one HTLV-1 epitope, namely, Tax11-19. In the present study, we analyzed HLA-A2-restricted HTLV-1 Tax11-19-specific cytotoxic T cells from three patients with HAM/TSP. An analysis of the T-cell receptor (TCR) repertoire of these cells revealed an absence of restricted variable (V) region usage. Different combinations of TCR V alpha and V beta genes were utilized between, but also within, the individual patients for the recognition of Tax11-19. Sequence analysis of the TCR showed evidence for an oligoclonal expansion of few founder T cells in each patient. Apparent structural motifs were identified for the CDR3 regions of the TCR beta chains. One T-cell clone could be detected within the same patient over a period of 3 years. We suggest that these in vivo clonally expanded T cells might play a role in the pathogenesis of HAM/TSP and provide information on HTLV-1-specific TCR which may elucidate the nature of the T cells that infiltrate the central nervous system in HAM/TSP patients.

[Comparison study on two operations for treatment of extra-articular distal tibial fracture].

PubMed

Qi, Haotian; Li, Weikang; Zhao, Yongjie; Zhang, Yinguang; Liu, Zhaojie; Jia, Jian

2013-11-01

To compare the effectiveness between minimally invasive plate osteosynthesis (MIPO) and open reduction and internal fixation (ORIF) for treatment of extra-articular distal tibial fracture. Between March 2009 and March 2012, 57 patients with extra-articular distal tibial fractures were treated, and the clinical data were retrospectively analyzed. Of 57 cases, 31 were treated with MIPO (MIPO group), and 26 with ORIF (ORIF group). There was no significant difference in gender, age, cause of injury, type of fractures, complication, and time from injury to operation between 2 groups (P > 0.05). The operation time, intraoperative blood loss, fracture healing time, and complications were compared between 2 groups. There was no significant difference in operation time and intraoperative blood loss between 2 groups (P > 0.05). Wound infection occurred in 5 cases [2 in MIPO group (6.5%) and 3 in ORIF group (11.5%)] showing no significant difference (Chi(2)=0.651, P=0.499). The other wound obtained healing by first intention. All cases were followed up 13-24 months (mean, 15 months). No significant difference was found in the average healing time between 2 groups and between patients with types A and B by AO classification (P > 0.05); in patients with type C, the healing time in MIPO group was significantly shorter than that in ORIF group (t= -2.277, P=0.033). Delayed union was observed in 3 cases of MIPO group (9.7%) and in 4 cases of ORIF group (15.4%), showing no significant difference (Chi(2)=0.428, P=0.691). Mal-union occurred in 4 cases of MIPO group (12.9%) and in 1 case of ORIF group (3.8%), showing no significant difference (Chi(2)=1.449, P=0.362). No significant difference was found in Mazur score between 2 groups (t=0.480, P=0.633). The excellent and good rate was 93.5% in MIPO group (excellent in 24 cases, good in 5 cases, fair in 1 case, and poor in 1 case) and was 92.3% in ORIF group (excellent in 18 cases, good in 6 cases, and poor in 2 cases), and the

Obtaining T1-T2 distribution functions from 1-dimensional T1 and T2 measurements: The pseudo 2-D relaxation model

NASA Astrophysics Data System (ADS)

Williamson, Nathan H.; Röding, Magnus; Galvosas, Petrik; Miklavcic, Stanley J.; Nydén, Magnus

2016-08-01

We present the pseudo 2-D relaxation model (P2DRM), a method to estimate multidimensional probability distributions of material parameters from independent 1-D measurements. We illustrate its use on 1-D T1 and T2 relaxation measurements of saturated rock and evaluate it on both simulated and experimental T1-T2 correlation measurement data sets. Results were in excellent agreement with the actual, known 2-D distribution in the case of the simulated data set. In both the simulated and experimental case, the functional relationships between T1 and T2 were in good agreement with the T1-T2 correlation maps from the 2-D inverse Laplace transform of the full 2-D data sets. When a 1-D CPMG experiment is combined with a rapid T1 measurement, the P2DRM provides a double-shot method for obtaining a T1-T2 relationship, with significantly decreased experimental time in comparison to the full T1-T2 correlation measurement.

Hematological malignancies with t(9;11)(p21-22;q23)--a laboratory and clinical study of 125 cases. European 11q23 Workshop participants.

PubMed

Swansbury, G J; Slater, R; Bain, B J; Moorman, A V; Secker-Walker, L M

1998-05-01

This paper reports clinical and cytogenetic data from 125 cases with t(9;11)(p21-22;q32) which were accepted for a European Union Concerted Action Workshop on 11q23. This chromosome abnormality is known to occur predominantly in acute myeloid leukemia (AML) FAB type M5a and less often in AML M4; in this series it was also found to occur, uncommonly, in other AML FAB types, in childhood acute lymphoblastic leukemia (ALL) (nine cases), in relatively young patients with myelodysplastic syndrome (MDS) (five cases), acute biphenotypic leukemia (two cases), and acute undifferentiated leukemia (one case). All age groups were represented but 50% of the patients were aged less than 15 years. The t(9;11) was the sole abnormality in 57 cases with AML; trisomy 8 was the most common additional abnormality (23 cases, including seven with further abnormalities), and 28 cases had other additional abnormalities. Among the t(9;11)+ve patients with AML, the white cell count (WBC) and age group were significant predictors of event-free survival; central nervous system (CNS) involvement or karyotype class (sole, with trisomy 8, or with other), also contributed to prognosis although our data could not show these to be independent factors. The best outcome was for patients aged 1-9 years, with low WBC, and with absence of CNS disease or presence of trisomy 8. For patients aged less than 15 years, the event-free survival for ALL patients was not significantly worse than that of AML patients.

Selective bispecific T cell recruiting antibody and antitumor activity of adoptive T cell transfer.

PubMed

Kobold, Sebastian; Steffen, Julius; Chaloupka, Michael; Grassmann, Simon; Henkel, Jonas; Castoldi, Raffaella; Zeng, Yi; Chmielewski, Markus; Schmollinger, Jan C; Schnurr, Max; Rothenfußer, Simon; Schendel, Dolores J; Abken, Hinrich; Sustmann, Claudio; Niederfellner, Gerhard; Klein, Christian; Bourquin, Carole; Endres, Stefan

2015-01-01

One bottleneck for adoptive T cell therapy (ACT) is recruitment of T cells into tumors. We hypothesized that combining tumor-specific T cells, modified with a marker antigen and a bispecific antibody (BiAb) that selectively recognizes transduced T cells and tumor cells would improve T cell recruitment to tumors and enhance therapeutic efficacy. SV40 T antigen-specific T cells from T cell receptor (TCR)-I-transgenic mice were transduced with a truncated human epidermal growth factor receptor (EGFR) as a marker protein. Targeting and killing by combined ACT and anti-EGFR-anti-EpCAM BiAb therapy was analyzed in C57Bl/6 mice (n = six to 12 per group) carrying subcutaneous tumors of the murine gastric cancer cell line GC8 (SV40(+) and EpCAM(+)). Anti-EGFR x anti-c-Met BiAb was used for targeting of human tumor-specific T cells to c-Met(+) human tumor cell lines. Differences between experimental conditions were analyzed using the Student's t test, and differences in tumor growth with two-way analysis of variance. Overall survival was analyzed by log-rank test. All statistical tests were two-sided. The BiAb linked EGFR-transduced T cells to tumor cells and enhanced tumor cell lysis. In vivo, the combination of ACT and Biab produced increased T cell infiltration of tumors, retarded tumor growth, and prolonged survival compared with ACT with a control antibody (median survival 95 vs 75 days, P < .001). In human cells, this strategy enhanced recruitment of human EGFR-transduced T cells to immobilized c-Met and recognition of tyrosinase(+) melanoma cells by TCR-, as well as of CEA(+) colon cancer cells by chimeric antigen receptor (CAR)-modified T cells. BiAb recruitment of tumor-specific T cells transduced with a marker antigen to tumor cells may enhance efficacy of ACT. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia

PubMed Central

Bueno, Clara; Prieto, Cristina; Acha, Pamela; Stam, Ronald W.; Marschalek, Rolf; Menéndez, Pablo

2015-01-01

Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinical management and survival (∼85-90%) of childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival <35%. Among MLL-r infant B-ALL, t(4;11)+ patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and a pro-B/mixed phenotype. Studies in monozygotic twins and archived blood spots have provided compelling evidence of a single cell of prenatal origin as the target for MA4 fusion, explaining the brief leukemia latency. Despite its aggressiveness and short latency, current progress on its etiology, pathogenesis, and cellular origin is limited as evidenced by the lack of mouse/human models recapitulating the disease phenotype/latency. We propose this is because infant cancer is from an etiologic and pathogenesis standpoint distinct from adult cancer and should be seen as a developmental disease. This is supported by whole-genome sequencing studies suggesting that opposite to the view of cancer as a “multiple-and-sequential-hit” model, t(4;11) alone might be sufficient to spawn leukemia. The stable genome of these patients suggests that, in infant developmental cancer, one “big-hit” might be sufficient for overt disease and supports a key contribution of epigenetics and a prenatal cell of origin during a critical developmental window of stem cell vulnerability in the leukemia pathogenesis. Here, we revisit the biology of t(4;11)+ infant B-ALL with an emphasis on its origin, genetics, and disease models. PMID:26463423

The P-T-fO 2 stability of deerite, Fe{12/2+}Fe{6/3+}[Si12O40](OH)10

NASA Astrophysics Data System (ADS)

Lattard, Dominique; Le Breton, Nicole

1994-02-01

New equilibrium experiments have been performed in the 20 27 kbar range to determine the upper thermal stability limit of endmember deerite, Fe{12/2+}Fe{6/3+}[Si12O40](OH)10. In this pressure range, the maximum thermal stability limit is represented by the oxygen-conserving reaction: deerite(De)=9 ferrosilite(Fs)+3 magnetite(Mag)+3 quartz(Qtz)+5 H2O(W) (1). Under the oxygen fugacities of the Ni-NiO buffer the breakdown-reduction reaction: De=12 Fs+2 Mag+5 W+1/2 O2 (10) takes place at lower temperatures (e.g. ΔT=63° at 27 kbar). The experimental brackets can be fitted using thermodynamic data for ferrosilite, magnetite and quartz from Berman (1988) and the following 1 bar, 298 K data for deerite (per gfw): Vo=55.74 J.bar-1, So=1670 J.K-1, ΔH{f/o}=-18334 kJ, α=2.5x10-5K-1, β=-0.18x10-5 bar-1. Using these data in conjunction with literature data on coesite, grunerite, minnesotaite, and greenalite, the P-T stability field of endmember deerite has been calculated for P s= P H 2O. This field is limited by 6 univariant oxygenconserving dehydration curves, from which three have positive d P/d T slopes, the other three negative slopes. The lower pressure end of the stability field of endmember deerite is thus located at an invariant point at 250±70°C and 10+-1.5 kbar. Deerite rich in the endmember can thus appear only in environments with geothermal gradients lower than 10°C/km and at pressures higher than about 10 kbar, which is in agreement with 4 out of 5 independent P-T estimates for known occurrences. The presence of such deerite places good constraints on minimum pressure and maximum temperature conditions. From log f O 2- T diagrams constructed with the same data base at different pressures, it appears that endmember deerite is, at temperatures near those of its upper stability limit, stable only over a narrow range of oxygen fugacities within the magnetite field. With decreasing temperatures, deerite becomes stable towards slightly higher oxygen fugacities

Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison.

PubMed

Ramos, Sandra; Brenu, Ekua; Broadley, Simon; Kwiatek, Richard; Ng, Jennifer; Nguyen, Thao; Freeman, Susan; Staines, Donald; Marshall-Gradisnik, Sonya

2016-12-01

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), and Multiple Sclerosis (MS) may share some similarities in relation to reduced NK cell activity. It is likely that other cells such as regulatory T (Tregs), invariant Natural Killer T (iNKT) and gamma delta T (γδ T) cells may also be dysregulated in CFS/ME and MS. To evaluate and compare specific immune regulatory cells of patients with CFS/ME, patients with MS and healthy controls. Sixty three volunteers were included in this study: 24 were CFS/ME patients, 11 were MS patients and 27 were healthy controls. Blood samples were obtained from all participants for flow cytometry analysis of iNKT cells, Tregs and γδ T cell phenotypes. We observed a significant increase in Tregs in the CFS/ME group (p≤0.05) compared to the healthy control group. Total γδ and γδ2 T cells were significantly reduced in MS patients in comparison with the healthy control group. Conversely, CD4+iNKT percentage of iNKT, was significantly increased in the CFS/ME group compared with healthy controls and the double-negative iNKT percentage of iNKT significantly decreased compared with the healthy control group. This study has not identified any immunological disturbances that are common in both MS and CFS/ME patients. However, the differential expression of cell types between the conditions investigated suggests different pathways of disease. These differences need to be explored in further studies.

The Analgesic Effects of Morphine and Tramadol Added to Intra-articular Levobupivacaine-Tenoxicam Combination for Arthroscopic Knee Surgery on Postoperative Pain; a Randomized Clinical Trial

PubMed Central

Oral, Ebru Gelici; Hanci, Ayse; Ulufer Sivrikaya, Gulcihan; Dobrucali, Hale; Turkoglu Kilinc, Leyla

2015-01-01

Background: Arthroscopic knee surgery is commonly performed as an outpatient procedure and is often associated with postoperative pain. Objectives: We aimed to compare the effects of intra-articular levobupivacaine-tenoxicam-tramadol and levobupivacaine-tenoxicam-morphine combinations on postoperative pain in patients undergoing elective arthroscopic knee surgery. Materials and Methods: A total of 90 ASA I-II patients undergoing elective arthroscopic meniscectomy under general anesthesia were enrolled. The participants were randomly allocated to three groups to receive the following intra-articular medications after completion of the surgery and before deflation of the tourniquet: Group S, 20 mL of saline; Group T, 35 mg of levobupivacaine, 20 mg of tenoxicam, and 100 mg of tramadol in 20 mL saline; and Group M, 35 mg of levobupivacaine, 20 mg of tenoxicam, and 4 mg of morphine in 20 mL saline. Visual analogue scale values at rest (VASr) and at active flexion of knee (VASa) at postoperation hours 1, 2, 4, 8, 12, and 24, duration of analgesia, total analgesic consumption, and number of rescue analgesia at 24 hours were evaluated. Results: VASr and VASa were significantly higher in group S in comparison to other groups (P < 0.05). Duration of analgesia was significantly longer in Group T and Group M than in Group S (P < 0.05). The difference between group T and group M was also significant (P < 0.05). Number of rescue analgesia and total analgesic consumption at postoperative hour 24 was significantly fewer in group M compared with other groups (P < 0.05). Conclusions: Intra-articular levobupivacaine-tenoxicam-morphine combination provides effective pain relief, longer analgesic duration, and less analgesic requirement when compared with intra-articular levobupivacaine-tenoxicam-tramadol combination and saline after knee arthroscopic surgery. PMID:26161321

Clinical Control of HIV-1 by Cytotoxic T Cells Specific for Multiple Conserved Epitopes.

PubMed

Murakoshi, Hayato; Akahoshi, Tomohiro; Koyanagi, Madoka; Chikata, Takayuki; Naruto, Takuya; Maruyama, Rie; Tamura, Yoshiko; Ishizuka, Naoki; Gatanaga, Hiroyuki; Oka, Shinichi; Takiguchi, Masafumi

2015-05-01

Identification and characterization of CD8(+) T cells effectively controlling HIV-1 variants are necessary for the development of AIDS vaccines and for studies of AIDS pathogenesis, although such CD8(+) T cells have been only partially identified. In this study, we sought to identify CD8(+) T cells controlling HIV-1 variants in 401 Japanese individuals chronically infected with HIV-1 subtype B, in which protective alleles HLA-B*57 and HLA-B*27 are very rare, by using comprehensive and exhaustive methods. We identified 13 epitope-specific CD8(+) T cells controlling HIV-1 in Japanese individuals, though 9 of these epitopes were not previously reported. The breadths of the T cell responses to the 13 epitopes were inversely associated with plasma viral load (P = 2.2 × 10(-11)) and positively associated with CD4 count (P = 1.2 × 10(-11)), indicating strong synergistic effects of these T cells on HIV-1 control in vivo. Nine of these epitopes were conserved among HIV-1 subtype B-infected individuals, whereas three out of four nonconserved epitopes were cross-recognized by the specific T cells. These findings indicate that these 12 epitopes are strong candidates for antigens for an AIDS vaccine. The present study highlighted a strategy to identify CD8(+) T cells controlling HIV-1 and demonstrated effective control of HIV-1 by those specific for 12 conserved or cross-reactive epitopes. HLA-B*27-restricted and HLA-B*57-restricted cytotoxic T lymphocytes (CTLs) play a key role in controlling HIV-1 in Caucasians and Africans, whereas it is unclear which CTLs control HIV-1 in Asian countries, where HLA-B*57 and HLA-B*27 are very rare. A recent study showed that HLA-B*67:01 and HLA-B*52:01-C*12:02 haplotypes were protective alleles in Japanese individuals, but it is unknown whether CTLs restricted by these alleles control HIV-1. In this study, we identified 13 CTLs controlling HIV-1 in Japan by using comprehensive and exhaustive methods. They included 5 HLA-B*52:01-restricted

Clinical Control of HIV-1 by Cytotoxic T Cells Specific for Multiple Conserved Epitopes

PubMed Central

Murakoshi, Hayato; Akahoshi, Tomohiro; Koyanagi, Madoka; Chikata, Takayuki; Naruto, Takuya; Maruyama, Rie; Tamura, Yoshiko; Ishizuka, Naoki; Gatanaga, Hiroyuki; Oka, Shinichi

2015-01-01

ABSTRACT Identification and characterization of CD8+ T cells effectively controlling HIV-1 variants are necessary for the development of AIDS vaccines and for studies of AIDS pathogenesis, although such CD8+ T cells have been only partially identified. In this study, we sought to identify CD8+ T cells controlling HIV-1 variants in 401 Japanese individuals chronically infected with HIV-1 subtype B, in which protective alleles HLA-B*57 and HLA-B*27 are very rare, by using comprehensive and exhaustive methods. We identified 13 epitope-specific CD8+ T cells controlling HIV-1 in Japanese individuals, though 9 of these epitopes were not previously reported. The breadths of the T cell responses to the 13 epitopes were inversely associated with plasma viral load (P = 2.2 × 10−11) and positively associated with CD4 count (P = 1.2 × 10−11), indicating strong synergistic effects of these T cells on HIV-1 control in vivo. Nine of these epitopes were conserved among HIV-1 subtype B-infected individuals, whereas three out of four nonconserved epitopes were cross-recognized by the specific T cells. These findings indicate that these 12 epitopes are strong candidates for antigens for an AIDS vaccine. The present study highlighted a strategy to identify CD8+ T cells controlling HIV-1 and demonstrated effective control of HIV-1 by those specific for 12 conserved or cross-reactive epitopes. IMPORTANCE HLA-B*27-restricted and HLA-B*57-restricted cytotoxic T lymphocytes (CTLs) play a key role in controlling HIV-1 in Caucasians and Africans, whereas it is unclear which CTLs control HIV-1 in Asian countries, where HLA-B*57 and HLA-B*27 are very rare. A recent study showed that HLA-B*67:01 and HLA-B*52:01-C*12:02 haplotypes were protective alleles in Japanese individuals, but it is unknown whether CTLs restricted by these alleles control HIV-1. In this study, we identified 13 CTLs controlling HIV-1 in Japan by using comprehensive and exhaustive methods. They included 5 HLA-B*52

Estimated plasma bupivacaine concentration after single dose and eight-hour continuous intra-articular infusion of bupivacaine in normal dogs.

PubMed

Bubenik, Loretta; Hosgood, Giselle; Barker, Steven; Hicks, Merrin; Serra, Verna; Stout, Rhett

2007-12-01

To estimate maximum plasma concentration (C(max)) and time to maximum plasma (t(max)) bupivacaine concentration after intra-articular administration of bupivacaine for single injection (SI) and injection followed by continuous infusion (CI) in normal dogs. Cross-over design with a 2-week washout period. Healthy Coon Hound dogs (n=8). Using gas chromatography/mass spectrometry, canine plasma bupivacaine concentration was measured before and after SI (1.5 mg/kg) and CI (1.5 mg/kg and 0.3 mg/kg/h). Software was used to establish plasma concentration-time curves and estimate C(max), T(max) and other pharmacokinetic variables for comparison of SI and CI. Bupivacaine plasma concentration after SI and CI best fit a 3 exponential model. For SI, mean maximum concentration (C(max), 1.33+/-0.954 microg/mL) occurred at 11.37+/-4.546 minutes. For CI, mean C(max) (1.13+/-0.509 microg/mL) occurred at 10.37+/-4.109 minutes. The area under the concentration-time curve was smaller for SI (143.59+/-118.390 microg/mL x min) than for CI (626.502+/-423.653 microg/mL x min, P=.02) and half-life was shorter for SI (61.33+/-77.706 minutes) than for CI (245.363+/-104.415 minutes, P=.01). The highest plasma bupivacaine concentration for any dog was 3.2 microg/mL for SI and 2.3 microg/mL for CI. Intra-articular bupivacaine administration results in delayed absorption from the stifle into the systemic circulation with mean C(max) below that considered toxic and no systemic drug accumulation. Intra-articular bupivacaine can be administered with small risk of reaching toxic plasma concentrations in dogs, though toxic concentrations may be approached. Caution should be exercised with multimodal bupivacaine administration because plasma drug concentration may rise higher than with single intra-articular injection.

Myeloid Conditioning with c-kit-Targeted CAR-T Cells Enables Donor Stem Cell Engraftment.

PubMed

Arai, Yasuyuki; Choi, Uimook; Corsino, Cristina I; Koontz, Sherry M; Tajima, Masaki; Sweeney, Colin L; Black, Mary A; Feldman, Steven A; Dinauer, Mary C; Malech, Harry L

2018-05-02

We report a novel approach to bone marrow (BM) conditioning using c-kit-targeted chimeric antigen receptor T (c-kit CAR-T) cells in mice. Previous reports using anti-c-kit or anti-CD45 antibody linked to a toxin such as saporin have been promising. We developed a distinctly different approach using c-kit CAR-T cells. Initial studies demonstrated in vitro killing of hematopoietic stem cells by c-kit CAR-T cells but poor expansion in vivo and poor migration of CAR-T cells into BM. Pre-treatment of recipient mice with low-dose cyclophosphamide (125 mg/kg) together with CXCR4 transduction in the CAR-T cells enhanced trafficking to and expansion in BM (<1%-13.1%). This resulted in significant depletion of the BM c-kit + population (9.0%-0.1%). Because congenic Thy1.1 CAR-T cells were used in the Thy1.2-recipient mice, anti-Thy1.1 antibody could be used to deplete CAR-T cells in vivo before donor BM transplant. This achieved 20%-40% multilineage engraftment. We applied this conditioning to achieve an average of 28% correction of chronic granulomatous disease mice by wild-type BM transplant. Our findings provide a proof of concept that c-kit CAR-T cells can achieve effective BM conditioning without chemo-/radiotherapy. Our work also demonstrates that co-expression of a trafficking receptor can enhance targeting of CAR-T cells to a designated tissue. Published by Elsevier Inc.

T-cell receptor repertoire of human peripheral CD161hiTRAV1-2+ MAIT cells revealed by next generation sequencing and single cell analysis.

PubMed

Held, Kathrin; Beltrán, Eduardo; Moser, Markus; Hohlfeld, Reinhard; Dornmair, Klaus

2015-09-01

Mucosal-associated invariant T (MAIT) cells are a T-cell subset that expresses a conserved TRAV1-2 (Vα7.2) T-cell receptor (TCR) chain and the surface marker CD161. They are involved in the defence against microbes as they recognise small organic molecules of microbial origin that are presented by the non-classical MHC molecule 1 (MR1). MAIT cells express a semi-restricted TCR α chain with TRAV1-2 preferentially linked to TRAJ33, TRAJ12, or TRAJ20 which pairs with a limited set of β chains. To investigate the TCR repertoire of human CD161(hi)TRAV1-2(+) T cells in depth we analysed the α and β chains of this T-cell subset by next generation sequencing. Concomitantly we analysed 132 paired α and β chains from single cells to assess the αβ pairing preferences. We found that the CD161(hi)TRAV1-2(+) TCR repertoire in addition to the typical MAIT TCRs further contains polyclonal elements reminiscent of classical αβ T cells. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Interleukin-12 (-1188) A/C and interferon-γ (+874) A/T gene polymorphisms in subacute sclerosing panencephalitis patients.

PubMed

Dundar, Nihal Olgac; Gencpinar, Pinar; Sallakci, Nilgun; Duman, Ozgur; Haspolat, Senay; Anlar, Banu; Yegin, Olcay

2016-10-01

The two polymorphisms [IL-12 (-1188) A/C and the IFN-γ (+874) A/T)] are known to have functional consequences and henceforth were analyzed in subacute sclerosing panencephalitis (SSPE) patients to reveal a possible relation with these polymorphisms and this debilitating disease. For the IL-12 (-1188) A/C polymorphism, 78 patients and 90 healthy individuals were analyzed. An increase in the AA genotype was determined (p = 0.02, OR = 2.06). There was also a statistically significant difference between the control group and the patients with respect to the allele frequencies (p = 0.04, OR = 1.65). For the IFN-γ (+874) A/T polymorphism, 69 SSPE patients and 115 controls were studied and there was not a significant difference between the two groups. Our findings suggested that not the IFN-γ (+874) A/T but the IL-12 (-1188) A/C polymorphism is correlated with SSPE and having an AA genotype or A allele decreases the risk of developing SSPE by 2.06- and 1.65-fold, respectively.

T-wave loop area from a pre-implant 12-lead ECG is associated with appropriate ICD shocks

PubMed Central

Hnatkova, Katerina; Friede, Tim; Malik, Marek; Zabel, Markus

2017-01-01

Aims In implantable cardioverter-defibrillator (ICD) patients, predictors of ICD shocks and mortality are needed to improve patient selection. Electrocardiographic (ECG) markers are simple to obtain and have been demonstrated to predict mortality. We aimed to assess the association of T-wave loop area and circularity with ICD shocks. Methods The study investigated patients with ICDs implanted between 1998 and 2010 for whom digital 12-lead ECGs (Schiller CS200 ECG-Network) of sufficient quality were obtained within 1 month prior to the implantation. T-wave loop area and circularity were calculated. Follow-up data of appropriate shocks were obtained during ICD clinic visits that included reviews of device stored electrograms. Results A total of 605 patients (82% males) were included; 68% had ischemic cardiomyopathy and 72% were treated for primary prevention. Over 3.8±1.4 years of follow-up, 114 patients (19%) experienced appropriate shock(s). Those with smaller T-wave loop area received fewer shocks (TLA, hazard ratio, HR, per increase of 1 technical unit, 0.71; [95% confidence interval, 0.53–0.94]; P = 0.02) and those with larger T-wave loop circularity (TLC) representing rounder T wave loop received more shocks (HR per 1% TLC increase 2.96; [0.85–10.36]; P = 0.09). When the quartile containing the largest TLA and TLC values, respectively, were compared to the remaining cases, TLA remained significantly associated with fewer and TLC with more frequent shocks also after multivariate adjustment for clinical variables (HR, 0.59 [0.35–0.99], P = 0.044; and 1.64 [1.08–2.49], P = 0.021, respectively). Conclusions The size and shape of the T-wave loop calculated from pre-implantation 12-lead ECGs are associated with appropriate ICD shocks. PMID:28291831

RNase MRP cleaves pre-tRNASer-Met in the tRNA maturation pathway.

PubMed

Saito, Yuichiro; Takeda, Jun; Adachi, Kousuke; Nobe, Yuko; Kobayashi, Junya; Hirota, Kouji; Oliveira, Douglas V; Taoka, Masato; Isobe, Toshiaki

2014-01-01

Ribonuclease mitochondrial RNA processing (RNase MRP) is a multifunctional ribonucleoprotein (RNP) complex that is involved in the maturation of various types of RNA including ribosomal RNA. RNase MRP consists of a potential catalytic RNA and several protein components, all of which are required for cell viability. We show here that the temperature-sensitive mutant of rmp1, the gene for a unique protein component of RNase MRP, accumulates the dimeric tRNA precursor, pre-tRNA(Ser-Met). To examine whether RNase MRP mediates tRNA maturation, we purified the RNase MRP holoenzyme from the fission yeast Schizosaccharomyces pombe and found that the enzyme directly and selectively cleaves pre-tRNA(Ser-Met), suggesting that RNase MRP participates in the maturation of specific tRNA in vivo. In addition, mass spectrometry-based ribonucleoproteomic analysis demonstrated that this RNase MRP consists of one RNA molecule and 11 protein components, including a previously unknown component Rpl701. Notably, limited nucleolysis of RNase MRP generated an active catalytic core consisting of partial mrp1 RNA fragments, which constitute "Domain 1" in the secondary structure of RNase MRP, and 8 proteins. Thus, the present study provides new insight into the structure and function of RNase MRP.

RNase MRP Cleaves Pre-tRNASer-Met in the tRNA Maturation Pathway

PubMed Central

Adachi, Kousuke; Nobe, Yuko; Kobayashi, Junya; Hirota, Kouji; Oliveira, Douglas V.; Taoka, Masato; Isobe, Toshiaki

2014-01-01

Ribonuclease mitochondrial RNA processing (RNase MRP) is a multifunctional ribonucleoprotein (RNP) complex that is involved in the maturation of various types of RNA including ribosomal RNA. RNase MRP consists of a potential catalytic RNA and several protein components, all of which are required for cell viability. We show here that the temperature-sensitive mutant of rmp1, the gene for a unique protein component of RNase MRP, accumulates the dimeric tRNA precursor, pre-tRNASer-Met. To examine whether RNase MRP mediates tRNA maturation, we purified the RNase MRP holoenzyme from the fission yeast Schizosaccharomyces pombe and found that the enzyme directly and selectively cleaves pre-tRNASer-Met, suggesting that RNase MRP participates in the maturation of specific tRNA in vivo. In addition, mass spectrometry–based ribonucleoproteomic analysis demonstrated that this RNase MRP consists of one RNA molecule and 11 protein components, including a previously unknown component Rpl701. Notably, limited nucleolysis of RNase MRP generated an active catalytic core consisting of partial mrp1 RNA fragments, which constitute “Domain 1” in the secondary structure of RNase MRP, and 8 proteins. Thus, the present study provides new insight into the structure and function of RNase MRP. PMID:25401760

SLP-76-ADAP adaptor module regulates LFA-1 mediated costimulation and T cell motility.

PubMed

Wang, Hongyan; Wei, Bin; Bismuth, Georges; Rudd, Christopher E

2009-07-28

Although adaptor ADAP (FYB) and its binding to SLP-76 has been implicated in TcR-induced "inside-out" signaling for LFA-1 activation in T cells, little is known regarding its role in LFA-1-mediated "outside-in" signaling. In this study, we demonstrate that ADAP and SLP-76-ADAP binding are coupled to LFA-1 costimulation of IL-2 production, F-actin clustering, cell polarization, and T cell motility. LFA-1 enhancement of anti-CD3-induced IL-2 production was completely dependent on SLP-76-ADAP binding. Further, anti-CD3 was found to require CD11a ligation by antibody or ICAM1 to cause T cell polarization. ADAP augmented this polarization induced by anti-CD3/CD11a, but not by anti-CD3 alone. ADAP expression with LFA-1 ligation alone was sufficient to polarize T cells directly and to increase T cell motility whereas the loss of ADAP in ADAP-/- primary T cells reduced motility. A mutant lacking SLP-76-binding sites (M12) blocked LFA-1 costimulation of IL-2 production, polarization, and motility. LFA-1-ADAP polarization was also dependent on src kinases, Rho GTPases, phospholipase C, and phosphoinositol 3-kinase. Our findings provide evidence of an obligatory role for the SLP-76-ADAP module in LFA-1-mediated costimulation in T cells.

T-T Neutron Spectrum from Inertial Confinement Implosions

NASA Astrophysics Data System (ADS)

Bacher, A. D.; Casey, D. T.; Frenje, J. A.; Gatu Johnson, M. J.; Manuel, M.; Sinenian, N.; Zylstra, A. B.; Séguin, F. H.; Li, C. K.; Petrasso, R. D.; Glebov, V. Yu; Radha, P. B.; Meyerhofer, D. D.; Sangster, T. C.; McNabb, D. P.; Amendt, P. A.; Boyd, R. N.; Caggiano, J. A.; Hatchett, S. P.; Pino, J. E.; Quaglioni, S.; Rygg, J. R.; Thompson, I. J.; Herrmann, H. W.; Kim, Y. H.

2013-08-01

A new technique that uses inertial confinement implosions for measuring low-energy nuclear reactions important to nuclear astrophysics is described. Simultaneous measurements of n-D and n-T elastic scattering at 14.1 MeV using deuterium-tritium gas-filled capsules provide a proof of principle for this technique. Measurements have been made of D(d,p)T (dd) and T(t,2n)4He (tt) reaction yields relative to the D(t,n)4He (dt) reaction yield for deuterium-tritium mixtures with f T / f D between 0.62 and 0.75 and for a wide range of ion temperatures to test our understanding of the implosion processes. Measurements of the shape of the neutron spectrum from the T(t,2n)4He reaction have been made for each of these target configurations.

NCHRP report 350 test 3-11 of the modified T8 bridge rail.

DOT National Transportation Integrated Search

2009-04-01

A new flexible bridge rail system, referred to as the T8 rail, was designed as a replacement for the T6 rail in high-speed applications on culverts and thin deck structures. The T8 rail failed a crash test when the breakaway posts failed the thin dec...

EBV-Positive T/NK-Cell Lymphoproliferative Disease of Childhood

PubMed Central

Hong, Mineui; Yoo, Keon Hee; Koo, Hong Hoe; Kim, Seok Jin; Kim, Won Seog

2013-01-01

Background Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH), EBV-positive systemic T-cell lymphoproliferative disease (STLPD) of childhood, and chronic active EBV (CAEBV) infection may develop after primary EBV infection. This study reviewed the clinicopathological spectrum of EBV-associated T- and natural killer (NK)-cell LPD, including STLPD and CAEBV infection, with an analysis of T-cell clonality. Methods Clinicopathological features of seven patients with EBV-associated HLH or STLPD and 12 patients with CAEBV infection were reviewed. Immunohistochemical staining and a T-cell receptor (TCR) gene rearrangement study were performed. Results STLPD and EBV-positive HLH showed significantly overlapping clinicopathological findings. One patient with STLPD and one patient with EBV-positive HLH demonstrated moderate to severe atypia of the infiltrating lymphocytes, whereas the remaining patients lacked significant atypia. Twelve patients had CAEBV infection, four of whom suffered mosquito-bite hypersensitivity, five showed NK lymphocytosis, and one suffered hydroa vacciniforme. Infiltrating lymphocytes were predominantly small and devoid of atypia. Hemophagocytic histiocytosis was found in seven of 11 patients. Monoclonality was detected in three (50%) of the six patients with successful TCR gene analysis. Conclusions EBV-positive HLH and STLPD share similar clinicopathological findings and may constitute a continuous spectrum of acute EBV-associated T- or NK-cell proliferative disorders. The distinction of EBV-positive T-cell LPD from EBV-positive HLH may be difficult during routine diagnoses because of the technical limitations of clonality assessment. PMID:23667373

EBV-Positive T/NK-Cell Lymphoproliferative Disease of Childhood.

PubMed

Hong, Mineui; Ko, Young Hyeh; Yoo, Keon Hee; Koo, Hong Hoe; Kim, Seok Jin; Kim, Won Seog; Park, Heejung

2013-04-01

Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH), EBV-positive systemic T-cell lymphoproliferative disease (STLPD) of childhood, and chronic active EBV (CAEBV) infection may develop after primary EBV infection. This study reviewed the clinicopathological spectrum of EBV-associated T- and natural killer (NK)-cell LPD, including STLPD and CAEBV infection, with an analysis of T-cell clonality. Clinicopathological features of seven patients with EBV-associated HLH or STLPD and 12 patients with CAEBV infection were reviewed. Immunohistochemical staining and a T-cell receptor (TCR) gene rearrangement study were performed. STLPD and EBV-positive HLH showed significantly overlapping clinicopathological findings. One patient with STLPD and one patient with EBV-positive HLH demonstrated moderate to severe atypia of the infiltrating lymphocytes, whereas the remaining patients lacked significant atypia. Twelve patients had CAEBV infection, four of whom suffered mosquito-bite hypersensitivity, five showed NK lymphocytosis, and one suffered hydroa vacciniforme. Infiltrating lymphocytes were predominantly small and devoid of atypia. Hemophagocytic histiocytosis was found in seven of 11 patients. Monoclonality was detected in three (50%) of the six patients with successful TCR gene analysis. EBV-positive HLH and STLPD share similar clinicopathological findings and may constitute a continuous spectrum of acute EBV-associated T- or NK-cell proliferative disorders. The distinction of EBV-positive T-cell LPD from EBV-positive HLH may be difficult during routine diagnoses because of the technical limitations of clonality assessment.

17 CFR 230.702(T)-230.703(T) - [Reserved

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false [Reserved] 230.702(T)-230.703(T) Section 230.702(T)-230.703(T) Commodity and Securities Exchanges SECURITIES AND EXCHANGE... Small Business Investment Companies §§ 230.702(T)-230.703(T) [Reserved] Exemptions for Cross-Border...

[Application of tibial mechanical axis locator in tibial extra-articular deformity in total knee arthroplasty].

PubMed

Li, Guoliang; Han, Guangpu; Zhang, Jinxiu; Ma, Shiqiang; Guo, Donghui; Yuan, Fulu; Qi, Bingbing; Shen, Runbin

2013-07-01

To explore the application value of self-made tibial mechanical axis locator in tibial extra-articular deformity in total knee arthroplasty (TKA) for improving the lower extremity force line. Between January and August 2012, 13 cases (21 knees) of osteoarthritis with tibial extra-articular deformity were treated, including 5 males (8 knees) and 8 females (13 knees) with an average age of 66.5 years (range, 58-78 years). The disease duration was 2-5 years (mean, 3.5 years). The knee society score (KSS) was 45.5 +/- 15.5. Extra-articular deformities included 1 case of knee valgus (2 knees) and 12 cases of knee varus (19 knees). Preoperative full-length X-ray films of lower extremities showed 10-21 degrees valgus or varus deformity of tibial extra joint. Self-made tibial mechanical axis locator was used to determine and mark coronal tibial mechanical axis under X-ray before TKA, and then osteotomy was performed with extramedullary positioning device according to the mechanical axis marker.' All incisions healed by first intention, without related complications of infection and joint instability. All patients were followed up 5-12 months (mean, 8.3 months). The X-ray examination showed < 2 degrees knee deviation angle in the others except 1 case of 2.9 degrees knee deviation angle at 3 days after operation, and the accurate rate was 95.2%. No loosening or instability of prosthesis occurred during follow-up. KSS score was 85.5 +/- 15.0 at last follow-up, showing significant difference when compared with preoperative score (t=12.82, P=0.00). The seft-made tibial mechanical axis locator can improve the accurate rate of the lower extremity force line in TKA for tibia extra-articular deformity.

The n-by-T Target Discharge Strategy for Inpatient Units.

PubMed

Parikh, Pratik J; Ballester, Nicholas; Ramsey, Kylie; Kong, Nan; Pook, Nancy

2017-07-01

Ineffective inpatient discharge planning often causes discharge delays and upstream boarding. While an optimal discharge strategy that works across all units at a hospital is likely difficult to identify and implement, a strategy that provides a reasonable target to the discharge team appears feasible. We used observational and retrospective data from an inpatient trauma unit at a Level 2 trauma center in the Midwest US. Our proposed novel n-by-T strategy-discharge n patients by the Tth hour-was evaluated using a validated simulation model. Outcome measures included 2 measures: time-based (mean discharge completion and upstream boarding times) and capacity-based (increase in annual inpatient and upstream bed hours). Data from the pilot implementation of a 2-by-12 strategy at the unit was obtained and analyzed. The model suggested that the 1-by-T and 2-by-T strategies could advance the mean completion times by over 1.38 and 2.72 h, respectively (for 10 AM ≤ T ≤ noon, occupancy rate = 85%); the corresponding mean boarding time reductions were nearly 11% and 15%. These strategies could increase the availability of annual inpatient and upstream bed hours by at least 2,469 and 500, respectively. At 100% occupancy rate, the hospital-favored 2-by-12 strategy reduced the mean boarding time by 26.1%. A pilot implementation of the 2-by-12 strategy at the unit corroborated with the model findings: a 1.98-h advancement in completion times (P<0.0001) and a 14.5% reduction in boarding times (P = 0.027). Target discharge strategies, such as the n-by-T, can help substantially reduce discharge lateness and upstream boarding, especially during high unit occupancy. To sustain implementation, necessary commitment from the unit staff and physicians is vital, and may require some training.

Accumulation of human T lymphotropic virus (HTLV)-I-specific T cell clones in HTLV-I-associated myelopathy/tropical spastic paraparesis patients.

PubMed

Höger, T A; Jacobson, S; Kawanishi, T; Kato, T; Nishioka, K; Yamamoto, K

1997-08-15

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraperesis (HAM/TSP) is a slowly progressive neurologic disorder following infection with HTLV-I. It is characterized by spasticity and hyper-reflexia of the lower extremities, urinary bladder disturbance, lower extremity muscle weakness, and sensory disturbances. HTLV-I, as an inducer of a strong humoral and cytotoxic response, is a well-known pathogenic factor for the progression of HAM/TSP. Peptides derived from proviral tax and env genes provide epitopes recognized by T cells. We herein report an accumulation of distinct clonotypes of alpha/beta TCR+ peripheral blood T lymphocytes from HAM/TSP patients in comparison with that observed in both asymptomatic carriers and healthy controls, using the reverse-transcriptase PCR/single-strand conformation polymorphism method. We also found that some of the accumulated T cell clones in the peripheral blood and cerebrospinal fluid are HTLV-I Tax(11-19) peptide specific. Such clones were found to expand strongly after being cultured with an HTLV-I Tax(11-19) peptide. Moreover, the cultured samples exhibited a strong MHC class I-restricted cytotoxic activity against HTLV-I Tax(11-19) peptide-expressing targets, and therefore most likely also include the disease-associated T cell clones observed in the patients. This is the first report of a direct assessment of Ag-specific T cell responses in fresh PBL and cerebrospinal fluid.

A comparative analysis of immunorestoration and recovery with conventional and immunotherapeutic protocols in canine generalized demodicosis: a newer insight of immunotherapeutic efficacy of T11TS.

PubMed

Sarkar, P; Mukherjee, J; Ghosh, A; Bhattacharjee, M; Mahato, S; Chakraborty, A; Mondal, M; Banerjee, C; Chaudhuri, Swapna

2004-01-01

Demodex canis is a natural inhabiting mite of canine skin. Immunological disorder or genetic disorder induces the Demodex population to proliferate vigorously resulting in generalized demodicosis with consequent chronic immunosuppression. Signs of generalized demodicosis include alopecia, crysting, erythema, secondary pyoderma etc. Amitraz, an acaricide, is used conventionally for the treatment of generalized demodicosis. In many instances, the disease relapses due to the residual immunosuppression. The need of an immunorestorative therapy has been urged in generalized demodicosis. Two immunorestorative drugs, namely, Immuplus, a herbal drug, and T11TS, a sheep erythrocyte surface glycoprotein, has been used in two separate groups of dogs having generalized demodicosis and receiving Amitraz treatment. It was observed that though Amitraz treated group responded to the therapy showing increased E-rosettes and nonspecific cytotoxic efficacy of T-lymphocytes and decrease in phagocytic potential of macrophages, the groups treated with the immunotherapeutics like Immuplus and T11TS, responded better. However, the group treated with T11TS showed best recovery. These results emphasize the need for an immunorestorative therapy in generalized demodicosis and provide data in favor of T11TS as a better immunomodulator in comparison to Immuplus.

Magnetic properties of GdT 2Zn 20 (T = Fe, Co) investigated by x-ray diffraction and spectroscopy

DOE PAGES

J. R. L. Mardegan; Fabbris, G.; Francoual, S.; ...

2016-01-26

In this study, we investigate the magnetic and electronic properties of the GdT 2Zn 20 (T=Fe and Co) compounds using x-ray resonant magnetic scattering (XRMS), x-ray absorption near-edge structure (XANES), and x-ray magnetic circular dichroism (XMCD). The XRMS measurements reveal that GdCo 2Zn 20 has a commensurate antiferromagnetic spin structure with a magnetic propagation vector →/ τ = (12,12,12) below the Néel temperature (T N ~ 5.7 K). Only the Gd ions carry a magnetic moment forming an antiferromagnetic structure with magnetic representation Γ 6. For the ferromagnetic GdFe 2Zn 20 compound, an extensive investigation was performed at low temperaturemore » and under magnetic field using XANES and XMCD. A strong XMCD signal of about 12.5% and 9.7% is observed below the Curie temperature (T C ~ 85K) at the Gd L 2 and L 3 edges, respectively. In addition, a small magnetic signal of about 0.06% of the jump is recorded at the Zn K edge, suggesting that the Zn 4p states are spin polarized by the Gd 5d extended orbitals.« less

7 CFR 29.3154 - Tips (T Group).

Code of Federal Regulations, 2011 CFR

2011-01-01

... stalk. (See Rule 12.) Grades Grade names and specifications T3F Good Tan Tips. Medium body, mature to...″ in length, 85 percent uniform, and 15 percent injury tolerance. T4F Fair Tan Tips. Medium body..., and 20 percent injury tolerance. T5F Low Tan Tips. Medium body, mature, firm, wrinkly, dingy finish...

7 CFR 29.3154 - Tips (T Group).

Code of Federal Regulations, 2010 CFR

2010-01-01

... stalk. (See Rule 12.) Grades Grade names and specifications T3F Good Tan Tips. Medium body, mature to...″ in length, 85 percent uniform, and 15 percent injury tolerance. T4F Fair Tan Tips. Medium body..., and 20 percent injury tolerance. T5F Low Tan Tips. Medium body, mature, firm, wrinkly, dingy finish...

Antimicrobial Activity and Chemical Composition of “Kpètè-Kpètè”: A Starter of Benin Traditional Beer Tchoukoutou